Addressing ethical issues in H3Africa research – the views of research ethics committee members

In June 2014, the H3Africa Working Group on Ethics organised a workshop with members of over 40 research ethics committees from across Africa to discuss the ethical challenges raised in H3Africa research, and to receive input on the proposed H3Africa governance framework. Prominent amongst a myriad of ethical issues raised by meeting participants were concerns over consent for future use of samples and data, the role of community engagement in large international collaborative projects, and particular features of the governance of sample sharing. This report describes these concerns in detail and will be informative to researchers wishing to conduct genomic research on diseases pertinent to the African research context

Implementation of family psychosocial risk assessment in pediatric cancer with the Psychosocial Assessment Tool (PAT): study protocol for a cluster-randomized comparative effectiveness trial

BACKGROUND: Childhood cancer affects and is affected by multiple levels of the social ecology, including social and relational determinants of health (e.g., economic stability, housing, childcare, healthcare access, child and family problems). The 2015 Standards of Psychosocial Care in Pediatric Cancer outline optimal psychosocial care sensitive to these ecological factors, starting with assessment of psychosocial healthcare needs to promote medical and psychosocial outcomes across all children with cancer. To address the first standard of family psychosocial assessment, the Psychosocial Assessment Tool (PAT) is a validated screener ready for broad implementation. METHOD: The PAT will be implemented across a national sample of 18 pediatric cancer programs ranging in size (annual new patients) in a mixed methods, comparative effectiveness study, guided by the Interactive Systems Framework for Dissemination and Implementation, comparing two implementation strategies. It is hypothesized that implementation will be more successful at the patient/family, provider, and institutional level when training (strategy I) is combined with implementation expanded resources (strategy II). There are three aims: (1) Refine the two implementation strategies using semi-structured qualitative interviews with 19 stakeholders including parent advocates, providers, pediatric oncology organization representatives, healthcare industry leaders; (2) Compare the two theoretically based and empirically informed strategies to implement the PAT in English and Spanish using a cluster-randomized controlled trial across 18 sites. Stratified by size, sites will be randomized to cohort (3) and strategy (2). Outcomes include adoption and penetration of screening (patient/family), staff job satisfaction/burnout (provider), and cost-effective use of resources consistent with family risk (institution); (3) Based on the results of the trial and feedback from the first and second aim, we will develop and disseminate a web-based PAT Implementation Toolkit. DISCUSSION: Use of the PAT across children\u27s cancer programs nationally can achieve the assessment standard and inform equitable delivery of psychosocial care matched to family need for all patients. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04446728 , registered 23 June 2020

A perpetual source of DNA or something really different: ethical issues in the creation of cell lines for African genomics research

Background: The rise of genomic studies in Africa – not least due to projects funded under H3Africa – is associated with the development of a small number of biorepositories across Africa. For the ultimate success of these biorepositories, the creation of cell lines including those from selected H3Africa samples would be beneficial. In this paper, we map ethical challenges in the creation of cell lines. Discussion: The first challenge we identified relates to the moral status of cells living in culture. There is no doubt that cells in culture are alive, and the question is how this characteristic is relevant to ethical decision-making. The second challenge relates to the fact that cells in culture are a source of cell products and mitochondrial DNA. In combination with other technologies, cells in culture could also be used to grow human tissue. Whilst on the one hand, this feature increases the potential utility of the sample and promotes science, on the other it also enables further scientific work that may not have been specifically consented to or approved. The third challenge relates to ownership over samples, particularly in cases where cell lines are created by a biobank, and in a different country than where samples were collected. Relevant questions here concern the export of samples, approval of secondary use and the acceptability of commercialisation. A fourth challenge relates to perceptions of blood and bodily integrity, which may be particularly relevant for African research participants from certain cultures or backgrounds. Finally, we discuss challenges around informed consent and ethical review. Summary: In this paper, we sought to map the myriad of ethical challenges that need to be considered prior to making cell line creation a reality in the H3Africa project. Considering the relative novelty of this practice in Africa, such challenges will need to be considered, discussed and potentially be resolved before cell line creation in Africa becomes financially feasible and sustainable. We suggest that discussions need to be undertaken between stakeholders internationally, considering the international character of the H3Africa project. We also map out avenues for empirical research

