Benchmark – Evidence-Based Practice Project: PICOT Paper NUR 550

Benchmark – Evidence-Based Practice Project: PICOT Paper NUR 550

Benchmark – Evidence-Based Practice Project: PICOT Paper SAMPLE

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Participating in evidence-based practice (EBP) projects is one of the most practical interventions for dealing with health issues. Nurses use research-based nursing interventions to improve health outcomes. The population, intervention, and expected outcome are all described in this paper. It also explains the implementation time and the use of nursing science, social determinants of health, and epidemiologic, genomic, and genetic data to support the health management of obese children.

Demographics and Health Concerns in the Population

The EBP project’s target population consists of preschool-aged children (2-5 years) and school-aged children (6-11 years). Preschool-aged children are typically highly reliant on their parents’ choices, which include nutritional health, hobbies, and overall lifestyle. Children become more reliant on certain choices as they progress from pre-school to school age. They begin to pursue hobbies and form relationships that influence their daily habits.

Childhood obesity is a serious public health issue in the United States, and its prevalence is rising, putting children at risk of poor health. Skinner et al. (2018) discovered that the prevalence of childhood obesity remains high in the United States, with 1 in every 5 children obese. Children are becoming more vulnerable to the immediate and long-term risks of obesity as the prevalence of obesity rises. Obese children are more likely to develop heart disease, type 2 diabetes, and cancer (Lindberg et al., 2020). Overall, children’s health is deteriorating, and they are not as productive as they should be.

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It is disappointing to see a proportional risk in risk factors as the populace, government, and health care providers intensify measures to combat obesity. According to Tester et al. (2018), low physical activity lifestyle changes are continuously exposing children to obesity. Another risk factor is the consumption of fast foods. Pearson et al. (2020) proposed that sedentary lifestyles characterized by excessive screen time be addressed in order to reduce childhood obesity prevalence. Gaming, long-term television viewing, and social interaction via mobile phones can all be blamed for children’s lack of physical activity. Regulation is required as parents, educators, and health care providers work together to promote physical activity in the home, school, and community.

Benchmark – Evidence-Based Practice Project: PICOT Paper NUR 550

This is a capstone project class. All the way to NUR 590, we will focus on writing assignments that focus on your PICOT Question. Indeed, we will create the PICOT for you from week 1 of the present class. Kindly trust us with it.

Refer to the PICOT you developed for your evidence-based practice project proposal. If your PICOT required revision, include those revisions in this assignment. You will use your PICOT paper for all subsequent assignments you develop as part of your evidence-based practice project proposal in this course and in NUR-590, during which you will synthesize all of the sections into a final written paper detailing your evidence-based practice project proposal.

Also Check Out: NUR 550 Benchmark – Evidence-Based Practice Project PICOT Paper

Write a 750-1,000-word paper that describes your PICOT.

  1. Describe the population’s demographics and health concerns.
  2. Describe the proposed evidence-based intervention and explain how your proposed intervention Benchmark – Evidence-Based Practice Project PICOT Paper NUR 550incorporates health policies and goals that support health care equity for the population of focus.
  3. Compare your intervention to previous practice or research.
  4. Explain what the expected outcome is for the intervention.
  5. Describe the time for implementing the intervention and evaluating the outcome.
  6. Explain how nursing science, social determinants of health, and epidemiologic, genomic, and genetic data are applied or synthesized to support population health management for the selected population.
  7. Create an Appendix for your paper and attach the PICOT. Be sure to review feedback from your previous submission and revise your PICOT accordingly.
  8. Complete the “APA Writing Checklist” to ensure that your paper adheres to APA style and formatting criteria and general guidelines for academic writing. Include the completed checklist as the final appendix at the end of your paper.

Refer to the “Evidence-Based Practice Project Proposal – Assignment Overview” document for an overview of the evidence-based practice project proposal assignments.

You are required to cite at least four to six peer-reviewed sources to complete this assignment. Sources must be published within the last 5 years and appropriate for the assignment criteria and nursing content. Benchmark – Evidence-Based Practice Project: PICOT Paper NUR 550

Prepare this assignment according to the guidelines found in the APA Style Guide, located in the Student Success Center. An abstract is not required.

