Atoll sources are accreting neutron star (NS) low-mass X-ray binaries. We present a spectral analysis of four persistent atoll sources (GX 3+1, 4U 1702−429, 4U 0614+091, and 4U 1746−371) observed for ...∼20 ks each with NuSTAR to determine the extent of the inner accretion disk. These sources range from an apparent luminosity of 0.006-0.11 of the Eddington limit (assuming the empirical limit of 3.8 × 1038 erg s−1). Broad Fe emission features shaped by Doppler and relativistic effects close to the NS were firmly detected in three of these sources. The position of the disk appears to be close to the innermost stable circular orbit (ISCO) in each case. For GX 3+1, we determine (90% confidence level) and an inclination of 27°-31°. For 4U 1702−429, we find a and inclination of 53°-64°. For 4U 0614+091, the disk has a position of and inclination of 50°-62°. If the disk does not extend to the innermost stable circular orbit, we can place conservative limits on the magnetic field strength in these systems in the event that the disk is truncated at the Alfvén radius. This provides the limit at the poles of B ≤ 6.7 × 108 G, 3.3 × 108 G, and 14.5 × 108 G for GX 3+1, 4U 1702−429, and 4U 0614+091, respectively. For 4U 1746−371, we argue that the most plausible explanation for the lack of reflection features is a combination of source geometry and strong Comptonization. We place these sources among the larger sample of NSs that have been observed with NuSTAR.
ABSTRACT
We present the first intensive continuum reverberation mapping study of the high accretion-rate Seyfert galaxy Mrk 110. The source was monitored almost daily for more than 200 d with the ...Swift X-ray and ultraviolet (UV)/optical telescopes, supported by ground-based observations from Las Cumbres Observatory, the Liverpool Telescope, and the Zowada Observatory, thus extending the wavelength coverage to 9100 Å. Mrk 110 was found to be significantly variable at all wavebands. Analysis of the intraband lags reveals two different behaviours, depending on the time-scale. On time-scales shorter than 10 d the lags, relative to the shortest UV waveband (∼1928 Å), increase with increasing wavelength up to a maximum of ∼2 d lag for the longest waveband (∼9100 Å), consistent with the expectation from disc reverberation. On longer time-scales, however, the g-band lags the Swift BAT hard X-rays by ∼10 d, with the z-band lagging the g-band by a similar amount, which cannot be explained in terms of simple reprocessing from the accretion disc. We interpret this result as an interplay between the emission from the accretion disc and diffuse continuum radiation from the broad-line region.
Body mass index (BMI) and mortality in old adults from the general population have been related in a U‐shaped or J‐shaped curve. However, limited information is available for elderly nursing home ...populations, particularly about specific cause of death. A systematic PubMed/EMBASE/CINAHL/SCOPUS search until 31 May 2014 without language restrictions was conducted. As no published study reported mortality in standard BMI groups (<18.5, 18.5–24.9, 25–29.9, ≥30 kg/m²), the most adjusted hazard ratios (HRs) according to a pre‐defined list of covariates were obtained from authors and pooled by random‐effect model across each BMI category. Out of 342 hits, 20 studies including 19,538 older nursing home residents with 5,223 deaths during a median of 2 years of follow‐up were meta‐analysed. Compared with normal weight, all‐cause mortality HRs were 1.41 (95% CI = 1.26–1.58) for underweight, 0.85 (95% CI = 0.73–0.99) for overweight and 0.74 (95% CI = 0.57–0.96) for obesity. Underweight was a risk factor for higher mortality caused by infections (HR = 1.65 95% CI = 1.13–2.40). RR results corroborated primary HR results, with additionally lower infection‐related mortality in overweight and obese than in normal‐weight individuals. Like in the general population, underweight is a risk factor for mortality in old nursing home residents. However, uniquely, not only overweight but also obesity is protective, which has relevant nutritional goal implications in this population/setting.
To propose standardized consensus definitions for important clinical endpoints in transcatheter aortic valve implantation (TAVI), investigations in an effort to improve the quality of clinical ...research and to enable meaningful comparisons between clinical trials. To make these consensus definitions accessible to all stakeholders in TAVI clinical research through a peer reviewed publication, on behalf of the public health.
Transcatheter aortic valve implantation may provide a worthwhile less invasive treatment in many patients with severe aortic stenosis and since its introduction to the medical community in 2002, there has been an explosive growth in procedures. The integration of TAVI into daily clinical practice should be guided by academic activities, which requires a harmonized and structured process for data collection, interpretation, and reporting during well-conducted clinical trials.
