Objective To determine the incidence of and mortality from bullous pemphigoid and pemphigus vulgaris in the United Kingdom.Design Retrospective historical cohort study.Setting Computerised medical ...records from the health improvement network, a large population based UK general practice database.Participants Patients with pemphigus vulgaris and bullous pemphigoid diagnostic codes and age, sex, and practice matched controls.Main outcome measures Incidence and mortality compared with the control population by calendar period, age group, sex, geographical region, and degree of social deprivation.Results 869 people with bullous pemphigoid and 138 people with pemphigus vulgaris were identified. The median age at presentation for bullous pemphigoid was 80 (range 23-102) years, and 534 (61%) patients were female. The median age at presentation for pemphigus vulgaris was 71 (21-102) years, and 91 (66%) patients were female. Incidences of bullous pemphigoid and pemphigus vulgaris were 4.3 (95% confidence interval 4.0 to 4.6) and 0.7 (0.6 to 0.8) per 100 000 person years. The incidence of bullous pemphigoid increased over time; the average yearly increase was 17% (incidence rate ratio=1.2, 95% confidence interval 1.1 to 1.2). An average yearly increase in incidence of pemphigus vulgaris of 11% (incidence rate ratio=1.1, 1.0 to 1.2) occurred. The risk of death for patients with bullous pemphigoid was twice as great as for controls (adjusted hazard ratio=2.3, 95% confidence interval 2.0 to 2.7). For pemphigus vulgaris, the risk of death was three times greater than for controls (adjusted hazard ratio=3.3, 2.2 to 5.2).Conclusions Incidences of bullous pemphigoid and pemphigus vulgaris are increasing. The reasons for the changes in incidence are not clearly understood but have implications for identifying causative factors. Both disorders are associated with a high risk of death. Previous estimates may have underestimated the risk of death associated with these diseases.
Previous studies have shown that the incidence of idiopathic pulmonary fibrosis (IPF) is rising in the U.K. and U.S.A. Death registrations and primary care data were used to determine the current ...trends in IPF incidence in the U.K. Because routine clinical data sets were used, the term IPF clinical syndrome (IPF-CS) is used to describe individuals in this study.
Age- and stratum-specific death registration rates between 1968 and 2008 were calculated and these were applied to the 2008 population to generate annual standardised expected number of deaths. Annual mortality rate ratios were calculated using Poisson regression. Computerised primary care records were used to determine incidence rates of IPF-CS between 2000 and 2008 stratified by age, sex and geographical region, and survival rates between calendar periods were compared.
Annual death certificate recording of IPF-CS rose sixfold across the study period from 0.92 per 100,000 in the 1968-1972 calendar periods to 5.10 per 100,000 in the 2006-2008 calendar period, and were higher in men and the older age groups. The incidence of IPF-CS in primary care increased by 35% from 2000 to 2008, with an overall incidence rate of 7.44 per 100,000 person-years (95% CI 7.12 to 7.77). Incidence was higher in men, the older population and in Northwest England.
The incidence of IPF-CS in primary care and registered deaths from this cause in the U.K. continues to rise in the 21st century. The current findings suggest that there are >5000 new cases diagnosed each year in the U.K.
Limiting global warming to 1.5 or 2.0°C requires strong mitigation of anthropogenic greenhouse gas (GHG) emissions. Concurrently, emissions of anthropogenic aerosols will decline, due to coemission ...with GHG, and measures to improve air quality. However, the combined climate effect of GHG and aerosol emissions over the industrial era is poorly constrained. Here we show the climate impacts from removing present‐day anthropogenic aerosol emissions and compare them to the impacts from moderate GHG‐dominated global warming. Removing aerosols induces a global mean surface heating of 0.5–1.1°C, and precipitation increase of 2.0–4.6%. Extreme weather indices also increase. We find a higher sensitivity of extreme events to aerosol reductions, per degree of surface warming, in particular over the major aerosol emission regions. Under near‐term warming, we find that regional climate change will depend strongly on the balance between aerosol and GHG forcing.
Plain Language Summary
To keep within 1.5 or 2° of global warming, we need massive reductions of greenhouse gas emissions. At the same time, aerosol emissions will be strongly reduced. We show how cleaning up aerosols, predominantly sulfate, may add an additional half a degree of global warming, with impacts that strengthen those from greenhouse gas warming. The northern hemisphere is found to be more sensitive to aerosol removal than greenhouse gas warming, because of where the aerosols are emitted today. This means that it does not only matter whether or not we reach international climate targets. It also matters how we get there.
