112 research outputs found
Lifshitz transition enabling superconducting dome around the quantum critical point in TiSe
Superconductivity often emerges as a dome around a quantum critical point
(QCP) where long-range order is suppressed to zero temperature. So far, this
has been mostly studied in magnetically ordered materials. By contrast, the
interplay between charge order and superconductivity at a QCP is not fully
understood. Here, we present resistance measurements proving that a dome of
superconductivity surrounds the charge-density-wave (CDW) QCP in pristine
samples of 1-TiSe tuned with hydrostatic pressure. Furthermore, we use
quantum oscillation measurements to show that the superconductivity sets in at
a Lifshitz transition in the electronic band structure. We use density
functional theory to identify the Fermi pockets enabling superconductivity:
large electron and hole pockets connected by the CDW wave vector
which emerge upon partial suppression of the zero-pressure CDW gap. Hence, we
conclude that superconductivity is of interband type enabled by the presence of
hole and electron bands connected by the CDW vector. Earlier
calculations show that interband interactions are repulsive, which suggests
that unconventional s superconductivity is realised in TiSe -
similar to the iron pnictides. These results highlight the importance of
Lifshitz transitions in realising unconventional superconductivity and help
understand its interaction with CDW order in numerous materials.Comment: 21 pages, 5 figure
Does melatonin improve sleep in older people? A randomised crossover trial
Abstract Study objective: to determine whether melatonin will improve quality of sleep in healthy older people with age-related sleep maintenance problems. Design: a double blind randomised placebo controlled crossover trial in healthy older volunteers. Setting: a largely urban population, Auckland, New Zealand. Participants: participants were part of the larger Possible Role of Melatonin in Sleep of Elders study. People 65 years or more of age were recruited through widespread advertising. We screened 414 potential participants by mail using the Pittsburgh Sleep Quality Index, and selected 194 for clinic interview. Exclusions included depression, cognitive impairment, hypnosedative medications, sleep phase abnormalities, medical and/or environmental problems that might impair sleep. Twenty normal and 20 problem sleepers were randomly allocated for this study from a larger sample of 60 normal and 60 problem sleepers. Measurements and results: 24-hour urine 6-sulphatoxymelatonin was measured to estimate melatonin secretion in each participant. Five milligrams of melatonin, or matching placebo were each taken at bedtime for 4 weeks, separated by a 4-week washout period. Sleep quality was measured using sleep diaries, the Leeds Sleep Evaluation Questionnaire, and actigraphy. There was a significant difference between the groups in self-reported sleep quality indicators at entry, but no difference in melatonin secretion. Melatonin did not significantly improve any sleep parameter measured in either group. Conclusion: 5 mg of fast release melatonin taken at bedtime does not improve the quality of sleep in older people with age-related sleep maintenance problems
Infectious causes of microcephaly: epidemiology, pathogenesis, diagnosis, and management.
Microcephaly is an important sign of neurological malformation and a predictor of future disability. The 2015-16 outbreak of Zika virus and congenital Zika infection brought the world's attention to links between Zika infection and microcephaly. However, Zika virus is only one of the infectious causes of microcephaly and, although the contexts in which they occur vary greatly, all are of concern. In this Review, we summarise important aspects of major congenital infections that can cause microcephaly, and describe the epidemiology, transmission, clinical features, pathogenesis, management, and long-term consequences of these infections. We include infections that cause substantial impairment: cytomegalovirus, herpes simplex virus, rubella virus, Toxoplasma gondii, and Zika virus. We highlight potential issues with classification of microcephaly and show how some infants affected by congenital infection might be missed or incorrectly diagnosed. Although Zika virus has brought the attention of the world to the problem of microcephaly, prevention of all infectious causes of microcephaly and appropriately managing its consequences remain important global public health priorities
The relative importance of COVIDâ19 pandemic impacts on biodiversity conservation globally
Abstract: The COVIDâ19 pandemic has had an enormous impact on almost all aspects of human society and endeavor; the natural world and its conservation have not been spared. Through a process of expert consultation, we identified and categorized, into 19 themes and 70 subthemes, the ways in which biodiversity and its conservation have been or could be affected by the pandemic globally. Nearly 60% of the effects have been broadly negative. Subsequently, we created a compendium of all themes and subthemes, each with explanatory text, and in August 2020 a diverse group of experienced conservationists with expertise from across sectors and geographies assessed each subtheme for its likely impact on biodiversity conservation globally. The 9 subthemes ranked highest all have a negative impact. These were, in rank order, governments sidelining the environment during their economic recovery, reduced wildlifeâbased tourism income, increased habitat destruction, reduced government funding, increased plastic and other solid waste pollution, weakening of natureâfriendly regulations and their enforcement, increased illegal harvest of wild animals, reduced philanthropy, and threats to survival of conservation organizations. In combination, these impacts present a worrying future of increased threats to biodiversity conservation but reduced capacity to counter them. The highest ranking positive impact, at 10, was the beneficial impact of wildlifeâtrade restrictions. More optimistically, among impacts ranked 11â20, 6 were positive and 4 were negative. We hope our assessment will draw attention to the impacts of the pandemic and, thus, improve the conservation community's ability to respond to such threats in the future
BLOOM: A 176B-Parameter Open-Access Multilingual Language Model
Large language models (LLMs) have been shown to be able to perform new tasks
based on a few demonstrations or natural language instructions. While these
capabilities have led to widespread adoption, most LLMs are developed by
resource-rich organizations and are frequently kept from the public. As a step
towards democratizing this powerful technology, we present BLOOM, a
176B-parameter open-access language model designed and built thanks to a
collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer
language model that was trained on the ROOTS corpus, a dataset comprising
hundreds of sources in 46 natural and 13 programming languages (59 in total).
