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Heritable human genome editing has garnered significant attention in scholarly and lay media, yet questions remain about whether, when, and how heritable genome editing ought to proceed. Drawing on interviews with scientists who use genome editing in their research and professionals engaged in human genome editing governance efforts, we examine their views on the permissibility of heritable genome editing and the governance strategies they see as necessary and realistic. For both issues, we found divergent views from respondents. We place the views of these scientists and governance professionals within the context of the larger bioethical discussion of heritable genome editing governance, along a continuum of hard to soft approaches. These respondents’ views highlight the challenges of various hard forms of governance and the potential virtues of soft governance approaches.

We demonstrate the fruitfulness of using card sort activities as an engagement method by detailing community consultation for ethical, legal, and social implications of sociogenomics. Readers are provided with a user-guide for card sort engagement through: (1) an overview of the card sort activity and its merits for engagement, (2) detailed methods of sorting for values-elicitation and prioritization goals, and (3) strategies to design this approach for other participatory research designs. Our intent is to add to meaningful exchanges between community engaged researchers and empirical bioethicists. [ABSTRACT FROM AUTHOR]

Clinical research regularly includes required, nontherapeutic procedures to answer research questions. Optional procedures usually offer minimal or no personal benefit and may involve harms and burdens.Members from the Bangkok SEARCH010/RV254 HIV research cohort of individuals acutely HIV-infected are recruited to six optional procedures varying in invasiveness: leukapheresis, genital secretions collection, lumbar puncture, brain MRI/MRS/DTI, colon biopsy, and lymph node biopsy. We surveyed cohort members about their first recruitment for each procedure to examine factors associated with decision making and attitudes about compensation.406 members (68%) completed the survey. Reported procedure participation ranged from 71% (MRI) to 27% (lymph node biopsy). Respondents underwent 0–6 procedure types (median 3). Ordinal regression indicated that lower perceived HIV impact and HIV remission trial participation were associated with more procedures completed. Reports of decision difficulty varied, and feeling pressured by research staff was low overall. Notably, those who declined procedures and those who underwent more invasive procedures reported greater decision difficulty and perceived pressure. Most respondents felt compensation amounts were appropriate, although opinions differed by procedure, and for some procedures, between people who agreed and declined.There is limited literature regarding consent to and attitudes about optional research procedures. Researchers must consider how to best support voluntary decisions for procedures with little personal benefit, particularly in lower-income or marginalized populations. In this longitudinal research cohort, perceived pressure to participate may be a concern, although our finding of variation in participation rates corresponding to invasiveness is reassuring. Data from different research contexts would provide important comparators.

Abstract The objective of this study was to investigate the association between dietary diversity, child growth and child developmental outcomes. This was a prospective cohort study. Developmental outcomes were assessed by communication, fine motor, gross motor, personal social, problem solving and combined developmental scores measured by the Extended Ages and Stages Questionnaire (EASQ) at a 6‐month follow‐up visit. Height and weight were measured at baseline and a 6‐month follow‐up. Baseline minimum dietary diversity (MDD) for children 6–23 months old was defined by consumption of five or more of the following food groups: (1) breast milk; (2) grains, roots and tubers; (3) legumes and nuts; (4) dairy products; (5) flesh foods; (6) eggs; (7) vitamin A‐rich fruits and vegetables and (8) other fruits and vegetables. Participants were 117 children 6–23 months of age. Linear growth faltering was defined as a significant decline (p

