case study critical discussion

Organizing Your Social Sciences Research Assignments

• Annotated Bibliography
• Analyzing a Scholarly Journal Article
• Group Presentations
• Dealing with Nervousness
• Using Visual Aids
• Grading Someone Else's Paper
• Types of Structured Group Activities
• Group Project Survival Skills
• Leading a Class Discussion
• Multiple Book Review Essay
• Reviewing Collected Works
• Writing a Case Analysis Paper
• Writing a Case Study
• About Informed Consent
• Writing Field Notes
• Writing a Policy Memo
• Writing a Reflective Paper
• Writing a Research Proposal
• Generative AI and Writing
• Acknowledgments

A case study research paper examines a person, place, event, condition, phenomenon, or other type of subject of analysis in order to extrapolate  key themes and results that help predict future trends, illuminate previously hidden issues that can be applied to practice, and/or provide a means for understanding an important research problem with greater clarity. A case study research paper usually examines a single subject of analysis, but case study papers can also be designed as a comparative investigation that shows relationships between two or more subjects. The methods used to study a case can rest within a quantitative, qualitative, or mixed-method investigative paradigm.

Case Studies. Writing@CSU. Colorado State University; Mills, Albert J. , Gabrielle Durepos, and Eiden Wiebe, editors. Encyclopedia of Case Study Research . Thousand Oaks, CA: SAGE Publications, 2010 ; “What is a Case Study?” In Swanborn, Peter G. Case Study Research: What, Why and How? London: SAGE, 2010.

How to Approach Writing a Case Study Research Paper

General information about how to choose a topic to investigate can be found under the " Choosing a Research Problem " tab in the Organizing Your Social Sciences Research Paper writing guide. Review this page because it may help you identify a subject of analysis that can be investigated using a case study design.

However, identifying a case to investigate involves more than choosing the research problem . A case study encompasses a problem contextualized around the application of in-depth analysis, interpretation, and discussion, often resulting in specific recommendations for action or for improving existing conditions. As Seawright and Gerring note, practical considerations such as time and access to information can influence case selection, but these issues should not be the sole factors used in describing the methodological justification for identifying a particular case to study. Given this, selecting a case includes considering the following:

• The case represents an unusual or atypical example of a research problem that requires more in-depth analysis? Cases often represent a topic that rests on the fringes of prior investigations because the case may provide new ways of understanding the research problem. For example, if the research problem is to identify strategies to improve policies that support girl's access to secondary education in predominantly Muslim nations, you could consider using Azerbaijan as a case study rather than selecting a more obvious nation in the Middle East. Doing so may reveal important new insights into recommending how governments in other predominantly Muslim nations can formulate policies that support improved access to education for girls.
• The case provides important insight or illuminate a previously hidden problem? In-depth analysis of a case can be based on the hypothesis that the case study will reveal trends or issues that have not been exposed in prior research or will reveal new and important implications for practice. For example, anecdotal evidence may suggest drug use among homeless veterans is related to their patterns of travel throughout the day. Assuming prior studies have not looked at individual travel choices as a way to study access to illicit drug use, a case study that observes a homeless veteran could reveal how issues of personal mobility choices facilitate regular access to illicit drugs. Note that it is important to conduct a thorough literature review to ensure that your assumption about the need to reveal new insights or previously hidden problems is valid and evidence-based.
• The case challenges and offers a counter-point to prevailing assumptions? Over time, research on any given topic can fall into a trap of developing assumptions based on outdated studies that are still applied to new or changing conditions or the idea that something should simply be accepted as "common sense," even though the issue has not been thoroughly tested in current practice. A case study analysis may offer an opportunity to gather evidence that challenges prevailing assumptions about a research problem and provide a new set of recommendations applied to practice that have not been tested previously. For example, perhaps there has been a long practice among scholars to apply a particular theory in explaining the relationship between two subjects of analysis. Your case could challenge this assumption by applying an innovative theoretical framework [perhaps borrowed from another discipline] to explore whether this approach offers new ways of understanding the research problem. Taking a contrarian stance is one of the most important ways that new knowledge and understanding develops from existing literature.
• The case provides an opportunity to pursue action leading to the resolution of a problem? Another way to think about choosing a case to study is to consider how the results from investigating a particular case may result in findings that reveal ways in which to resolve an existing or emerging problem. For example, studying the case of an unforeseen incident, such as a fatal accident at a railroad crossing, can reveal hidden issues that could be applied to preventative measures that contribute to reducing the chance of accidents in the future. In this example, a case study investigating the accident could lead to a better understanding of where to strategically locate additional signals at other railroad crossings so as to better warn drivers of an approaching train, particularly when visibility is hindered by heavy rain, fog, or at night.
• The case offers a new direction in future research? A case study can be used as a tool for an exploratory investigation that highlights the need for further research about the problem. A case can be used when there are few studies that help predict an outcome or that establish a clear understanding about how best to proceed in addressing a problem. For example, after conducting a thorough literature review [very important!], you discover that little research exists showing the ways in which women contribute to promoting water conservation in rural communities of east central Africa. A case study of how women contribute to saving water in a rural village of Uganda can lay the foundation for understanding the need for more thorough research that documents how women in their roles as cooks and family caregivers think about water as a valuable resource within their community. This example of a case study could also point to the need for scholars to build new theoretical frameworks around the topic [e.g., applying feminist theories of work and family to the issue of water conservation].

Eisenhardt, Kathleen M. “Building Theories from Case Study Research.” Academy of Management Review 14 (October 1989): 532-550; Emmel, Nick. Sampling and Choosing Cases in Qualitative Research: A Realist Approach . Thousand Oaks, CA: SAGE Publications, 2013; Gerring, John. “What Is a Case Study and What Is It Good for?” American Political Science Review 98 (May 2004): 341-354; Mills, Albert J. , Gabrielle Durepos, and Eiden Wiebe, editors. Encyclopedia of Case Study Research . Thousand Oaks, CA: SAGE Publications, 2010; Seawright, Jason and John Gerring. "Case Selection Techniques in Case Study Research." Political Research Quarterly 61 (June 2008): 294-308.

Structure and Writing Style

The purpose of a paper in the social sciences designed around a case study is to thoroughly investigate a subject of analysis in order to reveal a new understanding about the research problem and, in so doing, contributing new knowledge to what is already known from previous studies. In applied social sciences disciplines [e.g., education, social work, public administration, etc.], case studies may also be used to reveal best practices, highlight key programs, or investigate interesting aspects of professional work.

In general, the structure of a case study research paper is not all that different from a standard college-level research paper. However, there are subtle differences you should be aware of. Here are the key elements to organizing and writing a case study research paper.

I.  Introduction

As with any research paper, your introduction should serve as a roadmap for your readers to ascertain the scope and purpose of your study . The introduction to a case study research paper, however, should not only describe the research problem and its significance, but you should also succinctly describe why the case is being used and how it relates to addressing the problem. The two elements should be linked. With this in mind, a good introduction answers these four questions:

• What is being studied? Describe the research problem and describe the subject of analysis [the case] you have chosen to address the problem. Explain how they are linked and what elements of the case will help to expand knowledge and understanding about the problem.
• Why is this topic important to investigate? Describe the significance of the research problem and state why a case study design and the subject of analysis that the paper is designed around is appropriate in addressing the problem.
• What did we know about this topic before I did this study? Provide background that helps lead the reader into the more in-depth literature review to follow. If applicable, summarize prior case study research applied to the research problem and why it fails to adequately address the problem. Describe why your case will be useful. If no prior case studies have been used to address the research problem, explain why you have selected this subject of analysis.
• How will this study advance new knowledge or new ways of understanding? Explain why your case study will be suitable in helping to expand knowledge and understanding about the research problem.

Each of these questions should be addressed in no more than a few paragraphs. Exceptions to this can be when you are addressing a complex research problem or subject of analysis that requires more in-depth background information.

II.  Literature Review

The literature review for a case study research paper is generally structured the same as it is for any college-level research paper. The difference, however, is that the literature review is focused on providing background information and  enabling historical interpretation of the subject of analysis in relation to the research problem the case is intended to address . This includes synthesizing studies that help to:

• Place relevant works in the context of their contribution to understanding the case study being investigated . This would involve summarizing studies that have used a similar subject of analysis to investigate the research problem. If there is literature using the same or a very similar case to study, you need to explain why duplicating past research is important [e.g., conditions have changed; prior studies were conducted long ago, etc.].
• Describe the relationship each work has to the others under consideration that informs the reader why this case is applicable . Your literature review should include a description of any works that support using the case to investigate the research problem and the underlying research questions.
• Identify new ways to interpret prior research using the case study . If applicable, review any research that has examined the research problem using a different research design. Explain how your use of a case study design may reveal new knowledge or a new perspective or that can redirect research in an important new direction.
• Resolve conflicts amongst seemingly contradictory previous studies . This refers to synthesizing any literature that points to unresolved issues of concern about the research problem and describing how the subject of analysis that forms the case study can help resolve these existing contradictions.
• Point the way in fulfilling a need for additional research . Your review should examine any literature that lays a foundation for understanding why your case study design and the subject of analysis around which you have designed your study may reveal a new way of approaching the research problem or offer a perspective that points to the need for additional research.
• Expose any gaps that exist in the literature that the case study could help to fill . Summarize any literature that not only shows how your subject of analysis contributes to understanding the research problem, but how your case contributes to a new way of understanding the problem that prior research has failed to do.
• Locate your own research within the context of existing literature [very important!] . Collectively, your literature review should always place your case study within the larger domain of prior research about the problem. The overarching purpose of reviewing pertinent literature in a case study paper is to demonstrate that you have thoroughly identified and synthesized prior studies in relation to explaining the relevance of the case in addressing the research problem.

III.  Method

In this section, you explain why you selected a particular case [i.e., subject of analysis] and the strategy you used to identify and ultimately decide that your case was appropriate in addressing the research problem. The way you describe the methods used varies depending on the type of subject of analysis that constitutes your case study.

If your subject of analysis is an incident or event . In the social and behavioral sciences, the event or incident that represents the case to be studied is usually bounded by time and place, with a clear beginning and end and with an identifiable location or position relative to its surroundings. The subject of analysis can be a rare or critical event or it can focus on a typical or regular event. The purpose of studying a rare event is to illuminate new ways of thinking about the broader research problem or to test a hypothesis. Critical incident case studies must describe the method by which you identified the event and explain the process by which you determined the validity of this case to inform broader perspectives about the research problem or to reveal new findings. However, the event does not have to be a rare or uniquely significant to support new thinking about the research problem or to challenge an existing hypothesis. For example, Walo, Bull, and Breen conducted a case study to identify and evaluate the direct and indirect economic benefits and costs of a local sports event in the City of Lismore, New South Wales, Australia. The purpose of their study was to provide new insights from measuring the impact of a typical local sports event that prior studies could not measure well because they focused on large "mega-events." Whether the event is rare or not, the methods section should include an explanation of the following characteristics of the event: a) when did it take place; b) what were the underlying circumstances leading to the event; and, c) what were the consequences of the event in relation to the research problem.

If your subject of analysis is a person. Explain why you selected this particular individual to be studied and describe what experiences they have had that provide an opportunity to advance new understandings about the research problem. Mention any background about this person which might help the reader understand the significance of their experiences that make them worthy of study. This includes describing the relationships this person has had with other people, institutions, and/or events that support using them as the subject for a case study research paper. It is particularly important to differentiate the person as the subject of analysis from others and to succinctly explain how the person relates to examining the research problem [e.g., why is one politician in a particular local election used to show an increase in voter turnout from any other candidate running in the election]. Note that these issues apply to a specific group of people used as a case study unit of analysis [e.g., a classroom of students].

If your subject of analysis is a place. In general, a case study that investigates a place suggests a subject of analysis that is unique or special in some way and that this uniqueness can be used to build new understanding or knowledge about the research problem. A case study of a place must not only describe its various attributes relevant to the research problem [e.g., physical, social, historical, cultural, economic, political], but you must state the method by which you determined that this place will illuminate new understandings about the research problem. It is also important to articulate why a particular place as the case for study is being used if similar places also exist [i.e., if you are studying patterns of homeless encampments of veterans in open spaces, explain why you are studying Echo Park in Los Angeles rather than Griffith Park?]. If applicable, describe what type of human activity involving this place makes it a good choice to study [e.g., prior research suggests Echo Park has more homeless veterans].

If your subject of analysis is a phenomenon. A phenomenon refers to a fact, occurrence, or circumstance that can be studied or observed but with the cause or explanation to be in question. In this sense, a phenomenon that forms your subject of analysis can encompass anything that can be observed or presumed to exist but is not fully understood. In the social and behavioral sciences, the case usually focuses on human interaction within a complex physical, social, economic, cultural, or political system. For example, the phenomenon could be the observation that many vehicles used by ISIS fighters are small trucks with English language advertisements on them. The research problem could be that ISIS fighters are difficult to combat because they are highly mobile. The research questions could be how and by what means are these vehicles used by ISIS being supplied to the militants and how might supply lines to these vehicles be cut off? How might knowing the suppliers of these trucks reveal larger networks of collaborators and financial support? A case study of a phenomenon most often encompasses an in-depth analysis of a cause and effect that is grounded in an interactive relationship between people and their environment in some way.

NOTE:   The choice of the case or set of cases to study cannot appear random. Evidence that supports the method by which you identified and chose your subject of analysis should clearly support investigation of the research problem and linked to key findings from your literature review. Be sure to cite any studies that helped you determine that the case you chose was appropriate for examining the problem.

IV.  Discussion

The main elements of your discussion section are generally the same as any research paper, but centered around interpreting and drawing conclusions about the key findings from your analysis of the case study. Note that a general social sciences research paper may contain a separate section to report findings. However, in a paper designed around a case study, it is common to combine a description of the results with the discussion about their implications. The objectives of your discussion section should include the following:

Reiterate the Research Problem/State the Major Findings Briefly reiterate the research problem you are investigating and explain why the subject of analysis around which you designed the case study were used. You should then describe the findings revealed from your study of the case using direct, declarative, and succinct proclamation of the study results. Highlight any findings that were unexpected or especially profound.

Explain the Meaning of the Findings and Why They are Important Systematically explain the meaning of your case study findings and why you believe they are important. Begin this part of the section by repeating what you consider to be your most important or surprising finding first, then systematically review each finding. Be sure to thoroughly extrapolate what your analysis of the case can tell the reader about situations or conditions beyond the actual case that was studied while, at the same time, being careful not to misconstrue or conflate a finding that undermines the external validity of your conclusions.

Relate the Findings to Similar Studies No study in the social sciences is so novel or possesses such a restricted focus that it has absolutely no relation to previously published research. The discussion section should relate your case study results to those found in other studies, particularly if questions raised from prior studies served as the motivation for choosing your subject of analysis. This is important because comparing and contrasting the findings of other studies helps support the overall importance of your results and it highlights how and in what ways your case study design and the subject of analysis differs from prior research about the topic.

Consider Alternative Explanations of the Findings Remember that the purpose of social science research is to discover and not to prove. When writing the discussion section, you should carefully consider all possible explanations revealed by the case study results, rather than just those that fit your hypothesis or prior assumptions and biases. Be alert to what the in-depth analysis of the case may reveal about the research problem, including offering a contrarian perspective to what scholars have stated in prior research if that is how the findings can be interpreted from your case.

Acknowledge the Study's Limitations You can state the study's limitations in the conclusion section of your paper but describing the limitations of your subject of analysis in the discussion section provides an opportunity to identify the limitations and explain why they are not significant. This part of the discussion section should also note any unanswered questions or issues your case study could not address. More detailed information about how to document any limitations to your research can be found here .

Suggest Areas for Further Research Although your case study may offer important insights about the research problem, there are likely additional questions related to the problem that remain unanswered or findings that unexpectedly revealed themselves as a result of your in-depth analysis of the case. Be sure that the recommendations for further research are linked to the research problem and that you explain why your recommendations are valid in other contexts and based on the original assumptions of your study.

V.  Conclusion

As with any research paper, you should summarize your conclusion in clear, simple language; emphasize how the findings from your case study differs from or supports prior research and why. Do not simply reiterate the discussion section. Provide a synthesis of key findings presented in the paper to show how these converge to address the research problem. If you haven't already done so in the discussion section, be sure to document the limitations of your case study and any need for further research.

The function of your paper's conclusion is to: 1) reiterate the main argument supported by the findings from your case study; 2) state clearly the context, background, and necessity of pursuing the research problem using a case study design in relation to an issue, controversy, or a gap found from reviewing the literature; and, 3) provide a place to persuasively and succinctly restate the significance of your research problem, given that the reader has now been presented with in-depth information about the topic.

Consider the following points to help ensure your conclusion is appropriate:

• If the argument or purpose of your paper is complex, you may need to summarize these points for your reader.
• If prior to your conclusion, you have not yet explained the significance of your findings or if you are proceeding inductively, use the conclusion of your paper to describe your main points and explain their significance.
• Move from a detailed to a general level of consideration of the case study's findings that returns the topic to the context provided by the introduction or within a new context that emerges from your case study findings.

Note that, depending on the discipline you are writing in or the preferences of your professor, the concluding paragraph may contain your final reflections on the evidence presented as it applies to practice or on the essay's central research problem. However, the nature of being introspective about the subject of analysis you have investigated will depend on whether you are explicitly asked to express your observations in this way.

Problems to Avoid

Overgeneralization One of the goals of a case study is to lay a foundation for understanding broader trends and issues applied to similar circumstances. However, be careful when drawing conclusions from your case study. They must be evidence-based and grounded in the results of the study; otherwise, it is merely speculation. Looking at a prior example, it would be incorrect to state that a factor in improving girls access to education in Azerbaijan and the policy implications this may have for improving access in other Muslim nations is due to girls access to social media if there is no documentary evidence from your case study to indicate this. There may be anecdotal evidence that retention rates were better for girls who were engaged with social media, but this observation would only point to the need for further research and would not be a definitive finding if this was not a part of your original research agenda.

Failure to Document Limitations No case is going to reveal all that needs to be understood about a research problem. Therefore, just as you have to clearly state the limitations of a general research study , you must describe the specific limitations inherent in the subject of analysis. For example, the case of studying how women conceptualize the need for water conservation in a village in Uganda could have limited application in other cultural contexts or in areas where fresh water from rivers or lakes is plentiful and, therefore, conservation is understood more in terms of managing access rather than preserving access to a scarce resource.

Failure to Extrapolate All Possible Implications Just as you don't want to over-generalize from your case study findings, you also have to be thorough in the consideration of all possible outcomes or recommendations derived from your findings. If you do not, your reader may question the validity of your analysis, particularly if you failed to document an obvious outcome from your case study research. For example, in the case of studying the accident at the railroad crossing to evaluate where and what types of warning signals should be located, you failed to take into consideration speed limit signage as well as warning signals. When designing your case study, be sure you have thoroughly addressed all aspects of the problem and do not leave gaps in your analysis that leave the reader questioning the results.

Case Studies. Writing@CSU. Colorado State University; Gerring, John. Case Study Research: Principles and Practices . New York: Cambridge University Press, 2007; Merriam, Sharan B. Qualitative Research and Case Study Applications in Education . Rev. ed. San Francisco, CA: Jossey-Bass, 1998; Miller, Lisa L. “The Use of Case Studies in Law and Social Science Research.” Annual Review of Law and Social Science 14 (2018): TBD; Mills, Albert J., Gabrielle Durepos, and Eiden Wiebe, editors. Encyclopedia of Case Study Research . Thousand Oaks, CA: SAGE Publications, 2010; Putney, LeAnn Grogan. "Case Study." In Encyclopedia of Research Design , Neil J. Salkind, editor. (Thousand Oaks, CA: SAGE Publications, 2010), pp. 116-120; Simons, Helen. Case Study Research in Practice . London: SAGE Publications, 2009;  Kratochwill,  Thomas R. and Joel R. Levin, editors. Single-Case Research Design and Analysis: New Development for Psychology and Education .  Hilldsale, NJ: Lawrence Erlbaum Associates, 1992; Swanborn, Peter G. Case Study Research: What, Why and How? London : SAGE, 2010; Yin, Robert K. Case Study Research: Design and Methods . 6th edition. Los Angeles, CA, SAGE Publications, 2014; Walo, Maree, Adrian Bull, and Helen Breen. “Achieving Economic Benefits at Local Events: A Case Study of a Local Sports Event.” Festival Management and Event Tourism 4 (1996): 95-106.

Writing Tip

At Least Five Misconceptions about Case Study Research

Social science case studies are often perceived as limited in their ability to create new knowledge because they are not randomly selected and findings cannot be generalized to larger populations. Flyvbjerg examines five misunderstandings about case study research and systematically "corrects" each one. To quote, these are:

Misunderstanding 1 :  General, theoretical [context-independent] knowledge is more valuable than concrete, practical [context-dependent] knowledge. Misunderstanding 2 :  One cannot generalize on the basis of an individual case; therefore, the case study cannot contribute to scientific development. Misunderstanding 3 :  The case study is most useful for generating hypotheses; that is, in the first stage of a total research process, whereas other methods are more suitable for hypotheses testing and theory building. Misunderstanding 4 :  The case study contains a bias toward verification, that is, a tendency to confirm the researcher’s preconceived notions. Misunderstanding 5 :  It is often difficult to summarize and develop general propositions and theories on the basis of specific case studies [p. 221].

While writing your paper, think introspectively about how you addressed these misconceptions because to do so can help you strengthen the validity and reliability of your research by clarifying issues of case selection, the testing and challenging of existing assumptions, the interpretation of key findings, and the summation of case outcomes. Think of a case study research paper as a complete, in-depth narrative about the specific properties and key characteristics of your subject of analysis applied to the research problem.

Flyvbjerg, Bent. “Five Misunderstandings About Case-Study Research.” Qualitative Inquiry 12 (April 2006): 219-245.

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Methodology or method? A critical review of qualitative case study reports

Despite on-going debate about credibility, and reported limitations in comparison to other approaches, case study is an increasingly popular approach among qualitative researchers. We critically analysed the methodological descriptions of published case studies. Three high-impact qualitative methods journals were searched to locate case studies published in the past 5 years; 34 were selected for analysis. Articles were categorized as health and health services ( n= 12), social sciences and anthropology ( n= 7), or methods ( n= 15) case studies. The articles were reviewed using an adapted version of established criteria to determine whether adequate methodological justification was present, and if study aims, methods, and reported findings were consistent with a qualitative case study approach. Findings were grouped into five themes outlining key methodological issues: case study methodology or method, case of something particular and case selection, contextually bound case study, researcher and case interactions and triangulation, and study design inconsistent with methodology reported. Improved reporting of case studies by qualitative researchers will advance the methodology for the benefit of researchers and practitioners.

Case study research is an increasingly popular approach among qualitative researchers (Thomas, 2011 ). Several prominent authors have contributed to methodological developments, which has increased the popularity of case study approaches across disciplines (Creswell, 2013b ; Denzin & Lincoln, 2011b ; Merriam, 2009 ; Ragin & Becker, 1992 ; Stake, 1995 ; Yin, 2009 ). Current qualitative case study approaches are shaped by paradigm, study design, and selection of methods, and, as a result, case studies in the published literature vary. Differences between published case studies can make it difficult for researchers to define and understand case study as a methodology.

Experienced qualitative researchers have identified case study research as a stand-alone qualitative approach (Denzin & Lincoln, 2011b ). Case study research has a level of flexibility that is not readily offered by other qualitative approaches such as grounded theory or phenomenology. Case studies are designed to suit the case and research question and published case studies demonstrate wide diversity in study design. There are two popular case study approaches in qualitative research. The first, proposed by Stake ( 1995 ) and Merriam ( 2009 ), is situated in a social constructivist paradigm, whereas the second, by Yin ( 2012 ), Flyvbjerg ( 2011 ), and Eisenhardt ( 1989 ), approaches case study from a post-positivist viewpoint. Scholarship from both schools of inquiry has contributed to the popularity of case study and development of theoretical frameworks and principles that characterize the methodology.

The diversity of case studies reported in the published literature, and on-going debates about credibility and the use of case study in qualitative research practice, suggests that differences in perspectives on case study methodology may prevent researchers from developing a mutual understanding of practice and rigour. In addition, discussion about case study limitations has led some authors to query whether case study is indeed a methodology (Luck, Jackson, & Usher, 2006 ; Meyer, 2001 ; Thomas, 2010 ; Tight, 2010 ). Methodological discussion of qualitative case study research is timely, and a review is required to analyse and understand how this methodology is applied in the qualitative research literature. The aims of this study were to review methodological descriptions of published qualitative case studies, to review how the case study methodological approach was applied, and to identify issues that need to be addressed by researchers, editors, and reviewers. An outline of the current definitions of case study and an overview of the issues proposed in the qualitative methodological literature are provided to set the scene for the review.

Definitions of qualitative case study research

Case study research is an investigation and analysis of a single or collective case, intended to capture the complexity of the object of study (Stake, 1995 ). Qualitative case study research, as described by Stake ( 1995 ), draws together “naturalistic, holistic, ethnographic, phenomenological, and biographic research methods” in a bricoleur design, or in his words, “a palette of methods” (Stake, 1995 , pp. xi–xii). Case study methodology maintains deep connections to core values and intentions and is “particularistic, descriptive and heuristic” (Merriam, 2009 , p. 46).

As a study design, case study is defined by interest in individual cases rather than the methods of inquiry used. The selection of methods is informed by researcher and case intuition and makes use of naturally occurring sources of knowledge, such as people or observations of interactions that occur in the physical space (Stake, 1998 ). Thomas ( 2011 ) suggested that “analytical eclecticism” is a defining factor (p. 512). Multiple data collection and analysis methods are adopted to further develop and understand the case, shaped by context and emergent data (Stake, 1995 ). This qualitative approach “explores a real-life, contemporary bounded system (a case ) or multiple bounded systems (cases) over time, through detailed, in-depth data collection involving multiple sources of information … and reports a case description and case themes ” (Creswell, 2013b , p. 97). Case study research has been defined by the unit of analysis, the process of study, and the outcome or end product, all essentially the case (Merriam, 2009 ).

The case is an object to be studied for an identified reason that is peculiar or particular. Classification of the case and case selection procedures informs development of the study design and clarifies the research question. Stake ( 1995 ) proposed three types of cases and study design frameworks. These include the intrinsic case, the instrumental case, and the collective instrumental case. The intrinsic case is used to understand the particulars of a single case, rather than what it represents. An instrumental case study provides insight on an issue or is used to refine theory. The case is selected to advance understanding of the object of interest. A collective refers to an instrumental case which is studied as multiple, nested cases, observed in unison, parallel, or sequential order. More than one case can be simultaneously studied; however, each case study is a concentrated, single inquiry, studied holistically in its own entirety (Stake, 1995 , 1998 ).

Researchers who use case study are urged to seek out what is common and what is particular about the case. This involves careful and in-depth consideration of the nature of the case, historical background, physical setting, and other institutional and political contextual factors (Stake, 1998 ). An interpretive or social constructivist approach to qualitative case study research supports a transactional method of inquiry, where the researcher has a personal interaction with the case. The case is developed in a relationship between the researcher and informants, and presented to engage the reader, inviting them to join in this interaction and in case discovery (Stake, 1995 ). A postpositivist approach to case study involves developing a clear case study protocol with careful consideration of validity and potential bias, which might involve an exploratory or pilot phase, and ensures that all elements of the case are measured and adequately described (Yin, 2009 , 2012 ).

Current methodological issues in qualitative case study research

The future of qualitative research will be influenced and constructed by the way research is conducted, and by what is reviewed and published in academic journals (Morse, 2011 ). If case study research is to further develop as a principal qualitative methodological approach, and make a valued contribution to the field of qualitative inquiry, issues related to methodological credibility must be considered. Researchers are required to demonstrate rigour through adequate descriptions of methodological foundations. Case studies published without sufficient detail for the reader to understand the study design, and without rationale for key methodological decisions, may lead to research being interpreted as lacking in quality or credibility (Hallberg, 2013 ; Morse, 2011 ).

There is a level of artistic license that is embraced by qualitative researchers and distinguishes practice, which nurtures creativity, innovation, and reflexivity (Denzin & Lincoln, 2011b ; Morse, 2009 ). Qualitative research is “inherently multimethod” (Denzin & Lincoln, 2011a , p. 5); however, with this creative freedom, it is important for researchers to provide adequate description for methodological justification (Meyer, 2001 ). This includes paradigm and theoretical perspectives that have influenced study design. Without adequate description, study design might not be understood by the reader, and can appear to be dishonest or inaccurate. Reviewers and readers might be confused by the inconsistent or inappropriate terms used to describe case study research approach and methods, and be distracted from important study findings (Sandelowski, 2000 ). This issue extends beyond case study research, and others have noted inconsistencies in reporting of methodology and method by qualitative researchers. Sandelowski ( 2000 , 2010 ) argued for accurate identification of qualitative description as a research approach. She recommended that the selected methodology should be harmonious with the study design, and be reflected in methods and analysis techniques. Similarly, Webb and Kevern ( 2000 ) uncovered inconsistencies in qualitative nursing research with focus group methods, recommending that methodological procedures must cite seminal authors and be applied with respect to the selected theoretical framework. Incorrect labelling using case study might stem from the flexibility in case study design and non-directional character relative to other approaches (Rosenberg & Yates, 2007 ). Methodological integrity is required in design of qualitative studies, including case study, to ensure study rigour and to enhance credibility of the field (Morse, 2011 ).

Case study has been unnecessarily devalued by comparisons with statistical methods (Eisenhardt, 1989 ; Flyvbjerg, 2006 , 2011 ; Jensen & Rodgers, 2001 ; Piekkari, Welch, & Paavilainen, 2009 ; Tight, 2010 ; Yin, 1999 ). It is reputed to be the “the weak sibling” in comparison to other, more rigorous, approaches (Yin, 2009 , p. xiii). Case study is not an inherently comparative approach to research. The objective is not statistical research, and the aim is not to produce outcomes that are generalizable to all populations (Thomas, 2011 ). Comparisons between case study and statistical research do little to advance this qualitative approach, and fail to recognize its inherent value, which can be better understood from the interpretive or social constructionist viewpoint of other authors (Merriam, 2009 ; Stake, 1995 ). Building on discussions relating to “fuzzy” (Bassey, 2001 ), or naturalistic generalizations (Stake, 1978 ), or transference of concepts and theories (Ayres, Kavanaugh, & Knafl, 2003 ; Morse et al., 2011 ) would have more relevance.

Case study research has been used as a catch-all design to justify or add weight to fundamental qualitative descriptive studies that do not fit with other traditional frameworks (Merriam, 2009 ). A case study has been a “convenient label for our research—when we ‘can't think of anything ‘better”—in an attempt to give it [qualitative methodology] some added respectability” (Tight, 2010 , p. 337). Qualitative case study research is a pliable approach (Merriam, 2009 ; Meyer, 2001 ; Stake, 1995 ), and has been likened to a “curious methodological limbo” (Gerring, 2004 , p. 341) or “paradigmatic bridge” (Luck et al., 2006 , p. 104), that is on the borderline between postpositivist and constructionist interpretations. This has resulted in inconsistency in application, which indicates that flexibility comes with limitations (Meyer, 2001 ), and the open nature of case study research might be off-putting to novice researchers (Thomas, 2011 ). The development of a well-(in)formed theoretical framework to guide a case study should improve consistency, rigour, and trust in studies published in qualitative research journals (Meyer, 2001 ).

Assessment of rigour

The purpose of this study was to analyse the methodological descriptions of case studies published in qualitative methods journals. To do this we needed to develop a suitable framework, which used existing, established criteria for appraising qualitative case study research rigour (Creswell, 2013b ; Merriam, 2009 ; Stake, 1995 ). A number of qualitative authors have developed concepts and criteria that are used to determine whether a study is rigorous (Denzin & Lincoln, 2011b ; Lincoln, 1995 ; Sandelowski & Barroso, 2002 ). The criteria proposed by Stake ( 1995 ) provide a framework for readers and reviewers to make judgements regarding case study quality, and identify key characteristics essential for good methodological rigour. Although each of the factors listed in Stake's criteria could enhance the quality of a qualitative research report, in Table I we present an adapted criteria used in this study, which integrates more recent work by Merriam ( 2009 ) and Creswell ( 2013b ). Stake's ( 1995 ) original criteria were separated into two categories. The first list of general criteria is “relevant for all qualitative research.” The second list, “high relevance to qualitative case study research,” was the criteria that we decided had higher relevance to case study research. This second list was the main criteria used to assess the methodological descriptions of the case studies reviewed. The complete table has been preserved so that the reader can determine how the original criteria were adapted.

Framework for assessing quality in qualitative case study research.

Adapted from Stake ( 1995 , p. 131).

Study design

The critical review method described by Grant and Booth ( 2009 ) was used, which is appropriate for the assessment of research quality, and is used for literature analysis to inform research and practice. This type of review goes beyond the mapping and description of scoping or rapid reviews, to include “analysis and conceptual innovation” (Grant & Booth, 2009 , p. 93). A critical review is used to develop existing, or produce new, hypotheses or models. This is different to systematic reviews that answer clinical questions. It is used to evaluate existing research and competing ideas, to provide a “launch pad” for conceptual development and “subsequent testing” (Grant & Booth, 2009 , p. 93).

Qualitative methods journals were located by a search of the 2011 ISI Journal Citation Reports in Social Science, via the database Web of Knowledge (see m.webofknowledge.com). No “qualitative research methods” category existed in the citation reports; therefore, a search of all categories was performed using the term “qualitative.” In Table II , we present the qualitative methods journals located, ranked by impact factor. The highest ranked journals were selected for searching. We acknowledge that the impact factor ranking system might not be the best measure of journal quality (Cheek, Garnham, & Quan, 2006 ); however, this was the most appropriate and accessible method available.

International Journal of Qualitative Studies on Health and Well-being.

Search strategy

In March 2013, searches of the journals, Qualitative Health Research , Qualitative Research , and Qualitative Inquiry were completed to retrieve studies with “case study” in the abstract field. The search was limited to the past 5 years (1 January 2008 to 1 March 2013). The objective was to locate published qualitative case studies suitable for assessment using the adapted criterion. Viewpoints, commentaries, and other article types were excluded from review. Title and abstracts of the 45 retrieved articles were read by the first author, who identified 34 empirical case studies for review. All authors reviewed the 34 studies to confirm selection and categorization. In Table III , we present the 34 case studies grouped by journal, and categorized by research topic, including health sciences, social sciences and anthropology, and methods research. There was a discrepancy in categorization of one article on pedagogy and a new teaching method published in Qualitative Inquiry (Jorrín-Abellán, Rubia-Avi, Anguita-Martínez, Gómez-Sánchez, & Martínez-Mones, 2008 ). Consensus was to allocate to the methods category.

Outcomes of search of qualitative methods journals.

In Table III , the number of studies located, and final numbers selected for review have been reported. Qualitative Health Research published the most empirical case studies ( n= 16). In the health category, there were 12 case studies of health conditions, health services, and health policy issues, all published in Qualitative Health Research . Seven case studies were categorized as social sciences and anthropology research, which combined case study with biography and ethnography methodologies. All three journals published case studies on methods research to illustrate a data collection or analysis technique, methodological procedure, or related issue.

The methodological descriptions of 34 case studies were critically reviewed using the adapted criteria. All articles reviewed contained a description of study methods; however, the length, amount of detail, and position of the description in the article varied. Few studies provided an accurate description and rationale for using a qualitative case study approach. In the 34 case studies reviewed, three described a theoretical framework informed by Stake ( 1995 ), two by Yin ( 2009 ), and three provided a mixed framework informed by various authors, which might have included both Yin and Stake. Few studies described their case study design, or included a rationale that explained why they excluded or added further procedures, and whether this was to enhance the study design, or to better suit the research question. In 26 of the studies no reference was provided to principal case study authors. From reviewing the description of methods, few authors provided a description or justification of case study methodology that demonstrated how their study was informed by the methodological literature that exists on this approach.

The methodological descriptions of each study were reviewed using the adapted criteria, and the following issues were identified: case study methodology or method; case of something particular and case selection; contextually bound case study; researcher and case interactions and triangulation; and, study design inconsistent with methodology. An outline of how the issues were developed from the critical review is provided, followed by a discussion of how these relate to the current methodological literature.

Case study methodology or method

A third of the case studies reviewed appeared to use a case report method, not case study methodology as described by principal authors (Creswell, 2013b ; Merriam, 2009 ; Stake, 1995 ; Yin, 2009 ). Case studies were identified as a case report because of missing methodological detail and by review of the study aims and purpose. These reports presented data for small samples of no more than three people, places or phenomenon. Four studies, or “case reports” were single cases selected retrospectively from larger studies (Bronken, Kirkevold, Martinsen, & Kvigne, 2012 ; Coltart & Henwood, 2012 ; Hooghe, Neimeyer, & Rober, 2012 ; Roscigno et al., 2012 ). Case reports were not a case of something, instead were a case demonstration or an example presented in a report. These reports presented outcomes, and reported on how the case could be generalized. Descriptions focussed on the phenomena, rather than the case itself, and did not appear to study the case in its entirety.

Case reports had minimal in-text references to case study methodology, and were informed by other qualitative traditions or secondary sources (Adamson & Holloway, 2012 ; Buzzanell & D'Enbeau, 2009 ; Nagar-Ron & Motzafi-Haller, 2011 ). This does not suggest that case study methodology cannot be multimethod, however, methodology should be consistent in design, be clearly described (Meyer, 2001 ; Stake, 1995 ), and maintain focus on the case (Creswell, 2013b ).

To demonstrate how case reports were identified, three examples are provided. The first, Yeh ( 2013 ) described their study as, “the examination of the emergence of vegetarianism in Victorian England serves as a case study to reveal the relationships between boundaries and entities” (p. 306). The findings were a historical case report, which resulted from an ethnographic study of vegetarianism. Cunsolo Willox, Harper, Edge, ‘My Word’: Storytelling and Digital Media Lab, and Rigolet Inuit Community Government (2013) used “a case study that illustrates the usage of digital storytelling within an Inuit community” (p. 130). This case study reported how digital storytelling can be used with indigenous communities as a participatory method to illuminate the benefits of this method for other studies. This “case study was conducted in the Inuit community” but did not include the Inuit community in case analysis (Cunsolo Willox et al., 2013 , p. 130). Bronken et al. ( 2012 ) provided a single case report to demonstrate issues observed in a larger clinical study of aphasia and stroke, without adequate case description or analysis.

Case study of something particular and case selection

Case selection is a precursor to case analysis, which needs to be presented as a convincing argument (Merriam, 2009 ). Descriptions of the case were often not adequate to ascertain why the case was selected, or whether it was a particular exemplar or outlier (Thomas, 2011 ). In a number of case studies in the health and social science categories, it was not explicit whether the case was of something particular, or peculiar to their discipline or field (Adamson & Holloway, 2012 ; Bronken et al., 2012 ; Colón-Emeric et al., 2010 ; Jackson, Botelho, Welch, Joseph, & Tennstedt, 2012 ; Mawn et al., 2010 ; Snyder-Young, 2011 ). There were exceptions in the methods category ( Table III ), where cases were selected by researchers to report on a new or innovative method. The cases emerged through heuristic study, and were reported to be particular, relative to the existing methods literature (Ajodhia-Andrews & Berman, 2009 ; Buckley & Waring, 2013 ; Cunsolo Willox et al., 2013 ; De Haene, Grietens, & Verschueren, 2010 ; Gratton & O'Donnell, 2011 ; Sumsion, 2013 ; Wimpenny & Savin-Baden, 2012 ).

