27 research outputs found

    Very Large Array And Atca Search For Natal Star Clusters In Nearby Star-Forming Galaxies

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    In order to investigate the relationship between the local environment and the properties of natal star clusters, we obtained radio observations of 25 star-forming galaxies within 20 Mpc using the Very Large Array and the Australia Telescope Compact Array. Natal star-forming regions can be identified by their characteristic thermal radio emission, which is manifest in their spectral index at centimeter wavelengths. The host galaxies in our sample were selected based upon their likelihood of harboring young star formation. In star-forming regions, the ionizing flux of massive embedded stars powers the dominant thermal free-free emission of those sources, resulting in a spectral index of {alpha} {approx}\u3e -0.2 (where S{sub {nu}} {proportional_to} {nu}{sup {alpha}}), which we compute. With the current sensitivity, we find that of the 25 galaxies in this sample only 5 have radio sources with spectral indices that are only consistent with a thermal origin, 4 have radio sources that are only consistent with a non-thermal origin, 6 have radio sources whose nature is ambiguous due to uncertainties in the spectral index, and 16 have no detected radio sources. For those sources that appear to be dominated by thermal emission, we infer the ionizing flux of the star clusters andmore » the number of equivalent O7.5 V stars that are required to produce the observed radio flux densities. The most radio-luminous clusters that we detect have an equivalent of {approx}7 x 10{sup 3} O7.5 V stars, and the smallest only have an equivalent of {approx}10{sup 2} O7.5 V stars; thus these star-forming regions span the range of large OB associations to moderate \u27super star clusters\u27. With the current detection limits, we also place upper limits on the masses of clusters that could have recently formed; for a number of galaxies we can conclusively rule out the presence of natal clusters significantly more massive than the Galactic star-forming region W49A ({approx}5 x 10{sup 4} M{sub sun}). The dearth of current massive cluster formation in these galaxies suggests that either their current star formation intensities have fallen to near or below that of the Milky Way and/or the evolutionary state that gives rise to thermal radio emission is short-lived.« les

    Num. 11

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    Emerging evidence suggests that dopamine may modulate learning and memory with important implications for understanding the neurobiology of memory and future therapeutic targeting. An influential hypothesis posits that dopamine biases reinforcement learning. More recent data also suggest an influence during both consolidation and retrieval. Eighteen Parkinson’s disease patients learned through feedback ON or OFF medication with memory tested 24 hours later ON or OFF medication (4 conditions, within-subjects design with matched healthy control group). Patients OFF medication during learning decreased in memory accuracy over the following 24 hours. In contrast to previous studies, however, dopaminergic medication during learning and testing did not affect expression of positive or negative reinforcement. Two further experiments were run without the 24-hour delay, but they too failed to reproduce effects of dopaminergic medication on reinforcement learning. While supportive of a dopaminergic role in consolidation, this study failed to replicate previous findings on reinforcement learning

    Analogy-Making as a Core Primitive in the Software Engineering Toolbox

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    An analogy is an identification of structural similarities and correspondences between two objects. Computational models of analogy making have been studied extensively in the field of cognitive science to better understand high-level human cognition. For instance, Melanie Mitchell and Douglas Hofstadter sought to better understand high-level perception by developing the Copycat algorithm for completing analogies between letter sequences. In this paper, we argue that analogy making should be seen as a core primitive in software engineering. We motivate this argument by showing how complex software engineering problems such as program understanding and source-code transformation learning can be reduced to an instance of the analogy-making problem. We demonstrate this idea using Sifter, a new analogy-making algorithm suitable for software engineering applications that adapts and extends ideas from Copycat. In particular, Sifter reduces analogy-making to searching for a sequence of update rule applications. Sifter uses a novel representation for mathematical structures capable of effectively representing the wide variety of information embedded in software. We conclude by listing major areas of future work for Sifter and analogy-making in software engineering.Comment: Conference paper at SPLASH 'Onward!' 2020. Code is available at https://github.com/95616ARG/sifte

    Autoinflammatory periodic fever, immunodeficiency, and thrombocytopenia (PFIT) caused by mutation in actin-regulatory gene WDR1

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    The importance of actin dynamics in the activation of the inflammasome is becoming increasingly apparent. IL-1β, which is activated by the inflammasome, is known to be central to the pathogenesis of many monogenic autoinflammatory diseases. However, evidence from an autoinflammatory murine model indicates that IL-18, the other cytokine triggered by inflammasome activity, is important in its own right. In this model, autoinflammation was caused by mutation in the actin regulatory gene WDR1 We report a homozygous missense mutation in WDR1 in two siblings causing periodic fevers with immunodeficiency and thrombocytopenia. We found impaired actin dynamics in patient immune cells. Patients had high serum levels of IL-18, without a corresponding increase in IL-18-binding protein or IL-1β, and their cells also secreted more IL-18 but not IL-1β in culture. We found increased caspase-1 cleavage within patient monocytes indicative of increased inflammasome activity. We transfected HEK293T cells with pyrin and wild-type and mutated WDR1 Mutant protein formed aggregates that appeared to accumulate pyrin; this could potentially precipitate inflammasome assembly. We have extended the findings from the mouse model to highlight the importance of WDR1 and actin regulation in the activation of the inflammasome, and in human autoinflammation

    Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

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    BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

    Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

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    SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication
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