Key Points
Aerosol emission removal can warm the climate by more than 0.5°C
Key climate variables are more sensitive to aerosol removal than to GHG increase
Regional impacts of 1.5°C warming depend on the balance between aerosol and GHG forcing
Context. A new class of super-luminous transients has recently been identified. These objects reach absolute luminosities of Mu < −21, lack hydrogen in their spectra, and are exclusively ...discovered by non-targeted surveys because they are associated with very faint galaxies. Aims. We aim to contribute to a better understanding of these objects by studying SN 2006oz, a newly-recognized member of this class. Methods. We present multi-color light curves of SN 2006oz from the SDSS-II SN Survey that cover its rise time, as well as an optical spectrum that shows that the explosion occurred at z ~ 0.376. We fitted black-body functions to estimate the temperature and radius evolution of the photosphere and used the parametrized code SYNOW to model the spectrum. We constructed a bolometric light curve and compared it with explosion models. In addition, we conducted a deep search for the host galaxy with the 10 m GTC telescope. Results. The very early light curves show a dip in the g- and r-bands and a possible initial cooling phase in the u-band before rising to maximum light. The bolometric light curve shows a precursor plateau with a duration of 6–10 days in the rest-frame. A lower limit of Mu < − 21.5 can be placed on the absolute peak luminosity of the SN, while the rise time is constrained to be at least 29 days. During our observations, the emitting sphere doubled its radius to ~2 × 1015 cm, while the temperature remained hot at ~15 000 K. As for other similar SNe, the spectrum is best modeled with elements including O ii and Mg ii, while we tentatively suggest that Fe iii might be present. The host galaxy is detected in gri with 25.74 ± 0.19, 24.43 ± 0.06, and 24.14 ± 0.12, respectively. It is a faint dwarf galaxy with Mg = −16.9. Conclusions. We suggest that the precursor plateau might be related to a recombination wave in a circumstellar medium (CSM) and discuss whether this is a common property of all similar explosions. The subsequent rise can be equally well described by input from a magnetar or by ejecta-CSM interaction, but the models are not well constrained owing to the lack of post-maximum observations, and CSM interaction has difficulties accounting for the precursor plateau self-consistently. Radioactive decay is less likely to be the mechanism that powers the luminosity. The host is a moderately young and star-forming, but not a starburst, galaxy.
Genetic variation can affect drug response in multiple ways, although it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, ...collaborating with the Pharmacogenomics Research Network, began eMERGE‐PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of “precision medicine.” The February 2015 eMERGE‐PGx data release includes sequence‐derived data from ∼5,000 clinical subjects. We present the variant frequency spectrum categorized by variant type, ancestry, and predicted function. We found 95.12% of genes have variants with a scaled Combined Annotation‐Dependent Depletion score above 20, and 96.19% of all samples had one or more Clinical Pharmacogenetics Implementation Consortium Level A actionable variants. These data highlight the distribution and scope of genetic variation in relevant pharmacogenes, identifying challenges associated with implementing clinical sequencing for drug treatment at a broader level, underscoring the importance for multifaceted research in the execution of precision medicine.
Objectives
The aim of the study was to assess the impact of the gain in body mass index (BMI) observed immediately after antiretroviral therapy (ART) initiation on the subsequent risk of ...cardiovascular disease (CVD) and diabetes.
Methods
We analysed data from the Data Collection on Adverse Events of Anti‐HIV Drugs (D:A:D) cohort study. Outcomes were development of (i) CVD (composite of myocardial infarction/stroke/coronary procedure) and (ii) diabetes. The main exposure variable was change in BMI from ART initiation (pre‐ART) to 1 year after initiation (continuous variable) in treatment‐naïve individuals initiating ART with no history of CVD or diabetes (for respective outcomes). BMI weight (kg)/(height (m))2 was categorized as underweight (< 18.5), normal (18.5–25), overweight (25–30) and obese (> 30). Poisson regression models were fitted stratified for each pre‐ART BMI category to allow for category‐specific estimates of incidence rate ratio (IRR). Models were adjusted for pre‐ART BMI and CD4 count, key known risk factors (time‐updated where possible) and calendar year.
Results
A total of 97 CVD events occurred in 43 982 person‐years (n = 9321) and 125 diabetes events in 43 278 person‐years (n = 9193). In fully adjusted analyses for CVD, the IRR/unit gain in BMI (95% confidence interval) in the first year of ART, by pre‐ART BMI category, was: underweight, 0.90 (0.60–1.37); normal, 1.18 (1.05–1.33); overweight, 0.87 (0.70–1.10), and obese, 0.95 (0.71–1.28) (P for interaction = 0.04). For diabetes, the IRR/unit gain in BMI was 1.11 (95% confidence interval 1.03 to 1.21), regardless of pre‐ART BMI (P for interaction > 0.05).
