Reports of ChAdOx1 vaccine-associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations ...between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0-27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41-13.83), with an estimated incidence of 1.13 (0.62-1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29-3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12-1.34) 0-27 d after vaccination, with an SCCS RR of 0.97 (0.93-1.02). For hemorrhagic events 0-27 d after vaccination, the aRR was 1.48 (1.12-1.96), with an SCCS RR of 0.95 (0.82-1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events.
Full text
Available for:
GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
ABSTRACT The physics of cosmic rays (CRs) is a promising candidate for explaining the driving of galactic winds and outflows. Recent galaxy formation simulations have demonstrated the need for active ...CR transport either in the form of diffusion or streaming to successfully launch winds in galaxies. However, due to computational limitations, most previous simulations have modeled CR transport isotropically. Here, we discuss high-resolution simulations of isolated disk galaxies in a 1011 M halo with the moving-mesh code Arepo that include injection of CRs from supernovae, advective transport, CR cooling, and CR transport through isotropic or anisotropic diffusion. We show that either mode of diffusion leads to the formation of strong bipolar outflows. However, they develop significantly later in the simulation with anisotropic diffusion compared to the simulation with isotropic diffusion. Moreover, we find that isotropic diffusion allows most of the CRs to quickly diffuse out of the disk, while in the simulation with anisotropic diffusion, most CRs remain in the disk once the magnetic field becomes dominated by its azimuthal component, which occurs after ∼300 Myr. This has important consequences for the gas dynamics in the disk. In particular, we show that isotropic diffusion strongly suppresses the amplification of the magnetic field in the disk compared to anisotropic or no diffusion models. We therefore conclude that reliable simulations which include CR transport inevitably need to account for anisotropic diffusion.
The emerging understanding of gut microbiota as 'metabolic machinery' influencing many aspects of physiology has gained substantial attention in the field of psychiatry. This is largely due to the ...many overlapping pathophysiological mechanisms associated with both the potential functionality of the gut microbiota and the biological mechanisms thought to be underpinning mental disorders. In this systematic review, we synthesised the current literature investigating differences in gut microbiota composition in people with the major psychiatric disorders, major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ), compared to 'healthy' controls. We also explored gut microbiota composition across disorders in an attempt to elucidate potential commonalities in the microbial signatures associated with these mental disorders. Following the PRISMA guidelines, databases were searched from inception through to December 2021. We identified 44 studies (including a total of 2510 psychiatric cases and 2407 controls) that met inclusion criteria, of which 24 investigated gut microbiota composition in MDD, seven investigated gut microbiota composition in BD, and 15 investigated gut microbiota composition in SZ. Our syntheses provide no strong evidence for a difference in the number or distribution (α-diversity) of bacteria in those with a mental disorder compared to controls. However, studies were relatively consistent in reporting differences in overall community composition (β-diversity) in people with and without mental disorders. Our syntheses also identified specific bacterial taxa commonly associated with mental disorders, including lower levels of bacterial genera that produce short-chain fatty acids (e.g. butyrate), higher levels of lactic acid-producing bacteria, and higher levels of bacteria associated with glutamate and GABA metabolism. We also observed substantial heterogeneity across studies with regards to methodologies and reporting. Further prospective and experimental research using new tools and robust guidelines hold promise for improving our understanding of the role of the gut microbiota in mental and brain health and the development of interventions based on modification of gut microbiota.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
ABSTRACT
We analyse the physical properties of a large, homogeneously selected sample of ALMA-located sub-millimetre galaxies (SMGs). This survey, AS2UDS, identified 707 SMGs across the ∼1 deg2 ...field, including ∼17 per cent, which are undetected at K ≳ 25.7 mag. We interpret their ultraviolet-to-radio data using magphys and determine a median redshift of z = 2.61 ± 0.08 (1σ range of z = 1.8–3.4) with just ∼6 per cent at z > 4. Our survey provides a sample of massive dusty galaxies at z ≳ 1, with median dust and stellar masses of Md = (6.8 ± 0.3) × 108 M⊙ (thus, gas masses of ∼1011 M⊙) and M* = (1.26 ± 0.05) × 1011 M⊙. We find no evolution in dust temperature at a constant far-infrared luminosity across z ∼ 1.5–4. The gas mass function of our sample increases to z ∼ 2–3 and then declines at z > 3. The space density and masses of SMGs suggest that almost all galaxies with M* ≳ 3 × 1011 M⊙ have passed through an SMG-like phase. The redshift distribution is well fit by a model combining evolution of the gas fraction in haloes with the growth of halo mass past a critical threshold of Mh ∼ 6 × 1012 M⊙, thus SMGs may represent the highly efficient collapse of gas-rich massive haloes. We show that SMGs are broadly consistent with simple homologous systems in the far-infrared, consistent with a centrally illuminated starburst. Our study provides strong support for an evolutionary link between the active, gas-rich SMG population at z > 1 and the formation of massive, bulge-dominated galaxies across the history of the Universe.