Case selection processes were sometimes insufficient to understand why the case was selected from the global population of cases, or what study of this case would contribute to knowledge as compared with other possible cases (Adamson & Holloway, 2012 ; Bronken et al., 2012 ; Colón-Emeric et al., 2010 ; Jackson et al., 2012 ; Mawn et al., 2010 ). In two studies, local cases were selected (Barone, 2010 ; Fourie & Theron, 2012 ) because the researcher was familiar with and had access to the case. Possible limitations of a convenience sample were not acknowledged. Purposeful sampling was used to recruit participants within the case of one study, but not of the case itself (Gallagher et al., 2013 ). Random sampling was completed for case selection in two studies (Colón-Emeric et al., 2010 ; Jackson et al., 2012 ), which has limited meaning in interpretive qualitative research.

To demonstrate how researchers provided a good justification for the selection of case study approaches, four examples are provided. The first, cases of residential care homes, were selected because of reported occurrences of mistreatment, which included residents being locked in rooms at night (Rytterström, Unosson, & Arman, 2013 ). Roscigno et al. ( 2012 ) selected cases of parents who were admitted for early hospitalization in neonatal intensive care with a threatened preterm delivery before 26 weeks. Hooghe et al. ( 2012 ) used random sampling to select 20 couples that had experienced the death of a child; however, the case study was of one couple and a particular metaphor described only by them. The final example, Coltart and Henwood ( 2012 ), provided a detailed account of how they selected two cases from a sample of 46 fathers based on personal characteristics and beliefs. They described how the analysis of the two cases would contribute to their larger study on first time fathers and parenting.

Contextually bound case study

The limits or boundaries of the case are a defining factor of case study methodology (Merriam, 2009 ; Ragin & Becker, 1992 ; Stake, 1995 ; Yin, 2009 ). Adequate contextual description is required to understand the setting or context in which the case is revealed. In the health category, case studies were used to illustrate a clinical phenomenon or issue such as compliance and health behaviour (Colón-Emeric et al., 2010 ; D'Enbeau, Buzzanell, & Duckworth, 2010 ; Gallagher et al., 2013 ; Hooghe et al., 2012 ; Jackson et al., 2012 ; Roscigno et al., 2012 ). In these case studies, contextual boundaries, such as physical and institutional descriptions, were not sufficient to understand the case as a holistic system, for example, the general practitioner (GP) clinic in Gallagher et al. ( 2013 ), or the nursing home in Colón-Emeric et al. ( 2010 ). Similarly, in the social science and methods categories, attention was paid to some components of the case context, but not others, missing important information required to understand the case as a holistic system (Alexander, Moreira, & Kumar, 2012 ; Buzzanell & D'Enbeau, 2009 ; Nairn & Panelli, 2009 ; Wimpenny & Savin-Baden, 2012 ).

In two studies, vicarious experience or vignettes (Nairn & Panelli, 2009 ) and images (Jorrín-Abellán et al., 2008 ) were effective to support description of context, and might have been a useful addition for other case studies. Missing contextual boundaries suggests that the case might not be adequately defined. Additional information, such as the physical, institutional, political, and community context, would improve understanding of the case (Stake, 1998 ). In Boxes 1 and 2 , we present brief synopses of two studies that were reviewed, which demonstrated a well bounded case. In Box 1 , Ledderer ( 2011 ) used a qualitative case study design informed by Stake's tradition. In Box 2 , Gillard, Witt, and Watts ( 2011 ) were informed by Yin's tradition. By providing a brief outline of the case studies in Boxes 1 and 2 , we demonstrate how effective case boundaries can be constructed and reported, which may be of particular interest to prospective case study researchers.

Article synopsis of case study research using Stake's tradition

Ledderer ( 2011 ) used a qualitative case study research design, informed by modern ethnography. The study is bounded to 10 general practice clinics in Denmark, who had received federal funding to implement preventative care services based on a Motivational Interviewing intervention. The researcher question focussed on “why is it so difficult to create change in medical practice?” (Ledderer, 2011 , p. 27). The study context was adequately described, providing detail on the general practitioner (GP) clinics and relevant political and economic influences. Methodological decisions are described in first person narrative, providing insight on researcher perspectives and interaction with the case. Forty-four interviews were conducted, which focussed on how GPs conducted consultations, and the form, nature and content, rather than asking their opinion or experience (Ledderer, 2011 , p. 30). The duration and intensity of researcher immersion in the case enhanced depth of description and trustworthiness of study findings. Analysis was consistent with Stake's tradition, and the researcher provided examples of inquiry techniques used to challenge assumptions about emerging themes. Several other seminal qualitative works were cited. The themes and typology constructed are rich in narrative data and storytelling by clinic staff, demonstrating individual clinic experiences as well as shared meanings and understandings about changing from a biomedical to psychological approach to preventative health intervention. Conclusions make note of social and cultural meanings and lessons learned, which might not have been uncovered using a different methodology.

Article synopsis of case study research using Yin's tradition

Gillard et al. ( 2011 ) study of camps for adolescents living with HIV/AIDs provided a good example of Yin's interpretive case study approach. The context of the case is bounded by the three summer camps of which the researchers had prior professional involvement. A case study protocol was developed that used multiple methods to gather information at three data collection points coinciding with three youth camps (Teen Forum, Discover Camp, and Camp Strong). Gillard and colleagues followed Yin's ( 2009 ) principles, using a consistent data protocol that enhanced cross-case analysis. Data described the young people, the camp physical environment, camp schedule, objectives and outcomes, and the staff of three youth camps. The findings provided a detailed description of the context, with less detail of individual participants, including insight into researcher's interpretations and methodological decisions throughout the data collection and analysis process. Findings provided the reader with a sense of “being there,” and are discovered through constant comparison of the case with the research issues; the case is the unit of analysis. There is evidence of researcher immersion in the case, and Gillard reports spending significant time in the field in a naturalistic and integrated youth mentor role.

This case study is not intended to have a significant impact on broader health policy, although does have implications for health professionals working with adolescents. Study conclusions will inform future camps for young people with chronic disease, and practitioners are able to compare similarities between this case and their own practice (for knowledge translation). No limitations of this article were reported. Limitations related to publication of this case study were that it was 20 pages long and used three tables to provide sufficient description of the camp and program components, and relationships with the research issue.

Researcher and case interactions and triangulation

Researcher and case interactions and transactions are a defining feature of case study methodology (Stake, 1995 ). Narrative stories, vignettes, and thick description are used to provoke vicarious experience and a sense of being there with the researcher in their interaction with the case. Few of the case studies reviewed provided details of the researcher's relationship with the case, researcher–case interactions, and how these influenced the development of the case study (Buzzanell & D'Enbeau, 2009 ; D'Enbeau et al., 2010 ; Gallagher et al., 2013 ; Gillard et al., 2011 ; Ledderer, 2011 ; Nagar-Ron & Motzafi-Haller, 2011 ). The role and position of the researcher needed to be self-examined and understood by readers, to understand how this influenced interactions with participants, and to determine what triangulation is needed (Merriam, 2009 ; Stake, 1995 ).

Gillard et al. ( 2011 ) provided a good example of triangulation, comparing data sources in a table (p. 1513). Triangulation of sources was used to reveal as much depth as possible in the study by Nagar-Ron and Motzafi-Haller ( 2011 ), while also enhancing confirmation validity. There were several case studies that would have benefited from improved range and use of data sources, and descriptions of researcher–case interactions (Ajodhia-Andrews & Berman, 2009 ; Bronken et al., 2012 ; Fincham, Scourfield, & Langer, 2008 ; Fourie & Theron, 2012 ; Hooghe et al., 2012 ; Snyder-Young, 2011 ; Yeh, 2013 ).

Study design inconsistent with methodology

Good, rigorous case studies require a strong methodological justification (Meyer, 2001 ) and a logical and coherent argument that defines paradigm, methodological position, and selection of study methods (Denzin & Lincoln, 2011b ). Methodological justification was insufficient in several of the studies reviewed (Barone, 2010 ; Bronken et al., 2012 ; Hooghe et al., 2012 ; Mawn et al., 2010 ; Roscigno et al., 2012 ; Yeh, 2013 ). This was judged by the absence, or inadequate or inconsistent reference to case study methodology in-text.

In six studies, the methodological justification provided did not relate to case study. There were common issues identified. Secondary sources were used as primary methodological references indicating that study design might not have been theoretically sound (Colón-Emeric et al., 2010 ; Coltart & Henwood, 2012 ; Roscigno et al., 2012 ; Snyder-Young, 2011 ). Authors and sources cited in methodological descriptions were inconsistent with the actual study design and practices used (Fourie & Theron, 2012 ; Hooghe et al., 2012 ; Jorrín-Abellán et al., 2008 ; Mawn et al., 2010 ; Rytterström et al., 2013 ; Wimpenny & Savin-Baden, 2012 ). This occurred when researchers cited Stake or Yin, or both (Mawn et al., 2010 ; Rytterström et al., 2013 ), although did not follow their paradigmatic or methodological approach. In 26 studies there were no citations for a case study methodological approach.

The findings of this study have highlighted a number of issues for researchers. A considerable number of case studies reviewed were missing key elements that define qualitative case study methodology and the tradition cited. A significant number of studies did not provide a clear methodological description or justification relevant to case study. Case studies in health and social sciences did not provide sufficient information for the reader to understand case selection, and why this case was chosen above others. The context of the cases were not described in adequate detail to understand all relevant elements of the case context, which indicated that cases may have not been contextually bounded. There were inconsistencies between reported methodology, study design, and paradigmatic approach in case studies reviewed, which made it difficult to understand the study methodology and theoretical foundations. These issues have implications for methodological integrity and honesty when reporting study design, which are values of the qualitative research tradition and are ethical requirements (Wager & Kleinert, 2010a ). Poorly described methodological descriptions may lead the reader to misinterpret or discredit study findings, which limits the impact of the study, and, as a collective, hinders advancements in the broader qualitative research field.

The issues highlighted in our review build on current debates in the case study literature, and queries about the value of this methodology. Case study research can be situated within different paradigms or designed with an array of methods. In order to maintain the creativity and flexibility that is valued in this methodology, clearer descriptions of paradigm and theoretical position and methods should be provided so that study findings are not undervalued or discredited. Case study research is an interdisciplinary practice, which means that clear methodological descriptions might be more important for this approach than other methodologies that are predominantly driven by fewer disciplines (Creswell, 2013b ).

Authors frequently omit elements of methodologies and include others to strengthen study design, and we do not propose a rigid or purist ideology in this paper. On the contrary, we encourage new ideas about using case study, together with adequate reporting, which will advance the value and practice of case study. The implications of unclear methodological descriptions in the studies reviewed were that study design appeared to be inconsistent with reported methodology, and key elements required for making judgements of rigour were missing. It was not clear whether the deviations from methodological tradition were made by researchers to strengthen the study design, or because of misinterpretations. Morse ( 2011 ) recommended that innovations and deviations from practice are best made by experienced researchers, and that a novice might be unaware of the issues involved with making these changes. To perpetuate the tradition of case study research, applications in the published literature should have consistencies with traditional methodological constructions, and deviations should be described with a rationale that is inherent in study conduct and findings. Providing methodological descriptions that demonstrate a strong theoretical foundation and coherent study design will add credibility to the study, while ensuring the intrinsic meaning of case study is maintained.

The value of this review is that it contributes to discussion of whether case study is a methodology or method. We propose possible reasons why researchers might make this misinterpretation. Researchers may interchange the terms methods and methodology, and conduct research without adequate attention to epistemology and historical tradition (Carter & Little, 2007 ; Sandelowski, 2010 ). If the rich meaning that naming a qualitative methodology brings to the study is not recognized, a case study might appear to be inconsistent with the traditional approaches described by principal authors (Creswell, 2013a ; Merriam, 2009 ; Stake, 1995 ; Yin, 2009 ). If case studies are not methodologically and theoretically situated, then they might appear to be a case report.

Case reports are promoted by university and medical journals as a method of reporting on medical or scientific cases; guidelines for case reports are publicly available on websites ( http://www.hopkinsmedicine.org/institutional_review_board/guidelines_policies/guidelines/case_report.html ). The various case report guidelines provide a general criteria for case reports, which describes that this form of report does not meet the criteria of research, is used for retrospective analysis of up to three clinical cases, and is primarily illustrative and for educational purposes. Case reports can be published in academic journals, but do not require approval from a human research ethics committee. Traditionally, case reports describe a single case, to explain how and what occurred in a selected setting, for example, to illustrate a new phenomenon that has emerged from a larger study. A case report is not necessarily particular or the study of a case in its entirety, and the larger study would usually be guided by a different research methodology.

This description of a case report is similar to what was provided in some studies reviewed. This form of report lacks methodological grounding and qualities of research rigour. The case report has publication value in demonstrating an example and for dissemination of knowledge (Flanagan, 1999 ). However, case reports have different meaning and purpose to case study, which needs to be distinguished. Findings of our review suggest that the medical understanding of a case report has been confused with qualitative case study approaches.

In this review, a number of case studies did not have methodological descriptions that included key characteristics of case study listed in the adapted criteria, and several issues have been discussed. There have been calls for improvements in publication quality of qualitative research (Morse, 2011 ), and for improvements in peer review of submitted manuscripts (Carter & Little, 2007 ; Jasper, Vaismoradi, Bondas, & Turunen, 2013 ). The challenging nature of editor and reviewers responsibilities are acknowledged in the literature (Hames, 2013 ; Wager & Kleinert, 2010b ); however, review of case study methodology should be prioritized because of disputes on methodological value.

Authors using case study approaches are recommended to describe their theoretical framework and methods clearly, and to seek and follow specialist methodological advice when needed (Wager & Kleinert, 2010a ). Adequate page space for case study description would contribute to better publications (Gillard et al., 2011 ). Capitalizing on the ability to publish complementary resources should be considered.

Limitations of the review

There is a level of subjectivity involved in this type of review and this should be considered when interpreting study findings. Qualitative methods journals were selected because the aims and scope of these journals are to publish studies that contribute to methodological discussion and development of qualitative research. Generalist health and social science journals were excluded that might have contained good quality case studies. Journals in business or education were also excluded, although a review of case studies in international business journals has been published elsewhere (Piekkari et al., 2009 ).

The criteria used to assess the quality of the case studies were a set of qualitative indicators. A numerical or ranking system might have resulted in different results. Stake's ( 1995 ) criteria have been referenced elsewhere, and was deemed the best available (Creswell, 2013b ; Crowe et al., 2011 ). Not all qualitative studies are reported in a consistent way and some authors choose to report findings in a narrative form in comparison to a typical biomedical report style (Sandelowski & Barroso, 2002 ), if misinterpretations were made this may have affected the review.

Case study research is an increasingly popular approach among qualitative researchers, which provides methodological flexibility through the incorporation of different paradigmatic positions, study designs, and methods. However, whereas flexibility can be an advantage, a myriad of different interpretations has resulted in critics questioning the use of case study as a methodology. Using an adaptation of established criteria, we aimed to identify and assess the methodological descriptions of case studies in high impact, qualitative methods journals. Few articles were identified that applied qualitative case study approaches as described by experts in case study design. There were inconsistencies in methodology and study design, which indicated that researchers were confused whether case study was a methodology or a method. Commonly, there appeared to be confusion between case studies and case reports. Without clear understanding and application of the principles and key elements of case study methodology, there is a risk that the flexibility of the approach will result in haphazard reporting, and will limit its global application as a valuable, theoretically supported methodology that can be rigorously applied across disciplines and fields.

Conflict of interest and funding

The authors have not received any funding or benefits from industry or elsewhere to conduct this study.

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What the Case Study Method Really Teaches

• Nitin Nohria

Seven meta-skills that stick even if the cases fade from memory.

It’s been 100 years since Harvard Business School began using the case study method. Beyond teaching specific subject matter, the case study method excels in instilling meta-skills in students. This article explains the importance of seven such skills: preparation, discernment, bias recognition, judgement, collaboration, curiosity, and self-confidence.

During my decade as dean of Harvard Business School, I spent hundreds of hours talking with our alumni. To enliven these conversations, I relied on a favorite question: “What was the most important thing you learned from your time in our MBA program?”

• Nitin Nohria is the George F. Baker Jr. and Distinguished Service University Professor. He served as the 10th dean of Harvard Business School, from 2010 to 2020.

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How to Critically Discuss

Many students dread writing ‘critical discussion’ essays. This is partly because they don’t understand what is required of them.

So, how do you ‘critically discuss’ in an essay? Well, first and foremost, make sure you’ve truly considered all sides of the argument. You also need to think carefully about whether the source(s) you are discussing are reliable and valid. Finally, you need to develop a ‘thesis statement’ so that you can structure your critical discussion essay effectively.

Critical discussion essays can cause headaches, but they can also be incredibly rewarding if you approach them with the right attitude. Here are some tips to set you off in the right direction!

What does ‘critically discuss’ actually mean?

Before attempting a critical discussion, check you understand what is required of you. Let’s turn to the Oxford English Dictionary for a useful definition.

So, in short, a critical discussion requires you to weigh up the strengths and weaknesses of a theory, concept (or work of some sort), and write about this in detail – taking into account various relevant issues and viewpoints.

I would go one step further and say that to ‘critically discuss’, you should also emphasise the significance of your critiques. In other words, why does your critical opinion matter? (more on this later).

What critical discussion is NOT…

Before moving on to show you how to write a critical discussion, let’s take a look at what a ‘critical discussion’ is NOT:

Pure negativity – Some students fall into the trap of thinking that critical discussion requires you to be excessively negative. Whilst you should consider the weaknesses of a theory or argument, you should also consider its strengths and/or new applications.

A repetition of others’ critiques – Whilst you can (and typically should) use other theorists’ critiques to support your essay, you should also try to say something original in your critical discussion. Don’t only repeat other people’s ideas.

Describing – Remember, you are not only being asked to describe a particular work of art/literature/science. Part of your essay will probably include description, as you set the scene, but you must include a critical opinion of the theory, concept or work you are discussing.

Quick and Easy – Unfortunately, writing a critical discussion is not a straightforward task. You should give yourself plenty of time to read the material, digest it, reflect upon it, critique it, and then formulate an argument for your essay.

An example of critical discussion

Learning from examples is often the best way. So, here is an excerpt from an essay which critically discusses whether pay-for-performance schemes motivate employees – written by one of our PhD Experts:

Theory X states that, because employees are primarily motivated by pay, a pay-for-performance system will be motivational (McGregor, 1960). However, this theory was not supported by empirical data, thus its validity is questionable. Moreover, up-to-date research suggests that employees are not primarily motivated by pay, but are instead motivated by intrinsic factors (e.g., flexible working hours, autonomy, and creating impactful work) (Kaleb, 2015). This undermines the suggestion that pay-for-performance would be motivating. Indeed, further research has found that pay-for-performance can actually “crowd out” intrinsic motivators, since it overly monetises the employer-employee relationship, thereby resulting in poorer motivation (David, 2018). There is more empirical research to support the more recent findings than theory X, thus, it seems pay-for-performance schemes are unlikely to motivate employees.

Let’s take a closer look at the characteristics of this critical discussion so that you can try to replicate it for yourself.  

Compare two (or more) theories

Notice how this single paragraph contains three references to three different theories. In order to critically discuss competently, you will need to be able to compare and contrast different theories and perspectives. This is one of the reasons why critical discussion essays are time-consuming, i.e., because you need to spend time researching material to cover both sides of the argument.

Critique the methodologies

Notice how the above paragraph has critiqued the validity/reliability of the research mentioned. Namely, theory X was criticised for having a lack of empirical (experimental) evidence to support it, whereas the later theories were deemed more valid because there is quite a lot of empirical research to support them.

Depending on what subject you are studying at university, you might need to critique the methods in more depth (e.g., consider sample size, procedure, method of data analysis, etc.).

Keep your thesis statement (or argument) in mind at all times

Remember we said that you need to emphasise why your critiques matter? This is key because it will help you to achieve first-class grades. Let’s dive a little deeper into what I mean by this…

Before writing your essay, think of a thesis statement . In the above case, it would be ‘pay-for-performance does not boost employee motivation’. Now, when you are critically discussing your evidence (and comparing and contrasting theories), be sure to finish each paragraph by returning to the thesis statement.

In other words, be sure to emphasise why each point of critique is significant for your argument. You will notice, for example, that the above paragraph finishes by stating that ‘thus, it seems pay-for-performance schemes are unlikely to motivate employees’.

So, sticking to your thesis statement will allow you to consistently emphasise why your critical points are relevant and significant. If you can do this then, say hello to first-class grades!

Tips for writing a critical discussion

Critical discussions aren’t easy, but if you approach them in the right way, you can make things simpler for yourself.

In fact, our writers say that critical discussion essays are the most enjoyable to write because they are stimulating and challenging.

That said, try out these tips when preparing for your next critical discussion essay (and hopefully you won’t find it such a painful process!).

Start reading ASAP

When preparing for a critical discussion essay, it’s easy to fall into the trap of procrastination. There’s so much to read, yet so little time (or energy) to do the reading, right?

Well, try not to fall into this trap. Choose the texts/theories that interest you the most and try your best to really engross yourself in them. If you can become truly engaged in the research you’re reading, your energy and enthusiasm will ‘flow’ naturally.

Play devil’s advocate

One hurdle often faced by students is that they agree with everything a particular theorist is saying, and thus they don’t feel confident in critiquing the theory. In this case, it’s time to play devil’s advocate.

What does this mean? Well, to play devil’s advocate means to adopt the opposing side of the argument, even if you don’t agree with it, in order to make the discussion more interesting.

So, let’s say you are completely against animal testing, and you agree with Peter Singer’s theories (which are also against animal testing). However, for the purposes of writing a good critical discussion, you should be willing to engage with the opposing side of the argument.

Imagine, for a moment, that you are ‘for’ animal testing. What reasoning would you use? And how could this reasoning be used to discredit Peter Singer’s theory?

Plan, Plan, Plan

It’s best to make at least a rough plan of your critical discussion essay before you begin. As mentioned, your critique should be tied to a broader ‘thesis statement’ so consider this thesis statement when planning your essay.

Each paragraph should make a broad point that relates back to your thesis statement. Remember to use signposting to link back to the thesis statement and help keep your reader on track.

The final tip is the most important tip of all – be bold. To earn first-class grades, you need to demonstrate an ability to think independently and critically about a specific topic.

This means you must be willing to say what you really think and not just parrot another person’s argument. Indeed, the opportunity to ‘be bold’ demonstrates why critical discussion essays are so enjoyable to write.

So, next time you are tasked with writing a critical discussion essay, see it as an opportunity to be bold, confident, and creative! Though it might be quite a time-consuming task, you’ll certainly feel satisfied once you’ve got your argument down on paper.

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• > Radical Hope
• > How to Write a Critical Case Study

Book contents

• Frontmatter
• List of Illustrations
• Acknowledgements
• Update: COVID-19

Introduction

• 1 Poverty-Aware Social Work: a Paradigmatic Proposal
• Part I Transformation
• Part II Recognition
• Part III Rights
• Part IV Solidarity

3 - How to Write a Critical Case Study

Published online by Cambridge University Press:  18 March 2021

Semadar, an experienced social worker, wrote the intervention story that forms the core of this chapter for the purpose of a professional consultation in the framework of group supervision. She read the text aloud to the group. The question on which she wanted consultation was not rhetorical, but practical: how do you deal with a family in which children are at risk, with whom all previous attempts to assist have not fared well? When I heard Semadar, I felt that the rhetoric of the text – the specific words that she chose to describe the family – revealed a difficulty in their relationship. Although there was no doubt that the children's situation was worrying, I was concerned about Semadar's difficulty in presenting the family in a way that would reveal both the subjectivity of each of its members and the complexity of the context of their life. After Semadar finished reading the text, we analysed it in the group, noting the principles of writing a critical intervention story. During the week before our next meeting, I commented on Semadar's text and she rewrote it, giving consideration to my comments.

This chapter is based on that supervision and on the later use that I made of the text for the purposes of teaching and training. The chapter includes three versions of that text: the first is the original version written by Semadar that already includes the comments I wrote to her after the first discussion; the second version is the corrected version that Semadar wrote; and the third version was written by me in light of the new information that arose in our second discussion. In addition, the chapter outlines the guidelines for writing a critical psychosocial report.

One of the basic ideas of the PAP is simple: professionals constantly need to make an effort to recognise the subjectivity of the people they work with, to view service users as complete people and to bring this recognition to the relationship. In order to recognise service users’ subjectivity, one has to also acknowledge the context of poverty in which they live. Therefore, we have subjectivity, on the one hand, and the context of poverty, on the other.

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• How to Write a Critical Case Study
• Michal Krumer-Nevo
• Book: Radical Hope
• Online publication: 18 March 2021
• Chapter DOI: https://doi.org/10.46692/9781447354925.006

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Mastering Case Study Analysis: Techniques & Examples

Unveiling the art of case study analysis: techniques, examples, and pitfalls to avoid.

In the realm of academia, mastering the art of case study analysis is akin to unlocking a treasure trove of critical thinking, analytical prowess, and scholarly excellence. Whether you’re a budding student or a seasoned academic, delving into the depths of case study analysis is an indispensable skill that transcends disciplinary boundaries. In this introductory segment, we’ll navigate through the labyrinth of case study analysis, unraveling its significance and priming ourselves for the intricate journey of effective academic paper writing .

Significance of Case Study Analysis

Case study analysis serves as a cornerstone in academic inquiry, offering a multifaceted lens through which complex phenomena can be dissected, scrutinized, and comprehensively understood. Unlike traditional theoretical frameworks, case studies provide a real-world context, allowing scholars to bridge the gap between theory and practice. Whether exploring intricate business dilemmas, unraveling historical conundrums, or dissecting sociopolitical dynamics, case study analysis empowers researchers to navigate the nuances of multifaceted scenarios, fostering a deeper understanding of the subject matter at hand.

Furthermore, case study analysis cultivates a myriad of invaluable skills essential for academic and professional success. From honing critical thinking and problem-solving abilities to refining communication and research prowess, the process of dissecting and interpreting case studies fosters intellectual agility and scholarly acumen. Moreover, the collaborative nature of case study analysis encourages vibrant discourse and interdisciplinary collaboration, enriching the academic landscape with diverse perspectives and insights.

At its core, effective academic paper writing transcends the mere dissemination of information; it embodies a meticulous process of inquiry, analysis, and synthesis. By setting the stage for effective academic paper writing, we embark on a transformative journey characterized by intellectual exploration, scholarly rigor, and eloquent expression.

To embark on this journey, it is imperative to lay a solid foundation rooted in meticulous preparation and strategic planning. From identifying the research question to conducting comprehensive literature reviews, the pre-writing phase sets the tone for the subsequent stages of academic paper writing. Moreover, cultivating a discerning eye for detail and adhering to scholarly conventions and ethical standards are indispensable prerequisites for crafting a compelling academic paper.

In essence, understanding the significance of case study analysis and setting the stage for effective academic paper writing are not mere academic exercises; they are transformative endeavors that empower scholars to transcend the confines of conventional thinking and embark on a journey of intellectual discovery and scholarly excellence. As we embark on this odyssey, let us embrace the challenges and opportunities that lie ahead, armed with the tools and techniques essential for navigating the intricate terrain of academia with finesse and fortitude.

Deciphering the Structure: Anatomy of a Case Study Analysis

In the intricate world of academia, mastering the art of case study analysis requires not only a keen intellect but also a structured approach. Just as a skilled surgeon navigates through the complexities of the human anatomy, a proficient scholar meticulously dissects the layers of a case study to uncover its underlying insights and implications. Let’s embark on this journey of exploration as we unravel the anatomy of a case study analysis, segment by segment.

• Introduction: Crafting a Compelling Opening Statement

The introduction serves as the proverbial gateway to your case study analysis, setting the stage for what lies ahead. Much like a captivating prologue in a novel, it entices the reader’s curiosity and provides a roadmap for the ensuing discussion. In crafting your opening statement, strive to succinctly outline the purpose of your analysis, establish the relevance of the case study, and highlight the key questions or issues at hand. By captivating the reader’s attention from the onset, you lay a solid foundation for engaging them in the subsequent exploration of the case study.

• Background: Providing Context and Setting the Scene

No case study exists in a vacuum; each scenario is intricately woven into the fabric of its broader context. The background section of your analysis serves to provide the necessary context and background information essential for understanding the case study. Here, you elucidate the historical, social, economic, or cultural factors that underpin the case, shedding light on the circumstances that gave rise to the issues under scrutiny. By painting a vivid picture of the contextual landscape, you enable readers to grasp the significance of the case study within its broader framework, thus facilitating a deeper understanding of the ensuing analysis.

• Analysis: Delving into the Core Issues and Presenting Arguments

At the heart of every case study analysis lies the critical examination of core issues and the presentation of cogent arguments. In this segment, you embark on a systematic exploration of the case study, dissecting its intricacies, and unraveling its underlying complexities. Here, analytical rigor reigns supreme as you apply theoretical frameworks, empirical evidence, and logical reasoning to deconstruct the case study and elucidate its underlying dynamics. Whether exploring organizational challenges, ethical dilemmas, or strategic decisions, your analysis serves to illuminate key insights and unearth actionable insights.

• Recommendations: Proposing Solutions and Actionable Insights

Armed with a comprehensive understanding of the case study, the recommendations segment represents the culmination of your analytical endeavors. Here, you leverage your insights and expertise to propose viable solutions and actionable recommendations aimed at addressing the issues identified in the case study. Whether advocating for organizational restructuring, policy reforms, or strategic initiatives, your recommendations should be grounded in sound analysis, feasibility, and alignment with the broader objectives of the case study. By offering practical guidance and strategic foresight, you empower stakeholders to navigate the challenges posed by the case study with confidence and efficacy.

• Conclusion: Summarizing Key Findings and Concluding Remarks

In the final act of your case study analysis, the conclusion serves as a reflective summary of the key findings, insights, and implications gleaned from your exploration. Here, you distill the essence of your analysis, reaffirming its significance and relevance within the broader context of academic inquiry. Whether summarizing the main arguments, reiterating the importance of your recommendations, or offering avenues for future research, the conclusion encapsulates the overarching narrative of your case study analysis, leaving readers with a lasting impression of your scholarly contribution.

In essence, the anatomy of a case study analysis embodies a systematic journey of exploration, analysis, and synthesis, guided by the principles of scholarly rigor and intellectual inquiry. By mastering each segment of the analysis, you unlock the transformative power of case studies, empowering yourself to unravel the complexities of real-world scenarios and generate actionable insights that drive positive change. As you embark on your own journey of case study analysis, remember to wield your analytical tools with precision, curiosity, and a relentless pursuit of scholarly excellence.

Mastering the Art: Writing Techniques for a Stellar Analysis

As we delve deeper into the realm of case study analysis, it becomes increasingly evident that the effectiveness of our analysis hinges not only on the depth of our insights but also on the clarity and precision with which we communicate them. In this segment, we will explore four essential writing techniques that are indispensable for crafting a stellar case study analysis.

1. Clarity over Complexity: The Importance of Clear and Concise Writing

In the pursuit of academic excellence, clarity reigns supreme. Clear and concise writing not only enhances the readability of your analysis but also fosters a deeper understanding of the subject matter. To achieve clarity, strive to articulate your ideas in simple, straightforward language, avoiding unnecessary jargon or convoluted terminology. Moreover, organize your thoughts in a logical manner, using headings, subheadings, and transitions to guide the reader through your analysis. By prioritizing clarity over complexity, you empower readers to engage with your analysis more effectively, thus maximizing the impact of your scholarly endeavors.

2. Utilizing Evidence: Incorporating Data and Facts to Support Your Analysis

In the realm of academia, assertions devoid of evidence hold little sway. To bolster the credibility of your analysis, it is imperative to incorporate relevant data, facts, and empirical evidence to substantiate your arguments. Whether citing statistical trends, referencing scholarly studies, or presenting case examples, evidence serves as the bedrock upon which your analysis rests. Moreover, critically evaluate the quality and reliability of your sources, prioritizing peer-reviewed research and authoritative sources. By grounding your analysis in tangible evidence, you not only fortify your arguments but also demonstrate your commitment to scholarly rigor and integrity.

3. Critical Thinking: Questioning Assumptions and Exploring Multiple Perspectives

At the heart of effective case study analysis lies the spirit of critical inquiry. Critical thinking entails questioning assumptions, challenging conventional wisdom, and exploring alternative perspectives. As you navigate through the nuances of the case study, adopt a skeptical mindset, probing beneath the surface to unearth underlying assumptions and biases. Moreover, consider the diverse array of perspectives and interpretations that may exist, recognizing that there are often multiple truths to be uncovered. By embracing critical thinking, you enrich your analysis with nuance and depth, elevating it beyond mere description to a nuanced exploration of underlying dynamics and implications.

4. Coherence and Cohesion: Ensuring Seamless Flow and Logical Progression

A well-crafted case study analysis is akin to a finely woven tapestry, characterized by coherence and cohesion. To achieve this, pay meticulous attention to the organization and structure of your analysis, ensuring that each section flows seamlessly into the next. Utilize transitional phrases and logical connectors to maintain the reader’s momentum and guide them through your analysis. Moreover, adopt a holistic perspective, considering the overarching narrative arc of your analysis and how each component contributes to the broader storyline. By prioritizing coherence and cohesion, you create a roadmap that facilitates the reader’s journey through your analysis, ensuring that they arrive at the destination with clarity and comprehension.

In essence, mastering the art of case study analysis requires more than just analytical prowess; it demands a mastery of the craft of scholarly writing. By prioritizing clarity, incorporating evidence, fostering critical thinking, and ensuring coherence and cohesion, you empower yourself to craft a stellar analysis that resonates with readers and makes a lasting scholarly impact. As you hone your writing techniques, remember that excellence is not a destination but a continuous journey of refinement and growth.

Pitfalls to Avoid: Common Mistakes in Case Study Analysis

In the pursuit of mastering the art of case study analysis, it is imperative to be mindful of the common pitfalls that can undermine the effectiveness and credibility of your analysis. By steering clear of these pitfalls, you can elevate your analysis to new heights of scholarly excellence and insight. Let’s explore three prevalent mistakes that researchers often encounter in case study analysis.

Superficial Analysis: Scratching the Surface Without Delving Deeper

One of the most glaring pitfalls in case study analysis is the temptation to skim the surface, providing a cursory overview of the case study without delving into its underlying complexities. Superficial analysis fails to unearth the rich insights and nuances embedded within the case study, resulting in a shallow understanding of the subject matter. To avoid this pitfall, commit yourself to thorough and comprehensive analysis, scrutinizing each facet of the case study with rigor and depth. Take the time to probe beneath the surface, interrogating assumptions, identifying patterns, and unraveling the intricacies that lie hidden beneath. By embracing the ethos of depth over breadth, you enrich your analysis with valuable insights and elevate it from a mere recounting of facts to a nuanced exploration of underlying dynamics and implications.

Overreliance on Opinions: Backing Arguments with Subjective Viewpoints Rather Than Empirical Evidence

In the realm of academic inquiry, opinions hold little weight without the backing of empirical evidence. Yet, a common pitfall in case study analysis is the tendency to rely too heavily on subjective viewpoints and personal opinions, rather than grounding arguments in tangible evidence. While it is essential to acknowledge and incorporate diverse perspectives, it is equally important to anchor your analysis in empirical data, facts, and scholarly research. Resist the temptation to extrapolate conclusions based solely on intuition or personal beliefs, and instead prioritize evidence-based reasoning and logical analysis. By substantiating your arguments with empirical evidence, you bolster the credibility and persuasiveness of your analysis, fostering a deeper appreciation for the insights you present.

Neglecting the Bigger Picture: Failing to Consider Broader Implications and External Factors

A myopic focus on the minutiae of the case study can obscure the broader context and implications that underpin the subject matter. Neglecting the bigger picture not only limits the scope of your analysis but also undermines its relevance and applicability in real-world contexts. To avoid this pitfall, adopt a holistic perspective, considering the broader societal, economic, political, and cultural factors that may influence the case study. Explore the ripple effects and downstream consequences of the issues under scrutiny, recognizing that every action has far-reaching implications beyond the immediate context of the case study. Moreover, remain attuned to external factors and emerging trends that may shape the trajectory of the case study, ensuring that your analysis remains dynamic and responsive to evolving realities. By embracing a panoramic view of the subject matter, you enrich your analysis with depth and foresight, positioning yourself as a thoughtful and insightful scholar capable of navigating the complexities of the world with clarity and acumen.

In conclusion, by avoiding the pitfalls of superficial analysis, overreliance on opinions, and neglecting the bigger picture, you can elevate your case study analysis to new heights of scholarly rigor and relevance. By committing yourself to thorough analysis, evidence-based reasoning, and holistic perspective-taking, you empower yourself to unravel the complexities of the case study with nuance and insight, leaving a lasting scholarly impact.

Case Study Analysis in Action: Real-Life Examples

Real-life case studies offer invaluable insights into the complexities of human behavior, organizational dynamics, and societal phenomena. By examining exemplary analyses from renowned scholars and experts, we can glean valuable lessons and insights that inform our own approach to case study analysis. Let’s explore some notable examples that showcase the transformative power of case study analysis in action.

1. Harvard Business School Case Studies

Harvard Business School (HBS) is renowned for its extensive collection of case studies spanning various industries, disciplines, and geographic regions. These case studies provide a rich tapestry of real-world scenarios, offering a glimpse into the challenges and opportunities faced by organizations across the globe. One notable example is the case study on “Netflix: Disrupting the Video Rental Industry,” authored by Professor Willy Shih and Stephen Kaufman. This case study delves into Netflix’s innovative business model and disruptive impact on the traditional video rental industry. Through rigorous analysis and strategic insights, the authors unravel the key success factors that propelled Netflix to prominence, while also exploring the challenges and dilemmas encountered along the way. By examining this case study, scholars and practitioners alike can extract valuable lessons on innovation, strategic management, and market disruption.

2. Medical Case Studies

Medical case studies offer a window into the intricate world of clinical diagnosis, treatment, and patient care. One notable example is the case study on “Patient X: A Case of Rare Neurological Disorder,” authored by Dr. Linda Smith and Dr. James Lee. This case study presents a challenging diagnostic dilemma encountered by medical practitioners, wherein a patient presents with perplexing symptoms that defy conventional classification. Through meticulous analysis and interdisciplinary collaboration, the medical team navigates through the diagnostic maze, ultimately unraveling the underlying neurological disorder and devising a tailored treatment plan. By dissecting this case study, medical professionals can glean valuable insights into diagnostic reasoning, clinical decision-making, and patient-centered care.

