The Andromeda Galaxy (M31) is a nearby (\(\sim\)780 kpc) galaxy similar to our own Milky Way. Observational evidence suggests that it resides in a large halo of dark matter (DM), making it a good ...target for DM searches. We present a search for gamma rays from M31 using 1017 days of data from the High Altitude Water Cherenkov (HAWC) Observatory. With its wide field of view and constant monitoring, HAWC is well-suited to search for DM in extended targets like M31. No DM annihilation or decay signal was detected for DM masses from 1 to 100 TeV in the \(b\bar{b}\), \(t\bar{t}\), \(\tau^{+}\tau^{-}\), \(\mu^{+}\mu^{-}\), and \(W^{+}W^{-}\) channels. Therefore we present limits on those processes. Our limits nicely complement the existing body of DM limits from other targets and instruments. Specifically the DM decay limits from our benchmark model are the most constraining for DM masses from 25 TeV to 100 TeV in the \(b\bar{b}, t\bar{t}\) and \(\mu^{+}\mu{-}\) channels. In addition to DM-specific limits, we also calculate general gamma-ray flux limits for M31 in 5 energy bins from 1 TeV to 100 TeV.
The impact of donor‐specific HLA alloantibodies (DSA) on short‐ and long‐term liver transplant outcome is not clearly defined. While it is clear that not all levels of allosensitization produce overt ...clinical injury, and that liver allografts possess some degree of alloantibody resistance, alloantibody‐mediated adverse consequences are increasingly being recognized. To better define the current state of this topic, we assembled experts to provide insights, explore controversies and develop recommendations for future research on the consequences of DSA in liver transplantation. This article summarizes the proceedings of this inaugural meeting. Several insights emerged. Acute antibody‐mediated rejection (AMR), although rarely diagnosed, is increasingly understood to overlap with T cell–mediated rejection. Isolated liver allograft recipients are at increased risk of early allograft immunologic injury when preformed DSA are high titer and persist posttransplantation. Persons who undergo simultaneous liver–kidney transplantation are at risk of renal AMR when Class II DSA persist posttransplantation. Other under‐appreciated DSA associations include ductopenia and fibrosis, plasma cell hepatitis, biliary strictures and accelerated fibrosis associated with recurrent liver disease. Standardized DSA testing and diagnostic criteria for both acute and chronic AMR are needed to distil existing associations into etiological processes in order to develop responsive therapeutic strategies.
Assembled experts provide insights, explore controversies, and develop recommendations for future research on the consequences of donor‐specific alloantibodies in liver transplantation.
The second phase of the Global Land‐Atmosphere Coupling Experiment (GLACE‐2) is aimed at quantifying, with a suite of long‐range forecast systems, the degree to which realistic land surface ...initialization contributes to the skill of subseasonal precipitation and air temperature forecasts. Results, which focus here on North America, show significant contributions to temperature prediction skill out to two months across large portions of the continent. For precipitation forecasts, contributions to skill are much weaker but are still significant out to 45 days in some locations. Skill levels increase markedly when calculations are conditioned on the magnitude of the initial soil moisture anomaly.
The BNT162b2 mRNA (Pfizer–BioNTech) and ChAdOx1 nCoV-19 (Oxford–AstraZeneca) COVID-19 vaccines have shown high efficacy against disease in phase 3 clinical trials and are now being used in national ...vaccination programmes in the UK and several other countries. Studying the real-world effects of these vaccines is an urgent requirement. The aim of our study was to investigate the association between the mass roll-out of the first doses of these COVID-19 vaccines and hospital admissions for COVID-19.
We did a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19—EAVE II—database comprising linked vaccination, primary care, real-time reverse transcription-PCR testing, and hospital admission patient records for 5·4 million people in Scotland (about 99% of the population) registered at 940 general practices. Individuals who had previously tested positive were excluded from the analysis. A time-dependent Cox model and Poisson regression models with inverse propensity weights were fitted to estimate effectiveness against COVID-19 hospital admission (defined as 1–adjusted rate ratio) following the first dose of vaccine.
Between Dec 8, 2020, and Feb 22, 2021, a total of 1 331 993 people were vaccinated over the study period. The mean age of those vaccinated was 65·0 years (SD 16·2). The first dose of the BNT162b2 mRNA vaccine was associated with a vaccine effect of 91% (95% CI 85–94) for reduced COVID-19 hospital admission at 28–34 days post-vaccination. Vaccine effect at the same time interval for the ChAdOx1 vaccine was 88% (95% CI 75–94). Results of combined vaccine effects against hospital admission due to COVID-19 were similar when restricting the analysis to those aged 80 years and older (83%, 95% CI 72–89 at 28–34 days post-vaccination).