Re: Topic 3 DQ 2

Under FDA regulations, an Institutional Review Board is group that has been formally designated to review and monitor biomedical research involving human subjects. The purpose of IRB review is to assure, both in advance and by periodic review, that appropriate steps are taken to protect the rights and welfare of humans participating as subjects in the research. To accomplish this purpose, IRBs use a group process to review research protocols and related materials (e.g., informed consent documents and investigator brochures) to ensure protection of the rights and welfare of human subjects of research (FDA, n.d).

From a public health perspective, it is important to recognize an ethical standard that respects community autonomy. This standard can be achieved by requiring community collaboration (ie, at a minimum, establishing a community advisory board) to protect against exploiting vulnerable populations, to ensure fair terms of cooperation, to ratify that the interventions to be tested are acceptable to community members, and to minimize potential misunderstandings about the research. Such community advisory boards should have responsibility for determining whether the research goals are valuable to local community members and the methods are acceptable before the research is allowed to proceed (Buchanan & Miller, 2006).

In this era of translational research, social injustice is one of the crucial ethical concerns. Resource-rich countries conducting translational medical research in resource-poor countries are common and if the results of the research are not expected to be beneficial/less beneficial to the resource-poor country, then arises the issue of social injustice and disparity. Examples include research undertaken on diseases that are rare or the resulting intervention/product is too expensive to implement, in developing countries (Mandal et al., 2017).

References

Buchanan, D. R., & Miller, F. G. (2006). A public health perspective on research ethics. Journal of medical ethics32(12), 729–733. https://doi.org/10.1136/jme.2006.015891

Mandal, J., Ponnambath, D. K., & Parija, S. C. (2017). Ethics of translational medical research. Tropical parasitology7(2), 62–64. https://doi.org/10.4103/tp.TP_47_17

FDA (n.d). Institutional Review Boards (IRBs) and Protection of Human Subjects in Clinical Trials. Retrieved from https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/institutional-review-boards-irbs-and-protection-human-subjects-clinical-trials

 

RESPOND HERE (150 WORDS, 2 REFERENCES)

 

 

KELLI

Re: Topic 3 DQ 2

Unfortunately, many countries including the United States have conducted unethical clinical trials in the past and because of that, we have implemented policies and regulations to keep human participants safe. The Institutional Review Board (IRB) was implemented to keep safeguards in place for these clinical trials. They have three basic ethical principles to stand by; respect for person, beneficence, and justice (Qiao, 2018).

Respect for persons is kept in balance by ensuring patient autonomy. This is where informed consent comes to play. Patients need to be fully informed about the trial they are participating in, including requirements expected of the patient and any adverse effects the patient may experience. They have to voluntary agree to participate in the trial and be informed that they can choose to drop out of the trial at any time (Pietrzykowski & Smilowska, 2021).

The beneficence is focused on protecting the patient or study participant (Qiao, 2018). Ensuring patient safety is at utmost importance during every step of the trial. Justice will be kept in balance by ensuring equity. Health equity has been a hot topic recently where many of the minority population may not have access to clinical trials or the knowledge to be comfortable with becoming a participant.

References

Pietrzykowski, T., & Smilowska, K. (2021). The reality of informed consent: Empirical studies on patient comprehension—systematic review. Trials22(1). https://doi.org/10.1186/s13063-020-04969-w

Qiao, H. (2018). A brief introduction to institutional review boards in the united states. Pediatric Investigation2(1), 46–51. https://doi.org/10.1002/ped4.12023

 

This assignment uses a rubric. Please review the rubric prior to beginning the assignment to become familiar with the expectations for successful completion.

You are required to submit this assignment to LopesWrite. A link to the LopesWrite technical support articles is located in Class Resources if you need assistance.

Benchmark – Evidence-Based Practice Project: PICOT Paper NUR 550

Benchmark – Evidence-Based Practice Project: PICOT Paper SAMPLE

Engaging in evidence-based practice (EBP) projects is among the most practical interventions for addressing health problems. Nurses use nursing interventions founded on research to enhance health outcomes. This paper describes the population, intervention, and expected outcome. It also explains the implementation time and the application of nursing science, social determinants of health, and epidemiologic, genomic, and genetic data in supporting the health management of children with obesity. Benchmark – Evidence-Based Practice Project: PICOT Paper NUR 550

Population’s Demographics and Health Concerns

The focus population for the EBP project is children usually categorized as preschool-aged children (2-5 years) and school-aged children (6-11 years). Preschool-aged children are usually highly dependent on parents’ choices, including nutritional health, hobbies, and general lifestyle. As they move from pre-school to school age, children become somewhat dependent on some choices. They start choosing hobbies and establish relationships that influence their daily habits.

