The Formation of the First Low-Mass Stars From Gas With Low Carbon and Oxygen Abundances

The first stars in the Universe are predicted to have been much more massive than the Sun. Gravitational condensation accompanied by cooling of the primordial gas due to molecular hydrogen, yields a minimum fragmentation scale of a few hundred solar masses. Numerical simulations indicate that once a gas clump acquires this mass, it undergoes a slow, quasi-hydrostatic contraction without further fragmentation. Here we show that as soon as the primordial gas - left over from the Big Bang - is enriched by supernovae to a carbon or oxygen abundance as small as ~0.01-0.1% of that found in the Sun, cooling by singly-ionized carbon or neutral oxygen can lead to the formation of low-mass stars. This mechanism naturally accommodates the discovery of solar mass stars with unusually low (10^{-5.3} of the solar value) iron abundance but with a high (10^{-1.3} solar) carbon abundance. The minimum stellar mass at early epochs is partially regulated by the temperature of the cosmic microwave background. The derived critical abundances can be used to identify those metal-poor stars in our Milky Way galaxy with elemental patterns imprinted by the first supernovae.Comment: 14 pages, 2 figures (appeared today in Nature

Predictors of inhospital mortality and re-hospitalization in older adults with community-acquired pneumonia: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>A better understanding of potentially modifiable predictors of in-hospital mortality and re-admission to the hospital following discharge may help to improve management of community-acquired pneumonia in older adults. We aimed to assess the associations of potentially modifiable factors with mortality and re-hospitalization in older adults hospitalized with community-acquired pneumonia.</p> <p>Methods</p> <p>A prospective cohort study was conducted from July 2003 to April 2005 in two Canadian cities. Patients aged 65 years or older hospitalized for community-acquired pneumonia were followed up for up to 30 days from initial hospitalization for mortality and these patients who were discharged alive within 30 days of initial hospitalization were followed up to 90 days of initial hospitalization for re-hospitalization. Separate logistic regression analyses were performed identify the predictors of mortality and re-hospitalization.</p> <p>Results</p> <p>Of 717 enrolled patients hospitalized for community-acquired pneumonia, 49 (6.8%) died within 30 days of hospital admission. Among these patients, 526 were discharged alive within 30 days of hospitalization of whom 58 (11.2%) were re-hospitalized within 90 days of initial hospitalization. History of hip fracture (odds ratio (OR) = 4.00, 95% confidence interval (CI) = (1.46, 10.96), P = .007), chronic obstructive pulmonary disease (OR = 2.31, 95% CI = (1.18, 4.50), P = .014), cerebrovascular disease (OR = 2.11, 95% CI = (1.03, 4.31), P = .040) were associated with mortality. Male sex (OR = 2.35, 95% CI = (1.13, 4.85), P = .022) was associated with re-hospitalization while vitamin E supplementation was protective (OR = 0.37 (0.16, 0.90), P = .028). Lower socioeconomic status, prior influenza and pneumococcal vaccinations, appropriate antibiotic prescription upon admission, and lower nutrition risk were not significantly associated with mortality or re-hospitalization.</p> <p>Conclusion</p> <p>Chronic comorbidities appear to be the most important predictors of death and re-hospitalization in older adults hospitalized with community-acquired pneumonia while vitamin E supplementation was protective.</p

Assessing, treating and preventing community acquired pneumonia in older adults: findings from a community-wide survey of emergency room and family physicians

BACKGROUND: Respiratory infections, like pneumonia, represent an important threat to the health of older Canadians. Our objective was to determine, at a community level, family and emergency room physicians' knowledge and beliefs about community acquired pneumonia (CAP) in older adults and to describe their self-reported assessment, management and prevention strategies. METHODS: All active ER and family physicians in Brant County received a mailed questionnaire. An advance notification letter and three follow-up mailings were used to maximize physician participation rate. The questionnaire collected information about physicians' assessment, management, and prevention strategies for CAP in older adults (≥60 years of age) plus demographic, training, and practice characteristics. The analysis highlights differences in approaches between office-based and emergency department physicians. RESULTS: Seventy-seven percent of physicians completed and returned the survey. Although only 16% of physicians were very confident in assessing CAP in older adults, more than half reported CAP to be a very important health concern in their practices. In-service training for family physicians was associated with increased confidence in CAP assessment and more frequent use of diagnostic tests. Family physicians who reported always requesting chest x-rays were also more likely to request pulse oximetry (OR 5.6, 95% CI 1.40 to 22.5) and recommend both follow-up x-rays (OR 5.4, 95% CI 1.7 to 16.6) and pneumococcal vaccination (OR 3.4, 95% CI 1.1 to 10.0). CONCLUSION: The findings of this study provide a snapshot of how non-specialists from a non-urban Ontario community assess, manage and prevent CAP in older adults and highlight differences between office-based and emergency department physicians. This information can guide researchers and clinicians in their efforts to improve the management and prevention of CAP in older adults

An in-frame deletion at the polymerase active site of POLD1 causes a multisystem disorder with lipodystrophy