Using a complete, magnitude-limited sample of active galaxies from the Sloan Digital Sky Survey, we show that the fraction of broad-line (type 1) active galactic nuclei (AGNs) increases with ...luminosity of the isotropically emitted Oiii narrow emission line. Our results are quantitatively in agreement with, and far less uncertain than, similar trends found from studies of X-ray and radio-selected active galaxies. While the correlation between broad-line fraction and luminosity is qualitatively consistent with the receding torus model, its slope is shallower and we therefore propose a modification to this model where the height of the torus increases slowly with AGN luminosity. We demonstrate that the faint-end slope of the AGN luminosity function steepens significantly when a correction for ‘missing’ type 2 objects is made, and that this can substantially affect the overall AGN luminosity density extrapolated from samples of more luminous objects.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
We discuss new methods to integrate the cosmic ray (CR) evolution equations coupled to magnetohydrodynamics on an unstructured moving mesh, as realized in the massively parallel arepo code for ...cosmological simulations. We account for diffusive shock acceleration of CRs at resolved shocks and at supernova remnants in the interstellar medium (ISM) and follow the advective CR transport within the magnetized plasma, as well as anisotropic diffusive transport of CRs along the local magnetic field. CR losses are included in terms of Coulomb and hadronic interactions with the thermal plasma. We demonstrate the accuracy of our formalism for CR acceleration at shocks through simulations of plane-parallel shock tubes that are compared to newly derived exact solutions of the Riemann shock-tube problem with CR acceleration. We find that the increased compressibility of the post-shock plasma due to the produced CRs decreases the shock speed. However, CR acceleration at spherically expanding blast waves does not significantly break the self-similarity of the Sedov-Taylor solution; the resulting modifications can be approximated by a suitably adjusted, but constant adiabatic index. In first applications of the new CR formalism to simulations of isolated galaxies and cosmic structure formation, we find that CRs add an important pressure component to the ISM that increases the vertical scaleheight of disc galaxies and thus reduces the star formation rate. Strong external structure formation shocks inject CRs into the gas, but the relative pressure of this component decreases towards halo centres as adiabatic compression favours the thermal over the CR pressure.
Abstract
We present a new exploration of the cosmic star formation history and dust obscuration in massive galaxies at redshifts 0.5 < z < 6. We utilize the deepest 450- and 850-μm imaging from ...SCUBA-2 CLS, covering 230 arcmin2 in the AEGIS, COSMOS and UDS fields, together with 100–250 μm imaging from Herschel. We demonstrate the capability of the t-phot deconfusion code to reach below the confusion limit, using multiwavelength prior catalogues from CANDELS/3D-HST. By combining IR and UV data, we measure the relationship between total star formation rate (SFR) and stellar mass up to z ∼ 5, indicating that UV-derived dust corrections underestimate the SFR in massive galaxies. We investigate the relationship between obscuration and the UV slope (the IRX–β relation) in our sample, which is similar to that of low-redshift starburst galaxies, although it deviates at high stellar masses. Our data provide new measurements of the total SFR density (SFRD) in $M_{\ast }>10^{10}\,\textrm{M}_{\odot }$ galaxies at 0.5 < z < 6. This is dominated by obscured star formation by a factor of >10. One third of this is accounted for by 450-μm-detected sources, while one-fifth is attributed to UV-luminous sources (brighter than $L_{\rm UV}^\ast$), although even these are largely obscured. By extrapolating our results to include all stellar masses, we estimate a total SFRD that is in good agreement with previous results from IR and UV data at z ≲ 3, and from UV-only data at z ∼ 5. The cosmic star formation history undergoes a transition at z ∼ 3–4, as predominantly unobscured growth in the early Universe is overtaken by obscured star formation, driven by the build-up of the most massive galaxies during the peak of cosmic assembly.