Childhood obesity is a serious health concern in the United States whose prevalence is increasing and putting children at risk of poor health. Skinner et al. (2018) found that childhood obesity’s prevalence is still high in the US since 1 in every 5 children has obesity. As the prevalence of obesity increases, children are more exposed to immediate and long term risks of obesity. Vulnerability to heart disease, type 2 diabetes, and cancer is high in children with obesity (Lindberg et al., 2020). Overall, the quality of health declines and children are not productive as desired. Benchmark – Evidence-Based Practice Project: PICOT Paper NUR 550

As the populace, government, and health care providers intensify measures to fight obesity, it is disappointing to experience a proportional risk in risk factors. According to Tester et al. (2018), lifestyle changes characterized by low physical activity are continuously exposing children to obesity. Fast foods’ consumption is another risk factor. Pearson et al. (2020) suggested that sedentary living characterized by too much screen time must be addressed to reduce childhood’s obesity prevalence. Gaming, watching television for extended periods, and social interaction through mobile phones can be blamed for the reduced physical activity among children. Regulation is necessary as parents, educators, and health care providers collaborate to encourage physical activity at homes, schools, and communities.

Evidence-Based Intervention

As proposed in the PICOT (Appendix 1), the identified intervention is educating parents and children on reducing screen time and increasing physical activity. Increased screen time increases obesity prevalence since it is associated with too much energy intake and low physical activity (Schwarzfischer et al., 2020). Educating parents and children is expected to trigger a positive behavior change as parents regulate children and children avoid spending too much time on the screens since they understand the implications. The intervention incorporates health policies and goals that support health equity for children since it focuses on ensuring that children attain their full health potential. Health equity is achieved when disadvantaged groups are protected from health disparities and helped to acquire a decent living standard. Keeping children free from obesity is a significant step towards achieving this critical goal.

Intervention Comparison to Previous Research

Previous research confirm that parents are responsible for modeling children’s behaviors by regulating screen time, and awareness to embrace this role is necessary. Pearson et al. (2020) found that shortage of parent- and home-focused interventions to address unhealthy behaviors such as intake of energy-dense snack foods and excessive screen time increases childhood obesity rates. Parental confidence and awareness of the association between screen time and unhealthy behaviors are also recommended. Goncalves et al. (2019) found that parental confidence and self-efficacy to reduce screen time is instrumental in addressing overweight problems among children. With research confirming the central role parents play in regulating screen time, it is essential to encourage them to embrace this critical role and serve as role models of healthy behaviors. Benchmark – Evidence-Based Practice Project: PICOT Paper NUR 550

Expected Outcome

Educating parents and children on the implications of too much screen time is expected to be the foundation of behavior change. As a nursing intervention, the education program will improve knowledge on the connection between obesity in children and screen time as a risk factor. Minimizing screen time will lead to a proportional reduction in obesity rates among children, which has become a public health concern since its trend has taken an upward trajectory in the past decade (Skinner et al., 2018). The overall outcome is creating a healthy populace by reducing obesity rates among school-age children.

Time for Implementing and Evaluation

Implementation should be immediate. Since the focus population and intervention are known, parents and children’s education on screen time should be done instantly. Doing so will help to achieve the target objective within six months as proposed in the PICOT. Outcome evaluation will be progressive (monthly) and summative (after six months). Progressive evaluation will help to identify areas that need improvement, and summative evaluation will be used to deduce whether the target objectives were achieved.