3. Social Science Case Studies

In the realm of social science research, case studies offer a powerful tool for exploring complex social phenomena and human behavior. One exemplary case study is the research on “Community Resilience in the Aftermath of Natural Disasters,” conducted by Dr. Sarah Johnson and Dr. Michael Chen. This case study examines the resilience of communities in the wake of natural disasters, drawing upon empirical evidence and qualitative interviews to elucidate the factors that contribute to community resilience and recovery. Through in-depth analysis and theoretical synthesis, the researchers uncover the interplay of social, economic, and environmental factors that shape community resilience, offering valuable insights for disaster preparedness and response efforts.

In essence, these real-life examples underscore the transformative potential of case study analysis in elucidating complex phenomena, informing strategic decision-making, and driving positive change. By studying exemplary analyses from renowned scholars and experts, we can extract valuable lessons and insights that enrich our own approach to case study analysis, empowering us to navigate the complexities of the world with clarity, insight, and scholarly rigor.

In the realm of academia and beyond, the art of case study analysis serves as a powerful vehicle for unraveling the intricacies of real-world phenomena, informing strategic decision-making, and driving positive change. Through our exploration of the anatomy of case study analysis, we have navigated through its various components, from crafting a compelling introduction to delving into the core issues, proposing actionable recommendations, and reflecting on key findings.

We have also examined the importance of writing techniques such as clarity, evidence utilization, critical thinking, coherence, and cohesion in crafting a stellar analysis. By prioritizing these techniques, scholars can effectively communicate their insights, engage readers, and make a lasting scholarly impact.

Moreover, we have identified common pitfalls to avoid in case study analysis, such as superficial analysis, overreliance on opinions, and neglecting the bigger picture. By steering clear of these pitfalls, scholars can elevate their analysis to new heights of scholarly rigor and relevance.

Finally, we have explored real-life examples of exemplary case study analyses from renowned scholars and experts, extracting valuable lessons and insights that inform our own approach to case study analysis.

In conclusion, mastering the art of case study analysis is not merely an academic exercise; it is a transformative journey characterized by intellectual curiosity, scholarly rigor, and a commitment to excellence. By embracing the principles of thorough analysis, evidence-based reasoning, critical inquiry, and holistic perspective-taking, scholars can unlock the transformative potential of case study analysis, empowering themselves to navigate the complexities of the world with insight, clarity, and scholarly acumen. As we embark on this journey of discovery, let us remain steadfast in our pursuit of knowledge, driven by a relentless curiosity to uncover the truths that lie hidden beneath the surface.

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• How to Write a Discussion Section | Tips & Examples

How to Write a Discussion Section | Tips & Examples

Published on August 21, 2022 by Shona McCombes . Revised on July 18, 2023.

The discussion section is where you delve into the meaning, importance, and relevance of your results .

It should focus on explaining and evaluating what you found, showing how it relates to your literature review and paper or dissertation topic , and making an argument in support of your overall conclusion. It should not be a second results section.

There are different ways to write this section, but you can focus your writing around these key elements:

• Summary : A brief recap of your key results
• Interpretations: What do your results mean?
• Implications: Why do your results matter?
• Limitations: What can’t your results tell us?
• Recommendations: Avenues for further studies or analyses

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What not to include in your discussion section, step 1: summarize your key findings, step 2: give your interpretations, step 3: discuss the implications, step 4: acknowledge the limitations, step 5: share your recommendations, discussion section example, other interesting articles, frequently asked questions about discussion sections.

There are a few common mistakes to avoid when writing the discussion section of your paper.

• Don’t introduce new results: You should only discuss the data that you have already reported in your results section .
• Don’t make inflated claims: Avoid overinterpretation and speculation that isn’t directly supported by your data.
• Don’t undermine your research: The discussion of limitations should aim to strengthen your credibility, not emphasize weaknesses or failures.

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Start this section by reiterating your research problem and concisely summarizing your major findings. To speed up the process you can use a summarizer to quickly get an overview of all important findings. Don’t just repeat all the data you have already reported—aim for a clear statement of the overall result that directly answers your main research question . This should be no more than one paragraph.

Many students struggle with the differences between a discussion section and a results section . The crux of the matter is that your results sections should present your results, and your discussion section should subjectively evaluate them. Try not to blend elements of these two sections, in order to keep your paper sharp.

• The results indicate that…
• The study demonstrates a correlation between…
• This analysis supports the theory that…
• The data suggest that…

The meaning of your results may seem obvious to you, but it’s important to spell out their significance for your reader, showing exactly how they answer your research question.

The form of your interpretations will depend on the type of research, but some typical approaches to interpreting the data include:

• Identifying correlations , patterns, and relationships among the data
• Discussing whether the results met your expectations or supported your hypotheses
• Contextualizing your findings within previous research and theory
• Explaining unexpected results and evaluating their significance
• Considering possible alternative explanations and making an argument for your position

You can organize your discussion around key themes, hypotheses, or research questions, following the same structure as your results section. Alternatively, you can also begin by highlighting the most significant or unexpected results.

• In line with the hypothesis…
• Contrary to the hypothesized association…
• The results contradict the claims of Smith (2022) that…
• The results might suggest that x . However, based on the findings of similar studies, a more plausible explanation is y .

As well as giving your own interpretations, make sure to relate your results back to the scholarly work that you surveyed in the literature review . The discussion should show how your findings fit with existing knowledge, what new insights they contribute, and what consequences they have for theory or practice.

Ask yourself these questions:

• Do your results support or challenge existing theories? If they support existing theories, what new information do they contribute? If they challenge existing theories, why do you think that is?
• Are there any practical implications?

Your overall aim is to show the reader exactly what your research has contributed, and why they should care.

• These results build on existing evidence of…
• The results do not fit with the theory that…
• The experiment provides a new insight into the relationship between…
• These results should be taken into account when considering how to…
• The data contribute a clearer understanding of…
• While previous research has focused on  x , these results demonstrate that y .

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Even the best research has its limitations. Acknowledging these is important to demonstrate your credibility. Limitations aren’t about listing your errors, but about providing an accurate picture of what can and cannot be concluded from your study.

Limitations might be due to your overall research design, specific methodological choices , or unanticipated obstacles that emerged during your research process.

Here are a few common possibilities:

• If your sample size was small or limited to a specific group of people, explain how generalizability is limited.
• If you encountered problems when gathering or analyzing data, explain how these influenced the results.
• If there are potential confounding variables that you were unable to control, acknowledge the effect these may have had.

After noting the limitations, you can reiterate why the results are nonetheless valid for the purpose of answering your research question.

• The generalizability of the results is limited by…
• The reliability of these data is impacted by…
• Due to the lack of data on x , the results cannot confirm…
• The methodological choices were constrained by…
• It is beyond the scope of this study to…

Based on the discussion of your results, you can make recommendations for practical implementation or further research. Sometimes, the recommendations are saved for the conclusion .

Suggestions for further research can lead directly from the limitations. Don’t just state that more studies should be done—give concrete ideas for how future work can build on areas that your own research was unable to address.

• Further research is needed to establish…
• Future studies should take into account…
• Avenues for future research include…

If you want to know more about AI for academic writing, AI tools, or research bias, make sure to check out some of our other articles with explanations and examples or go directly to our tools!

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In the discussion , you explore the meaning and relevance of your research results , explaining how they fit with existing research and theory. Discuss:

• Your  interpretations : what do the results tell us?
• The  implications : why do the results matter?
• The  limitation s : what can’t the results tell us?

The results chapter or section simply and objectively reports what you found, without speculating on why you found these results. The discussion interprets the meaning of the results, puts them in context, and explains why they matter.

In qualitative research , results and discussion are sometimes combined. But in quantitative research , it’s considered important to separate the objective results from your interpretation of them.

In a thesis or dissertation, the discussion is an in-depth exploration of the results, going into detail about the meaning of your findings and citing relevant sources to put them in context.

The conclusion is more shorter and more general: it concisely answers your main research question and makes recommendations based on your overall findings.

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Home » Case Study – Methods, Examples and Guide

Case Study – Methods, Examples and Guide

Table of Contents

A case study is a research method that involves an in-depth examination and analysis of a particular phenomenon or case, such as an individual, organization, community, event, or situation.

It is a qualitative research approach that aims to provide a detailed and comprehensive understanding of the case being studied. Case studies typically involve multiple sources of data, including interviews, observations, documents, and artifacts, which are analyzed using various techniques, such as content analysis, thematic analysis, and grounded theory. The findings of a case study are often used to develop theories, inform policy or practice, or generate new research questions.

Types of Case Study

Types and Methods of Case Study are as follows:

Single-Case Study

A single-case study is an in-depth analysis of a single case. This type of case study is useful when the researcher wants to understand a specific phenomenon in detail.

For Example , A researcher might conduct a single-case study on a particular individual to understand their experiences with a particular health condition or a specific organization to explore their management practices. The researcher collects data from multiple sources, such as interviews, observations, and documents, and uses various techniques to analyze the data, such as content analysis or thematic analysis. The findings of a single-case study are often used to generate new research questions, develop theories, or inform policy or practice.

Multiple-Case Study

A multiple-case study involves the analysis of several cases that are similar in nature. This type of case study is useful when the researcher wants to identify similarities and differences between the cases.

For Example, a researcher might conduct a multiple-case study on several companies to explore the factors that contribute to their success or failure. The researcher collects data from each case, compares and contrasts the findings, and uses various techniques to analyze the data, such as comparative analysis or pattern-matching. The findings of a multiple-case study can be used to develop theories, inform policy or practice, or generate new research questions.

Exploratory Case Study

An exploratory case study is used to explore a new or understudied phenomenon. This type of case study is useful when the researcher wants to generate hypotheses or theories about the phenomenon.

For Example, a researcher might conduct an exploratory case study on a new technology to understand its potential impact on society. The researcher collects data from multiple sources, such as interviews, observations, and documents, and uses various techniques to analyze the data, such as grounded theory or content analysis. The findings of an exploratory case study can be used to generate new research questions, develop theories, or inform policy or practice.

Descriptive Case Study

A descriptive case study is used to describe a particular phenomenon in detail. This type of case study is useful when the researcher wants to provide a comprehensive account of the phenomenon.

For Example, a researcher might conduct a descriptive case study on a particular community to understand its social and economic characteristics. The researcher collects data from multiple sources, such as interviews, observations, and documents, and uses various techniques to analyze the data, such as content analysis or thematic analysis. The findings of a descriptive case study can be used to inform policy or practice or generate new research questions.

Instrumental Case Study

An instrumental case study is used to understand a particular phenomenon that is instrumental in achieving a particular goal. This type of case study is useful when the researcher wants to understand the role of the phenomenon in achieving the goal.

For Example, a researcher might conduct an instrumental case study on a particular policy to understand its impact on achieving a particular goal, such as reducing poverty. The researcher collects data from multiple sources, such as interviews, observations, and documents, and uses various techniques to analyze the data, such as content analysis or thematic analysis. The findings of an instrumental case study can be used to inform policy or practice or generate new research questions.

Case Study Data Collection Methods

Here are some common data collection methods for case studies:

Interviews involve asking questions to individuals who have knowledge or experience relevant to the case study. Interviews can be structured (where the same questions are asked to all participants) or unstructured (where the interviewer follows up on the responses with further questions). Interviews can be conducted in person, over the phone, or through video conferencing.

Observations

Observations involve watching and recording the behavior and activities of individuals or groups relevant to the case study. Observations can be participant (where the researcher actively participates in the activities) or non-participant (where the researcher observes from a distance). Observations can be recorded using notes, audio or video recordings, or photographs.

Documents can be used as a source of information for case studies. Documents can include reports, memos, emails, letters, and other written materials related to the case study. Documents can be collected from the case study participants or from public sources.

Surveys involve asking a set of questions to a sample of individuals relevant to the case study. Surveys can be administered in person, over the phone, through mail or email, or online. Surveys can be used to gather information on attitudes, opinions, or behaviors related to the case study.

Artifacts are physical objects relevant to the case study. Artifacts can include tools, equipment, products, or other objects that provide insights into the case study phenomenon.

How to conduct Case Study Research

Conducting a case study research involves several steps that need to be followed to ensure the quality and rigor of the study. Here are the steps to conduct case study research:

• Define the research questions: The first step in conducting a case study research is to define the research questions. The research questions should be specific, measurable, and relevant to the case study phenomenon under investigation.
• Select the case: The next step is to select the case or cases to be studied. The case should be relevant to the research questions and should provide rich and diverse data that can be used to answer the research questions.
• Collect data: Data can be collected using various methods, such as interviews, observations, documents, surveys, and artifacts. The data collection method should be selected based on the research questions and the nature of the case study phenomenon.
• Analyze the data: The data collected from the case study should be analyzed using various techniques, such as content analysis, thematic analysis, or grounded theory. The analysis should be guided by the research questions and should aim to provide insights and conclusions relevant to the research questions.
• Draw conclusions: The conclusions drawn from the case study should be based on the data analysis and should be relevant to the research questions. The conclusions should be supported by evidence and should be clearly stated.
• Validate the findings: The findings of the case study should be validated by reviewing the data and the analysis with participants or other experts in the field. This helps to ensure the validity and reliability of the findings.
• Write the report: The final step is to write the report of the case study research. The report should provide a clear description of the case study phenomenon, the research questions, the data collection methods, the data analysis, the findings, and the conclusions. The report should be written in a clear and concise manner and should follow the guidelines for academic writing.

Examples of Case Study

Here are some examples of case study research:

• The Hawthorne Studies : Conducted between 1924 and 1932, the Hawthorne Studies were a series of case studies conducted by Elton Mayo and his colleagues to examine the impact of work environment on employee productivity. The studies were conducted at the Hawthorne Works plant of the Western Electric Company in Chicago and included interviews, observations, and experiments.
• The Stanford Prison Experiment: Conducted in 1971, the Stanford Prison Experiment was a case study conducted by Philip Zimbardo to examine the psychological effects of power and authority. The study involved simulating a prison environment and assigning participants to the role of guards or prisoners. The study was controversial due to the ethical issues it raised.
• The Challenger Disaster: The Challenger Disaster was a case study conducted to examine the causes of the Space Shuttle Challenger explosion in 1986. The study included interviews, observations, and analysis of data to identify the technical, organizational, and cultural factors that contributed to the disaster.
• The Enron Scandal: The Enron Scandal was a case study conducted to examine the causes of the Enron Corporation’s bankruptcy in 2001. The study included interviews, analysis of financial data, and review of documents to identify the accounting practices, corporate culture, and ethical issues that led to the company’s downfall.
• The Fukushima Nuclear Disaster : The Fukushima Nuclear Disaster was a case study conducted to examine the causes of the nuclear accident that occurred at the Fukushima Daiichi Nuclear Power Plant in Japan in 2011. The study included interviews, analysis of data, and review of documents to identify the technical, organizational, and cultural factors that contributed to the disaster.

Application of Case Study

Case studies have a wide range of applications across various fields and industries. Here are some examples:

Business and Management

Case studies are widely used in business and management to examine real-life situations and develop problem-solving skills. Case studies can help students and professionals to develop a deep understanding of business concepts, theories, and best practices.

Case studies are used in healthcare to examine patient care, treatment options, and outcomes. Case studies can help healthcare professionals to develop critical thinking skills, diagnose complex medical conditions, and develop effective treatment plans.

Case studies are used in education to examine teaching and learning practices. Case studies can help educators to develop effective teaching strategies, evaluate student progress, and identify areas for improvement.

Social Sciences

Case studies are widely used in social sciences to examine human behavior, social phenomena, and cultural practices. Case studies can help researchers to develop theories, test hypotheses, and gain insights into complex social issues.

Law and Ethics

Case studies are used in law and ethics to examine legal and ethical dilemmas. Case studies can help lawyers, policymakers, and ethical professionals to develop critical thinking skills, analyze complex cases, and make informed decisions.

Purpose of Case Study

The purpose of a case study is to provide a detailed analysis of a specific phenomenon, issue, or problem in its real-life context. A case study is a qualitative research method that involves the in-depth exploration and analysis of a particular case, which can be an individual, group, organization, event, or community.

The primary purpose of a case study is to generate a comprehensive and nuanced understanding of the case, including its history, context, and dynamics. Case studies can help researchers to identify and examine the underlying factors, processes, and mechanisms that contribute to the case and its outcomes. This can help to develop a more accurate and detailed understanding of the case, which can inform future research, practice, or policy.

Case studies can also serve other purposes, including:

• Illustrating a theory or concept: Case studies can be used to illustrate and explain theoretical concepts and frameworks, providing concrete examples of how they can be applied in real-life situations.
• Developing hypotheses: Case studies can help to generate hypotheses about the causal relationships between different factors and outcomes, which can be tested through further research.
• Providing insight into complex issues: Case studies can provide insights into complex and multifaceted issues, which may be difficult to understand through other research methods.
• Informing practice or policy: Case studies can be used to inform practice or policy by identifying best practices, lessons learned, or areas for improvement.

Advantages of Case Study Research

There are several advantages of case study research, including:

• In-depth exploration: Case study research allows for a detailed exploration and analysis of a specific phenomenon, issue, or problem in its real-life context. This can provide a comprehensive understanding of the case and its dynamics, which may not be possible through other research methods.
• Rich data: Case study research can generate rich and detailed data, including qualitative data such as interviews, observations, and documents. This can provide a nuanced understanding of the case and its complexity.
• Holistic perspective: Case study research allows for a holistic perspective of the case, taking into account the various factors, processes, and mechanisms that contribute to the case and its outcomes. This can help to develop a more accurate and comprehensive understanding of the case.
• Theory development: Case study research can help to develop and refine theories and concepts by providing empirical evidence and concrete examples of how they can be applied in real-life situations.
• Practical application: Case study research can inform practice or policy by identifying best practices, lessons learned, or areas for improvement.
• Contextualization: Case study research takes into account the specific context in which the case is situated, which can help to understand how the case is influenced by the social, cultural, and historical factors of its environment.

Limitations of Case Study Research

There are several limitations of case study research, including:

• Limited generalizability : Case studies are typically focused on a single case or a small number of cases, which limits the generalizability of the findings. The unique characteristics of the case may not be applicable to other contexts or populations, which may limit the external validity of the research.
• Biased sampling: Case studies may rely on purposive or convenience sampling, which can introduce bias into the sample selection process. This may limit the representativeness of the sample and the generalizability of the findings.
• Subjectivity: Case studies rely on the interpretation of the researcher, which can introduce subjectivity into the analysis. The researcher’s own biases, assumptions, and perspectives may influence the findings, which may limit the objectivity of the research.
• Limited control: Case studies are typically conducted in naturalistic settings, which limits the control that the researcher has over the environment and the variables being studied. This may limit the ability to establish causal relationships between variables.
• Time-consuming: Case studies can be time-consuming to conduct, as they typically involve a detailed exploration and analysis of a specific case. This may limit the feasibility of conducting multiple case studies or conducting case studies in a timely manner.
• Resource-intensive: Case studies may require significant resources, including time, funding, and expertise. This may limit the ability of researchers to conduct case studies in resource-constrained settings.

About the author

Muhammad Hassan

Researcher, Academic Writer, Web developer

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How to Critically Discuss in An Essay

Published by Carmen Troy at September 19th, 2023 , Revised On January 5, 2024

Writing an essay often involves more than just relaying information or expressing an opinion. For many academic and professional purposes, you are required to critically discuss topics, demonstrate an understanding of various perspectives and showcase your analytical skills. 

So, what does it mean to critically discuss something in an essay? And more importantly, how can you do it effectively?

What is Critical Discussion?

Before diving into the how-to, grasping what critical discussion entails is essential. Essay writing help often emphasises the importance of this step. Critical discussion requires a deeper level of analysis where you explain a topic and evaluate and dissect its various facets.

Imagine an object in the middle of a room, with observers standing at different points around it. Each person sees the object from a unique angle. Similarly, when you critically discuss a topic, you are trying to view it from multiple angles, considering various perspectives and arguments and avoiding biases where certain perspectives might be overlooked.

How to Critically Discuss

Consider the following steps to critically discuss an essay. 

Start with Thorough Research

To critically discuss a topic, you need to understand its nuances. This requires in-depth research:

• Diverse Sources: Instead of relying on a single type of source, such as books, expand your horizons. Use academic journals, reputable news articles, podcasts, interviews, and more. Essay services can be an invaluable tool in this stage for collating resources.
• Contrasting Opinions: Deliberately seek out sources that disagree with each other. This will provide a more holistic view of the topic and help you understand the key debates in the field. 

Organise your Thoughts

Begin by brainstorming. Jot down the key points, arguments, counterarguments, and evidence you have gathered. Categorise them and try to identify connections or patterns.

Structure your Essay for Critical Discussion

Critical discussion typically follows this essay structure :

• Introduction of an Essay : Introduce the topic and highlight its significance. Outline the main points you intend to discuss, backed up by scholarly source references.
• Main Body: This is where the meat of your critical discussion will lie and where techniques like the rhetorical analysis of an essay can be invaluable.
• Present Different Angles: Every paragraph should tackle a unique perspective or argument. Discuss its strengths and weaknesses. If you are discussing a controversial topic, you might delve into the argumentative essay.
• Use Evidence: Always back up your statements with evidence. Quotations, statistics, and examples can bolster your claims.
• Contrast and Compare: Highlight how different perspectives agree or differ from one another. This comparative approach will enrich your analysis.
• Conclusion: Summarise the main points discussed and reiterate their significance. You might also want to mention areas for further research or exploration.

Question Everything

When critically discussing, you are essentially playing the devil’s advocate. Some questions to pose include:

• What are the underlying assumptions here?
• How might someone oppose this perspective?
• Are there any weaknesses or limitations?
• What real-world implications does this have?

Avoid Bias and Stay Objective

While it is challenging to be entirely free from biases, strive for objectivity. Remember, a critical discussion is not about what you believe; it’s about presenting a rounded view of the topic.

Write with Clarity

Complex topics demand clear writing. Avoid jargon unless it is essential, and ensure your sentences are concise and straightforward. Each paragraph should have a clear focus, and the flow from one paragraph to another should be logical.

Incorporate Feedback

Once you have written your essay, share it with peers, mentors, or tutors. Their feedback will provide fresh perspectives and highlight areas requiring more clarity or depth.

Revise and Refine

Like any essay, the first draft might not be perfect. Dedicate time to revising your work, refining your arguments, and ensuring the essay flows smoothly.

Conclude with Forward-Thinking

A hallmark of an excellent critical discussion is leaving the reader with something to ponder. Highlight areas where research is still ongoing, or propose questions that have not been addressed adequately.

What Critical Discussion is Not

Critical discussion is essential for deepening understanding, stimulating creative thought, and promoting a collaborative environment. However, certain behaviors and attitudes are not conducive to critical discussion. Here is what critical discussion is not:

Ad Hominem Attacks

A critical discussion does not involve attacking a person’s character, motives, or other personal attributes. The focus should be on the content of the argument, not on the person making it.

Appeal to Emotion

While emotions can be involved, a critical discussion should not be based solely on emotional appeals, nor should it be used to manipulate participants.

Straw Man Fallacy

Misrepresenting or oversimplifying an opponent’s argument to make it easier to attack is not genuine discussion.

Dodging questions, changing the topic abruptly, or not addressing the central issues is not a part of critical discussion.

Closed-mindedness

A true critical discussion requires participants to be open to new ideas and willing to change their minds if presented with compelling evidence.

Talking Over Others

Dominating the conversation, interrupting, or not allowing others to speak does not foster a healthy discussion.

Confirmation Bias

Only seeking out or acknowledging information that confirms one’s pre-existing beliefs is not the essence of critical discussion.

Appeal to Authority

Simply stating that an authority figure believes something does not make it true or end the discussion.

Overgeneralisations

Making broad statements without sufficient evidence or specifics undermines a constructive dialogue.

False Dichotomies

Presenting issues as if there are only two sides or solutions when there might be a spectrum of possibilities, in reality, is not conducive to critical exploration.

Circular Arguments

Arguing a point by merely restating it in different words does not add depth or clarity to a discussion.

Unwillingness to Listen

Entering a discussion with the intent to lecture rather than also to listen, learn, and potentially adjust your views stifles genuine discourse.

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Critical Discussion Example

let’s set up a scenario for a critical discussion:

Topic: The Impact of Social Media on Mental Health

Participants: Alex and Jamie

Alex: I have read a lot of articles recently that suggest social media has a negative impact on the mental health of users, particularly young people. There’s a correlation between increased social media use and increased rates of depression, anxiety, and loneliness.

Jamie: That is a valid point, Alex. There have been studies that suggest that. However, correlation does not imply causation. People who are already feeling lonely or depressed may be simply more likely to spend time on social media. How do we know that social media is the cause and not just a symptom?

Alex: That is a fair point. Some studies have shown that excessive use of social media can lead to feelings of inadequacy, especially when people compare their lives to others. The constant barrage of highlight reels from other people’s lives can make users feel like they’re not doing enough or not leading fulfilling lives.

Jamie: True, comparison can be detrimental. But social media also has its benefits. It is a way for people to connect, especially those who might feel isolated in their real lives. For some, it offers a community and a sense of belonging. Shouldn’t we consider these positive aspects as well?

Alex: Absolutely, I agree that social media can provide vital connections for many. But there is also the element of screen time. Being constantly connected can disrupt sleep patterns and reduce face-to-face social interactions, which are crucial for emotional and social development.

Jamie: Yes, moderation is key. Users need to be self-aware and ensure that their online interactions enhance their lives rather than detract from them. Healthy social media use education might be more beneficial than demonising the platforms.

This is a simplified example, but it highlights some features of critical discussion, similar to what you would find in a discursive essay :

• Respectful Exchange: Both participants listened to each other’s viewpoints.
• Exploration of Ideas: The participants delved into the complexities of the issue.
• Use of Evidence: Alex and Jamie provided reasons and evidence for their perspectives.
• Open-Mindedness: Both were open to adjusting their views or considering the other’s viewpoint.

Seeking Understanding: Instead of trying to “win” the argument, they aimed for a clearer understanding of the topic.

Frequently Asked Questions

What does critically discuss mean.

“Critically discuss” means analysing and evaluating a topic or argument thoroughly, considering its strengths and weaknesses. It involves a detailed assessment rather than a mere description, often requiring one to question assumptions, recognise biases, and provide evidence to support the analysis. It is a deep, balanced examination of a subject.

How to answer a critically discuss question?

To answer a “critically discuss” question:

• Introduce the topic briefly.
• Present key arguments or points.
• Analyse the strengths and weaknesses of each.
• Use evidence to support your analysis.
• Consider alternative viewpoints.
• Conclude with a balanced assessment.
• Ensure clarity, coherence, and proper referencing throughout.

How to critically discuss a theory?

To critically discuss a theory:

• Outline the theory’s main propositions.
• Examine its historical and academic context.
• Evaluate its strengths and weaknesses.
• Compare with alternative theories.
• Highlight empirical evidence supporting or refuting it.
• Analyse underlying assumptions.
• Conclude with a balanced perspective, acknowledging its relevance and limitations.

How to critically discuss a topic?

To critically discuss a topic:

• Introduce the topic succinctly.
• Present key facts or arguments.
• Analyse strengths and limitations.
• Reference relevant evidence or research.
• Consider opposing views or counterarguments.
• Assess the implications or significance.
• Conclude with an informed perspective, reflecting a comprehensive understanding.

How to critically discuss in psychology?

• Introduce the psychological concept/theory.
• Detail its historical development and key proponents.
• Evaluate empirical evidence supporting and opposing it.
• Examine methodological strengths and limitations.
• Compare with alternative theories or explanations.
• Discuss real-world implications or applications.
• Conclude, reflecting on its overall validity and relevance.

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Case Method Teaching and Learning

What is the case method? How can the case method be used to engage learners? What are some strategies for getting started? This guide helps instructors answer these questions by providing an overview of the case method while highlighting learner-centered and digitally-enhanced approaches to teaching with the case method. The guide also offers tips to instructors as they get started with the case method and additional references and resources.

On this page:

What is case method teaching.

• Case Method at Columbia

Why use the Case Method?

Case method teaching approaches, how do i get started.

• Additional Resources

The CTL is here to help!

For support with implementing a case method approach in your course, email [email protected] to schedule your 1-1 consultation .

Cite this resource: Columbia Center for Teaching and Learning (2019). Case Method Teaching and Learning. Columbia University. Retrieved from [today’s date] from https://ctl.columbia.edu/resources-and-technology/resources/case-method/  

Case method 1 teaching is an active form of instruction that focuses on a case and involves students learning by doing 2 3 . Cases are real or invented stories 4  that include “an educational message” or recount events, problems, dilemmas, theoretical or conceptual issue that requires analysis and/or decision-making.

Case-based teaching simulates real world situations and asks students to actively grapple with complex problems 5 6 This method of instruction is used across disciplines to promote learning, and is common in law, business, medicine, among other fields. See Table 1 below for a few types of cases and the learning they promote.

Table 1: Types of cases and the learning they promote.

For a more complete list, see Case Types & Teaching Methods: A Classification Scheme from the National Center for Case Study Teaching in Science.

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Case Method Teaching and Learning at Columbia

The case method is actively used in classrooms across Columbia, at the Morningside campus in the School of International and Public Affairs (SIPA), the School of Business, Arts and Sciences, among others, and at Columbia University Irving Medical campus.

Faculty Spotlight:

Professor Mary Ann Price on Using Case Study Method to Place Pre-Med Students in Real-Life Scenarios

Read more  

Professor De Pinho on Using the Case Method in the Mailman Core

Case method teaching has been found to improve student learning, to increase students’ perception of learning gains, and to meet learning objectives 8 9 . Faculty have noted the instructional benefits of cases including greater student engagement in their learning 10 , deeper student understanding of concepts, stronger critical thinking skills, and an ability to make connections across content areas and view an issue from multiple perspectives 11 . 

Through case-based learning, students are the ones asking questions about the case, doing the problem-solving, interacting with and learning from their peers, “unpacking” the case, analyzing the case, and summarizing the case. They learn how to work with limited information and ambiguity, think in professional or disciplinary ways, and ask themselves “what would I do if I were in this specific situation?”

The case method bridges theory to practice, and promotes the development of skills including: communication, active listening, critical thinking, decision-making, and metacognitive skills 12 , as students apply course content knowledge, reflect on what they know and their approach to analyzing, and make sense of a case. 

Though the case method has historical roots as an instructor-centered approach that uses the Socratic dialogue and cold-calling, it is possible to take a more learner-centered approach in which students take on roles and tasks traditionally left to the instructor. 

Cases are often used as “vehicles for classroom discussion” 13 . Students should be encouraged to take ownership of their learning from a case. Discussion-based approaches engage students in thinking and communicating about a case. Instructors can set up a case activity in which students are the ones doing the work of “asking questions, summarizing content, generating hypotheses, proposing theories, or offering critical analyses” 14 . 

The role of the instructor is to share a case or ask students to share or create a case to use in class, set expectations, provide instructions, and assign students roles in the discussion. Student roles in a case discussion can include: 

• discussion “starters” get the conversation started with a question or posing the questions that their peers came up with; 
• facilitators listen actively, validate the contributions of peers, ask follow-up questions, draw connections, refocus the conversation as needed; 
• recorders take-notes of the main points of the discussion, record on the board, upload to CourseWorks, or type and project on the screen; and 
• discussion “wrappers” lead a summary of the main points of the discussion. 

Prior to the case discussion, instructors can model case analysis and the types of questions students should ask, co-create discussion guidelines with students, and ask for students to submit discussion questions. During the discussion, the instructor can keep time, intervene as necessary (however the students should be doing the talking), and pause the discussion for a debrief and to ask students to reflect on what and how they learned from the case activity. 

Note: case discussions can be enhanced using technology. Live discussions can occur via video-conferencing (e.g., using Zoom ) or asynchronous discussions can occur using the Discussions tool in CourseWorks (Canvas) .

Table 2 includes a few interactive case method approaches. Regardless of the approach selected, it is important to create a learning environment in which students feel comfortable participating in a case activity and learning from one another. See below for tips on supporting student in how to learn from a case in the “getting started” section and how to create a supportive learning environment in the Guide for Inclusive Teaching at Columbia . 

Table 2. Strategies for Engaging Students in Case-Based Learning

Approaches to case teaching should be informed by course learning objectives, and can be adapted for small, large, hybrid, and online classes. Instructional technology can be used in various ways to deliver, facilitate, and assess the case method. For instance, an online module can be created in CourseWorks (Canvas) to structure the delivery of the case, allow students to work at their own pace, engage all learners, even those reluctant to speak up in class, and assess understanding of a case and student learning. Modules can include text, embedded media (e.g., using Panopto or Mediathread ) curated by the instructor, online discussion, and assessments. Students can be asked to read a case and/or watch a short video, respond to quiz questions and receive immediate feedback, post questions to a discussion, and share resources. 

For more information about options for incorporating educational technology to your course, please contact your Learning Designer .

To ensure that students are learning from the case approach, ask them to pause and reflect on what and how they learned from the case. Time to reflect  builds your students’ metacognition, and when these reflections are collected they provides you with insights about the effectiveness of your approach in promoting student learning.

Well designed case-based learning experiences: 1) motivate student involvement, 2) have students doing the work, 3) help students develop knowledge and skills, and 4) have students learning from each other.  

Designing a case-based learning experience should center around the learning objectives for a course. The following points focus on intentional design. 

Identify learning objectives, determine scope, and anticipate challenges. 

• Why use the case method in your course? How will it promote student learning differently than other approaches? 
• What are the learning objectives that need to be met by the case method? What knowledge should students apply and skills should they practice? 
• What is the scope of the case? (a brief activity in a single class session to a semester-long case-based course; if new to case method, start small with a single case). 
• What challenges do you anticipate (e.g., student preparation and prior experiences with case learning, discomfort with discussion, peer-to-peer learning, managing discussion) and how will you plan for these in your design? 
• If you are asking students to use transferable skills for the case method (e.g., teamwork, digital literacy) make them explicit. 

Determine how you will know if the learning objectives were met and develop a plan for evaluating the effectiveness of the case method to inform future case teaching. 

• What assessments and criteria will you use to evaluate student work or participation in case discussion? 
• How will you evaluate the effectiveness of the case method? What feedback will you collect from students? 
• How might you leverage technology for assessment purposes? For example, could you quiz students about the case online before class, accept assignment submissions online, use audience response systems (e.g., PollEverywhere) for formative assessment during class? 

Select an existing case, create your own, or encourage students to bring course-relevant cases, and prepare for its delivery

• Where will the case method fit into the course learning sequence? 
• Is the case at the appropriate level of complexity? Is it inclusive, culturally relevant, and relatable to students? 
• What materials and preparation will be needed to present the case to students? (e.g., readings, audiovisual materials, set up a module in CourseWorks). 

Plan for the case discussion and an active role for students

• What will your role be in facilitating case-based learning? How will you model case analysis for your students? (e.g., present a short case and demo your approach and the process of case learning) (Davis, 2009). 
• What discussion guidelines will you use that include your students’ input? 
• How will you encourage students to ask and answer questions, summarize their work, take notes, and debrief the case? 
• If students will be working in groups, how will groups form? What size will the groups be? What instructions will they be given? How will you ensure that everyone participates? What will they need to submit? Can technology be leveraged for any of these areas? 
• Have you considered students of varied cognitive and physical abilities and how they might participate in the activities/discussions, including those that involve technology? 

Student preparation and expectations

• How will you communicate about the case method approach to your students? When will you articulate the purpose of case-based learning and expectations of student engagement? What information about case-based learning and expectations will be included in the syllabus?
• What preparation and/or assignment(s) will students complete in order to learn from the case? (e.g., read the case prior to class, watch a case video prior to class, post to a CourseWorks discussion, submit a brief memo, complete a short writing assignment to check students’ understanding of a case, take on a specific role, prepare to present a critique during in-class discussion).

Andersen, E. and Schiano, B. (2014). Teaching with Cases: A Practical Guide . Harvard Business Press. 

Bonney, K. M. (2015). Case Study Teaching Method Improves Student Performance and Perceptions of Learning Gains†. Journal of Microbiology & Biology Education , 16 (1), 21–28. https://doi.org/10.1128/jmbe.v16i1.846

Davis, B.G. (2009). Chapter 24: Case Studies. In Tools for Teaching. Second Edition. Jossey-Bass. 

Garvin, D.A. (2003). Making the Case: Professional Education for the world of practice. Harvard Magazine. September-October 2003, Volume 106, Number 1, 56-107.

Golich, V.L. (2000). The ABCs of Case Teaching. International Studies Perspectives. 1, 11-29. 

Golich, V.L.; Boyer, M; Franko, P.; and Lamy, S. (2000). The ABCs of Case Teaching. Pew Case Studies in International Affairs. Institute for the Study of Diplomacy. 

Heath, J. (2015). Teaching & Writing Cases: A Practical Guide. The Case Center, UK. 

Herreid, C.F. (2011). Case Study Teaching. New Directions for Teaching and Learning. No. 128, Winder 2011, 31 – 40. 

Herreid, C.F. (2007). Start with a Story: The Case Study Method of Teaching College Science . National Science Teachers Association. Available as an ebook through Columbia Libraries. 

Herreid, C.F. (2006). “Clicker” Cases: Introducing Case Study Teaching Into Large Classrooms. Journal of College Science Teaching. Oct 2006, 36(2). https://search.proquest.com/docview/200323718?pq-origsite=gscholar  

Krain, M. (2016). Putting the Learning in Case Learning? The Effects of Case-Based Approaches on Student Knowledge, Attitudes, and Engagement. Journal on Excellence in College Teaching. 27(2), 131-153. 

Lundberg, K.O. (Ed.). (2011). Our Digital Future: Boardrooms and Newsrooms. Knight Case Studies Initiative. 

Popil, I. (2011). Promotion of critical thinking by using case studies as teaching method. Nurse Education Today, 31(2), 204–207. https://doi.org/10.1016/j.nedt.2010.06.002

Schiano, B. and Andersen, E. (2017). Teaching with Cases Online . Harvard Business Publishing. 

Thistlethwaite, JE; Davies, D.; Ekeocha, S.; Kidd, J.M.; MacDougall, C.; Matthews, P.; Purkis, J.; Clay D. (2012). The effectiveness of case-based learning in health professional education: A BEME systematic review . Medical Teacher. 2012; 34(6): e421-44. 

Yadav, A.; Lundeberg, M.; DeSchryver, M.; Dirkin, K.; Schiller, N.A.; Maier, K. and Herreid, C.F. (2007). Teaching Science with Case Studies: A National Survey of Faculty Perceptions of the Benefits and Challenges of Using Cases. Journal of College Science Teaching; Sept/Oct 2007; 37(1). 

Weimer, M. (2013). Learner-Centered Teaching: Five Key Changes to Practice. Second Edition. Jossey-Bass.

Additional resources 

Teaching with Cases , Harvard Kennedy School of Government. 

Features “what is a teaching case?” video that defines a teaching case, and provides documents to help students prepare for case learning, Common case teaching challenges and solutions, tips for teaching with cases. 

Promoting excellence and innovation in case method teaching: Teaching by the Case Method , Christensen Center for Teaching & Learning. Harvard Business School. 

National Center for Case Study Teaching in Science . University of Buffalo. 