Mass roll-out of the first doses of the BNT162b2 mRNA and ChAdOx1 vaccines was associated with substantial reductions in the risk of hospital admission due to COVID-19 in Scotland. There remains the possibility that some of the observed effects might have been due to residual confounding.
UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK.
ABSTRACT Most of the celestial γ rays detected by the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope originate from the interstellar medium when energetic cosmic rays ...interact with interstellar nucleons and photons. Conventional point-source and extended-source studies rely on the modeling of this diffuse emission for accurate characterization. Here, we describe the development of the Galactic Interstellar Emission Model (GIEM), which is the standard adopted by the LAT Collaboration and is publicly available. This model is based on a linear combination of maps for interstellar gas column density in Galactocentric annuli and for the inverse-Compton emission produced in the Galaxy. In the GIEM, we also include large-scale structures like Loop I and the Fermi bubbles. The measured gas emissivity spectra confirm that the cosmic-ray proton density decreases with Galactocentric distance beyond 5 kpc from the Galactic Center. The measurements also suggest a softening of the proton spectrum with Galactocentric distance. We observe that the Fermi bubbles have boundaries with a shape similar to a catenary at latitudes below 20° and we observe an enhanced emission toward their base extending in the north and south Galactic directions and located within ∼4° of the Galactic Center.
Simulations of dark matter show a discrepancy between the expected number of Galactic dark matter sub-halos and how many have been optically observed. Some of these unseen satellites may exist as ...dark dwarf galaxies: sub-halos like dwarf galaxies with no luminous counterpart. Assuming WIMP dark matter, it may be possible to detect these unseen sub-halos from gamma-ray signals originating from dark matter annihilation. The High Altitude Water Cherenkov Observatory (HAWC) is a very high energy (500 GeV to 100 TeV) gamma ray detector with a wide field-of-view and near continuous duty cycle, making HAWC ideal for unbiased sky surveys. We perform such a search for gamma ray signals from dark dwarfs in the Milky Way halo. We perform a targeted search of HAWC gamma-ray sources which have no known association with lower-energy counterparts, based on an unbiased search of the entire sky. With no sources found to strongly prefer dark matter models, we calculate the ability of HAWC to observe dark dwarfs. We also compute the HAWC sensitivity to potential future detections for a given model of dark matter substructure.
The formation of white etching cracks (WECs) in steel rolling element bearings can lead to the premature rolling contact fatigue (RCF) failure mode called white structure flaking. Driving mechanisms ...are still debated but are proposed to be combinations of mechanical, tribochemical and electrical effects. A number of studies have been conducted to record and map WECs in RCF-tested samples and bearings failed from the field. For the first time, this study uses serial sectioning metallography techniques on non-hydrogen charged test samples over a range of test durations to capture the evolution of WEC formation from their initiation to final flaking. Clear evidence for subsurface initiation at non-metallic inclusions was observed at the early stages of WEC formation, and with increasing test duration the propagation of these cracks from the subsurface region to the contact surface eventually causing flaking. In addition, an increase in the amount of associated microstructural changes adjacent to the cracks is observed, this being indicative of the crack being a prerequisite of the microstructural alteration.
Extracellular vesicles (EVs) play a pivotal role in cell-to-cell communication and have been shown to take part in several physiological and pathological processes. EVs have traditionally been ...purified by ultracentrifugation (UC), however UC has limitations, including resulting in, operator-dependant yields, EV aggregation and altered EV morphology, and moreover is time consuming. Here we show that commercially available bind-elute size exclusion chromatography (BE-SEC) columns purify EVs with high yield (recovery ~ 80%) in a time-efficient manner compared to current methodologies. This technique is reproducible and scalable, and surface marker analysis by bead-based flow cytometry revealed highly similar expression signatures compared with UC-purified samples. Furthermore, uptake of eGFP labelled EVs in recipient cells was comparable between BE-SEC and UC samples. Hence, the BE-SEC based EV purification method represents an important methodological advance likely to facilitate robust and reproducible studies of EV biology and therapeutic application.