While somatic cell editing to treat disease is widely accepted, the use of human genome editing for "enhancement" remains contested. Scientists and policy‐makers routinely cite the prospect of enhancement as a salient ethical challenge for human genome editing research. If preventive genome editing projects are perceived as pursuing human enhancement, they could face heightened barriers to scientific, public, and regulatory approval. This article outlines what we call "preventive strengthening research" (or "PSR") to explore, through this example, how working to strengthen individuals' resistance to disease beyond what biomedicine considers to be the human functional range may be interpreted as pursuing human enhancement. Those involved in developing guidance for PSR will need to navigate the interface between preventive goals and enhancement implications. This article identifies and critiques three of these ideas in the interest of anticipating the wider emergence of PSR and the need for a normative approach for its pursuit. All three "candidate criteria" merit attention, but each also faces challenges that will need to be addressed as further research policy is developed. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionThe literature on the ethics of biobanking often overlooks the practical operations of biobanks. The ethics of stewardship requires that biobank resources are used to conduct beneficial science. Networked biobanks have emerged to increase the scientific benefit of biobank resources, but little is known about whether and how operations of networking may accomplish this goal.As part of a larger study on the ethical, legal, and social implications (ELSI) of networked biobanking, we conducted 38 interviews with representatives of 31 networked biobanks. Interviews explored operations of the networks. We used thematic analysis to examine how respondents describe three topics associated with stewarding biobank resources—funding, utilization, and sustainability.Our results highlight that funding, utilization, and sustainability are critical not only to the operation of biobanks, but also to the ethical obligations that biobankers owe to stakeholders to steward the resources. Based on prior research, we hypothesized that respondents would describe networking as beneficial to increasing funding, utilization, and sustainability of the network. Respondents generally found value in networked biobanking, but networking did not necessarily increase funding, utilization, and sustainability.The results presented here support inclusion of funding, utilization, and sustainability as topics of ethical concern in the practice of biobanking and networked biobanking. These issues are rooted in the stewardship obligations that biobankers feel to their partners, client investigators, and participants. The goal of promoting stewardship through networking requires significant time and effort to build governance models that honor the obligations of each individual biobank to their donors and advance the collective goals of the network. We conclude with suggestions offered by respondents to address improving these aspects of stewardship. [ABSTRACT FROM AUTHOR]

Understanding sex differences when assessing personality in older adults is important for researchers and clinicians. The current study utilized differential item functioning (DIF) to compare male and female older adults’ responses on the NEO-FFI to detect potential sources of measurement bias. Participants included 244 older adults (98 males, 146 females, mean age = 73). DIF by sex was determined using ordinal logistic regression and item response theory.Non-uniform DIF was present in item 31, and uniform DIF was present in item 26 in the Neuroticism scale. In the Extraversion scale, non-uniform DIF was present in items 32 and 37. In the Openness scale, non-uniform DIF was present in items 23 and 48; uniform DIF was present in items 53 and 58. Following Monte Carlo simulations to prevent overidentification, non-uniform DIF was present in item 31 in the Neuroticism scale and item 32 in the Extraversion scale. Results suggest that the NEO-FFI is a minimally biased measurement tool based on sex.

Recent evidence suggests that physical activity may influence the functional connectivity of the aging brain. The purpose of this study was to examine the influence of physical activity on the association between executive function and functional connectivity of key brain networks and graph theory metrics in community-dwelling older adults. Participants were 47 older adults (M = 73 years; SD = 5.92) who participated in neuropsychological testing, physical activity measurements, and magnetic resonance imaging (MRI). Seed-to-voxel moderation analyses and graph theory analyses were conducted. Physical activity was significantly positively associated with default mode network functional connectivity (DMN FC; Posterior Cingulate Gyrus, p-FDR = 0.005; Frontal Pole (L), p-FDR = 0.005; Posterior Cingulate Gyrus, p-FDR = 0.006; Superior Frontal Gyrus (L), p-FDR = 0.016) and dorsal attention network functional connectivity (DAN FC; Inferior Frontal Gyrus Pars Opercularis (R), p-FDR = 0.044). The interaction between physical activity and executive function on the DMN FC and DAN FC was analyzed. The interaction between executive function and physical activity was significantly associated with DMN FC. When this significant interaction was probed, the association between physical activity and DMN FC differed between levels of high and low executive function such that the association was only significant at levels of high executive function. These results suggest that greater physical activity in later life is associated with greater DMN and DAN FC and provides evidence for the importance of physical activity in cognitively healthy older adults.

Objetivo: Determinar la utilidad del gasto urinario alto como predictor temprano de bajo costo para hipoparatiroidismo posoperatorio. Método: Se realizó un estudio retrospectivo unicéntrico a 1 año en adultos sometidos a tiroidectomía total en The American British Cowdray Medical Center I.A.P., calculando el gasto urinario en 24 horas, utilizando valores de calcio sérico corregido por albúmina con una tabla de correlación e identificando a los pacientes que recibieron calcio suplementario en las primeras horas de posoperatorio. Se dividieron en pacientes con hipoparatiroidismo posoperatorio y con valores normales de calcio en el primer día, diferenciando a los que recibieron suplementación oral de calcio profiláctico. Resultados: Se estudiaron 47 pacientes, 19 (40%) en el grupo con hipocalcemia posoperatoria y 28 (59.5%) en el grupo sin hipocalcemia posoperatoria. La media de gasto urinario en las primeras 8 horas de posoperatorio fue mayor en el grupo de hipocalcemia posoperatoria en comparación con el grupo sin hipocalcemia, sin diferencia significativa (p = 0.392), y tampoco durante las primeras 16 horas (p = 0.435). Conclusiones: En nuestro estudio no existe relación entre el incremento del gasto urinario y la predicción de hipoparatiroidismo posoperatorio. Se necesitan estudios con muestras de mayor tamaño y con un diseño metodológico más fuerte (prospectivo) para determinar si en realidad la diferencia obtenida puede figurar como predictor.