 

References

Goncalves, W. S. F., Byrne, R., Viana, M. T., & Trost, S. G. (2019). Parental influences on screen time and weight status among preschool children from Brazil: A cross-sectional study. International Journal of Behavioral Nutrition and Physical Activity16(1), 1-8. doi: https://dx.doi.org/10.1186%2Fs12966-019-0788-3

Lindberg, L., Danielsson, P., Persson, M., Marcus, C., & Hagman, E. (2020). Association of childhood obesity with risk of early all-cause and cause-specific mortality: A Swedish prospective cohort study. PLoS Medicine17(3), e1003078. https://doi.org/10.1371/journal.pmed.1003078

Pearson, N., Biddle, S. J., Griffiths, P., Sherar, L. B., McGeorge, S., & Haycraft, E. (2020). Reducing screen-time and unhealthy snacking in 9–11 year old children: the Kids FIRST pilot randomised controlled trial. BMC Public Health20(1), 1-14. doi: 10.1186/s12889-020-8232-9

Schwarzfischer, P., Gruszfeld, D., Socha, P., Luque, V., Closa-Monasterolo, R., Rousseaux, D., … & Grote, V. (2020). Effects of screen time and playing outside on anthropometric measures in preschool aged children. PloS One15(3), e0229708. https://doi.org/10.1371/journal.pone.0229708

Tester, J. M., Phan, T. L. T., Tucker, J. M., Leung, C. W., Gillette, M. L. D., Sweeney, B. R., … & Eneli, I. U. (2018). Characteristics of children 2 to 5 years of age with severe obesity. Pediatrics141(3). doi: https://doi.org/10.1542/peds.2017-3228

Skinner, A. C., Ravanbakht, S. N., Skelton, J. A., Perrin, E. M., & Armstrong, S. C. (2018). Prevalence of obesity and severe obesity in US children, 1999–2016. Pediatrics141(3). https://doi.org/10.1542/peds.2017-3459

Benchmark Information

This benchmark assignment assesses the following programmatic competencies:

MBA-MSNMSN-Nursing Education; MSN Acute Care Nurse Practitioner-Adult-Gerontology; MSN Family Nurse Practitioner; MSN-Health Informatics; MSN-Health Care Quality and Patient Safety; MSN-Leadership in Health Care Systems; MSN-Public Health Nursing

MS Nursing: Public Health

MS Nursing: Education

MS Nursing: Acute Care Nurse Practitioner

MS Nursing: Family Nurse Practitioner

MS Nursing: Health Care Quality and Patient Safety

4.1: Synthesize nursing science, determinants of health, and epidemiologic, genomic, and genetic data in the management of population health.

Evidence, tools, and data from various sources are used in population health management for children. Nursing science contributes to the development of theories and practical concepts for the management of conditions. It offers scientific methods for providing better health care. The social determinants of health (SDOH) are closely related to living conditions. In this case, health care providers investigate how childhood environments, beliefs, and socioeconomic status influence obesity and other illnesses, as well as appropriate interventions. Epidemiological data is used to determine disease prevalence and potential causes. Genomic and genetic data are inextricably linked. As genetic data investigates the acquired characteristics of children and their influence on health, genomic data investigates functional information in DNA. PICOT Paper NUR 550: Benchmark – Evidence-Based Practice Project

Finally, children deserve good health and should be protected from risks such as obesity. Nurses should respond by using their knowledge and influence to promote quality public health. They should play a central role in identifying critical problems that impede people’s productivity and developing long-term solutions. Addressing childhood obesity by educating parents and children about the importance of limiting screen time is a long-term, evidence-based solution.

Expected Outcome for Intervention 10.0% The expected outcome is for the intervention is omitted. The expected outcome is for the intervention is incomplete. The expected outcome is for the intervention is summarized. More information and supporting evidence is needed. The expected outcome for the intervention is explained using sufficient evidence. The expected outcome for the intervention is thoroughly explained using substantial evidence.

Time Estimated for Implementing Intervention and Evaluating Outcome 10.0% A description of the timeline is not included. A description of the timeline is incomplete or incorrect. A description of the timeline is included but lacks evidence. A description of the timelines is complete and includes a sufficient amount of evidence. A description of the timeline is extremely thorough with substantial evidence.

Support for Population Health Management for Selected Population (C 4.1) 10.0% Explanation of how nursing science; social determinants of health; and epidemiologic, genomic, and genetic data are applied or synthesized to support population health management for the selected population is omitted. Explanation of how nursing science; social determinants of health; and epidemiologic, genomic, and genetic data are applied or synthesized to support population health management for the selected population is incomplete. There are major inaccuracies. Explanation of how nursing science; social determinants of health; and epidemiologic, genomic, and genetic data are applied or synthesized to support population health management for the selected population is summarized. More information and support are needed. Explanation of how nursing science; social determinants of health; and epidemiologic, genomic, and genetic data are applied or synthesized to support population health management for the selected population is adequate. Some detail is needed for accuracy or clarity. Explanation of how nursing science; social determinants of health; and epidemiologic, genomic, and genetic data are applied or synthesized to support population health management for the selected population is thorough. The narrative is insightful and demonstrates an understanding of how the various aspects contribute to population health management for selected populations.

