Governing Gene Drive Technologies:A Qualitative Interview Study

Background: Gene drive technologies (GDTs) bias the inheritance of a genetic element within a population of non-human organisms, promoting its progressive spread across this population. If successful, GDTs may be used to counter intractable problems such as vector-borne diseases. A key issue in the debate on GDTs relates to what governance is appropriate for these technologies. While governance mechanisms for GDTs are to a significant extent proposed and shaped by professional experts, the perspectives of these experts have not been explored in depth. Methods: A total of 33 GDT experts from different professional disciplines were interviewed to identify, better understand, and juxtapose their perspectives on GDT governance. The pseudonymized transcripts were analyzed thematically. Results: Three main themes were identified: (1) engagement of communities, stakeholders, and publics; (2) power dynamics, and (3) decision-making. There was broad consensus amongst respondents that it is important to engage communities, stakeholders, and publics. Nonetheless, respondents had diverging views on the reasons for doing so and the timing and design of engagement. Respondents also outlined complexities and challenges related to engagement. Moreover, they brought up the power dynamics that are present in GDT research. Respondents stressed the importance of preventing the recurrence of historical injustices and reflected on dilemmas regarding whether and to what extent (foreign) researchers can legitimately make demands regarding local governance. Finally, respondents had diverging views on whether decisions about GDTs should be made in the same way as decisions about other environmental interventions, and on the decision-making model that should be used to decide about GDT deployment. Conclusions: The insights obtained in this interview study give rise to recommendations for the design and evaluation of GDT governance. Moreover, these insights point to unresolved normative questions that need to be addressed to move from general commitments to concrete obligations

Guidance on stakeholder engagement practices to inform the development of areawide vector control methods

This is the final version. Available from the publisher via the DOI in this record.British Academ

Circadian changes and sex-related differences in fetal heart rate parameters

BACKGROUND: Previous researchers have studied circadian changes in the fetal heart rate (FHR) on small sample sizes and in a strictly controlled environment. This study was undertaken to investigate these changes during the late second and third trimesters, using a portable fetal electrocardiogram recording device (Monica AN24) in pregnant women in home and hospital environments with unrestricted mobility. METHODS: This was a prospective cohort study of 54 pregnant women with uncomplicated singleton pregnancies between 25 and 40 weeks gestation. FHR recordings were made up to 16 h at home or in the hospital setting in the United Kingdom. FHR data over 90 min periods were averaged and the day (7:00 am-11:00 pm) and night (11:00 pm-7:00 am) data from the same individual were compared. Data were examined for evidence of sex-related differences. RESULTS: During the night, there was a significant reduction in basal heart rate (bFHR) and a significant increase in short term variation (STV) and long term variation (LTV) (P < 0.05). Basal FHR decreased (P < 0.002), whereas LTV increased (P = 0.014) with advancing gestation. Male fetuses showed greater day: night variation than females regardless of gestation (P = 0.014). There was a higher bFHR in fetuses monitored during the day in hospital (P = 0.04). CONCLUSION: This study demonstrates that there are sex-, environment and time-related differences in the FHR parameters measured. These differences may need to be considered taken when interpreting FHR data

Public Access to Genome-Wide Data: Five Views on Balancing Research with Privacy and Protection

Introductory paragraph: Just over twelve months ago, PLoS Genetics published a paper [1] demonstrating that, given genome-wide genotype data from an individual, it is, in principle, possible to ascertain whether that individual is a member of a larger group defined solely by aggregate genotype frequencies, such as a forensic sample or a cohort of participants in a genome-wide association study (GWAS). As a consequence, the National Institutes of Health (NIH) and Wellcome Trust agreed to shut down public access not just to individual genotype data but even to aggregate genotype frequency data from each study published using their funding. Reactions to this decision span the full breadth of opinion, from ‘‘too little, too late—the public trust has been breached’’ to ‘‘a heavy-handed bureaucratic response to a practically minimal risk that will unnecessarily inhibit scientific research.’’ Scientific concerns have also been raised over the conditions under which individual identity can truly be accurately determined from GWAS data. These concerns are addressed in two papers published in this month’s issue of PLoS Genetics [2,3]. We received several submissions on this topic and decided to assemble these viewpoints as a contribution to the debate and ask readers to contribute their thoughts through the PLoS online commentary features. Five viewpoints are included. The Public Population Project in Genomics (P3G) is calling for a universal researcher ID with an access permit mechanism for bona fide researchers. The contribution by Catherine Heeney, Naomi Hawkins, Jantina de Vries, Paula Boddington, and Jane Kaye of the University of Oxford Ethox Centre outlines some of the concerns over possible misuse of individual identification in conjunction with medical and family history data, and points out that if geneticists mishandle public trust, it will backfire on their ability to conduct further research. George Church posits that actions directed toward restricting data access are likely to exclude researchers who might provide the most novel insights into the data and instead makes the argument that full disclosure and consent to the release of genomic information should be sought from study participants, rather than making difficult-to-guarantee promises of anonymity. Martin Bobrow weighs the risks and benefits and proposes four steps that represent a middle ground: Retain restricted access for now, make malicious de-identification practices illegal, increase public awareness of the issues, and encourage recognition that scientists have a special professional relationship of trust with study participants. Finally, Bruce Weir provides a commentary on the contribution of the two research articles from Braun et al. [2] and Visscher and Hill [3]

Routes for breaching and protecting genetic privacy

We are entering the era of ubiquitous genetic information for research, clinical care, and personal curiosity. Sharing these datasets is vital for rapid progress in understanding the genetic basis of human diseases. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we technically map threats to genetic privacy and discuss potential mitigation strategies for privacy-preserving dissemination of genetic data.Comment: Draft for comment

