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How to Write a Conclusion for Research Papers (with Examples)

The conclusion of a research paper is a crucial section that plays a significant role in the overall impact and effectiveness of your research paper. However, this is also the section that typically receives less attention compared to the introduction and the body of the paper. The conclusion serves to provide a concise summary of the key findings, their significance, their implications, and a sense of closure to the study. Discussing how can the findings be applied in real-world scenarios or inform policy, practice, or decision-making is especially valuable to practitioners and policymakers. The research paper conclusion also provides researchers with clear insights and valuable information for their own work, which they can then build on and contribute to the advancement of knowledge in the field.

The research paper conclusion should explain the significance of your findings within the broader context of your field. It restates how your results contribute to the existing body of knowledge and whether they confirm or challenge existing theories or hypotheses. Also, by identifying unanswered questions or areas requiring further investigation, your awareness of the broader research landscape can be demonstrated.

Remember to tailor the research paper conclusion to the specific needs and interests of your intended audience, which may include researchers, practitioners, policymakers, or a combination of these.

Table of Contents

What is a conclusion in a research paper, summarizing conclusion, editorial conclusion, externalizing conclusion, importance of a good research paper conclusion, how to write a conclusion for your research paper, research paper conclusion examples.

• How to write a research paper conclusion with Paperpal? 

Frequently Asked Questions

A conclusion in a research paper is the final section where you summarize and wrap up your research, presenting the key findings and insights derived from your study. The research paper conclusion is not the place to introduce new information or data that was not discussed in the main body of the paper. When working on how to conclude a research paper, remember to stick to summarizing and interpreting existing content. The research paper conclusion serves the following purposes: 1

• Warn readers of the possible consequences of not attending to the problem.
• Recommend specific course(s) of action.
• Restate key ideas to drive home the ultimate point of your research paper.
• Provide a “take-home” message that you want the readers to remember about your study.

Types of conclusions for research papers

In research papers, the conclusion provides closure to the reader. The type of research paper conclusion you choose depends on the nature of your study, your goals, and your target audience. I provide you with three common types of conclusions:

A summarizing conclusion is the most common type of conclusion in research papers. It involves summarizing the main points, reiterating the research question, and restating the significance of the findings. This common type of research paper conclusion is used across different disciplines.

An editorial conclusion is less common but can be used in research papers that are focused on proposing or advocating for a particular viewpoint or policy. It involves presenting a strong editorial or opinion based on the research findings and offering recommendations or calls to action.

An externalizing conclusion is a type of conclusion that extends the research beyond the scope of the paper by suggesting potential future research directions or discussing the broader implications of the findings. This type of conclusion is often used in more theoretical or exploratory research papers.

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The conclusion in a research paper serves several important purposes:

• Offers Implications and Recommendations : Your research paper conclusion is an excellent place to discuss the broader implications of your research and suggest potential areas for further study. It’s also an opportunity to offer practical recommendations based on your findings.
• Provides Closure : A good research paper conclusion provides a sense of closure to your paper. It should leave the reader with a feeling that they have reached the end of a well-structured and thought-provoking research project.
• Leaves a Lasting Impression : Writing a well-crafted research paper conclusion leaves a lasting impression on your readers. It’s your final opportunity to leave them with a new idea, a call to action, or a memorable quote.

Writing a strong conclusion for your research paper is essential to leave a lasting impression on your readers. Here’s a step-by-step process to help you create and know what to put in the conclusion of a research paper: 2

• Research Statement : Begin your research paper conclusion by restating your research statement. This reminds the reader of the main point you’ve been trying to prove throughout your paper. Keep it concise and clear.
• Key Points : Summarize the main arguments and key points you’ve made in your paper. Avoid introducing new information in the research paper conclusion. Instead, provide a concise overview of what you’ve discussed in the body of your paper.
• Address the Research Questions : If your research paper is based on specific research questions or hypotheses, briefly address whether you’ve answered them or achieved your research goals. Discuss the significance of your findings in this context.
• Significance : Highlight the importance of your research and its relevance in the broader context. Explain why your findings matter and how they contribute to the existing knowledge in your field.
• Implications : Explore the practical or theoretical implications of your research. How might your findings impact future research, policy, or real-world applications? Consider the “so what?” question.
• Future Research : Offer suggestions for future research in your area. What questions or aspects remain unanswered or warrant further investigation? This shows that your work opens the door for future exploration.
• Closing Thought : Conclude your research paper conclusion with a thought-provoking or memorable statement. This can leave a lasting impression on your readers and wrap up your paper effectively. Avoid introducing new information or arguments here.
• Proofread and Revise : Carefully proofread your conclusion for grammar, spelling, and clarity. Ensure that your ideas flow smoothly and that your conclusion is coherent and well-structured.

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Remember that a well-crafted research paper conclusion is a reflection of the strength of your research and your ability to communicate its significance effectively. It should leave a lasting impression on your readers and tie together all the threads of your paper. Now you know how to start the conclusion of a research paper and what elements to include to make it impactful, let’s look at a research paper conclusion sample.

How to write a research paper conclusion with Paperpal?

A research paper conclusion is not just a summary of your study, but a synthesis of the key findings that ties the research together and places it in a broader context. A research paper conclusion should be concise, typically around one paragraph in length. However, some complex topics may require a longer conclusion to ensure the reader is left with a clear understanding of the study’s significance. Paperpal, an AI writing assistant trusted by over 800,000 academics globally, can help you write a well-structured conclusion for your research paper. 

• Sign Up or Log In: Create a new Paperpal account or login with your details.  
• Navigate to Features : Once logged in, head over to the features’ side navigation pane. Click on Templates and you’ll find a suite of generative AI features to help you write better, faster.  
• Generate an outline: Under Templates, select ‘Outlines’. Choose ‘Research article’ as your document type.  
• Select your section: Since you’re focusing on the conclusion, select this section when prompted.  
• Choose your field of study: Identifying your field of study allows Paperpal to provide more targeted suggestions, ensuring the relevance of your conclusion to your specific area of research. 
• Provide a brief description of your study: Enter details about your research topic and findings. This information helps Paperpal generate a tailored outline that aligns with your paper’s content. 
• Generate the conclusion outline: After entering all necessary details, click on ‘generate’. Paperpal will then create a structured outline for your conclusion, to help you start writing and build upon the outline.  
• Write your conclusion: Use the generated outline to build your conclusion. The outline serves as a guide, ensuring you cover all critical aspects of a strong conclusion, from summarizing key findings to highlighting the research’s implications. 
• Refine and enhance: Paperpal’s ‘Make Academic’ feature can be particularly useful in the final stages. Select any paragraph of your conclusion and use this feature to elevate the academic tone, ensuring your writing is aligned to the academic journal standards. 

By following these steps, Paperpal not only simplifies the process of writing a research paper conclusion but also ensures it is impactful, concise, and aligned with academic standards. Sign up with Paperpal today and write your research paper conclusion 2x faster .  

The research paper conclusion is a crucial part of your paper as it provides the final opportunity to leave a strong impression on your readers. In the research paper conclusion, summarize the main points of your research paper by restating your research statement, highlighting the most important findings, addressing the research questions or objectives, explaining the broader context of the study, discussing the significance of your findings, providing recommendations if applicable, and emphasizing the takeaway message. The main purpose of the conclusion is to remind the reader of the main point or argument of your paper and to provide a clear and concise summary of the key findings and their implications. All these elements should feature on your list of what to put in the conclusion of a research paper to create a strong final statement for your work.

A strong conclusion is a critical component of a research paper, as it provides an opportunity to wrap up your arguments, reiterate your main points, and leave a lasting impression on your readers. Here are the key elements of a strong research paper conclusion: 1. Conciseness : A research paper conclusion should be concise and to the point. It should not introduce new information or ideas that were not discussed in the body of the paper. 2. Summarization : The research paper conclusion should be comprehensive enough to give the reader a clear understanding of the research’s main contributions. 3 . Relevance : Ensure that the information included in the research paper conclusion is directly relevant to the research paper’s main topic and objectives; avoid unnecessary details. 4 . Connection to the Introduction : A well-structured research paper conclusion often revisits the key points made in the introduction and shows how the research has addressed the initial questions or objectives. 5. Emphasis : Highlight the significance and implications of your research. Why is your study important? What are the broader implications or applications of your findings? 6 . Call to Action : Include a call to action or a recommendation for future research or action based on your findings.

The length of a research paper conclusion can vary depending on several factors, including the overall length of the paper, the complexity of the research, and the specific journal requirements. While there is no strict rule for the length of a conclusion, but it’s generally advisable to keep it relatively short. A typical research paper conclusion might be around 5-10% of the paper’s total length. For example, if your paper is 10 pages long, the conclusion might be roughly half a page to one page in length.

In general, you do not need to include citations in the research paper conclusion. Citations are typically reserved for the body of the paper to support your arguments and provide evidence for your claims. However, there may be some exceptions to this rule: 1. If you are drawing a direct quote or paraphrasing a specific source in your research paper conclusion, you should include a citation to give proper credit to the original author. 2. If your conclusion refers to or discusses specific research, data, or sources that are crucial to the overall argument, citations can be included to reinforce your conclusion’s validity.

The conclusion of a research paper serves several important purposes: 1. Summarize the Key Points 2. Reinforce the Main Argument 3. Provide Closure 4. Offer Insights or Implications 5. Engage the Reader. 6. Reflect on Limitations

Remember that the primary purpose of the research paper conclusion is to leave a lasting impression on the reader, reinforcing the key points and providing closure to your research. It’s often the last part of the paper that the reader will see, so it should be strong and well-crafted.

• Makar, G., Foltz, C., Lendner, M., & Vaccaro, A. R. (2018). How to write effective discussion and conclusion sections. Clinical spine surgery, 31(8), 345-346.
• Bunton, D. (2005). The structure of PhD conclusion chapters.  Journal of English for academic purposes ,  4 (3), 207-224.

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Home » Research Paper Conclusion – Writing Guide and Examples

Research Paper Conclusion – Writing Guide and Examples

Table of Contents

Research Paper Conclusion

Definition:

A research paper conclusion is the final section of a research paper that summarizes the key findings, significance, and implications of the research. It is the writer’s opportunity to synthesize the information presented in the paper, draw conclusions, and make recommendations for future research or actions.

The conclusion should provide a clear and concise summary of the research paper, reiterating the research question or problem, the main results, and the significance of the findings. It should also discuss the limitations of the study and suggest areas for further research.

Parts of Research Paper Conclusion

The parts of a research paper conclusion typically include:

Restatement of the Thesis

The conclusion should begin by restating the thesis statement from the introduction in a different way. This helps to remind the reader of the main argument or purpose of the research.

Summary of Key Findings

The conclusion should summarize the main findings of the research, highlighting the most important results and conclusions. This section should be brief and to the point.

Implications and Significance

In this section, the researcher should explain the implications and significance of the research findings. This may include discussing the potential impact on the field or industry, highlighting new insights or knowledge gained, or pointing out areas for future research.

Limitations and Recommendations

It is important to acknowledge any limitations or weaknesses of the research and to make recommendations for how these could be addressed in future studies. This shows that the researcher is aware of the potential limitations of their work and is committed to improving the quality of research in their field.

Concluding Statement

The conclusion should end with a strong concluding statement that leaves a lasting impression on the reader. This could be a call to action, a recommendation for further research, or a final thought on the topic.

How to Write Research Paper Conclusion

Here are some steps you can follow to write an effective research paper conclusion:

• Restate the research problem or question: Begin by restating the research problem or question that you aimed to answer in your research. This will remind the reader of the purpose of your study.
• Summarize the main points: Summarize the key findings and results of your research. This can be done by highlighting the most important aspects of your research and the evidence that supports them.
• Discuss the implications: Discuss the implications of your findings for the research area and any potential applications of your research. You should also mention any limitations of your research that may affect the interpretation of your findings.
• Provide a conclusion : Provide a concise conclusion that summarizes the main points of your paper and emphasizes the significance of your research. This should be a strong and clear statement that leaves a lasting impression on the reader.
• Offer suggestions for future research: Lastly, offer suggestions for future research that could build on your findings and contribute to further advancements in the field.

Remember that the conclusion should be brief and to the point, while still effectively summarizing the key findings and implications of your research.

Example of Research Paper Conclusion

Here’s an example of a research paper conclusion:

Conclusion :

In conclusion, our study aimed to investigate the relationship between social media use and mental health among college students. Our findings suggest that there is a significant association between social media use and increased levels of anxiety and depression among college students. This highlights the need for increased awareness and education about the potential negative effects of social media use on mental health, particularly among college students.

Despite the limitations of our study, such as the small sample size and self-reported data, our findings have important implications for future research and practice. Future studies should aim to replicate our findings in larger, more diverse samples, and investigate the potential mechanisms underlying the association between social media use and mental health. In addition, interventions should be developed to promote healthy social media use among college students, such as mindfulness-based approaches and social media detox programs.

Overall, our study contributes to the growing body of research on the impact of social media on mental health, and highlights the importance of addressing this issue in the context of higher education. By raising awareness and promoting healthy social media use among college students, we can help to reduce the negative impact of social media on mental health and improve the well-being of young adults.

Purpose of Research Paper Conclusion

The purpose of a research paper conclusion is to provide a summary and synthesis of the key findings, significance, and implications of the research presented in the paper. The conclusion serves as the final opportunity for the writer to convey their message and leave a lasting impression on the reader.

The conclusion should restate the research problem or question, summarize the main results of the research, and explain their significance. It should also acknowledge the limitations of the study and suggest areas for future research or action.

Overall, the purpose of the conclusion is to provide a sense of closure to the research paper and to emphasize the importance of the research and its potential impact. It should leave the reader with a clear understanding of the main findings and why they matter. The conclusion serves as the writer’s opportunity to showcase their contribution to the field and to inspire further research and action.

When to Write Research Paper Conclusion

The conclusion of a research paper should be written after the body of the paper has been completed. It should not be written until the writer has thoroughly analyzed and interpreted their findings and has written a complete and cohesive discussion of the research.

Before writing the conclusion, the writer should review their research paper and consider the key points that they want to convey to the reader. They should also review the research question, hypotheses, and methodology to ensure that they have addressed all of the necessary components of the research.

Once the writer has a clear understanding of the main findings and their significance, they can begin writing the conclusion. The conclusion should be written in a clear and concise manner, and should reiterate the main points of the research while also providing insights and recommendations for future research or action.

Characteristics of Research Paper Conclusion

The characteristics of a research paper conclusion include:

• Clear and concise: The conclusion should be written in a clear and concise manner, summarizing the key findings and their significance.
• Comprehensive: The conclusion should address all of the main points of the research paper, including the research question or problem, the methodology, the main results, and their implications.
• Future-oriented : The conclusion should provide insights and recommendations for future research or action, based on the findings of the research.
• Impressive : The conclusion should leave a lasting impression on the reader, emphasizing the importance of the research and its potential impact.
• Objective : The conclusion should be based on the evidence presented in the research paper, and should avoid personal biases or opinions.
• Unique : The conclusion should be unique to the research paper and should not simply repeat information from the introduction or body of the paper.

Advantages of Research Paper Conclusion

The advantages of a research paper conclusion include:

• Summarizing the key findings : The conclusion provides a summary of the main findings of the research, making it easier for the reader to understand the key points of the study.
• Emphasizing the significance of the research: The conclusion emphasizes the importance of the research and its potential impact, making it more likely that readers will take the research seriously and consider its implications.
• Providing recommendations for future research or action : The conclusion suggests practical recommendations for future research or action, based on the findings of the study.
• Providing closure to the research paper : The conclusion provides a sense of closure to the research paper, tying together the different sections of the paper and leaving a lasting impression on the reader.
• Demonstrating the writer’s contribution to the field : The conclusion provides the writer with an opportunity to showcase their contribution to the field and to inspire further research and action.

Limitations of Research Paper Conclusion

While the conclusion of a research paper has many advantages, it also has some limitations that should be considered, including:

• I nability to address all aspects of the research: Due to the limited space available in the conclusion, it may not be possible to address all aspects of the research in detail.
• Subjectivity : While the conclusion should be objective, it may be influenced by the writer’s personal biases or opinions.
• Lack of new information: The conclusion should not introduce new information that has not been discussed in the body of the research paper.
• Lack of generalizability: The conclusions drawn from the research may not be applicable to other contexts or populations, limiting the generalizability of the study.
• Misinterpretation by the reader: The reader may misinterpret the conclusions drawn from the research, leading to a misunderstanding of the findings.

About the author

Muhammad Hassan

Researcher, Academic Writer, Web developer

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Organizing Your Social Sciences Research Paper

• 9. The Conclusion
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The conclusion is intended to help the reader understand why your research should matter to them after they have finished reading the paper. A conclusion is not merely a summary of the main topics covered or a re-statement of your research problem, but a synthesis of key points derived from the findings of your study and, if applicable, where you recommend new areas for future research. For most college-level research papers, two or three well-developed paragraphs is sufficient for a conclusion, although in some cases, more paragraphs may be required in describing the key findings and their significance.

