Risk factors for poor virological outcome at 12 months in a workplace-based antiretroviral therapy programme in South Africa: A cohort study

<p>Abstract</p> <p>Background</p> <p>Reasons for the variation in reported treatment outcomes from antiretroviral therapy (ART) programmes in developing countries are not clearly defined.</p> <p>Methods</p> <p>Among ART-naïve individuals in a workplace ART programme in South Africa we determined virological outcomes at 12 months, and risk factors for suboptimal virological outcome, defined as plasma HIV-1 viral load >= 400 copies/ml.</p> <p>Results</p> <p>Among 1760 individuals starting ART before July 2004, 1172 were in follow-up at 12 months of whom 953 (81%) had a viral load measurement (median age 41 yrs, 96% male, median baseline CD4 count 156 × 10⁶/l). 71% (681/953) had viral load < 400 copies/ml at 12 months. In a multivariable analysis, independent predictors of suboptimal virological outcome at 12 months were <1 log decrease in viral load at six weeks (odds ratio [OR] 4.71, 95% confidence interval [CI] 2.56–8.68), viral load at baseline (OR 3.63 [95% CI 1.88–7.00] and OR 3.54 [95% CI 1.79–7.00] for 10,001–100,000 and >100,000 compared to <= 10,000 copies/ml, respectively), adherence at six weeks (OR 3.50 [95% CI 1.92–6.35]), WHO stage (OR 2.08 [95% CI 1.28–3.34] and OR 2.03 [95% CI 1.14–3.62] for stage 3 and 4 compared to stage 1–2, respectively) and site of ART delivery. Site of delivery remained an independent risk factor even after adjustment for individual level factors. At 6 weeks, of 719 patients with self-reported adherence and viral load, 72 (10%) reported 100% adherence but had <1 log decrease in viral load; conversely, 60 (8%) reported <100% adherence but had >= 1 log decrease in viral load.</p> <p>Conclusion</p> <p>Virological response at six weeks after ART start was the strongest predictor of suboptimal virological outcome at 12 months, and may identify individuals who need interventions such as additional adherence support. Self reported adherence was less strongly associated but identified different patients compared with viral load at 6 weeks. Site of delivery had an important influence on virological outcomes; factors at the health system level which influence outcome need further investigation to guide development of effective ART programmes.</p

Infections With the Tick-Borne Bacterium "Candidatus Neoehrlichia mikurensis” Mimic Noninfectious Conditions in Patients With B Cell Malignancies or Autoimmune Diseases

We present a comprehensive study of a new infectious disease in immune compromised patients, neoehrlichiosis. The clinical picture of the disease can be misleading because the symptoms may be misinterpreted to be a worsening of the underlying diseas

Environmental drivers of population-level variation in the migratory and diving ontogeny of an Arctic top predator

This work is an output of the ARISE project (NE/P006035/1 and NE/P00623X/1), part of the Changing Arctic Ocean programme jointly funded by the UKRI Natural Environment Research Council (NERC) and the German Federal Ministry of Education and Research (BMBF). Fieldwork in Canada was carried out under a Canadian Council on Animal Care permit no. NAFC2017–2 and funded by Fisheries and Oceans Canada and a bursary from Department for Business, Energy and Industrial Strategy (BEIS) administered by the NERC Arctic Office. Fieldwork in the Greenland Sea was approved by the Greenland Ministry of Fisheries, Hunting and Agriculture and the Norwegian Food Safety Authority (permit no. 11546) as part of the Northeast Greenland Environmental Study Program 2017–2018 (by the Danish Centre for Environment and Energy at Aarhus University, The Greenland Institute of Natural Resources and the Environmental Agency for Mineral Resource Activities of the Government of Greenland) and financed by oil licence holders in the area.The development of migratory strategies that enable juveniles to survive to sexual maturity is critical for species that exploit seasonal niches. For animals that forage via breath-hold diving, this requires a combination of both physiological and foraging skill development. Here, we assess how migratory and dive behaviour develop over the first year of life for a migratory Arctic top predator, the harp seal Pagophilus groenlandicus, tracked using animal-borne satellite relay data loggers. We reveal similarities in migratory movements and differences in diving behaviour between 38 juveniles tracked from the Greenland Sea and Northwest Atlantic breeding populations. In both regions, periods of resident and transitory behaviour during migration were associated with proxies for food availability: sea ice concentration and bathymetric depth. However, while ontogenetic development of dive behaviour was similar for both populations of juveniles over the first 25 days, after this time Greenland Sea animals performed shorter and shallower dives and were more closely associated with sea ice than Northwest Atlantic animals. Together, these results highlight the role of both intrinsic and extrinsic factors in shaping early life behaviour. Variation in the environmental conditions experienced during early life may shape how different populations respond to the rapid changes occurring in the Arctic ocean ecosystem.Publisher PDFPeer reviewe

