Moving beyond narrow definitions of gene drive: Diverse perspectives and frames enable substantive dialogue among science and humanities teachers in the United States and United Kingdom

Gene drive is an emerging biotechnology with applications in global health, conservation and agriculture. Scientists are preparing for field trials, triggering debate about when and how to release gene-drive organisms. These decisions depend on public understandings of gene drive, which are shaped by language. While some studies on gene drive communication assume the need to persuade publics of expert definitions of gene drive, we highlight the importance of meaning-making in communication and engagement. We conducted focus groups with humanities and science teachers in the United Kingdom and United States to explore how different media framings stimulated discussions of gene drive. We found diversity in the value of these framings for public debate. Interestingly, the definition favoured by gene drive scientists was the least popular among participants. Rather than carefully curating language, we need opportunities for publics to make sense and negotiate the meanings of a technology on their own terms

The influence of tumor regression, solar elastosis, and patient age on pathologists\u27 interpretation of melanocytic skin lesions.

It is not known whether patient age or tumor characteristics such as tumor regression or solar elastosis influence pathologists\u27 interpretation of melanocytic skin lesions (MSLs). We undertook a study to determine the influence of these factors, and to explore pathologist\u27s characteristics associated with the direction of diagnosis. To meet our objective, we designed a cross-sectional survey study of pathologists\u27 clinical practices and perceptions. Pathologists were recruited from diverse practices in 10 states in the United States. We enrolled 207 pathologist participants whose practice included the interpretation of MSLs. Our findings indicated that the majority of pathologists (54.6%) were influenced toward a less severe diagnosis when patients were70 years of age, or by the presence of tumor regression or solar elastosis (58.5%, 71.0%, and 57.0%, respectively). Generally, pathologists with dermatopathology board certification and/or a high caseload of MSLs were more likely to be influenced, whereas those with more years\u27 experience interpreting MSL were less likely to be influenced. Our findings indicate that the interpretation of MSLs is influenced by patient age, tumor regression, and solar elastosis; such influence is associated with dermatopathology training and higher caseload, consistent with expertise and an appreciation of lesion complexity

Proceedings of an expert workshop on community agreement for gene drive research in Africa - Co-organised by KEMRI, PAMCA and Target Malaria.

Gene drive research is progressing towards future field evaluation of modified mosquitoes for malaria control in sub-Saharan Africa. While many literature sources and guidance point to the inadequacy of individual informed consent for any genetically modified mosquito release, including gene drive ones, (outside of epidemiological studies that might require blood samples) and at the need for a community-level decision, researchers often find themselves with no specific guidance on how that decision should be made, expressed and by whom. Target Malaria, the Kenya Medical Research Institute and the Pan African Mosquito Control Association co-organised a workshop with researchers and practitioners on this topic to question the model proposed by Target Malaria in its research so far that involved the release of genetically modified sterile male mosquitoes and how this could be adapted to future studies involving gene drive mosquito releases for them to offer reflections about potential best practices. This paper shares the outcomes of that workshop and highlights the remaining topics for discussion before a comprehensive model can be designed

Proceedings of an expert workshop on community agreement for gene drive research in Africa - Co-organised by KEMRI, PAMCA and Target Malaria.

Gene drive research is progressing towards future field evaluation of modified mosquitoes for malaria control in sub-Saharan Africa. While many literature sources and guidance point to the inadequacy of individual informed consent for any genetically modified mosquito release, including gene drive ones, (outside of epidemiological studies that might require blood samples) and at the need for a community-level decision, researchers often find themselves with no specific guidance on how that decision should be made, expressed and by whom. Target Malaria, the Kenya Medical Research Institute and the Pan African Mosquito Control Association co-organised a workshop with researchers and practitioners on this topic to question the model proposed by Target Malaria in its research so far that involved the release of genetically modified sterile male mosquitoes and how this could be adapted to future studies involving gene drive mosquito releases for them to offer reflections about potential best practices. This paper shares the outcomes of that workshop and highlights the remaining topics for discussion before a comprehensive model can be designed

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

A protective role of transmembrane channel-like proteins in human papillomavirus infection