Conclusions. The Writing Center. University of North Carolina; Conclusions. The Writing Lab and The OWL. Purdue University.

Importance of a Good Conclusion

A well-written conclusion provides you with important opportunities to demonstrate to the reader your understanding of the research problem. These include:

• Presenting the last word on the issues you raised in your paper . Just as the introduction gives a first impression to your reader, the conclusion offers a chance to leave a lasting impression. Do this, for example, by highlighting key findings in your analysis that advance new understanding about the research problem, that are unusual or unexpected, or that have important implications applied to practice.
• Summarizing your thoughts and conveying the larger significance of your study . The conclusion is an opportunity to succinctly re-emphasize  your answer to the "So What?" question by placing the study within the context of how your research advances past research about the topic.
• Identifying how a gap in the literature has been addressed . The conclusion can be where you describe how a previously identified gap in the literature [first identified in your literature review section] has been addressed by your research and why this contribution is significant.
• Demonstrating the importance of your ideas . Don't be shy. The conclusion offers an opportunity to elaborate on the impact and significance of your findings. This is particularly important if your study approached examining the research problem from an unusual or innovative perspective.
• Introducing possible new or expanded ways of thinking about the research problem . This does not refer to introducing new information [which should be avoided], but to offer new insight and creative approaches for framing or contextualizing the research problem based on the results of your study.

Bunton, David. “The Structure of PhD Conclusion Chapters.” Journal of English for Academic Purposes 4 (July 2005): 207–224; Conclusions. The Writing Center. University of North Carolina; Kretchmer, Paul. Twelve Steps to Writing an Effective Conclusion. San Francisco Edit, 2003-2008; Conclusions. The Writing Lab and The OWL. Purdue University; Assan, Joseph. "Writing the Conclusion Chapter: The Good, the Bad and the Missing." Liverpool: Development Studies Association (2009): 1-8.

Structure and Writing Style

I.  General Rules

The general function of your paper's conclusion is to restate the main argument . It reminds the reader of the strengths of your main argument(s) and reiterates the most important evidence supporting those argument(s). Do this by clearly summarizing the context, background, and necessity of pursuing the research problem you investigated in relation to an issue, controversy, or a gap found in the literature. However, make sure that your conclusion is not simply a repetitive summary of the findings. This reduces the impact of the argument(s) you have developed in your paper.

When writing the conclusion to your paper, follow these general rules:

• Present your conclusions in clear, concise language. Re-state the purpose of your study, then describe how your findings differ or support those of other studies and why [i.e., what were the unique, new, or crucial contributions your study made to the overall research about your topic?].
• Do not simply reiterate your findings or the discussion of your results. Provide a synthesis of arguments presented in the paper to show how these converge to address the research problem and the overall objectives of your study.
• Indicate opportunities for future research if you haven't already done so in the discussion section of your paper. Highlighting the need for further research provides the reader with evidence that you have an in-depth awareness of the research problem but that further investigations should take place beyond the scope of your investigation.

Consider the following points to help ensure your conclusion is presented well:

• If the argument or purpose of your paper is complex, you may need to summarize the argument 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 end of your paper to describe your main points and explain their significance.
• Move from a detailed to a general level of consideration that returns the topic to the context provided by the introduction or within a new context that emerges from the data [this is opposite of the introduction, which begins with general discussion of the context and ends with a detailed description of the research problem]. 

The conclusion also provides a place for you to persuasively and succinctly restate the research problem, given that the reader has now been presented with all the information about the topic . Depending on the discipline you are writing in, the concluding paragraph may contain your reflections on the evidence presented. However, the nature of being introspective about the research you have conducted will depend on the topic and whether your professor wants you to express your observations in this way. If asked to think introspectively about the topics, do not delve into idle speculation. Being introspective means looking within yourself as an author to try and understand an issue more deeply, not to guess at possible outcomes or make up scenarios not supported by the evidence.

II.  Developing a Compelling Conclusion

Although an effective conclusion needs to be clear and succinct, it does not need to be written passively or lack a compelling narrative. Strategies to help you move beyond merely summarizing the key points of your research paper may include any of the following:

• If your essay deals with a critical, contemporary problem, warn readers of the possible consequences of not attending to the problem proactively.
• Recommend a specific course or courses of action that, if adopted, could address a specific problem in practice or in the development of new knowledge leading to positive change.
• Cite a relevant quotation or expert opinion already noted in your paper in order to lend authority and support to the conclusion(s) you have reached [a good source would be from your literature review].
• Explain the consequences of your research in a way that elicits action or demonstrates urgency in seeking change.
• Restate a key statistic, fact, or visual image to emphasize the most important finding of your paper.
• If your discipline encourages personal reflection, illustrate your concluding point by drawing from your own life experiences.
• Return to an anecdote, an example, or a quotation that you presented in your introduction, but add further insight derived from the findings of your study; use your interpretation of results from your study to recast it in new or important ways.
• Provide a "take-home" message in the form of a succinct, declarative statement that you want the reader to remember about your study.

III. Problems to Avoid

Failure to be concise Your conclusion section should be concise and to the point. Conclusions that are too lengthy often have unnecessary information in them. The conclusion is not the place for details about your methodology or results. Although you should give a summary of what was learned from your research, this summary should be relatively brief, since the emphasis in the conclusion is on the implications, evaluations, insights, and other forms of analysis that you make. Strategies for writing concisely can be found here .

Failure to comment on larger, more significant issues In the introduction, your task was to move from the general [the field of study] to the specific [the research problem]. However, in the conclusion, your task is to move from a specific discussion [your research problem] back to a general discussion framed around the implications and significance of your findings [i.e., how your research contributes new understanding or fills an important gap in the literature]. In short, the conclusion is where you should place your research within a larger context [visualize your paper as an hourglass--start with a broad introduction and review of the literature, move to the specific analysis and discussion, conclude with a broad summary of the study's implications and significance].

Failure to reveal problems and negative results Negative aspects of the research process should never be ignored. These are problems, deficiencies, or challenges encountered during your study. They should be summarized as a way of qualifying your overall conclusions. If you encountered negative or unintended results [i.e., findings that are validated outside the research context in which they were generated], you must report them in the results section and discuss their implications in the discussion section of your paper. In the conclusion, use negative results as an opportunity to explain their possible significance and/or how they may form the basis for future research.

Failure to provide a clear summary of what was learned In order to be able to discuss how your research fits within your field of study [and possibly the world at large], you need to summarize briefly and succinctly how it contributes to new knowledge or a new understanding about the research problem. This element of your conclusion may be only a few sentences long.

Failure to match the objectives of your research Often research objectives in the social and behavioral sciences change while the research is being carried out. This is not a problem unless you forget to go back and refine the original objectives in your introduction. As these changes emerge they must be documented so that they accurately reflect what you were trying to accomplish in your research [not what you thought you might accomplish when you began].

Resist the urge to apologize If you've immersed yourself in studying the research problem, you presumably should know a good deal about it [perhaps even more than your professor!]. Nevertheless, by the time you have finished writing, you may be having some doubts about what you have produced. Repress those doubts! Don't undermine your authority as a researcher by saying something like, "This is just one approach to examining this problem; there may be other, much better approaches that...." The overall tone of your conclusion should convey confidence to the reader about the study's validity and realiability.

Assan, Joseph. "Writing the Conclusion Chapter: The Good, the Bad and the Missing." Liverpool: Development Studies Association (2009): 1-8; Concluding Paragraphs. College Writing Center at Meramec. St. Louis Community College; Conclusions. The Writing Center. University of North Carolina; Conclusions. The Writing Lab and The OWL. Purdue University; Freedman, Leora  and Jerry Plotnick. Introductions and Conclusions. The Lab Report. University College Writing Centre. University of Toronto; Leibensperger, Summer. Draft Your Conclusion. Academic Center, the University of Houston-Victoria, 2003; Make Your Last Words Count. The Writer’s Handbook. Writing Center. University of Wisconsin Madison; Miquel, Fuster-Marquez and Carmen Gregori-Signes. “Chapter Six: ‘Last but Not Least:’ Writing the Conclusion of Your Paper.” In Writing an Applied Linguistics Thesis or Dissertation: A Guide to Presenting Empirical Research . John Bitchener, editor. (Basingstoke,UK: Palgrave Macmillan, 2010), pp. 93-105; Tips for Writing a Good Conclusion. Writing@CSU. Colorado State University; Kretchmer, Paul. Twelve Steps to Writing an Effective Conclusion. San Francisco Edit, 2003-2008; Writing Conclusions. Writing Tutorial Services, Center for Innovative Teaching and Learning. Indiana University; Writing: Considering Structure and Organization. Institute for Writing Rhetoric. Dartmouth College.

Writing Tip

Don't Belabor the Obvious!

Avoid phrases like "in conclusion...," "in summary...," or "in closing...." These phrases can be useful, even welcome, in oral presentations. But readers can see by the tell-tale section heading and number of pages remaining that they are reaching the end of your paper. You'll irritate your readers if you belabor the obvious.

Assan, Joseph. "Writing the Conclusion Chapter: The Good, the Bad and the Missing." Liverpool: Development Studies Association (2009): 1-8.

Another Writing Tip

New Insight, Not New Information!

Don't surprise the reader with new information in your conclusion that was never referenced anywhere else in the paper. This why the conclusion rarely has citations to sources. If you have new information to present, add it to the discussion or other appropriate section of the paper. Note that, although no new information is introduced, the conclusion, along with the discussion section, is where you offer your most "original" contributions in the paper; the conclusion is where you describe the value of your research, demonstrate that you understand the material that you’ve presented, and position your findings within the larger context of scholarship on the topic, including describing how your research contributes new insights to that scholarship.

Assan, Joseph. "Writing the Conclusion Chapter: The Good, the Bad and the Missing." Liverpool: Development Studies Association (2009): 1-8; Conclusions. The Writing Center. University of North Carolina.

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• How to Write Discussions and Conclusions

The discussion section contains the results and outcomes of a study. An effective discussion informs readers what can be learned from your experiment and provides context for the results.

What makes an effective discussion?

When you’re ready to write your discussion, you’ve already introduced the purpose of your study and provided an in-depth description of the methodology. The discussion informs readers about the larger implications of your study based on the results. Highlighting these implications while not overstating the findings can be challenging, especially when you’re submitting to a journal that selects articles based on novelty or potential impact. Regardless of what journal you are submitting to, the discussion section always serves the same purpose: concluding what your study results actually mean.

A successful discussion section puts your findings in context. It should include:

• the results of your research,
• a discussion of related research, and
• a comparison between your results and initial hypothesis.

Tip: Not all journals share the same naming conventions.

You can apply the advice in this article to the conclusion, results or discussion sections of your manuscript.

Our Early Career Researcher community tells us that the conclusion is often considered the most difficult aspect of a manuscript to write. To help, this guide provides questions to ask yourself, a basic structure to model your discussion off of and examples from published manuscripts. 

Questions to ask yourself:

• Was my hypothesis correct?
• If my hypothesis is partially correct or entirely different, what can be learned from the results? 
• How do the conclusions reshape or add onto the existing knowledge in the field? What does previous research say about the topic? 
• Why are the results important or relevant to your audience? Do they add further evidence to a scientific consensus or disprove prior studies? 
• How can future research build on these observations? What are the key experiments that must be done? 
• What is the “take-home” message you want your reader to leave with?

How to structure a discussion

Trying to fit a complete discussion into a single paragraph can add unnecessary stress to the writing process. If possible, you’ll want to give yourself two or three paragraphs to give the reader a comprehensive understanding of your study as a whole. Here’s one way to structure an effective discussion:

Writing Tips

While the above sections can help you brainstorm and structure your discussion, there are many common mistakes that writers revert to when having difficulties with their paper. Writing a discussion can be a delicate balance between summarizing your results, providing proper context for your research and avoiding introducing new information. Remember that your paper should be both confident and honest about the results! 

• Read the journal’s guidelines on the discussion and conclusion sections. If possible, learn about the guidelines before writing the discussion to ensure you’re writing to meet their expectations. 
• Begin with a clear statement of the principal findings. This will reinforce the main take-away for the reader and set up the rest of the discussion. 
• Explain why the outcomes of your study are important to the reader. Discuss the implications of your findings realistically based on previous literature, highlighting both the strengths and limitations of the research. 
• State whether the results prove or disprove your hypothesis. If your hypothesis was disproved, what might be the reasons? 
• Introduce new or expanded ways to think about the research question. Indicate what next steps can be taken to further pursue any unresolved questions. 
• If dealing with a contemporary or ongoing problem, such as climate change, discuss possible consequences if the problem is avoided. 
• Be concise. Adding unnecessary detail can distract from the main findings. 

Don’t

• Rewrite your abstract. Statements with “we investigated” or “we studied” generally do not belong in the discussion. 
• Include new arguments or evidence not previously discussed. Necessary information and evidence should be introduced in the main body of the paper. 
• Apologize. Even if your research contains significant limitations, don’t undermine your authority by including statements that doubt your methodology or execution. 
• Shy away from speaking on limitations or negative results. Including limitations and negative results will give readers a complete understanding of the presented research. Potential limitations include sources of potential bias, threats to internal or external validity, barriers to implementing an intervention and other issues inherent to the study design. 
• Overstate the importance of your findings. Making grand statements about how a study will fully resolve large questions can lead readers to doubt the success of the research. 

Snippets of Effective Discussions:

Consumer-based actions to reduce plastic pollution in rivers: A multi-criteria decision analysis approach

Identifying reliable indicators of fitness in polar bears

• How to Write a Great Title
• How to Write an Abstract
• How to Write Your Methods
• How to Report Statistics
• How to Edit Your Work

The contents of the Peer Review Center are also available as a live, interactive training session, complete with slides, talking points, and activities. …

The contents of the Writing Center are also available as a live, interactive training session, complete with slides, talking points, and activities. …

There’s a lot to consider when deciding where to submit your work. Learn how to choose a journal that will help your study reach its audience, while reflecting your values as a researcher…

Conclusions

What this handout is about.

This handout will explain the functions of conclusions, offer strategies for writing effective ones, help you evaluate conclusions you’ve drafted, and suggest approaches to avoid.

About conclusions

Introductions and conclusions can be difficult to write, but they’re worth investing time in. They can have a significant influence on a reader’s experience of your paper.

Just as your introduction acts as a bridge that transports your readers from their own lives into the “place” of your analysis, your conclusion can provide a bridge to help your readers make the transition back to their daily lives. Such a conclusion will help them see why all your analysis and information should matter to them after they put the paper down.

Your conclusion is your chance to have the last word on the subject. The conclusion allows you to have the final say on the issues you have raised in your paper, to synthesize your thoughts, to demonstrate the importance of your ideas, and to propel your reader to a new view of the subject. It is also your opportunity to make a good final impression and to end on a positive note.

Your conclusion can go beyond the confines of the assignment. The conclusion pushes beyond the boundaries of the prompt and allows you to consider broader issues, make new connections, and elaborate on the significance of your findings.

Your conclusion should make your readers glad they read your paper. Your conclusion gives your reader something to take away that will help them see things differently or appreciate your topic in personally relevant ways. It can suggest broader implications that will not only interest your reader, but also enrich your reader’s life in some way. It is your gift to the reader.

Strategies for writing an effective conclusion

One or more of the following strategies may help you write an effective conclusion:

• Play the “So What” Game. If you’re stuck and feel like your conclusion isn’t saying anything new or interesting, ask a friend to read it with you. Whenever you make a statement from your conclusion, ask the friend to say, “So what?” or “Why should anybody care?” Then ponder that question and answer it. Here’s how it might go: You: Basically, I’m just saying that education was important to Douglass. Friend: So what? You: Well, it was important because it was a key to him feeling like a free and equal citizen. Friend: Why should anybody care? You: That’s important because plantation owners tried to keep slaves from being educated so that they could maintain control. When Douglass obtained an education, he undermined that control personally. You can also use this strategy on your own, asking yourself “So What?” as you develop your ideas or your draft.
• Return to the theme or themes in the introduction. This strategy brings the reader full circle. For example, if you begin by describing a scenario, you can end with the same scenario as proof that your essay is helpful in creating a new understanding. You may also refer to the introductory paragraph by using key words or parallel concepts and images that you also used in the introduction.
• Synthesize, don’t summarize. Include a brief summary of the paper’s main points, but don’t simply repeat things that were in your paper. Instead, show your reader how the points you made and the support and examples you used fit together. Pull it all together.
• Include a provocative insight or quotation from the research or reading you did for your paper.
• Propose a course of action, a solution to an issue, or questions for further study. This can redirect your reader’s thought process and help them to apply your info and ideas to their own life or to see the broader implications.
• Point to broader implications. For example, if your paper examines the Greensboro sit-ins or another event in the Civil Rights Movement, you could point out its impact on the Civil Rights Movement as a whole. A paper about the style of writer Virginia Woolf could point to her influence on other writers or on later feminists.