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.DNA polymerase δ, whose catalytic subunit is encoded by POLD1, is responsible for lagging-strand DNA synthesis during DNA replication. It carries out this synthesis with high fidelity owing to its intrinsic 3'- to 5'-exonuclease activity, which confers proofreading ability. Missense mutations affecting the exonuclease domain of POLD1 have recently been shown to predispose to colorectal and endometrial cancers. Here we report a recurring heterozygous single-codon deletion in POLD1 affecting the polymerase active site that abolishes DNA polymerase activity but only mildly impairs 3'- to 5'-exonuclease activity. This mutation causes a distinct multisystem disorder that includes subcutaneous lipodystrophy, deafness, mandibular hypoplasia and hypogonadism in males. This discovery suggests that perturbing the function of the ubiquitously expressed POLD1 polymerase has unexpectedly tissue-specific effects in humans and argues for an important role for POLD1 function in adipose tissue homeostasis.This work was supported by NIHR Exeter Clinical Research Facility through funding for SE and ATH and general infrastructure. The authors thank Michael Day, Annet Damhuis and Richard Gilbert for technical assistance. We thank Karen Knapp for providing the data for the DEXA calculations. SE, ATH, SO are supported by Wellcome Weedon et al. Page 6 Nat Genet. Author manuscript; available in PMC 2014 February 01. Europe PMC Funders Author Manuscripts Europe PMC Funders Author Manuscripts Trust Senior Investigator awards. DS and RKS (098498/Z/12/Z) are supported by Wellcome Trust Senior Research Fellowships in Clinical Science. MNW is supported by the Wellcome Trust as part of the WT Biomedical Informatics Hub funding. RO is supported by Diabetes UK. DS, RKS and SO are supported by the UK National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. KJG is supported by the Agency for Science, Technology and Research, Singapore (A*STAR). LAL and MJP are supported by grants NCI-61-6845 and 62-4860

An ultraviolet-optical flare from the tidal disruption of a helium-rich stellar core

The flare of radiation from the tidal disruption and accretion of a star can be used as a marker for supermassive black holes that otherwise lie dormant and undetected in the centres of distant galaxies. Previous candidate flares have had declining light curves in good agreement with expectations, but with poor constraints on the time of disruption and the type of star disrupted, because the rising emission was not observed. Recently, two `relativistic' candidate tidal disruption events were discovered, each of whose extreme X-ray luminosity and synchrotron radio emission were interpreted as the onset of emission from a relativistic jet. Here we report the discovery of a luminous ultraviolet-optical flare from the nuclear region of an inactive galaxy at a redshift of 0.1696. The observed continuum is cooler than expected for a simple accreting debris disk, but the well-sampled rise and decline of its light curve follows the predicted mass accretion rate, and can be modelled to determine the time of disruption to an accuracy of two days. The black hole has a mass of about 2 million solar masses, modulo a factor dependent on the mass and radius of the star disrupted. On the basis of the spectroscopic signature of ionized helium from the unbound debris, we determine that the disrupted star was a helium-rich stellar core.Comment: To appear in Nature on May 10, 201

A cluster randomized controlled trial of a clinical pathway for hospital treatment of heart failure: study design and population

<p>Abstract</p> <p>Background</p> <p>The hospital treatment of heart failure frequently does not follow published guidelines, potentially contributing to the high morbidity, mortality and economic cost of this disorder. Consequently the development of clinical pathways has the potential to reduce the current variability in care, enhance guideline adherence, and improve outcomes for patients. Despite enthusiasm and diffusion, the widespread acceptance of clinical pathways remain questionable because very little prospective controlled data demonstrated their effectiveness. The Experimental Prospective Study on the Effectiveness and Efficiency of the Implementation of Clinical Pathways was designed in order to conduct a rigorous evaluation of clinical pathways in hospital treatment of acute heart failure. The primary objective of the trial was to evaluate the effectiveness of the implementation of clinical pathways for hospital treatment of heart failure in Italian hospitals.</p> <p>Methods/design</p> <p>Two-arm, cluster-randomized trial. 14 community hospitals were randomized either to arm 1 (clinical pathway: appropriate use of practice guidelines and supplies of drugs and ancillary services, new organization and procedures, patient education, etc.) or to arm 2 (no intervention, usual care). 424 patients sample (212 in each group), 80% of power at the 5% significance level (two-sided). The primary outcome measure is in-hospital mortality. We will also analyze the impact of the clinical pathways comparing the length and the appropriateness of the stay, the rate of unscheduled readmissions, the customers' satisfaction and the costs treating the patients with the pathways and with the current practice along all the observation period. The quality of the care will be assessed by monitoring the use of diagnostic and therapeutic procedures during hospital stay and by measuring key quality indicators at discharge.</p> <p>Discussion</p> <p>This paper examines the design of the evaluation of a complex intervention. Since clinical pathways are made up of various interconnecting parts we have chosen the cluster-randomized controlled trial because is widely accepted as the most reliable method of determining effectiveness when measuring cost-effectiveness in real practice.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID [NCT00519038]</p

KRILLBASE: a circumpolar database of Antarctic krill and salp numerical densities, 1926–2016

Antarctic krill (Euphausia superba) and salps are major macroplankton contributors to Southern Ocean food webs and krill are also fished commercially. Managing this fishery sustainably, against a backdrop of rapid regional climate change, requires information on distribution and time trends. Many data on the abundance of both taxa have been obtained from net sampling surveys since 1926, but much of this is stored in national archives, sometimes only in notebooks. In order to make these important data accessible we have collated available abundance data (numerical density, no.

