A Microchip CD4 Counting Method for HIV Monitoring in Resource-Poor Settings

BACKGROUND: More than 35 million people in developing countries are living with HIV infection. An enormous global effort is now underway to bring antiretroviral treatment to at least 3 million of those infected. While drug prices have dropped considerably, the cost and technical complexity of laboratory tests essential for the management of HIV disease, such as CD4 cell counts, remain prohibitive. New, simple, and affordable methods for measuring CD4 cells that can be implemented in resource-scarce settings are urgently needed. METHODS AND FINDINGS: Here we describe the development of a prototype for a simple, rapid, and affordable method for counting CD4 lymphocytes. Microliter volumes of blood without further sample preparation are stained with fluorescent antibodies, captured on a membrane within a miniaturized flow cell and imaged through microscope optics with the type of charge-coupled device developed for digital camera technology. An associated computer algorithm converts the raw digital image into absolute CD4 counts and CD4 percentages in real time. The accuracy of this prototype system was validated through testing in the United States and Botswana, and showed close agreement with standard flow cytometry (r = 0.95) over a range of absolute CD4 counts, and the ability to discriminate clinically relevant CD4 count thresholds with high sensitivity and specificity. CONCLUSION: Advances in the adaptation of new technologies to biomedical detection systems, such as the one described here, promise to make complex diagnostics for HIV and other infectious diseases a practical global reality

Undergraduate educational environment, perceived preparedness for postgraduate clinical training, and pass rate on the National Medical Licensure Examination in Japan

<p>Abstract</p> <p>Background</p> <p>We investigated the views of newly graduating physicians on their preparedness for postgraduate clinical training, and evaluated the relationship of preparedness with the educational environment and the pass rate on the National Medical Licensure Examination (NMLE).</p> <p>Methods</p> <p>Data were obtained from 2429 PGY-1 physicians-in-training (response rate, 36%) using a mailed cross-sectional survey. The Dundee Ready Education Environment Measure (DREEM) inventory was used to assess the learning environment at 80 Japanese medical schools. Preparedness was assessed based on 6 clinical areas related to the Association of American Medical Colleges Graduation Questionnaire.</p> <p>Results</p> <p>Only 17% of the physicians-in-training felt prepared in the area of general clinical skills, 29% in basic knowledge of diagnosis and management of common conditions, 48% in communication skills, 19% in skills associated with evidence-based medicine, 54% in professionalism, and 37% in basic skills required for a physical examination. There were substantial differences among the medical schools in the perceived preparedness of their graduates. Significant positive correlations were found between preparedness for all clinical areas and a better educational environment (all p < 0.01), but there were no significant associations between the pass rate on the NMLE and perceived preparedness for any clinical area, as well as pass rate and educational environment (all p > 0.05).</p> <p>Conclusion</p> <p>Different educational environments among universities may be partly responsible for the differences in perceived preparedness of medical students for postgraduate clinical training. This study also highlights the poor correlation between self-assessed preparedness for practice and the NMLE.</p

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Impact of Pre-adapted HIV Transmission

Human Leukocyte Antigen class I (HLA) restricted CD8+ T lymphocyte (CTL) responses are critical to HIV-1 control. Although HIV can evade these responses, the longer-term impact of viral escape mutants remains unclear, since these variants can also reduce intrinsic viral fitness. To address this question, we here develop a metric to determine the degree of HIV adaptation to an HLA profile. We demonstrate that transmission of viruses pre-adapted to the HLA molecules expressed in the recipient is associated with impaired immunogenicity, elevated viral load and accelerated CD4 decline. Furthermore, the extent of pre-adaptation among circulating viruses explains much of the variation in outcomes attributed to expression of certain HLA alleles. Thus, viral pre-adaptation exploits “holes” in the immune response. Accounting for these holes may be critical for vaccine strategies seeking to elicit functional responses from viral variants, and to HIV cure strategies requiring broad CTL responses to achieve successful eradication of HIV reservoirs

Electron and photon energy calibration with the ATLAS detector using 2015–2016 LHC proton-proton collision data

This paper presents the electron and photon energy calibration obtained with the ATLAS detector using about 36 fb−1 of LHC proton-proton collision data recorded at √s = 13 TeV in 2015 and 2016. The different calibration steps applied to the data and the optimization of the reconstruction of electron and photon energies are discussed. The absolute energy scale is set using a large sample of Z boson decays into electron-positron pairs. The systematic uncertainty in the energy scale calibration varies between 0.03% to 0.2% in most of the detector acceptance for electrons with transverse momentum close to 45 GeV. For electrons with transverse momentum of 10 GeV the typical uncertainty is 0.3% to 0.8% and it varies between 0.25% and 1% for photons with transverse momentum around 60 GeV. Validations of the energy calibration with J/ψ → e + e − decays and radiative Z boson decays are also presented

Study of the hard double-parton scattering contribution to inclusive four-lepton production in pp collisions at √s=8 TeV with the ATLAS detector

The inclusive production of four isolated charged leptons in pp collisions is analysed for the presence of hard double-parton scattering, using 20.2fb−1of data recorded in the ATLAS detector at the LHC at centre-of-mass energy √s=8TeV. In the four-lepton invariant-mass range of 80 <m4<1000GeV, an artificial neural network is used to enhance the separation between single-and double-parton scattering based on the kinematics of the four leptons in the final state. An upper limit on the fraction of events originating from double-parton scattering is determined at 95% confidence level to be fDPS=0.042, which results in an estimated lower limit on the effective cross section at 95% confidence level of 1.0mb

Measurement of VH, H → b b ¯ production as a function of the vector-boson transverse momentum in 13 TeV pp collisions with the ATLAS detector

Cross-sections of associated production of a Higgs boson decaying into bottom-quark pairs and an electroweak gauge boson, W or Z, decaying into leptons are measured as a function of the gauge boson transverse momentum. The measurements are performed in kinematic fiducial volumes defined in the `simplified template cross-section' framework. The results are obtained using 79.8 fb-1 of proton-proton collisions recorded by the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 13 TeV. All measurements are found to be in agreement with the Standard Model predictions, and limits are set on the parameters of an effective Lagrangian sensitive to modifications of the Higgs boson couplings to the electroweak gauge bosons