The Valve Academic Research Consortium established an independent collaboration between Academic Research organizations and specialty societies (cardiology and cardiac surgery) in the USA and Europe. Two meetings, in San Francisco, California (September 2009) and in Amsterdam, the Netherlands (December 2009), including key physician experts, and representatives from the US Food and Drug Administration (FDA) and device manufacturers, were focused on creating consistent endpoint definitions and consensus recommendations for implementation in TAVI clinical research programs. Important considerations in developing endpoint definitions included (i) respect for the historical legacy of surgical valve guidelines; (ii) identification of pathophysiological mechanisms associated with clinical events; (iii) emphasis on clinical relevance. Consensus criteria were developed for the following endpoints: mortality, myocardial infarction, stroke, bleeding, acute kidney injury, vascular complications, and prosthetic valve performance. Composite endpoints for TAVI safety and effectiveness were also recommended.
Although consensus criteria will invariably include certain arbitrary features, an organized multidisciplinary process to develop specific definitions for TAVI clinical research should provide consistency across studies that can facilitate the evaluation of this new important catheter-based therapy. The broadly based consensus endpoint definitions described in this document may be useful for regulatory and clinical trial purposes.
AimsHyperphosphorylated tau neuronal cytoplasmic inclusions (ht‐NCI) are the best protein correlate of clinical decline in Alzheimer's disease (AD). Qualitative evidence identifies ht‐NCI ...accumulating in the isodendritic core before the entorhinal cortex. Here, we used unbiased stereology to quantify ht‐NCI burden in the locus coeruleus (LC) and dorsal raphe nucleus (DRN), aiming to characterize the impact of AD pathology in these nuclei with a focus on early stages.MethodsWe utilized unbiased stereology in a sample of 48 well‐characterized subjects enriched for controls and early AD stages. ht‐NCI counts were estimated in 60‐μm‐thick sections immunostained for p‐tau throughout LC and DRN. Data were integrated with unbiased estimates of LC and DRN neuronal population for a subset of cases.ResultsIn Braak stage 0, 7.9% and 2.6% of neurons in LC and DRN, respectively, harbour ht‐NCIs. Although the number of ht‐NCI+ neurons significantly increased by about 1.9× between Braak stages 0 to I in LC (P = 0.02), we failed to detect any significant difference between Braak stage I and II. Also, the number of ht‐NCI+ neurons remained stable in DRN between all stages 0 and II. Finally, the differential susceptibility to tau inclusions among nuclear subdivisions was more notable in LC than in DRN.ConclusionsLC and DRN neurons exhibited ht‐NCI during AD precortical stages. The ht‐NCI increases along AD progression on both nuclei, but quantitative changes in LC precede DRN changes.
Stereological analysis of tau pathology in the locus coeruleus and dorsal raphe nucleus in early Alzheimer's disease demonstrate that early involvement of brain stem nuclei has important functional implications.
We have developed conceptual designs of two petawatt-class pulsed-power accelerators: Z 300 and Z 800. The designs are based on an accelerator architecture that is founded on two concepts: ...single-stage electrical-pulse compression and impedance matching Phys. Rev. ST Accel. Beams 10, 030401 (2007). The prime power source of each machine consists of 90 linear-transformer-driver (LTD) modules. Each module comprises LTD cavities connected electrically in series, each of which is powered by 5-GW LTD bricks connected electrically in parallel. (A brick comprises a single switch and two capacitors in series.) Six water-insulated radial-transmission-line impedance transformers transport the power generated by the modules to a six-level vacuum-insulator stack. The stack serves as the accelerator’s water-vacuum interface. The stack is connected to six conical outer magnetically insulated vacuum transmission lines (MITLs), which are joined in parallel at a 10-cm radius by a triple-post-hole vacuum convolute. The convolute sums the electrical currents at the outputs of the six outer MITLs, and delivers the combined current to a single short inner MITL. The inner MITL transmits the combined current to the accelerator’s physics-package load. Z 300 is 35 m in diameter and stores 48 MJ of electrical energy in its LTD capacitors. The accelerator generates 320 TW of electrical power at the output of the LTD system, and delivers 48 MA in 154 ns to a magnetized-liner inertial-fusion (MagLIF) target Phys. Plasmas 17, 056303 (2010). The peak electrical power at the MagLIF target is 870 TW, which is the highest power throughout the accelerator. Power amplification is accomplished by the centrally located vacuum section, which serves as an intermediate inductive-energy-storage device. The principal goal of Z 300 is to achieve thermonuclear ignition; i.e., a fusion yield that exceeds the energy transmitted by the accelerator to the liner. 2D magnetohydrodynamic (MHD) simulations suggest Z 300 will deliver 4.3 MJ to the liner, and achieve a yield on the order of 18 MJ. Z 800 is 52 m in diameter and stores 130 MJ. This accelerator generates 890 TW at the output of its LTD system, and delivers 65 MA in 113 ns to a MagLIF target. The peak electrical power at the MagLIF liner is 2500 TW. The principal goal of Z 800 is to achieve high-yield thermonuclear fusion; i.e., a yield that exceeds the energy initially stored by the accelerator’s capacitors. 2D MHD simulations suggest Z 800 will deliver 8.0 MJ to the liner, and achieve a yield on the order of 440 MJ. Z 300 and Z 800, or variations of these accelerators, will allow the international high-energy-density-physics community to conduct advanced inertial-confinement-fusion, radiation-physics, material-physics, and laboratory-astrophysics experiments over heretofore-inaccessible parameter regimes.
