Although the link between long γ-ray bursts (GRBs) and supernovae has been established, hitherto there have been no observations of the beginning of a supernova explosion and its intimate link to a ...GRB. In particular, we do not know how the jet that defines a γ-ray burst emerges from the star's surface, nor how a GRB progenitor explodes. Here we report observations of the relatively nearby GRB 060218 (ref. 5) and its connection to supernova SN 2006aj (ref. 6). In addition to the classical non-thermal emission, GRB 060218 shows a thermal component in its X-ray spectrum, which cools and shifts into the optical/ultraviolet band as time passes. We interpret these features as arising from the break-out of a shock wave driven by a mildly relativistic shell into the dense wind surrounding the progenitor. We have caught a supernova in the act of exploding, directly observing the shock break-out, which indicates that the GRB progenitor was a Wolf-Rayet star.
We present the first results from a reverberation-mapping campaign undertaken during the first half of 2012, with additional data on one active galactic nucleus (AGN) (NGC 3227) from a 2014 campaign. ...Our main goals are (1) to determine the black hole masses from continuum-Hβ reverberation signatures, and (2) to look for velocity-dependent time delays that might be indicators of the gross kinematics of the broad-line region. We successfully measure Hβ time delays and black hole masses for five AGNs, four of which have previous reverberation mass measurements. The values measured here are in agreement with earlier estimates, though there is some intrinsic scatter beyond the formal measurement errors. We observe velocity-dependent Hβ lags in each case, and find that the patterns have changed in the intervening five years for three AGNs that were also observed in 2007.
Applying systems science in public health trials is a recent innovation in childhood obesity prevention. This paper aims to use systems science conventions to propose a theory of change for ...community-based interventions aiming to build capacity and use exemplars from systems science for obesity prevention to describe how this approach works.
Participants were community-based researchers. A dynamic hypothesis was created in workshops conducted in 2020 and 2021 by identifying variables critical to building community capacity for systems thinking. These were used to develop stock and flow diagrams representing individual causal relationships, feedback loops, and the overall theory of change.
The resultant model identified 9 stocks and 4 pairs of central balancing and reinforcing feedback loops. These represented building commitment through relationships, mutual learning, strengthening collaboration, and embedding capacity. The model is described using examples from 3 trials involving 25 communities across Victoria, Australia.
This nonlinear and practice-based model illustrates the process of community-based obesity prevention. The model integrates >20 years of community-based intervention implementation experience, providing an overarching theory of how such interventions work to create change and prevent obesity.
BackgroundA vaccine is needed to prevent human immunodeficiency virus type 1 (HIV-1) infection MethodsA double-blind, randomized trial of a recombinant HIV-1 envelope glycoprotein subunit (rgp120) ...vaccine was conducted among men who have sex with men and among women at high risk for heterosexual transmission of HIV-1. Volunteers received 7 injections of either vaccine or placebo (ratio, 2:1) over 30 months. The primary end point was HIV-1 seroconversion over 36 months ResultsA total of 5403 volunteers (5095 men and 308 women) were evaluated. The vaccine did not prevent HIV-1 acquisition: infection rates were 6.7% in 3598 vaccinees and 7.0% in 1805 placebo recipients; vaccine efficacy (VE) was estimated as 6% (95% confidence interval, −17% to 24%). There were no significant differences in viral loads, rates of antiretroviral-therapy initiation, or the genetic characteristics of the infecting HIV-1 strains between treatment arms. Exploratory subgroup analyses showed nonsignificant trends toward efficacy in preventing infection in the highest risk (VE, 43%; n=247) and nonwhite (VE, 47%; n=914) volunteers (P=.10, adjusted for multiple subgroup comparisons) ConclusionsThere was no overall protective effect. The efficacy trends in subgroups may provide clues for the development of effective immunization approaches
Genome‐wide association studies have linked the ORM (yeast)–like protein isoform 3 (ORMDL3) to asthma severity. Although ORMDL3 is a member of a family that negatively regulates serine ...palmitoyltransferase (SPT) and thus biosynthesis of sphingolipids, it is still unclear whether ORMDL3 and altered sphingolipid synthesis are causally related to non‐Th2 severe asthma associated with a predominant neutrophil inflammation and high interleukin‐17 (IL‐17) levels. Here, we examined the effects of ORMDL3 overexpression in a preclinical mouse model of allergic lung inflammation that is predominantly neutrophilic and recapitulates many of the clinical features of severe human asthma. ORMDL3 overexpression reduced lung and circulating levels of dihydrosphingosine, the product of SPT. However, the most prominent effect on sphingolipid levels was reduction of circulating S1P. The LPS/OVA challenge increased markers of Th17 inflammation with a predominant infiltration of neutrophils into the lung. A significant decrease of neutrophil infiltration was observed in the Ormdl3 transgenic mice challenged with LPS/OVA compared to the wild type and concomitant decrease in IL‐17, that plays a key role in the pathogenesis of neutrophilic asthma. LPS decreased survival of murine neutrophils, which was prevented by co‐treatment with S1P. Moreover, S1P potentiated LPS‐induced chemotaxis of neutrophil, suggesting that S1P can regulate neutrophil survival and recruitment following LPS airway inflammation. Our findings reveal a novel connection between ORMDL3 overexpression, circulating levels of S1P, IL‐17 and neutrophil recruitment into the lung, and questions the potential involvement of ORMDL3 in the pathology, leading to development of severe neutrophilic asthma.
