Predictors of Over-Reporting HIV Pre-exposure Prophylaxis (PrEP) Adherence Among Young Men Who Have Sex With Men (YMSM) in Self-Reported Versus Biomarker Data

Young men who have sex with men (YMSM) face a disproportionately high burden of HIV. Oral pre-exposure prophylaxis (PrEP) is effective in preventing HIV acquisition, but adherence to PrEP among YMSM may be inadequate. Medication adherence may be assessed via biomarkers, which are expensive and invasive, or via self-report through Audio Computer Assisted Self-Interview (ACASI), which may result in over-reporting of adherence. In this paper we assess the potential of a new method of self-report, the Interactive Questionnaire System (iQS), in validly estimating true adherence rates. PrEP adherence among 167 YMSM aged 15-23 was measured via dried blood spot (DBS), ACASI, and iQS twice over a 24-week study period. Both ACASI- and iQS-reported data revealed that over 40% of individuals self-reporting adequate PrEP adherence had DBS-estimated drug levels indicating inadequate adherence. Adjusted logistic repeated measures random intercept regression analyses indicated that younger YMSM had higher odds of over-reporting adherence than older YMSM-each 1 year increase in age was associated with 0.79 times the odds of over-reporting adherence (95% CI 0.63, 0.98; p value = 0.031), and being African American was associated with 3.22 times greater odds of over-reporting than non-African Americans (95% CI 1.51, 6.90; p-value = 0.0003). These results suggest that ACASI and iQS methods of self-report significantly overestimate true PrEP adherence rates among YMSM, and that the odds of over-reporting adherence may be affected by both age and race

Low Temperature Waste Immobilization Testing Vol. I

The Pacific Northwest National Laboratory (PNNL) is evaluating low-temperature technologies to immobilize mixed radioactive and hazardous waste. Three waste forms—alkali-aluminosilicate hydroceramic cement, “Ceramicrete” phosphate-bonded ceramic, and “DuraLith” alkali-aluminosilicate geopolymer—were selected through a competitive solicitation for fabrication and characterization of waste-form properties. The three contractors prepared their respective waste forms using simulants of a Hanford secondary waste and Idaho sodium bearing waste provided by PNNL and characterized their waste forms with respect to the Toxicity Characteristic Leaching Procedure (TCLP) and compressive strength. The contractors sent specimens to PNNL, and PNNL then conducted durability (American National Standards Institute/American Nuclear Society [ANSI/ANS] 16.1 Leachability Index [LI] and modified Product Consistency Test [PCT]) and compressive strength testing (both irradiated and as-received samples). This report presents the results of these characterization tests

In Situ Detection of HY-Specific T Cells in Acute Graft-versus-Host Disease–Affected Male Skin after Sex-Mismatched Stem Cell Transplantation

HY-specific T cells are presumed to play a role in acute graft-versus-host disease (aGVHD) after female-to-male stem cell transplantation (SCT). However, infiltrates of these T cells in aGVHD-affected tissues have not yet been reported. We evaluated the application of HLA-A2/HY dextramers for the in situ detection of HY-specific T cells in cryopreserved skin biopsy specimens. We applied the HLA-A2/HY dextramers on cryopreserved skin biopsy specimens from seven male HLA-A2+ pediatric patients who underwent stem cell transplantation with confirmed aGVHD involving the skin. The dextramers demonstrated the presence of HY-specific T cells. In skin biopsy specimens of three male recipients of female grafts, 68% to 78% of all skin-infiltrating CD8+ T cells were HY-specific, whereas these cells were absent in biopsy specimens collected from sex-matched patient–donor pairs. Although this study involved a small and heterogeneous patient group, our results strongly support the hypothesis that HY-specific T cells are actively involved in the pathophysiology of aGVHD after sex-mismatched stem cell transplantation