Strategies to avoid

• Beginning with an unnecessary, overused phrase such as “in conclusion,” “in summary,” or “in closing.” Although these phrases can work in speeches, they come across as wooden and trite in writing.
• Stating the thesis for the very first time in the conclusion.
• Introducing a new idea or subtopic in your conclusion.
• Ending with a rephrased thesis statement without any substantive changes.
• Making sentimental, emotional appeals that are out of character with the rest of an analytical paper.
• Including evidence (quotations, statistics, etc.) that should be in the body of the paper.

Four kinds of ineffective conclusions

• The “That’s My Story and I’m Sticking to It” Conclusion. This conclusion just restates the thesis and is usually painfully short. It does not push the ideas forward. People write this kind of conclusion when they can’t think of anything else to say. Example: In conclusion, Frederick Douglass was, as we have seen, a pioneer in American education, proving that education was a major force for social change with regard to slavery.
• The “Sherlock Holmes” Conclusion. Sometimes writers will state the thesis for the very first time in the conclusion. You might be tempted to use this strategy if you don’t want to give everything away too early in your paper. You may think it would be more dramatic to keep the reader in the dark until the end and then “wow” them with your main idea, as in a Sherlock Holmes mystery. The reader, however, does not expect a mystery, but an analytical discussion of your topic in an academic style, with the main argument (thesis) stated up front. Example: (After a paper that lists numerous incidents from the book but never says what these incidents reveal about Douglass and his views on education): So, as the evidence above demonstrates, Douglass saw education as a way to undermine the slaveholders’ power and also an important step toward freedom.
• The “America the Beautiful”/”I Am Woman”/”We Shall Overcome” Conclusion. This kind of conclusion usually draws on emotion to make its appeal, but while this emotion and even sentimentality may be very heartfelt, it is usually out of character with the rest of an analytical paper. A more sophisticated commentary, rather than emotional praise, would be a more fitting tribute to the topic. Example: Because of the efforts of fine Americans like Frederick Douglass, countless others have seen the shining beacon of light that is education. His example was a torch that lit the way for others. Frederick Douglass was truly an American hero.
• The “Grab Bag” Conclusion. This kind of conclusion includes extra information that the writer found or thought of but couldn’t integrate into the main paper. You may find it hard to leave out details that you discovered after hours of research and thought, but adding random facts and bits of evidence at the end of an otherwise-well-organized essay can just create confusion. Example: In addition to being an educational pioneer, Frederick Douglass provides an interesting case study for masculinity in the American South. He also offers historians an interesting glimpse into slave resistance when he confronts Covey, the overseer. His relationships with female relatives reveal the importance of family in the slave community.

Works consulted

We consulted these works while writing this handout. This is not a comprehensive list of resources on the handout’s topic, and we encourage you to do your own research to find additional publications. Please do not use this list as a model for the format of your own reference list, as it may not match the citation style you are using. For guidance on formatting citations, please see the UNC Libraries citation tutorial . We revise these tips periodically and welcome feedback.

Douglass, Frederick. 1995. Narrative of the Life of Frederick Douglass, an American Slave, Written by Himself. New York: Dover.

Hamilton College. n.d. “Conclusions.” Writing Center. Accessed June 14, 2019. https://www.hamilton.edu//academics/centers/writing/writing-resources/conclusions .

Holewa, Randa. 2004. “Strategies for Writing a Conclusion.” LEO: Literacy Education Online. Last updated February 19, 2004. https://leo.stcloudstate.edu/acadwrite/conclude.html.

You may reproduce it for non-commercial use if you use the entire handout and attribute the source: The Writing Center, University of North Carolina at Chapel Hill

Make a Gift

In a short paper—even a research paper—you don’t need to provide an exhaustive summary as part of your conclusion. But you do need to make some kind of transition between your final body paragraph and your concluding paragraph. This may come in the form of a few sentences of summary. Or it may come in the form of a sentence that brings your readers back to your thesis or main idea and reminds your readers where you began and how far you have traveled.

So, for example, in a paper about the relationship between ADHD and rejection sensitivity, Vanessa Roser begins by introducing readers to the fact that researchers have studied the relationship between the two conditions and then provides her explanation of that relationship. Here’s her thesis: “While socialization may indeed be an important factor in RS, I argue that individuals with ADHD may also possess a neurological predisposition to RS that is exacerbated by the differing executive and emotional regulation characteristic of ADHD.”

In her final paragraph, Roser reminds us of where she started by echoing her thesis: “This literature demonstrates that, as with many other conditions, ADHD and RS share a delicately intertwined pattern of neurological similarities that is rooted in the innate biology of an individual’s mind, a connection that cannot be explained in full by the behavioral mediation hypothesis.”  

Highlight the “so what”  

At the beginning of your paper, you explain to your readers what’s at stake—why they should care about the argument you’re making. In your conclusion, you can bring readers back to those stakes by reminding them why your argument is important in the first place. You can also draft a few sentences that put those stakes into a new or broader context.

In the conclusion to her paper about ADHD and RS, Roser echoes the stakes she established in her introduction—that research into connections between ADHD and RS has led to contradictory results, raising questions about the “behavioral mediation hypothesis.”

She writes, “as with many other conditions, ADHD and RS share a delicately intertwined pattern of neurological similarities that is rooted in the innate biology of an individual’s mind, a connection that cannot be explained in full by the behavioral mediation hypothesis.”  

Leave your readers with the “now what”  

After the “what” and the “so what,” you should leave your reader with some final thoughts. If you have written a strong introduction, your readers will know why you have been arguing what you have been arguing—and why they should care. And if you’ve made a good case for your thesis, then your readers should be in a position to see things in a new way, understand new questions, or be ready for something that they weren’t ready for before they read your paper.

In her conclusion, Roser offers two “now what” statements. First, she explains that it is important to recognize that the flawed behavioral mediation hypothesis “seems to place a degree of fault on the individual. It implies that individuals with ADHD must have elicited such frequent or intense rejection by virtue of their inadequate social skills, erasing the possibility that they may simply possess a natural sensitivity to emotion.” She then highlights the broader implications for treatment of people with ADHD, noting that recognizing the actual connection between rejection sensitivity and ADHD “has profound implications for understanding how individuals with ADHD might best be treated in educational settings, by counselors, family, peers, or even society as a whole.”

To find your own “now what” for your essay’s conclusion, try asking yourself these questions:

• What can my readers now understand, see in a new light, or grapple with that they would not have understood in the same way before reading my paper? Are we a step closer to understanding a larger phenomenon or to understanding why what was at stake is so important?  
• What questions can I now raise that would not have made sense at the beginning of my paper? Questions for further research? Other ways that this topic could be approached?  
• Are there other applications for my research? Could my questions be asked about different data in a different context? Could I use my methods to answer a different question?  
• What action should be taken in light of this argument? What action do I predict will be taken or could lead to a solution?  
• What larger context might my argument be a part of?  

What to avoid in your conclusion  

• a complete restatement of all that you have said in your paper.  
• a substantial counterargument that you do not have space to refute; you should introduce counterarguments before your conclusion.  
• an apology for what you have not said. If you need to explain the scope of your paper, you should do this sooner—but don’t apologize for what you have not discussed in your paper.  
• fake transitions like “in conclusion” that are followed by sentences that aren’t actually conclusions. (“In conclusion, I have now demonstrated that my thesis is correct.”)
• picture_as_pdf Conclusions

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• Writing Tips

How to Write a Conclusion for a Research Paper

3-minute read

• 29th August 2023

If you’re writing a research paper, the conclusion is your opportunity to summarize your findings and leave a lasting impression on your readers. In this post, we’ll take you through how to write an effective conclusion for a research paper and how you can:

·   Reword your thesis statement

·   Highlight the significance of your research

·   Discuss limitations

·   Connect to the introduction

·   End with a thought-provoking statement

Rewording Your Thesis Statement

Begin your conclusion by restating your thesis statement in a way that is slightly different from the wording used in the introduction. Avoid presenting new information or evidence in your conclusion. Just summarize the main points and arguments of your essay and keep this part as concise as possible. Remember that you’ve already covered the in-depth analyses and investigations in the main body paragraphs of your essay, so it’s not necessary to restate these details in the conclusion.

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Highlighting the Significance of Your Research

The conclusion is a good place to emphasize the implications of your research . Avoid ambiguous or vague language such as “I think” or “maybe,” which could weaken your position. Clearly explain why your research is significant and how it contributes to the broader field of study.

Here’s an example from a (fictional) study on the impact of social media on mental health:

Discussing Limitations

Although it’s important to emphasize the significance of your study, you can also use the conclusion to briefly address any limitations you discovered while conducting your research, such as time constraints or a shortage of resources. Doing this demonstrates a balanced and honest approach to your research.

Connecting to the Introduction

In your conclusion, you can circle back to your introduction , perhaps by referring to a quote or anecdote you discussed earlier. If you end your paper on a similar note to how you began it, you will create a sense of cohesion for the reader and remind them of the meaning and significance of your research.

Ending With a Thought-Provoking Statement

Consider ending your paper with a thought-provoking and memorable statement that relates to the impact of your research questions or hypothesis. This statement can be a call to action, a philosophical question, or a prediction for the future (positive or negative). Here’s an example that uses the same topic as above (social media and mental health):

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How to write a strong conclusion for your research paper

Last updated

17 February 2024

Reviewed by

Writing a research paper is a chance to share your knowledge and hypothesis. It's an opportunity to demonstrate your many hours of research and prove your ability to write convincingly.

Ideally, by the end of your research paper, you'll have brought your readers on a journey to reach the conclusions you've pre-determined. However, if you don't stick the landing with a good conclusion, you'll risk losing your reader’s trust.

Writing a strong conclusion for your research paper involves a few important steps, including restating the thesis and summing up everything properly.

Find out what to include and what to avoid, so you can effectively demonstrate your understanding of the topic and prove your expertise.

• Why is a good conclusion important?

A good conclusion can cement your paper in the reader’s mind. Making a strong impression in your introduction can draw your readers in, but it's the conclusion that will inspire them.

• What to include in a research paper conclusion

There are a few specifics you should include in your research paper conclusion. Offer your readers some sense of urgency or consequence by pointing out why they should care about the topic you have covered. Discuss any common problems associated with your topic and provide suggestions as to how these problems can be solved or addressed.

The conclusion should include a restatement of your initial thesis. Thesis statements are strengthened after you’ve presented supporting evidence (as you will have done in the paper), so make a point to reintroduce it at the end.

Finally, recap the main points of your research paper, highlighting the key takeaways you want readers to remember. If you've made multiple points throughout the paper, refer to the ones with the strongest supporting evidence.

• Steps for writing a research paper conclusion

Many writers find the conclusion the most challenging part of any research project . By following these three steps, you'll be prepared to write a conclusion that is effective and concise.

• Step 1: Restate the problem

Always begin by restating the research problem in the conclusion of a research paper. This serves to remind the reader of your hypothesis and refresh them on the main point of the paper. 

When restating the problem, take care to avoid using exactly the same words you employed earlier in the paper.

• Step 2: Sum up the paper

After you've restated the problem, sum up the paper by revealing your overall findings. The method for this differs slightly, depending on whether you're crafting an argumentative paper or an empirical paper.

Argumentative paper: Restate your thesis and arguments

Argumentative papers involve introducing a thesis statement early on. In crafting the conclusion for an argumentative paper, always restate the thesis, outlining the way you've developed it throughout the entire paper.

It might be appropriate to mention any counterarguments in the conclusion, so you can demonstrate how your thesis is correct or how the data best supports your main points.

Empirical paper: Summarize research findings

Empirical papers break down a series of research questions. In your conclusion, discuss the findings your research revealed, including any information that surprised you.

Be clear about the conclusions you reached, and explain whether or not you expected to arrive at these particular ones.

• Step 3: Discuss the implications of your research

Argumentative papers and empirical papers also differ in this part of a research paper conclusion. Here are some tips on crafting conclusions for argumentative and empirical papers.

Argumentative paper: Powerful closing statement

In an argumentative paper, you'll have spent a great deal of time expressing the opinions you formed after doing a significant amount of research. Make a strong closing statement in your argumentative paper's conclusion to share the significance of your work.

You can outline the next steps through a bold call to action, or restate how powerful your ideas turned out to be.

Empirical paper: Directions for future research

Empirical papers are broader in scope. They usually cover a variety of aspects and can include several points of view.

To write a good conclusion for an empirical paper, suggest the type of research that could be done in the future, including methods for further investigation or outlining ways other researchers might proceed.

If you feel your research had any limitations, even if they were outside your control, you could mention these in your conclusion.

After you finish outlining your conclusion, ask someone to read it and offer feedback. In any research project you're especially close to, it can be hard to identify problem areas. Having a close friend or someone whose opinion you value read the research paper and provide honest feedback can be invaluable. Take note of any suggested edits and consider incorporating them into your paper if they make sense.

• Things to avoid in a research paper conclusion

Keep these aspects to avoid in mind as you're writing your conclusion and refer to them after you've created an outline.

Dry summary

Writing a memorable, succinct conclusion is arguably more important than a strong introduction. Take care to avoid just rephrasing your main points, and don't fall into the trap of repeating dry facts or citations.

You can provide a new perspective for your readers to think about or contextualize your research. Either way, make the conclusion vibrant and interesting, rather than a rote recitation of your research paper’s highlights.

Clichéd or generic phrasing

Your research paper conclusion should feel fresh and inspiring. Avoid generic phrases like "to sum up" or "in conclusion." These phrases tend to be overused, especially in an academic context and might turn your readers off.

The conclusion also isn't the time to introduce colloquial phrases or informal language. Retain a professional, confident tone consistent throughout your paper’s conclusion so it feels exciting and bold.

New data or evidence

While you should present strong data throughout your paper, the conclusion isn't the place to introduce new evidence. This is because readers are engaged in actively learning as they read through the body of your paper.

By the time they reach the conclusion, they will have formed an opinion one way or the other (hopefully in your favor!). Introducing new evidence in the conclusion will only serve to surprise or frustrate your reader.

Ignoring contradictory evidence

If your research reveals contradictory evidence, don't ignore it in the conclusion. This will damage your credibility as an expert and might even serve to highlight the contradictions.

Be as transparent as possible and admit to any shortcomings in your research, but don't dwell on them for too long.

Ambiguous or unclear resolutions

The point of a research paper conclusion is to provide closure and bring all your ideas together. You should wrap up any arguments you introduced in the paper and tie up any loose ends, while demonstrating why your research and data are strong.

Use direct language in your conclusion and avoid ambiguity. Even if some of the data and sources you cite are inconclusive or contradictory, note this in your conclusion to come across as confident and trustworthy.

• Examples of research paper conclusions

Your research paper should provide a compelling close to the paper as a whole, highlighting your research and hard work. While the conclusion should represent your unique style, these examples offer a starting point:

Ultimately, the data we examined all point to the same conclusion: Encouraging a good work-life balance improves employee productivity and benefits the company overall. The research suggests that when employees feel their personal lives are valued and respected by their employers, they are more likely to be productive when at work. In addition, company turnover tends to be reduced when employees have a balance between their personal and professional lives. While additional research is required to establish ways companies can support employees in creating a stronger work-life balance, it's clear the need is there.

Social media is a primary method of communication among young people. As we've seen in the data presented, most young people in high school use a variety of social media applications at least every hour, including Instagram and Facebook. While social media is an avenue for connection with peers, research increasingly suggests that social media use correlates with body image issues. Young girls with lower self-esteem tend to use social media more often than those who don't log onto social media apps every day. As new applications continue to gain popularity, and as more high school students are given smartphones, more research will be required to measure the effects of prolonged social media use.

What are the different kinds of research paper conclusions?

There are no formal types of research paper conclusions. Ultimately, the conclusion depends on the outline of your paper and the type of research you’re presenting. While some experts note that research papers can end with a new perspective or commentary, most papers should conclude with a combination of both. The most important aspect of a good research paper conclusion is that it accurately represents the body of the paper.

Can I present new arguments in my research paper conclusion?

Research paper conclusions are not the place to introduce new data or arguments. The body of your paper is where you should share research and insights, where the reader is actively absorbing the content. By the time a reader reaches the conclusion of the research paper, they should have formed their opinion. Introducing new arguments in the conclusion can take a reader by surprise, and not in a positive way. It might also serve to frustrate readers.

How long should a research paper conclusion be?

There's no set length for a research paper conclusion. However, it's a good idea not to run on too long, since conclusions are supposed to be succinct. A good rule of thumb is to keep your conclusion around 5 to 10 percent of the paper's total length. If your paper is 10 pages, try to keep your conclusion under one page.

What should I include in a research paper conclusion?