Approaches based on linear mixed models (LMMs) have recently gained popularity for modelling population substructure and relatedness in genome-wide association studies. In the last few years, a ...bewildering variety of different LMM methods/software packages have been developed, but it is not always clear how (or indeed whether) any newly-proposed method differs from previously-proposed implementations. Here we compare the performance of several LMM approaches (and software implementations, including EMMAX, GenABEL, FaST-LMM, Mendel, GEMMA and MMM) via their application to a genome-wide association study of visceral leishmaniasis in 348 Brazilian families comprising 3626 individuals (1972 genotyped). The implementations differ in precise details of methodology implemented and through various user-chosen options such as the method and number of SNPs used to estimate the kinship (relatedness) matrix. We investigate sensitivity to these choices and the success (or otherwise) of the approaches in controlling the overall genome-wide error-rate for both real and simulated phenotypes. We compare the LMM results to those obtained using traditional family-based association tests (based on transmission of alleles within pedigrees) and to alternative approaches implemented in the software packages MQLS, ROADTRIPS and MASTOR. We find strong concordance between the results from different LMM approaches, and all are successful in controlling the genome-wide error rate (except for some approaches when applied naively to longitudinal data with many repeated measures). We also find high correlation between LMMs and alternative approaches (apart from transmission-based approaches when applied to SNPs with small or non-existent effects). We conclude that LMM approaches perform well in comparison to competing approaches. Given their strong concordance, in most applications, the choice of precise LMM implementation cannot be based on power/type I error considerations but must instead be based on considerations such as speed and ease-of-use.
Certain copy number variants (CNVs) greatly increase the risk of autism. The authors conducted a genetics-first study to investigate whether heterogeneity in the clinical presentation of autism is ...underpinned by specific genotype-phenotype relationships.
This international study included 547 individuals (mean age, 12.3 years SD=4.2, 54% male) who were ascertained on the basis of having a genetic diagnosis of a rare CNV associated with high risk of autism (82 16p11.2 deletion carriers, 50 16p11.2 duplication carriers, 370 22q11.2 deletion carriers, and 45 22q11.2 duplication carriers), as well as 2,027 individuals (mean age, 9.1 years SD=4.9, 86% male) with autism of heterogeneous etiology. Assessments included the Autism Diagnostic Interview-Revised and IQ testing.
The four genetic variant groups differed in autism symptom severity, autism subdomain profile, and IQ profile. However, substantial variability was observed in phenotypic outcome in individual genetic variant groups (74%-97% of the variance, depending on the trait), whereas variability between groups was low (1%-21%, depending on the trait). CNV carriers who met autism criteria were compared with individuals with heterogeneous autism, and a range of profile differences were identified. When clinical cutoff scores were applied, 54% of individuals with one of the four CNVs who did not meet full autism diagnostic criteria had elevated levels of autistic traits.
Many CNV carriers do not meet full diagnostic criteria for autism but nevertheless meet clinical cutoffs for autistic traits. Although profile differences between variants were observed, there is considerable variability in clinical symptoms in the same variant.
Omicron spike (S) encoding vaccines as boosters, are a potential strategy to improve COVID-19 vaccine efficacy against Omicron. Here, macaques (mostly females) previously immunized with Ad26.COV2.S, ...are boosted with Ad26.COV2.S, Ad26.COV2.S.529 (encoding Omicron BA.1 S) or a 1:1 combination of both vaccines. All booster vaccinations elicit a rapid antibody titers increase against WA1/2020 and Omicron S. Omicron BA.1 and BA.2 antibody responses are most effectively boosted by vaccines including Ad26.COV2.S.529. Independent of vaccine used, mostly WA1/2020-reactive or WA1/2020-Omicron BA.1 cross-reactive B cells are detected. Ad26.COV2.S.529 containing boosters provide only slightly higher protection of the lower respiratory tract against Omicron BA.1 challenge compared with Ad26.COV2.S-only booster. Antibodies and cellular immune responses are identified as complementary correlates of protection. Overall, a booster with an Omicron-spike based vaccine provide only moderately improved immune responses and protection compared with the original Wuhan-Hu-1-spike based vaccine, which still provide robust immune responses and protection against Omicron.
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