B Physics at the Tevatron: Run II and Beyond

This report provides a comprehensive overview of the prospects for B physics at the Tevatron. The work was carried out during a series of workshops starting in September 1999. There were four working groups: 1) CP Violation, 2) Rare and Semileptonic Decays, 3) Mixing and Lifetimes, 4) Production, Fragmentation and Spectroscopy. The report also includes introductory chapters on theoretical and experimental tools emphasizing aspects of B physics specific to hadron colliders, as well as overviews of the CDF, D0, and BTeV detectors, and a Summary.Comment: 583 pages. Further information on the workshops, including transparencies, can be found at the workshop's homepage: http://www-theory.lbl.gov/Brun2/. The report is also available in 2-up http://www-theory.lbl.gov/Brun2/report/report2.ps.gz or chapter-by-chapter http://www-theory.lbl.gov/Brun2/report

Report of the NAMMCO-ICES Workshop on Seal Modelling (WKSEALS 2020)

To support sustainable management of apex predator populations, it is important to estimate population size and understand the drivers of population trends to anticipate the consequences of human decisions. Robust population models are needed, which must be based on realistic biological principles and validated with the best available data. A team of international experts reviewed age-structured models of North Atlantic pinniped populations, including Grey seal (Halichoerus grypus), Harp seal (Pagophilus groenlandicus), and Hooded seal (Cystophora cristata). Statistical methods used to fit such models to data were compared and contrasted. Differences in biological assumptions and model equations were driven by the data available from separate studies, including observation methodology and pre-processing. Counts of pups during the breeding season were used in all models, with additional counts of adults and juveniles available in some. The regularity and frequency of data collection, including survey counts and vital rate estimates, varied. Important differences between the models concerned the nature and causes of variation in vital rates (age-dependent survival and fecundity). Parameterisation of age at maturity was detailed and time-dependent in some models and simplified in others. Methods for estimation of model parameters were reviewed and compared. They included Bayesian and maximum likelihood (ML) approaches, implemented via bespoke coding in C, C++, TMB or JAGS. Comparative model runs suggested that as expected, ML-based implementations were rapid and computationally efficient, while Bayesian approaches, which used MCMC or sequential importance sampling, required longer for inference. For grey seal populations in the Netherlands, where preliminary ML-based TMB results were compared with the outputs of a Bayesian JAGS implementation, some differences in parameter estimates were apparent. For these seal populations, further investigations are recommended to explore differences that might result from the modelling framework and model-fitting methodology, and their importance for inference and management advice. The group recommended building on the success of this workshop via continued collaboration with ICES and NAMMCO assessment groups, as well as other experts in the marine mammal modelling community. Specifically, for Northeast Atlantic harp and hooded seal populations, the workshop represents the initial step towards a full ICES benchmark process aimed at revising and evaluating new assessment models.Publisher PDFPeer reviewe

CADD: predicting the deleteriousness of variants throughout the human genome

Combined Annotation-Dependent Depletion (CADD) is a widely used measure of variant deleteriousness that can effectively prioritize causal variants in genetic analyses, particularly highly penetrant contributors to severe Mendelian disorders. CADD is an integrative annotation built from more than 60 genomic features, and can score human single nucleotide variants and short insertion and deletions anywhere in the reference assembly. CADD uses a machine learning model trained on a binary distinction between simulated de novo variants and variants that have arisen and become fixed in human populations since the split between humans and chimpanzees; the former are free of selective pressure and may thus include both neutral and deleterious alleles, while the latter are overwhelmingly neutral (or, at most, weakly deleterious) by virtue of having survived millions of years of purifying selection. Here we review the latest updates to CADD, including the most recent version, 1.4, which supports the human genome build GRCh38. We also present updates to our website that include simplified variant lookup, extended documentation, an Application Program Interface and improved mechanisms for integrating CADD scores into other tools or applications. CADD scores, software and documentation are available at https://cadd.gs.washington.edu

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO