The relationships between filamentary structures, star formation, and magnetic fields in Vela C

Molecular clouds contain a number of structural features representing stages in their fragmentation to form stars. This project focuses on dense, elongated filamentary structures that have recently been found to be ubiquitous throughout molecular clouds, whose role in the star formation process is currently the subject of much research. The specifics of that role are unclear as is the general role of magnetic fields in structure formation. This project aims to elucidate the relationships between filamentary structure, magnetic fields, and star formation activity in the South- and Centre-ridges of the Vela C Molecular Cloud. Those regions contain more complex filamentary structures than previously characterised, requiring the development of two novel methods for their study as part of this project. Observations by the infrared Herschel Space Observatory delineate the filamentary structures, while radio Mopra CS and 13CO (1-0) data are used to confirm their velocity coherence. Australia Telescope Compact Array radio observations of the three lowest ammonia (NH3) inversion transitions reveal the cool, dense clumps and probe their physical properties. Balloon-borne Large-Aperture Submillimeter Telescope for Polarimetry infrared observations trace the magnetic field orientation. I examine relationships between the filaments, NH3 clumps and a catalogue of pre- and protostellar clumps and cores as well, as those between the filaments, NH3 clumps, and magnetic field. I find that the filaments and clumps are dominated by supersonic, non-thermal motions. Localised filament sections have supercritical mass-per-unit-length. Evidence of a number of relationships between the filaments, NH3 clumps, and pre- and protostellar catalogue sources are found, consistent with filaments representing a uniquely advantageous, preferential location for star formation. The parallel relative orientation between the clumps and their parent filaments is consistent with clump formation through gravitational fragmentation. The highest column density filaments are found to be preferentially misaligned with respect to the magnetic field, in agreement with theories of structure formation under the influence of magnetic fields. This relative orientation trend flows down to the clump scale. The results of this project have significant ramifications, contributing to the shift in the star formation paradigm from one centering on spherical collapse to one based on filamentary fragmentation

Dense circum-nuclear molecular gas in starburst galaxies

We present results from a study of the dense circum-nuclear molecular gas of starburst galaxies. The study aims to investigate the interplay between starbursts, active galactic nuclei and molecular gas. We characterise the dense gas traced by HCN, HCO$^{+}$ and HNC and examine its kinematics in the circum-nuclear regions of nine starburst galaxies observed with the Australia Telescope Compact Array. We detect HCN (1$-$0) and HCO$^{+}$ (1$-$0) in seven of the nine galaxies and HNC (1$-$0) in four. Approximately 7 arcsec resolution maps of the circum-nuclear molecular gas are presented. The velocity integrated intensity ratios, HCO$^{+}$ (1$-$0)/HCN (1$-$0) and HNC (1$-$0)/HCN (1$-$0), are calculated. Using these integrated intensity ratios and spatial intensity ratio maps we identify photon dominated regions (PDRs) in NGC 1097, NGC 1365 and NGC 1808. We find no galaxy which shows the PDR signature in only one part of the observed nuclear region. We also observe unusually strong HNC emission in NGC 5236, but it is not strong enough to be consistent with X-ray dominated region (XDR) chemistry. Rotation curves are derived for five of the galaxies and dynamical mass estimates of the inner regions of three of the galaxies are made.Comment: Accepted for publication in MNRAS, 22 December 2015. Main manuscript is 13 pages, containing 3 figures. Also has 4 appendices of 13 pages total containing numerous figures and details of calculation

Social contact and inequalities in depressive symptoms and loneliness among older adults: a mediation analysis of the English Longitudinal Study of Ageing