A good research paper conclusion should always include a sense of urgency, so the reader can see how and why the topic should matter to them. You can also note some recommended actions to help fix the problem and some obstacles they might encounter. A conclusion should also remind the reader of the thesis statement, along with the main points you covered in the paper. At the end of the conclusion, add a powerful closing statement that helps cement the paper in the mind of the reader.

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Writing a Paper: Conclusions

Writing a conclusion.

A conclusion is an important part of the paper; it provides closure for the reader while reminding the reader of the contents and importance of the paper. It accomplishes this by stepping back from the specifics in order to view the bigger picture of the document. In other words, it is reminding the reader of the main argument. For most course papers, it is usually one paragraph that simply and succinctly restates the main ideas and arguments, pulling everything together to help clarify the thesis of the paper. A conclusion does not introduce new ideas; instead, it should clarify the intent and importance of the paper. It can also suggest possible future research on the topic.

An Easy Checklist for Writing a Conclusion

It is important to remind the reader of the thesis of the paper so he is reminded of the argument and solutions you proposed.

Think of the main points as puzzle pieces, and the conclusion is where they all fit together to create a bigger picture. The reader should walk away with the bigger picture in mind.

Make sure that the paper places its findings in the context of real social change.

Make sure the reader has a distinct sense that the paper has come to an end. It is important to not leave the reader hanging. (You don’t want her to have flip-the-page syndrome, where the reader turns the page, expecting the paper to continue. The paper should naturally come to an end.)

No new ideas should be introduced in the conclusion. It is simply a review of the material that is already present in the paper. The only new idea would be the suggesting of a direction for future research.

Conclusion Example

As addressed in my analysis of recent research, the advantages of a later starting time for high school students significantly outweigh the disadvantages. A later starting time would allow teens more time to sleep--something that is important for their physical and mental health--and ultimately improve their academic performance and behavior. The added transportation costs that result from this change can be absorbed through energy savings. The beneficial effects on the students’ academic performance and behavior validate this decision, but its effect on student motivation is still unknown. I would encourage an in-depth look at the reactions of students to such a change. This sort of study would help determine the actual effects of a later start time on the time management and sleep habits of students.

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How to Write a Conclusion for a Research Paper

Last Updated: June 29, 2023 Approved

This article was co-authored by Christopher Taylor, PhD . Christopher Taylor is an Adjunct Assistant Professor of English at Austin Community College in Texas. He received his PhD in English Literature and Medieval Studies from the University of Texas at Austin in 2014. wikiHow marks an article as reader-approved once it receives enough positive feedback. This article received 42 testimonials and 82% of readers who voted found it helpful, earning it our reader-approved status. This article has been viewed 2,257,835 times.

The conclusion of a research paper needs to summarize the content and purpose of the paper without seeming too wooden or dry. Every basic conclusion must share several key elements, but there are also several tactics you can play around with to craft a more effective conclusion and several you should avoid to prevent yourself from weakening your paper's conclusion. Here are some writing tips to keep in mind when creating a conclusion for your next research paper.

Sample Conclusions

Writing a basic conclusion.

• Do not spend a great amount of time or space restating your topic.
• A good research paper will make the importance of your topic apparent, so you do not need to write an elaborate defense of your topic in the conclusion.
• Usually a single sentence is all you need to restate your topic.
• An example would be if you were writing a paper on the epidemiology of infectious disease, you might say something like "Tuberculosis is a widespread infectious disease that affects millions of people worldwide every year."
• Yet another example from the humanities would be a paper about the Italian Renaissance: "The Italian Renaissance was an explosion of art and ideas centered around artists, writers, and thinkers in Florence."

• A thesis is a narrowed, focused view on the topic at hand.
• This statement should be rephrased from the thesis you included in your introduction. It should not be identical or too similar to the sentence you originally used.
• Try re-wording your thesis statement in a way that complements your summary of the topic of your paper in your first sentence of your conclusion.
• An example of a good thesis statement, going back to the paper on tuberculosis, would be "Tuberculosis is a widespread disease that affects millions of people worldwide every year. Due to the alarming rate of the spread of tuberculosis, particularly in poor countries, medical professionals are implementing new strategies for the diagnosis, treatment, and containment of this disease ."

• A good way to go about this is to re-read the topic sentence of each major paragraph or section in the body of your paper.
• Find a way to briefly restate each point mentioned in each topic sentence in your conclusion. Do not repeat any of the supporting details used within your body paragraphs.
• Under most circumstances, you should avoid writing new information in your conclusion. This is especially true if the information is vital to the argument or research presented in your paper.
• For example, in the TB paper you could summarize the information. "Tuberculosis is a widespread disease that affects millions of people worldwide. Due to the alarming rate of the spread of tuberculosis, particularly in poor countries, medical professionals are implementing new strategies for the diagnosis, treatment, and containment of this disease. In developing countries, such as those in Africa and Southeast Asia, the rate of TB infections is soaring. Crowded conditions, poor sanitation, and lack of access to medical care are all compounding factors in the spread of the disease. Medical experts, such as those from the World Health Organization are now starting campaigns to go into communities in developing countries and provide diagnostic testing and treatments. However, the treatments for TB are very harsh and have many side effects. This leads to patient non-compliance and spread of multi-drug resistant strains of the disease."

• Note that this is not needed for all research papers.
• If you already fully explained what the points in your paper mean or why they are significant, you do not need to go into them in much detail in your conclusion. Simply restating your thesis or the significance of your topic should suffice.
• It is always best practice to address important issues and fully explain your points in the body of your paper. The point of a conclusion to a research paper is to summarize your argument for the reader and, perhaps, to call the reader to action if needed.

• Note that a call for action is not essential to all conclusions. A research paper on literary criticism, for instance, is less likely to need a call for action than a paper on the effect that television has on toddlers and young children.
• A paper that is more likely to call readers to action is one that addresses a public or scientific need. Let's go back to our example of tuberculosis. This is a very serious disease that is spreading quickly and with antibiotic-resistant forms.
• A call to action in this research paper would be a follow-up statement that might be along the lines of "Despite new efforts to diagnose and contain the disease, more research is needed to develop new antibiotics that will treat the most resistant strains of tuberculosis and ease the side effects of current treatments."

• For example, if you are writing a history paper, then you might discuss how the historical topic you discussed matters today. If you are writing about a foreign country, then you might use the conclusion to discuss how the information you shared may help readers understand their own country.

Making Your Conclusion as Effective as Possible

• Since this sort of conclusion is so basic, you must aim to synthesize the information rather than merely summarizing it.
• Instead of merely repeating things you already said, rephrase your thesis and supporting points in a way that ties them all together.
• By doing so, you make your research paper seem like a "complete thought" rather than a collection of random and vaguely related ideas.

• Ask a question in your introduction. In your conclusion, restate the question and provide a direct answer.
• Write an anecdote or story in your introduction but do not share the ending. Instead, write the conclusion to the anecdote in the conclusion of your paper.
• For example, if you wanted to get more creative and put a more humanistic spin on a paper on tuberculosis, you might start your introduction with a story about a person with the disease, and refer to that story in your conclusion. For example, you could say something like this before you re-state your thesis in your conclusion: "Patient X was unable to complete the treatment for tuberculosis due to severe side effects and unfortunately succumbed to the disease."
• Use the same concepts and images introduced in your introduction in your conclusion. The images may or may not appear at other points throughout the research paper.

• Include enough information about your topic to back the statement up but do not get too carried away with excess detail.
• If your research did not provide you with a clear-cut answer to a question posed in your thesis, do not be afraid to indicate as much.
• Restate your initial hypothesis and indicate whether you still believe it or if the research you performed has begun swaying your opinion.
• Indicate that an answer may still exist and that further research could shed more light on the topic at hand.

• This may not be appropriate for all types of research papers. Most research papers, such as one on effective treatment for diseases, will have the information to make the case for a particular argument already in the paper.
• A good example of a paper that might ask a question of the reader in the ending is one about a social issue, such as poverty or government policy.
• Ask a question that will directly get at the heart or purpose of the paper. This question is often the same question, or some version of it, that you may have started with when you began your research.
• Make sure that the question can be answered by the evidence presented in your paper.
• If desired you can briefly summarize the answer after stating the question. You could also leave the question hanging for the reader to answer, though.

• Even without a call to action, you can still make a recommendation to your reader.
• For instance, if you are writing about a topic like third-world poverty, you can various ways for the reader to assist in the problem without necessarily calling for more research.
• Another example would be, in a paper about treatment for drug-resistant tuberculosis, you could suggest donating to the World Health Organization or research foundations that are developing new treatments for the disease.

Avoiding Common Pitfalls

• These sayings usually sound stiff, unnatural, or trite when used in writing.
• Moreover, using a phrase like "in conclusion" to begin your conclusion is a little too straightforward and tends to lead to a weak conclusion. A strong conclusion can stand on its own without being labeled as such.

• Always state the main argument or thesis in the introduction. A research paper is an analytical discussion of an academic topic, not a mystery novel.
• A good, effective research paper will allow your reader to follow your main argument from start to finish.
• This is why it is best practice to start your paper with an introduction that states your main argument and to end the paper with a conclusion that re-states your thesis for re-iteration.

• All significant information should be introduced in the body of the paper.
• Supporting evidence expands the topic of your paper by making it appear more detailed. A conclusion should narrow the topic to a more general point.
• A conclusion should only summarize what you have already stated in the body of your paper.
• You may suggest further research or a call to action, but you should not bring in any new evidence or facts in the conclusion.

• Most often, a shift in tone occurs when a research paper with an academic tone gives an emotional or sentimental conclusion.
• Even if the topic of the paper is of personal significance for you, you should not indicate as much in your paper.
• If you want to give your paper a more humanistic slant, you could start and end your paper with a story or anecdote that would give your topic more personal meaning to the reader.
• This tone should be consistent throughout the paper, however.

• Apologetic statements include phrases like "I may not be an expert" or "This is only my opinion."
• Statements like this can usually be avoided by refraining from writing in the first-person.
• Avoid any statements in the first-person. First-person is generally considered to be informal and does not fit with the formal tone of a research paper.

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• ↑ http://owl.english.purdue.edu/owl/resource/724/04/
• ↑ http://www.crlsresearchguide.org/18_Writing_Conclusion.asp
• ↑ http://writing.wisc.edu/Handbook/PlanResearchPaper.html#conclusion
• ↑ http://writingcenter.unc.edu/handouts/conclusions/
• ↑ http://writing2.richmond.edu/writing/wweb/conclude.html

About This Article

To write a conclusion for a research paper, start by restating your thesis statement to remind your readers what your main topic is and bring everything full circle. Then, briefly summarize all of the main points you made throughout your paper, which will help remind your readers of everything they learned. You might also want to include a call to action if you think more research or work needs to be done on your topic by writing something like, "Despite efforts to contain the disease, more research is needed to develop antibiotics." Finally, end your conclusion by explaining the broader context of your topic and why your readers should care about it, which will help them understand why your topic is relevant and important. For tips from our Academic co-author, like how to avoid common pitfalls when writing your conclusion, scroll down! Did this summary help you? Yes No

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How to Write a Research Paper Conclusion Section

What is a conclusion in a research paper?

The conclusion in a research paper is the final paragraph or two in a research paper. In scientific papers, the conclusion usually follows the Discussion section , summarizing the importance of the findings and reminding the reader why the work presented in the paper is relevant.

However, it can be a bit confusing to distinguish the conclusion section/paragraph from a summary or a repetition of your findings, your own opinion, or the statement of the implications of your work. In fact, the conclusion should contain a bit of all of these other parts but go beyond it—but not too far beyond! 

The structure and content of the conclusion section can also vary depending on whether you are writing a research manuscript or an essay. This article will explain how to write a good conclusion section, what exactly it should (and should not) contain, how it should be structured, and what you should avoid when writing it.  

Table of Contents:

What does a good conclusion section do, what to include in a research paper conclusion.

• Conclusion in an Essay
• Research Paper Conclusion 
• Conclusion Paragraph Outline and Example
• What Not to Do When Writing a Conclusion

The conclusion of a research paper has several key objectives. It should:

• Restate your research problem addressed in the introduction section
• Summarize your main arguments, important findings, and broader implications
• Synthesize key takeaways from your study

The specific content in the conclusion depends on whether your paper presents the results of original scientific research or constructs an argument through engagement with previously published sources.

You presented your general field of study to the reader in the introduction section, by moving from general information (the background of your work, often combined with a literature review ) to the rationale of your study and then to the specific problem or topic you addressed, formulated in the form of the statement of the problem in research or the thesis statement in an essay.

In the conclusion section, in contrast, your task is to move from your specific findings or arguments back to a more general depiction of how your research contributes to the readers’ understanding of a certain concept or helps solve a practical problem, or fills an important gap in the literature. The content of your conclusion section depends on the type of research you are doing and what type of paper you are writing. But whatever the outcome of your work is, the conclusion is where you briefly summarize it and place it within a larger context. It could be called the “take-home message” of the entire paper.

What to summarize in the conclusion

Your conclusion section needs to contain a very brief summary of your work , a very brief summary of the main findings of your work, and a mention of anything else that seems relevant when you now look at your work from a bigger perspective, even if it was not initially listed as one of your main research questions. This could be a limitation, for example, a problem with the design of your experiment that either needs to be considered when drawing any conclusions or that led you to ask a different question and therefore draw different conclusions at the end of your study (compared to when you started out).

Once you have reminded the reader of what you did and what you found, you need to go beyond that and also provide either your own opinion on why your work is relevant (and for whom, and how) or theoretical or practical implications of the study , or make a specific call for action if there is one to be made.   

How to Write an Essay Conclusion

Academic essays follow quite different structures than their counterparts in STEM and the natural sciences. Humanities papers often have conclusion sections that are much longer and contain more detail than scientific papers. There are three main types of academic essay conclusions.

Summarizing conclusion

The most typical conclusion at the end of an analytical/explanatory/argumentative essay is a summarizing conclusion . This is, as the name suggests, a clear summary of the main points of your topic and thesis. Since you might have gone through a number of different arguments or subtopics in the main part of your essay, you need to remind the reader again what those were, how they fit into each other, and how they helped you develop or corroborate your hypothesis.

For an essay that analyzes how recruiters can hire the best candidates in the shortest time or on “how starving yourself will increase your lifespan, according to science”, a summary of all the points you discussed might be all you need. Note that you should not exactly repeat what you said earlier, but rather highlight the essential details and present those to your reader in a different way. 

Externalizing conclusion

If you think that just reminding the reader of your main points is not enough, you can opt for an externalizing conclusion instead, that presents new points that were not presented in the paper so far. These new points can be additional facts and information or they can be ideas that are relevant to the topic and have not been mentioned before.

Such a conclusion can stimulate your readers to think about your topic or the implications of your analysis in a whole new way. For example, at the end of a historical analysis of a specific event or development, you could direct your reader’s attention to some current events that were not the topic of your essay but that provide a different context for your findings.

Editorial conclusion

In an editorial conclusion , another common type of conclusion that you will find at the end of papers and essays, you do not add new information but instead present your own experiences or opinions on the topic to round everything up. What makes this type of conclusion interesting is that you can choose to agree or disagree with the information you presented in your paper so far. For example, if you have collected and analyzed information on how a specific diet helps people lose weight, you can nevertheless have your doubts on the sustainability of that diet or its practicability in real life—if such arguments were not included in your original thesis and have therefore not been covered in the main part of your paper, the conclusion section is the place where you can get your opinion across.    

How to Conclude an Empirical Research Paper

An empirical research paper is usually more concise and succinct than an essay, because, if it is written well, it focuses on one specific question, describes the method that was used to answer that one question, describes and explains the results, and guides the reader in a logical way from the introduction to the discussion without going on tangents or digging into not absolutely relevant topics.

Summarize the findings

In a scientific paper, you should include a summary of the findings. Don’t go into great detail here (you will have presented your in-depth  results  and  discussion  already), but do clearly express the answers to the  research questions  you investigated.

Describe your main findings, even if they weren’t necessarily the ones anticipated, and explain the conclusion they led you to. Explain these findings in as few words as possible.

Instead of beginning with “ In conclusion, in this study, we investigated the effect of stress on the brain using fMRI …”, you should try to find a way to incorporate the repetition of the essential (and only the essential) details into the summary of the key points. “ The findings of this fMRI study on the effect of stress on the brain suggest that …” or “ While it has been known for a long time that stress has an effect on the brain, the findings of this fMRI study show that, surprisingly… ” would be better ways to start a conclusion. 

You should also not bring up new ideas or present new facts in the conclusion of a research paper, but stick to the background information you have presented earlier, to the findings you have already discussed, and the limitations and implications you have already described. The one thing you can add here is a practical recommendation that you haven’t clearly stated before—but even that one needs to follow logically from everything you have already discussed in the discussion section.

