Improved Emergency Egress Lighting System for the ISS

Emergency lights provide illumination in corridors, stairwells, ramps, escalators, aisles, and exit passageways during power failures. Safety and visibility are critical during a power outage. If emergency lights fail to operate properly, the building occupants can become disoriented. Four documents in a collection discuss different topics relating to a proposed improved emergency egress lighting system (EELS) for the International Space Station (ISS). While the present EELS is designed around rows of green-light-emitting diodes, the proposed system contains strips of electroluminescent tape using different colors for each egress path. The proposed EELS can be powered by the same battery currently used by the present EELS, but would require an inverter because electroluminescent devices require AC. Electroluminescent devices also require significantly less current and, depending on the color, would emit 3 to 8 times the light of the present EELS. In addition, they could operate for up to 75 hours (versus .20 minutes for the present system). The first document contains a one-page summary of the proposal and an evaluation of technical merit. The second document summarizes the motivation for, and the design of, the proposed EELS. The third document addresses relevant aspects of the measurement of spectral sensitivity and the psychophysics of perception of light. The fourth document presents additional background information and technical specifications for the electroluminescent tapes

Reflections on the first year of integrity hour: An online community of practice for academic integrity

Integrity Hour first convened in March 2020, in response to the rapid pivot to emergency remote teaching during COVID-19. After a year, this online community of practice (CoP) is still going strong. We collectively reflect on how the first year of Integrity Hour has informed our understanding of how to uphold and enact academic integrity and impacted how we work with students, support our colleagues, and make decisions

Structural study of a new HIV-1 entry inhibitor and interaction with the HIV-1 fusion peptide in dodecylphosphocholine micelles

Previous studies support the hypothesis that the envelope GB virus C (GBV-C) E1 protein interferes the HIV-1 entry and that a peptide, derived from the region 139-156 of this protein, has been defined as a novel HIV-1 entry inhibitor. In this work, we firstly focus on the characterization of the structural features of this peptide, which are determinant for its anti-HIV-1 activity and secondly, on the study of its interaction with the proposed viral target (i.e., the HIV-1 fusion peptide). We report the structure of the peptide determined by NMR spectroscopy in dodecylphosphocholine (DPC) micelles solved by using restrained molecular dynamics calculations. The acquisition of different NMR experiments in DPC micelles (i.e., peptide-peptide titration, diffusion NMR spectroscopy, and addition of paramagnetic relaxation agents) allows a proposal of an inhibition mechanism. We conclude that a 18-mer peptide from the non-pathogenic E1 GBV-C protein, with a helix-turn-helix structure inhibits HIV-1 by binding to the HIV-1 fusion peptide at the membrane level, thereby interfering with those domains in the HIV-1, which are critical for stabilizing the six-helix bundle formation in a membranous environment.Peer ReviewedPostprint (author's final draft

The incidence and prevalence of diabetes in patients with serious mental illness in North West Wales: Two cohorts, 1875–1924 & 1994–2006 compared

<p>Abstract</p> <p>Background</p> <p>Against a background of interest in rates of diabetes in schizophrenia and related psychoses and claims that data from historical periods demonstrate a link that antedates modern antipsychotics, we sought to establish the rate of diabetes in first onset psychosis and subsequent prevalence in historical and contemporary cohorts.</p> <p>Methods</p> <p>Analysis of two epidemiologically complete databases of individuals admitted for mental illness. 3170 individuals admitted to the North Wales Asylum between 1875–1924 and tracked over 18,486 patient years and 394 North West Wales first admissions for schizophrenia and related psychoses between 1994 and 2006 and tracked after treatment.</p> <p>Results</p> <p>The prevalence of Type 2 diabetes among patients with psychoses at time of first admission in both historical and contemporary samples was 0%. The incidence of diabetes remained 0% in the historical sample throughout 15 years of follow-up but rose in the contemporary sample after 3, 5 and 6 years of treatment with an incidence rate double the expected population rate so that the 15 year prevalence is likely to be over 8%.</p> <p>Conclusion</p> <p>No association was found between diabetes and serious mental illness, but there may be an association between diabetes and treatment.</p

Are Adolescents with ADHD Interested in Genetic Testing for Nicotine Addiction Susceptibility?