A cluster randomized trial to assess the impact of clinical pathways for patients with stroke: rationale and design of the Clinical Pathways for Effective and Appropriate Care Study [NCT00673491]

<p>Abstract</p> <p>Background</p> <p>Patients with stroke should have access to a continuum of care from organized stroke units in the acute phase, to appropriate rehabilitation and secondary prevention measures. Moreover to improve the outcomes for acute stroke patients from an organizational perspective, the use of multidisciplinary teams and the delivery of continuous stroke education both to the professionals and to the public, and the implementation of evidence-based stroke care are recommended. Clinical pathways are complex interventions that can be used for this purpose. However in stroke care the use of clinical pathways remains questionable because little prospective controlled data has demonstrated their effectiveness. The purpose of this study is to determine whether clinical pathways could improve the quality of the care provided to the patients affected by stroke in hospital and through the continuum of the care.</p> <p>Methods</p> <p>Two-arm, cluster-randomized trial with hospitals and rehabilitation long-term care facilities as randomization units. 14 units will be randomized either to arm 1 (clinical pathway) or to arm 2 (no intervention, usual care). The sample will include 238 in each group, this gives a power of 80%, at 5% significance level. The primary outcome measure is 30-days mortality. The impact of the clinical pathways along the continuum of care will also be analyzed by comparing the length of hospital stay, the hospital re-admissions rates, the institutionalization rates after hospital discharge, the patients' dependency levels, and complication rates. The quality of the care provided to the patients will be assessed by monitoring the use of diagnostic and therapeutic procedures during hospital stay and rehabilitation, and by the use of key quality indicators at discharge. The implementation of organized care will be also evaluated.</p> <p>Conclusion</p> <p>The management of patients affected by stroke involves the expertise of several professionals, which can result in poor coordination or inefficiencies in patient treatment, and clinical pathways can significantly improve the outcomes of these patients. It is proposed that this study will test a new hypothesis and provide evidence of how clinical pathways can work.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID [NCT00673491]</p

Remote Electrical Stimulation by Means of Implanted Rectifiers

Miniaturization of active implantable medical devices is currently compromised by the available means for electrically powering them. Most common energy supply techniques for implants – batteries and inductive couplers – comprise bulky parts which, in most cases, are significantly larger than the circuitry they feed. Here, for overcoming such miniaturization bottleneck in the case of implants for electrical stimulation, it is proposed to make those implants act as rectifiers of high frequency bursts supplied by remote electrodes. In this way, low frequency currents will be generated locally around the implant and these low frequency currents will perform stimulation of excitable tissues whereas the high frequency currents will cause only innocuous heating. The present study numerically demonstrates that low frequency currents capable of stimulation can be produced by a miniature device behaving as a diode when high frequency currents, neither capable of thermal damage nor of stimulation, flow through the tissue where the device is implanted. Moreover, experimental evidence is provided by an in vivo proof of concept model consisting of an anesthetized earthworm in which a commercial diode was implanted. With currently available microelectronic techniques, very thin stimulation capsules (diameter <500 µm) deliverable by injection are easily conceivable

Mutation of HIV-1 Genomes in a Clinical Population Treated with the Mutagenic Nucleoside KP1461

The deoxycytidine analog KP1212, and its prodrug KP1461, are prototypes of a new class of antiretroviral drugs designed to increase viral mutation rates, with the goal of eventually causing the collapse of the viral population. Here we present an extensive analysis of viral sequences from HIV-1 infected volunteers from the first “mechanism validation” phase II clinical trial of a mutagenic base analog in which individuals previously treated with antiviral drugs received 1600 mg of KP1461 twice per day for 124 days. Plasma viral loads were not reduced, and overall levels of viral mutation were not increased during this short-term study, however, the mutation spectrum of HIV was altered. A large number (N = 105 per sample) of sequences were analyzed, each derived from individual HIV-1 RNA templates, after 0, 56 and 124 days of therapy from 10 treated and 10 untreated control individuals (>7.1 million base pairs of unique viral templates were sequenced). We found that private mutations, those not found in more than one viral sequence and likely to have occurred in the most recent rounds of replication, increased in treated individuals relative to controls after 56 (p = 0.038) and 124 (p = 0.002) days of drug treatment. The spectrum of mutations observed in the treated group showed an excess of A to G and G to A mutations (p = 0.01), and to a lesser extent T to C and C to T mutations (p = 0.09), as predicted by the mechanism of action of the drug. These results validate the proposed mechanism of action in humans and should spur development of this novel antiretroviral approach.Koronis Pharmaceutical