In this open-label trial of first-line treatment for HIV-1 in Cameroon, a dolutegravir-based regimen was found to be noninferior to a low-dose efavirenz–based regimen as initial antiretroviral ...therapy. However, more weight gain and a higher incidence of obesity occurred in the dolutegravir group.
We report the discovery of WTS-2 b, an unusually close-in 1.02-d hot Jupiter (M
P
= 1.12M
J, R
P
= 1.30R
J) orbiting a K2V star, which has a possible gravitationally bound M-dwarf companion at 0.6 ...arcsec separation contributing ∼20 per cent of the total flux in the observed J-band light curve. The planet is only 1.5 times the separation from its host star at which it would be destroyed by Roche lobe overflow, and has a predicted remaining lifetime of just ∼40 Myr, assuming a tidal dissipation quality factor of
.
is a key factor in determining how frictional processes within a host star affect the orbital evolution of its companion giant planets, but it is currently poorly constrained by observations. We calculate that the orbital decay of WTS-2 b would correspond to a shift in its transit arrival time of T
shift ∼ 17 s after 15 yr assuming
. A shift less than this would place a direct observational constraint on the lower limit of
in this system. We also report a correction to the previously published expected T
shift for WASP-18 b, finding that T
shift = 356 s after 10 yr for
, which is much larger than the estimated 28 s quoted in WASP-18 b discovery paper. We attempted to constrain
via a study of the entire population of known transiting hot Jupiters, but our results were inconclusive, requiring a more detailed treatment of transit survey sensitivities at long periods. We conclude that the most informative and straightforward constraints on
will be obtained by direct observational measurements of the shift in transit arrival times in individual hot Jupiter systems. We show that this is achievable across the mass spectrum of exoplanet host stars within a decade, and will directly probe the effects of stellar interior structure on tidal dissipation.
The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to ...explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. These findings highlight the nasal susceptibility to SARS-CoV-2 with likely subsequent aspiration-mediated virus seeding to the lung in SARS-CoV-2 pathogenesis. These reagents provide a foundation for investigations into virus-host interactions in protective immunity, host susceptibility, and virus pathogenesis.
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•A SARS-CoV-2 infectious cDNA clone and reporter viruses are generated•SARS-CoV-2 and SARS-CoV neutralization assays show limited cross neutralization•SARS-CoV-2 shows a gradient infectivity from the proximal to distal respiratory tract•Ciliated airway cells and AT-2 cells are primary targets for SARS-CoV-2 infection
Hou et al. present a reverse genetics system for SARS-CoV-2, which is then used to make reporter viruses to quantify the ability of patient sera and antibodies to neutralize infectious virus and to examine viral tropism along the human respiratory tract.
With the emergence and rapid spreading of NDM-1 and existence of clinically relevant VIM-1 and IMP-1, discovery of pan inhibitors targeting metallo-beta-lactamases (MBLs) became critical in our ...battle against bacterial infection. Concurrent with our fragment and high-throughput screenings, we performed a knowledge-based search of known metallo-beta-lactamase inhibitors (MBLIs) to identify starting points for early engagement of medicinal chemistry. A class of compounds exemplified by 11, discovered earlier as B. fragilis metallo-beta-lactamase inhibitors, was selected for in silico virtual screening. From these efforts, compound 12 was identified with activity against NDM-1 only. Initial exploration on metal binding design followed by structure-guided optimization led to the discovery of a series of compounds represented by 23 with a pan MBL inhibition profile. In in vivo studies, compound 23 in combination with imipenem (IPM) robustly lowered the bacterial burden in a murine infection model and became the lead for the invention of MBLI clinical candidates.
We carried out a large randomized trial of a brief form of cognitive therapy, manual-assisted cognitive behaviour therapy (MACT) versus treatment as usual (TAU) for deliberate self-harm.
Patients ...presenting with recurrent deliberate self-harm in five centres were randomized to either MACT or (TAU) and followed up over 1 year. MACT patients received a booklet based on cognitive behaviour therapy (CBT) principles and were offered up to five plus two booster sessions of CBT from a therapist in the first 3 months of the study. Ratings of parasuicide risk, anxiety, depression, social functioning and global function, positive and negative thinking, and quality of life were measured at baseline and after 6 and 12 months.