It has been well-established that some adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for cigarette smoking. Current research on the genetic basis of this association could ultimately translate into genetic tests capable of identifying smoking-prone adolescents with ADHD. In this study we examined 81 ADHD affected adolescents’ (age 13–21) interest in genetic testing for nicotine addiction susceptibility. Fifty-seven percent of adolescents indicated a fair amount of interest or more in testing. Most adolescents indicated that the personal information revealed from testing would be either useful (29%) or interesting (37%). Implications for genetically-informed smoking prevention and cessation interventions in high risk adolescents with ADHD are discussed

Tisotumab Vedotin in Combination with Carboplatin, Pembrolizumab, or Bevacizumab in Recurrent or Metastatic Cervical Cancer:Results from the innovaTV 205/GOG-3024/ENGOT-cx8 Study

PURPOSE Tissue factor is highly expressed in cervical carcinoma and can be targeted by tisotumab vedotin (TV), an antibody-drug conjugate. This phase Ib/II study evaluated TV in combination with bevacizumab, pembrolizumab, or carboplatin for recurrent or metastatic cervical cancer (r/mCC). METHODS This open-label, multicenter study (ClinicalTrials.gov identifier: NCT03786081) included dose-escalation arms that assessed dose-limiting toxicities (DLTs) and identified the recommended phase II dose (RP2D) of TV in combination with bevacizumab (arm A), pembrolizumab (arm B), or carboplatin (arm C). The dose-expansion arms evaluated TV antitumor activity and safety at RP2D in combination with carboplatin as first-line (1L) treatment (arm D) or with pembrolizumab as 1L (arm E) or second-/third-line (2L/3L) treatment (arm F). The primary end point of dose expansion was objective response rate (ORR). RESULTS A total of 142 patients were enrolled. In dose escalation (n = 41), no DLTs were observed; the RP2D was TV 2 mg/kg plus bevacizumab 15 mg/kg on day 1 once every 3 weeks, pembrolizumab 200 mg on day 1 once every 3 weeks, or carboplatin AUC 5 on day 1 once every 3 weeks. In dose expansion (n = 101), the ORR was 54.5% (n/N, 18/33; 95% CI, 36.4 to 71.9) with 1L TV + carboplatin (arm D), 40.6% (n/N, 13/32; 95% CI, 23.7 to 59.4) with 1L TV + pembrolizumab (arm E), and 35.3% (12/34; 19.7 to 53.5) with 2L/3L TV + pembrolizumab (arm F). The median duration of response was 8.6 months, not reached, and 14.1 months, in arms D, E, and F, respectively. Grade ≥3 adverse events (≥15%) were anemia, diarrhea, nausea, and thrombocytopenia in arm D and anemia in arm F (none ≥15%, arm E).CONCLUSION TV in combination with bevacizumab, carboplatin, or pembrolizumab demonstrated manageable safety and encouraging antitumor activity in treatment-naive and previously treated r/mCC.</p

DNAm-based signatures of accelerated aging and mortality in blood are associated with low renal function

Background The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies. Results We identified 23 significant associations in our large trans-ethnic meta-analysis (p < 1.43E-03 and consistent direction of effect across studies). Age acceleration measured by the Extrinsic and PhenoAge estimators, as well as Zhang's 10-CpG epigenetic mortality risk score (MRS), were associated with all parameters of poor kidney health (lower eGFR, prevalent CKD, higher uACR, microalbuminuria and higher serum urate). Six of these associations were independently observed in European and African American populations. MRS in particular was consistently associated with eGFR (beta = - 0.12, 95% CI = [- 0.16, - 0.08] change in log-transformed eGFR per unit increase in MRS, p = 4.39E-08), prevalent CKD (odds ratio (OR) = 1.78 [1.47, 2.16], p = 2.71E-09) and higher serum urate levels (beta = 0.12 [0.07, 0.16], p = 2.08E-06). The first-generation clocks (Hannum, Horvath) and GrimAge showed different patterns of association with the kidney traits. Three of the DNAm-estimated components of GrimAge, namely adrenomedullin, plasminogen-activation inhibition 1 and pack years, were positively associated with higher uACR, serum urate and microalbuminuria. Conclusion DNAmAge acceleration and DNAm mortality predictors estimated in whole blood were associated with multiple kidney traits, including eGFR and CKD, in this multi-ethnic study. Epigenetic biomarkers which reflect the systemic effects of age-related mechanisms such as immunosenescence, inflammaging and oxidative stress may have important mechanistic or prognostic roles in kidney disease. Our study highlights new findings linking kidney disease to biological aging, and opportunities warranting future investigation into DNA methylation biomarkers for prognostic or risk stratification in kidney disease