Discuss the implications

After summing up your key arguments or findings, conclude the paper by stating the broader implications of the research , whether in methods , approach, or findings. Express practical or theoretical takeaways from your paper. This often looks like a “call to action” or a final “sales pitch” that puts an exclamation point on your paper.

If your research topic is more theoretical in nature, your closing statement should express the significance of your argument—for example, in proposing a new understanding of a topic or laying the groundwork for future research.

Future research example

Future research into education standards should focus on establishing a more detailed picture of how novel pedagogical approaches impact young people’s ability to absorb new and difficult concepts. Moreover, observational studies are needed to gain more insight into how specific teaching models affect the retention of relationships and facts—for instance, how inquiry-based learning and its emphasis on lateral thinking can be used as a jumping-off point for more holistic classroom approaches.

Research Conclusion Example and Outline

Let’s revisit the study on the effect of stress on the brain we mentioned before and see what the common structure for a conclusion paragraph looks like, in three steps. Following these simple steps will make it easy for you to wrap everything up in one short paragraph that contains all the essential information: 

One: Short summary of what you did, but integrated into the summary of your findings:

While it has been known for a long time that stress has an effect on the brain, the findings of this fMRI study in 25 university students going through mid-term exams show that, surprisingly, one’s attitude to the experienced stress significantly modulates the brain’s response to it. 

Note that you don’t need to repeat any methodological or technical details here—the reader has been presented with all of these before, they have read your results section and the discussion of your results, and even (hopefully!) a discussion of the limitations and strengths of your paper. The only thing you need to remind them of here is the essential outcome of your work. 

Two: Add implications, and don’t forget to specify who this might be relevant for: 

Students could be considered a specific subsample of the general population, but earlier research shows that the effect that exam stress has on their physical and mental health is comparable to the effects of other types of stress on individuals of other ages and occupations. Further research into practical ways of modulating not only one’s mental stress response but potentially also one’s brain activity (e.g., via neurofeedback training) are warranted.

This is a “research implication”, and it is nicely combined with a mention of a potential limitation of the study (the student sample) that turns out not to be a limitation after all (because earlier research suggests we can generalize to other populations). If there already is a lot of research on neurofeedback for stress control, by the way, then this should have been discussed in your discussion section earlier and you wouldn’t say such studies are “warranted” here but rather specify how your findings could inspire specific future experiments or how they should be implemented in existing applications. 

Three: The most important thing is that your conclusion paragraph accurately reflects the content of your paper. Compare it to your research paper title , your research paper abstract , and to your journal submission cover letter , in case you already have one—if these do not all tell the same story, then you need to go back to your paper, start again from the introduction section, and find out where you lost the logical thread. As always, consistency is key.    

Problems to Avoid When Writing a Conclusion 

• Do not suddenly introduce new information that has never been mentioned before (unless you are writing an essay and opting for an externalizing conclusion, see above). The conclusion section is not where you want to surprise your readers, but the take-home message of what you have already presented.
• Do not simply copy your abstract, the conclusion section of your abstract, or the first sentence of your introduction, and put it at the end of the discussion section. Even if these parts of your paper cover the same points, they should not be identical.
• Do not start the conclusion with “In conclusion”. If it has its own section heading, that is redundant, and if it is the last paragraph of the discussion section, it is inelegant and also not really necessary. The reader expects you to wrap your work up in the last paragraph, so you don’t have to announce that. Just look at the above example to see how to start a conclusion in a natural way.
• Do not forget what your research objectives were and how you initially formulated the statement of the problem in your introduction section. If your story/approach/conclusions changed because of methodological issues or information you were not aware of when you started, then make sure you go back to the beginning and adapt your entire story (not just the ending). 

Consider Receiving Academic Editing Services

When you have arrived at the conclusion of your paper, you might want to head over to Wordvice AI’s AI Writing Assistant to receive a free grammar check for any academic content. 

After drafting, you can also receive English editing and proofreading services , including paper editing services for your journal manuscript. If you need advice on how to write the other parts of your research paper , or on how to make a research paper outline if you are struggling with putting everything you did together, then head over to the Wordvice academic resources pages , where we have a lot more articles and videos for you.

Organizing Academic Research Papers: 9. The Conclusion

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• Narrowing a Topic Idea
• Broadening a Topic Idea
• Extending the Timeliness of a Topic Idea
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• Choosing a Title
• Making an Outline
• Paragraph Development
• Executive Summary
• Background Information
• The Research Problem/Question
• Theoretical Framework
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• Evaluating Sources
• Primary Sources
• Secondary Sources
• Tertiary Sources
• What Is Scholarly vs. Popular?
• Qualitative Methods
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• Using Non-Textual Elements
• Limitations of the Study
• Common Grammar Mistakes
• Avoiding Plagiarism
• Footnotes or Endnotes?
• Further Readings
• Annotated Bibliography
• Dealing with Nervousness
• Using Visual Aids
• Grading Someone Else's Paper
• How to Manage Group Projects
• Multiple Book Review Essay
• Reviewing Collected Essays
• About Informed Consent
• Writing Field Notes
• Writing a Policy Memo
• Writing a Research Proposal
• Acknowledgements

The conclusion is intended to help the reader understand why your research should matter to them after they have finished reading the paper. A conclusion is not merely a summary of your points or a re-statement of your research problem but a synthesis of key points. For most essays, one well-developed paragraph is sufficient for a conclusion, although in some cases, a two-or-three paragraph conclusion may be required.

Importance of a Good Conclusion

A well-written conclusion provides you with several important opportunities to demonstrate your overall understanding of the research problem to the reader. These include:

• Presenting the last word on the issues you raised in your paper . Just as the introduction gives a first impression to your reader, the conclusion offers a chance to leave a lasting impression. Do this, for example, by highlighting key points in your analysis or findings.
• Summarizing your thoughts and conveying the larger implications of your study . The conclusion is an opportunity to succinctly answer the "so what?" question by placing the study within the context of past research about the topic you've investigated.
• Demonstrating the importance of your ideas . Don't be shy. The conclusion offers you a chance to elaborate on the significance of your findings.
• Introducing possible new or expanded ways of thinking about the research problem . This does not refer to introducing new information [which should be avoided], but to offer new insight and creative approaches for framing/contextualizing the research problem based on the results of your study.

Conclusions . The Writing Center. University of North Carolina; Kretchmer, Paul. Twelve Steps to Writing an Effective Conclusion . San Francisco Edit, 2003-2008.

Structure and Writing Style

https://writing.wisc.edu/wp-content/uploads/sites/535/2018/07/conclusions_uwmadison_writingcenter_aug2012.pdf I.  General Rules

When writing the conclusion to your paper, follow these general rules:

• State your conclusions in clear, simple language.
• Do not simply reiterate your results or the discussion.
• Indicate opportunities for future research, as long as you haven't already done so in the discussion section of your paper.

The function of your paper's conclusion is to restate the main argument . It reminds the reader of the strengths of your main argument(s) and reiterates the most important evidence supporting those argument(s). Make sure, however, that your conclusion is not simply a repetitive summary of the findings because this reduces the impact of the argument(s) you have developed in your essay.

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

• If the argument or point of your paper is complex, you may need to summarize the argument 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 end of your paper to describe your main points and explain their significance.
• Move from a detailed to a general level of consideration that returns the topic to the context provided by the introduction or within a new context that emerges from the data.

The conclusion also provides a place for you to persuasively and succinctly restate your research problem, given that the reader has now been presented with all the information about the topic . Depending on the discipline you are writing in, the concluding paragraph may contain your reflections on the evidence presented, or on the essay's central research problem. However, the nature of being introspective about the research you have done will depend on the topic and whether your professor wants you to express your observations in this way.

NOTE : Don't delve into idle speculation. Being introspective means looking within yourself as an author to try and understand an issue more deeply not to guess at possible outcomes.

II.  Developing a Compelling Conclusion

Strategies to help you move beyond merely summarizing the key points of your research paper may include any of the following.

• If your essay deals with a contemporary problem, warn readers of the possible consequences of not attending to the problem.
• Recommend a specific course or courses of action.
• Cite a relevant quotation or expert opinion to lend authority to the conclusion you have reached [a good place to look is research from your literature review].
• Restate a key statistic, fact, or visual image to drive home the ultimate point of your paper.
• If your discipline encourages personal reflection, illustrate your concluding point with a relevant narrative drawn from your own life experiences.
• Return to an anecdote, an example, or a quotation that you introduced in your introduction, but add further insight that is derived from the findings of your study; use your interpretation of results to reframe it in new ways.
• Provide a "take-home" message in the form of a strong, succient statement that you want the reader to remember about your study.

III. Problems to Avoid Failure to be concise The conclusion section should be concise and to the point. Conclusions that are too long often have unnecessary detail. The conclusion section is not the place for details about your methodology or results. Although you should give a summary of what was learned from your research, this summary should be relatively brief, since the emphasis in the conclusion is on the implications, evaluations, insights, etc. that you make. Failure to comment on larger, more significant issues In the introduction, your task was to move from general [the field of study] to specific [your research problem]. However, in the conclusion, your task is to move from specific [your research problem] back to general [your field, i.e., how your research contributes new understanding or fills an important gap in the literature]. In other words, the conclusion is where you place your research within a larger context. Failure to reveal problems and negative results Negative aspects of the research process should never be ignored. Problems, drawbacks, and challenges encountered during your study should be included as a way of qualifying your overall conclusions. If you encountered negative results [findings that are validated outside the research context in which they were generated], you must report them in the results section of your paper. In the conclusion, use the negative results as an opportunity to explain how they provide information on which future research can be based. Failure to provide a clear summary of what was learned In order to be able to discuss how your research fits back into your field of study [and possibly the world at large], you need to summarize it briefly and directly. Often this element of your conclusion is only a few sentences long. Failure to match the objectives of your research Often research objectives change while the research is being carried out. This is not a problem unless you forget to go back and refine your original objectives in your introduction, as these changes emerge they must be documented so that they accurately reflect what you were trying to accomplish in your research [not what you thought you might accomplish when you began].

Resist the urge to apologize If you've immersed yourself in studying the research problem, you now know a good deal about it, perhaps even more than your professor! Nevertheless, by the time you have finished writing, you may be having some doubts about what you have produced. Repress those doubts!  Don't undermine your authority by saying something like, "This is just one approach to examining this problem; there may be other, much better approaches...."

Concluding Paragraphs. College Writing Center at Meramec. St. Louis Community College; Conclusions . The Writing Center. University of North Carolina; Conclusions . The Writing Lab and The OWL. Purdue University; Freedman, Leora  and Jerry Plotnick. Introductions and Conclusions . The Lab Report. University College Writing Centre. University of Toronto; Leibensperger, Summer. Draft Your Conclusion. Academic Center, the University of Houston-Victoria, 2003; Make Your Last Words Count . The Writer’s Handbook. Writing Center. University of Wisconsin, Madison; Tips for Writing a Good Conclusion . Writing@CSU. Colorado State University; Kretchmer, Paul. Twelve Steps to Writing an Effective Conclusion . San Francisco Edit, 2003-2008; Writing Conclusions . Writing Tutorial Services, Center for Innovative Teaching and Learning. Indiana University; Writing: Considering Structure and Organization . Institute for Writing Rhetoric. Dartmouth College.

Writing Tip

Don't Belabor the Obvious!

Avoid phrases like "in conclusion...," "in summary...," or "in closing...." These phrases can be useful, even welcome, in oral presentations. But readers can see by the tell-tale section heading and number of pages remaining to read, when an essay is about to end. You'll irritate your readers if you belabor the obvious.

Another Writing Tip

New Insight, Not New Information!

Don't surprise the reader with new information in your Conclusion that was never referenced anywhere else in the paper. If you have new information to present, add it to the Discussion or other appropriate section of the paper.  Note that, although no actual new information is introduced, the conclusion is where you offer your most "original" contributions in the paper; it's where you describe the value of your research, demonstrate your understanding of the material that you’ve presented, and locate your findings within the larger context of scholarship on the topic.

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What the data says about crime in the U.S.

A growing share of Americans say reducing crime should be a top priority for the president and Congress to address this year. Around six-in-ten U.S. adults (58%) hold that view today, up from 47% at the beginning of Joe Biden’s presidency in 2021.

We conducted this analysis to learn more about U.S. crime patterns and how those patterns have changed over time.

The analysis relies on statistics published by the FBI, which we accessed through the Crime Data Explorer , and the Bureau of Justice Statistics (BJS), which we accessed through the  National Crime Victimization Survey data analysis tool .

To measure public attitudes about crime in the U.S., we relied on survey data from Pew Research Center and Gallup.

Additional details about each data source, including survey methodologies, are available by following the links in the text of this analysis.

With the issue likely to come up in this year’s presidential election, here’s what we know about crime in the United States, based on the latest available data from the federal government and other sources.

How much crime is there in the U.S.?

It’s difficult to say for certain. The  two primary sources of government crime statistics  – the Federal Bureau of Investigation (FBI) and the Bureau of Justice Statistics (BJS) – paint an incomplete picture.

The FBI publishes  annual data  on crimes that have been reported to law enforcement, but not crimes that haven’t been reported. Historically, the FBI has also only published statistics about a handful of specific violent and property crimes, but not many other types of crime, such as drug crime. And while the FBI’s data is based on information from thousands of federal, state, county, city and other police departments, not all law enforcement agencies participate every year. In 2022, the most recent full year with available statistics, the FBI received data from 83% of participating agencies .

BJS, for its part, tracks crime by fielding a  large annual survey of Americans ages 12 and older and asking them whether they were the victim of certain types of crime in the past six months. One advantage of this approach is that it captures both reported and unreported crimes. But the BJS survey has limitations of its own. Like the FBI, it focuses mainly on a handful of violent and property crimes. And since the BJS data is based on after-the-fact interviews with crime victims, it cannot provide information about one especially high-profile type of offense: murder.

All those caveats aside, looking at the FBI and BJS statistics side-by-side  does  give researchers a good picture of U.S. violent and property crime rates and how they have changed over time. In addition, the FBI is transitioning to a new data collection system – known as the National Incident-Based Reporting System – that eventually will provide national information on a much larger set of crimes , as well as details such as the time and place they occur and the types of weapons involved, if applicable.

Which kinds of crime are most and least common?

Property crime in the U.S. is much more common than violent crime. In 2022, the FBI reported a total of 1,954.4 property crimes per 100,000 people, compared with 380.7 violent crimes per 100,000 people.  

By far the most common form of property crime in 2022 was larceny/theft, followed by motor vehicle theft and burglary. Among violent crimes, aggravated assault was the most common offense, followed by robbery, rape, and murder/nonnegligent manslaughter.

BJS tracks a slightly different set of offenses from the FBI, but it finds the same overall patterns, with theft the most common form of property crime in 2022 and assault the most common form of violent crime.

How have crime rates in the U.S. changed over time?

Both the FBI and BJS data show dramatic declines in U.S. violent and property crime rates since the early 1990s, when crime spiked across much of the nation.

Using the FBI data, the violent crime rate fell 49% between 1993 and 2022, with large decreases in the rates of robbery (-74%), aggravated assault (-39%) and murder/nonnegligent manslaughter (-34%). It’s not possible to calculate the change in the rape rate during this period because the FBI  revised its definition of the offense in 2013 .

The FBI data also shows a 59% reduction in the U.S. property crime rate between 1993 and 2022, with big declines in the rates of burglary (-75%), larceny/theft (-54%) and motor vehicle theft (-53%).

Using the BJS statistics, the declines in the violent and property crime rates are even steeper than those captured in the FBI data. Per BJS, the U.S. violent and property crime rates each fell 71% between 1993 and 2022.

While crime rates have fallen sharply over the long term, the decline hasn’t always been steady. There have been notable increases in certain kinds of crime in some years, including recently.

In 2020, for example, the U.S. murder rate saw its largest single-year increase on record – and by 2022, it remained considerably higher than before the coronavirus pandemic. Preliminary data for 2023, however, suggests that the murder rate fell substantially last year .

How do Americans perceive crime in their country?

Americans tend to believe crime is up, even when official data shows it is down.

In 23 of 27 Gallup surveys conducted since 1993 , at least 60% of U.S. adults have said there is more crime nationally than there was the year before, despite the downward trend in crime rates during most of that period.

While perceptions of rising crime at the national level are common, fewer Americans believe crime is up in their own communities. In every Gallup crime survey since the 1990s, Americans have been much less likely to say crime is up in their area than to say the same about crime nationally.

Public attitudes about crime differ widely by Americans’ party affiliation, race and ethnicity, and other factors . For example, Republicans and Republican-leaning independents are much more likely than Democrats and Democratic leaners to say reducing crime should be a top priority for the president and Congress this year (68% vs. 47%), according to a recent Pew Research Center survey.

How does crime in the U.S. differ by demographic characteristics?

Some groups of Americans are more likely than others to be victims of crime. In the  2022 BJS survey , for example, younger people and those with lower incomes were far more likely to report being the victim of a violent crime than older and higher-income people.