Training of Instrumentalists and Development of New Technologies on SOFIA

This white paper is submitted to the Astronomy and Astrophysics 2010 Decadal Survey (Astro2010)1 Committee on the State of the Profession to emphasize the potential of the Stratospheric Observatory for Infrared Astronomy (SOFIA) to contribute to the training of instrumentalists and observers, and to related technology developments. This potential goes beyond the primary mission of SOFIA, which is to carry out unique, high priority astronomical research. SOFIA is a Boeing 747SP aircraft with a 2.5 meter telescope. It will enable astronomical observations anywhere, any time, and at most wavelengths between 0.3 microns and 1.6 mm not accessible from ground-based observatories. These attributes, accruing from the mobility and flight altitude of SOFIA, guarantee a wealth of scientific return. Its instrument teams (nine in the first generation) and guest investigators will do suborbital astronomy in a shirt-sleeve environment. The project will invest $10M per year in science instrument development over a lifetime of 20 years. This, frequent flight opportunities, and operation that enables rapid changes of science instruments and hands-on in-flight access to the instruments, assure a unique and extensive potential - both for training young instrumentalists and for encouraging and deploying nascent technologies. Novel instruments covering optical, infrared, and submillimeter bands can be developed for and tested on SOFIA by their developers (including apprentices) for their own observations and for those of guest observers, to validate technologies and maximize observational effectiveness.Comment: 10 pages, no figures, White Paper for Astro 2010 Survey Committee on State of the Professio

Optimising a person-centred approach to stopping medicines in older people with multimorbidity and polypharmacy using the DExTruS framework: a realist review

Background: Tackling problematic polypharmacy requires tailoring the use of medicines to individual circumstances and may involve the process of deprescribing. Deprescribing can cause anxiety and concern for clinicians and patients. Tailoring medication decisions often entails beyond protocol decision-making, a complex process involving emotional and cognitive work for healthcare professionals and patients. We undertook realist review to highlight and understand the interactions between different factors involved in deprescribing and to develop a final programme theory that identifies and explains components of good practice that support a person-centred approach to deprescribing in older patients with multimorbidity and polypharmacy. Methods: The realist approach involves identifying underlying causal mechanisms and exploring how, and under what conditions they work. We conducted a search of electronic databases which were supplemented by citation checking and consultation with stakeholders to identify other key documents. The review followed the key steps outlined by Pawson et al. and followed the RAMESES standards for realist syntheses. Results: We included 119 included documents from which data were extracted to produce context-mechanism-outcome configurations (CMOCs) and a final programme theory. Our programme theory recognises that deprescribing is a complex intervention influenced by a multitude of factors. The components of our final programme theory include the following: a supportive infrastructure that provides clear guidance around professional responsibilities and that enables multidisciplinary working and continuity of care, consistent access to high-quality relevant patient contextual data, the need to support the creation of a shared explanation and understanding of the meaning and purpose of medicines and a trial and learn approach that provides space for monitoring and continuity. These components may support the development of trust which may be key to managing the uncertainty and in turn optimise outcomes. These components are summarised in the novel DExTruS framework. Conclusion: Our findings recognise the complex interpretive practice and decision-making involved in medication management and identify key components needed to support best practice. Our findings have implications for how we design medication review consultations, professional training and for patient records/data management. Our review also highlights the role that trust plays both as a central element of tailored prescribing and a potential outcome of good practice in this area

Guideline for feedback of individual genetic research findings for genomics research in Africa.

As human genomics research in Africa continues to generate large amounts of data, ethical issues arise regarding how actionable genetic information is shared with research participants. The Human Heredity and Health in Africa Consortium (H3Africa) Ethics and Community Engagement Working group acknowledged the need for such guidance, identified key issues and principles relevant to genomics research in Africa and developed a practical guideline for consideration of feeding back individual genetic results of health importance in African research projects. This included a decision flowchart, providing a logical framework to assist in decision-making and planning for human genomics research projects. Although presented in the context of the H3Africa Consortium, we believe the principles described, and the decision flowchart presented here is applicable more broadly in African genomics research

Psychiatric and medical comorbidities of eating disorders : findings from a rapid review of the literature