Background: Social contact, including remote contact (by telephone, email, letter or text), could help reduce social inequalities in depressive symptoms and loneliness among older adults. Methods: Data were from the 8th wave of the English Longitudinal Study of Aging (2016/17), stratified by age (n=1,578 aged <65; n=4,026 aged 65+). Inverse probability weighting was used to estimate average effects of weekly in-person and remote social contact on depressive symptoms (score of 3+ on 8-item CES-D scale) and two measures of loneliness (sometimes/often feels lonely vs hardly ever/never; and top quintile of UCLA loneliness scale vs all others). We also estimated controlled direct effects of education, partner status, and wealth on loneliness and depressive symptoms under two scenarios: 1) universal infrequent (<weekly) in-person social contact; and 2) universal weekly remote social contact. Results: Weekly in-person social contact was associated on average with reduced odds of loneliness, but associations with remote social contact were weak. Lower education raised odds of depressive symptoms and loneliness, but differences were attenuated with infrequent in-person contact. Respondents living alone experienced more depressive symptoms and loneliness than those living with a partner, and less wealth was associated with more depressive symptoms. With universal infrequent in-person contact, these differences narrowed among those aged under 65 but widened among those aged 65+. Universal weekly remote contact had relatively little impact on inequalities. Conclusions: Reduced in-person social contact may increase depressive symptoms and loneliness among older adults, especially for those aged 65+ who live alone. Reliance on remote social contact seems unlikely to compensate for social inequalities

Corrected and Republished from: "A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against Lethal Streptococcus pneumoniae Challenge"

Current vaccination against Streptococcus pneumoniae uses vaccines based on capsular polysaccharides from selected serotypes and has led to nonvaccine serotype replacement disease. We have investigated an alternative serotype-independent approach, using multiple-antigen vaccines (MAV) prepared from S. pneumoniae TIGR4 lysates enriched for surface proteins by a chromatography step after culture under conditions that induce expression of heat shock proteins (Hsp; thought to be immune adjuvants). Proteomics and immunoblot analyses demonstrated that, compared to standard bacterial lysates, MAV was enriched with Hsps and contained several recognized protective protein antigens, including pneumococcal surface protein A (PspA) and pneumolysin (Ply). Vaccination of rodents with MAV induced robust antibody responses to multiple serotypes, including nonpneumococcal conjugate vaccine serotypes. Homologous and heterologous strains of S. pneumoniae were opsonized after incubation in sera from vaccinated rodents. In mouse models, active vaccination with MAV significantly protected against pneumonia, while passive transfer of rabbit serum from MAV-vaccinated rabbits significantly protected against sepsis caused by both homologous and heterologous S. pneumoniae strains. Direct comparison of MAV preparations made with or without the heat shock step showed no clear differences in protein antigen content and antigenicity, suggesting that the chromatography step rather than Hsp induction improved MAV antigenicity. Overall, these data suggest that the MAV approach may provide serotype-independent protection against S. pneumoniae

Mental health and health behaviours before and during the initial phase of the COVID-19 lockdown: longitudinal analyses of the UK Household Longitudinal Study.

Background There are concerns that COVID-19 mitigation measures, including the ‘lockdown’, may have unintended health consequences. We examined trends in mental health and health behaviours in the UK before and during the initial phase of the COVID-19 lockdown and differences across population subgroups. Methods Repeated cross-sectional and longitudinal analysis of the UK Household Longitudinal Study, including representative samples of over 27,000 adults (aged 18+) interviewed in four survey waves between 2015 and 2020. A total of 9748 adults had complete data for longitudinal analyses. Outcomes included psychological distress (General Health Questionnaire-12), loneliness, current cigarette smoking, use of e-cigarettes and alcohol consumption. Cross-sectional prevalence estimates were calculated and multilevel Poisson regression assessed associations between time period and the outcomes of interest, as well as differential associations by age, gender, education level and ethnicity. Results Psychological distress increased 1 month into lockdown with the prevalence rising from 19.4% (95% CI 18.7% to 20.1%) in 2017–2019 to 30.6% (95% CI 29.1% to 32.3%) in April 2020 (RR=1.3, 95% CI 1.2 to 1.4). Groups most adversely affected included women, young adults, people from an Asian background and those who were degree educated. Loneliness remained stable overall (RR=0.9, 95% CI 0.6 to 1.5). Smoking declined (RR=0.9, 95% CI=0.8,1.0) and the proportion of people drinking four or more times per week increased (RR=1.4, 95% CI 1.3 to 1.5), as did binge drinking (RR=1.5, 95% CI 1.3 to 1.7). Conclusions Psychological distress increased 1 month into lockdown, particularly among women and young adults. Smoking declined, but adverse alcohol use generally increased. Effective measures are required to mitigate negative impacts on health