A collection of peer-reviewed STEM cases to teach scientific concepts and content, promote process skills and critical thinking. The Center welcomes case submissions. Case classification scheme of case types and teaching methods:

• Different types of cases: analysis case, dilemma/decision case, directed case, interrupted case, clicker case, a flipped case, a laboratory case. 
• Different types of teaching methods: problem-based learning, discussion, debate, intimate debate, public hearing, trial, jigsaw, role-play. 

Columbia Resources

Resources available to support your use of case method: The University hosts a number of case collections including: the Case Consortium (a collection of free cases in the fields of journalism, public policy, public health, and other disciplines that include teaching and learning resources; SIPA’s Picker Case Collection (audiovisual case studies on public sector innovation, filmed around the world and involving SIPA student teams in producing the cases); and Columbia Business School CaseWorks , which develops teaching cases and materials for use in Columbia Business School classrooms.

Center for Teaching and Learning

The Center for Teaching and Learning (CTL) offers a variety of programs and services for instructors at Columbia. The CTL can provide customized support as you plan to use the case method approach through implementation. Schedule a one-on-one consultation. 

Office of the Provost

The Hybrid Learning Course Redesign grant program from the Office of the Provost provides support for faculty who are developing innovative and technology-enhanced pedagogy and learning strategies in the classroom. In addition to funding, faculty awardees receive support from CTL staff as they redesign, deliver, and evaluate their hybrid courses.

The Start Small! Mini-Grant provides support to faculty who are interested in experimenting with one new pedagogical strategy or tool. Faculty awardees receive funds and CTL support for a one-semester period.

Explore our teaching resources.

• Blended Learning
• Contemplative Pedagogy
• Inclusive Teaching Guide
• FAQ for Teaching Assistants
• Metacognition

CTL resources and technology for you.

• Overview of all CTL Resources and Technology
• The origins of this method can be traced to Harvard University where in 1870 the Law School began using cases to teach students how to think like lawyers using real court decisions. This was followed by the Business School in 1920 (Garvin, 2003). These professional schools recognized that lecture mode of instruction was insufficient to teach critical professional skills, and that active learning would better prepare learners for their professional lives. ↩
• Golich, V.L. (2000). The ABCs of Case Teaching. International Studies Perspectives. 1, 11-29. ↩
• Herreid, C.F. (2007). Start with a Story: The Case Study Method of Teaching College Science . National Science Teachers Association. Available as an ebook through Columbia Libraries. ↩
• Davis, B.G. (2009). Chapter 24: Case Studies. In Tools for Teaching. Second Edition. Jossey-Bass. ↩
• Andersen, E. and Schiano, B. (2014). Teaching with Cases: A Practical Guide . Harvard Business Press. ↩
• Lundberg, K.O. (Ed.). (2011). Our Digital Future: Boardrooms and Newsrooms. Knight Case Studies Initiative. ↩
• Heath, J. (2015). Teaching & Writing Cases: A Practical Guide. The Case Center, UK. ↩
• Bonney, K. M. (2015). Case Study Teaching Method Improves Student Performance and Perceptions of Learning Gains†. Journal of Microbiology & Biology Education , 16 (1), 21–28. https://doi.org/10.1128/jmbe.v16i1.846 ↩
• Krain, M. (2016). Putting the Learning in Case Learning? The Effects of Case-Based Approaches on Student Knowledge, Attitudes, and Engagement. Journal on Excellence in College Teaching. 27(2), 131-153. ↩
• Thistlethwaite, JE; Davies, D.; Ekeocha, S.; Kidd, J.M.; MacDougall, C.; Matthews, P.; Purkis, J.; Clay D. (2012). The effectiveness of case-based learning in health professional education: A BEME systematic review . Medical Teacher. 2012; 34(6): e421-44. ↩
• Yadav, A.; Lundeberg, M.; DeSchryver, M.; Dirkin, K.; Schiller, N.A.; Maier, K. and Herreid, C.F. (2007). Teaching Science with Case Studies: A National Survey of Faculty Perceptions of the Benefits and Challenges of Using Cases. Journal of College Science Teaching; Sept/Oct 2007; 37(1). ↩
• Popil, I. (2011). Promotion of critical thinking by using case studies as teaching method. Nurse Education Today, 31(2), 204–207. https://doi.org/10.1016/j.nedt.2010.06.002 ↩
• Weimer, M. (2013). Learner-Centered Teaching: Five Key Changes to Practice. Second Edition. Jossey-Bass. ↩
• Herreid, C.F. (2006). “Clicker” Cases: Introducing Case Study Teaching Into Large Classrooms. Journal of College Science Teaching. Oct 2006, 36(2). https://search.proquest.com/docview/200323718?pq-origsite=gscholar ↩

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10 Case Study Examples to Inspire Your Marketing Efforts

Sudarshan Somanathan

Head of Content

June 20, 2024

When your prospects are nearing a decision in their buyer’s journey, a strong case study can sway them your way. After all, everyone, even corporate decision-makers, loves a good story.

That’s why having satisfied customers showcase your strengths is more impactful than any self-promotion. It boosts credibility and earns you valuable recognition when potential customers come across these case studies.

No matter what you offer, case studies work because they build trust. They showcase real-life success stories , their detailed analysis proving your expertise and the quality of your products or services. 

That’s why they’re crucial for organizational growth.

Intrigued? Read on to explore the different types of case studies, their practical applications, and some marketing case study examples. 

By the end of this blog post, you will also have learned how to write a case study using a case study template. ✍️

Understanding Case Studies 

1. illustrative case studies, 2. exploratory case studies, 3. descriptive case studies, 4. cumulative case studies, 5. critical instance case studies, 6. instrumental case studies, 1. lucanet and hubspot, 2. cartoon network and clickup , 3. callingly and zapier , 4. philips and github , 5. google ads and samsung, 6. movingwaldo and mailchimp, 7. shutterstock and workday, 8. pidilite and salesforce , 9. sentinelone and storylane , 10. benchling and airtable , stage 1: research and preparation, stage 2: producing the case study, use the clickup case study template.

A case study is a detailed study of how your product or service has helped past customers. 

It acts as a track record of your company’s association with past customers and an insight into how they benefitted from your product offerings.

You can think of case studies as story-telling based on real-world data and results. 

Potential customers trust them because of their attention to detail in describing exactly how you delivered results for past customers. And if the past customer is someone they know or identify with, acquiring their trust is far easier.

According to the Content Marketing Institute, 73% of marketers use case studies , as they are proven tactics to drive sales. 

These studies are tailored to various industries, from business and marketing to psychology, technology, and healthcare. 

Creating compelling business case studies requires precision and clarity, like drafting a professional document. That’s where creative brief templates come in handy. They provide a structured framework to outline key details and create case study examples that resonate with your target audience.

Types of Case Studies 

Knowing the distinct kinds of case studies will help you use the best combination to influence your potential customers. We’ll also cover a few case study examples later on so you can see the different ways in which you or your marketing team can create your own case studies.

While one type of case study may help customers solve a business problem through a product/solution, others may be more suited for studying a specific event or business phenomenon. 

Let’s explore the commonly used types and case study examples.

Illustrative case studies describe a particular situation, phenomenon, or event. They use two or more instances to show just what a situation is like . The aim is to provide context, make the unfamiliar more accessible, and provide a real-world context for abstract concepts or theories.

For instance, SaaS case study examples highlight how a software solution significantly improved a client’s sales and efficiency.

Lids, a leading sports apparel retailer, has experienced rapid growth in recent years. To manage this growth effectively, Lids implemented ClickUp , a project management platform, to expedite workflows, save time, streamline administration, and improve results.

With ClickUp, our teams are more collaborative, efficient and we’re all more on-top of our work. It has made the way we work so much better.

The case study demonstrates how integrating a robust project management platform like ClickUp can streamline operations, enhance efficiency, and support substantial organizational growth.

Exploratory case studies are conducted before a large-scale investigation to help pinpoint research questions and methods for a more extensive study. 

These are often used when there is limited prior knowledge or existing theories about the subject. They are more frequently employed in social science disciplines.

For example, a research case study investigates the link between mental health disorders and social media usage in younger populations.

Researchers conducted a systematic review focusing on the impact of social media use on mental health . The study aimed to provide insights for future mental health strategies by analyzing the relationship between social media use and mental health outcomes. 

Utilizing research plan templates can help structure such investigations, ensuring an in-depth analysis and data collection and analysis efficiency.

A descriptive case study starts with a descriptive theory as a foundation. It then attempts to find connections between the subject of discussion and the theory. These case studies rely on detailed qualitative data analysis to develop an argument.

Let’s consider a descriptive case study example on the usage of technology in classrooms focused on an elementary school in a suburban district during the 2011-2012 academic year.

This compelling case study highlights the importance of detailed, qualitative data in developing its argument.

A cumulative case study collects information from various sources to summarize past studies without increasing costs or time. It aims to aggregate data from multiple sources to draw broader conclusions.

For example, a case study on the impact of climate change on the Indian coastline aggregates data from various sources to provide a comprehensive summary of past research. 

It highlights that climate change and climate variability pose significant challenges to this ecosystem.

Critical instance case studies focus on a unique or critical event to learn more about its causes and consequences. They are often used to investigate rare or significant events.

For instance, Blackboard utilized Amazon EC2 Spot Instances to scale its virtual classroom solution amidst the COVID-19 pandemic. 

This case study demonstrates how Blackboard effectively managed a staggering 4,800% surge in video conferencing usage while optimizing costs and enhancing performance.

Instrumental case studies use a specific case to generate insights into a broader issue or to refine a theoretical explanation. They are more frequently used to explore complex concepts or theories.

The story of Accenture’s Global SAP System serves as an instrumental case study example. 

It uses Accenture’s journey to create a unified SAP system to generate strategic insights into broader issues related to aligning business and IT strategies, standardizing business processes, and establishing global governance structures.

10 Case Study Examples for Different Use Cases 

Exploring a variety of case study examples can help you understand the nuances of their formatting, data presentation, and brand positioning. Here are ten case study examples to inspire you.

LucaNet is an international finance company that provides performance management solutions. With a global customer base, it wanted to opt for automated, personalized marketing in addition to handling complex lead management. 

HubSpot helped LucaNet automate its global marketing operations and bring all customer data into a centralized hub.

What do we like best about this case study presentation? HubSpot immediately showcases its key achievements at the top and provides compelling data on time savings, lead generation, and increase in MQLs.

✔️Takeaway : Highlight your measurable impact to showcase your ability to deliver tangible outcomes.

Cartoon Network’s social media team struggled with managing complicated workflows across different project management tools. 

ClickUp provided them with a unified platform to execute their social media management needs and ensure all team members are on the same page.

ClickUp’s case study of Cartoon Network is a good example of the appropriate use of supporting visuals. Rather than simply stating that ClickUp’s flexible views improved Cartoon Network’s project management, it demonstrates them in practical use.

✔️Takeaway : Create separate sections highlighting your client’s problem and the benefits offered by your solution in bullet points. The usage of supporting visuals is a major plus.

Callingly noticed that Zapier customers tend to get more value from their platform. To capitalize on this, they wanted to educate their customers on how to use Zapier effectively. 

Callingly embedded Zapier into its app, allowing customers to discover, create, and edit Zaps directly within the platform. This integration aims to give customers more control over their workflows and automate tasks seamlessly.

The integration makes it easier for customers to discover and use Zapier, reducing the need for customers to switch between platforms or manually set up Zaps.

This makes for one of the brilliant business case study examples, thoughtfully capturing how the company helped Callingly through compelling video demonstrations.

Their ‘why’ and ‘how’ sections are particularly impressive.

✔️Takeaway : Use impactful videos to engage users and educate customers on how your product works and help clients achieve impressive results.

GitHub’s case study of Philips concisely lists the customer’s problems, solutions, and products right on top for readers prone to TL; DR. It introduces the customer before presenting figures on how collaborating with GitHub helps Philips centralize their codebase. 

You’ll also find excerpts from conversations with several Philips employees, including the principal engineer and the program director, who elaborate on their need for software and how GitHub assisted. 

This case study example isn’t limited to products and solutions—it’s about listening to customers and providing real-world value.

✔️Takeaway : Having a well-written case study summary helps. Real conversations with customers and end-users can add interesting detail and value to otherwise serious (and sometimes boring) textual documents.

Google’s case study of Samsung is well-documented. It elaborately covers how Samsung utilized Performance Max, a goal-based campaign that lets advertisers access their advertising campaign across all of Google’s products from a single interface. 

What we like about the case study example is how it is a potential guide for newer businesses to experiment with Performance Max for their own ad campaigns.  

As with all of Google’s UI, the case study is minimalistic and straightforward. Yet, it leaves you wanting to experiment and try things out yourself.

✔️Takeaway : A good case study and a how-to guide don’t always need to be different. Great case studies don’t just make a point; they compel readers to take action and see the results for themselves.

Mailchimp’s case study is a detailed report on how MovingWaldo leveraged features like email and marketing automation, segmentation, A/B testing, and email marketing. It addresses the ‘how’, ‘why’, and ‘when.’ 

The case study page provides specific dates detailing when MovingWaldo implemented solutions and began observing their impact. They have also posted a short video describing the process, which breaks the monotony of reading long documents. 

Another highlight is a brief section detailing the future course of action, conveying that the journey of success is ongoing with additional feature enhancements. The case study transcends from being an account of the past to offering insights for the future.

✔️Takeaway : Specificity, such as adding exact dates, helps strengthen your case studies. Video and other multimedia content can take it up a notch.

Workday offers glimpses of its case studies, letting you choose between reading the story or watching the video. 

The case study begins with a powerful quote from the customer that demonstrates the impact of the solution. It then provides a brief description of the success metrics and highlights the core impact of the integration. 

It addresses Shutterstock’s pain points, such as diverse data sources, team members, and workflows, and showcases Workday’s effectiveness in countering those. 

While Workday keeps the case study short, it includes all the key details to educate the customer about the implementation. This is a great example of crafting a brief yet powerful case study.

✔️Takeaway : Short case studies are effective when well written because they pack a punch and tell a compelling story. Utilizing relevant quotes is also helpful.

 In this case study example, Salesforce brings out its value with the opening lines. It then lists each point of impact created by the software integration and explains its process. 

One of the best things about this case study is its organization (value summarized upfront) and thorough explanation of Pidilite’s challenges and how they were solved. 

They also feature a ‘what next’ section detailing the next steps Pidilite plans to take in its collaboration with Salesforce, implying that they continue providing value to the customer. 

✔️Takeaway : End your case study with a brief overview of your future collaboration plans with your customer. This tells your readers that the collaboration is ongoing and that you aim to keep improving your services to add value.

This case study example is an excellent showcase of customer success. What stands out is the use of a tabular format to list different use cases of Storylane’s software and provide a before-and-after for each use case. 

The table works well to summarize key achievements in a way that’s easy on the eye. The ‘Before’ column details the company’s pain points, and the ‘After’ column highlights the results that were brought about once Storylane entered the picture.

✔️Takeaway : Using ‘before’ and ‘after’ succinctly in your case studies helps drive impact and make your case studies stand out.

We liked this case study example because it simply explains how Airtable assists Benchling in prioritizing collaboration and addressing customer needs. 

It explains the functioning of the biology-first platform in a way that helps even non-technical readers understand the context. 

The case study ends with an insight into Airtable and Benchling’s future collaboration plans, indicating that more is to come in the years ahead. 

✔️Takeaway : Write a case study using simple language so customers can easily understand the product and software integration.

How to Create Your Own Case Study

We hope these case study examples have inspired you to portray your success over the years with some fantastic case studies.

While you may have ideas, feeling stuck with the marketing planning process is natural. 

Here’s how you can create your own case study in six easy steps. We’ll divide the process into two stages, research and prep, and production.

• Choose the customer: First, choose a customer willing to share their story and provide a testimonial and results. It’s important to choose a customer who has experienced significant benefits from your product or service since this will make your case study more compelling

Pro Tip: Not sure how to write an effective outreach email to enlist customer support for your case study program? Take help from ClickUp Brain’ s AI Writer to write persuasive copy. Moreover, you can email your customers directly from ClickUp!

• Outline the customer’s journey: Detail the customer’s journey from start to finish, including their actions before, during, and after using your services

Pro Tip: Storyboard your case study with your team using collaborative ClickUp Whiteboards . Once you’re happy with the outcome, create a ClickUp Task directly from the whiteboard. Assign it to the relevant owners, add tags for easy filtering, and use ClickUp Brain to generate sub-tasks and a brief task description automatically.

• Collect data: Gather quantitative and qualitative data on the company’s performance after using your services. This could include metrics like increased sales, improved efficiency, or higher customer satisfaction
• Draft the case study: Begin writing the case study by introducing the company and providing background information. Next, discuss the challenges they faced before using your product or service. Then, detail the solution you provided and how it was implemented. Finally, showcase the results and benefits the customer experienced after using your product or service, using the data you collected to support these points

Pro Tip: Brainstorm possible case study formats and outlines with ClickUp Brain, your creative partner in this endeavor.

• Get approval from the customer: Once you’ve drafted the case study, share it with the customer for their feedback and approval. This ensures that all the information is accurate and that the customer is comfortable with how their story is presented. It also provides an opportunity to make any necessary revisions

Pro Tip: Create a shareable case study in ClickUp Docs and share it with your customer in a single click for approval

• Publish and promote: After obtaining the customer’s approval, publish the case study on your website, blog, or other relevant platforms. Promote it through various channels such as social media, email newsletters, and sales presentations

Pro Tip: When your case study is ready to be distributed, add the relevant owners for social media and email distribution by simply mentioning them in a task comment

Instead of the process we just outlined, you can also use ClickUp’s free case study templates to plan, structure, and execute your case studies to maximize the efficiency of your content marketing efforts.

With ClickUp’s Case Study Template , you can: 

• Gather data from distinct sources to analyze it and identify key takeaways
• Craft compelling stories using an organized template to drive real impact 
• Collect ideas and note testimonials from clients to showcase real-life results
• Create a visual journey of the customer’s software integration steps
• Monitor and analyze the case study’s engagement
• Collaborate with marketing team members to create the case study together

ClickUp helps marketing teams optimize the entire process of writing a case study, from collecting data to finally sending customers an email for approval.

Craft Effective Case Studies with ClickUp 

Case studies are an excellent way to build trust with prospective clients and provide evidence for your claims. They exemplify how your products and services have aided others in reaching their business and marketing goals . Studying popular case study examples can help you ideate and find the perfect format for your own customer stories.

Collaborative work management platforms like ClickUp can help you plan and execute your case study project with ease. Draft customer success case studies showcasing results effectively using ClickUp’s Case Study Template. It not only provides you with a rough layout but also improves team collaboration, helps maintain consistency with the format, collects data, and much more.

Use the integrated AI assistant, ClickUp Brain, to generate outlines, write catchy copy, and brainstorm ideas. Put your case story together, along with the relevant links, images, and rich formatting, in ClickUp Docs and share it with stakeholders for input and approval.

Sign up for ClickUp today to create the most impactful marketing case studies to attain your marketing goals.

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• Open access
• Published: 26 June 2024

Radiological and functional outcomes of Reverdin Isham osteotomy in moderate Hallux Valgus: a systematic review and meta-analysis

• Victoria Sanchís-Soria 1 ,
• Elena Nieto-González 2 ,
• Eduardo Nieto-García 2 ,
• Nadia Fernández-Ehrling 2 ,
• Javier Ferrer-Torregrosa 2 &
• Rubén Lorca-Gutiérrez 2  

Scientific Reports volume  14 , Article number:  14781 ( 2024 ) Cite this article

Metrics details

• Outcomes research

This systematic review and meta-analysis addresses the effects of minimally invasive surgical techniques, specifically the Reverdin Isham osteotomy, on functional and radiological outcomes in patients with moderate Hallux Valgus, a common foot deformity. The review included randomized and non-randomized controlled trials, as well as case reports, assessing the osteotomy in adults with moderate to severe Hallux Valgus. Searches were conducted in electronic databases such as MEDLINE and Web of Science up until July 2023, and the Joanna Briggs Institute’s critical appraisal tool was used to assess the risk of bias. Meta-analytical analyses employed a random-effects model with small-sample correction, presenting results as standardized mean differences and mean differences with 95% confidence intervals. Seven studies involving 554 patients and 643 operated feet were included, showing significant improvements in AOFAS scores (an average improvement of 36 points from 28.61 to 45.16) and reductions in radiological angles such as the distal metatarsal angle and hallux valgus angle post-surgery (IMA improved by − 3.07° from − 4.68 to − 1.46, DMAA by − 6.12° from − 9.52 to − 2.71, and HVangle by − 15.27° from − 17.98 to − 12.57). Despite these positive outcomes, most studies exhibited risks of bias and other methodological limitations, impacting the generalizability of the results. Overall, the findings highlight the efficacy of the Reverdin Isham osteotomy in improving both functional and radiological parameters in patients with moderate Hallux Valgus, although further research is warranted to solidify these results. No specific funding was received for this study, and the protocol was registered on PROSPERO with the number CRD-42023445886.

Introduction

Hallux Abductus Valgus (HAV) was first described by Carl Hueter 1 and is characterized as one of the most common foot deformities seen in clinical practice 2 , 3 . It typically presents with pain and is caused by abnormal biomechanics of the first metatarsophalangeal joint (MTPJ) during the propulsive phase of gait 4 . The hallux adopts a valgus position due to the action of the adductor muscle, resulting in lateral deviation of the proximal phalanx over the head of the first metatarsal. The first metatarsal becomes positioned in varus, leading to contracture of the lateral capsule and elongation of the medial capsule. While the transverse ligament keeps the sesamoids anchored to the second metatarsal, the first metatarsal laterally shifts and flattens its crest 1 , 5 . The cumulative effect of these movements includes progressive abduction and pronation of the first phalanx, adduction, pronation, and elevation of the first metatarsal, and lateral contracture of the capsular structure at the first MTPJ 2 .

Minimally invasive surgery (such as Reverdin Isham and Akin, Bosch and Minimally Invasive Chevron and Akin) represents a series of surgical techniques aimed at treating foot pathologies with minimal incisions, leading to definitive outcomes 6 . These techniques have exhibited remarkable efficacy in patient populations 7 . One notable advantage of these approaches is the elimination of the requirement for hemostasis, as controlled bleeding facilitates the removal of bone debris and mitigates the generation of heat during bone milling 8 . Moreover, these procedures are associated with minimally invasive techniques, owing to the utilization of small incisions that minimize damage to neighboring soft tissues, thereby resulting in accelerated recovery times 6 . The employment of intracapsular osteotomies contributes to favorable wound healing outcomes, while simultaneously reducing the duration of surgical intervention and the need for extensive instrumentation 9 . Furthermore, external fixation is limited, often accomplished through the utilization of compression bandages, thus obviating the need for osteosynthesis materials. Consequently, immediate weight-bearing is feasible with the aid of a rigid, flat-soled shoe 8 , 10 .

The chosen technique for the minimally invasive surgical treatment of moderate HAV is the Reverdin-Isham and Akin osteotomy. Reverdin Isham is a percutaneous surgical procedure without osteosynthesis 11 in which an intracapsular wedge-shaped osteotomy is performed at the medial neck of the metatarsal bone, with a dorsal distal to plantar proximal angle of approximately 25°–45° 11 , 12 , 13 . In 1981, Isham refined the Reverdin technique initially described in 1881 for HAV by modifying the angulation of the osteotomy 14 . This technique achieves the realignment of the articular surface, corrects Distal Metatarsal Articular Angle (DMAA), improves the Hallux Abductus Valgus angle (HV angle ), and stabilizes the forces at the head of the first metatarsophalangeal joint 15 , 16 . The intracapsular osteotomy becomes a highly stable procedure, obviating the need for internal fixation 12 . This surgery is indicated for patients with symptomatic medial bunion, with a normal range of motion at the first metatarsophalangeal joint without crepitus or degenerative changes. It is also recommended for congruent deviated joints with an intermetatarsal angle (IMA) of less than 20° for a straight foot and less than 16° for a foot in adduction with increased DMAA 12 .

HAV is a common foot deformity that can significantly impact a person's quality of life, causing pain, discomfort, and functional limitations. Understanding the effectiveness of Reverdin-Isham and Akin procedures is essential to guide healthcare professionals in making informed treatment decisions. Currently, there has been a notable increase in the number of case series published in the scientific literature such as Biz et al. 15 , Restuccia et al. 17 , Ribeiro et al. 13 , Severyns et al. 12 , Rodriguez-Reyes et al. 18 , Bauer et al. 11 , Bauer et al. 19 . Indeed, a meta-analysis conducted by Kaufmann et al. 20 discussed a similar research question. However, these authors did not provide adequate reporting on critical aspects such as meta-regressions, and complications. By conducting this systematic review and meta-analysis, we can advance our understanding of the efficacy and safety of Reverdin-Isham and Akin surgical procedures, ultimately improving the care and outcomes for patients with moderate HAV. Therefore, the main objective of this systematic review and meta-analysis was to analyze the effect of Reverdin Isham and Akin surgical procedure on functional (i.e., The American Orthopedic Foot & Ankle Society [AOFAS scores]) and radiological (i.e., IMA, HV angle and DMAA) in patients with moderate HAV. However, given the paramount importance of safety when performing surgical procedures, the second objective of this study was to provide a comprehensive assessment of the complications associated with these surgical procedures. Finally, meta-regressions were conducted to explore the relationship between baseline scores of the included outcomes and improvements achieved after the Reverdin surgical procedure.

Registry of systematic review protocol

This systematic review and meta-analysis was developed using the Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement guidelines 21 . See Supplementary File 1 . In addition, the Prisma in Exercise, Rehabilitation, Sport medicine and Sports science (PERSiT) was also implemented 22 . The protocol was pre-registered on PROSPERO.

Eligibility criteria

To be included, studies had to adhere to the following criteria:

Type of studies: randomized and non-randomized controlled trials were included to evaluate the effect of the Reverdin-Isham and Akin surgical technique. Studies published in both Spanish and English languages were considered for analysis. Additionally, due to the nature of the surgical procedure, case reports were also included, allowing for the inclusion of studies where all available data was reported. Type of participant: participants needed to be above 18 years of age and exhibit a moderate/severe degree of HAV. Patients with moderate hallux valgus display a hallux abductus angle ranging between 20° and 40°, and a first intermetatarsal angle of 8° to 15°. In the case of severe hallux valgus, these values exceed those observed in moderate hallux valgus 23 .

Types of interventions: the interventions had to include exostectomies, Reverdin-Isham osteotomy, Akin osteotomy, tenotomy of adductus tendon and lateral capsulotomy. Type of outcome measures: the outcomes of interest were AOFAS scores, IMA, DMAA and, HV angle .

Search strategy

The primary search focused on studies reporting the effect Reverdin Isham and Akin surgical technique on functional and radiological outcomes. The final search date July 18 th , 2023. Searches were performed through MEDLINE via PubMed and Web of Science. A PICO strategy was used to build search criteria for electronic databases. The PICO consisted of terms for Reverdin Isham and Akin surgical technique on functional (i.e., AOFAS scores) and radiological outcomes (i.e., IMA, DMAA and HV angle ). The search string used for MEDLINE/PubMed was: ("Minimally Invasive Surgical Procedures"[MeSH Terms] OR ("reverdin isham"[Title/Abstract] OR "reverdin isham osteotomy"[Title/Abstract] OR "reverdin isham percutaneous"[Title/Abstract] OR "reverdin isham percutaneous osteotomy"[Title/Abstract] OR "reverdin isham procedure"[Title/Abstract])) AND ("Podiatry"[MeSH Terms] OR "Hallux Valgus"[MeSH Terms] OR ("Podiatry"[Title/Abstract] OR "Hallux Valgus"[Title/Abstract])). The searches strings used for other databases were adapted using Polyglot Search Translator Tool ( https://sr-accelerator.com/#/polyglot ) 24 .These searches strings are reported in Supplementary File 2 .

Study selection

To remove duplicate references, an online tool ( https://www.sr-accelerator.com/#/deduplicator ) was used first, followed by manual removal using the Mendeley reference manager. Two authors (Author 1 and Author 4) independently reviewed titles and abstracts for initial eligibility using an online tool ( https://www.sr-accelerator.com/#/disputatron ). Any disagreements were resolved through discussion, and if necessary, the third reviewer (Author 4) was consulted.

Study coding and data extraction

All data extraction was made independently by two authors (Author 1 and Author 2). From the included studies, the following data was extracted and coded: (1) authors, year of publication, (2) the number of participants in the study and characteristics such as sex, age, body mass, body mass index, height, and (3) follow-up. Mean and standard deviation of AOFAS scores as well as mean and standard deviation of radiological outcomes (i.e., IMA, HV angle and DMAA) were collected in a single Excel spreadsheet. In addition, number of surgeon, partial and/or absolute reliability scores were also obtained.

Methodological quality and risk of bias

Two researchers (Author 1 and Author 5) independently assessed the Joanna Briggs Institute (JBI) critical appraisal tool for case series studies. This tool includes 10 questions addressing the internal validity and risk of bias of case series designs, particularly confounding, selection, and information bias, in addition to the importance of clear reporting 25 . A complete description of this tool as well as the GRADE system is found in Supplementary Table 1 (Supplementary File 3 ).

Statistical analysis

The sample size, and means, standard deviation, 95% confident intervals (CI 95% ) for AOFAS scores, as well as radiological outcomes were extracted independently by two authors (Author 1 and Author 5). The effect size calculations (i.e., standardized mean differences [SMD] and mean differences [MD]) as well as meta-analytical statistical procedures is explained in Supplementary File 4 . Briefly, a random-effects meta-analysis was performed for each separate outcome using Hartung-Knapp/Sidik-Jakman adjustment to calculate model parameters for small-sample correction 26 .

Ethical approval and consent to participate

This study design and protocol were performed in accordance with the PRISMA Statement. The protocol was registered previously on PROSPERO CRD-42023445886.

Search results

Figure  1 presents the flow chart detailing the various stages of the literature search and the selection of studies included in this review. The initial search of electronic databases yielded 352 records. Before the screening process, a total of 16 studies were removed due to filters set for journal articles and those not written in English or Spanish, dated. Duplicate studies were then removed (k = 120 through automated tool and 13 manually), after which an additional 169 studies were excluded based on the title and abstract screening. Furthermore, 27 studies were excluded after full-text assessment (see Supplementary File 5 ). A total of 7 studies (Biz et al. 15 , Restuccia et al. 17 , Ribeiro et al. 13 , Severyns et al. 12 , Rodriguez-Reyes et al. 18 , Bauer et al. 11 , Bauer et al. 19 . Indeed, a meta-analysis conducted by Kaufmann et al. 20 were therefore included.

PRISMA flow diagram chart.

Participants and interventions characteristics

The cumulative sample size across all studies was 554 patients, encompassing 643 operated feet. 78 were males and 298 were females. Only one study reported body mass. Information regarding the number of surgeons was provided by merely two studies; in the Biz et al. 15 study, all surgeries were conducted by a single surgeon, whereas the surgeries in the Ribeiro et al. 13 study were performed by two surgeons. More information can be found in Supplementary Table 2 (Supplementary File 6 ).

Risk of bias

Table 1  summarized the JBI appraisal tool scores for selected studies. From a quantitative point of view, item 1 was label as “Yes” in k = 6 (86%), “unclear” in k = 1 (14%) and “No” in k = 0 (0%). Item 2 was label as “Yes” in k = 4 (57%), “unclear” in k = 2 (29%) and “No” in k = 1 (14%). Item 3 was label as “Yes” in k = 5 (71%), “unclear” in k = 2 (29%) and “No” in k = 0 (0%). Item 4 was label as “Yes” in k = 3 (43%), “unclear” in k = 4 (57%) and “No” in k = 0 (0%). Item 5 was label as “Yes” in k = 6 (86%), “unclear” in k = 1 (14%) and “No” in k =  = 0 (0%). Item 6 was label as “No” in k = 7 (100%). Item 7 was label as “Yes” in k = 4 (57%), “unclear” in k = 0 (0%) and “No” in k = 3 (43%). Item 8 was label as “Yes” in k = 6 (86%), “unclear” in k = 0 (0%) and “No” in k = 1 (14%). Item 9 was label as “Yes” in k = 5 (71%), “unclear” in k = 0 (0%) and “No” in k = 2 (29%). Item 10 was label as “Yes” in k = 4 (57%), “unclear” in k = 3 (43%) and “No” in k = 0 (0%).

Meta-analysis results

After Reverdin surgical procedure the univariate meta-analysis revealed a statistically significant increase on AOFAS scores (SMD = 3.29 [1.66–4.92], t 6  = 4.94, p  = 0.003 and MD = 36.89 [28.61–45.16], t 6  = 10.91, p  < 0.0001). The heterogeneity obtained correspond to I 2  = 96% (94–98%). On the other hand, prediction interval ranged from 13 to 61. Figure  2  summarized the forest plot for AOFAS scores MD. Risk of bias and GRADE are summarized in Tables 1 and 3 , respectively.

Forest plot for American Orthopedic Foot & Ankle Society (AOFAS) scores after Reverdin surgical procedure. N = total sample size, MD = mean differences, 95%CI = 95% confident interval.

Regarding IMA, the univariate meta-analysis revealed a statistically significant increase after Reverdin intervention (SMD = − 1.06 [− 1.55 to − 0.58], t 6  = 5.40, p  = 0.002 and MD = − 3.07° [− 4.68 to − 1.46], t 6  = − 4.68, p  = 0.003). The heterogeneity obtained correspond to I 2  = 95% (91% to 97%). On the other hand, prediction interval ranged from − 8 to 1.56. Figure  3  summarized the forest plot for IMA scores MD. Risk of bias and GRADE are summarized in Tables 1 and 3 , respectively.

Forest plot for Intermetatarsal Angle (IMA) scores after Reverdin surgical procedure.

Results were expressed in degrees ( ° )

In relation to DMAA, the univariate meta-analysis demonstrated a statistically significant increase following the Reverdin intervention (SMD = − 1.05 [− 1.62 to − 0.47], t 5  = 4.69, p  = 0.005 and MD = − 6.12 [− 9.52 to − 2.71], t 5  = − 4.62, p  = 0.006). The heterogeneity obtained correspond to I 2  = 96% (93–98%). On the other hand, prediction interval ranged from − 16 to 3. Figure  4  summarized the forest plot for DMAA scores MD. Risk of bias and GRADE are summarized in Tables 1 and 3 , respectively.

Forest plot for Distal Metatarsal Articular Angle (DMAA) scores after Reverdin surgical procedure. N = total sample size, MD = mean differences, 95% CI = 95% confident interval. Results were expressed in degrees (°).

Regarding HV angle , the univariate meta-analysis revealed a statistically significant increase after Reverdin intervention (SMD = − 2.05 [− 2.54 to − 1.57], t 5  = − 10.88, p  = 0.0001 and MD = − 15.27 [− 17.98 to − 12.57], t 5  = − 14.50, p  < 0.0001). The heterogeneity obtained correspond to I 2  = 93% (87–96%). On the other hand, prediction interval ranged from − 23 to 8. Figure  5  summarized the forest plot for DMAA scores MD. Risk of bias and GRADE are summarized in Tables 1 and 3 , respectively.

Forest plot for Hallux Valgus Angle (HV angle ) scores after Reverdin surgical procedure. N = total sample size, MD = mean differences, 95%CI = 95% confident interval. Results were expressed in degrees (°).

Complications

The studies included in the present systematic review and meta-analysis have reported the following complications associated with the Reverdin surgical technique. In the study conducted by Biz et al. 15 , a total of 25 patients encountered complications, out of which 6 (24%) patients experienced serious complications, such as recurrence and severe stiffness. The remaining 19 (76%) patients dealt with minor complications like slight loss of normal range of motion in the MTP joint and delayed wound healing. On the contrary, Retuccia et al. 17 did not report any major complications. However, among their 25 patients, minor complications were noted, including incomplete correction of deformities, transfer metatarsalgia, and HV overcorrection. Ribeiro et al. 13 documented complications in 8 (25%) patients, with 2 having serious complications, namely recurrence and third metatarsal stress fracture, while 6 (75%) faced minor complications like Hallux hypoesthesia, transfer metatarsalgia, and type 1 complex regional pain syndrome. Severyns et al. 12 identified complications in 15 (7%) patients, including one case of deep vein thrombosis and 14 (93%) minor complications like transfer metatarsalgia, delayed cutaneous healing, recurrences, and hallux hypoesthesia. In Bauer et al. 19 study, 10 patients experienced complications, with 5 (50%) facing serious complications such as deep vein thrombosis and stiffness of the first MTP joint, while the other 5 (50%) developed type 2 complex regional pain syndrome. In another study by Bauer et al. 11 , 24 complications were reported, with 14 (58%) being major complications like fractures, stiffness of the first MTP joint, and recurrences, while 10 (42%) were minor complications such as DMAA overcorrection, complex regional pain syndrome, and transfer metatarsalgia. Lastly, the article by Rodriguez-Reyes et al. 18 did not provide any information about complications.

Meta-regressions

The improvements observed in all outcomes included in this meta-analysis were found to be associated with the baseline scores of each variable. The results obtained from the analysis are presented and described in Table 2 and Fig.  6 .

The meta-regression results were obtained after analyzing the relationship between baseline scores and improvement following the Reverdin surgical procedure. ( A ) AOFAS vs. AOFAS baseline, ( B ) IMA versus IMA baseline, ( C *) DMAA versus DMAA baseline and, ( D ) HV angle versus HV angle baseline. The blue line represents the regression line, while the grey shaded areas denote the 95% confidence intervals.

The results of the meta-regressions, Fig.  7 , which examined the relationship between age and improvements in outcomes (i.e., AOFAS, IMA, DMAA, and HV angle ), were as follows: The associations between AOFAS and age, as well as DMAA and age, did not exhibit statistical significance (estimate = − 0.26, p  = 0.768 and estimate = 0.36, p  = 0.339, respectively). However, statistically significant relationships were identified when comparing age with IMA (estimate = − 0.31, p  = 0.0003, R 2  = 81%) and with HV angle (estimate = − 0.60, p  < 0.0001, R 2  = 97%).

The meta-regression results were obtained after analyzing the relationship between age and improvement following the Reverdin surgical procedure. ( A ) AOFAS versus age, ( B ) IMA versus age, ( C *) DMAA versus age and, ( D ) HV angle versus age. The blue line represents the regression line, while the grey shaded areas denote the 95% confidence intervals.

GRADE system

The GRADE system for AOFAS, IMA, DMAA and HV angle is summarized in Table 3 .

Publication bias

No publication bias was detected both from a visual point of view (i.e., funnel plots, see Fig.  8 ) and statistical point of view (i.e., egger test).

Funnel Plot for American Orthopedic Foot & Ankle Society (AOFAS) scores, Intermetatarsal Angle (IMA), Distal Metatarsal Articular Angle (DMAA), and Hallux Valgus Angle (HV angle ).

The results obtained for egger tests for AOFAS, IMA, DMAA and HV angle are summarized in Table 4 .