Introduction: The South East Asia Research Collaboration in HIV (SEARCH) RV411 clinical trial in Thailand was a systematic investigation of analytic treatment interruption (ATI) in individuals diagnosed and treated since Fiebig stage I acute HIV infection. Here, we explore decision-making processes and perceptions of trial participation in a phase I trial that raised important ethical considerations, to identify potential areas of improvement in this relatively new field of HIV research. Similar considerations apply to other HIV phase I trials, especially those involving ATI, making this trial a model to identify challenges and opportunities in promoting informed choice. Methods: Using longitudinal semi-structured interviews and a validated questionnaire, we examined how decisions to join or decline the trial were made, whether there was evidence of decisional conflict, and reactions to the trial outcomes. We also explored contrasting views and experiences in this small trial cohort. We report analyses of data from these questionnaires and interviews, conducted from February through December of 2016 with the 14 SEARCH cohort participants who either joined (n = 8) or declined (n = 6) participation in RV411. Results: The eight participants and six decliners had low overall decisional conflict, which remained low over time. Decision making was more difficult for decliners than participants, at least initially. While all interviewees described being satisfied with their decisions, our study identified important negative consequences for a few individuals, including seroconversion, negative experiences with optional procedures and disappointment due to rapid viral rebound. Conclusions: Although our results reflect the experiences of a small group invited to join this trial, our overall finding of low decisional conflict even while some individuals reported negative experiences provides lessons for clinical trial investigators. We developed points-to-consider in helping participants make informed choices, to support participants during the trial and to support decliners in their decisions. Keywords: phase I clinical trials; HIV clinical trials; analytic treatment interruption; research ethics; informed consent; qualitative research, 1 | INTRODUCTION In 2009, the South East Asia Research Collaboration in HIV (SEARCH) at the Thai Red Cross AIDS Research Centre began diagnosing and treating individuals with acute HIV [...]

Collaborations between clinical investigators and behavioral and social science researchers (BSSR) produce many benefits, but also may generate challenges and complexities. Ongoing relationships between teams may affect the research carried out by the BSSR team and the way they interpret their findings. Here we describe our experiences conducting the HIV Remission (‘Cure’) Trials Decision-Making Study (DMS), in Thailand; these trials include potentially risky interventions and interruption of standard antiretroviral treatment, with little personal benefit. The DMS is a longitudinal study of the experiences of individuals recruited to such early-phase trials, and conducted alongside these trials. It originated in clinical investigators' concerns about the ability of those recruited to make voluntary and informed decisions about scientifically complex studies, and is led by an independent group of BSSR and ethics researchers. In conducting this study, we experienced three overarching challenges to achieving a successful and dynamic collaboration: managing emerging findings as data were collected alongside clinical trial participation; evolving interconnectedness and shifting partnership boundaries among investigators; and the process of incorporating new research questions. By describing these challenges, we provide experiential evidence on how to manage multidimensional aspects of these collaborations. We describe how our research teams came together as well as the challenges and opportunities we experienced along the way. Our aim is to raise awareness of the scientific, practical, and ethical complexities of establishing and maintaining this kind of broad multidisciplinary collaboration over time. By describing our experiences, we hope to advance an agenda for others who undertake similar partnerships.