Appendix 5.0% The appendix and required resources are omitted. The APA Writing Checklist and PICOT are attached, but an appendix has not been created. The paper does not reflect the use of the APA Writing Checklist during development. The APA Writing Checklist and PICOT are attached in the appendix. The APA Writing Checklist was generally used in development of the paper, but some aspects are inconsistent with the paper format or quality. The APA Writing Checklist and PICOT are attached in the appendix. It is apparent that the APA Writing Checklist was used in development of the paper. The APA Writing Checklist and PICOT are attached in the appendix. It is clearly evident by the quality of the paper that the APA Writing Checklist was used in development. Benchmark – Evidence-Based Practice Project: PICOT Paper NUR 550

Required Sources 5.0% Sources are not included. Number of required sources is only partially met. Number of required sources is met, but sources are outdated or inappropriate. Number of required sources is met. Sources are current, but not all sources are appropriate for the assignment criteria and nursing content. Number of required resources is met. Sources are current and appropriate for the assignment criteria and nursing content.

Organization and Effectiveness 20.0%
Thesis Development and Purpose 7.0% Paper lacks any discernible overall purpose or organizing claim. Thesis is insufficiently developed or vague. Purpose is not clear. Thesis is apparent and appropriate to purpose. Thesis is clear and forecasts the development of the paper. Thesis is descriptive and reflective of the arguments and appropriate to the purpose. Thesis is comprehensive and contains the essence of the paper. Thesis statement makes the purpose of the paper clear.

Argument Logic and Construction 8.0% Statement of purpose is not justified by the conclusion. The conclusion does not support the claim made. Argument is incoherent and uses noncredible sources. Sufficient justification of claims is lacking. Argument lacks consistent unity. There are obvious flaws in the logic. Some sources have questionable credibility. Argument is orderly, but may have a few inconsistencies. The argument presents minimal justification of claims. Argument logically, but not thoroughly, supports the purpose. Sources used are credible. Introduction and conclusion bracket the thesis. Argument shows logical progressions. Techniques of argumentation are evident. There is a smooth progression of claims from introduction to conclusion. Most sources are authoritative. Clear and convincing argument that presents a persuasive claim in a distinctive and compelling manner. All sources are authoritative.

Mechanics of Writing (includes spelling, punctuation, grammar, language use) 5.0% Surface errors are pervasive enough that they impede communication of meaning. Inappropriate word choice or sentence construction is used. Frequent and repetitive mechanical errors distract the reader. Inconsistencies in language choice (register) or word choice are present. Sentence structure is correct but not varied. Some mechanical errors or typos are present, but they are not overly distracting to the reader. Correct and varied sentence structure and audience-appropriate language are employed. Prose is largely free of mechanical errors, although a few may be present. The writer uses a variety of effective sentence structures and figures of speech. Writer is clearly in command of standard, written, academic English.

Format 10.0%
Paper Format (Use of appropriate style for the major and assignment) 5.0% Template is not used appropriately or documentation format is rarely followed correctly. Template is used, but some elements are missing or mistaken; lack of control with formatting is apparent. Template is used, and formatting is correct, although some minor errors may be present. Template is fully used; There are virtually no errors in formatting style. All format elements are correct.  Benchmark – Evidence-Based Practice Project: PICOT Paper NUR 550

Documentation of Sources (citations, footnotes, references, bibliography, etc., as appropriate to assignment and style) 5.0% Sources are not documented. Documentation of sources is inconsistent or incorrect, as appropriate to assignment and style, with numerous formatting errors. Sources are documented, as appropriate to assignment and style, although some formatting errors may be present. Sources are documented, as appropriate to assignment and style, and format is mostly correct. Sources are completely and correctly documented, as appropriate to assignment and style, and format is free of error.

