1,056 research outputs found

    Primaquine radical cure in patients with Plasmodium falciparum malaria in areas co-endemic for P falciparum and Plasmodium vivax (PRIMA): a multicentre, open-label, superiority randomised controlled trial

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    Background In areas co-endemic for Plasmodium vivax and Plasmodium falciparum there is an increased risk of P vivax parasitaemia following P falciparum malaria. Radical cure is currently only recommended for patients presenting with P vivax malaria. Expanding the indication for radical cure to patients presenting with P falciparum malaria could reduce their risk of subsequent P vivax parasitaemia. Methods We did a multicentre, open-label, superiority randomised controlled trial in five health clinics in Bangladesh, Indonesia, and Ethiopia. In Bangladesh and Indonesia, patients were excluded if they were younger than 1 year, whereas in Ethiopia patients were excluded if they were younger than 18 years. Patients with uncomplicated P falciparum monoinfection who had fever or a history of fever in the 48 h preceding clinic visit were eligible for enrolment and were required to have a glucose-6-dehydrogenase (G6PD) activity of 70% or greater. Patients received blood schizontocidal treatment (artemether–lumefantrine in Ethiopia and Bangladesh and dihydroartemisinin–piperaquine in Indonesia) and were randomly assigned (1:1) to receive either high-dose short-course oral primaquine (intervention arm; total dose 7 mg/kg over 7 days) or standard care (standard care arm; single dose oral primaquine of 0·25 mg/kg). Random assignment was done by an independent statistician in blocks of eight by use of sealed envelopes. All randomly assigned and eligible patients were included in the primary and safety analyses. The per-protocol analysis excluded those who did not complete treatment or had substantial protocol violations. The primary endpoint was the incidence risk of P vivax parasitaemia on day 63. This trial is registered at ClinicalTrials.gov, NCT03916003. Findings Between Aug 18, 2019, and March 14, 2022, a total of 500 patients were enrolled and randomly assigned, and 495 eligible patients were included in the intention-to-treat analysis (246 intervention and 249 control). The incidence risk of P vivax parasitaemia at day 63 was 11·0% (95% CI 7·5–15·9) in the standard care arm compared with 2·5% (1·0–5·9) in the intervention arm (hazard ratio 0·20, 95% CI 0·08–0·51; p=0·0009). The effect size differed with blood schizontocidal treatment and site. Routine symptom reporting on day 2 and day 7 were similar between groups. In the first 42 days, there were a total of four primaquine-related adverse events reported in the standard care arm and 26 in the intervention arm; 132 (92%) of all 143 adverse events were mild. There were two serious adverse events in the intervention arm, which were considered unrelated to the study drug. None of the patients developed severe anaemia (defined as haemoglobin <5 g/dL). Interpretation In patients with a G6PD activity of 70% or greater, high-dose short-course primaquine was safe and relatively well tolerated and reduced the risk of subsequent P vivax parasitaemia within 63 days by five fold. Universal radical cure therefore potentially offers substantial clinical, public health, and operational benefits, but these benefits will vary with endemic setting. Funding Australian Academy of Science Regional Collaborations Program, Bill & Melinda Gates Foundation, and National Health and Medical Research Council

    Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

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    Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface

    Scientific complications and controversies noted in the field of CdS/CdTe thin film solar cells and the way forward for further development

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    Cadmium telluride-based solar cell is the most successfully commercialised thin film solar cell today. The laboratory-scale small devices have achieved ~ 22%, and commercial solar panels have reached ~ 18% conversion efficiencies. However, there are various technical complications and some notable scientific contradictions that appear in the scientific literature published since the early 1970s. This review paper discusses some of these major complications and controversies in order to focus future research on issues of material growth and characterisation, post-growth processing, device architectures and interpretation of the results. Although CdTe can be grown using more than 14 different growth techniques, successful commercialisation has been taken place using close-space sublimation and electrodeposition techniques only. The experimental results presented in this review are mainly based on electrodeposition. Historical trends of research and commercial successes have also been discussed compared to the timeline of novel breakthroughs in this field. Deeper understanding of these issues may lead to further increase in conversion efficiencies of this solar cell. Some novel ideas for further development of thin film solar cells are also discussed towards the end of this paper

    Detection of carbon monoxide's 4.6 micron fundamental band structure in WASP-39b's atmosphere with JWST NIRSpec G395H

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    Carbon monoxide (CO) is predicted to be the dominant carbon-bearing molecule in giant planet atmospheres and, along with water, is important for discerning the oxygen and therefore carbon-to-oxygen ratio of these planets. The fundamental absorption mode of CO has a broad, double-branched structure composed of many individual absorption lines from 4.3 to 5.1 Όm, which can now be spectroscopically measured with JWST. Here we present a technique for detecting the rotational sub-band structure of CO at medium resolution with the NIRSpec G395H instrument. We use a single transit observation of the hot Jupiter WASP-39b from the JWST Transiting Exoplanet Community Early Release Science (JTEC ERS) program at the native resolution of the instrument (R ~ 2700) to resolve the CO absorption structure. We robustly detect absorption by CO, with an increase in transit depth of 264 ± 68 ppm, in agreement with the predicted CO contribution from the best-fit model at low resolution. This detection confirms our theoretical expectations that CO is the dominant carbon-bearing molecule in WASP-39b's atmosphere and further supports the conclusions of low C/O and supersolar metallicities presented in the JTEC ERS papers for WASP-39b

    Search for rare quark-annihilation decays, B --> Ds(*) Phi

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    We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

    Search for R-parity-violating supersymmetry in events with four or more leptons in sqrt(s) =7 TeV pp collisions with the ATLAS detector

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    A search for new phenomena in final states with four or more leptons (electrons or muons) is presented. The analysis is based on 4.7 fb−1 of s=7  TeV \sqrt{s}=7\;\mathrm{TeV} proton-proton collisions delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in two signal regions: one that requires moderate values of missing transverse momentum and another that requires large effective mass. The results are interpreted in a simplified model of R-parity-violating supersymmetry in which a 95% CL exclusion region is set for charged wino masses up to 540 GeV. In an R-parity-violating MSUGRA/CMSSM model, values of m 1/2 up to 820 GeV are excluded for 10 < tan ÎČ < 40

    Search for high-mass resonances decaying to dilepton final states in pp collisions at s√=7 TeV with the ATLAS detector

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    The ATLAS detector at the Large Hadron Collider is used to search for high-mass resonances decaying to an electron-positron pair or a muon-antimuon pair. The search is sensitive to heavy neutral Zâ€Č gauge bosons, Randall-Sundrum gravitons, Z * bosons, techni-mesons, Kaluza-Klein Z/Îł bosons, and bosons predicted by Torsion models. Results are presented based on an analysis of pp collisions at a center-of-mass energy of 7 TeV corresponding to an integrated luminosity of 4.9 fb−1 in the e + e − channel and 5.0 fb−1 in the ÎŒ + ÎŒ −channel. A Z â€Č boson with Standard Model-like couplings is excluded at 95 % confidence level for masses below 2.22 TeV. A Randall-Sundrum graviton with coupling k/MPl=0.1 is excluded at 95 % confidence level for masses below 2.16 TeV. Limits on the other models are also presented, including Technicolor and Minimal Zâ€Č Models
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