Introduction The ethical skills fundamental to medical practice encompass a large portion of the Accreditation Council for Graduate Medical Education (ACGME) professionalism milestones. Yet many ethical practices are difficult to reduce to milestone frameworks given the variety of traditions of moral reasoning that clinician-trainees and their colleagues might properly employ. Methods We developed an observed standardized clinical examination (OSCE) simulation with standardized patients to assess the ethical skills captured in professionalism milestones in pediatrics. The OSCE included four vignettes based on actual cases that presented problems without a correct answer. Residents discussed ethically challenging issues with standardized patients and were evaluated on specific ethical tenets contained in the professionalism milestones. Our assessment guide for preceptors offered content for debriefing and assessment. We piloted this OSCE with seven preceptors and 17 pediatric residents in two different medical settings. Results Residents all agreed that the four cases were realistic. All but two residents agreed that OSCEs like this one are an appropriate or objective way of assessing the ACGME professionalism milestones. All preceptors reported that they strongly agreed the assessment improved their ability to assess the professionalism milestones. Discussion This OSCE offers a structured method to assess professionalism milestones and a forum to discuss ethical problem solving. It can also be used solely as a training exercise in ethical decision making and having difficult conversations.

Translational research has tended to ignore the question of whether receiving a genomic diagnosis provides utility in community care contexts outside of doctors' offices and hospitals. However, empirical research with parents has highlighted numerous ways that a genomic diagnosis might be of practical value in the care provided by teachers, physical or occupational therapists, speech‐language pathologists, behavior analysts, and nonphysician mental health providers. In this essay, we propose a new conceptual model of genomic utility that offers the opportunity to better capture a broad range of potential implications of genomic technologies for families in various social and organizational systems. We explore crucial research directions to better understand how redefined utility might affect families and nonphysician professionals. [ABSTRACT FROM AUTHOR]

Background: Posttransplant lymphoproliferative disorder (PTLD) is a major complication following kidney transplantation. Objective: We undertook this study to characterize PTLD in kidney transplant patients in British Columbia with regard to incidence, patient and graft survival, histological subtypes, treatment modalities, and management of immunosuppression. Design: Retrospective cohort analysis. Setting: British Columbia. Patients: All adult patients who underwent kidney transplantation in British Columbia between January 1, 1996, and December 31, 2012, were included. Patients less than 18 years of age at the time of first transplant and multiple organ transplant recipients were excluded from analysis. Measurements: Patients with lymphoproliferative disorders that occurred subsequent to kidney transplantation were considered to have developed PTLD. Methods: Cases of PTLD were identified by cross-referencing data abstracted from the provincial transplant agency’s clinical database with the provincial cancer agency’s lymphoma registry. Patients were followed up for the development of PTLD until December 31, 2012, and for outcomes of death and graft failure until December 31, 2014. Data collection was completed via an electronic chart review. Results: Of 2217 kidney transplant recipients, 37 (1.7%) developed PTLD. Nine cases were early-onset PTLD, occurring within 1 year of transplant; of these cases, 6 were known/presumed Epstein-Barr virus mismatch, compared with only 2 of 28 late-onset cases. Patient survival for early-onset PTLD was 100% at 2 years post diagnosis. Late-onset PTLD had survival rates of 71.4% and 67.9% at 1 and 2 years, respectively. PTLD was associated with significantly decreased patient survival ( P = .031) and graft survival (uncensored for death, P = .017), with median graft survival of PTLD and non-PTLD patients being 9.5 and 16 years, respectively. Immunosuppressant therapy was reduced in the majority of patients; additional therapies included rituximab monotherapy, CHOP-R, radiation, and surgery. Limitations: Limitations to this study include its retrospective nature and the unknown adherence of patients to prescribed immunosuppressant regimens. In addition, cumulative doses of immunosuppression received and the degree of immunosuppression reduction for PTLD management were not effectively captured. Conclusions: The incidence of PTLD in British Columbia following kidney transplantation was low and consistent with rates reported in the literature. The incidence of late-onset PTLD and its association with reduced patient and graft survival warrant further analysis of patients’ long-term immunosuppression.

OBJECTIVE:Estimates indicate that 20-70% of renal transplant recipients are medication non-adherent, significantly increasing the risk of organ rejection. Medication adherence is negatively impacted by lower everyday problem solving ability, and associations between depressive symptoms, self-efficacy, and adherence are reported in renal transplant recipients. Nonetheless, to date, these associations have not been examined concurrently. Given the relationship between non-adherence and organ rejection, it is critical to gain a better understanding of the predictors of adherence in renal transplant recipients. To this end, we modeled relationships among cognitive abilities, depressive symptoms, self-efficacy, and adherence in this group. METHODS:Participants (N = 211) underwent renal transplant at least one year prior to participation. Adherence was measured via self-report, medication possession ratio, and immunosuppressant blood-level. Traditionally-measured neurocognitive and everyday problem-solving abilities were assessed. Depressive symptoms were measured via self-report, as were general and medication adherence related self-efficacy. Structural equation modeling was used to assess the fit of the model to available data. RESULTS:Everyday problem solving and self-efficacy had direct positive associations with adherence. Depressive symptoms were negatively associated with self-efficacy, but not adherence. Traditionally-measured neurocognitive abilities were positively associated with self-efficacy, and negatively associated with depressive symptoms. CONCLUSIONS:We present a comprehensive investigation of relationships between cognitive and psychosocial factors and adherence in medically stable renal transplant recipients. Findings confirm the importance of everyday problem solving and self-efficacy in predicting adherence and suggest that influences of depressive symptoms and neurocognitive abilities are indirect. Findings have important implications for future development of interventions to improve medication adherence in renal transplant recipients.