Ph.D. University of Hawaii at Manoa 2010.Includes bibliographical references.The identification of certain viral infections as the etiological agents responsible for inducing cancer has provided opportunities for prevention, detection, and treatments of these cancers. A rare genodermitosis known as Epidermodysplasia Verruciformis (EV) results in elevated levels of human papillomavirus (HPV) infection that frequently lead to squamous cell carcinoma (SCC) on sun-exposed areas of the skin. EV has long been thought to be a model for viral-induced cancer, but it was not until the year 2000 that mutations in two related genes were identified as being responsible for this disorder. Unfortunately, there is very little understanding of the function of their protein products: Transmembrane Channel-Like (TMC) proteins-6 and-8. We used Western blotting and immunohistochemical techniques to demonstrate that TMC8 is highly expressed in the skin and in particular the basal cells, which are key to HPV infection. We also demonstrate that TMC8 interacts with two proteins through the carboxyl terminus of TMC8: Non-Metastatic cell protein 1 (NME1) and Peroxiredoxin 2 (PRDX2). This study showed that TMC8 expression is affected by ROS generated by exposure to mitochondrial disruptors. We also tested the effect of TMC8 over expression on cell viability and found that it had a significant negative affect. Based on this data and the presentation of EV, the life cycle of HPV, and previous data, TMC8 appears to be a ROS-sensitive mediator of apoptosis. This study has produced valuable new data and also important new questions regarding TMC proteins. By continuing to expand this area of inquiry, hopefully knowledge can be gained to help relieve the suffering of those with EV, those with sporadic TMC mutations, and for immune compromised individuals that develop SCC that are associated with beta papillomaviruses

Submitted to Machine Learning. Summary

DNA micro-arrays now permit scientists to screen thousands of genes simultaneously and determine whether those genes are active, hyperactive or silent in normal or cancerous tissue. Because these new micro-array devices generate bewildering amounts of raw data, new analytical methods must be developed to sort out whether cancer tissues have distinctive signatures of gene expression over normal tissues or other types of cancer tissues. In this paper, we address the problem of selection of a small subset of genes from broad patterns of gene expression data, recorded on DNA micro-arrays. Using available training examples from cancer and normal patients, we build a classifier suitable for genetic diagnosis, as well as drug discovery. Previous attempts to address this problem select genes with correlation techniques. We propose a new method of gene selection utilizing Support Vector Machine methods based on Recursive Feature Elimination (RFE). We demonstrate experimentally that the genes selected by our techniques yield better classification performance and are biologically relevant to cancer. In contrast with the baseline method, our method eliminates gene redundancy automatically and yields better and more compact gene subsets. In patients with leukemia our method discovered 2 genes that yield zero leave-one-out error, while 64 genes are necessary for the baseline method to get the best result (one leave-one-out error). In the colon cancer database, using only 4 genes our method is 98 % accurate, while the baseline method is only 86 % accurate

Combating Dengue: A US Military Perspective

Throughout history, dengue virus infections have negatively impacted the mission capabilities of US Service Members. Currently, the expansion of dengue into new regions via the spread of the Aedes genus along with the global presence of the US Military, poses an increased risk for Service Members to contract the virus. Dengue virus infection would not only lead to significant medical costs and a lack of military readiness, but to mission impairment and failure. Therefore, it is important that the US Military explore the virulence, outbreaks, and treatments of dengue virus infection to help prevent its spread and determine solutions for its eradication. This review examines current dengue epidemiology by Combatant Commands, field detection, treatments, preventive measures, prophylactic capabilities, and directions of future research

Rodent gene drives for conservation: opportunities and data needs

Invasive rodents impact biodiversity, human health and food security worldwide. The biodiversity impacts are particularly significant on islands, which are the primary sites of vertebrate extinctions and where we are reaching the limits of current control technologies. Gene drives may represent an effective approach to this challenge, but knowledge gaps remain in a number of areas. This paper is focused on what is currently known about natural and developing synthetic gene drive systems in mice, some key areas where key knowledge gaps exist, findings in a variety of disciplines relevant to those gaps and a brief consideration of how engagement at the regulatory, stakeholder and community levels can accompany and contribute to this effort. Our primary species focus is the house mouse, Mus musculus, as a genetic model system that is also an important invasive pest. Our primary application focus is the development of gene drive systems intended to reduce reproduction and potentially eliminate invasive rodents from islands. Gene drive technologies in rodents have the potential to produce significant benefits for biodiversity conservation, human health and food security. A broad-based, multidisciplinary approach is necessary to assess this potential in a transparent, effective and responsible manner