Stream turbidity responses to storm events in a pristine rainforest watershed on the Coral Coast of southern Fiji

© 2016 International Research and Training Centre on Erosion and Sedimentation/the World Association for Sedimentation and Erosion Research On the Coral Coast of Viti Levu Island in Fiji, inadequate knowledge of suspended sediment delivery patterns in small pristine coastal watersheds hinders any future assessment of accelerated erosion in disturbed areas nearby. This study adopts a rainfall–stream turbidity monitoring approach in the Votua Creek, which drains a small, steep but minimally-disturbed coastal rainforest catchment. Storm rainfall characteristics, stream depth and water turbidity were continuously monitored over one complete Fiji wet season from October 2009 to April 2010. The aim was to evaluate whether these parameters provide sufficient information to illustrate basic features of storm–sediment transport responses, in the case of limited stream gauging and very simple sediment rating curves. This is important because Pacific Island nations like Fiji do not have the resources to initiate long-term gauging and sediment sampling programmes across numerous small catchments. A significant power function demonstrates that turbidity (T) is a suitable proxy for total suspended solids (TSS) for turbidity measurements above 5 NTU, with TSS=0.930T1.111 (r=0.98, P\u3c0.001). Over the study period, 10 individual storms 11.2–120.1 mm in size produced a ‘significant turbidity response’ (STR) in the Votua Creek. Rainfall parameters (totals and intensities) showed positive linear relationships (r=0.72–0.94) with stream turbidity parameters (mean, maximum, duration), whilst relationships of similar strength (r=0.76–0.98) were also derived between stream flow depth and turbidity. This implies that for small rainforest watersheds in Fiji, rainfall parameters offer no substantial disadvantage over flow as predictors of stream sediment responses to major storms. Event-based analysis revealed that negative (anticlockwise) hysteresis is a typical flow–turbidity pattern for STR events. Negative hysteresis is produced when secondary episodes of renewed (heavy) rainfall occur after maximum intensity, in the later phase of storm events. Tropical Cyclone Mick in December 2009 generated the largest flood and the greatest turbidity response (Tmax=1021 NTU, Tmean=207 NTU). This concurs with earlier work confirming that tropical cyclones are the most important events for sediment transport in Fiji stream networks

Flexible Working, Individual Performance and Employee Attitudes: Comparing Formal and Informal Arrangements

In the context of a wider trend to individualize HRM, this paper examines the relationship between flexible working arrangements and individual performance. Drawing on a range of theories, it examines potential indirect effects on employee performance via job satisfaction and organizational commitment and analyses whether these relationships vary according to whether the arrangement was set up through a formal process, or negotiated informally between the employee and their line manager. Extant research has tended to focus on formal arrangements, however, informal arrangements are widespread and may better accommodate work-life preferences, thereby potentially fostering more positive attitudes from employees. Survey data from 2617 employees in four large organizations with well-established flexible working policies are analysed. Results from structural equation models show average positive indirect effects from informal, but also negative direct effects, from formal flexible working. When two forms of flexible working amenable to being set up by both formal and informal means are examined separately: formal arrangements for flexibility over working hours are found to be negatively associated with performance, but also a source of greater job satisfaction; informal remote working arrangements have positive indirect effects via organizational commitment and job satisfaction on worker performance