We find that BLOOM achieves competitive performance on a wide variety of
benchmarks, with stronger results after undergoing multitask prompted
finetuning. To facilitate future research and applications using LLMs, we
publicly release our models and code under the Responsible AI License
Safety, immunogenicity, and efficacy of a COVID-19 vaccine (NVX-CoV2373) co-administered with seasonal influenza vaccines: an exploratory substudy of a randomised, observer-blinded, placebo-controlled, phase 3 trial
Background: Safety and immunogenicity of COVID-19 vaccines when co-administered with influenza vaccines have not yet been reported.
Methods: A sub-study on influenza vaccine co-administration was conducted as part of the phase 3 randomised trial of NVX-CoV2373âs safety and efficacy; ~400 participants meeting main study entry criteria, with no contraindications to influenza vaccination, were enroled. After randomisation to receive NVX-CoV2373 or placebo, sub-study participants received an open-label influenza vaccine at the same time as the first dose of NVX-CoV2373. Reactogenicity was evaluated for 7 days post-vaccination plus monitoring for unsolicited adverse events (AEs), medically-attended AEs (MAAEs), and serious AEs (SAEs). Vaccine efficacy against COVID-19 was assessed.
Findings: Sub-study participants were younger (median age 39; 6.7 % â„65 years), more racially diverse, and had fewer comorbid conditions than main study participants. Reactogenicity events more common in co-administration group included tenderness (70.1% vs 57.6%) or pain (39.7% vs 29.3%) at injection site, fatigue (27.7% vs 19.4%), and muscle pain (28.3% vs 21.4%). Rates of unsolicited AEs, MAAEs, and SAEs were low and balanced between the two groups. Co-administration resulted in no change to influenza vaccine immune response, while a reduction in antibody responses to the NVX-CoV2373 vaccine was noted. Vaccine efficacy against COVID-19 was 87.5% (95% CI: -0.2, 98.4) in those 18-<65 years in the sub-study while efficacy in the main study was 89.8% (95% CI: 79.7, 95.5).Â
Interpretation: This is the first study to demonstrate safety, immunogenicity, and efficacy of a COVID-19 vaccine when co-administered with influenza vaccines
Efficacy and safety of baricitinib or ravulizumab in adult patients with severe COVID-19 (TACTIC-R): a randomised, parallel-arm, open-label, phase 4 trial
Background
From early in the COVID-19 pandemic, evidence suggested a role for cytokine dysregulation and complement activation in severe disease. In the TACTIC-R trial, we evaluated the efficacy and safety of baricitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2, and ravulizumab, a monoclonal inhibitor of complement C5 activation, as an adjunct to standard of care for the treatment of adult patients hospitalised with COVID-19.
Methods
TACTIC-R was a phase 4, randomised, parallel-arm, open-label platform trial that was undertaken in the UK with urgent public health designation to assess the potential of repurposing immunosuppressants for the treatment of severe COVID-19, stratified by a risk score. Adult participants (aged â„18 years) were enrolled from 22 hospitals across the UK. Patients with a risk score indicating a 40% risk of admission to an intensive care unit or death were randomly assigned 1:1:1 to standard of care alone, standard of care with baricitinib, or standard of care with ravulizumab. The composite primary outcome was the time from randomisation to incidence (up to and including day 14) of the first event of death, invasive mechanical ventilation, extracorporeal membrane oxygenation, cardiovascular organ support, or renal failure. The primary interim analysis was triggered when 125 patient datasets were available up to day 14 in each study group and we included in the analysis all participants who were randomly assigned. The trial was registered on ClinicalTrials.gov (NCT04390464).
Findings
Between May 8, 2020, and May 7, 2021, 417 participants were recruited and randomly assigned to standard of care alone (145 patients), baricitinib (137 patients), or ravulizumab (135 patients). Only 54 (39%) of 137 patients in the baricitinib group received the maximum 14-day course, whereas 132 (98%) of 135 patients in the ravulizumab group received the intended dose. The trial was stopped after the primary interim analysis on grounds of futility. The estimated hazard ratio (HR) for reaching the composite primary endpoint was 1·11 (95% CI 0·62â1·99) for patients on baricitinib compared with standard of care alone, and 1·53 (0·88â2·67) for ravulizumab compared with standard of care alone. 45 serious adverse events (21 deaths) were reported in the standard-of-care group, 57 (24 deaths) in the baricitinib group, and 60 (18 deaths) in the ravulizumab group.
Interpretation
Neither baricitinib nor ravulizumab, as administered in this study, was effective in reducing disease severity in patients selected for severe COVID-19. Safety was similar between treatments and standard of care. The short period of dosing with baricitinib might explain the discrepancy between our findings and those of other trials. The therapeutic potential of targeting complement C5 activation product C5a, rather than the cleavage of C5, warrants further evaluation
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