This paper analyses the activities of five organizations shaping the debate over the global governance of genome editing in order to assess current approaches to public engagement (PE). We compare the recommendations of each group with its own practices. All recommend broad engagement with the general public, but their practices vary from expert-driven models dominated by scientists, experts, and civil society groups to citizen deliberation-driven models that feature bidirectional consultation with local citizens, as well as hybrid models that combine elements of both approaches. Only one group practices PE that seeks community perspectives to advance equity. In most cases, PE does little more than record already well-known views held by the most vocal groups, and thus is unlikely to produce more just or equitable processes or policy outcomes. Our exploration of the strengths, weaknesses, and possibilities of current forms of PE suggests a need to rethink both "public" and "engagement." [ABSTRACT FROM AUTHOR]

Children with disabilities and rare or undiagnosed conditions and their families have faced numerous hardships of living during the COVID-19 pandemic. For those with undiagnosed conditions, the diagnostic odyssey can be long, expensive, and marked by uncertainty. We, therefore, sought to understand whether and how COVID-19 impacted the trajectory of children's care. We conducted semi-structured qualitative interviews with 25 caregivers who, prior to the pandemic, were on a diagnostic odyssey for their children. Most caregivers did not report any interruptions to their child's diagnostic odyssey. The greatest impact was access to therapy services, including the suspension or loss of their child's in-person therapeutic care and difficulties with virtual therapies. This therapy gap caused caregivers to fear that their children were not making progress. Although much has been written about the challenges of diagnostic odysseys for children and their families, this study illustrates the importance of expanding the focus of these studies to include therapeutic odysseys. Because therapeutic odysseys continue regardless of whether diagnoses are made, future research should investigate how to support caregivers through children's therapies within and outside of the COVID-19 context. [ABSTRACT FROM AUTHOR]

Two tick-borne diseases with expanding case and vector distributions are ehrlichiosis (transmitted by Amblyomma americanum) and rickettiosis (transmitted by A. maculatum and Dermacentor variabilis). There is a critical need to identify the specific habitats where each of these species is likely to be encountered to classify and pinpoint risk areas. Consequently, an in-depth tick prevalence study was conducted on the dominant ticks in the southeast. Vegetation, soil, and remote sensing data were used to test the hypothesis that habitat and vegetation variables can predict tick abundances. No variables were significant predictors of A. americanum adult and nymph tick abundance, and no clustering was evident because this species was found throughout the study area. For A. maculatum adult tick abundance was predicted by NDVI and by the interaction between habitat type and plant diversity; two significant population clusters were identified in a heterogeneous area suitable for quail habitat. For D. variabilis no environmental variables were significant predictors of adult abundance; however, D. variabilis collections clustered in three significant areas best described as agriculture areas with defined edges. This study identified few landscape and vegetation variables associated with tick presence. While some variables were significantly associated with tick populations, the amount of explained variation was not useful for predicting reliably where ticks occur; consequently, additional research that includes multiple sampling seasons and locations throughout the southeast are warranted. This low amount of explained variation may also be due to the use of hosts for dispersal, and potentially to other abiotic and biotic variables. Host species play a large role in the establishment, maintenance, and dispersal of a tick species, as well as the maintenance of disease cycles, dispersal to new areas, and identification of risk areas.

BACKGROUND: The pp65 cytomegalovirus (CMV) antigenemia assay has been used as a means of guiding the pre-emptive therapy of CMV disease in solid organ transplant (SOT) recipients. Recently, concerns have been raised regarding the utility of the test to accurately and precisely detect viral activity early enough to reduce the morbidity and mortality associated with CMV.