The primary aim of this systematic review and meta-analysis was to examine the impact of the Reverdin-Isham and Akin surgical procedures on functional and radiological outcomes in patients diagnosed with moderate HAV. The main findings indicated that the Reverdin and Akin surgical technique was a safe and beneficial technique for addressing moderate HAV. The functional assessment, as measured by AOFAS scores, exhibited a significant average improvement of 36 points, indicating enhanced foot function and reduced pain for patients. Moreover, notable improvements were observed in radiological outcomes, with reductions of − 3.07°,− 6.12°, and − 15.27° observed in IMA, DMAA, and HV angle , respectively. On the other hand, the primary complications reported in the included studies were recurrence, deep vein thrombosis and fracture. Finally, a substantial, statistically significant, and negative relationship was observed between the baseline scores and the improvements following the Reverdin surgical procedure. That is, patients with poorer scores in both functional and radiological outcomes demonstrated a more favorable response in the analyzed outcomes after surgical procedure. These findings underscore the effectiveness of the Reverdin-Isham and Akin surgical technique in improving both functional and radiological parameters in patients with moderate HAV. However, these results come from studies with some concerns or high risk of bias. Overall, the study highlights the potential benefits of these surgical interventions in enhancing patient outcomes and provides valuable insights for healthcare professionals when considering treatment options for moderate HAV.

The AOFAS scale is recognized as a valuable instrument for outcome assessment in numerous studies 18 , 27 . However, in this meta-analysis, although we found values ranging from 0 out to 100 and represented as pre-post mean differences, we did not find any studies that breakdown each aspect of the scale in the same manner as specified by Naranjo-Ruiz et al. 28 , i.e., representing the scores obtained on each dimension. This limitation hinders the individual analysis of critical variables such as pain, function, and alignment, which could provide new perspectives in evaluating each surgical intervention.

Several studies have compared functional outcomes after Reverdin osteotomy versus Chevron osteotomy for hallux valgus, using the AOFAS scale. A study by Kaufmann et al. 20 , with 49 patients (59 feet), found a notably greater improvement in AOFAS scores after Reverdin osteotomy (increasing from 48 to 91 points) compared to Chevron osteotomy (improving from 65 to 95 points). These findings align with our results; however, in our meta-analysis, we identified an improvement exceeding 36 points. Interestingly, meta-regression results showed a negative and statistically significant relationship between baseline AOFAS scores and the AOFAS effect size (see Table 2 ). That is, the range of improvement of those patients with lower AOFAS scores will be larger than those patients with higher values. Nevertheless, the GRADE system provided a very low overall quality for AOFAS, mainly due to inconsistency and risk of bias in the included studies.

The Reverdin technique has demonstrated significant improvements in radiological angles like the IMA, HVangle, and DMAA. On average, reductions of − 3.07° (ranging from − 4.68° to − 1.46°) for the IMA angle, − 15.27° (ranging from − 17.98° to − 12.57°) for the HVangle, and − 6.12° (ranging from − 9.52° to − 2.71°) for the DMAA angle were observed. Additionally, the Reverdin technique is characterized as a minimally invasive procedure with a short recovery duration and low risk of complications. Notably, the meta-regression results revealed negative and statistically significant relationships between baseline angle scores and the corresponding effect sizes after the Reverdin surgery. Patients with higher initial HVangle and IMA angle values experienced greater improvements in correcting these radiological parameters compared to those with lower baseline angles. These findings suggest that the Reverdin osteotomy may be particularly effective for patients with more severe deformities prior to the surgical intervention, enabling substantial correction of intermetatarsal and hallux valgus angles.

The risk of bias analysis highlights specific issues with the standardization of procedures for collecting and reporting results in the field of orthopedics, particularly regarding items 6 and 7. These items pertain to the reporting of participant demographics and clinical information in studies. The lack of standardized procedures for these aspects can lead to data inconsistencies, which in turn might affect the validity and reproducibility of the studies. This is critical as demographics and clinical information are fundamental to understanding the context and applicability of study results to broader populations. The non-standardization in these areas risks undermining confidence in the findings and limits the ability to generalize results, potentially biasing the interpretations and conclusions drawn from such studies.

The meta-regression results from our study revealed significant associations between baseline scores and improvements in IMA, DMAA, and HVangle after Reverdin surgery (see Fig.  6 ), consistent with the literature 11 , 15 , 19 . The meta-analysis identified varying effects of age on the enhancement of different measurements after minimally invasive surgery. There was no statistically significant impact of age on the improvement in clinical AOFAS scores or DMAA angle after surgery, suggesting that changes in these measures are independent of age.

Several limitations might be considered when interpreting the results obtained in this meta-analysis. Firstly, from a methodological point of view, the absence of control groups in the included studies was a notable limitation. While the obtained effect sizes are promising and provide a general indication of the potential outcomes following the application of the Reverdin surgical technique, it is crucial to acknowledge that various confounding factors may influence the observed results. Nevertheless, in situations where there is a limited availability of high-quality experimental studies assessing effectiveness, case series may serve as the most valuable evidence to guide clinical practice 25 . Furthermore, it is worthing to highlight that the heterogeneity scores obtained in this meta-analysis were high. The presence of substantial heterogeneity suggests that there are differences among the included studies in terms of populations, or other relevant factors (such as the number of surgeons or the specific procedures during rehabilitation or estimated data from original studies such as Pearson correlations coefficients or SD´s). This heterogeneity may impact the overall validity and generalizability of the findings. Therefore, caution should be exercised when interpreting the results, and further research is needed to explore and address the sources of heterogeneity to obtain more robust and reliable conclusions. The absence of meta-regression or subgroup analysis (apart from baseline scores or age) in this study was attributed to the lack of homogeneity in terms of patient characteristics across the included studies. For future studies, it is recommended to systematically report information regarding patient characteristics, such as body mass, number of surgeons, exercise practices, or post-surgical procedure protocols. Including these details in a more standardized manner would enhance the comprehensiveness and reliability of the research findings, allowing for a more thorough analysis of the potential impact of these factors on outcomes.

Conclusions

In conclusion, although the studies included in the review exhibit some degree of bias risk, the findings suggest that the Reverdin and Akin techniques are safe and effective in improving both functional and radiological parameters in patients with moderate to severe hallux valgus. Furthermore, the negative relationship observed between baseline factors and post-surgical improvements underscores the efficacy of these surgical techniques. This implies that patients with poorer initial conditions tend to experience more significant improvements following surgery, reaffirming the importance of considering these procedures as a valid and potentially transformative option for treating hallux valgus.

Data availability

The data presented in this study are available upon request to the corresponding author.

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Sanchís-Soria, V., Nieto-González, E., Nieto-García, E. et al. Radiological and functional outcomes of Reverdin Isham osteotomy in moderate Hallux Valgus: a systematic review and meta-analysis. Sci Rep 14 , 14781 (2024). https://doi.org/10.1038/s41598-024-65440-3

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Research Article

The water adaptation techniques atlas: A new geospatial library of solutions to water scarcity in the U.S. Southwest

Roles Conceptualization, Data curation, Investigation, Methodology, Project administration, Supervision, Visualization, Writing – original draft, Writing – review & editing

* E-mail: [email protected]

Affiliation USDA Southwest Climate Hub, Las Cruces, New Mexico, United States of America

Roles Conceptualization, Funding acquisition, Project administration, Supervision, Writing – review & editing

Roles Data curation, Investigation, Writing – review & editing

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Affiliation Resource and Rural Economics Division, USDA Economic Research Service, Washington, District of Columbia, United States of America

Roles Conceptualization, Funding acquisition, Supervision, Writing – review & editing

Affiliation Sustainable Agricultural Water Systems, USDA Agricultural Research Service, Davis, California, United States of America

Affiliations USDA Southwest Climate Hub, Las Cruces, New Mexico, United States of America, Sustainable Agricultural Water Systems, USDA Agricultural Research Service, Davis, California, United States of America, Institute of the Environment, University of California, Davis, Davis, California, United States of America

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Affiliations USDA California Climate Hub, Davis, California, United States of America, Institute of the Environment, University of California, Davis, Davis, California, United States of America

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Affiliation Jornada Experimental Range, USDA Agricultural Research Service, Las Cruces, New Mexico, United States of America

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Affiliation Center for Watershed Sciences, University of California, Davis, Davis, California, United States of America

• Noah Silber-Coats, 
• Emile Elias, 
• Caiti Steele, 
• Katherine Fernald, 
• Mason Gagliardi, 
• Aaron Hrozencik, 
• Lucia Levers, 
• Steve Ostoja, 
• Lauren Parker, 

• Published: June 26, 2024
• https://doi.org/10.1371/journal.pwat.0000246
• Reader Comments

As climate change, population demands, and economic growth put increasing pressure on finite water resources in the southwestern United States, there is a critical need for adaptation to increasing water scarcity in the region. The Water Adaptation Techniques Atlas (WATA) is a new web-based compendium of geospatially-referenced solutions to problems posed by water scarcity. Developed by the USDA Southwest and California Climate Hubs, WATA arranges these solutions as case studies pinpointed on an interactive, user-friendly map viewer. Cases include research outcomes and practices that impact water use and availability to alleviate the mismatch between supply and demand. Organization of case studies by type of practice, specific crops, types of water user and water use allows a broad base of users to locate adaptations of particular interest. An example use case presented in this article shows how WATA can be used to investigate alternatives to alfalfa, one of the biggest water-consuming crops in the region. The development of WATA is an ongoing, iterative process, informed by new research and by feedback from agricultural professionals and others concerned with water scarcity in the Southwest.

Citation: Silber-Coats N, Elias E, Steele C, Fernald K, Gagliardi M, Hrozencik A, et al. (2024) The water adaptation techniques atlas: A new geospatial library of solutions to water scarcity in the U.S. Southwest. PLOS Water 3(6): e0000246. https://doi.org/10.1371/journal.pwat.0000246

Editor: Jean-Marc Mwenge Kahinda, University of the Witwatersrand Johannesburg Faculty of Engineering and the Built Environment, SOUTH AFRICA

Received: December 13, 2023; Accepted: May 14, 2024; Published: June 26, 2024

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Data Availability: All data are available in the manuscript and on the WATA website (embed link: https://webapps.jornada.nmsu.edu/wata/ ).

Funding: This work is a contribution of the USDA Southwest Climate Hub. Manuscript development was supported by the USDA, Agricultural Research Service, Rangeland Management Research Unit based at the Jornada Experimental Range with funding by the USDA Agricultural Research Service (CRIS Project # 3050-12610-001-00D to EE), USDA Economic Research Service (agreement # 60-3050-1-006 to EE) and USDA Office of the Chief Economist (agreement # 60-3050-1-002 to EE). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Introduction

Contemporary water scarcity in the southwest: the need for adaptation.

Despite prevailing dry climatic conditions, the southwestern United States (Southwest) contains some of the most productive agricultural regions in the world and many of the fastest-growing cities in the country. The dramatic expansion of both agriculture and urban areas in the Southwest over the past century has relied on monumental infrastructure for capture, storage, and distribution of surface water as well as intensified extraction of groundwater [ 1 , 2 ]. As a result of global climate change driven by anthropogenically mediated heat-trapping gas emissions, the Southwest experienced its driest period in over a thousand years from 2000 to 2021 [ 3 ], and the Intergovernmental Panel on Climate Change (IPCC) projects that the region will face more severe, more frequent, longer-lasting droughts as global temperatures continue to rise [ 4 ]. As the severity of drought has intensified, with periods of extreme heat and prolonged dry spells leading to declining river flows and drier soils, some scientists now suggest that this trend be labeled aridification rather than drought, indicating an effectively permanent change to drier conditions in the region [ 5 ].

Given the increased demand for, and reduced availability of, water resources in the Southwest, adaptations to water scarcity will be required to offset major harmful impacts on society [ 6 ]. Dissemination of information about adaptation options is also critical. The Water Adaptation Techniques Atlas (WATA) responds to this need, providing a new compilation of information on techniques for addressing water scarcity, specifically in the six states covered by the United States Department of Agriculture (USDA) Southwest and California Climate Hubs ( Fig 1 ).

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Aridity (annual average 1970–2000) data are from the Global Aridity Index and Potential Evapotranspiration Climate Database v3 . Irrigated land data are from US Geological Survey MODIS Irrigated Agriculture Datasets for the Conterminous United States . Rivers of the U.S . from National Weather Service. National borders from ESRI World Countries , state boundaries from ESRI USA States Generalized Boundaries .

https://doi.org/10.1371/journal.pwat.0000246.g001

This article establishes the context of and need for WATA. It describes WATA’s purpose and the process of developing it, gives an overview of the database and how to use and contribute to it, and provides examples of how it can be used to synthesize information on a given topic. Finally, a summary of findings to date and opportunities to expand and improve WATA are presented.

Adaptation to water scarcity in the Southwest: Historical context

The necessity of adapting to water scarcity is a fundamental feature of human-environment relations in arid environments. The histories of indigenous peoples in the Southwest show reliance on a variety of strategies to manage scarce water resources, including flood-recession agriculture, capturing water from seasonal storms, channeling runoff to favored plants, and seasonal migration [ 7 ]. WATA includes examples of such adaptations, categorized as “indigenous or ancestral techniques”, as they may be instructional and relevant for the 21st century. Beginning in the 16th century indigenous water resources management was supplanted due to Euro-American colonization, and since the mid-19th century, the predominant adaptations to water scarcity in the western U.S. have been the dams, reservoirs, canals, pipelines, pumps, and wells that make up the region’s contemporary water infrastructure. WATA also includes examples of this type of adaptation.

In more recent decades, there is some evidence of a shift in the approach of water management towards reducing demand through conservation efforts, many examples of which are included in WATA. Since 1965, even as irrigated agriculture has expanded in the Southwest, the amount of water applied per acre has generally declined [ 8 ]. Even in Arizona, which uses the most irrigation water per irrigated land area of all U.S. states, water applied declined by roughly 20% between the years 2000 and 2018 [ 8 , 9 ], and total agricultural water use in the Southwest declined by nearly one third between its peak in 1980 and 2010 [ 10 ]. Many cities in the region have also successfully decoupled population growth from increased water use, registering declines in both per capita and total water use from 2000–2015 [ 11 ]. Despite apparent successes like these, information about water scarcity adaptation efforts across the Southwest tends to be fragmented by academic discipline and geographic divides.

The genesis of WATA

Recognizing the increasing pressures on water resources in the Southwest, the USDA California and Southwest Climate Hubs began a project in 2020 to develop and share geospatially referenced examples of water scarcity solutions to support water adaptation techniques across this region. The resulting product, WATA, meets the project’s goals of documenting solutions to water scarcity that are being implemented, providing a platform for disseminating this information broadly, and facilitating knowledge transfer to foster future resilience.

Part of the impetus for creating WATA was the experience of several co-authors with responses to exceptional drought in the Four Corners region of Arizona, Utah, Colorado, and New Mexico in 2018 and to severe droughts in California from 2012–2016 and 2020–2022. Through communication with local resource managers during a period of exceptional drought on the Colorado Plateau in 2018, Southwest Climate Hub staff learned of a variety of efforts being undertaken by communities and individuals in that area, including establishing shortage-sharing agreements for rotating limited water supplies among irrigators, water hauling for livestock and wildlife, hand-watering of high-value crops, and fallowing of lower-value ones [ 12 ]. This experience helped shape the idea for documenting adaptations to water scarcity in the Southwest and creating a tool for documenting these kinds of practices.

The vision for WATA

WATA is meant to be a dynamic platform that will allow resource managers, researchers, and educators to identify practices that can be used to mitigate the effects of both temporary water shortage and expected longer-term water scarcity. The results are presented in a geospatial platform, with location-specific case studies.

With over 200 entries completed, and more being added regularly, the atlas provides a wide range of information that may be relevant to many kinds of users. Corresponding to the high share of water used by agriculture in the region, the bulk of case studies concern cropping and irrigation practices, with often highly technical information summarized in a way that is both accurate and accessible to non-specialists. The design of the tool allows users to curate a set of case studies that best suits their purpose and interests.

What WATA is not

WATA is not a prescriptive simulation model that accepts inputs and calculates outputs. Rather, it is a browsable map-based tool–an atlas–for obtaining information about, and visualizing the spatial context of, many types of adaptive responses to water scarcity in the Southwest. Case studies are presented in appropriate scientific detail without being overly reliant on discipline-specific technical jargon. Each case study is rigorously documented, with links to sources from both peer-reviewed and gray literature, providing a point of entry for users to delve more deeply into a given intervention.

Despite its broad scope WATA does not purport to be a completed inventory of all projects, practices, and policies for addressing water scarcity in the region. Instead, it is meant to grow in topical and geographic focus through the steady addition of additional case studies. WATA may assist users interested in gauging parameters such as prevalence or effectiveness of various strategies, but it does not explicitly perform that function itself. The apparent geographic bias towards Arizona and New Mexico, for example, reflects the process of building the tool by initially focusing on those states and then gradually scaling up across the region, rather than a greater prevalence of certain practices in that part of the region. Finally, case studies are intended to provide objective analysis of adaptations, not advocacy for any specific practice.

Tool design: Concept

WATA is designed to share information on adaptations to an increasingly arid climate in a region that has been characterized by arid and semi-arid conditions for the last 11,000 years [ 13 ]. Arid lands are defined by the scarcity of water (or evapotranspiration exceeding precipitation), so adaptation to this condition is necessary for all life in such environments. While climate models generally predict hotter, drier conditions in the Southwest [ 14 ], adaptation to aridity is necessary in this region even absent these trends. Given these conditions, WATA does not distinguish between adaptations to aridity in general and those undertaken in response to climate change.

The case studies collected in WATA include a broad range of practices, projects, and policies for addressing water scarcity, or the imbalance between demand for water use and its availability. However, rather than collecting only examples of apparently successful adaptation, this effort recognizes that adaptation and maladaptation exist on a continuum [ 15 ], and any ostensibly adaptive action may also come with negative tradeoffs. WATA includes a broad range of interventions in the water cycle that affect water use and availability within the study region–even if these actions may reduce water scarcity at one scale while exacerbating it at another.

The text of each case study is original writing by WATA developers, drawing on published source material that is cited within the tool. Any images re-produced in the tool are open source with attribution or with permission of the copyright owner.

Development process for WATA

WATA was developed through a non-systematic literature review aimed at identifying case studies of practices, projects, and policies for addressing water scarcity in the Southwest. This process follows the approach of a “realist review,” which seeks to gather the “vast experience of the options and possibilities” [ 16 ] for intervening in a system, to answer the question, “what works for whom, in what circumstances, in what respects and how?” [ 17 ].

Following Cooper’s (1988) categorization of literature reviews by focus , goal , perspective , coverage , organization , and audience [ 18 ], this process can be characterized by a focus on research outcomes and practical applications of interventions to address water scarcity. In addition to taking place within the Southwest region as defined above, the focus is further limited to research or practice with a tangible intervention (i.e., not purely modeled outcomes), where evidence of the effect of this intervention on water use or availability is provided. The goal is to create a common framework for analyzing these case studies, which are drawn from a wide range of literature types and disciplines. The perspective is a neutral position, presenting information as given in original sources and representing all sides when disagreement is evident. Coverage of the review aims to be exhaustive, while recognizing that this ideal is not practically attainable.

Drawing on the practice of the “Critical Interpretive Review” [ 19 ], the research process is iterative, allowing for search results to suggest new practices, spurring further searches to identify new case studies. To date, this process has identified over six hundred sources. The organization of the review, rather than being presented in a single narrative, is contained within WATA, where users can search and sort for case studies using multiple criteria. The intended audience is water management professionals in a broad sense–this may include researchers from multiple disciplines, practitioners, and policymakers with diverse perspectives. To reach these diverse audiences, case studies are written to be accessible to the general public while containing a level of detail relevant to specialists.

A key part of the iterative process followed here was the development of a typology of the types of practices, projects, and policies for addressing water scarcity. Existing typologies such as those of Richter et al. [ 20 ], provided initial search terms, which were paired with geographic terms (e.g., names of states, watersheds) which were used in querying Google Scholar, the National Agricultural Library, and government agency and NGO websites (e.g., Bureau of Reclamation, USDA Natural Resource Conservation Service, The Nature Conservancy, Sonoran Institute). As results are identified, the typology of categories is continually refined. This typology, discussed below, is one of the principal ways case studies are organized in WATA, allowing users to identify relevant information. A decision tree outlining the procedure for conducting this review and building the database appears in Fig 2 .

https://doi.org/10.1371/journal.pwat.0000246.g002

Tool architecture

WATA is designed to be stable and easy to update. New entries are created on an Excel spreadsheet which includes geographic location coordinates. This spreadsheet is converted to a feature layer using ArcGIS Online, which serves the data to the website hosted by the Jornada Experimental Range (the host of the USDA Southwest Climate Hub at New Mexico State University). Updates to the data are reflected in the tool with no changes needed on the back end—for example, if a new category or crop is listed on the spreadsheet it will appear as an option in the filter.

Distinctiveness: WATA’s relationship to other tools

While the scope of WATA is unique, it fits into a category of tool in which information is organized into a collection of geospatially-referenced case studies. The design of WATA pulls from tools including the Environmental Justice Atlas (EJA) [ 21 – 23 ] and the Conservation and Adaptation Resources Toolbox (CART) [ 24 ]. The EJA documents cases of conflict over and resistance to ecologically damaging extraction and development projects around the world. The design of the EJA, with case studies containing descriptive information represented as points on a map, along with capabilities for searching and filtering, provided the general model for WATA. The EJA is crowd-sourced, allowing anyone to submit a case study. WATA contains a similar capability through a comment form that allows anyone to submit suggestions which are reviewed by the editors before being posted.

CART, a project led by the U.S. Fish and Wildlife Service, also informed the design of WATA. CART presents case studies of resource management pinned to geographic locations, covering a broad range of topics with a focus on methods and lessons learned. Several cases posted there are relevant to water scarcity in the Southwest, and these are included in WATA adapted to its format, along with several case studies co-developed between the two platforms. However, CART has a broader topical and geographic focus, while WATA provides more comprehensive coverage of water scarcity solutions in the Southwest.

Other existing tools present descriptive information about water management in the western U.S., such as the Bureau of Reclamation’s WaterSMART Data Visualization Tool [ 25 ], the California Groundwater Projects Tool [ 26 ] and the Water for Colorado Projects Map [ 27 ]. While some of the projects documented in these tools may be eligible for inclusion in WATA, their main focus is on tracking expenditures for state and federal grant funds related to water sustainability. WATA includes a broader suite of practices, policies, and projects than these tools, and rather than a tendency to present successful outcomes of public expenditures, includes information about limitations and tradeoffs of these options.

Organizational structure of the WATA database

The basic unit of information in WATA is the case study. The database currently contains just over 200 entries, with a similar number identified as candidates for inclusion (Figs 3 – 5 ). While the geospatial arrangement of these case studies on an interactive map is central to WATA’s functionality, the spatial data contained in the atlas is simple and limited—each case study is pinned to a single point on the map (although some cases that span multiple locations have several inter-linked pins). This approach is intentional, to avoid cluttering the map with different types of data. Essentially, WATA is a library of case studies with their location on the map as one option the user can employ to find relevant information. Options for searching and filtering, discussed below, provide another alternative. A forthcoming video tutorial will aid users in navigating the site.

Basemap from ESRI Streets (with Relief).

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Basemap from ESRI Imagery Hybrid.

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https://doi.org/10.1371/journal.pwat.0000246.g005

Case study descriptions contain information on the background of the problem and solution being discussed, the adaptation actions being implemented or proposed, the evidence for their impact, and the potential tradeoffs that they may entail. This description is accessed by clicking on an individual case study. A succinct description will also appear when a user hovers over a case study point on the map. Each case is tagged according to the type of intervention, the crop or ecosystem type involved, and the type of water use and water users involved.

Cases can be found in multiple ways. Because they are arranged on a map, users may begin by looking for items in a geographic area of interest. The search bar at the top of the case-viewer window combs text of all titles and descriptions to provide exact matches. This could be useful for finding cases involving a specific organization, which are listed in an “Actors” field for each entry. For example, typing “Salt River Project”—the name of a major water provider in central Arizona—returns fifteen results.

The filter tool, accessed by clicking on the funnel icon in the top bar of the case study viewer, provides an additional way to find case studies by subject area. Here, cases falling within certain categories can be selected. Results will appear both on the map and in the “View Case List” button (three horizontal lines) at the top of the viewer.

Categories of adaptation techniques

Categories are not mutually exclusive, and a given entry may be tagged with as many as five categories. Table 1 shows the structure of the categories designed to reduce water demand, providing an example case for each category or subcategory. Numbers in parentheses indicate the number of cases tagged in that category in February 2024. As cases are continually added, these numbers will increase over time. These values provide an indication of areas with relatively robust information (e.g., “Crop Choice and Rotation” and “Irrigation Technology and Timing”), as well as areas that are ripe for future expansion (e.g., “Shortage Sharing Agreement” and “Drought Plan”). While some categories currently have few entries, the inclusion of at least one representative case for each provides a marker for types of adaptation practices to be identified as the project expands.

https://doi.org/10.1371/journal.pwat.0000246.t001

Wastewater reuse and water harvesting feature the most cases in strategies intended to increase supply ( Table 2 ), whereas use of brackish groundwater and desalination are emerging as possible solutions with fewer examples. Nearly half of the cases within the Law, Policy, Planning, and Markets meta-category feature market-based solutions ( Table 3 ). Ecosystem focused solutions include desert and grasslands restoration (5 cases), in-stream flow (20 cases), and riparian and wetland restoration (27 cases) ( Table 4 ). A set of secondary themes, which do not describe the type of management intervention but rather areas that may be impacted by the practices encompassed in the categories above, includes water security and water quality.

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https://doi.org/10.1371/journal.pwat.0000246.t003

https://doi.org/10.1371/journal.pwat.0000246.t004

Additional options for filtering cases include water use categories (e.g., agriculture, urban, environment), water user types (e.g., agricultural producer, irrigation organization, water supply system operator). Some cases have associated images or videos which will also appear in the case study viewer. References are provided at the bottom of each case study with links to original sources.

Applications of WATA

WATA has many potential applications, especially for agricultural professionals wishing to learn about water conservation practices. Formal and informal educators will find information on a variety of topics that could enhance curriculum and outreach activities related to water and agriculture, for example, cases on indigenous water management practices and heritage crops for arid lands. WATA cases dealing with multi-stakeholder partnerships to solve water challenges to the benefit of different users, such as cases addressing water for the environment, may be of greatest interest to practitioners in this area from government agencies, NGOs, and community groups. Cases dealing with uses for treated wastewater may inform urban planners and municipal officials. Policymakers may find useful information in WATA about water-sharing agreements. Engineers and inventors can find information about technologies for capturing atmospheric moisture, or recirculating water in closed agricultural systems. A detailed example of one use for WATA is developed below.

An example: Using WATA to investigate alternatives to alfalfa

To provide an example of how WATA might be used, this section considers entries containing information on alternatives to alfalfa, a cattle feed crop that is one of the most economically important and highest water-demanding crops across the western U.S. In the Colorado River Basin, irrigation of cattle-feed crops accounts for 55% of water use, while alfalfa alone accounts for 37% of all consumptive water use [ 82 ]. In the states covered by WATA, water use for alfalfa ranges from 2.1 acre-feet per acre (6,400 cubic meters per hectare) in Utah to 5.8 acre-feet per acre (18,000 cubic meters per hectare) in Arizona where the year-round growing season results in the highest productivity and is reflected in the higher water demand [ 9 , 83 ].

Given the central role that alfalfa and other cattle-feed crops play in water use in the Southwest, solutions that can curb this consumption are central to addressing water scarcity in the region. While some have argued for fallowing of irrigated agriculture as the most cost-effective solution [ 82 ], such efforts are not typically well received by farmers. And, because of the important place of dairy and beef cattle in rural economies across the West, disruptions in feed supply could have consequences across the agricultural sector. Although exports of alfalfa have increased dramatically since 2013 and account for roughly 20% of production, most alfalfa is still consumed domestically [ 82 – 84 ]. Setting aside broader questions about the sustainability of cattle-based industries (which also account for roughly 3% of U.S. greenhouse gas emissions [ 85 ]), adaptations that reduce water use for cattle feed while meeting the demand for high-quality forage would fill an immediate need.

WATA can be used to identify alternative forage crops and cropping systems, providing information on production practices, water management, and potential yields and nutritional value. Producers and other agricultural professionals such as crop advisors or extension personnel could use this information to guide decisions on transitioning from alfalfa to alternative crops. To identify relevant cases for this application, the user can navigate to the filter tab (funnel icon), expand the “Crop or Ecosystem” field, expand the “Grains and Forage” crop category, and select “Forage (excl. alfalfa)” ( Fig 6 ). Given the important role of alfalfa as a forage crop in the Southwest, it has been given its own tag while all other forage crops are grouped together. After making this selection, the user can select “View case list” (three horizontal bars), which gives a summary of the results. These results are presented in Table 5 , with numbers assigned to the results for purposes of the ensuing discussion. The results can be further filtered to identify crops with a particular seasonality using the “Crop Duration and Photosynthetic Pathway” filter, which identifies crops as warm- or cool-season annuals or perennials, and according to their use of C 3, C 4, or CAM pathways.

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https://doi.org/10.1371/journal.pwat.0000246.t005

Five of the results–cases 2, 8, 9, 10, and 14 –address salinity tolerance and suitability of crops for irrigation with relatively saline water. In these cases, the volume of water required for irrigation may not be less than that for alfalfa, but the salt tolerance of the plant creates the possibility of using water sources that are not suitable for other crops, including brackish groundwater and brine produced in a desalination process. These cases provide possible solutions for situations where abundant water is available but not of suitable quality for irrigation of alfalfa or other crops. These include experiments with Southwest native plants quailbush ( Atriplex lentiformis , case 2 [ 86 ]), nipa ( Distichlis palmeri , case 8 [ 87 ]), and saltgrass ( Distichlis spicata , case 10 [ 88 ]), and with more familiar crops irrigated with water of varying salinity, including corn (case 9 [ 89 ]) and triticale (case 14 [ 90 ]).

Two of the results–cases 3 and 4 –address practices that can affect soil moisture conservation, with specific attention to their impact on subsequent growth of forage crops. Case 3 draws on a pair of studies looking at conservation tillage–either no-till or strip-till–practices in corn grown for silage (fermented forage) [ 91 ]. Results show higher moisture in soil under no-till treatment, with similar yields to conventional tillage. In case 4, researchers planted winter cover crops ahead of summer forage sorghum and corn [ 30 , 31 ]. Cover crop adoption has been limited in semi-arid regions in part because of concern about reducing soil moisture availability for subsequent crops. However, this research found that cutting the cover crop and leaving the residue on the soil surface as mulch reduces evaporation and improves plant growth. Cover crops were found to deplete soil moisture in the spring when their growth takes off, meaning that establishment irrigation is essential for the subsequent crop. But as evaporative demand picks up in the summer, the fields mulched with cover crop residue showed a clear advantage.

The remaining seven cases consider crops that can be grown as alternatives to alfalfa using less water for irrigation. Case 1 draws on a study of an heirloom variety of corn called ‘Mexican June’ (MJ) which was widely planted in the Southwest in the early 20th century [ 92 ]. Growing both MJ and hybrids with equal irrigation in the hot and dry conditions of Las Cruces, New Mexico, researchers found grain yields from MJ were comparable to hybrids. Forage yields were not measured, but historic use of MJ as a forage crop is discussed.

Forage yields for corn and sorghum under limited irrigation conditions are compared in case 11, which is based on a study finding that sorghum ( Sorghum bicolor ) produced superior yields to corn under restricted irrigation [ 93 ]. Other possible forage crops included in these results include kenaf ( Hibiscus cannabinus , case 6 [ 94 ]), pearl millet and finger millet ( Cenchrus americanus and Eleusine coracana , case 7 [ 95 – 98 ]), and teff ( Eragrostis tef , cases 12 and 13 [ 99 ]).

Case 5 documents a unique solution among those found here–substituting cool-season crops for water-intensive summer forage [ 100 ]. These crops included mixes of different grains and legumes irrigated either only once before planting or provided with one subsequent irrigation. Results show little benefit from the second irrigation. With only one irrigation, these crop mixes received 20 centimeters of water, compared with 60–100 centimeters typically applied to an alfalfa crop in the area. The highest performing mixes, wheat-pea and triticale-pea yielded approximately 4.5–5 metric tons per hectare, with 17% protein content. This is a similar protein content to high-quality alfalfa [ 101 ], and just under half the average biomass yield for New Mexico alfalfa growers [ 102 ]. However, if these yields can be achieved with less than half the water required for alfalfa as suggested by this study, cool season forage mixes may result in a greater water use efficiency.

While these cases provide detailed information about more than a dozen alternative crops and crop management practices, it will be up to the individual user to determine the applicability of this information to a specific context. Each case provides as much information as possible about suitable conditions for raising each crop, but the results are not tailored to the present or future climate or other environmental conditions of a specific location. For instance, the cases on teff discuss the temperature parameters for this crop, with extended periods above 90F (32C) known to be detrimental. In this case, consulting additional resources such as the National Integrated Heat Health Information System’s map of current and projected days above 90 degrees Fahrenheit [ 103 ] could help in determining the suitability of teff for a given location. For all cases, users must rely on their own knowledge of local conditions and context in evaluating the suitability of a given solution.

Conclusions and future directions

The atlas tool described in this article provides a powerful platform for documenting adaptations to increasingly scarce and over-allocated water resources in an arid environment trending towards greater aridity. Reflecting the high proportion of consumptive water use attributable to agriculture in this region, the bulk of the case studies collected thus far address water conservation solutions for crop production. However, WATA also includes and holds space for further inclusion of a wide range of practices and policies for addressing the imbalance between water supply and demand in the Southwest. This includes urban and industrial water conservation efforts, and infrastructure projects to bring safe and secure water supplies to underserved rural communities. It also explicitly includes practices that address water scarcity issues for water users and uses that have been marginalized by historic water allocation in the region, namely Native American tribes, and water for the benefit of ecosystem health. The atlas has a wide range of possible applications for different purposes and audiences. As in the example of alternative forage crops outlined above, it contains a wealth of information about cropping and irrigation systems that can be applied to challenges faced by producers and conservation professionals who serve them in various capacities. Making different selections using the search or filter functions can quickly curate a set of case studies relevant to the specific interests of a broad range of water and agricultural professionals.

The development of WATA is ongoing, and readers are invited to contribute case study suggestions. The geographic scope is currently expanding from the initial focus on Arizona and New Mexico to include cases in Nevada, Utah, California, and will eventually include case studies in Hawaii and the U.S.-affiliated Pacific Islands which are also served by the Southwest Climate Hub. Of course, state and international boundaries do not necessarily correspond to hydrological, ecological, and socio-cultural regions, and WATA will be enriched by including cases from across a broader landscape. WATA’s development team has had preliminary discussions with partners in West Texas and Colorado and welcomes additional collaborators to help build out the atlas in other regions. This need not be limited to the western U.S.—responses to short- or long-term water scarcity anywhere could be included on the map. During the summer of 2023, parts of the Midwest and South from Minnesota to Louisiana experienced severe drought [ 104 ], responses to which could become part of WATA in collaboration with local partners. Another short-term goal for WATA is to include case studies from primary sources such as interviews with agricultural producers who have adopted water conservation techniques, and collaboration in collecting and curating these case studies is welcome.

An important future direction for WATA will be moving from a constellation of individual case studies to syntheses that evaluate the effectiveness of different adaptations. The IPCC Working Group II 6th Assessment Report [ 105 ] provides an entry point for conceptualizing such an assessment. In the approach there, climate change adaptations involving water are assessed along a continuum of positive and negative outcome in five dimensions: economic and financial indicators, impacts on vulnerable people, water-related impacts, ecological and environmental impacts, and institutional and sociocultural impacts. A similar approach could be applied to the case studies included in WATA to assess their effectiveness in general terms; however, the challenge identified by the IPCC that “the context-specific nature of adaptation…make[s] long-term projections of adaptation effectiveness of limited use for decision-making on the ground” remains. Recognition of this challenge is built into WATA, as detailed context-specific information is provided for each case study. The challenge going forward will be to develop ways of condensing this information to address the needs of resource managers “on the ground”: which cultivars, crops, cropping systems, soil moisture conservation practices, or irrigation technologies are appropriate for a given context, limit the risk of maladaptation, and provide multiple benefits? Future work will focus on creating these sorts of assessments of context-specific solutions.

Acknowledgments

The authors would like to thank Maude Dinan, David Donaldson, Susanna Eden, Sam Fernald, Cody Knutson, Amy Kremen, Jonathan Long, Charlie Luce, Jamie McEvoy, Sharon Megdal, Gabriela Perez Quesada, Kelly Smith, Spiro Stefanou, and Kelly Thorp for their helpful comments and insightful questions. Sophia Tanner played an important role in conceptualizing the project and securing the cooperative agreement with the USDA-ERS, as well as comments on manuscript drafts.

The findings and conclusions in this manuscript are those of the authors and should not be construed to represent any official USDA or U.S. government determination or policy.

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Introduction, background and methods, limitations, acknowledgements, data availability.

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Advancing drug-response prediction using multi-modal and -omics machine learning integration (MOMLIN): a case study on breast cancer clinical data

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Md Mamunur Rashid, Kumar Selvarajoo, Advancing drug-response prediction using multi-modal and -omics machine learning integration (MOMLIN): a case study on breast cancer clinical data, Briefings in Bioinformatics , Volume 25, Issue 4, July 2024, bbae300, https://doi.org/10.1093/bib/bbae300

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The inherent heterogeneity of cancer contributes to highly variable responses to any anticancer treatments. This underscores the need to first identify precise biomarkers through complex multi-omics datasets that are now available. Although much research has focused on this aspect, identifying biomarkers associated with distinct drug responders still remains a major challenge. Here, we develop MOMLIN, a multi-modal and -omics machine learning integration framework, to enhance drug-response prediction. MOMLIN jointly utilizes sparse correlation algorithms and class–specific feature selection algorithms, which identifies multi-modal and -omics–associated interpretable components. MOMLIN was applied to 147 patients’ breast cancer datasets (clinical, mutation, gene expression, tumor microenvironment cells and molecular pathways) to analyze drug-response class predictions for non-responders and variable responders. Notably, MOMLIN achieves an average AUC of 0.989, which is at least 10% greater when compared with current state-of-the-art (data integration analysis for biomarker discovery using latent components, multi-omics factor analysis, sparse canonical correlation analysis). Moreover, MOMLIN not only detects known individual biomarkers such as genes at mutation/expression level, most importantly, it correlates multi-modal and -omics network biomarkers for each response class. For example, an interaction between ER-negative-HMCN1-COL5A1 mutations-FBXO2-CSF3R expression-CD8 emerge as a multimodal biomarker for responders, potentially affecting antimicrobial peptides and FLT3 signaling pathways. In contrast, for resistance cases, a distinct combination of lymph node-TP53 mutation-PON3-ENSG00000261116 lncRNA expression-HLA-E-T-cell exclusions emerged as multimodal biomarkers, possibly impacting neurotransmitter release cycle pathway. MOMLIN, therefore, is expected advance precision medicine, such as to detect context–specific multi-omics network biomarkers and better predict drug-response classifications.