Cloud e-learning for mechatronics: CLEM

his paper describes results of the CLEM project, Cloud E-learning for Mechatronics. CLEM is an example of a domain-specific cloud that is especially tuned to the needs of VET (Vocational, Education and Training) teachers. An interesting development has been the creation of remote laboratories in the cloud. Learners can access such laboratories to support their practical learning of mechatronics without the need to set up laboratories at their own institutions. The cloud infrastructure enables multiple laboratories to come together virtually to create an ecosystem for educators and learners. From such a system, educators can pick and mix materials to create suitable courses for their students and the learners can experience different types of devices and laboratories through the cloud. The paper provides an overview of this new cloud-based e-learning approach and presents the results. The paper explains how the use of cloud computing has enabled the development of a new method, showing how a holistic e-learning experience can be obtained through use of static, dynamic and interactive material together with facilities for collaboration and innovation

Catching Element Formation In The Act

Gamma-ray astronomy explores the most energetic photons in nature to address some of the most pressing puzzles in contemporary astrophysics. It encompasses a wide range of objects and phenomena: stars, supernovae, novae, neutron stars, stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays and relativistic-particle acceleration, and the evolution of galaxies. MeV gamma-rays provide a unique probe of nuclear processes in astronomy, directly measuring radioactive decay, nuclear de-excitation, and positron annihilation. The substantial information carried by gamma-ray photons allows us to see deeper into these objects, the bulk of the power is often emitted at gamma-ray energies, and radioactivity provides a natural physical clock that adds unique information. New science will be driven by time-domain population studies at gamma-ray energies. This science is enabled by next-generation gamma-ray instruments with one to two orders of magnitude better sensitivity, larger sky coverage, and faster cadence than all previous gamma-ray instruments. This transformative capability permits: (a) the accurate identification of the gamma-ray emitting objects and correlations with observations taken at other wavelengths and with other messengers; (b) construction of new gamma-ray maps of the Milky Way and other nearby galaxies where extended regions are distinguished from point sources; and (c) considerable serendipitous science of scarce events -- nearby neutron star mergers, for example. Advances in technology push the performance of new gamma-ray instruments to address a wide set of astrophysical questions.Comment: 14 pages including 3 figure

NeurIPS 2020 EfficientQA Competition: Systems, Analyses and Lessons Learned

We review the EfficientQA competition from NeurIPS 2020. The competition focused on open-domain question answering (QA), where systems take natural language questions as input and return natural language answers. The aim of the competition was to build systems that can predict correct answers while also satisfying strict on-disk memory budgets. These memory budgets were designed to encourage contestants to explore the trade-off between storing retrieval corpora or the parameters of learned models. In this report, we describe the motivation and organization of the competition, review the best submissions, and analyze system predictions to inform a discussion of evaluation for open-domain QA

Early-Warning Signals of Individual Tree Mortality Based on Annual Radial Growth

Tree mortality is a key driver of forest dynamics and its occurrence is projected to increase in the future due to climate change. Despite recent advances in our understanding of the physiological mechanisms leading to death, we still lack robust indicators of mortality risk that could be applied at the individual tree scale. Here, we build on a previous contribution exploring the differences in growth level between trees that died and survived a given mortality event to assess whether changes in temporal autocorrelation, variance, and synchrony in time-series of annual radial growth data can be used as early warning signals of mortality risk. Taking advantage of a unique global ring-width database of 3065 dead trees and 4389 living trees growing together at 198 sites (belonging to 36 gymnosperm and angiosperm species), we analyzed temporal changes in autocorrelation, variance, and synchrony before tree death (diachronic analysis), and also compared these metrics between trees that died and trees that survived a given mortality event (synchronic analysis). Changes in autocorrelation were a poor indicator of mortality risk. However, we found a gradual increase in inter- annual growth variability and a decrease in growth synchrony in the last similar to 20 years before mortality of gymnosperms, irrespective of the cause of mortality. These changes could be associated with drought-induced alterations in carbon economy and allocation patterns. In angiosperms, we did not find any consistent changes in any metric. Such lack of any signal might be explained by the relatively high capacity of angiosperms to recover after a stress-induced growth decline. Our analysis provides a robust method for estimating early-warning signals of tree mortality based on annual growth data. In addition to the frequently reported decrease in growth rates, an increase in inter-annual growth variability and a decrease in growth synchrony may be powerful predictors of gymnosperm mortality risk, but not necessarily so for angiosperms.Peer reviewe

Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting.

Abstract Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance