Accelerating Development of SARS-CoV-2 Vaccines — The Role for Controlled Human Infection Models

The third coronavirus outbreak in the past 20 years, the SARS-CoV-2 pandemic has caused unprecedented morbidity, mortality, and economic disruption. Safe, effective, and deployable SARS-CoV-2 vaccines are urgently needed to mitigate the consequences of the pandemic and protect from future outbreaks. The accelerated response to Covid-19 includes investments in preclinical and clinical testing and manufacture of multiple vaccine candidates, with efficacy trials in the United States anticipated to start in July 2020

Endothelial, Inflammatory, Coagulation, Metabolic Effects and Safety of Etravirine in HIV-Uninfected Volunteers

Abstract The innate proatherosclerotic properties of non-nucleoside reverse transcriptase inhibitors have not previously been examined. Therefore, we performed a pilot study of etravirine (ETR) in healthy volunteers over 28 days. This investigation also allowed us to evaluate the safety of ETR over a period commonly used for HIV postexposure prophylaxis. ETR 200 mg twice daily was given to 28 healthy HIV-uninfected volunteers over 28 days. Flow-mediated dilation (FMD) of the brachial artery and circulating markers of inflammation, coagulation, and metabolism were measured at entry and at day 28. These circulating markers were also measured at day 35. Of the initial 28 subjects, 23 completed both entry and day 28 procedures. Two subjects were discontinued due to development of rash. No other major toxicities developed. The change in FMD over 28 days was minimal and not significant (0.03 [ -3.21, 0.97] %; p = 0.36). The post hoc estimated detectable absolute change in FMD with the 23 subjects in our study was 2.26%, which is an effect size that has been associated with future cardiovascular event rates in the general population; thus our study had sufficient power to find clinically relevant changes in FMD. In addition, there were no significant changes in any of the circulating markers from entry to day 28 or from day 28 to day 35. ETR did not demonstrate any innate proatherosclerotic properties over 28 days in these HIV-uninfected volunteers. ETR was generally well tolerated. Larger studies are warranted to confirm that ETR can be used safely as part of HIV postexposure prophylaxis regimens

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK

The Need for Laboratory Measurements and Ab Initio Studies to Aid Understanding of Exoplanetary Atmospheres

Laboratory astrophysics and astrochemistr

Software Experience Bases: A Consolidated Evaluation and Status Report

Abstract. The paper studies the potential success of using software experience bases for organizational learning. First, a survey of some previous efforts in the area is presented, together with experiences from related fields. The NASA-SEL Experience Factory will be especially commented. We note, that, modern network technologies like the Web provide new possibilities for distributed storage, access and dissemination of relevant knowledge. However, the main problem lies in internalizing formal knowledge (learning), not in externalizing experiences (model building). Then we present an empirical study of four software experience bases in the Norwegian SPIQ project for software process improvement, done in 1997-99. The SPIQ project proposes a pragmatical, overall method for how to plan, establish, use and evaluate software experience bases. The actual hypotheses and research method are presented, followed by a characterization of the studied experience bases and their actual usage and role in the associated companies. The most critical success factors are found to be incremental startup with a low ambition level, usefulness of the knowledge being offered, and, most importantly, stable company strategies and key personnel (may seem obvious, but still not easy). Some advice for introducing and evaluating software experience bases are finally given.