The advent of high-throughput sequencing technologies has revolutionized our ability to collect various ‘omics’ data types, such as deoxyribonucleic acid (DNA) methylations, ribonucleic acid (RNA) expressions, proteomics, metabolomics and bioimaging datasets, from the same samples or patients with unprecedented details [ 1 ]. By far, most studies have performed single omics analytics, which capture only a fraction of biological complexity. The integration of these multiple omics datasets offers a more comprehensive understanding of the underlying complex biological processes than single-omic analyses, particularly in human diseases like cancer and cardiovascular disease, where it significantly enhances prediction of clinical outcomes [ 2 , 3 ].

Cancer is a highly complex and deadly disease if left unchecked, and its heterogeneity poses significant challenges for treatment [ 4 ]. Standard treatments, including chemotherapy with or without targeted therapies, aim to reduce tumor burden and improve patient outcomes such as survival rate and quality of life [ 5–7 ]. However, even for the most advanced therapies, such as immunotherapies, treatment effectiveness varies widely across cancer types and even between patients with same diagnosis [ 8 ]. This heterogeneity is believed to be due to tumor microenvironment heterogeneity and their effects on the resultant complex and myriad molecular interactions within cells and tissues [ 9 , 10 ]. This variability underscores the urgent need to identify precise biomarkers to predict individual patient responses and potential adverse reactions to a particular therapy [ 11 ]. This can be made possible through multi-omics data integration analyses at the individual patient scale [ 12 ].

To assess treatment response, such as pathologic complete response (pCR) and residual cancer burden (RCB), current clinical practice relies on clinical parameters (e.g. tumor size/volume and hormone receptor status), along with genetic biomarkers (e.g. TP53 mutations) [ 13–15 ]. However, these approaches do not fully capture the complex intracellular regulatory dynamics [ 16 , 17 ] or the tumor-immune microenvironment (TiME) interactions that influence outcomes [ 18 , 19 ]. Thus, to enhance personalized cancer treatments, we need novel methodologies that can handle large, complex molecular (omics) and clinical datasets. Machine learning (ML) methods integrating multi-omics data offer a promising avenue to improve prediction accuracy and uncover robust biomarkers across drug-response classes [ 20 ], which may be overlooked by single-omics analytics. This approach can predict patients benefiting from standard treatments and those requiring alternative plans like combination therapies or clinical trials.

The current drug-response prediction methods can be broadly categorized into ML-based and network-based approaches. ML methods often analyze each data type (e.g. mutations and gene expression) independently using univariable selection [ 21 , 22 ] or dimension reduction methods [ 23 ]. These results are then integrated using various classifiers or regressors [e.g. support vector machine, elastic-net regressor, logistic regression (LR) and random forest (RF)] [ 24–26 ] and ensemble classifier to make predictions [ 9 ]. However, these methods often overlooked the crucial interactions among different data modalities. Deep learning methods, while gaining popularity, are limited by the need for large clinical sample sizes to achieve sufficient accuracy [ 27 ]. Recent ML advancements have focused on integrating multimodal omics features with patient phenotypes to improve predictive performance [ 28 , 29 ]. To discover multimodal biomarker, techniques such as multi-omics factor analysis (MOFA) and sparse canonical correlation analysis (SCCA), including its variant multiset SCCA (SMCCA) offer realistic strategies for integrating diverse data modalities [ 30–32 ]. However, although these methods are suitable for classification tasks, they are unsupervised and do not directly incorporate phenotypic information (e.g. disease status) to integrate diverse data types. As a result, they are limited to identify phenotype-specific biomarkers.

Recently, advanced supervised approaches like data integration analysis for biomarker discovery using latent components (DIABLO) by Sing et al. (2019) have emerged to overcome these limitations [ 28 ]. DIABLO is an extension of generalized SCCA (GSCCA), considers cross-modality relationships and extracts a set of common factors associated with different response categories. Network-based methods, like unsupervised network fusion or random walk with restart approaches construct drug–target interaction and sample similarity networks that are effective for patient stratification [ 20 , 33 ]. However, these methods lack a specific feature selection design, limiting their utility for identifying biomarkers for patient classification. Nevertheless, none of these ML methods are rigorous in terms of task/class-specific biomarker discovery and interpretability, and both SMCCA and GSCCA struggle with gradient dominance problem due to naive data fusion strategies [ 34 ]. Therefore, it is essential to develop novel interpretable methods for identifying robust multimodal network biomarkers across diverse data types to advance our understanding of the complex factors that influence drug responses.

In this study, we introduce MOMLIN, a multi-modal and -omics ML integration framework to enhance the prediction of anticancer drug responses. MOMLIN integrates weighted multi-class SCCA (WMSCCA) that identifies interpretable components and enables effective feature selection across multi-modal and -omics datasets. Our method contributes in three keyways: (i) innovates a class-specific feature selection strategy with SCCA methods for associating multimodal biomarkers, (ii) includes an adaptive weighting scheme into multiple pairwise SCCA models to balance the influence of different data modalities, preventing dominance during training process and (iii) ensures robust feature selection by employing a combined constraint mechanism that integrate lasso and GraphNet constraints to select both the individual features and subset of co-expressed features, thereby preventing overfitting to high-dimensional data.

We applied MOMLIN to a multimodal breast cancer (BC) dataset of 147 patients comprising clinical features, DNA mutation, RNA expression, tumor microenvironment and molecular pathway data [ 9 ], to predict drug-response classes, specifically distinguishing responders and non-responders. Our results demonstrate MOMLIN’s superiority in terms of outperforming state-of-the-art methods and interpretability of the underlying biological mechanisms driving these distinct response classes.

Overview of our proposed method for treatment response prediction

The workflow of our proposed method MOMLIN for identifying class- or task-specific biomarkers from multimodal data is shown in Fig. 1 . The core of this pipeline involves three stages: (i) identification of response-specific sparse components, in terms of input features and patients, (ii) development of drug-response predictor using latent components of patients and (iii) interpretation of sparse components and multi-modal and -omics biomarker discovery.

Schematic representation of the proposed framework. In stage 1, multimodal datasets from cancer patients (e.g. BC) were sourced from a published study [ 9 ]. This dataset comprises clinical features, DNA mutations, and gene expression from pre-treatment tumors, alongside post-treatment response classes (pCR, RCB-I to III). TiME and pathway activity were derived from transcriptomic data using statistical algorithms. For identifying class-specific correlated biomarkers, class binarization and oversampling were used to balance between classes. WMSCCA models the multimodal associations across different biomarkers and identifies response-specific sparse components on diverse input features and patients. In stage 2, a binary LR classifier then utilizes these patient latent components for predicting response to therapies, evaluated by AUROC. Next in stage 3, class–specific sparse components are shown in a heatmap, highlighting key signatures (non-zero loading) in colors. Finally, the identified multi-modal and -omics signatures then formed a correlation network, revealing pathways associations with multi-modal and -omics biomarkers for each response class. Nodes with colors in the network indicate multimodal features.

The rationales underpinned of this approach is that effective biomarkers are: (i) response–related multimodal features including genes, cell types and pathways, and (ii) features that demonstrate prediction capabilities on unseen patients. The first stage, a ‘feature selection step’ that selects multimodal features on the generated sparse components based on their relevance to drug-response categories (pCR and RCB-I to III). Features with high loading identified are considered as potential biomarker candidates. The second stage, a ‘classification step’, validates these biomarkers by assessing their predictive power in distinguishing responders from non-responders to anticancer therapy; any predictions indicating chemo-resistant tumors should be considered for enrolment in clinical trials for novel therapies. The third stage, an ‘interpretation step,’ analyzes the candidate biomarkers in a multi-modal and-omics network associated with relevant biological pathways. This step aims to elucidate the underlying biological processes differentiating between drug–response phenotypes.

Stage 1. Identification of response-associated sparse components in terms of input features and patients

Multi-modal and -omics data overview and preparation.

This study utilized clinical attributes, DNA mutation and gene expression (transcriptome) data from147 matched samples of early and locally advanced BC patients (categorized as pCR, n  = 38, RCB-I, n  = 23, or RCB-II, n  = 61, or RCB-III, n  = 25), obtained from the TransNEO cohort at Cambridge University Hospitals NHS Foundation [ 9 ]. The dataset includes clinical attributes (8 features, summary attributes are available in Supplementary Table S1 available online at http://bib.oxfordjournals.org/ ), genomic features (31 DNA mutation genes, applying a strict criterion of genes mutated in at least 10 patients) and RNA-sequencing (RNA-Seq) features (18 393 genes), covering major BC subtypes-normal-like, basal-like, Her2, luminalA and luminalB. Although DNA mutation genes typically represent binary data, we used mutation frequencies to construct a mutation count matrix. Initial data pre-processing involved a log2 transformation on the RNA-Seq features after filtering out less informative features at 25th percentile (in terms of mean and standard deviation) using interquartile range. For integrative modeling, we used the top 40% of variable genes (3748 genes, based on median absolute deviation ranking) from the RNA-Seq datasets. Finally, each feature was normalized dividing by its Frobenius norm, adjusting the offset between high and low intensities across different data modalities.

To characterize TiME and pathway markers, we applied various statistical algorithms on the RNA-Seq data. The GSVA algorithm [ 35 ] calculated (i) the GGI gene sets [ 36 ] and (ii) STAT1 immune signature scores [ 37 ]. For immune cell enrichment, three methods were used: (i) MCPcounter [ 37 ] with voom-normalized RNA-Seq counts; (ii) enrichment over 14 cell types using 60 gene markers, employing log2-transformed geometric mean of transcript per million (TPM) expression [ 38 ]; and (iii) z -score scaling of cancer immunity parameters [ 39 ] to classify four immune processes (major histocompatibility complex molecules, immunomodulators, effector cells and suppressor cells). Additionally, the TIDE algorithm [ 40 ] computed T-cell dysfunction and exclusion metrics for each tumor sample using log2-transformed TPM matrix of counts, which can serve as a surrogate biomarker to predict the response to immune checkpoint blockade. Pathway activity scores for each tumor sample were computed using the GSVA algorithm with input gene sets from Reactome [ 41 ], PIP [ 42 ] and BioCarta databases within the MSigDB C2 pathway database [ 43 ].

Sparse multiset canonical correlation analysis

In this study, lowercase letters denote a vector, and uppercase ones denote matrices, respectively. The term |${\left\Vert .\right\Vert}_{1,1}$| denotes the matrix |${l}_1$| -norm, and |${\left\Vert .\right\Vert}_{gn}$| denotes the GraphNet regularization. The sparse multiset canonical correlation analysis (SMCCA) is an extension of dual-view SCCA, proposed to model associations among multiple types of datasets [ 31 ]. Given the multiple types of datasets, let |$X\in{\mathcal{R}}^{n\times p}$| represent gene expression data with |$p$| features, and |${Y}_k\in{\mathcal{R}}^{n\times{q}_k}$| represent the |$k$| -th data modality (e.g. clinical, DNA mutation and tumors microenvironment) with |${q}_k$| features. Both |$X$| and |${Y}_k$| have |$n$| samples, and |$k=\left(1,\dots, K\right)$|⁠ , where |$K$| denotes the number of different data modalities. The objective function of SMCCA is defined as follows:

where |$u$| and |${v}_k$| are the canonical weight vectors corresponding to |$X$| and |${Y}_k$|⁠ , indicating the importance of each respective biomarkers. The term |${\left\Vert .\right\Vert}_1$| represents the |${l}_1$| regularization to detect small subset of discriminative biomarkers and prevent model overfitting. |${\lambda}_u,{\lambda}_{vk}$| are non-negative tuning parameters balancing between the loss function and regularization terms. The term |${\left\Vert .\right\Vert}_2^2$| denotes the squared Euclidean norm to constraint weight vectors |$u$| and as unit length |${v}_k$|⁠ , respectively.

However, SMCCA has limitations: (i) it is naturally unsupervised, meaning SMCCA cannot leverage phenotypic information (e.g. disease status and drug-response classes); (ii) pairwise association among multiple data types can vary significantly and can lead to gradient dominance issues during optimization; and (iii) SMCCA mines a common subset of biomarkers for classifying different tasks, which diminishes its relevance, as each task might require distinct features sets.

Weighted multi-class sparse canonical correlation analysis

To address the above limitations, here we propose weighted multi-class SCCA (WMSCCA), a formal model for class/tasks-specific feature selection, different from the conventional SMCCA. Throughout this study, we used the terms tasks/classes/drug-response classes interchangeably. WMSCCA includes phenotypic information as an additional data type, employs a weighting scheme to resolve the gradient dominance issue and innovates traditional class–specific feature selection strategies through the one-versus-all strategies into its core objective function. In this study, the underlying motivation is WMSCCA can jointly identify drug-response class–specific multimodal biomarkers to improve drug-response prediction. For ease of presentation, we consider |$n$| patients with data matrices |${X}_c\in{\mathcal{R}}^{n\times p},{Y}_{ck}\in{\mathcal{R}}^{n\times{q}_k}$|⁠ , and |$Z\in{\mathcal{R}}^{n\times C}$| from C different drug-response classes. Here, |${X}_c$| denotes |$p$| features from gene expression datasets, |${Y}_{ck}$| denotes |${q}_k$| features from |$k$| -th data modality (e.g. mutation, clinical features, TiME and pathway activity), |${Z}_c$| denotes |$c$| response class, and |$k=\left(1,\dots, K\right)$|⁠ , |$K$| denotes the number of data modalities. The WMSCCA optimization problem can be formulated as follows:

where |$U\in{\mathcal{R}}^{p\times C},{V}_k\in{\mathcal{R}}^{q_k\times C}$| are canonical loading matrices correspond to |$X$| and |${Y}_k$|⁠ , representing the importance of candidate biomarkers for each class |$C$|⁠ , respectively. In this equation, the first term models associations among |$X$|⁠ , and |${Y}_k$| datasets; the second- and third terms correlate class labels |${Z}_c$| with |$X$| and |${Y}_k$| data modalities for each |${C}^{th}$| class, aiming to identify class-specific features and their relationships; |$\psi (U)$| and |$\psi \left({V}_k\right)$| represent sparsity constraints on |$U$| and |${V}_k$|⁠ , to select a subset of discriminative feature. As mentioned in Equation ( 1 ), to address gradient dominance, the adjusting weight parameter |${\sigma}_{xy}$|⁠ , |${\sigma}_{xz}$| and |${\sigma}_{yz}$| can be defined as:

where |$k=\left(1,\dots, K\right)$|⁠ , |$K$| denotes the number of data modalities. |${\sigma}_{..}$| adjusts a larger weight if the non-squared loss (denominator term) between datasets is small and vice versa.

Given high-dimensional datasets, the model in Equation ( 2 ) encounters an overfitting problem. Therefore, the use of a sparsity constraint is appropriate to address this issue. We hypothesized that gene expression biomarkers can be either single genes or co-expressed sets; thus, a combined penalty is designed for the |$X$| dataset. Therefore, |$\psi (U)$| for |$X$| takes the following form:

where, |${\mathrm{\alpha}}_u,\beta$| are nonnegative tuning parameters. |$\beta$| balances between the effect of co-expressed and individual feature selection. The first sparsity constraint is matrix |${l}_{1,1}$| -norm, which is defined as follows:

This penalty promotes class-specific features on |$U$|⁠ . The second sparsity constraint GraphNet regularization, defined as follows:

where |${L}_c$| represents the Laplacian matrices of the connectivity in |$\boldsymbol{X}$| matrices. The Laplacian matrix is defined as |$L=D-A$|⁠ , where |$D$| is the degree matrix of connectivity matrix |$A$| (e.g. gene co-expression or correlation network). This penalty term promotes a subset of connected features to discriminate each response on |$U$|⁠ .

Besides, neither every mutation marker nor every clinical/TiME/pathways involves in predicting response classes, therefore, the |${l}_{1,1}$| -norm is used on the |${Y}_k$| datasets to select individual markers, i.e. |$\psi \left({V}_k\right)$| for the |${\boldsymbol{Y}}_k$| data modalities take the following form:

where |${\mathrm{\alpha}}_{vk}$| is non-negative tuning parameter.

Finally, we obtained C pairs of canonical weight matrices |$\big({U}_c{V}_{ck}\big)\left(c=1,\dots, C;k=1,\dots, K\right)$| using an iterative alternative algorithm by solving Equation ( 2 ) [ 44 , 45 ]. Detected features with non-zero weights in each class in the weight vectors were extracted as correlated sets.

The WMSCCA method involves parameters |${\mathrm{\alpha}}_u,\mathrm{\beta}, and\ {\mathrm{\alpha}}_{vk}$| |$\left(k=1, \dots, K\right)$|⁠ . Given the limited number of samples, we applied a nested cross-validation (CV) strategy on training sets and evaluated the maximum correlation on the test datasets. Optimal values for the regularization parameters were determined within each training set via internal five-fold CV.

Stage 2. Drug-response prediction using latent components of patients

To predict drug-response categories, we trained LR classifier using the latent components of patients (or raw multimodal features) generated by MOMLIN in Fig. 1 : stages 1 and 2. We used a binary classification scheme, distinguishing pCR versus non-pCR, RCB-I versus non-RCB-I, RCB-II versus non-RCB-II and RCB-III versus non-RCB-III, to evaluate model performance. In addition, we performed analyses with existing multi-omics methods, including SMCCA+LR, MOFA+LR, DIABLO and latent principal component analysis (PCA) features, with LR classifiers. To assess prediction performance for the response to treatment in an unbiased manner, we used five-fold cross-validated performance and repeated the process over 100 runs. The partitioning of data was kept consistent across all models for fair comparisons. The accuracy of response prediction was evaluated using area under the receiver operating characteristic curve (AUROC).

Stage 3. Interpretation of sparse components and multi-omics biomarker discovery and their networks

After learning sparse latent components of features across different data modalities using MOMLIN, we identify the most relevant feature based on the loading weight of genes, TiME and pathways, which reveal underlying interactions for discriminating response classes. The larger the loading weight, the more important the pair of features in discriminating response categories. We then use these selected features to construct a sample correlation network, or a relationship matrix based on their canonical weights [ 46 ]. In this network, nodes represent selected features, and the edge weights between two interconnected features indicate correlation or relatedness. The generated network is visualized using the ggraph package in R ( https://cran.r-project.org ). Finally, we prioritize multi-omics biomarkers based on their degree centrality within the interconnected correlation network.

Derivation of response-associated latent components from BC data with MOMLIN

We applied MOMLIN to analyze a breast cancer (BC) dataset to predict treatment response and gain molecular insights. The dataset comprised 147 BC patients with early and locally advanced pretherapy tumors [ 9 ], categorized as follows: pCR with 38 patients, RCB-I (good response) with 23 patients, RCB-II (moderate response) with 61 patients and RCB-III (resistance) with 25 patients. After preprocessing and filtering least informative features, the final dataset comprised 3748 RNA genes (top 40% out of 9371 genes), 31 mutation genes, 8 clinical attributes, 64 TiME and 178 pathways activities ( Fig. 1 : stage 1). Supplementary Table S1 available online at http://bib.oxfordjournals.org/ summarizes overall clinical characteristics by patients’ response classes.

While our proposed framework offers general applicability for identifying context-specific multi-omics biomarkers, this study specifically focused on discovering drug-response–specific biomarkers to enhance the prediction of pCR and RCB resistance. MOMLIN decomposed the input multimodal data into response-associated sparse latent components of input-features and patients. These sparse components reveal patterns of how various features (e.g. genes and mutations) and clinical attributes related to treatment outcomes ( Fig. 1 : stage 1–3), and their effectiveness was evaluated by measuring prediction performance. We assessed the predictive ability of MOMLIN through five-fold CV repeated 100 times. In each iteration, the dataset is divided into five-folds, with one random fold assigned as the held-out test set, and the remaining folds used as the training set. MOMLIN was trained using the training dataset, including detection of predictive marker candidates, and its performance was evaluated on the ‘unseen’ test set. This process was repeated for all five-folds to ensure robust evaluation of MOMLIN’s generalizability. Performance was measured by the AUROC matrices ( Fig. 1 : stage 2).

Performance comparison with existing methods for drug-response prediction

To evaluate the prediction capability of MOMLIN, we modeled each response category as a binary classification problem and compared its prediction accuracy to existing multi-omics integration algorithms. For comparison, we randomly split the dataset into a training set (70%) and a test set (30% unseen data), with balanced inclusion of response classes. We employed LR as the classifier to assess predictive performance of multimodal biomarkers. We compared MOMLIN with four other classification algorithms for omics data: (i) SMCCA, which integrates multi-omics data by projecting it onto latent components for discriminant analysis; (ii) MOFA, which decomposes multi-omics data into common factors for discriminant analysis; (iii) sparse PCA; and (iv) DIABLO, a supervised integrative analysis method, represent the state-of-the-art in classification. All methods were trained on the same preprocessed data.

The classification results showed that MOMLIN outperformed the compared multi-omics integration methods in most classification tasks on unseen test samples ( Fig. 2A ). Notably, DIABLO, the next best performer, was 10 to 15% less effective than our MOMLIN. Additionally, we compared the performance of component-based LR models against raw feature-based LR models to predict RCB response classes. Although raw feature-based models showed improved prediction, their performance was notably dropped compared to component-based models ( Fig. 2B ). This indicates the superior adaptability and effectiveness of component-based models in leveraging multi-omics data for predictive purposes.

Performance comparison with existing methods and detection of informative data combination. All results in the plots depict test AUROC over five-fold CV obtained from 100 runs. (A) Box plots comparing response prediction performance of MOMLIN against existing state-of-the-art multi-omics methods. (B) Performance comparison between predictors based on latent components and those utilizing a selected subset of multimodal features. (C) Comparing AUROCs for the models with different data subset combinations (clinical, clinical + DNA, clinical + RNA and clinical + DNA + RNA) using MOMLIN.

Moreover, to test and demonstrate generalizability of this framework, we applied MOMLIN to a preprocessed multi-omics dataset of colorectal adenocarcinoma (COAD) with 256 patients [ 47 ]. This dataset included gene expression, copy number variations and micro-RNA expression data, which we used to classify COAD subtypes such as chromosomal instability (CIN, n  = 174), genomically stable (GS, n  = 34) and microsatellite instability (MSI, n  = 48). The performance results shown in Supplementary Table S2 available online at http://bib.oxfordjournals.org/ and Supplementary Figure S1 available online at http://bib.oxfordjournals.org/ , indicate that MOMLIN outperformed all state-of-the-art methods tested in classifying COAD subtypes. Moreover, when comparing the raw feature-based accuracies with sparse components-based (features derived from MOMLIN) accuracies, we found that raw feature-based classifier was superior against existing methods ( Figure S1A and B ), but lower than the components-based classifier. This consistent observation supports our findings with BC drug-response performances.

Importance of different omics data for treatment response prediction

To assess the added value of integrating multimodal data for predicting treatment response, we trained four prediction models with different feature combinations: (i) clinical features only, plus adding (ii) DNA, (iii) RNA and (iv) both DNA and RNA. We found that adding different data modalities improved prediction performance across all response classes ( Fig. 2C ). Notably, the models that combined clinical data with either RNA or both DNA and RNA demonstrated superior and comparable performance with an average AUROC of 0.978. In contrast, the model based on clinical features alone had much lower AUROC, ranging from 0.51 to 0.82. These results suggest that RNA transcriptome is the most informative data modality in this dataset. Thus, integrating gene expression with clinical features could significantly improve our ability to predict treatment outcomes in BC.

Interpretation of response-associated sparse components identified by MOMLIN

To understand the molecular landscape of treatment response in BC, we used MOMLIN to model response–specific bi-multivariate associations across multiple data modalities. We observed stronger correlations between RNA gene expression and both TiME ( r  = 0.701) and pathway activity ( r  = 0.868), indicating greater overlap or explained information between them. Conversely, moderate correlations were found between RNA gene expression and DNA mutations ( r  = 0.526), or clinical features ( r  = 0.488), indicating partially overlapping or independent information. These results suggest that multimodal biological features provide complementary information in a combinatorial manner.

When investigating the importance of each feature to predict response classes, MOMLIN identified four distinct loading vectors corresponding to pCR and RCB response classes, highlighting distinct weight patterns for pCR versus non-pCR and RCB versus non-RCB classes ( Fig. 3 ). For example, in the pCR (complete response) components—taking the top five molecular features across different modalities revealed distinct molecular patterns. Specifically, gene expression analysis showed that downregulation of FBXO2 and RPS28P7 inhibits tumor cell proliferation, and potentially may enhance treatment efficacy, and the upregulation of C2CD4D-AS1, CSF3R, and SMPDL3B genes may promote immune response, increasing tumor cell vulnerability and therapeutic effect ( Fig. 3A ). Mutational analysis revealed negative associations of marker genes HMCN1 and GATA3, but a positive association for COL5A1 ( Fig. 3C ). Additionally, tumor mutation burden (TMB), and homologous recombination deficiency (HRD)-Telomeric AI signatures were higher in pCR patients, suggesting high genomic instability compared to RCB patients [ 9 ]. TiME analysis showed reduced immunosuppressive mast cells and extracellular matrix (ECM), along with increased infiltration of neutrophils, TIM-3 and CD8+ T-cells ( Fig. 3D ). Subsequently, the pathway analysis further revealed potential downregulation of the PDGFRB pathway, involved in stromal cell activity and associated with improved patient response [ 49 ], while upregulation of pathways for antimicrobial peptides, FLT3 signaling, ephrin B reverse signaling and potential therapeutics for SARS ( Fig. 3E ), suggesting enhanced immune surveillance and interaction with tumor cells. In summary, MOMLIN reveals distinct genomic landscape with higher immune activity and genomic instability in pCR that characterizes its favorable treatment response.

Heatmaps illustrate the features importance on response-associated components identified by MOMLIN. Each row in the heatmap represents a drug-response class, pCR, RCB-I , RCB-II and RCB-III, with columns representing features across different data modalities. The color gradient indicates feature loading or importance, representing the strength of association with response classes. The sign (negative or positive) of gradient denotes the association directions to response classes. All results in the heatmaps depict an average over 100 runs of five-fold CV. (A–E) represents the response-associated candidate biomarkers detected in latent components in (A) gene expression data (highlighting DE genes), (B) clinical features, (C) DNA mutations (highlighting mutated genes), (D) TiME cells and (E) functional pathway profiles (highlighting altered pathways).

Similarly, in the RCB-I (good response) components—RNA expression analysis revealed that lower expression of genes GPX1P1 and HBB are linked to less aggressive tumors [ 48 ], while those of thiosulfate sulfurtransferase (TST), NPIPA5 and GSDMB were overexpressed, linked to enhanced immune response and therapeutic effectiveness [ 49 , 50 ]. Mutational analysis showed positive association for therapeutic targets signatures TP53, MUC16 and RYR2 [ 51 , 52 ], but a negative in NEB, and CIN scores. TiME analysis demonstrated increased infiltration of Tregs, cancer-associated fibroblast (CAF), monocytic lineage and natural killer (NK) cells, indicating more active of immune environment [ 9 ], with reduced TEM CD4 cells. Pathway analysis further identified downregulation of NOD1/2 signaling, EPHA-mediated growth cone collapse and toll-like receptor (TLR1, TLR2) pathways, involved in inflammation and immune response, with the upregulation of allograft rejection, and G0 and early G1 pathways. In summary, tumors that achieve RCB-I is marked by distinct genomics marker, active immune response, and lower CIN.

In RCB-II (moderate response) components: RNA expression analysis revealed overexpression of RPLP0P9, FTH1P20, RNF5P1 pseudogenes, following accumulation of overexpressed ERVMER34-1, and PON3 genes play an oncogenic role in BC [ 53 ]. Mutation analysis revealed positive association of HRD-LOH, RYR1 and MT-ND4, but negative association of MACF1 and neoantigen loads, in line with previous reports [ 54 , 55 ]. Analysis of TiME features demonstrated increased infiltration of IDO1 and TAP2, with reduced CTLA 4, NK cells and PD-L2 cells, indicating a less suppressive immune environment. Pathways analysis further revealed downregulation pathways of G1/S DNA damage checkpoints and TP53 regulation, highlighting DNA repair issues, with the upregulation of PDGFRB pathway, E2F targets and signaling by Hedgehog associated with cell proliferation. In summary, RCB-II patients display distinct genomics markers including pseudogenes, lack of suppressive immune environment and active proliferation.

In RCB-III (resistant) components: RNA gene expression analysis revealed lower expression of therapeutic target PON3, and FGFR4 [ 56 ], and flowed accumulation of lower expressed lncRNAc ENSG00000225489, ENSG00000261116 and RNF5P1. Mutation signature analysis identified a positive association of MT-ND1, but a negative association in therapeutic targets TP53, and MT-ND4 [ 7 , 52 ]. Neoantigen loads were higher following lower TMB indicate reduced tumor suppressor activity. TiME analysis revealed reduced activity of T-cell exclusion, and HLA-E, with increased ECM, HLA DPA1 and LAG3, suggesting an immune suppressive tumor environment. Pathway analysis revealed upregulation of pathways involved in neurotransmitter release, cell-cycle progression (RB-1) and immune system diseases, suggesting active cell signaling and proliferation, with downregulation of EPHB FWD pathway and nucleotide catabolism. In summary, patients that attained RCB-III, characterized by low mutational burden and an immune suppressive environment, leading to treatment resistance.

Linking biology to treatment response through biomarker network analysis

To further extract multimodal network biomarkers and understand the complex biological interactions in patients with pCR and RCB, we performed cross-interaction network analysis using candidate signatures identified by MOMLIN across different modalities. This analysis included clinical features, DNA mutations, gene expression, TiME cells and enriched pathways, aiming to elucidate the underlying biology associated with specific treatment responses. Figure 4 shows the interaction networks of selected multimodal features for each RCB class. To identify potential biomarkers associated with pCR and RCB response, we specifically focused on the top ten multimodal features based on network edge connections. For example, tumors that attained in pCR, the network analysis revealed co-enrichment of mutations in HMCN1 and COL5A1 genes, particularly in estrogen receptor (ER)-negative patients. HMCN1 and COL5A1 therapeutic targets like molecules encode proteins for ECM structure, and mutations of these genes regulate tumor architecture and cell adhesion, potentially facilitating immune cell infiltration [ 52 ]. We also observed elevated expressions of FBXO2, CSF3R, C2CD4D-AS1 and RPS28P7 genes, alongside increased infiltration of CD8+ T-cells [ 9 , 57 ]. FBXO2 is a component of the ubiquitin-proteasome system, which regulates protein degradation and influences cell cycle and apoptosis [ 58 ], while CSF3R plays a vital role in granulocyte production and immune response [ 59 ]. These gene expression patterns, coupled with increased CD8+ T-cell infiltration, suggest a robust anti-tumor immune response. Furthermore, these molecular perturbations may be linked to antimicrobial peptide pathways and FLT3 signaling, potentially contributing to the favorable outcome in achieving pCR [ 60 , 61 ]. Future work could specifically search for these complex interactions across different molecules to gain more clinically relevant insights into pCR tumors. Supplementary Table S3 available online at http://bib.oxfordjournals.org/ presents the more detailed list (top 30) of the multi-modal and -omics biomarkers identified using the MOMLIN pipeline.

Multimodal network biomarkers explain drug-response classes. The multimodal networks detail the candidate biomarkers and their interactions for each response class, (A) the pCR patients (B) the RCB-I patients (good response), (C) the RCB-II patients (moderate response) and (D) the RCB-III resistance patients. Nodes in the network represent candidate biomarkers derived from clinical features, DNA mutations, gene expression, enriched cell-types and pathways, each indicated in different colors in the figure legend. Negative edges are light green; positive edges are in light magenta. Edge width reflects the strength of the interaction between features. Node size corresponds to the number of connections (degree), and the font size of node labels scales with degree centrality, highlighting the most interconnected biomarkers.

Similarly, RCB-I tumors exhibited co-enriched mutations in MUC16 and TP53, particularly in HER2+ cases [ 14 ]. MUC16 (CA125) is therapeutic molecule associated with immune evasion and tumor growth [ 51 ], while TP53 mutations can lead to loss of cell cycle control and genomic instability [ 62 ]. We also observed elevated expression of TST involved in the detoxification processes and GPX1P1 [long non-coding RNA (lncRNA)] involved in oxidative stress response. The immune landscape of these tumors showed increased infiltration of TEM CD4 cells (adaptive immunity), monocytic lineage cells (phagocytosis and antigen presentation) and NK cells (innate immunity), as well as CAFs. This immune landscape, coupled with potential perturbations in the allograft rejection pathway, suggests an active but potentially incomplete immune response against the tumor, resulting in minimal residual disease.

RCB-II tumors had lower neoantigen loads compared to pCR, both in ER-negative and HER2+ patients. This reduced neoantigen load might contribute to a weaker immune response. Gene expression analysis showed elevated levels of specific lncRNAs, including FTH1P20 (associated with iron metabolism), RNF5P1 (potentially affecting protein degradation) and RPLP0P9 (involved in protein synthesis), along with ERVMER34-1, which can influence gene expression and immune response in BC patients. Numerous studies have underscored the key regulatory roles of lncRNAs in tumors and the immune system. Notably, increased expression of the immune checkpoint protein IDO1 negatively regulates the expression of CTLA-4, both known to modulate antitumor immune responses [ 63 ]. The combined effect of these molecular alterations suggests potential tumor survival mechanisms, including immune evasion and dysregulation of G1/S DNA damage [ 64 ] contributing to moderate residual disease.

In RCB-III tumors, we observed the reduced prevalence of TP53 and MT-ND4 mutations, typically associated with genomic instability and aggressive tumor behavior [ 51 ], coupled with a higher neoantigen load, suggesting an alternative mechanism (pathways) that drives tumor progression. Despite the higher neoantigen loads, increased expression of HLA-E immune checkpoints and T-cell exclusion in the tumor microenvironment hindered effective anti-tumor immune responses. Additionally, the low-expressed genes PON3, ENSG00000261116 (lncRNA) and RNF5P1 are involved in detoxification, gene regulation and protein degradation, respectively, represents an adaptive response to cellular stress in these tumors. Clinical markers indicating lymph node involvement suggest a more advanced disease state [ 9 ]. These findings, along with potential perturbations in the neurotransmitter release cycle pathway, collectively portray RCB-III tumors as genetically unstable, yet effectively evading immune surveillance, contributing to their significant treatment resistance. Overall, further investigation of these interactive molecular networks, comprising both positive and negative interactions offers a more depth understudying of these potential candidate biomarkers for distinguishing treatment-sensitive pCR and resistant RCB tumors.

The advent of multi-omics technologies has revolutionized our understanding of cancer biology, offering unprecedented insights into the complex molecular interactions that shape tumor behavior and treatment response. In this study, we presented MOMLIN (multi-modal and -omics ML integration), a novel method to enhance cancer drug-response prediction by integrating multi-omics data. MOMLIN specifically utilizes class-specific feature learning and sparse correlation algorithms to model multi-omics associations, enables the detection of class-specific multimodal biomarkers from different omics datasets. Applied to a BC multimodal dataset of 147 patients (comprising RNA expression, DNA mutation, tumor microenvironment, clinical features and pathway functional profiles), MOMLIN was highly predictive of responses to anticancer therapies and identified cohesive multi-modal and -omics network biomarkers associated with responder (pCR) and various levels of RCB (RCB-I: good response, RCB-II: moderate response and RCB-III: resistance).

Using MOMLIN, we identified that pCR is determined by an interactive set of multimodal network biomarkers driven by distinct genetic alterations, such as HMCN1 and COL5A1, particularly in ER-negative tumors [ 9 , 65 ]. Gene expression signatures, including FBXO2 and CSF3R were associated with the immune cell infiltration (CD8+ T-cells), which has been previously reported as a key determinant of response [ 57 ]. The association of these biomarkers with antimicrobial peptide and FLT3 signaling pathways suggests a robust immune response [ 61 ] as a critical driver of complete response. Additionally, C2CD4D-AS1, an lncRNA was identified, and its exact role with these complex molecular interactions in BC remains to be elucidated. Future work could specifically search for these complex interactions across different molecules to gain more clinically relevant insights into pCR tumors.

RCB-I tumors, despite responding well to response, were associated with a distinct multimodal molecular signature. These tumors were enriched for mutations in the therapeutic target MUC16 (CA125), known for its role in immune evasion [ 51 ], and the tumor suppressor gene TP53, particularly in HER2+ cases [ 14 ]. Elevated expression of TST and GPX1P1 (lncRNA involved in oxidative stress response) were associated with increased infiltration of diverse immune cells, including Tem CD4+ cells, monocytes and NK cells [ 10 ]. This active immune landscape and the intricate interactions of these signature with the potential perturbations in the allograft rejection pathway, suggests a robust yet potentially incomplete anti-tumor immune response, contributing to the minimal residual disease observed in this subtype.

RCB-II tumors showed lower neoantigen loads compared to pCR, which could contribute to a weaker immune response, particularly in ER-negative and HER2+ subtypes. Increased expression of lncRNAs, such as FTH1P20, RNF5P1, RPLP0P9 and ERVMER34–1, were associated with the immune checkpoint protein IDO1, and negatively regulate the CTLA-4 protein expression, suggests immune evasion and alterations in tumor cell metabolism and proliferation. These molecules altered intricate interactions implicate dysregulation of G1/S DNA damage as a possible mechanism for moderate treatment response [ 64 ].

RCB-III tumors, classified as resistant, were associated with a distinct multimodal molecular landscape driven by reduced TP53 and MT-ND4 mutations [ 52 ], accompanied with higher neoantigen loads compared to other response groups. This suggests an alternative mechanism driving tumor progression and immune evasion. Despite the high neoantigen load which could potentially trigger immune response, these tumors exhibited immune evasion through increased HLA-E immune checkpoints and T-cell exclusion [ 40 , 55 ]. Also, the downregulation of genes like PON3 and the lncRNA ENSG00000261116, along with lymph node involvement, pointed to advanced disease and cellular stress adaptation [ 9 ]. The presence of these complex interactions, including potential perturbations in the neurotransmitter release cycle pathway, could contribute to treatment resistance in RCB-III tumors. Future studies targeting these immunosuppressive mechanisms and exploring novel pathways could offer promising avenues to overcome resistance in this aggressive subtype.

These findings above emphasize the potential of MOMLIN to enable deeper understanding of complex biological mechanism correspondence to each response class, ultimately paving the way for personalized treatment strategies in cancer. MOMLIN also demonstrated the best prediction performance for unseen patients by utilizing these identified sets of network biomarkers. By identifying response-associated biomarkers, researchers can stratify patients based on their likelihood of achieving pCR or experiencing RCB to anticancer treatments, facilitating more informed treatment decisions and potentially improving patient outcomes. Moreover, the identified biomarkers could serve as valuable targets for the development of novel therapeutic interventions and new biological hypothesis generation. However, the clinical translation of multimodal biomarkers necessitates addressing the potential economic burden associated with multi-omics testing. Developing targeted biomarker panels and prioritizing key hub molecules from the large-scale candidate multimodal network biomarkers identified by MOMLIN could be a viable strategy for reducing costs while maintaining predictive accuracy. Furthermore, ongoing advancements in sequencing and diagnostic technologies are expected to make multi-omics testing more accessible and affordable over time.