There were no major differences in violent crime victimization rates between male and female respondents or between those who identified as White, Black or Hispanic. But the victimization rate among Asian Americans (a category that includes Native Hawaiians and other Pacific Islanders) was substantially lower than among other racial and ethnic groups.

The same BJS survey asks victims about the demographic characteristics of the offenders in the incidents they experienced.

In 2022, those who are male, younger people and those who are Black accounted for considerably larger shares of perceived offenders in violent incidents than their respective shares of the U.S. population. Men, for instance, accounted for 79% of perceived offenders in violent incidents, compared with 49% of the nation’s 12-and-older population that year. Black Americans accounted for 25% of perceived offenders in violent incidents, about twice their share of the 12-and-older population (12%).

As with all surveys, however, there are several potential sources of error, including the possibility that crime victims’ perceptions about offenders are incorrect.

How does crime in the U.S. differ geographically?

There are big geographic differences in violent and property crime rates.

For example, in 2022, there were more than 700 violent crimes per 100,000 residents in New Mexico and Alaska. That compares with fewer than 200 per 100,000 people in Rhode Island, Connecticut, New Hampshire and Maine, according to the FBI.

The FBI notes that various factors might influence an area’s crime rate, including its population density and economic conditions.

What percentage of crimes are reported to police? What percentage are solved?

Most violent and property crimes in the U.S. are not reported to police, and most of the crimes that  are  reported are not solved.

In its annual survey, BJS asks crime victims whether they reported their crime to police. It found that in 2022, only 41.5% of violent crimes and 31.8% of household property crimes were reported to authorities. BJS notes that there are many reasons why crime might not be reported, including fear of reprisal or of “getting the offender in trouble,” a feeling that police “would not or could not do anything to help,” or a belief that the crime is “a personal issue or too trivial to report.”

Most of the crimes that are reported to police, meanwhile,  are not solved , at least based on an FBI measure known as the clearance rate . That’s the share of cases each year that are closed, or “cleared,” through the arrest, charging and referral of a suspect for prosecution, or due to “exceptional” circumstances such as the death of a suspect or a victim’s refusal to cooperate with a prosecution. In 2022, police nationwide cleared 36.7% of violent crimes that were reported to them and 12.1% of the property crimes that came to their attention.

Which crimes are most likely to be reported to police? Which are most likely to be solved?

Around eight-in-ten motor vehicle thefts (80.9%) were reported to police in 2022, making them by far the most commonly reported property crime tracked by BJS. Household burglaries and trespassing offenses were reported to police at much lower rates (44.9% and 41.2%, respectively), while personal theft/larceny and other types of theft were only reported around a quarter of the time.

Among violent crimes – excluding homicide, which BJS doesn’t track – robbery was the most likely to be reported to law enforcement in 2022 (64.0%). It was followed by aggravated assault (49.9%), simple assault (36.8%) and rape/sexual assault (21.4%).

The list of crimes  cleared  by police in 2022 looks different from the list of crimes reported. Law enforcement officers were generally much more likely to solve violent crimes than property crimes, according to the FBI.

The most frequently solved violent crime tends to be homicide. Police cleared around half of murders and nonnegligent manslaughters (52.3%) in 2022. The clearance rates were lower for aggravated assault (41.4%), rape (26.1%) and robbery (23.2%).

When it comes to property crime, law enforcement agencies cleared 13.0% of burglaries, 12.4% of larcenies/thefts and 9.3% of motor vehicle thefts in 2022.

Are police solving more or fewer crimes than they used to?

Nationwide clearance rates for both violent and property crime are at their lowest levels since at least 1993, the FBI data shows.

Police cleared a little over a third (36.7%) of the violent crimes that came to their attention in 2022, down from nearly half (48.1%) as recently as 2013. During the same period, there were decreases for each of the four types of violent crime the FBI tracks:

• Police cleared 52.3% of reported murders and nonnegligent homicides in 2022, down from 64.1% in 2013.
• They cleared 41.4% of aggravated assaults, down from 57.7%.
• They cleared 26.1% of rapes, down from 40.6%.
• They cleared 23.2% of robberies, down from 29.4%.

The pattern is less pronounced for property crime. Overall, law enforcement agencies cleared 12.1% of reported property crimes in 2022, down from 19.7% in 2013. The clearance rate for burglary didn’t change much, but it fell for larceny/theft (to 12.4% in 2022 from 22.4% in 2013) and motor vehicle theft (to 9.3% from 14.2%).

Note: This is an update of a post originally published on Nov. 20, 2020.

• Criminal Justice

John Gramlich is an associate director at Pew Research Center

8 facts about Black Lives Matter

#blacklivesmatter turns 10, support for the black lives matter movement has dropped considerably from its peak in 2020, fewer than 1% of federal criminal defendants were acquitted in 2022, before release of video showing tyre nichols’ beating, public views of police conduct had improved modestly, most popular.

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SpaceX Dragon Set to Return from ISS Carrying Critical Science Experiments

O n Sunday, April 28, SpaceX Dragon is scheduled to depart the International Space Station (ISS), bringing with it a cargo of scientific samples and hardware. NASA, together with its international partners, is eagerly anticipating the return of this vital research material, weather conditions permitting.

NASA’s live coverage of the undocking procedures will commence at 12:45 p.m. EDT, accessible on NASA+ , NASA Television, the NASA app, YouTube , and the agency’s official website. Stream the event across various platforms, including social media, to ensure you don’t miss a moment of this significant event.

The departure sequence will start at 1:05 p.m. when the Dragon spacecraft, after receiving the go-signal from SpaceX’s ground control in Hawthorne, California, detaches from the Harmony module’s zenith port and propels itself away from the ISS.

Since its arrival at the space station on March 23, Dragon has been a vital conduit of over 6,000 pounds of supplies including crew provisions, research investigations, and station hardware following its March 21 launch from NASA’s Kennedy Space Center.

Upon re-entry to Earth’s atmosphere, Dragon will target a splashdown point off Florida’s coast. While the splashdown will not be broadcasted, NASA will post updates via the space station blog .

The Dragon is expected to return over 4,100 pounds of cargo, including scientific experiments that have taken advantage of the ISS’s unique microgravity environment. The proximity of the splashdown site to Florida expedites the delivery to NASA’s Space Systems Processing Facility at Kennedy Space Center, minimizing gravity exposure for the retrieved samples.

Noteworthy among the returning experiments is the Flawless Space Fibers-1, a study that successfully manufactured significant lengths of optical fiber in space, including a single-day record. The GEARS experiment monitored antibiotic-resistant organisms on the station, contributing to astronaut health and safety knowledge for longer missions. MISSE-18 assessed the impact of space on various materials, while Immune Cell Activation may inform future medical treatments for diseases and conditions like melanoma.

Such experiments are part of the hundreds of ongoing investigations at the ISS, which span diverse fields such as biology, biotechnology, and Earth and space science. These studies empower the health and safety of astronauts in space and underpin the technologies for exploration missions to the Moon and Mars under NASA’s Artemis program.

To keep updated with the latest news and features from the ISS, follow its presence on platforms like Instagram , Facebook , and Twitter .

Discover more about the ISS at this centralized link:

https://www.nasa.gov/international-space-station/

Contact information for further enquiries:

Josh Finch / Claire O’Shea

Headquarters, Washington

202-358-1100

[email protected] / claire.a.o’[email protected]

Sandra Jones

Johnson Space Center, Houston

281-483-5111

[email protected]

FAQ Section

What time will the SpaceX Dragon undock from the ISS?

The undocking is scheduled for 1:05 p.m. EDT on Sunday, April 28.

Will NASA broadcast the Dragon splashdown?

No, the splashdown will not be broadcasted, but updates will be available on NASA’s space station blog.

How much cargo is Dragon bringing back to Earth?

Over 4,100 pounds of supplies and scientific experiments will return to Earth with Dragon.

How can I watch the undocking event?

You can watch the coverage on NASA+, NASA Television, the NASA app, YouTube, or NASA’s website.

What is the significance of experiments like Flawless Space Fibers-1?

This experiment and others like it are significant for demonstrating the potential for manufacturing and scientific research in microgravity, which has implications for future space missions and industries on Earth.

The return of SpaceX Dragon from the ISS represents more than just the conclusion of another successful mission; it is a testament to the ongoing collaboration between NASA and its partners to push the boundaries of space research and exploration. As the scientific community awaits the return of invaluable experiments conducted in microgravity, NASA continues to foster advancements that will benefit humanity both on Earth and as we reach toward new horizons in space.

• Open access
• Published: 18 April 2024

The endothelium: gatekeeper to lung ischemia-reperfusion injury

• Huy Q. Ta 1 ,
• Maniselvan Kuppusamy 2 ,
• Swapnil K. Sonkusare 2 , 3 ,
• Mark E. Roeser 1 &
• Victor E. Laubach 1  

Respiratory Research volume  25 , Article number:  172 ( 2024 ) Cite this article

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The success of lung transplantation is limited by the high rate of primary graft dysfunction due to ischemia-reperfusion injury (IRI). Lung IRI is characterized by a robust inflammatory response, lung dysfunction, endothelial barrier disruption, oxidative stress, vascular permeability, edema, and neutrophil infiltration. These events are dependent on the health of the endothelium, which is a primary target of IRI that results in pulmonary endothelial barrier dysfunction. Over the past 10 years, research has focused more on the endothelium, which is beginning to unravel the multi-factorial pathogenesis and immunologic mechanisms underlying IRI. Many important proteins, receptors, and signaling pathways that are involved in the pathogenesis of endothelial dysfunction after IR are starting to be identified and targeted as prospective therapies for lung IRI. In this review, we highlight the more significant mediators of IRI-induced endothelial dysfunction discovered over the past decade including the extracellular glycocalyx, endothelial ion channels, purinergic receptors, kinases, and integrins. While there are no definitive clinical therapies currently available to prevent lung IRI, we will discuss potential clinical strategies for targeting the endothelium for the treatment or prevention of IRI. The accruing evidence on the essential role the endothelium plays in lung IRI suggests that promising endothelial-directed treatments may be approaching the clinic soon. The application of therapies targeting the pulmonary endothelium may help to halt this rapid and potentially fatal injury.

Introduction

While lung transplant rates continue to rise annually, the outcomes of lung transplantation are the worst of any solid organ transplant [ 1 ]. Approximately 50% of patients die within 5 years of transplant, and ~ 67% within 10 years, despite progress in lung preservation, surgical management and immuno-suppression therapies [ 2 ]. The success of lung transplantation is limited by a high rate of primary graft dysfunction (PGD) due to ischemia-reperfusion injury (IRI), which is a rapid and complex sterile inflammatory response characterized by dramatic elevations of extracellular adenosine triphosphate (ATP), oxidative stress, robust innate immune responses, rapid and potent release of proinflammatory signals, vascular permeability, edema, and endothelial and epithelial barrier dysfunction after transplant [ 3 , 4 , 5 , 6 ].

Lung IRI not only leads to PGD after transplantation, but IRI is also a risk factor for chronic lung allograft dysfunction, the major cause of mortality in recipients [ 7 , 8 ]. 29% of transplant patients with IRI will die within 90 days, compared to 5% of recipients without [ 9 ]. Furthermore, those transplant patients with IRI and PGD will experience protracted mechanical ventilation and inpatient hospital care, as well as increased risk of multi-organ failure [ 10 ]. Currently no therapeutic agents are clinically available to prevent IRI, and treatment strategies are limited to maintaining function.

The pulmonary endothelium is a primary target of IRI, and a key hallmark of IRI is endothelial cell (EC) dysfunction, which leads to increased pulmonary fluid accumulation (edema), impaired gas exchange, and decreased lung compliance [ 11 ]. IR stimulates the production of proinflammatory chemokines, cytokines, damage-associated molecular patterns (DAMPs), and reactive oxygen species (ROS) from a variety of cells including ECs, resulting in EC swelling and detachment from the basement membrane. This EC-mediated inflammatory response results in increased vascular permeability, which in turn activates innate immune cells and promotes leukocyte adherence and transmigration. Furthermore, these immune cells release additional inflammatory mediators that further damages the endothelium, ultimately leading to lung injury and graft failure. The leukocyte-endothelial interface is regulated by a complex signaling network of proteins, enzymes, receptors, and channels that perform crucial functions in the endothelium. While the mechanisms of lung IRI are not fully understood, a plethora of studies have determined that EC injury plays a critical role, and many of the regulators that influence endothelial dysfunction and IRI have been identified, providing promising therapeutic strategies to prevent IRI (Fig.  1 ). Therefore, in this review, we discuss the impact that the endothelium has on lung IRI, with a focus on the more recent and targetable mediators of EC dysfunction. We also present potential clinical strategies for targeting the endothelium for the treatment of IRI.

Endothelial events leading to lung IRI . Reperfusion can increase fluid shear stress and activate mechanosensitive Piezo1 channels at the cell membrane. Piezo1 channels are a crucial Ca 2+ entry pathway in endothelial cells. IR also increases extracellular ATP levels in the lung via Panx1 channels. Extracellular ATP can activate purinergic receptors, further increasing cytosolic Ca 2+ levels. ATP activation of purinergic P2Y2 receptors (P2Y2R) leads to increased activity of TRPV4 channels, another mechanically activated Ca 2+ entry pathway on endothelial cell membrane. FFA transporter CD36 elevates cytosolic FFA levels, in turn increasing Ca 2+ influx and ROS production and triggering a cytokine storm. These pro-inflammatory intracellular signaling events dismantle intercellular junctions and promote neutrophil infiltration, increased capillary fluid extravasation, and lung edema formation. Glycocalyx masks the endothelial surface adhesion molecules (ICAM, VCAM, P- and L-selectin) and has a protective effect against IR-mediated deleterious events. Integrins at the cell surface are also involved in increased vascular permeability after IR. IEL, internal elastic lamina; FFA, Free fatty acid; CD36, Cluster of differentiation 36

Endothelium

The vascular endothelium was once believed to be an inactive, stagnant structure. However, it is now appreciated as a highly specialized metabolically active organ that modulates several fundamental physiological, immunological, and synthesizing processes, such as leukocyte extravasation, intravascular clotting, vasomotor tone, inflammation, barrier permeability, production of chemokines, cytokines, growth factors, and ROS, as well as expression of receptors, signaling molecules, and adhesion molecules [ 12 , 13 , 14 , 15 ]. Lining the innermost layer of blood vessels, the vascular endothelium consists of a monolayer of mesenchyme-derived ECs, subcellular extracellular matrix (ECM) proteins, and lumenal glycocalyx. The glycocalyx structure functions as a permeable barrier segregating blood from lung tissue, regulating trafficking of proteins, nutrients, leukocytes, and fluids [ 16 , 17 ]. Furthermore, components within the EC membrane can also modulate intracellular signaling pathways that regulate fundamental biological functions, such as metabolism, gene expression, and cell structure, by sensing changes in fluid shear stress and hemodynamic pressure [ 18 , 19 ].

The integrity of the endothelium is regulated by intercellular junctions (tight junctions and adherens junctions) between neighboring ECs [ 16 ]. These junctions maintain barrier function and modulate signal transduction through interactions with cytoskeletal microtubules and actin microfilaments in response to forces exerted on the endothelium [ 20 ]. Cell surface integrins connect the monolayer of ECs at focal adhesion plaques. Although the integrity of the endothelium depends on both tight and adherens junctions, vascular permeability and subsequent edema develops mainly as a result of dysfunction of tight junctions [ 12 ]. Since interendothelial junctions are also covered by the endothelial glycocalyx, dysfunction of the glycocalyx can also cause leakage [ 21 ].

Given its roles in mechanosensation, secretion, and metabolism, it is not surprising that the endothelium is highly vulnerable to the damaging effects of IR [ 3 ]. Ischemia initiates a proinflammatory response within the endothelium that primes and sensitizes it to additional injury upon reperfusion, where a robust local and systemic inflammatory response extensively damages the integrity of the endothelial barrier through the formation of gaps and expression of transmembrane ion channels. Oxidative stress, ROS, and reactive nitrogen species (RNS) from ECs and transmigrating leukocytes recruited to the endothelium are major contributors to the degradation of the endothelium and EC dysfunction [ 22 ].

Mechanotransduction is the process that translates forces sensed by mechanosensors into biological signaling to modulate gene expression driving a multitude of cellular processes, including cell migration, proliferation, and differentiation. The endothelium converts mechanical forces into biological signals that trigger intracellular signaling pathways through the endothelial surface glycocalyx, activation of ion channels, receptor and nonreceptor kinases, and membrane-associated protein complexes [ 19 ].