Severe asthma is associated with a predominant inflammation and high levels of interleuking‐17 (IL‐17), which plays a key role in their accumulation in the airways. Ormdl3 transgenic mice with reduced circulating levels of the bioactive sphingolipid metabolite sphingosine‐1‐phosphate (S1P) had reduced neutrophil infiltration and IL‐17 after LPS/OVA challenge. This study revealed a new connection between Ormdl3 overexpression, circulating levels of S1P, IL‐17, and neutrophil recruitment into the lung.
Ground ice is abundant in the upper permafrost throughout the Arctic and fundamentally affects terrain responses to climate warming. Ice wedges, which form near the surface and are the dominant type ...of massive ice in the Arctic, are particularly vulnerable to warming. Yet processes controlling ice wedge degradation and stabilization are poorly understood. Here we quantified ice wedge volume and degradation rates, compared ground ice characteristics and thermal regimes across a sequence of five degradation and stabilization stages and evaluated biophysical feedbacks controlling permafrost stability near Prudhoe Bay, Alaska. Mean ice wedge volume in the top 3 m of permafrost was 21%. Imagery from 1949 to 2012 showed thermokarst extent (area of water‐filled troughs) was relatively small from 1949 (0.9%) to 1988 (1.5%), abruptly increased by 2004 (6.3%) and increased slightly by 2012 (7.5%). Mean annual surface temperatures varied by 4.9°C among degradation and stabilization stages and by 9.9°C from polygon center to deep lake bottom. Mean thicknesses of the active layer, ice‐poor transient layer, ice‐rich intermediate layer, thermokarst cave ice, and wedge ice varied substantially among stages. In early stages, thaw settlement caused water to impound in thermokarst troughs, creating positive feedbacks that increased net radiation, soil heat flux, and soil temperatures. Plant growth and organic matter accumulation in the degraded troughs provided negative feedbacks that allowed ground ice to aggrade and heave the surface, thus reducing surface water depth and soil temperatures in later stages. The ground ice dynamics and ecological feedbacks greatly complicate efforts to assess permafrost responses to climate change.
Key Points
Ground ice occupies a large volume of the top 3 m of Arctic permafrost
Ice wedge thawing creates positive feedbacks that enhance degradation
Ecological responses provide negative feedbacks that stabilize the surface
Chronic exposure to neonicotinoid insecticides has been linked to reduced survival of pollinating insects at both the individual and colony level, but so far only experimentally. Analyses of ...large-scale datasets to investigate the real-world links between the use of neonicotinoids and pollinator mortality are lacking. Moreover, the impacts of neonicotinoid seed coatings in reducing subsequent applications of foliar insecticide sprays and increasing crop yield are not known, despite the supposed benefits of this practice driving widespread use. Here, we combine large-scale pesticide usage and yield observations from oilseed rape with those detailing honey bee colony losses over an 11 year period, and reveal a correlation between honey bee colony losses and national-scale imidacloprid (a neonicotinoid) usage patterns across England and Wales. We also provide the first evidence that farmers who use neonicotinoid seed coatings reduce the number of subsequent applications of foliar insecticide sprays and may derive an economic return. Our results inform the societal discussion on the pollinator costs and farming benefits of prophylactic neonicotinoid usage on a mass flowering crop.