Background: Eating disorders (EDs) are potentially severe, complex, and life-threatening illnesses. The mortality rate of EDs is signifcantly elevated compared to other psychiatric conditions, primarily due to medical complications and suicide. The current rapid review aimed to summarise the literature and identify gaps in knowledge relating to any psychiatric and medical comorbidities of eating disorders. Methods: This paper forms part of a rapid review) series scoping the evidence base for the feld of EDs, conducted to inform the Australian National Eating Disorders Research and Translation Strategy 2021–2031, funded and released by the Australian Government. ScienceDirect, PubMed and Ovid/Medline were searched for English-language studies focused on the psychiatric and medical comorbidities of EDs, published between 2009 and 2021. High-level evidence such as meta-analyses, large population studies and Randomised Control Trials were prioritised. Results: A total of 202 studies were included in this review, with 58% pertaining to psychiatric comorbidities and 42% to medical comorbidities. For EDs in general, the most prevalent psychiatric comorbidities were anxiety (up to 62%), mood (up to 54%) and substance use and post-traumatic stress disorders (similar comorbidity rates up to 27%). The review also noted associations between specifc EDs and non-suicidal self-injury, personality disorders, and neurodevelopmental disorders. EDs were complicated by medical comorbidities across the neuroendocrine, skeletal, nutritional, gastrointestinal, dental, and reproductive systems. Medical comorbidities can precede, occur alongside or emerge as a complication of the ED. Conclusions: This review provides a thorough overview of the comorbid psychiatric and medical conditions cooccurring with EDs. High psychiatric and medical comorbidity rates were observed in people with EDs, with comorbidities contributing to increased ED symptom severity, maintenance of some ED behaviours, and poorer functioning as well as treatment outcomes. Early identifcation and management of psychiatric and medical comorbidities in people with an ED may improve response to treatment and overall outcomes

A framework for human microbiome research

A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies

Structure, function and diversity of the healthy human microbiome

Author Posting. © The Authors, 2012. This article is posted here by permission of Nature Publishing Group. The definitive version was published in Nature 486 (2012): 207-214, doi:10.1038/nature11234.Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.This research was supported in part by National Institutes of Health grants U54HG004969 to B.W.B.; U54HG003273 to R.A.G.; U54HG004973 to R.A.G., S.K.H. and J.F.P.; U54HG003067 to E.S.Lander; U54AI084844 to K.E.N.; N01AI30071 to R.L.Strausberg; U54HG004968 to G.M.W.; U01HG004866 to O.R.W.; U54HG003079 to R.K.W.; R01HG005969 to C.H.; R01HG004872 to R.K.; R01HG004885 to M.P.; R01HG005975 to P.D.S.; R01HG004908 to Y.Y.; R01HG004900 to M.K.Cho and P. Sankar; R01HG005171 to D.E.H.; R01HG004853 to A.L.M.; R01HG004856 to R.R.; R01HG004877 to R.R.S. and R.F.; R01HG005172 to P. Spicer.; R01HG004857 to M.P.; R01HG004906 to T.M.S.; R21HG005811 to E.A.V.; M.J.B. was supported by UH2AR057506; G.A.B. was supported by UH2AI083263 and UH3AI083263 (G.A.B., C. N. Cornelissen, L. K. Eaves and J. F. Strauss); S.M.H. was supported by UH3DK083993 (V. B. Young, E. B. Chang, F. Meyer, T. M. S., M. L. Sogin, J. M. Tiedje); K.P.R. was supported by UH2DK083990 (J. V.); J.A.S. and H.H.K. were supported by UH2AR057504 and UH3AR057504 (J.A.S.); DP2OD001500 to K.M.A.; N01HG62088 to the Coriell Institute for Medical Research; U01DE016937 to F.E.D.; S.K.H. was supported by RC1DE0202098 and R01DE021574 (S.K.H. and H. Li); J.I. was supported by R21CA139193 (J.I. and D. S. Michaud); K.P.L. was supported by P30DE020751 (D. J. Smith); Army Research Office grant W911NF-11-1-0473 to C.H.; National Science Foundation grants NSF DBI-1053486 to C.H. and NSF IIS-0812111 to M.P.; The Office of Science of the US Department of Energy under Contract No. DE-AC02-05CH11231 for P.S. C.; LANL Laboratory-Directed Research and Development grant 20100034DR and the US Defense Threat Reduction Agency grants B104153I and B084531I to P.S.C.; Research Foundation - Flanders (FWO) grant to K.F. and J.Raes; R.K. is an HHMI Early Career Scientist; Gordon&BettyMoore Foundation funding and institutional funding fromthe J. David Gladstone Institutes to K.S.P.; A.M.S. was supported by fellowships provided by the Rackham Graduate School and the NIH Molecular Mechanisms in Microbial Pathogenesis Training Grant T32AI007528; a Crohn’s and Colitis Foundation of Canada Grant in Aid of Research to E.A.V.; 2010 IBM Faculty Award to K.C.W.; analysis of the HMPdata was performed using National Energy Research Scientific Computing resources, the BluBioU Computational Resource at Rice University