Swift J0243.6+6124 is a newly discovered Galactic Be/X-ray binary, revealed in late 2017 September in a giant outburst with a peak luminosity of 2 × 1039(d/7 kpc)2 erg s−1 (0.1-10 keV), with no ...formerly reported activity. At this luminosity, Swift J0243.6+6124 is the first known galactic ultraluminous X-ray pulsar. We describe Neutron star Interior Composition Explorer (NICER) and Fermi Gamma-ray Burst Monitor (GBM) timing and spectral analyses for this source. A new orbital ephemeris is obtained for the binary system using spin frequencies measured with GBM and 15-50 keV fluxes measured with the Neil Gehrels Swift Observatory Burst Alert Telescope to model the system's intrinsic spin-up. Power spectra measured with NICER show considerable evolution with luminosity, including a quasi-periodic oscillation near 50 mHz that is omnipresent at low luminosity and has an evolving central frequency. Pulse profiles measured over the combined 0.2-100 keV range show complex evolution that is both luminosity and energy dependent. Near the critical luminosity of L ∼ 1038 erg s−1, the pulse profiles transition from single peaked to double peaked, the pulsed fraction reaches a minimum in all energy bands, and the hardness ratios in both NICER and GBM show a turnover to softening as the intensity increases. This behavior repeats as the outburst rises and fades, indicating two distinct accretion regimes. These two regimes are suggestive of the accretion structure on the neutron star surface transitioning from a Coulomb collisional stopping mechanism at lower luminosities to a radiation-dominated stopping mechanism at higher luminosities. This is the highest observed (to date) value of the critical luminosity, suggesting a magnetic field of B ∼ 1013 G.
IMPORTANCE: It is uncertain whether depressive symptoms are independently associated with subsequent risk of cardiovascular diseases (CVDs). OBJECTIVE: To characterize the association between ...depressive symptoms and CVD incidence across the spectrum of lower mood. DESIGN, SETTING, AND PARTICIPANTS: A pooled analysis of individual-participant data from the Emerging Risk Factors Collaboration (ERFC; 162 036 participants; 21 cohorts; baseline surveys, 1960-2008; latest follow-up, March 2020) and the UK Biobank (401 219 participants; baseline surveys, 2006-2010; latest follow-up, March 2020). Eligible participants had information about self-reported depressive symptoms and no CVD history at baseline. EXPOSURES: Depressive symptoms were recorded using validated instruments. ERFC scores were harmonized across studies to a scale representative of the Center for Epidemiological Studies Depression (CES-D) scale (range, 0-60; ≥16 indicates possible depressive disorder). The UK Biobank recorded the 2-item Patient Health Questionnaire 2 (PHQ-2; range, 0-6; ≥3 indicates possible depressive disorder). MAIN OUTCOMES AND MEASURES: Primary outcomes were incident fatal or nonfatal coronary heart disease (CHD), stroke, and CVD (composite of the 2). Hazard ratios (HRs) per 1-SD higher log CES-D or PHQ-2 adjusted for age, sex, smoking, and diabetes were reported. RESULTS: Among 162 036 participants from the ERFC (73%, women; mean age at baseline, 63 years SD, 9 years), 5078 CHD and 3932 stroke events were recorded (median follow-up, 9.5 years). Associations with CHD, stroke, and CVD were log linear. The HR per 1-SD higher depression score for CHD was 1.07 (95% CI, 1.03-1.11); stroke, 1.05 (95% CI, 1.01-1.10); and CVD, 1.06 (95% CI, 1.04-1.08). The corresponding incidence rates per 10 000 person-years of follow-up in the highest vs the lowest quintile of CES-D score (geometric mean CES-D score, 19 vs 1) were 36.3 vs 29.0 for CHD events, 28.0 vs 24.7 for stroke events, and 62.8 vs 53.5 for CVD events. Among 401 219 participants from the UK Biobank (55% were women, mean age at baseline, 56 years SD, 8 years), 4607 CHD and 3253 stroke events were recorded (median follow-up, 8.1 years). The HR per 1-SD higher depression score for CHD was 1.11 (95% CI, 1.08-1.14); stroke, 1.10 (95% CI, 1.06-1.14); and CVD, 1.10 (95% CI, 1.08-1.13). The corresponding incidence rates per 10 000 person-years of follow-up among individuals with PHQ-2 scores of 4 or higher vs 0 were 20.9 vs 14.2 for CHD events, 15.3 vs 10.2 for stroke events, and 36.2 vs 24.5 for CVD events. The magnitude and statistical significance of the HRs were not materially changed after adjustment for additional risk factors. CONCLUSIONS AND RELEVANCE: In a pooled analysis of 563 255 participants in 22 cohorts, baseline depressive symptoms were associated with CVD incidence, including at symptom levels lower than the threshold indicative of a depressive disorder. However, the magnitude of associations was modest.
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