The glycocalyx, a negatively charged extracellular layer of proteoglycans, glycoproteins, glycosaminoglycans, heparan sulfate, hyaluronic acid, and syndecans lining the luminal surface of ECs, is highly important in endothelial function, as it plays a role in many physiological processes, such as endothelial barrier function, oxidative stress, and inflammation [ 22 , 23 , 24 , 25 , 26 ]. Accessibility of macromolecules to the EC surface is regulated by the overall charge distribution and structural conformation of the glycocalyx [ 24 , 27 ]. Furthermore, the depth of the glycocalyx masks the interaction of leukocytes and plasma proteins with EC surface adhesion molecules, such as intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), as well as P- and L-Selectin. The presence of extracellular superoxide dismutase in the glycocalyx protects ECs from oxidative stress damage by quenching oxygen radicals and maintaining nitric oxide (NO) bioavailability [ 23 ]. Moreover, the glycocalyx can modulate an inflammatory response by binding or excluding certain cytokines, thereby providing or preventing access to cell surface receptors [ 23 , 28 , 29 ]. Thus, all these physiological functions of the glycocalyx contribute to the health of the endothelium and vascular homeostasis.

Damage to the glycocalyx occurs during IRI and contributes to endothelial dysfunction and barrier disruption [ 30 , 31 , 32 , 33 ]. Under normal conditions, the glycocalyx is continuously turned over, as the rate of synthesis of components of the glycocalyx equals the rate of degradation. However, IR drives the equilibrium towards degradation and shedding, thereby leading to the rapid dismantling of the glycocalyx and obstructing glycocalyx function [ 22 , 23 , 34 ]. In fact, degradation of the glycocalyx may be the earliest form of structural damage after IR [ 35 , 36 ]. By measuring increasing levels of components of the glycocalyx, syndecan-1 and heparan sulfate, in blood at different timepoints from patients undergoing surgery of the ascending aorta with global ischemia or regional ischemia, Rehm and colleagues were the first to present evidence of IRI-mediated endothelial glycocalyx shedding in humans [ 37 ]. Furthermore, higher concentrations of syndecan-1 and heparan sulfate were also observed in coronary effluent from guinea pig hearts exposed to hypoxia-reoxygenation, thereby supporting a role for IRI in the degradation of the glycocalyx [ 38 ]. Sladden et al. showed that the presence of elevated endothelial glycocalyx breakdown products in donor lungs for transplant was associated with poor pulmonary function, reduced acceptability for lung transplant, and PGD in transplant recipients [ 39 ]. Vascular sites with deteriorated glycocalyx are more susceptible to proinflammatory effects [ 22 ].

Loss of the glycocalyx exposes cellular adhesion molecules, thus increasing leukocyte adhesion and vascular permeability with subsequent edema formation. Treatment with hydrocortisone or antithrombin III prior to IR significantly decreased the shedding of glycocalyx constituents, syndecan-1 and heparan sulfate, and inhibited the adhesion of neutrophils, thus protecting the vascular endothelium against IRI [ 40 ]. In addition, Annecke and colleagues demonstrated that protection of the endothelial glycocalyx from IRI was achieved by an inhalational anesthetic gas given before ischemia or during reperfusion [ 41 ]. This group showed that Sevoflurane preconditioning and postconditioning attenuated the release of markers of glycocalyx shedding through the inhibition of lysosomal cathepsin B secretion and preserved the structure of the glycocalyx in guinea pig hearts exposed to IR, thus proposing that Sevoflurane protected the glycocalyx from IR-mediated damage [ 41 ]. In a study comparing patients anesthetized with sevoflurane or propofol during lung resection surgery with one lung ventilation, Kim et al. discovered that the protective effects on the glycocalyx provided by sevoflurane was similar to that supplied by the intravenous anesthetic propofol [ 42 ].

Disruption of the glycocalyx contributes to neutrophil activation and adhesion, a hallmark of IRI. Neutrophils contain proteases, elastase, and proteinase-3 that degrade certain components of the glycocalyx, and the destruction of the endothelial glycocalyx has been associated with increased vascular permeability, leukocyte adhesion, and inflammation in the lungs [ 43 , 44 ]. Pretreatment of guinea pig hearts subjected to 20 min of warm ischemia and 10 min of reperfusion with sevoflurane maintained the endothelium by reducing the shedding of glycocalyx constituents, which masked the adhesion molecules required for neutrophil binding [ 45 ]. Casanova and colleagues were the first to show that sevoflurane preconditioning before IRI preserved the pulmonary glycocalyx by attenuating the expression of inflammatory chemokines (MCP-1, MIP-1, and MIP-2) and leukocyte adhesion molecules (ICAM-1 and VCAM-1) in an in vivo lung autotransplant model [ 35 ]. Using a porcine lung autotransplant model, this group also demonstrated that continuous intravenous administration of lidocaine protected lungs from glycocalyx shedding, as they observed that the effects of IRI (i.e. decreased levels of syndecan-1 and heparan sulfate in lung tissue; elevated glycocalyx markers and adhesion molecules in blood; elevated levels of adhesion molecules and neutrophil activation) were significantly lower in the lidocaine cohort [ 36 ]. Moreover, mice treated with recombinant human vimentin (rhVim) prior to endotoxin exposure had significantly lower histologic acute lung injury scores compared to control mice [ 46 ]. In vitro adhesion and binding assays demonstrated that rhVim protected the vascular endothelium from neutrophil adhesion and infiltration by binding P-selectin and obstructing the interaction between P-selectin and P-selectin glycoprotein ligand-1 [ 46 ]. Although the exact mechanisms underlying glycocalyx destruction are not fully understood, these studies support a significant role for endothelial glycocalyx in IRI.

• Ion channels

Over the past decade, research has been focused on mechanosensitive ion channels, including transient receptor potential (TRP) channels and piezo channels, as potential mediators of IRI. TRP channels are non-selective transmembrane cation channels that regulate Ca 2+ influx and signaling in the pulmonary endothelium, among other cells [ 47 ]. Activated by a number of stimuli, including sheer stress, mechanical stretch, pH, temperature, ROS, extracellular ATP, inflammatory cytokines, and membrane potential changes, the TRP family consists of seven subtypes: TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPML (mucolipin), TRPP (polycystin), TRPA (ankyrin), and TRPN (nitric oxide-mechanoreceptor potential C) [ 4 , 48 , 49 ]. Lung ECs primarily express TRPC, TRPV, TRPM, and TRPP channels.

Evidence from multiple studies demonstrates that a major contributor to lung IRI is the dysregulation of mechanotransduction-mediated TRP channels. Ca 2+ influx through seven members of TRPC subfamily (TRPC1-7) can activate myosin light chain kinase (MLCK), inhibit cAMP generation, and reorganize cytoskeletal structures, resulting in increases in endothelial permeability, endothelial barrier failure, endothelial contraction, and subsequent extravasation of plasma macromolecules and immune cells [ 47 , 48 , 50 , 51 ]. For example, during the early stages of lung IRI, the rise in intracellular Ca 2+ concentration and NADPH oxidase 2 (NOX2)-derived ROS in ECs activates TRPC6, causing cell morphology changes and increasing endothelial leakage, ultimately resulting in pulmonary edema [ 50 , 52 , 53 ]. Stable lung weights and capillary filtration coefficient values from TRPC6 knockout mice before and after IR demonstrated that these mice were protected from IR-induced pulmonary edema [ 52 ]. Here, the specific contribution of TRPC6 to pulmonary oedema was underlined by the fact that lungs from TRPC1- and TRPC4-deficient mice were not protected from increased vascular permeability caused by IR. Furthermore, this study demonstrated that NOX2-generated ROS and phospholipase C-g-generated diacylglycerol precedes TRPC6 activation and IRI [ 52 ].

The TRPV subfamily consists of six members (TRPV1-6), of which TRPV4 is the most researched channel and has been discovered to be a crucial player in the regulation of lung endothelial barrier integrity [ 54 , 55 ]. TRPV4 channels are expressed in many cell types in the lung, including ECs, alveolar epithelial cells, macrophages, and neutrophils [ 56 ], and can be activated by many forces, such as temperature, membrane stretch, oxidative and sheer stress, among others [ 19 ]. Recent studies now indicate that TRPV4 channels on ECs, immune cells, and alveolar epithelial cells mediate acute lung injury [ 57 ]. Studies have described TRPV4 channels being involved in oxidative stress-induced endothelial barrier failure in that H 2 O 2 exposure induces Ca 2+ influx through TRPV4 channels in murine and human lung microvascular ECs in a Fyn-dependent manner, resulting in increased endothelial permeability [ 58 ]. Using the TRPV4 agonist GSK1016790A at doses that induce injury, Villalta and colleagues observed that lung edema (total protein in bronchoalveolar lavage (BAL) fluid and lung wet-to-dry weight ratio) increased in wild-type mice [ 59 ]. Furthermore, TRPV4 activation increased protein levels of the active forms of matrix metalloproteinase 2 (MMP2) and MMP9 along with decreased expression of tissue inhibitor of metalloproteinase 2 (TIMP2), an endogenous MMP inhibitor. This was the first evidence linking the downstream effectors MMP2 and MMP9 to TRPV4-induced increases in lung permeability and edema. These data indicated that TRPV4-mediated Ca 2+ influx elicited the activation of MMP2 and MMP9, which contributed to barrier permeability.

Our group demonstrated that endothelial cell-specific TRPV4 knockout mice as well as inhibition of TRPV4 in wild-type mice with GSK2193874 resulted in attenuation of lung dysfunction and edema following IR as demonstrated by improved oxygenation and compliance, and decreased edema, neutrophil infiltration, and proinflammatory cytokine expression [ 60 ]. This study was the first to demonstrate a role for endothelial TRPV4 in mediating edema after lung IR and highlighted the potential use of TRPV4 inhibitors as a therapeutic strategy to prevent lung IRI. Furthermore, the attenuation of proinflammatory cytokines in endothelial cell-specific TRPV4-deficient mice after IR [ 60 ] suggests that endothelial TRPV4 channels are important mediators of vascular inflammation and endothelial barrier disruption after IR.

The TRPM subfamily is a group of oxidant-activated cation channels that consists of eight members (TRPM1-8), of which TRPM2 is highly expressed in ECs. TRPM2 mediates Ca 2+ entry in response to intracellular ADP-ribose that is generated during oxidative stress [ 61 ]. In human pulmonary artery ECs, H 2 O 2 induces Ca 2+ influx through TRPM2 channels, resulting in increased endothelial permeability [ 62 ]. Conditional knockout of endothelial TRPM2 in mice reduced transmigration and sequestration of neutrophils in lungs following lipopolysaccharide (LPS) challenge [ 63 ]. Although less is known about the role of TRPM2 in lung IRI, Zhong et al. demonstrated a crucial role for TRPM2-mediated ferroptosis in hepatic IRI and that pharmacological inhibition of TRPM2 may provide an effective therapeutic strategy to attenuate hepatic IR injury [ 64 ]. In addition, Khanahmad et al. showed that TRPM2 deficient mice are resistant to renal IRI and that TRPM2 channels are activated by ROS and cyclic adenosine diphosphate ribose (cADPR) generated during renal IRI [ 65 ]. These data suggest that TRPM2 channels in ECs actively mediate endothelial barrier integrity by facilitating Ca 2+ influx by ECs and promoting the transmigration of neutrophils across the endothelium during IRI.

While TRP channels mediate Ca 2+ influx into cells, not all Ca 2+ influx occurs via TRP channels. Discovered in 2010, Piezo channels are non-selective cation channels that open in response to mechanical forces to allow the influx of cations, where PCa > PNa = PK [ 66 ]. Piezo channels respond to stimuli directly (e.g. mechanical stretch, chemical agonists), as well as indirectly (via other channels and upstream signals) [ 67 ]. Humans have two Piezo genes, PIEZO1 and PIEZO2 , and the resulting proteins share approximately 50% amino acid identity. In lungs, Piezo1 channels are highly expressed in pulmonary microvascular ECs as well as alveolar epithelial cells, and Piezo2 channels are highly expressed in airway-innervating sensory neurons [ 68 , 69 ]. Three main signaling pathways have been identified downstream of Piezo1: ATP-purinergic P2X/P2Y receptors [ 70 ], Ca 2+ -dependent calpain signaling [ 71 ], and Ca 2+ -dependent TRPV4 signaling [ 72 ]. These pathways play important roles in cellular function, cell-cell communication, cell cycle progression, proliferation, apoptosis, and angiogenesis.

Endothelial Piezo1 channels have been recently shown to play a role in endothelial barrier integrity. Jiang et al. showed that high tidal volume ventilation produces excessive mechanical stretch that drastically increases the influx of Ca 2+ through endothelial Piezo1 channels, which activates calpain signaling and promotes pulmonary endothelial hyperpermeability and edema as a result of the internalization and breakdown of VE-cadherin junctions [ 73 ]. Friedrich and colleagues used endothelial Piezo1-deficient mice to demonstrate that lung vascular hyperpermeability following increased capillary pressure is the result of Piezo1 activation and the breakdown of lung endothelial adherens junctions (AJs) and opening of paracellular routes [ 69 ]. Furthermore, the endothelial barrier was disrupted through Piezo1-dependent activation of calpain and subsequent proteolysis of VE-cadherin, b-catenin, and p120-catenin. Zhong et al. identified a novel adaptive role of EC-expressed Piezo1 in stabilizing the lung endothelial barrier in response to alveolar stretch [ 69 ]. They demonstrated that activation of Piezo1 channels in ECs elicited calcium signaling and activated calpain which cleaves Src tyrosine kinase, consequentially suppressing Src-mediated VE-cadherin phosphorylation, thereby preventing VE-cadherin internalization from AJs. Tyrosine phosphorylation of adhesion molecules by tyrosine kinases including Src may induce disassembly of catenin-cadherin complexes and microtubules [ 74 , 75 ]. These findings uncovered an adaptive feedback regulation by which alveolar stretch-induced Piezo1 activation in ECs preserves the lung endothelial barrier function. Although the role of Piezo1 in IRI has not been well studied, Guo et al. hypothesized that PIEZO1 may be involved in cerebral ischemia-reperfusion injury through ferroptosis regulation [ 76 ].

Purinergic receptors

During inflammatory injury such as IRI, cell surface pannexin 1 (Panx1) channels rapidly release ATP, a DAMP molecule, into the extracellular space, where the pro-inflammatory actions of extracellular ATP are exerted by members of the purinergic P2 receptor family such as P2X7 and P2Y2 receptors [ 4 , 77 ]. A study by Sugimoto et al. in 2009 was the first to demonstrate a role of extracellular ATP in lung IRI by showing that recipient animals treated with apyrase, which hydrolyzes ATP, resulted in significant attenuation of lung IRI and vascular injury after transplantation [ 78 ]. Our laboratory recently showed that endothelial Panx1 knockout mice, and wild type mice treated with Panx1 inhibitor, are protected against vascular permeability, inflammation, and edema after lung IR, suggesting that endothelial Panx1 and efflux of ATP play important roles in the pathogenesis of lung IRI [ 79 ].

Our laboratory recently used tamoxifen-inducible, endothelial-specific purinergic P2Y2 receptor (P2Y2R), Panx1, and TRPV4 knockout mice in combination with in vivo, ex vivo, and in vitro models of IR to show that lung IR induces endothelial Panx1 channel-mediated efflux of ATP, which then activates endothelial P2Y2R signaling. In turn, this P2Y2R activation stimulated endothelial TRPV4 channel activity, resulting in endothelial barrier disruption, lung edema, leukocyte infiltration, and lung dysfunction after IR [ 80 ]. Our finding that endothelial knockout of P2Y2R reduced the expression of inflammatory cytokines in lungs after IR suggests that the endothelium may also be a source of inflammatory cytokines in lung IRI. Another possibility is that P2Y2R knockout preserves the endothelial barrier after IR, thereby dampening overall inflammation and activation of innate immune cells. This study and those described above suggest that inhibitors of components of the Panx1-P2Y2R-TRPV4 signaling axis on endothelium may be an effective therapeutic strategy to prevent or treat lung IRI via preservation of endothelial barrier function, which supports future studies toward eventual translation of these therapies to human lung transplant patients.