Qualitative thematic analysis of consent forms used in cancer genome sequencing

<p>Abstract</p> <p>Background</p> <p>Large-scale whole genome sequencing (WGS) studies promise to revolutionize cancer research by identifying targets for therapy and by discovering molecular biomarkers to aid early diagnosis, to better determine prognosis and to improve treatment response prediction. Such projects raise a number of ethical, legal, and social (ELS) issues that should be considered. In this study, we set out to discover how these issues are being handled across different jurisdictions.</p> <p>Methods</p> <p>We examined informed consent (IC) forms from 30 cancer genome sequencing studies to assess (1) stated purpose of sample collection, (2) scope of consent requested, (3) data sharing protocols (4) privacy protection measures, (5) described risks of participation, (6) subject re-contacting, and (7) protocol for withdrawal.</p> <p>Results</p> <p>There is a high degree of similarity in how cancer researchers engaged in WGS are protecting participant privacy. We observed a strong trend towards both using samples for additional, unspecified research and sharing data with other investigators. IC forms were varied in terms of how they discussed re-contacting participants, returning results and facilitating participant withdrawal. Contrary to expectation, there were no consistent trends that emerged over the eight year period from which forms were collected.</p> <p>Conclusion</p> <p>Examining IC forms from WGS studies elucidates how investigators are handling ELS challenges posed by this research. This information is important for ensuring that while the public benefits of research are maximized, the rights of participants are also being appropriately respected.</p

The Mind and the Machine. On the Conceptual and Moral Implications of Brain-Machine Interaction

Brain-machine interfaces are a growing field of research and application. The increasing possibilities to connect the human brain to electronic devices and computer software can be put to use in medicine, the military, and entertainment. Concrete technologies include cochlear implants, Deep Brain Stimulation, neurofeedback and neuroprosthesis. The expectations for the near and further future are high, though it is difficult to separate hope from hype. The focus in this paper is on the effects that these new technologies may have on our ‘symbolic order’—on the ways in which popular categories and concepts may change or be reinterpreted. First, the blurring distinction between man and machine and the idea of the cyborg are discussed. It is argued that the morally relevant difference is that between persons and non-persons, which does not necessarily coincide with the distinction between man and machine. The concept of the person remains useful. It may, however, become more difficult to assess the limits of the human body. Next, the distinction between body and mind is discussed. The mind is increasingly seen as a function of the brain, and thus understood in bodily and mechanical terms. This raises questions concerning concepts of free will and moral responsibility that may have far reaching consequences in the field of law, where some have argued for a revision of our criminal justice system, from retributivist to consequentialist. Even without such a (unlikely and unwarranted) revision occurring, brain-machine interactions raise many interesting questions regarding distribution and attribution of responsibility

PIN71 QUALITY OF LIFE (QOL) AND OTHER ENDPOINTS COMPARISON IN THE TREATMENT OF FACIAL LIPOATROPHY WITH INJECTION OF POLY-L-LACTIC ACID

Context: Longitudinal data on bone mineral density(BMD) in children and adolescents with Prader-Willi Syndrome (PWS) during long-term GH treatment are not available. Objective: This study aimed to determine effects of long-term GH treatment and puberty on BMD of total body (BMDTB), lumbar spine (BMDLS), and bone mineral apparent density of the lumbar spine (BMAD(LS)) in children with PWS. Design and Setting: This was a prospective longitudinal study of a Dutch PWS cohort. Participants: Seventy-seven children with PWS who remained prepubertal during GH treatment for 4 years and 64 children with PWS who received GH treatment for 9 years participated in the study. Intervention: The children received GH treatment, 1 mg/m(2)/day (congruent to 0.035 mg/kg/d). Main Outcome Measures: BMDTB, BMDLS, and BMAD(LS) was measured by using the same dual-energy x-ray absorptiometry machine for all annual measurements. Results: In the prepubertal group, BMDTB standard deviation score (SDS) and BMDLSSDS significantly increased during 4 years of GH treatment whereas BMAD(LS)SDS remained stable. During adolescence, BMDTBSDS and BMAD(LS)SDS decreased significantly, in girls from the age of 11 years and in boys from the ages of 14 and 16 years, respectively, but all BMD parameters remained within the normal range. Higher Tanner stages tended to be associated with lower BMDTBSDS (P = .083) and a significantly lowerBMAD(LS)SDS (P = .016). After 9 years of GH treatment, lean body mass SDS was the most powerful predictor of BMDTBSDS and BMDLSSDS in adolescents with PWS. Conclusions: This long-term GH study demonstrates that BMDTB, BMDLS, and BMAD(LS) remain stable in prepubertal children with PWS but decreases during adolescence, parallel to incomplete pubertal development. Based on our findings, clinicians should start sex hormone therapy from the age of 11 years in girls and 14 years in boys unless there is a normal progression of puberty

Non-operative treatment for perforated gastro-duodenal peptic ulcer in Duchenne Muscular Dystrophy: a case report

BACKGROUND: Clinical characteristics and complications of Duchenne muscular dystrophy caused by skeletal and cardiac muscle degeneration are well known. Gastro-intestinal involvement has also been recognised in these patients. However an acute perforated gastro-duodenal peptic ulcer has not been documented up to now. CASE PRESENTATION: A 26-year-old male with Duchenne muscular dystrophy with a clinical and radiographic diagnosis of acute perforated gastro-duodenal peptic ulcer is treated non-operatively with naso-gastric suction and intravenous medication. Gastrointestinal involvement in Duchenne muscular dystrophy and therapeutic considerations in a high risk patient are discussed. CONCLUSION: Non-surgical treatment for perforated gastro-duodenal peptic ulcer should be considered in high risk patients, as is the case in patients with Duchenne muscular dystrophy. Patients must be carefully observed and operated on if non-operative treatment is unsuccessful