Purpose
Polypharmacy—the use of multiple medications by a single patient—is an important issue associated with various adverse clinical outcomes and rising costs. It is also a topic rarely addressed ...by clinical guidelines. We used routine Scottish health records to address the lack of data on the prevalence of polypharmacy in the broader, adult primary care population, particularly in relation to long-term conditions.
Methods
We conducted a cross-sectional analysis of adult electronic primary healthcare records and used linear regression models to examine the association between the number of medicines prescribed regularly and both multimorbidity and specific clinical conditions, adjusting for age, gender and socioeconomic deprivation.
Results
Overall, 16.9 % of the adults assessed were receiving four to nine medications, and 4.6 % were receiving ten or more medications, increasing with age (28.6 and 7.4 %, respectively, in those aged 60–69 years; 51.8 and 18.6 %, respectively, in those aged ≥80 years), but relatively unaffected by gender or deprivation. Of those patients with two clinical conditions, 20.8 % were receiving four to nine medications, and 1.1 % were receiving ten or more medications; in those patients with six or more comorbidities, these values were 47.7 and 41.7 %, respectively. The number of medications varied considerably between clinical conditions, with cardiovascular conditions associated with the greatest number of additional medications. The accumulation of additional medicines was less with concordant conditions.
Conclusions
Polypharmacy is common in UK primary care. The main factor associated with this is multimorbidity, although considerable variation exists between different conditions. The impact of clinical conditions on the number of medicines is generally less in the presence of co-existing concordant conditions.
α1-Adrenergic receptors (ARs) are catecholamine-activated G protein-coupled receptors (GPCRs) that are expressed in mouse and human myocardium and vasculature, and play essential roles in the ...regulation of cardiovascular physiology. Though α1-ARs are less abundant in the heart than β1-ARs, activation of cardiac α1-ARs results in important biologic processes such as hypertrophy, positive inotropy, ischemic preconditioning, and protection from cell death. Data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) indicate that nonselectively blocking α1-ARs is associated with a twofold increase in adverse cardiac events, including heart failure and angina, suggesting that α1-AR activation might also be cardioprotective in humans. Mounting evidence implicates the α1A-AR subtype in these adaptive effects, including prevention and reversal of heart failure in animal models by α1A agonists. In this review, we summarize recent advances in our understanding of cardiac α1A-ARs.
Summary Psoriasis is an immune-mediated chronic inflammatory disorder which manifests as dermatologic lesions, and psoriatic arthritis (PsA) in about 30% of cases. Psoriasis is associated with ...multiple comorbidities including metabolic syndrome, hypertension, diabetes, cardiovascular events, obesity and psychiatric disorders, which can all affect the course of sleep disorders. A systematic review of the literature on the relationship between psoriasis, PsA, and formal sleep disorders identified 33 studies. There is an increased prevalence of obstructive sleep apnea (OSA) with 36%–81.8% prevalence in psoriasis versus 2%–4% in the general population. There was also an increase in the prevalence of restless legs syndrome of 15.1%–18% in psoriasis versus 5%–10% in European and North American samples. The wide variety of insomnia criteria used in studies resulted in an insomnia prevalence of 5.9%–44.8% in psoriasis, which is insufficient to show an elevated prevalence when the general population has a 10% prevalence of chronic insomnia and 30–35% prevalence of transient insomnia. There is evidence that symptoms of insomnia in psoriasis are directly mediated by pruritus and pain. Treatments that decrease the cutaneous symptoms in psoriasis were successful in mitigating insomnia, but did not show improvements in OSA where the relationship with psoriasis is multifactorial.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
PDF