In conclusion, our study demonstrates MOMLIN’s capacity to uncover nuanced molecular signatures associated with different drug-response classes in BC. By integrating multi-modal and -omics datasets, we have highlighted the complex interplay between genetic alterations, gene expression, immune infiltration and cellular pathways that contribute to treatment response and resistance. Future research in this direction holds promise for refining risk stratification, optimizing treatment selection and ultimately improving patient outcomes.

While MOMLIN demonstrates promising results as shown, a key limitation lies in its reliance on correlation-based algorithms for multi-omics data integration. These algorithms are great at identifying associations, but they can fall short when it comes to inferring causality between different omics layers. This is a challenge faced by most current state-of-the-art methods [ 28 , 30 ]. In the future iterations of MOMLIN, we aim to incorporate causal inference methodologies alongside sparse correlation algorithms to better understand the complex causal relationships within multi-omics datasets.

We proposed MOMLIN, a novel framework designed to integrate multimodal data and identify response-associated network biomarkers, to understand biological mechanisms and regulatory roles.

MOMLIN employed an adaptive weighting for different data modalities and employs innovative regularization constraint to ensure robust feature selection to analyze high-dimensional omics data.

MOMLIN demonstrates significantly improved performance compared to current state-of-the-art methods.

MOMLIN identifies interpretable and phenotype-specific components, providing insights into the molecular mechanisms driving treatment response and resistance.

We thank Dr Yoshihiro Yamnishi and Mr Chen Yuzhou for their technical help.

This work was supported by the core research budget of Bioinformatics Institute, ASTAR.

Supplemental information and software are available at the Bib website. Our algorithm’s software is available for free download at https://github.com/mamun41/MOMLIN_softwar/tree/main