Conclusions
Short‐term gain in BMI following ART initiation appeared to increase the longer term risk of CVD, but only in those with pre‐ART BMI in the normal range. It was also associated with increased risk of diabetes regardless of pre‐ART BMI.
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are relentlessly progressive neurodegenerative disorders with overlapping clinical, genetic and pathological features. ...Cytoplasmic inclusions of fused in sarcoma (FUS) are the hallmark of several forms of FTLD and ALS patients with mutations in the
FUS
gene. FUS is a multifunctional, predominantly nuclear, DNA and RNA binding protein. Here, we report that transgenic mice overexpressing wild-type human FUS develop an aggressive phenotype with an early onset tremor followed by progressive hind limb paralysis and death by 12 weeks in homozygous animals. Large motor neurons were lost from the spinal cord accompanied by neurophysiological evidence of denervation and focal muscle atrophy. Surviving motor neurons in the spinal cord had greatly increased cytoplasmic expression of FUS, with globular and skein-like FUS-positive and ubiquitin-negative inclusions associated with astroglial and microglial reactivity. Cytoplasmic FUS inclusions were also detected in the brain of transgenic mice without apparent neuronal loss and little astroglial or microglial activation. Hemizygous FUS overexpressing mice showed no evidence of a motor phenotype or pathology. These findings recapitulate several pathological features seen in human ALS and FTLD patients, and suggest that overexpression of wild-type FUS in vulnerable neurons may be one of the root causes of disease. Furthermore, these mice will provide a new model to study disease mechanism, and test therapies.
On May 21, 2019 at 03:02:29 UTC Advanced LIGO and Advanced Virgo observed a short duration gravitational-wave signal, GW190521, with a three-detector network signal-to-noise ratio of 14.7, and an ...estimated false-alarm rate of 1 in 4900 yr using a search sensitive to generic transients. If GW190521 is from a quasicircular binary inspiral, then the detected signal is consistent with the merger of two black holes with masses of 85_{-14}^{+21} M_{⊙} and 66_{-18}^{+17} M_{⊙} (90% credible intervals). We infer that the primary black hole mass lies within the gap produced by (pulsational) pair-instability supernova processes, with only a 0.32% probability of being below 65 M_{⊙}. We calculate the mass of the remnant to be 142_{-16}^{+28} M_{⊙}, which can be considered an intermediate mass black hole (IMBH). The luminosity distance of the source is 5.3_{-2.6}^{+2.4} Gpc, corresponding to a redshift of 0.82_{-0.34}^{+0.28}. The inferred rate of mergers similar to GW190521 is 0.13_{-0.11}^{+0.30} Gpc^{-3} yr^{-1}.
We present first results of the H2O Southern Galactic Plane Survey (HOPS), using the Mopra Radio Telescope with a broad-band backend and a beam size of about 2 arcmin. We have observed 100 deg2 of ...the southern Galactic plane at 12 mm (19.5-27.5 GHz), including spectral line emission from H2O masers, multiple metastable transitions of ammonia, cyanoacetylene, methanol and radio recombination lines. In this paper, we report on the characteristics of the survey and H2O maser emission. We find 540 H2O masers, of which 334 are new detections. The strongest maser is 3933 Jy and the weakest is 0.7 Jy, with 62 masers over 100 Jy. In 14 maser sites, the spread in the velocity of the H2O maser emission exceeds 100 km s−1. In one region, the H2O maser velocities are separated by 351.3 km s−1. The rms noise levels are typically between 1 and 2 Jy, with 95 per cent of the survey under 2 Jy. We estimate completeness limits of 98 per cent at around 8.4 Jy and 50 per cent at around 5.5 Jy. We estimate that there are between 800 and 1500 H2O masers in the Galaxy that are detectable in a survey with similar completeness limits to HOPS. We report possible masers in NH3 (11,9) and (8,6) emission towards G19.61−0.23 and in the NH3 (3,3) line towards G23.33−0.30.
Since an atomic Bose-Einstein condensate, predicted by Einstein in 1925, was first produced in the laboratory in 1995, the study of ultracold Bose and Fermi gases has become one of the most active ...areas in contemporary physics. This book explains phenomena in ultracold gases from basic principles, without assuming a detailed knowledge of atomic, condensed matter, and nuclear physics. This new edition has been revised and updated, and includes new chapters on optical lattices, low dimensions, and strongly-interacting Fermi systems. This book provides a unified introduction to the physics of ultracold atomic Bose and Fermi gases for advanced undergraduate and graduate students, as well as experimentalists and theorists. Chapters cover the statistical physics of trapped gases, atomic properties, cooling and trapping atoms, interatomic interactions, structure of trapped condensates, collective modes, rotating condensates, superfluidity, interference phenomena, and trapped Fermi gases. Problems are included at the end of each chapter.
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