Extraordinary rocks from the peak ring of the Chicxulub impact crater: P-wave velocity, density, and porosity measurements from IODP/ICDP Expedition 364

Joint International Ocean Discovery Program and International Continental Scientific Drilling Program Expedition 364 drilled into the peak ring of the Chicxulub impact crater. We present P-wave velocity, density, and porosity measurements from Hole M0077A that reveal unusual physical properties of the peak-ring rocks. Across the boundary between post-impact sedimentary rock and suevite (impact melt-bearing breccia) we measure a sharp decrease in velocity and density, and an increase in porosity. Velocity, density, and porosity values for the suevite are 2900–3700 m/s, 2.06–2.37 g/cm3, and 20–35%, respectively. The thin (25 m) impact melt rock unit below the suevite has velocity measurements of 3650–4350 m/s, density measurements of 2.26–2.37 g/cm3, and porosity measurements of 19–22%. We associate the low velocity, low density, and high porosity of suevite and impact melt rock with rapid emplacement, hydrothermal alteration products, and observations of pore space, vugs, and vesicles. The uplifted granitic peak ring materials have values of 4000–4200 m/s, 2.39–2.44 g/cm3, and 8–13% for velocity, density, and porosity, respectively; these values differ significantly from typical unaltered granite which has higher velocity and density, and lower porosity. The majority of Hole M0077A peak-ring velocity, density, and porosity measurements indicate considerable rock damage, and are consistent with numerical model predictions for peak-ring formation where the lithologies present within the peak ring represent some of the most shocked and damaged rocks in an impact basin. We integrate our results with previous seismic datasets to map the suevite near the borehole. We map suevite below the Paleogene sedimentary rock in the annular trough, on the peak ring, and in the central basin, implying that, post impact, suevite covered the entire floor of the impact basin. Suevite thickness is 100–165 m on the top of the peak ring but 200 m in the central basin, suggesting that suevite flowed downslope from the collapsing central uplift during and after peak-ring formation, accumulating preferentially within the central basin

Relative Alignment between the Magnetic Field and Molecular Gas Structure in the Vela C Giant Molecular Cloud Using Low- and High-density Tracers

We compare the magnetic field orientation for the young giant molecular cloud Vela C inferred from 500 μm polarization maps made with the BLASTPol balloon-borne polarimeter to the orientation of structures in the integrated line emission maps from Mopra observations. Averaging over the entire cloud we find that elongated structures in integrated line-intensity or zeroth-moment maps, for low-density tracers such as 12CO and 13CO J → 1 – 0, are statistically more likely to align parallel to the magnetic field, while intermediate- or high-density tracers show (on average) a tendency for alignment perpendicular to the magnetic field. This observation agrees with previous studies of the change in relative orientation with column density in Vela C, and supports a model where the magnetic field is strong enough to have influenced the formation of dense gas structures within Vela C. The transition from parallel to no preferred/perpendicular orientation appears to occur between the densities traced by 13CO and by C18O J → 1 – 0. Using RADEX radiative transfer models to estimate the characteristic number density traced by each molecular line, we find that the transition occurs at a molecular hydrogen number density of approximately 103 cm−3. We also see that the Centre Ridge (the highest column density and most active star-forming region within Vela C) appears to have a transition at a lower number density, suggesting that this may depend on the evolutionary state of the cloud

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570