Topic 3 DQ 1

Discuss the ethical guidelines that would need to be implemented when conducting translational research. What are the ethical and legal considerations related to translating research into practice? Discuss what steps you would take as a member of a translational research team in order to establish ethical guidelines for conducting translational research.

Re: Topic 3 DQ 1

Translational Research (TR) looks to implement new practices and guidelines to biomedicine and clinical areas in preventions, treatment and knowledge. Research looks to improve outcomes for patients at the very end of the TR process, in order to obtain such positive outcomes, efficiency in the research process must be correctable (Lopez de la Vieja, 2016). Research can come with high costs during developmental and clinical trials as resources are used in order to observe and maintain safety. However, resources are finite which can considerably stunt the growth of TR. There is also the major consideration of resources being used in a fair and just manner as legal and ethical guidelines must be adhered to. Ethical decision making must contain aspects of justice, equality and quality in terms of respect, dignity, and responsibility during research (Lopez de la Vieja, 2016). Ensuring that resources are not wasted on unnecessary events or complete unfair practices during research should be prioritized just as much as safety measures as patient outcomes depend on the research relaying the most effective interventions for the best, safe outcomes (Lopez de la Vieja, 2016).

During TR, members must ensure that their individuals within clinical trials are consenting while upholding the integrity of knowledge of their participation. Members must also consider potentially harmful and questionable areas that can effectively place high risk in obtaining outcomes (Sofaer & Eyal, 2010). When establishing guidelines to ethical research, members are required to overlook these considerations at every step and interaction as to prevent legal divergence that can cause poor patient outcome which would jeopardize the integrity of the research. Policies and procedures as well as ethics committee consultation can assist in fool-proofing research from breaking ethical guidelines and beneficence (Lopez de la Vieja, 2016).

References:

Sofaer N, & Eyal N. (2010). The Diverse Ethics of Translational Research. American Journal of Bioethics, 10(8), 19–30. https://doi-org.lopes.idm.oclc.org/10.1080/15265161.2010.494214

López de la Vieja, M. T. (2016). Ethics and governance in translational research. Ethics, Medicine and Public Health, 2(2), 256–262. https://doi-org.lopes.idm.oclc.org/10.1016/j.jemep.2016.04.002

Topic 3 DQ 2

Discuss the role of the Institutional Review Board. Discuss ethical research considerations specific to population health. How are respect for the persons, potential benefits and burdens of the research, and justice kept in balance? Provide an example.

Re: Topic 3 DQ 2

The institutional review board is a board utilized prior to initiation of a study to ensure the research being proposed is held to high ethical standards. The FDA regulated IRB boards to formally review and monitor biomedical research involving human beings(FDA, 2019). An IRB holds a role in advance and in periodic review of clinical trials, and research, it also reviews protocols that involve human subjects to protect the human rights during a trials or study. Population health is the looking at the broad distribution of health within population(Nash et al., 2021), to ethically study a population one would have to ensure the study followed the ethics of a whole population, as well as maintaining an equitable benefit to the population in hand. Maintain justice and benefits of a translational study of population would have to maintain the benefit of the study was fair and equitable to all of the population regardless of race or color(Riva & Petrini, 2019). In the translation research of my EBP project looking at quantitative blood loss in postpartum women to identify and treat postpartum hemorrhage early, studies show women of different ethnicity background have a higher risk for PPH. To maintain high ethics the IRB would have to ensure the research around QBL must include and be beneficial for all women no matter race or socioeconomic status. In my research Women of different ethnicities do have barriers to care related to prenatal care predisposing them to higher risk pregnancies but utilizing QBL in every delivery is offered and given to each woman.

References

FDA. (2019, September 11). Institutional Review Boards and protection of Human Subjects in Clinical Trials. FDA U.S. Food & Drug Administration. Retrieved July 1, 2021, from https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/institutional-review-boards-irbs-and-protection-human-subjects-clinical-trials

Nash, D. B., MD, MBA, Skoufalos, A., EdD, MS, Fabius, R. J., MD, FACPE, & Oglesby, W. H., Phd, MBA, MSPH, FACHE. (2021). Population Health Creating a Culture of Wellness (3rd ed.) [e-book]. Jones & Bartlett Learning.

Riva, L., & Petrini, C. (2019). A few ethical issues in translational research for gene and cell therapy. Journal of Translational Medicine17(1). https://doi.org/10.1186/s12967-019-02154-5