Supernova (SN) 2015bh (or SNhunt275) was discovered in NGC 2770 on 2015 February with an absolute magnitude of Mr ~ -13.4 mag, and was initially classified as an SN impostor. Here, we present the ...photometric and spectroscopic evolution of SN 2015bh from discovery to late phases (~1 yr after). In addition, we inspect archival images of the host galaxy up to ~21 yr before discovery, finding a burst ~1 yr before discovery, and further signatures of stellar instability until late 2014. Later on, the luminosity of the transient slowly increases, and a broad light-curve peak is reached after about three months. We propose that the transient discovered in early 2015 could be a core-collapse SN explosion. The pre-SN luminosity variability history, the long-lasting rise and faintness first light-curve peak suggests that the progenitor was a very massive, unstable and blue star, which exploded as a faint SN because of severe fallback of material. Later on, the object experiences a sudden brightening of 3 mag, which results from the interaction of the SN ejecta with circumstellar material formed through repeated past mass-loss events. Spectroscopic signatures of interaction are however visible at all epochs. A similar chain of events was previously proposed for the similar interacting SN 2009ip.
Summary
Most adherence studies only consider treatment following a first prescription. Using an extended follow-up, we found that 60% of seniors starting oral bisphosphonate therapy were exposed for ...≥ 3 years (48% for ≥ 5 years). Studies are needed to examine the benefits and harms of continuing bisphosphonate therapy beyond 3 years.
Introduction
The purpose of this study was to identify and describe patterns of long-term oral bisphosphonate use among seniors using a novel methodological approach that considers extended follow-up.
Methods
Among Ontarians aged 66 years or older, we identified subjects with a first dispensing of alendronate or risedronate between November 2000 and December 2016. We followed them until death or December 2019 to identify patients with ≥ 3 years of bisphosphonate use, defined as a proportion of days covered ≥ 80%, using 3-year rolling windows. We calculated the proportion of patients with long-term therapy (≥ 3 years of use) using Kaplan-Meier estimates. We described patterns of long-term use and compared patient characteristics between patients with and without long-term therapy.
Results
We identified 260,784 eligible seniors initiating bisphosphonate therapy. Of these, 60% continued therapy ≥ 3 years (77% women), and 48% continued ≥ 5 years. Characteristics did not meaningfully differ between patients with or without long-term therapy. The median length of long-term therapy was 7.0 (IQR 5.1) years for women and 6.1 (IQR 4.3) years for men. Only 20% experienced a treatment gap before long-term therapy, yet 50% experienced a treatment gap of ≥ 120 days after a median 5.3 years of therapy. Eighty-one percent who returned to therapy following a treatment gap re-initiated an oral bisphosphonate, with 18% switching to denosumab.
Conclusions
Among seniors initiating oral bisphosphonates, we found that 60% receive at least 3 years of therapy when using an extended follow-up. Studies are needed to examine the benefits and harms of continuing bisphosphonate therapy beyond 3 years.
This study describes the epidemiology and outcome of 637 proximal humeral fractures in 629 elderly (≥ 65 years old) patients. Most were either minimally displaced (n = 278, 44%) or two-part fractures ...(n = 250, 39%) that predominantly occurred in women (n = 525, 82%) after a simple fall (n = 604, 95%), who lived independently in their own home (n = 560, 88%), and one in ten sustained a concomitant fracture (n = 76, 11.9%). The rate of mortality at one year was 10%, with the only independent predictor of survival being whether the patient lived in their own home (p = 0.025). Many factors associated with the patient's social independence significantly influenced the age and gender adjusted Constant score one year after the fracture. More than a quarter of the patients had a poor functional outcome, with those patients not living in their own home (p = 0.04), participating in recreational activities (p = 0.01), able to perform their own shopping (p < 0.001), or able to dress themselves (p = 0.02) being at a significantly increased risk of a poor outcome, which was independent of the severity of the fracture (p = 0.001). A poor functional outcome after a proximal humeral fracture is not independently influenced by age in the elderly, and factors associated with social independence are more predictive of outcome.
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