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View: Session 9A: Percolator: Theory and Praxis of Liberatory Justice in Public Service Organizations: Rewards, Challenges, and the Way Forward 08:30 , , and 08:30 important intermediate mechanisms in the causal linkage between PBF and student success. A few studies have examined PBF-driven shifts in spending patterns in public institutions, finding only marginal to null average treatment effects on financial priorities of public four-year institutions (Rabovsky, 2012; Kelchen & Stedrak, 2016; Hu et al., 2022). However, changes in institutional processes often take time and financial priorities of incentivized institutions may evolve over time as institutions learn and adapt to their changing state funding environments (Heinrich & Marschke, 2010; Mizrahi, 2020). This study examines the dynamic shifts in institutional spending in public four-year institutions subject to PBF policies and by minority-serving institution (MSI) status. The study leverages institution-level data from IPEDS and a comprehensive state-level PBF dataset and employs event study analysis. Understanding the dynamic changes in institutional spending over multiple periods may provide information on why PBF policies continue to yield limited improvements in college completion outcomes. Evidence on the dynamic shifts in institutional spending may also enable states to better design and implement performance incentives that induce desirable institutional changes and improve student outcomes ultimately.                08:45 , and 09:00 09:15 and 08:30 08:45 and 09:00 and 09:15 , and Our analysis employs multivariate regression and other methods, considering variables for major threat categories, consequences of terrorist attacks, and terrorist funding potential through irregular trade. Additional control variables include political, power, and demographic factors. This approach provides a more comprehensive assessment of terrorism risks and funding allocation efficiency. 08:30 and The latter has become especially salient in public administration, with social equity being elevated as a core public service value and the demonstrated performance benefits of a(n) (effectively managed) diverse workforce. More historically, public organizations have sought to be demographically representative institutions, with recognizable implications for responsiveness among street-level bureaucrats, especially in arenas with administrative discretion (Keiser et al., 2002). The objective of this paper is to address these policy-salient concerns by examining what qualities of public sector jobs are most attractive across age groups, as well as race and gender. To do so, we utilize a large-scale pre-registered conjoint experiment that allows us to make valid inferences on the impact of our independent variables on job attractiveness. Our contributions are two-fold: first, we compare the simultaneous effects of a range of variables on job attractiveness whereas previous work has examined them in isolation; and secondly, we devote specific attention to comparing differences in the needs and work values of individuals across age groups. The findings highlight what matters the most in how job seekers self-select into differing organizational/policy domains, professional contexts, as well as job characteristics. The paper ends with a discussion of the findings and future work to advance this area of research. 08:45 and This study focuses on one such stressed organizational context -child welfare services- and uses the job demands-resource model to unpack the reform needed to motivate and engage child welfare caseworkers. By doing so, it builds on the literature of how work engagement in public sector contexts, especially highly stressed ones, may be differently affected by clusters of job demands and resources. Using an explanatory sequential mixed method approach, the study first identifies the clusters of job demands and job resources that are antecedents of high satisfaction and overall work commitment in child welfare caseworkers. This is done by analyzing secondary survey data from the second cohort of the National Survey of Child and Adolescent Well-Being(NSCAW II). This analysis is followed by in-depth interviews with current child welfare caseworkers to understand the relative importance of the identified job demand and resource clusters. Additionally, the interviews will add richness to the study by unpacking the personal experiences of caseworkers in the post-pandemic public sector human service work environment. The study, therefore, will provide useful insights to better inform the design and implementation of human resource policy reforms in the public sector. 09:00 and In this paper, we develop a model for understanding where organizations fall on the continuum of preventing exclusion to promoting inclusion in their DEIA work. Preventing exclusion is associated with legal compliance, internal processes, and diversity inputs while promoting inclusion is associated with creating equitable environments where individuals feel a sense of belonging. We test this model using survey data from veteran serving organizations (VSOs) participating in 18 AmericaServes networks across the United States (n=1,000) and individual surveys of veterans utilizing services (n=2,731). We propose that how organizations define and do DEIA work has profound impacts for whether historically marginalized groups access and utilize services. We conclude with guidance for organizations to develop and implement substantive and systematic DEIA work. This work is funded by USAA and done in partnership with the D’Aniello Institute for Veteran and Military Families. 09:15 Specifically, this study explores the impact of organizational inclusion and justice on the behavioral pathways that employees strategically choose in response to harassment experiences and their willingness to report such incidents. The findings reveal diverse effects on behavioral choices: Enhanced justice significantly predicts both the willingness to report incidents and turnover intention, though it is not significantly associated with changes in assignment or transfer. Inclusion, conversely, exhibits nuanced effects across behavioral strategies, significantly predicting the willingness to report but demonstrating positive associations with turnover intention and transfer. Qualitative data further confirm that organizational inclusion and justice play a crucial role in reshaping policies to protect victims, although mixed perspectives exist among employees regarding their behavioral choices when addressing harassment experiences. The study highlights the substantial impact of organizational inclusion and justice as proactive measures in curbing misconduct within highly bureaucratic settings. However, it underscores the necessity for delicate management strategies to ensure effectiveness in addressing workplace harassment. 08:30 and 08:44 , and To address the gaps, we employ a quasi-experimental method, regression discontinuity (RD) design, based on school performance data and ratings from New York City public schools from 2007 to 2013. We find that performance signals affect overall turnover, but only at the lower end of performance ratings. Compared with schools earning a C grade, schools earning a D grade have higher levels of teacher turnover. Moreover, teachers from different racial groups respond to low-performance signals differently. Compared to their counterparts in schools that earned a C, white teachers in D schools are more likely to transfer to higher-rated schools. In contrast, Black teachers in D schools are more likely to exit NYC schools to join other districts or leave the profession entirely. This study deepens our understanding of employee turnover under performance regimes and shows an unintended effect of performance management: performance regimes drive minority teachers away and worsen the lack of representation. 08:58 , and This case study analyzes interviews with 23 CoC representatives, a survey of 114 CoCs (33% response rate), and HUD performance data. We find limited evidence that funding levels are associated with reported measures of performance. Broadly, our data show that governance complexities and environmental constraints violate many of the principal-agent assumptions embodied within performance management doctrine. At the same time, interviews suggest that some CoCs use HUD reporting requirements for varied purposes, including catalytic and discursive capacities (Musso and Weare, 2019; Moynihan, 2008; Nathan 2008). Overall, CoCs are building performance management systems capacities, but still face challenges regarding sustainable organizational culture. Impediments to performance include both internal organizational factors and external factors such as lack of housing, limited funding, and regulatory restrictions. Overall, the evidence supports a more cooperative and discursive model for capacity building rather than a top-down view of performance management governance in networked grant-in-aid systems. 09:12 and Our paper contributes to the collaborative performance literature. We argue that to understand shared data use during the implementation phase, we need to examine groups’ engagement with performance practices during the earlier planning and coordination phases using a temporal view. We also submit that the three mechanisms constitute broader theoretical streams that call for theorizing about specific causal pathways within them. We identify and examine three lower-level mechanisms that can help explain collective data use: ambiguity reduction, formality-informality complementarity, and identity creation. To develop and illustrate our arguments, we employ a mechanism-based case study. This approach relies on the use of explanatory narratives, and it is particularly appropriate if the unit of the analysis is a social, interactive process. As our case, we selected the Citizen Security Plan in Jamaica (2020-2023). The Plan is an initiative that aims to combine addressing crime and safety issues with efforts of community development. It was selected because it requires government to collaborate; it relies on the use of goals and data; and it allowed us to observe changes across project phases. 08:30 and This study conducts a nationwide survey of 50,000+ faculty at public postsecondary education institutions to assess what factors impact their awareness of student homelessness. We will conduct exploratory factor analysis to investigate a myriad of personal backgrounds, professional experience, university engagement, and campus resource item variables. We hypothesize that faculty with personal experience with homelessness, those in human service and social work fields, and those who frequently engage with their university resources are more likely to have increased awareness of student homelessness. Data collection was completed in December 2023. 08:45 To accomplish this, I will employ a two-way fixed-effect model using data sourced from the U.S. Census Bureau, Georgia Department of Education, Governor’s Office of Student Achievement, and National Center for Education Statistics (NCES). The dataset spans the school years from 2011 to 2019, with dependent variables of financial outcomes (total expenditure, instructional expenditure, fixed cost) and student outcomes (Georgia Milestones scores, graduation rate, school safety index). 09:00 09:15 08:30 , and To study this, we investigate disaster resilience planning in a rural county in the Southeast of the US exposed to several natural disasters, including tornadoes, ice storms, and strong winds. The county is characterized as having a high level of social vulnerability compared to the rest of the US (US Federal Emergency Management Administration, 2023). The empirical base includes data from observations of local government public meetings, content analysis of relevant planning documents, and interviews with collaborative partners. The data are analyzed using social network analysis methods, including descriptive and inferential techniques. The findings have implications for public management theory and practice in resilience planning. 08:45 , and 09:00 09:15 and 08:30 Ordinal representation pertains to altering the order of representation among bureaucrats when cardinal representation cannot be improved. For instance, in an organization with four bureaucrats where two are female and two are male regarding gender representation, cardinal representation cannot be enhanced. To address the question of whether ordinal representation holds significance in coproduction, this study examines the ordinal effects of gender representation on individuals’ decisions to coproduce. By employing two distinct policy areas—recycling and emergency preparedness—the study randomizes the order of female officials in a setting with two males and two females, where gender representation cannot be enhanced in a cardinal manner. Both experiments failed to consistently identify evidence of the ordinal effects resulting from placing females in different orders on citizens’ overall willingness to coproduce. However, the results revealed a pattern indicating that the gender of the chief leader influences an increase in the willingness of others of the same gender—and simultaneously decreases the willingness of their gender counterparts—to participate in coproduction. 08:45 09:00 , and 08:30 08:45 , and 09:00 and 09:15 08:30 and This paper addresses the widening academic gap and examines the role of public education in fostering academic equity. This study responds to the call for a more holistic understanding of what perpetuates academically successful youth from historically inequitable backgrounds by linking the individual with their greater environment (McCoy & Bowen, 2015). Specifically, we ask, “what individual and institutional factors promote equitable access to higher education across marginalized student identities?” We propose a two-level, intersectional public education equity framework. The framework is tested using data from surveys conducted among 1,400+ high school seniors and 50 guidance counselors in ten public high schools in the United States. The findings reveal misalignments between schools and individuals regarding perceptions of protective factors for social equity, indicating significant variations in the factors believed to impact access to higher education. Additionally, the study identifies certain risk factors for academic inequity, such as homelessness, first-generation status, lack of school resources, and financial constraints, which can be mitigated through protective factors such as societal expectations, family support, mentorship programs, and peer norming. 08:45 Research on place-based incentives has primarily focused on single incentive programs, concentrating on property values or job creation as desired outcomes. Few studies have compared multiple place-based investments or evaluated the combination of investments and resulting changes in equitable access to capital for neighborhood residents. This paper contributes to existing research by analyzing several programs—Community Development Block Grant (CDBG), Neighborhood Opportunity Fund (NOF), New Market Tax Credit (NMTC), Property Tax Abatement (PTA), Small Business Improvement Fund (SBIF), and Tax Increment Financing (TIF)—and how the related investments alter the racial composition of neighborhoods as a result of home loan approvals. In doing so, this paper offers a better understanding of and policy prescriptions for enhancing social equity when redeveloping and revitalizing local communities in need. 09:00 , and We explore these tensions by drawing on quality rating data from England's Care Quality Commission to compare service quality across health and social care organizations that are government-run, CICs "spun-out" of the state, or privately-founded CICs. Specifically, we use ordered logit regression models to compare over 2,000 quality ratings of these three types of providers across five dimensions: safe, effective, caring, responsive, well-led, plus an overall rating. We draw on a 'publicness' theoretical framework to explore whether and to what extent public or private ownership, as well as the loss of public ownership through the ‘spin-out’ of public services into independent social enterprises, impacts quality. Our initial results show that overall, both types of social enterprise CICs performed better than government-run services, whilst non-spin-out CICs performed best on caring and responsive and spin-out CICs performed best on safe and effective dimensions. 09:15 and 08:30 and 08:45 and Understanding this is important, first, because officials often have a more comprehensive view of local financial health than objective financial indicators can capture alone. Compared to information contained in financial statements, commonly used for indicators, local practitioners possess broader relevant data and a nuanced understanding of what it means in the local context. Second, local government officials, i.e. individuals positioned within a network of government and community actors, ultimately make local investment, policy, and programmatic decisions. As such, when it comes to understanding policy outputs, their perceptions of their municipality’s financial condition arguably matter more than objective measures. Drawing from open system theory and the literature on perceived organizational outcomes, this research aims to explore whether public managers holding positions in different city departments have systematically different views on financial health. This research examines survey data from city officials in 273 Kansas cities with populations over 500. The survey, conducted between September 2023 and January 2024, targeted professionals in five positions—City Administrator and Directors of Public Works, Planning and Finance. Through descriptive and empirical analysis, this research illuminates how perceived local financial conditions in influence the decisions and fiscal responses across different organizations. 09:00 and 09:15 , , , and 10:15 and Building upon previous works on policy designs of net energy metering, which have gained less attention despite its prevalence, we explore different tariff designs and create indexes encompassing various NEM tariffs. Using panel data (about 200 investor-owned utilities in 50 states from 2013 to 2021), we evaluate how different tariff designs have affected the penetration of distributed solar. By studying the correlation between policy designs and the adoption of DERs, our study contributes to policy design literature, understanding how various policy designs affect policy outcomes and how to design policies for other distributed resources. 10:30 and Strategic management is often touted as an approach for integrating strategy formulation and implementation in response to environmental challenges. As one of the popular approaches used by the public sector, strategic management is often touted as a means for effective public service delivery. However, it is unclear whether current strategic management approaches are up to the task of addressing climate-related threats to the sustainability of public services at the local level where problems are fundamentally transboundary and require coordination across typical silos. We address this gap by asking: What manager-led processes drive resource-constrained cities to adapt their capabilities to the accelerating impacts of climate change? Using a novel mixed methods approach combining survey, text analysis of planning documents, and interviews, we examine how resource-constrained cities in Indiana integrate their capabilities and planning in response to climate change in the context of GSI. 10:45 11:00 and While regulatory competition suggests a state would relax its enforcement on an entity when its corporate siblings (entities that belong to the same company) in other states have been penalized for violations, regulatory learning theory, predicts otherwise. When an entity’s corporate siblings become violators, it tarnishes the reputation of the whole company and indicates possible wrongdoing of the focal entity itself, prompting regulators to increase scrutiny on the focal entity. We test the two competing theories using a facility-level panel dataset of Clean Air Act enforcement actions. Preliminary results show a mixed pattern. While regulators increase enforcement on a facility when its same-industry siblings located in the same state become high priority violators (regulatory learning dominates), they relax enforcement on the focal facility if the same-industry violator siblings are in competitor states (regulatory competition dominates). 10:15 10:30 , , and 10:45 Public Administration scholars must pay attention to this restructuring and its impacts to agency adjudication practices. This working systematic review of the Federal Administrative Judiciary will analyze distinct approaches employed by legal and public administration scholars to explore the conceptual and very practical tension between judicial independence and bureaucratic discretion. As the first systematic review regarding this topic, I expect to chronicle the development of these positions within the federal government by exploring institutional collaboration and influences. And finally, I hope to identify topics that may bolster comprehension of administrative adjudication in the USA. This presentation is relevant to the overall theme of “Bringing Theory to Practice”. As a heavily applied social science, public administration scholars focusing in management must attend to the legal discourse, particularly regarding judicialized employees. ALJs are in such a position within an agency to provide a unique bridge between public administration and the legal discipline. With the ongoing restructuring of their position, there are ample opportunities for practice to also inform theoretical innovation. 10:15 and 10:29 , , , and 10:43 , and 10:57 and The aim of our review is twofold. First, given the potential of relational contracting as an alternative to traditional contracting in complex situations, we aim to examine how relational approaches may or may not be a viable alternative to traditional transactional approaches. Second, we aim to contribute to the existing literature by developing an integrative framework of relational contracting as a way of managing buyer-supplier relationships in public procurement. Using ASReview Lab, an open-source machine learning software, we identify, collect, and assess relevant articles on this topic. Based on the findings, we develop an integrative framework of relational contracting in public procurement and present a research agenda to tackle theoretical and empirical lacunas in research into relational contracting. 10:15 , , , and While previous literature discusses how politics and power structure shape global public policy and governance transformation, there is a notable gap in understanding grassroots-based practices that explore innovative narratives, actors, and strategies to establish a community of practices for poverty reduction in the global south. To address this research gap, we outline a processual, multilevel, network-centric perspective by investigating two community-based poverty reduction cases in Africa and China. Our findings reveal that development narratives, actors’ networks, and pragmatically evolutionary practices constitute the three key pillars for building a community of practice focused on poverty reduction in the global south. The paper contributes to the literatures on the role of action research in poverty reduction in the global south, aligning with the first priority of the Sustainable Development Goals (SDGs). Meanwhile, it highlights the significance of knowledge network in the formulation and implementation of public policies. The study also bridges the knowledge gap between development theory and practical applications in poverty reduction in the global south. 10:30 10:45 and 11:00 and Our mixed method study takes place in the Puget Sound Basin of Washington state, where we gather data on stakeholder perceptions from approximately 48 CGRs working on ecosystem recovery. We use an exploratory sequential design, starting with interviews to generate a list of indicators with which stakeholders evaluate usefulness of scientific information. We then draw on this list to develop a survey sent to approximately 800 stakeholders. Our initial data show that scientific information is considered most useful when it comes from a reputable source and is produced transparently. Unexpectedly, less valuable indicators of usability included peer-review and co-production with information users. Our study contributes to CGR theory on knowledge management, identifying qualities that may enhance likelihood that information influences joint decisions. It also offers policy implications for information producers, suggesting ways to enhance information’s usability for practitioners in ecosystem recovery. 10:15 , , and 10:30 and 10:45 and Our quantitative study investigates the link between learning organization and job satisfaction and the mediating role of psychological safety in a policing context. We use the dimensions of learning organization questionnaire (DLOQ) developed by Watkins and Marsick (1997), Edmonson’s (1999) instrument for measuring psychological safety and the short index of job satisfaction (Sinval & Marôco, 2020). The participants in our study are experienced German police officers selected for future leadership positions. 11:00 Seeking to identify effective and efficient outreach methods, in 2023 the Northeast Ohio Regional Sewer District conducted a field experiment involving 56,000 households in the Cleveland, Ohio metropolitan area. Using a conjoint design, the experiment randomly assigned households to a control condition or one of up to 56 combinations of treatments. Treatments included black and white postcards, color postcards, letters from the utility, letters from a community organization, English-only messages, bilingual messages, and multiple mailings. Some mailings framed assistance in terms of dollar value, while others expressed benefits as percentage discounts. Results indicate that direct mail significantly increased CAP inquiries, and that a single, simple black-and-white postcard was the most cost-effective medium. Surprisingly, messaging variables did not drive significantly different response rates. The study is a model of university-government collaboration, and its findings provide unprecedented evidence about direct mail as a means of reducing learning burdens for public assistance programs. 10:15 10:30 , , and 10:45 To understand data and data skills in city governments, this research proposal uses survey results from local government chief administrators in the census west region of the United States. The findings of this exploratory research suggest that 1) a data-skills gap exists in local government, 2) data skill expertise contributes indirectly to a chief administrator’s satisfaction in their organization’s overall data skills, and 3) data capture, curation, and analysis skills have smaller skill gaps compared to data communication and application skills. The findings provide important insight into the data skill needs of local governments and help identify important research questions for local governments and the acquisition of data skills. 11:00 , and To answer this question, we employ a conjoint experiment on high-level directors in local government to determine their interest in applying to management positions given different job characteristics. Our conjoint survey experiment asks respondents to make four discrete choices between paired job descriptions. These job descriptions vary in characteristics of the work of city managers including the flexibility of the schedule, after-hours commitments, paid time off, perceived stability of the position, and requirements for public engagement. The data is then analyzed considering the respondent characteristics, position, mentorship, and family life considerations to more comprehensively explore the propensity of women to seek out next-level managerial roles based on these job requirements. This paper disentangles the question of whether women would be more interested in applying to city management roles if the position was designed differently. This study offers local governments recommendations for rethinking the nature of the city manager role. 10:15 , and 10:30 , and 10:45 and Our findings indicate that self-motivation emerges as a significant factor positively influencing innovative behavior among national civil servants. Individuals who exhibit a strong internal drive and intrinsic motivation are more likely to engage in innovative practices, contributing to a culture of creativity within the public sector. Peer trust also emerges as a noteworthy factor associated with enhanced innovative behavior. Surprisingly, institutional support, often considered as a key determinant in fostering innovation, was not found to have a significant impact on innovative behavior in our study. Similarly, the presence of competition among organizations within the public sector was not found to significantly influence innovative behavior among national civil servants. This nuanced finding invites a deeper exploration of the nature of competition and its implications for fostering innovation within the unique dynamics of national civil service environments. The implications of these findings are substantial for public sector leaders and policymakers:.recognizing the importance of cultivating self-motivation and fostering peer trust can serve as a strategic approach to promote innovative behavior among civil servants. 11:00 and 10:15 10:30 10:45 and We argue that team leadership assignments are gendered in ways that will disadvantage women. Whereas men are likely to be given leadership assignments that are conducive to continuing career progress within their organizations, women are likely to be given leadership assignments that hamper their progress. One reason for this is *structural*: Women and men begin their careers in different types of teams, and consequently accumulate early-career experiences that delimit their future leadership opportunities in divergent ways. A second reason is *aspirational*: Women who are candidates for open leadership positions will be inclined to doubt their qualifications, to be skeptical of their leadership capabilities, and to experience anxiety about assuming formal team-level leadership responsibilities. And a third reason is *stereotypical*: Organizational stakeholders who have input into promotion decisions will harbor differing expectations about women's and men's leadership potential, expectations that will tend to be more negative when it comes to women's leadership capacities. We test these expectations using longitudinal, individual-level personnel data on United States federal employees. 10:15 However, in contrast to employees, politicians can be conceived as organizational outsiders. Instead, we therefore argue that political considerations affect how politicians assess and value performance measures. Specifically, we hypothesize that (a) politicians will perceive performance information featuring high and low performance signals differently, but also that (b) political ideology in terms of being aligned/opposed to the measured public services and (c) being affiliated/in opposition to the ruling political coalition will affect their perceptions. To test these hypotheses, we conducted a pre-registered survey experiment among political candidates for Danish regional councils charged primarily with governing health care services (n=885). Respondents were randomly exposed to either no information or true performance information (high/low) about their own region’s health care system. They were then asked to evaluate the validity, legitimacy, and usefulness of the information, and whether they wanted to receive additional information. The results have potentially important practical implications concerning when political decision-makers are willing to trust and use performance information and policy evidence. 10:30 The model captures three dimensions at which legitimacy can be created or undermined: the political articulation of public interests (input), the administrative implementation process (throughput), and the results achieved for citizens (output). A comprehensive review of the literature will be structured along the ITO model. Initial findings suggest that results for 1) input and 2) output are mixed, while they are most promising regarding 3) throughput legitimacy. First, while performance systems can increase political control, they are modest regarding strengthening minority interests. The management literature laments that a stronger results focus has not been accompanied by more resource autonomy, but such an increase in control is not a problem from a legitimacy perspective. At the same time, though performance systems can be pluralist in nature, evidence suggests they often reinforce existing power differentials. Second, research documents that performance systems improve outcomes, but gains may not be necessarily equitable. Third, they can enhance the evidence base for decision making, and bias here is less of an issue from a democratic perspective if it reflects political values. Performance systems create process legitimacy if they capture citizen feedback, structure interactions between government and civil society, and increase citizen trust. 10:45 and In this paper, we revisit the relationship between politics and administration, emphasizing how politics can influence agency performance even in the most professional and high performing agencies. We describe the mechanisms by which political alignment or misalignment influence performance. We detail how presidents work to 1) change outputs by directly influencing agency capacity (e.g., budget and personnel levels) and 2) change outputs without directly targeting capacity by using the tools of the administrative presidency to let capacity idle, reorient capacity, or diminish capacity indirectly. We test these relationships using newly created measures of agency performance for 139 U.S. federal agencies during the 2000-2022 period. The new measures combine dozens of subjective and objective measures of performance that vary across agencies and time. We conclude with the implications of our findings for future research focusing on the intersection of both politics and management. 11:00 10:15 , , and 10:30 10:45 and 10:15 , and 10:30 , and 10:45 , and Open access Published: 20 June 2024 Circulating small extracellular vesicles in Alzheimer’s disease: a case–control study of neuro-inflammation and synaptic dysfunction Rishabh Singh 1 , Sanskriti Rai 1 , Prahalad Singh Bharti 1 , Sadaqa Zehra 1 , Priya Kumari Gorai 2 , Gyan Prakash Modi 3 , Neerja Rani 2 , Kapil Dev 4 , Krishna Kishore Inampudi 1 , Vishnu V. Y. 5 , Prasun Chatterjee 6 , Fredrik Nikolajeff 7 & Saroj Kumar 1 , 7   BMC Medicine volume  22 , Article number:  254 ( 2024 ) Cite this article 264 Accesses 10 Altmetric Metrics details Alzheimer’s disease (AD) is a neurodegenerative disease characterized by Aβ plaques and neurofibrillary tangles. Chronic inflammation and synaptic dysfunction lead to disease progression and cognitive decline. Small extracellular vesicles (sEVs) are implicated in AD progression by facilitating the spread of pathological proteins and inflammatory cytokines. This study investigates synaptic dysfunction and neuroinflammation protein markers in plasma-derived sEVs (PsEVs), their association with Amyloid-β and tau pathologies, and their correlation with AD progression. A total of 90 [AD = 35, mild cognitive impairment (MCI) = 25, and healthy age-matched controls (AMC) = 30] participants were recruited. PsEVs were isolated using a chemical precipitation method, and their morphology was characterized by transmission electron microscopy. Using nanoparticle tracking analysis, the size and concentration of PsEVs were determined. Antibody-based validation of PsEVs was done using CD63, CD81, TSG101, and L1CAM antibodies. Synaptic dysfunction and neuroinflammation were evaluated with synaptophysin, TNF-α, IL-1β, and GFAP antibodies. AD-specific markers, amyloid-β (1–42), and p-Tau were examined within PsEVs using Western blot and ELISA. Our findings reveal higher concentrations of PsEVs in AD and MCI compared to AMC ( p  < 0.0001). Amyloid-β (1–42) expression within PsEVs is significantly elevated in MCI and AD compared to AMC. We could also differentiate between the amyloid-β (1–42) expression in AD and MCI. Similarly, PsEVs-derived p-Tau exhibited elevated expression in MCI compared with AMC, which is further increased in AD. Synaptophysin exhibited downregulated expression in PsEVs from MCI to AD ( p  = 0.047) compared to AMC, whereas IL-1β, TNF-α, and GFAP showed increased expression in MCI and AD compared to AMC. The correlation between the neuropsychological tests and PsEVs-derived proteins (which included markers for synaptic integrity, neuroinflammation, and disease pathology) was also performed in our study. The increased number of PsEVs correlates with disease pathological markers, synaptic dysfunction, and neuroinflammation. Conclusions Elevated PsEVs, upregulated amyloid-β (1–42), and p-Tau expression show high diagnostic accuracy in AD. The downregulated synaptophysin expression and upregulated neuroinflammatory markers in AD and MCI patients suggest potential synaptic degeneration and neuroinflammation. These findings support the potential of PsEV-associated biomarkers for AD diagnosis and highlight synaptic dysfunction and neuroinflammation in disease progression. Peer Review reports The progressive neurodegenerative condition known as Alzheimer’s disease (AD) is characterized by cognitive decline as a result of the formation of amyloid-β (Aβ) plaques, neurofibrillary tangles (NFTs), and chronic neuroinflammation that leads to neurodegeneration [ 1 , 2 , 3 ]. Synapse loss is a crucial pathophysiological event in disease progression, and synaptic proteins have been extensively studied due to earlier perturbations [ 4 , 5 ]. The pathological hallmark of AD, amyloid-β plaques, originates from the imprecise cleavage of the amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase generating amyloid-β peptide forms [ 6 , 7 , 8 , 9 ]. Primary amyloid-β peptide forms are Aβ40 and Aβ42, where the majority of the amyloid-β plaques in AD brains are composed of Aβ42 [ 10 ]. Many point mutations in APP and γ-secretase cause familial early-onset AD, favoring Aβ42 formation, causing amyloid-β peptides prone to aggregate as fibrils and plaques [ 9 , 11 , 12 , 13 , 14 ]. Hyperphosphorylation of tau causes the formation of NFTs. The combined effect of accumulation of NFTs, amyloid-β fibrils, and plaques leads to neuronal function loss and cell death [ 15 , 16 ]. Aβ plaques activate immune receptors on microglia, thereby releasing pro-inflammatory cytokines and chemokines that mediate neuroinflammation, which, if it reaches a chronic level, causes damage to brain cells, including axonal demyelination and synaptic pruning [ 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. In addition to these, other proteins, including the neurofilament light (NFL) protein, glial fibrillary acidic protein (GFAP), and synaptic proteins, have also been identified as AD biomarkers [ 24 , 25 , 26 , 27 , 28 ]. Understanding the intricate dynamics of AD in terms of its varied pathophysiological manifestations, such as neuroinflammation, synaptic loss, and proteinopathy, is essential for developing potential therapeutic interventions for AD and biomarker discovery. In clinical practice, cognitive assessment tools such as the Addenbrooke’s Cognitive Examination (ACE-III) and Mini-Mental State Examination (MMSE) are used to diagnose AD. These tools evaluate verbal fluency and temporal orientation, although results may be influenced by subject bias [ 29 , 30 , 31 ]. In recent years, small extracellular vesicles (sEVs) or exosomes have been acknowledged as crucial mediators of communication and signaling within the body, contributing significantly to the transmission of cellular cargo in various health and disease states. They also play a notable role in disseminating protein aggregates associated with neurodegenerative diseases [ 32 ]. sEVs are bi-layered membrane vesicles that have a heterogeneous group of (< 200 nm in diameter) that are found in different human body fluids, including blood, urine, saliva, and ascites, and that are actively released by all cell types [ 33 , 34 , 35 ]. For their functions in various physiological and pathological circumstances, sEVs are the most extensively researched type of EV [ 36 , 37 , 38 ]. sEVs exchange information between cells by transferring bioactive components (nucleic acids and proteins) [ 39 ]. As the sEVs’ composition bears the molecular signature of the secreting cell and bears an intrinsic property of transversing the blood–brain barrier (BBB) in both directions [ 40 , 41 ], they are a target of constant research in neurodegenerative disease. Furthermore, sEVs released by neuronal cells are crucial in transmitting signals to other nerve cells, influencing central nervous system (CNS) development, synaptic activity regulation, and nerve injury regeneration. Moreover, sEVs exhibit a dual function in neurodegenerative processes, as sEVs not only play an essential role in clearing misfolded proteins, thereby exerting detoxifying effects and providing neuroprotection [ 42 ]. On the other hand, they also have the potential to participate in the propagation and aggregation of misfolded proteins, particularly implicated in the pathological spread of Tau aggregates as indicated by both in vitro and in vivo studies [ 43 ]. As a protective mechanism, astrocytes (most abundant glial cells) accumulate at the locations where Aβ peptides are deposited, internalizing and breaking down aggregated peptides [ 44 ]. However, severe endosomal–lysosomal abnormalities arise in astrocytes when a significantly large amount of Aβ accumulates within astrocytes for a prolonged period without degradation [ 45 , 46 ]. Astrocytes then release engulfed amyloid-β (1-42) protofibrils through exosomes, leading to severe neurotoxicity to neighboring neurons [ 44 ]. Additionally, it has been found that the release of amyloid-β by microglia in association with large extracellular vesicles (Aβ-lEVs) damages synaptic plasticity and modifies the architecture of the dendritic spine [ 47 ]. Thus, sEVs can be a compelling subject for the investigation to understand AD’s inflammation and synaptic dysfunction [ 48 , 49 , 50 , 51 , 52 ]. In this study, we reported that protein levels are associated with AD pathology, neuroinflammation, and synaptic dysfunction in plasma-derived small extracellular vesicles (PsEVs). Our objective was to understand the pathophysiological process, neuroinflammation, synaptic dysfunction, and Aβ pathology through sEVs. Our study revealed a significant correlation between the concentration of cargo proteins derived from PsEVs and clinical diagnosis concerning ACE-III and MMSE scores. Furthermore, the levels of these studied proteins within PsEVs could differentiate between patients with MCI and AD. Thus, our study sheds light on the potential of PsEVs in understanding AD dynamics and offers insights into the underlying mechanisms of disease progression. Subject recruitment A total of n  = 35 AD patients and n  = 25 subjects with MCI were recruited from the Memory Clinic, Department of Geriatrics, All India Institute of Medical Sciences, New Delhi, India. Additionally, n  = 30 healthy AMC (volunteers) were recruited. The inclusion criteria were as follows: a clinical diagnosis of MCI and AD patients using ACE-III and MMSE tests. The exclusion criteria encompass medical conditions such as cancer, autoimmune disorders, liver disease, hematological disorders, or stroke, as well as psychiatric conditions, substance abuse, or any impediment to participation. Controls were healthy, age-matched adults without neurological symptoms. AMC was 60–71, MCI was 65–79, and AD was 70–80 years of age range (Table  1 ). Neuropsychological scores, viz., ACE-III and MMSE, were recorded before subject selection. Study ethical approval The institutional ethics committee of All India Institute of Medical Sciences, New Delhi, India, granted the study ethical permission. The study has been granted the ethical approval number IECPG-670/25.08.2022. Following the acquisition of the written informed consent, all participants were enrolled. Sample collection One milliliter of blood was drawn from each participant using venipuncture, and blood collection vials were kept on ice during collection. The blood was centrifuged at 1700 g for 20 min at 4 °C to remove the cells, and the straw-colored plasma was collected. It was further clarified by centrifuging for 30 mi at 4 °C at 10,000 g. Finally, cleared plasma was stored at − 80 °C until further use. The samples were used for the downstream experiment after being thawed on ice and centrifuged at 10,000 g. Isolation of PsEVs The PsEVs were extracted by chemical-based precipitation from the plasma samples of AD patients, MCI patients, and AMC, as discussed previously [ 53 , 54 ]. In brief, 180 μL of plasma sample was used and filtered with 0.22 μm filter (SFNY25R, Axiva), followed by overnight incubation with the chemical precipitant (14% polyethylene glycol 6000) (807,491, Sigma). The samples underwent an hour-long, 13,000 g centrifugation at 4 °C the next day. Before being resuspended in 200 μL of 1X PBS (ML116-500ML, HiMedia), the pellet was first cleaned twice with 1X PBS. Before downstream experiments, the sEVs-enriched fraction was further filtered through a 100-kDa filter (UFC5100, Millipore). Nanoparticle tracking analysis (NTA) 5000-fold dilution in 1X-PBS buffer was used for the NTA of PsEVs. In the ZetaView Twin system (Particle Metrix, Germany) sample chamber, 1 mL of diluted PsEVs sample was introduced. The following parameters were used throughout three cycles of scanning 11 cell locations each, and 60 frames per position were collected (video setting: high, focus: autofocus, shutter: 150, 488 nm internal laser, camera sensitivity: 80, cell temperature: 25 °C. CMOS cameras were used for recording, and the built-in ZetaView Software 8.05.12 (Particle Metrix, Germany) was used to analyze: 10 nm as minimum particle size, 1000 nm as maximum particle size, and 30 minimum particle brightness. Transmission electron microscopy for morphological characterization Transmission electron microscopy was employed to investigate PsEVs’ ultrastructural morphology. The resultant PsEVs pellet was diluted with PBS using 0.1 M phosphate buffer (pH 7.4). A carbon-coated copper grid of 300 mesh (01843, Ted Pella) was used to adsorb the separated PsEVs at room temperature for 30 min. After blot-drying, the adsorbed grids were dyed. For 10 s, 2% aqueous uranyl acetate solution (81,405, SRL Chem) as negative staining. After blotting the grids, they were inspected using a Talos S transmission electron microscope (ThermoScientific, USA). Western blot Based on the initial volume of biofluid input, all samples were normalized, i.e., 180 μL and the sample loading dye (2 × Laemmle Sample buffer) was mixed with PsEVs sample, and 20 μL equal volume was loaded to run on an 8–12% SDS PAGE [ 53 , 55 ]. After the completion of SDS-PAGE, protein from the gel was subjected to the Wet transfer onto the PVDF membrane of 0.22 μm (1,620,177, BioRad). The membrane-blocking with 3% bovine serum albumin (BSA) (D0024, BioBasic) in Tris (TB0194, BioBasic) base saline containing 0.1% of Tween 20 (65,296, SRL Chem) (TBST) using the BioRad Western blotting apparatus (BioRad, USA). Following this, overnight incubation of primary antibodies of CD63 (10628D, Invitrogen), CD81 (PA5-86,534, Invitrogen), TSG101 (MA1-23,296, Invitrogen), L1CAM (MA1-46,045, Invitrogen), synaptophysin (ADI-VAM-SV011-D, Enzo life sciences), GFAP (A19058, Abclonal), amyloid-β (1–42) oligomer (AHB0052, Invitrogen), phospho-Tau (s396) (35–5300, Invitrogen), interleukin 1β (IL-1β) (PA5-95,455, Invitrogen), tumor necrosis factor α (TNF-α) (E-AB-33121, Elabscience), and β-actin (AM4302, Invitrogen) were done at 4 °C. The membranes were washed with TBST buffer four times before at RT incubating with HRP-conjugated secondary antibodies, anti-rabbit (AB6721, Abcam), anti-mouse (31,430, Invitrogen). The Femto LUCENT™ PLUS-HRP kit (AD0023, GBiosciences) was used to develop the blot for visualizing the protein bands utilizing the method of enhanced chemiluminescence. Enzyme-linked Immunosorbent Assay (ELISA) According to the previous protocol, ELISA was carried out. [ 53 ]. PsEV samples were subjected to freeze–thaw cycles; next, PsEVs were ultrasonicated for two minutes, with a 30-s on-and-off cycle, at an amplitude of 25. Following this, they underwent a 10-min centrifugation at 10,000 g, at 4 °C, and the obtained supernatant was used. The samples were kept at 37 °C before loading into the ELISA plates. The bicinchoninic acid (BCA) protein assay kit (23,225, ThermoFisher Scientific) was used to quantify the total protein concentration using BSA (D0024, BioBasic) as a reference. The ELISA kit was used to detect the presence of protein in 100 μL of PsEV sample are as follows: amyloid-β (1–42) (E-EL-H0543, ELabsciences), p-Tau (s-396) (E-EL-H5314, ELabsciences), IL-1β (ITLK01270, GBiosciences), TNF-α (ITLK01190, GBiosciences), GFAP (E-EL-H6093, ELabsciences), and synaptophysin (E-EL-H2014, ELabsciences). The manufacturer’s instructions were followed for every step of the process. A 96-well microplate spectrophotometer (SpectraMax i3x Multi-Mode Microplate Reader, Molecular devices) was used to measure the absorbance at 450 nm. Data and statistical analysis The mean age values, ACE-III score, and MMSE score were ascertained using descriptive statistical analysis Table  1 . GraphPad Prism 8.0 was used for statistical data analysis, including NTA concentration, Western blotting densitometric analysis, and ELISA. Unpaired student t -test and ANOVA were used for group analysis, and statistical significance was determined. p  < 0.05 was used to assess significance. The Image J software (NIH, USA) was used for the densitometry analysis. The receiver operating characteristic (ROC) curve was used to analyze the efficiency of distinguishing the case from controls. Correlation analysis was conducted between the concentration of PsEVs and the levels of ELISA proteins, including amyloid-β (1–42), p-Tau, IL-1β, TNF-α, GFAP, and synaptophysin, and additionally between the PsEVs-derived levels of amyloid-β (1–42) β1-42, p-Tau, IL-1β, TNF-α, GFAP, and synaptophysin with ACE-III and MMSE values. ROC curve is a probability curve utilized to assess the accuracy of a test. The test’s ability to distinguish between groups is indicated by the area under the curve (AUC), which acts as a quantitative measure of separability. An outstanding test typically exhibits an AUC close to 1, signifying a high level of separability. Conversely, a subpar test tends to have an AUC closer to 0, indicating a poor ability to distinguish between the two classes. Characterization and validation of isolated sEVs PsEVs were isolated, characterized, and validated following Minimal Information for Studies of Extracellular Vesicles (MISEV) 2018 guidelines, which suggest a protocol for documenting work specifically with extracellular vesicles [ 56 ]. PsEVs from AMC, MCI, and AD subjects were morphologically characterized by transmission electron microscopy, and spherical lipid bi-layered vesicles were observed in the size range of sEVs (Fig.  1 A–C). In Fig.  1 D–F, the size distribution and concentration of PsEVs were observed in the size range of 30–200 nm in diameter by NTA, which is within the sEVs’ size range. The mean concentration of PsEVs in AMC, MCI, and AD patients were 5.12E + 10, 2.6E + 11, and 3.13E + 11 particle/ml, respectively, with higher concentrations of PsEVs in MCI and AD than in AMC ( p  < 0.0001) (Fig.  1 G). To differentiate AD from AMC, ROC and AUC analyses were performed where the AUC = 0.9748, with a sensitivity of 97.14% and specificity of 70.01% (Fig.  1 H), while in AMC versus MCI, AUC = 0.987, sensitivity of 96% and specificity of 86.67% (Fig.  1 I). Furthermore, we could also differentiate between MCI and AD, AUC = 0.629, sensitivity of 60%, and specificity of 56% (Fig.  1 J). Validation of PsEVs was done using immunoblot for sEVs-specific markers (CD63, CD81, and TSG101), which showed a significant increase in expressions in MCI and AD than in AMC (CD63, p  = 0.0489, 0.0478 (Additional File 1 : Fig. S1); CD81, p  = 0.0172, 0.0133 (Additional File 1 : Fig. S2); TSG101 p  = 0.0240, 0.0329 (Additional File 1 : Fig. S3)) for AD and MCI respectively (Fig.  2 A–D). Additionally, higher L1CAM (neuron-associated marker) expression was observed in MCI ( p  = 0.0100) and AD ( p  = 0.0184) (Additional File 1 : Fig. S4) compared to AMC (Fig.  2 E). All densitometric values were normalized against β-actin, which was used as a loading control (Additional File 1 : Fig. S7). Isolation and analysis of PsEVs. The isolated PsEV morphology characterize by transmission electron microscopy from age-matched healthy controls (AMC) ( A ), mild-cognitive impairment (MCI) patients ( B ), and Alzheimer’s disease (AD) ( C ). The size distribution of PsEVs subpopulation (nm) versus the concentration (particle/ml) in AMC ( D ), individuals with MCI ( E ), and AD ( F ). Comparison of the sEVs concentration of AD, MCI, and AMC patients ( G ). Receiver operating characteristic (ROC) curve of PsEVs concentration in AMC v/s AD ( H ), AMC v/s MCI ( I ), and MCI v/s AD ( J ) (scale bar 100 nm) Validation of PsEVs expression analysis of different markers in PsEVs in age-matched controls (AMC), mild cognitive impairment (MCI), and Alzheimer’s disease patients (AD) ( A ). Densitometric analysis of CD63 ( B ), densitometric analysis of CD81 ( C ), densitometric analysis of TSG101 ( D ), densitometric analysis of L1CAM ( E ), densitometric analysis of synaptophysin ( F ), densitometric analysis of GFAP ( G ), and densitometric analysis of amyloid-β (1–42) oligomer ( H ). All densitometric values were normalized against β-actin Differential expression of amyloid-β (1–42), p-Tau, synaptophysin, GFAP markers, and levels of IL-1β and TNF-α in PsEVs Using ELISA, we measured levels of amyloid-β (1–42) and p-Tau in PsEVs from AMC, MCI, and AD patients. The significant increase of amyloid-β (1–42) and p-Tau among the groups (Fig.  3 A–H). Amyloid-β (1–42) levels were higher in MCI compared to AMC ( p  < 0.0001) and more significant in AD than in MCI and AMC ( p  < 0.0001) (Fig.  3 A). Similarly, in comparison to MCI and AMC, p-Tau levels were significantly higher in AD ( p  < 0.0001) (Fig.  3 E). Similar levels of both markers were found in their Western blots (Fig.  2 ). We checked GFAP (astrocytic marker) and proinflammatory cytokines (TNF-α and IL-1β) to evaluate neuroinflammation. For proinflammatory markers, IL-1β and TNF-α levels showed a significant increase among the three groups ( p  < 0.0001 for IL-1β and TNF-α) (Fig.  3 I, M). When comparing AD to MCI and AMC, the GFAP concentration in PsEVs was significantly higher ( p  < 0.0001) (Fig.  3 Q). Similar trends were observed with Western blot analysis (Fig.  2 , Additional File 1 : Fig. S6, S9). Their elevated levels suggest prominent neuroinflammatory conditions contributing to potential neuronal damage. The elevated levels of these neuroinflammatory markers could be due to the activation of astrocytes and microglia and the subsequent increase in the secretion of PsEVs containing proinflammatory proteins, which suggests prominent neuroinflammatory conditions that may contribute to neuronal damage [ 57 ]. While synaptophysin concentration in PsEVs was downregulated in AD and MCI compared to AMC ( p  < 0.0001) in ELISA (Fig.  3 U), it shows synaptic dysfunction. We also checked synaptophysin levels in PsEVs in Western blotting, finding it was downregulated in AD compared to MCI and AMC ( p  = 0.0045, 0.0142), indicating synaptic degeneration in AD (Fig.  2 , Additional File 1 : Fig. S5). In MCI, synaptophysin levels did not significantly differ from AMC (Fig.  2 F). This aligns with synaptic loss in AD, reflected in lower neuropsychological test scores indicating more pronounced cognitive impairment compared to MCI and AMC. PsEVs derived amyloid-β (1–42), p-Tau, IL-1β, TNF-α, GFAP, and synaptophysin protein concentration was measured. ELISA results in A shows levels of PsEVs amyloid-β (1–42) in AMC, MCI, and AD and receiver operating characteristic (ROC) curve of PsEVs concentration in AMC v/s MCI ( B ), AMC v/s AD ( C ), and MCI v/s AD ( D ). Similarly, p-Tau concentration in AMC, MCI, and AD ( E ), ROC curve of PsEVs concentration in AMC v/s MCI ( F ), AMC v/s AD ( G ), and MCI v/s AD ( H ). PsEVs derived IL-1β concentration in AMC, MCI and AD ( I ), ROC curve of PsEVs concentration in AMC v/s MCI ( J ), AMC v/s AD ( K ), and MCI v/s AD ( L ). PsEVs derived TNF-α concentration in AMC, MCI and AD ( M ), ROC curve of PsEVs concentration in AMC v/s MCI ( N ), AMC v/s AD ( O ), and MCI v/s AD ( P ). Similarly, GFAP concentration in AMC, MCI, and AD ( Q ), ROC curve of PsEVs concentration in AMC v/s MCI ( R ), AMC v/s AD ( S ), and MCI v/s AD ( T ). For PsEVs-derived synaptophysin concentration in AMC, MCI, and AD ( U ), ROC curve of PsEVs concentration in AMC v/s MCI ( V ), AMC v/s AD ( W ), and MCI v/s AD ( X ). Abbreviations: AMC, age-matched control; MCI, mild-cognitive impairment patients; AD, Alzheimer’s disease patients; TNF-α, tumor necrosis factor-alpha; GFAP, glial fibrillary acidic protein Determining the diagnostic potential of PsEVs-derived amyloid-β (1–42), p-Tau, IL-1β, TNF-α, GFAP and synaptophysin We observed the levels of amyloid-β (1–42) and p-Tau in PsEVs, where the increase in amyloid-β (1–42) and p-Tau levels underscores their potential as biomarkers of MCI and AD. The diagnostic efficacy of amyloid-β (1–42) by ROC analysis was observed for AMC vs MCI [AUC = 0.9347, p  < 0.0001, sensitivity (Sn) = 92%, specificity (Sp) = 80%] (Fig.  3 B), AMC vs AD (AUC = 0.9862, p  < 0.0001, Sn = 91.43%, Sp = 96.67%) (Fig.  3 C), and MCI vs AD (AUC of 0.8457, p  < 0.0001, Sn = 80%, and Sp = 72%) (Fig.  3 D). Similarly, diagnostic efficacy of p-Tau by ROC analysis was observed for AMC vs MCI (AUC = 0.8760, p  < 0.0001, Sn = 88%, Sp = 83.33%) (Fig.  3 F), AMC vs AD (AUC = 0.9757, p  < 0.0001, Sn = 94.29%, Sp = 83.33%) (Fig.  3 G), and MCI vs AD (AUC of 0.9074, p  < 0.0001, Sn = 88.57%, and Sp = 92%) (Fig.  3 H). So, we observed that the pathological hallmarks of the disease, viz., amyloid-β (1–42) and p-Tau levels, are increased significantly in PsEVs cargo of AD and MCI groups. Furthermore, we also checked GFAP, TNF-α, IL-1β, and synaptophysin in PsEVs from MCI and AD groups. The diagnostic efficacy of IL-1β by ROC analysis was observed for AMC vs MCI (AUC = 0.9520, p  < 0.0001, Sn = 96%, Sp = 86.67%) (Fig.  3 J), AMC vs AD (AUC = 0.9857, p  < 0.0001, Sn = 94.29%, Sp = 90%) compared to AMC (Fig.  3 K), MCI vs AD (AUC = 0.9114, p  < 0.0001, Sn = 85.71%, Sp = 92%) (Fig.  3 L). Similarly, diagnostic efficacy of TNF-α by ROC analysis was observed for AMC vs MCI (AUC = 0.8920, p  < 0.0001, Sn = 84%, Sp = 80%) (Fig.  3 N), AMC vs AD (AUC = 0.9848, p  < 0.0001, Sn = 88.57%, Sp = 96.67%), and MCI vs AD (AUC = 0.9280, p  < 0.0001, Sn = 88.57%, Sp = 96%) (Fig.  3 P). So, we observed an elevated expression of neuroinflammatory markers within the PsEVs isolated from the AD and MCI groups. GFAP is an activation marker of astroglia, and in AD, this activation is associated with synaptic dysfunction [ 58 ]. In PsEVs, the diagnostic efficacy of GFAP by ROC analysis was observed as for AMC vs MCI (AUC = 0.8393, p  < 0.0001, Sn = 88%, Sp = 76.67%) (Fig.  3 R), AMC vs. AD (AUC = 0.8814, p  < 0.0001, Sn = 91.43%, Sp = 76.67%) compared to AMC (Fig.  3 S); MCI vs AD (AUC = 0.7657, p  < 0.0001, Sn = 74.29%, Sp = 72%) (Fig.  3 T). In addition to this, we also checked the level of presynaptic protein, i.e., synaptophysin, within the PsEVs, as the level of synaptophysin correlates with cognitive decline in AD [ 59 ]. The diagnostic efficacy of synaptophysin by ROC analysis was observed as follows for AMC vs MCI (AUC = 0.8507, p  < 0.0001, Sn = 80%, Sp = 86.67%) (Fig.  3 V), AMC vs AD (AUC = 0.9738, p  < 0.0001, Sn = 88.57%, Sp = 96.67%) compared to AMC (Fig.  3 W); MCI vs AD (AUC = 0.8291, p  < 0.0001, Sn = 85.71%, and Sp = 68%) (Fig.  3 X). Table 2 summarizes all the AUC, sensitivity, specificity, and p -value values for all the PsEVs-derived proteins. Correlations of PsEVs concentration values with protein levels of amyloid-β (1–42), p-Tau, IL-1β, TNF-α, GFAP, and synaptophysin in PsEVs As we found an elevated number of PsEVs in the diseased condition, we performed a correlation analysis between PsEVs concentration and the amyloid-β (1–42) level, p-Tau, IL-1β, and TNF-α within PsEV. We found that PsEV concentration was positively correlated with all the protein levels except synaptophysin, which showed a negative correlation (Fig.  4 ). In these correlations, amyloid-β (1–42) was positively correlated ( r  = 0.7196, p  < 0.0001) (Fig.  4 A); p-Tau positively correlates ( r  = 0.7960, p  < 0.0001) (Fig.  4 B); IL-1β also showed positive correlation ( r  = 0.7220, p  < 0.0001) (Fig.  4 C); and TNF-α also showed positive correlation ( r  = 0.6473, p  < 0.0001) (Fig.  4 D). GFAP showed a weak correlation with PsEVs concentration ( r  = 0.5155, p  < 0.0001) (Fig.  4 E), and synaptophysin showed a weak correlation ( r  = 0.5752, p  < 0.0001) (Fig.  4 F). Correlation analysis between PsEVs concentration and PsEVs derived AD pathology markers. The correlation between PsEVs concentration with the amyloid-β (1–42) ( A ), p-Tau ( B ), IL-1β ( C ), TNF-α ( D ), GFAP ( E ), and synaptophysin ( F ). Abbreviations: p-Tau, Phospho-Tau, TNF-α, tumor necrosis factor-alpha; GFAP, glial fibrillary acidic protein. Spearman correlation was used for correlation analysis Correlations of ACE-III and MMSE scores with protein levels of amyloid-β (1–42), p-Tau, IL-1β, and TNF-α in PsEVs We performed a correlation analysis between ACE-III and MMSE values with the level of amyloid-β (1–42), p-Tau, IL-1β, TNF-α, GFAP, and synaptophysin (Fig.  5 ). We found that ACE-III and MMSE values were negatively correlated with all the protein levels except synaptophysin, which showed a positive value for the correlation coefficient. ACE-III values showed a negative correlation with amyloid-β (1–42) ( r  =  − 0.5107, p  < 0.0001) (Fig.  5 A), p-Tau ( r  =  − 0.5055, p  < 0.0001) (Fig.  5 B), IL-1β ( r  =  − 0.5684, p  < 0.0001) (Fig.  5 C), and TNF-α ( r  =  − 0.6110, p  < 0.0001) (Fig.  5 D). ACE-III values showed a negative correlation with GFAP ( r  =  − 0.5024, p  < 0.0001) (Fig.  5 E), while synaptophysin showed a positive correlation ( r  = 0.5036, p  < 0.0001) (Fig.  5 F). In the case of MMSE, the values were as follows: for amyloid-β (1–42) ( r  =  − 0.5276, p  < 0.0001) (Fig.  5 G), p-Tau ( r  =  − 0.6081, p  < 0.0001) (Fig.  5 H), IL-1β ( r  =  − 0.5743, p  < 0.0001) (Fig.  5 I), TNF-α ( r  =  − 0.5522, p  < 0.0001) (Fig.  5 J), GFAP ( r  =  − 0.4596 p  = 0.0002) (Fig.  5 K), and synaptophysin ( r  = 0.5428, p  < 0.0001) (Fig.  5 L). Table 3 summarizes all the values of Correlation coefficients for all the PsEVs-derived proteins. Correlation between neuropsychological test (ACE-III and MMSE) and PsEV-derived AD pathology markers. Amyloid-β (1–42) β, p-Tau, IL-1β, TNF-α, GFAP, and synaptophysin protein concentration. A – F Correlation between ACE-III scores and amyloid-β (1–42) ( A ), pTau ( B ), IL-1β ( C ), TNF-α ( D ), GFAP ( E ), and synaptophysin ( F ) protein concentration. G – L A correlation between MMSE Score and amyloid-β (1–42) ( G ), p-Tau (H), IL-1β ( I ), TNF-α ( J ), GFAP ( K ), and synaptophysin ( L ) protein concentration. Abbreviations: ACE-III, Addenbrooke Cognitive Examination; MMSE, Mini-Mental State Examination; p-Tau, Phospho-Tau; TNF-α, tumor necrosis factor-alpha; GFAP, glial fibrillary acidic protein. Spearman correlation was used for correlation analysis In this study, we aimed to investigate the capacity of PsEVs to mirror pathological processes linked to AD and MCI. sEVs are extensively documented in the propagation of pathological processes associated with neurodegenerative and metabolic disorders [ 60 ]. The increased secretion of sEVs, coupled with the transmission of disease-related pathologies through sEVs-associated cargo, makes sEVs a viable candidate for understanding the physiological state of their originating cells, which is reflected in sEVs cargo [ 61 ]. To isolate the PsEVs, we employed a combined approach involving chemical precipitation followed by ultrafiltration, which effectively eliminates co-precipitants and minute protein contaminants such as albumin and LDL. We employed the neuronal protein L1CAM as a marker to ascertain the neuronal origin, although there is a debate surrounding its specificity for neuronal origin [ 62 ]. Nevertheless, in our study, the L1CAM marker is used to check for protein markers and not to confirm L1CAM affinity-based isolation. A two-step filtration procedure was used to accompany the sEV isolation method in our study to ensure high purity. Spherical lipid bi-layered vesicles within the typical size range of small extracellular vesicles (30–150 nm) were observed across AD, MCI, and AMC subjects (Fig.  1 A–C). NTA was employed to study the size distribution of sEVs in AD, MCI, and AMC. We observed that the isolated PsEVs come within the size range of < 200 nm, and there was a notable increase in the number of particles in diseased conditions compared to the control group. (Fig.  1 D–G). Validation using sEVs-specific markers (CD63, CD81, and TSG101) demonstrated a noteworthy upregulation in MCI and AD, indicating PsEVs numbers are increased in disease conditions (Fig.  2 A–D). Levels of sEV-specific markers in AD and MCI are elevated because PsEV numbers are increased in the disease condition. As documented by various studies in MCI and AD, there is an increase in cross-talk between different pathophysiological processes, which leads to an increase in sEVs number and sEVs specific marker as a cellular response to heightened cellular stress aggravating neuronal damage and synaptic dysfunction [ 33 , 63 , 64 ]. Neuroinflammation, a characteristic feature of AD and MCI, may lead to the release of sEVs with inflammatory markers. Synaptic dysfunction, evidenced by synaptic degeneration, could contribute to the increased sEV-specific markers, reflecting vesicle release in response to altered synaptic activity [ 9 , 65 ]. Additionally, cells undergoing stress might activate compensatory mechanisms, and the elevated sEV-specific markers could signify communication for potential repair or damage mitigation. Therefore, the increase in sEV-specific markers may be linked to the progression of neurodegenerative processes, indicating ongoing pathological changes in the brain as the disease progresses. Additionally, the elevated expression of L1CAM, a neuron-associated marker, in MCI and AD further strengthens the association between PsEVs and neurodegenerative processes (Fig.  2 E). Furthermore, our observations extend beyond AD and MCI, showing increased concentrations of sEVs in other health conditions where higher levels of these vesicles correlate with elevated levels of disease markers [ 53 , 54 , 55 ]. The results of our research provide valuable insight into the characterization, validation, and functional implications of plasma-derived small extracellular vesicles (PsEVs) in the context of AD and MCI. Our comprehensive analysis encompassed morphological, biochemical, and functional aspects, shedding light on the potential role of PsEVs as biomarkers and contributors to neurodegenerative processes. For this purpose, we performed the ELISA of amyloid-β (1–42) in PsEVs, where we observed higher protein concentrations of amyloid-β (1–42) in MCI. At the same time, in AD, the concentration also significantly increased (Fig.  3 A). In a similar study by A. Manolopoulos et al. [ 66 ], they studied levels of Aβ42, total Tau, and pro-brain-derived neurotrophic factor (BDNF) in both plasma neuron-derived extracellular vesicles (NDEVs) and plasma. The study reported a lack of correlation between the plasma and NDEVs, substantiating concerns about levels of the Aβ42 and total Tau measured in plasma originating from non-CNS sources. Multiple studies support the involvement of extracellular vesicles (EVs) in AD pathogenesis, where Aβ and Tau are released in association with EVs, influencing neuronal cell death and trans-synaptic spreading of the disease [ 7 , 15 , 54 , 67 ]. A progressive elevation in PsEV levels of p-Tau was observed in MCI, reaching a significantly higher AD concentration (Fig.  3 E). Previous research has revealed that p-tau alone effectively differentiates Frontotemporal Dementia (FTD) from AD with high specificity [ 68 , 69 ]. In our study, the alone analysis of p-Tau and amyloid-β (1–42) proved effective in distinguishing patients with MCI from AMC (Table  2 ). Consequently, studies have reported that the elevation of p-Tau suggests the future likelihood of AD development [ 70 ]. This dual elevation in amyloid-β (1–42) and p-Tau levels highlights their potential utility as concurrent biomarkers associated with MCI and AD diagnosis, as indicated by our ROC analysis. Therefore, the investigation into PsEV content revealed significant alterations in key markers associated with AD pathology, viz., amyloid-β (1–42) and p-Tau, which are a well-established marker of AD and exhibit an elevated level in PsEVs from AD and MCI patients compared to AMC in our study. Synaptic dysfunction is considered a core feature of AD. It is suggested to precede other pathophysiological events of AD rather than neurodegeneration, which manifests during the later stages of the disease [ 71 ]. Synaptic dysfunction interacts with other core pathophysiology events of AD, such as the amyloid-β cascade, tau pathology, and neuroinflammation, eventually progressing to irreversible neurodegeneration and atrophy [ 72 , 73 ]. In this context, the synchronized exchange of proteins involved in these pathological processes between the CNS and neuronal-derived sEVs highlights the potential of sEVs as reliable carriers of pathophysiological cascade occurring at the pathological site [ 74 ]. In Fig.  3 U, we observed downregulated synaptophysin levels, a synaptic vesicle marker, in AD PsEVs compared to MCI and AMC. This suggests synaptic degeneration, which has also been discussed in several studies [ 59 , 63 , 64 ]. Synaptic damage induced by amyloid-β deposition triggers a response from the glia to eliminate impaired synapses. As amyloid-β accumulates, the severity of synaptic dysfunction intensifies, leading to tau hyperphosphorylation and the formation of tau tangles. Our study’s findings contradict J. Utz et al. (2021), which showed increased synaptophysin levels in microvesicles isolated from cerebrospinal fluid (CSF) in AD [ 28 ]. This discrepancy could be due to different biofluid sources, cellular origins, or clearance mechanisms for synaptophysin in these compartments. Our study also differs from Utz J et al. (2021) as we have studied PsEVs compared to microvesicles; both differ in biogenesis, structure, and functions. Moreover, our study aligns with existing studies that reported lower synaptophysin levels in plasma neuronal-derived EVs. Goetzl et al. [ 75 ] investigated the synaptic protein levels in neuronal-derived exosomes in plasma (NDEs) of patients with FTD and AD, where the authors found significantly lower levels of synaptopodin, neurogranin, synaptophysin, and synaptotagmin-2 in both conditions compared to controls. Furthermore, our results also align with the overall synaptic loss seen in AD patient’s brains, where lower levels of synaptophysin in the hippocampus have been reported to correlate with cognitive decline in AD [ 59 ]. Our study found that no significant difference in synaptophysin levels between MCI and AMC was observed, indicating that synapse dysfunction is more pronounced due to neuronal loss in the advanced disease stage, and its indication is reflected in PsEVs. Since the PsEVs pool also contains neuronal-derived EVs, we interpolate that the reduction in synaptic proteins in brain tissue is reflected in our results. IL-1β, a potent immunomodulating cytokine, has previously been identified as a trigger for various inflammatory mediators in astrocytes and neurons [ 76 ]. Consistent evidence from post-mortem AD brain studies indicates the prevalent overexpression of IL-1β, with immunohistochemical analyses revealing its localization to microglia around plaques [ 77 ]. Moreover, pro-inflammatory markers (IL-1β and TNF-α) were significantly higher in PsEVs from AD and MCI subjects, as evidenced by ELISA and Western blot findings in our study (Fig. 3 I and M). Table 3 summarizes the correlation between PsEVs and neuroinflammatory markers. IL-1β plays a direct role in the pathophysiological changes associated with AD owing to its specific expression in the vicinity of plaques, and this localization suggests IL-1β as a mediator in the formation of plaques and tangles, thereby contributing to AD pathology [ 65 ]. TNF-α, another pro-inflammatory cytokine primarily secreted by activated macrophages and microglia, is recognized for its dual role in promoting cell survival and death in the central nervous system [ 78 , 79 ]. The cytoskeletal GFAP is found in astrocytic cells [ 80 ]. Increased plasma GFAP levels could result from “reactive astrogliosis,” another term for aberrant astrocytic function brought on by damage to neurons [ 81 ]. According to research on animal and cell models, reactive astrocytes encircle and penetrate amyloid-β plaques, contributing to the amyloid-β pathological process [ 82 , 83 ]. Research has demonstrated a correlation between amyloid-β burden, cognitive decline, and plasma GFAP [ 83 ]. PsEVs of GFAP were elevated in AD [ 27 ] and MCI (Fig.  3 Q). It is well known that sEVs play a pivotal role in the progression of disease pathologies in neurodegenerative and metabolic diseases [ 33 , 84 ]. The high levels of neuro-inflammatory markers (GFAP, TNF-α, and IL-1β) in PsEVs from MCI and AD subjects suggest a potential role of PsEVs in neuroinflammation. This activation of astrocytes and microglia precedes increased secretion of pro-inflammatory PsEVs and may contribute to neuronal damage and progressive cognitive impairment. Diseased conditions involve an increased secretion of sEVs and the cargo they carry, including pathological hallmark proteins or immunomodulatory cytokines [ 33 ]. Correlation analyses unveiled positive associations between PsEVs concentration and the protein levels of amyloid-β (1–42), p-Tau, IL-1β, TNF-α, GFAP, and synaptophysin (Fig.  4 ). Furthermore, our study also analyzed the correlation between cognitive examination scores (ACE-III and MMSE) and PsEV-associated protein levels (Fig.  5 ). The negative correlations observed imply that lower cognitive scores align with elevated levels of amyloid-β (1–42), p-Tau, IL-1β, and TNF-α in PsEVs Table  3 . This implies a strong connection between PsEV biomarkers and cognitive decline, reinforcing that PsEVs could serve as valuable diagnostic and prognostic tools. These findings underscore the potential of PsEVs as reliable disease progression and pathology indicators. The robust correlations further support the hypothesis that PsEVs may actively participate in disseminating neurodegenerative signals. Our study extensively studied the multiple pathophysiological processes associated with AD by checking the protein levels involved in these processes within PsEVs, including amyloid-β (1–42), p-Tau, neuroinflammatory markers (IL-1β, TNF-α, GFAP), and synaptic protein levels. This comprehensive approach enhances diagnostic accuracy by considering the synergistic effects of these processes, providing valuable insights into disease progression from MCI to AD. We have also performed a systematic comparison with MCI, which was lacking in previous studies. We observed a significant correlation between these investigated protein levels within PsEVs and neuropsychological tests, thus filling a research gap addressing the clinical relevance of these dysregulated pathophysiological processes. The observed downregulated synaptophysin levels in AD PsEVs compared to MCI and control subjects shed light on the combined role of neuroinflammation and proteinopathy in the cognitive decline observed as the disease progresses. This finding suggests that PsEVs may reflect synaptic degeneration, opening avenues for further exploration into the role of PsEVs in synaptic damage and dysfunction in neurodegenerative diseases. Our study provides a multifaceted examination of PsEVs, offering compelling evidence of their potential as biomarkers and functional contributors in AD. We have comprehensively discussed the synergistic role of synaptic dysfunction and neuroinflammation and their association with amyloid-β and tau pathologies within the PsEVs in AD progression. The pathophysiological conditions in the MCI and AD brain are reflected in PsEVs, as observed by the increased concentration of PsEVs containing disease-associated markers and markers for synaptic dysfunction and neuroinflammation. Therefore, the PsEVs can be exploited to understand the pathophysiological process involved in the progression and severity of MCI and AD. Availability of data and materials No datasets were generated or analysed during the current study. 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Open access funding provided by Lulea University of Technology. The Indian Council of Medical Research (ICMR, funding number 2020–1194), Council of Scientific and Industrial Research (CSIR, funding number 09/006(0533)/2021-EMR-I), and Department of Health Research (DHR, funding numbers GIA/2020/000595, YSS/2020/000158) provided funding for this research manuscript. Author information Authors and affiliations. Department of Biophysics, All India Institute of Medical Sciences, New Delhi, 110029, India Rishabh Singh, Sanskriti Rai, Prahalad Singh Bharti, Sadaqa Zehra, Krishna Kishore Inampudi & Saroj Kumar Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India Priya Kumari Gorai & Neerja Rani Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology BHU, Varanasi, India Gyan Prakash Modi Department of Biotechnology, Jamia Millia Islamia, New Delhi, India Department of Neurology, All India Institute of Medical Sciences, New Delhi, India Vishnu V. Y. Department of Geriatric Medicine, All India Institute of Medical Sciences, New Delhi, India Prasun Chatterjee Department of Health, Education, and Technology, Lulea University of Technology, Lulea, 97187, Sweden Fredrik Nikolajeff & Saroj Kumar You can also search for this author in PubMed   Google Scholar Contributions S.K. conceptualized and designed the study. R.S., S.R., P.S.B., and S.Z. performed the acquisition and analysis of data. R.S., S.R., P.S.B., S.Z., and P.K.G. performed the drafting the text or preparing the figures. R.S., S.R., P.S.B., N.R., K.D., K.K.I., P.C., V.V.Y, G.P.M., F.N., and S.K. performed the initial revision and proofreading of the manuscript. All authors read and approved the final manuscript. Corresponding author Correspondence to Saroj Kumar . Ethics declarations Ethics approval and consent to participate. The ethical clearance for this study was obtained from the institutional ethics committee of All Institute of Medical Sciences, New Delhi, India. The ethical clearance number is IECPG-670/25.08.2022. All subjects were recruited for the study after obtainment of the written informed consent form. A detailed written participant information sheet and participant informed consent form were provided to the subjects to take part in this study and their signatures were obtained. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Additional information Publisher’s note. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information 12916_2024_3475_moesm1_esm.docx. Additional file 1: Fig S1. [CD63 expression in age-matched controls (AMC), mild cognitive impairment (MCI), and Alzheimer’s disease (AD) and their densitometric analysis]. Fig S2. [CD81 expression in age-matched controls (AMC), mild cognitive impairment (MCI), and Alzheimer’s disease (AD) and their densitometric analysis]. Fig S3. [TSG101 expression in age-matched controls (AMC), mild cognitive impairment (MCI), and Alzheimer’s disease (AD) and their densitometric analysis]. Fig S4. [L1CAM expression in age-matched controls (AMC), mild cognitive impairment (MCI), and Alzheimer’s disease (AD) and their densitometric analysis]. Fig S5. [Synaptophysin (SYP) expression in age-matched controls (AMC), mild cognitive impairment (MCI), and Alzheimer’s disease (AD) and their densitometric analysis]. Fig S6. [Glial Fibrillary Acidic Protein (GFAP) expression in age-matched controls (AMC), mild cognitive impairment (MCI), and Alzheimer’s disease (AD) and their densitometric analysis]. Fig S7. [β-Actin expression in age-matched controls (AMC), mild cognitive impairment (MCI), and Alzheimer’s disease (AD) and their densitometric analysis]. Fig S8. [Amyloidβ-42 Oligomer expression in age-matched controls (AMC), mild cognitive impairment (MCI), and Alzheimer’s disease (AD) and their densitometric analysis]. Fig S9. [IL1β (A) and TNFα (B) expression in age-matched controls (AMC), mild cognitive impairment (MCI), and Alzheimer’s disease (AD) and their densitometric analysis]. Fig S10. [p-Tau expression in age-matched controls (AMC), mild cognitive impairment (MCI), and Alzheimer’s disease (AD) and their densitometric analysis]. 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Provided by the Springer Nature SharedIt content-sharing initiative Small extracellular vesicles Synaptic dysfunction Neuroinflammation BMC Medicine ISSN: 1741-7015 Submission enquiries: [email protected] General enquiries: [email protected] 287 IMAGES (PDF) Students’ Critical Thinking Skills in Group Discussion: The Case Suggested Guide to Conducting a Proper Case Analysis Write Online: Case Study Report Writing Guide How To Write A Critical Analysis Of A Case Study Group discussion case study topics in 2021 08-Case Study Critical Thinkers I .docx COMMENTS Writing a Case Analysis Paper A case analysis can be used to elicit critical thinking about current or future situations in practice, but the case itself is a narrative about something finite and that has taken place in the past. Multiple case studies can be used in a research study; case analysis involves examining a single scenario. 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Case Study Methods and Examples The purpose of case study research is twofold: (1) to provide descriptive information and (2) to suggest theoretical relevance. Rich description enables an in-depth or sharpened understanding of the case. It is unique given one characteristic: case studies draw from more than one data source. Case studies are inherently multimodal or mixed ... What Is a Case Study? A case study is a detailed study of a specific subject, such as a person, group, place, event, organization, or phenomenon. Case studies are commonly used in social, educational, clinical, and business research. ... Case studies tend to focus on qualitative data using methods such as interviews, observations, and analysis of primary and ... Writing a Case Study A case study research paper examines a person, place, event, condition, phenomenon, or other type of subject of analysis in order to extrapolate key themes and results that help predict future trends, illuminate previously hidden issues that can be applied to practice, and/or provide a means for understanding an important research problem with greater clarity. Methodology or method? A critical review of qualitative case study Definitions of qualitative case study research. Case study research is an investigation and analysis of a single or collective case, intended to capture the complexity of the object of study (Stake, 1995).Qualitative case study research, as described by Stake (), draws together "naturalistic, holistic, ethnographic, phenomenological, and biographic research methods" in a bricoleur design ... What the Case Study Method Really Teaches What the Case Study Method Really Teaches. Summary. It's been 100 years since Harvard Business School began using the case study method. Beyond teaching specific subject matter, the case study ... Writing a Case Study Analysis Identify the key problems and issues in the case study. Formulate and include a thesis statement, summarizing the outcome of your analysis in 1-2 sentences. Background. Set the scene: background information, relevant facts, and the most important issues. Demonstrate that you have researched the problems in this case study. Evaluation of the Case PDF How to Analyse a Case Study Step 3. Use the note taking sheet provided by ELS (back page) to record your ideas/analysis. to write the case study. An effective case study report should. Clearly identify the core problem(s) Analyse the issues underlying the problem. Discuss and justify alternative solutions using theory / experience. How to Critically Discuss in a way that expresses or involves an analysis of the merits and faults of a work of literature, music, or art. talk or write about (a topic) in detail, taking into account different issues or ideas. So, in short, a critical discussion requires you to weigh up the strengths and weaknesses of a theory, concept (or work of some sort), and write ... How to Critically Evaluate Case Studies in Social Work The purpose of this article is to develop guidelines to assist practitioners and researchers in evaluating and developing rigorous case studies. The main concern in evaluating a case study is to accurately assess its quality and ultimately to offer clients social work interventions informed by the best available evidence. How to Write a Critical Case Study (Chapter 3) Introduction. One of the basic ideas of the PAP is simple: professionals constantly need to make an effort to recognise the subjectivity of the people they work with, to view service users as complete people and to bring this recognition to the relationship. In order to recognise service users' subjectivity, one has to also acknowledge the ... Mastering Case Study Analysis: Techniques & Examples At the heart of every case study analysis lies the critical examination of core issues and the presentation of cogent arguments. In this segment, you embark on a systematic exploration of the case study, dissecting its intricacies, and unraveling its underlying complexities. Here, analytical rigor reigns supreme as you apply theoretical ... How to Write a Discussion Section Table of contents. What not to include in your discussion section. Step 1: Summarize your key findings. Step 2: Give your interpretations. Step 3: Discuss the implications. Step 4: Acknowledge the limitations. Step 5: Share your recommendations. Discussion section example. Other interesting articles. Case Study A single-case study is an in-depth analysis of a single case. This type of case study is useful when the researcher wants to understand a specific phenomenon in detail. ... Case studies can help lawyers, policymakers, and ethical professionals to develop critical thinking skills, analyze complex cases, and make informed decisions. Purpose of ... How to Critically Evaluate Case Studies in Social Work The main concern in evaluating a case study is to accurately assess its quality and ultimately to offer clients social work interventions informed by the best available evidence. To assess the ... The Power of Case Studies in Promoting Critical Thinking and Analysis Strategies for Educators to Enhance Critical Thinking and Analysis in Case Study Sessions Ask Thought-Provoking Questions: Encourage students to ask probing questions that delve beneath the ... 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