Kinase signaling

Intracellular signaling pathways involving kinases in ECs have been indicated to play critical roles in IRI, where the generation of ROS and rise in intracellular Ca 2+ through Ca 2+ influx from plasma membrane ion channels have been shown to promote endothelial permeability and dysfunction [ 81 , 82 , 83 ]. The Src tyrosine kinase family member Fyn associates with the fatty acid transporter CD36 in the endothelium [ 81 ]. In addition to serving as a membrane anchor for kinase activation, data suggests that CD36 also plays a critical role in Ca 2+ signaling, where loss of CD36 attenuates Ca 2+ influx following thapsigargin-induced store depletion [ 84 ]. CD36 also plays an important role in ROS and Ca 2+ signaling in the lung microvasculature. CD36 gene deficiency led to a significant attenuation of H 2 O 2 -induced Ca 2+ influx and endothelial permeability in vitro as well as protection from lung IRI in vivo [ 85 ]. These findings suggest that loss of CD36 protects against lung IRI, likely due to CD36-mediated changes in H 2 O 2 -induced Ca 2+ influx. Furthermore, the mechanism by which CD36 participates in this process may be by acting as a membrane scaffold for Fyn, allowing for the interactions between Fyn and TRPV4 to facilitate the phosphorylation and activation of TRPV4 in response to oxidative stress. Inhibition of another Src family member, c-Abl, protected against IRI by attenuating oxidative stress-induced endothelial barrier dysfunction and inflammation [ 86 ]. In an ex vivo IR model, lungs from New Zealand White rabbits demonstrated significantly better oxygenation and wet:dry weight ratio following IR and imatinib treatment, which inhibits c-Abl [ 86 ]. Moreover, there was remarkably less total protein in BAL fluid and infiltrating neutrophils in imatinib-treated lungs, and imatinib also abrogated DNA double-strand breaks and p53 upregulation after IR. Together, these data highlight the potential role of Src family kinases as IRI biomarkers and therapeutic targets.

Recent studies reported that p38 mitogen-activated protein kinase (MAPK) plays a role in the development of lung IRI by mediating lung endothelial barrier dysfunction. After treatment with a p38 MAPK inhibitor SB203580, left lungs of rats showed remarkably less alveolar wall thickening and inflammatory cell infiltration in an in vivo lung IRI model [ 87 ]. In addition, p38 MAPK inhibition attenuated total protein levels in BAL fluid and Evans blue dye staining, indicating that SB203580 diminished endothelial leakage after IRI. Furthermore, Western blot and immunofluorescence revealed that inhibition of p38 MAPK partially reversed the IR-induced disruption of the endothelial barrier, as expression of zonula occludens 1 (ZO-1, a key junction protein) and VE-cadherin (a critical endothelial adhesion molecule) were downregulated while ICAM-1 was upregulated [ 87 ]. Furthermore, in an in vitro IR model of lung transplantation, knockdown of p38 MAPK with small interfering RNAs in rat PMVECs reduced oxidative injury associated with inflammation, apoptosis, and cell cycle arrest [ 88 ]. Wang and colleagues demonstrated that the protective effects of p38 MAPK inhibition on IRI were enhanced when c-Jun NH 2 -terminal protein kinase was knockdown in rat PMVECs as well [ 89 ]. These studies suggest that the inhibition of p38 MAPK signaling could mitigate lung IRI-induced endothelial damage.

Sphingosine 1-Phosphate (S1P) is a sphingolipid that acts as a bioactive signal transducer, mediating intra- and extracellular signaling pathways that control endothelial barrier integrity, proliferation, cell survival, and immune cell migration [ 90 ]. ECs are the major source of S1P in the lungs [ 91 ]. Treatment of rat lung recipients with S1P prior to lung transplantation significantly improved oxygenation and lung graft wet:dry ratios compared to control recipients [ 92 ]. Furthermore, S1P treatment prevented neutrophil accumulation, reduced NF-κB-mediated proinflammatory cytokine levels (TNF-α, IL-1β, and MIP-2), and blunted the activation of Akt, p38, and JNK, indicating that S1P abrogated IRI after lung transplantation through the reduction of vascular permeability, neutrophil infiltration, proinflammatory cytokines, and EC apoptosis [ 92 ]. Our group showed that S1P-mediated protection from IRI signaled through the G-protein-coupled receptor, S1P receptor 1 (S1PR1), since a selective S1PR1 agonist, VPC01091, attenuated lung IRI and preserved endothelial barrier in mice [ 93 ]. In addition, our group found that modifying the S1P gradient (higher circulating S1P, lower tissue S1P) through the combination of S1P and sphingosine kinase 2 inhibition during ex vivo lung perfusion (EVLP) significantly improved lung compliance and vascular permeability in a murine lung IRI model [ 94 ]. While S1P and its analogues have been shown to reduce vascular leakage in small and large animal lung injury models [ 92 , 93 , 94 , 95 , 96 ], the clinical application is currently limited by systemic toxicity, as prolonged exposure to S1P agonists worsen vascular leakage and promote fibrosis [ 97 ]. Design of safer analogues with promising preclinical data will be required.

Rho-associated coiled-coil containing protein kinase 1 (ROCK1) is a serine/threonine kinase that is the downstream effector of the small GTPase Rho and negative regulator of endothelial barrier function [ 98 ]. In a rat lung transplant model, flushing the donor lungs with the ROCK1 inhibitor, Y-27632, prevented inflammatory cells from invading the alveolar space and decreased TNF-α levels in BAL fluid, leading to reduced pulmonary edema [ 99 ]. Furthermore, inhibition of ROCK1 by miR-144 mimetics resulted in the downregulation of ROCK1 and downstream target myosin phosphatase-targeting subunit 1 [ 100 ]. These events favor the inactivation of myosin light chain kinase, thereby stabilizing the endothelial barrier and limiting vascular leakage during lung injury. Thus, these data illustrate the important role that ROCK1 plays in the pathogenesis of lung IRI and endothelial barrier disruption.

Integrins, a family of cell surface receptors consisting of 24 members, each containing a single α subunit and single β subunit, regulate cellular proliferation, migration, cytokine secretion, and signaling, and thereby play critical roles in cell growth, apoptosis, inflammation, and endothelial barrier integrity [ 101 , 102 ]. These receptors link the intracellular cytoskeleton with the ECM, and thus transduce external and internal mechanochemical signals across the plasma membrane upon activation after ligand binding [ 101 ]. Several studies have shown that blockade of integrin αVβ5 with inhibitory monoclonal antibodies specifically prevented increases in lung vascular permeability, which has been considered a hallmark of lung injury that is largely responsible for its characteristic pulmonary edema formation. Su et al. demonstrated that both αVβ5 genetic deletion and blocking antibody (ALULA) prevented vascular permeability after IRI in rats [ 103 ]. Furthermore, treatment of donor lungs with ALULA significantly decreased extravascular lung water, neutrophil infiltration and total protein in BAL fluid, and improved arterial oxygenation, suggesting that αVβ5 blockade prevented IRI following transplantation [ 104 ]. Zhang and colleagues examined the role of αVβ5 in IR-induced endothelial cell apoptosis and autophagy and found that αVβ5 inhibition with ALULA reduced cell permeability and cleaved caspase-3 expression after IR [ 105 ]. Moreover, ALULA treatment enhanced endothelial autophagy levels, which was reflected in the increase in LC3-II expression and decrease in p62 levels [ 105 ]. Together, these data indicated that αVβ5 inhibition mitigates IR-induced endothelial cell apoptosis, leading to attenuation of lung IRI.

Current Therapeutics

Considerable research effort has been focused on a better understanding of the molecular mechanisms that cause lung endothelial barrier failure after IR in order to identify therapeutic targets to treat or prevent IRI. One of the endothelial protection methods that is often implemented in many transplantation clinics to reduce lung IRI and improve lung function is the “controlled reperfusion” or regulated reestablishment of blood flow during the early stages of reperfusion, combined with controlled ventilation to prevent hypercapnia [ 106 , 107 ]. Several novel strategies have emerged over the past years which show considerable promise for preservation or reconstitution of endothelial barrier function in vitro and in preclinical trials. However, there are no current therapeutic agents yet clinically available to prevent or treat IRI, and treatment strategies are limited to maintaining lung function (Table  1 ).

Since IRI involves glycocalyx damage, several therapeutics have been investigated, either targeted to the prevention of glycocalyx injury or restoration of the ultrastructure of the endothelium. Sevoflurane is an anesthetic and potent vasodilator that protects the endothelium following IR. Blood from sevoflurane-anesthetized pigs subjected to IRI (induced by a balloon catheter in the thoracic aorta) had low levels of negatively charged heparan sulfate compared to blood from propofol-anesthetized pigs, signifying a healthy glycocalyx [ 108 ]. In an in vivo lung autotransplant model in pigs, sevoflurane pretreatment preserved the pulmonary glycocalyx, reduced serum levels of heparan sulfate and syndecan, and decreased expression of adhesion molecules and chemokines [ 35 ].

A phase I clinical trial demonstrated mortality benefit in acute respiratory distress syndrome treated with interferon-β-1a [ 109 ]. The proposed mechanisms of benefit were modulation of inflammation (possibly neutrophil endothelial interactions) and endothelial barrier function via CD73-mediated dephosphorylation of AMP. While non-randomized, the mortality benefit (24% absolute reduction) in this study suggests that targeting the lung endothelium may hold promise as a viable therapeutic strategy in IRI.

An increase in intracellular calcium not only increases the permeability of ECs, but also contributes to neutrophil activation and EC inflammation. Since calcium influx plays a crucial role in the occurrence and development of lung IRI, blocking calcium influx into ECs may be an effective therapeutic strategy for lung injury. An orally active TRPV4 antagonist, GSK2193874, was effective in inhibiting lung edema induced by heart failure [ 110 ]. Two other TRPV4 inhibitors (GSK2220961, GSK2337429) ameliorated acute lung injury in mice when administered 30 min after exposure to hydrochloric acid or chlorine gas [ 54 ]. When GSK2193874 was administered 20 min before the induction of acute lung injury by acid instillation, key hallmarks of acute lung injury (i.e. lung edema, inflammation, poor gas exchange, lung dysfunction, and neutrophil infiltration) were attenuated in mice [ 111 ]. However, another TRPV4 inhibitor, HC-067047, applied 45 min after lung injury to simulate a clinically more relevant scenario, offered no protection from acute lung injury, suggesting that timing of treatment may be important in the effectiveness of TRPV4 inhibition in preventing IRI [ 111 ]. Blocking TRPV4 (e.g. with GSK2798745) was also proposed as a promising and feasible approach to protecting the alveolo-capillary barrier in lungs of Covid-19 patients [ 112 ]. In the first human clinical trial (NCT03511105), LPS-induced elevation of total protein and neutrophils in BAL fluid from the airway site after application of GSK2798745 was not different in comparison to placebo-treated controls [ 113 , 114 ]. However, the effectiveness of TRPV4 inhibition as a strategy to treat lung IRI after transplantation has not yet been tested. Therefore, although modulating TRPV4 channel activity may be useful as a therapeutic approach for lung IRI, cell type and injury model should be considered in order to establish clinically successful drugs.

Mibefradil and Flunarizine, two T-type Ca 2+ channel blockers, significantly decreased LPS-induced total cell number, protein concentration, and Evans blue dye extravasation in the lung, as well as TNF-α and IL-6 levels in BAL fluid [ 115 ]. In addition, Mibefradil also attenuated pathological alterations in lung tissue of LPS-challenged mice and suppressed the activity of MPO and NF-κB, a central transcription factor regulating gene expression of various inflammatory mediators [ 115 ]. Since influx of inflammatory cells, protein leakage, and cytokine storms are crucial events of IRI, these Ca 2+ channel inhibitors may provide protection against IR injury.

Tyrosine kinase inhibitor imatinib, which was originally developed to inhibit the chronic myelogenous leukemia-causing BCR-Abl fusion protein, has been shown to attenuate pulmonary vascular permeability induced by a broad range of mediators in a clinically relevant murine model of ARDS [ 116 ]. Imatinib also attenuated thrombin and histamine-induced barrier dysfunction in vitro [ 117 ]. Given its multiple sites of action, further mechanistic work is required to progress imatinib as a potential therapy in ARDS. We propose that imatinib may be a therapeutic option to prevent or treat lung IRI, which warrants further investigation.

Autophagy was implicated to be involved in the pathogenesis of lung IRI, as the inhibition of autophagy by 3-methyladenine (3-MA) resulted in reduced edema, oxidative stress, and neutrophil activation in a rat lung IRI model [ 118 ]. Furthermore, Liu et al. demonstrated that 3-MA inhibited apoptosis and enhanced proliferation to protect against IR-induced lung injury in a rat model of orthotopic left lung transplantation [ 119 ]. However, another study showed that promoting autophagy with rapamycin in human pulmonary microvascular endothelial cells and mice ameliorated tight junction damage and cell death, suggesting that autophagy was protective against IRI [ 120 ]. While there seems to be a paucity of research on the role autophagy plays in lung IRI, these studies advocate for more research on whether autophagy preserves or damages the endothelium.

The important, recent development of ex vivo lung perfusion (EVLP) has allowed the use of marginal donor lungs, such as donation after cardiac death (DCD) lungs, to help resolve the shortage of available donor lungs for transplantation. Steen and colleagues developed the “Lund protocol” that utilized a special perfusion solution (Steen solution) aimed directly at preserving the endothelium to reduce edema, and were the first group to successfully transplant DCD lungs [ 121 ]. Furthermore, they were also able to perform transplantations with marginal donor lungs using EVLP and Steen solution [ 122 ]. A group from Toronto modified the perfusion flow, perfusate composition and temperature, and respiratory rate, in the Lund protocol to create the “Toronto protocol” and successfully transplanted 372 EVLP-rehabilitated marginal donor lungs and DCD lungs [ 123 ]. These studies have encouraged the idea that EVLP can be used as a platform for therapeutic treatment to further recondition lungs to prevent primary graft dysfunction. Our group showed that EVLP with Steen solution supplemented with an adenosine A 2A receptor (A2AR) agonist significantly reduced pulmonary edema and interferon-γ and dramatically improved the oxygenation index, suggesting that acute IRI was attenuated in porcine lungs undergoing EVLP with A2AR-supplemented Steen solution [ 124 ]. This combination of EVLP and A2AR agonists has also been demonstrated to recondition DCD lungs for lung transplantation in preclinical murine and porcine models [ 125 , 126 , 127 ]. Furthermore, we determined that adenosine A 2B receptor antagonist treatment during EVLP significantly attenuated lung dysfunction, interleukin-8 production, and vascular permeability in a murine lung IRI model [ 128 ] as well as enabled successful transplantation of porcine DCD lungs [ 129 ]. As mentioned above, the combination of S1P and sphingosine kinase inhibitors during EVLP provided endothelial protection to improve lung function in a murine DCD model [ 94 ]. These studies give support for the use of EVLP in combination with therapies targeted towards the many mediators of IRI (especially to block endothelial barrier dysfunction) to prevent the detrimental effects of lung IRI.

Lung IRI is a complex, rapid and robust inflammatory response marked by lung dysfunction, endothelial barrier disruption, oxidative stress, increased vascular permeability, edema, alveolar damage, and neutrophil infiltration. Two key events during IRI are vascular permeability and neutrophil infiltration, which results in severe edema and neutrophil-mediated injury. Each of these events are connected and dependent on the health of the endothelium, consequently leading to endothelial barrier dysfunction and edema, a principal hallmark of IRI. Although early studies on mechanisms of lung IRI focused on the innate immune responses, more recent studies have focused more on the endothelium, which is beginning to unravel the multi-factorial pathogenesis and immunologic mechanisms underlying IRI. Many important mediators of endothelial dysfunction after IR have now been identified, as reviewed here (Fig. 1). Spanning from the extracellular glycocalyx to ion channels and purinergic receptors to kinases and possibly many others yet to be discovered, these mediators of endothelial barrier integrity and IRI may serve as prospective targets for lung IRI therapy. While there are no definitive clinical therapies currently available, the accumulating evidence on the critical role the endothelial barrier plays in IRI suggests that promising treatments targeting the endothelium may be approaching soon. The ability to halt this rapid and potentially fatal injury could be significantly enhanced through the application of endothelial-directed therapies, as well as combination therapies, where more than one signaling pathway may be targeted.

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

Acute respiratory distress syndrome

Adenosine triphosphate

Adherens junctions

Bronchoalveolar lavage

Breakpoint cluster region-Abelson

Damage-associated molecular patterns

Endothelial cell

Ex vivo lung perfusion

Extracellular matrix

Intercellular adhesion molecule 1

Interleukin

• Ischemia-reperfusion injury

Keratinocyte growth factor-2

Monocyte chemotactic protein 1

Macrophage inflammatory protein 1

Macrophage inflammatory protein 2

Matrix metalloproteinase 2

Mitogen-activated protein kinase

NADPH oxidase 2

Nitric oxide

Primary graft dysfunction

Recombinant human vimentin

reactive nitrogen species

Reactive oxygen species

Rho associated coiled-coil containing protein kinase 1

Severe acute respiratory syndrome coronavirus type 2

Sphingosine 1-phosphate

Transient receptor potential

Transient receptor potential canonical

Transient receptor potential melastatin

Transient receptor potential mucolipin

Transient receptor potential nitric oxide-mechanoreceptor potential C

Transient receptor potential polycystin

Transient receptor potential vanilloid

Vascular cell adhesion molecule 1

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Ta, H.Q., Kuppusamy, M., Sonkusare, S.K. et al. The endothelium: gatekeeper to lung ischemia-reperfusion injury. Respir Res 25 , 172 (2024). https://doi.org/10.1186/s12931-024-02776-4

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DOI : https://doi.org/10.1186/s12931-024-02776-4

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