Four hundred and eighty patients were randomized. Sixty per cent of the MACT group had both the booklet and CBT sessions. There were seven suicides, five in the TAU group. The main outcome measure, the proportion of those repeating deliberate self-harm in the 12 months of the study, showed no significant difference between those treated with MACT (39%) and treatment as usual (46%) (OR 0.78, 95% CI 0.53 to 1.14, P=0.20).
Brief cognitive behaviour therapy is of limited efficacy in reducing self-harm repetition, but the findings taken in conjunctin with the economic evaluation (Byford et al. 2003) indicate superiority of MACT over TAU in terms of cost and effectiveness combined.
Afshar et al. claim that their experiment shows a violation of the complementarity inequality. In this work, we study their claim using a modified Mach-Zehnder setup that represents a simpler version ...of the Afshar experiment. We find that our results are consistent with Afshar et al. experimental findings. However, we show that within standard quantum mechanics the results of the Afshar experiment do not lead to a violation of the complementarity inequality. We show that their claim originates from a particular technique they use to analyze their results. In their analysis, they assume a classical concept, that particles have a definite trajectory before detection, thus, they obtain which-way information by particle detection plus path extrapolation by applying momentum conservation. This analysis technique is standard in experimental particle physics. Important discoveries such as the detection of vector bosons have been made through the application of this technique. We note that particle detection plus path extrapolation is a suitable technique within de Broglie-Bohm theory of quantum mechanics.
The influence of cumulus cells (CC) on the lipid profile of bovine oocytes matured in two different lipid sources was investigated. Cumulus-oocyte complexes (COC) or denuded oocytes (DO) were matured ...in tissue culture medium (TCM) supplemented with fetal bovine serum (FBS) or serum substitute supplement (SSS). Lipid profiles of TCM, serum supplements, immature CC and oocyte (IO), and in vitro-matured oocytes from COC and DO were then analyzed by matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) and submitted to partial least squares-discriminant analysis (PLS-DA). The developmental competence of such oocytes was also assessed. Differences in lipid composition were observed between two types of sera and distinctly influenced the lipid profile of CC. As revealed by PLS-DA, the abundance of specific ions corresponding to triacylglycerols (TAG) or phospholipids (PL) were higher in COC compared to DO both supplemented with FBS or SSS and to some extent affected the subsequent DO in vitro embryo development. DO exposed to SSS had however a marked diminished ability to develop to the blastocyst stage. These results indicate a modulation by CC of the oocyte TAG and PL profiles associated with a specific cell response to the serum supplement used for in vitro maturation.
Objectives. Hopelessness about the future is a key element in suicidal behaviour. The aim of the present study was to examine possible components of hopelessness, in particular, to contrast positive ...and negative future thinking and to examine separately number, expectancy, and value of anticipated positive and negative future experiences.
Design. A correlational design.
Method. Repeat parasuicide patients (N=441) were administered the Beck Hopelessness Scale, the Hospital Anxiety and Depression Scale and the future thinking task, a measure of future positive and negative thinking that assesses number, perceived likelihood, and perceived value of anticipated future positive and negative events.
Results. Consistent with predictions, hopelessness correlated more strongly with lack of positive thoughts about the future than it did with presence of negative thoughts. Both positive and negative future thinking showed a relationship to hopelessness over and above their relationships to depression (positive future thinking) and anxiety (negative future thinking). Number and likelihood of positive events and likelihood and value of negative events showed both simple and partial relationships to hopelessness. Number of negative events related to hopelessness but only after the other future thinking variables had been controlled for and value of positive events no longer related to hopelessness after controlling for the other variables
Conclusions. Hopelessness about the future in suicidal individuals is a multi‐faceted construct but lack of positive future thinking is more important than presence of negative future thinking.
We measure the correlation between the spin of the top quark and the spin of the anti-top quark in (ttbar -> W+ W- b bbar -> l+ nu b l- nubar bbar) final states produced in ppbar collisions at a ...center of mass energy sqrt(s)=1.96 TeV, where l is an electron or muon. The data correspond to an integrated luminosity of 5.4 fb-1 and were collected with the D0 detector at the Fermilab Tevatron collider. The correlation is extracted from the angles of the two leptons in the t and tbar rest frames, yielding a correlation strength C= 0.10^{+0.45}_{-0.45}, in agreement with the NLO QCD prediction within two standard deviations, but also in agreement with the no correlation hypothesis.
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