Search for Gamma-ray Emission from Dark Matter Annihilation in the Large Magellanic Cloud with the Fermi Large Area Telescope

At a distance of 50 kpc and with a dark matter mass of $\sim10^{10}$ M$_{\odot}$, the Large Magellanic Cloud (LMC) is a natural target for indirect dark matter searches. We use five years of data from the Fermi Large Area Telescope (LAT) and updated models of the gamma-ray emission from standard astrophysical components to search for a dark matter annihilation signal from the LMC. We perform a rotation curve analysis to determine the dark matter distribution, setting a robust minimum on the amount of dark matter in the LMC, which we use to set conservative bounds on the annihilation cross section. The LMC emission is generally very well described by the standard astrophysical sources, with at most a $1-2\sigma$ excess identified near the kinematic center of the LMC once systematic uncertainties are taken into account. We place competitive bounds on the dark matter annihilation cross section as a function of dark matter particle mass and annihilation channel.Comment: 33 pages, 22 figures Version 2: minor corrections and clarifications after journal peer review proces

Search for Gamma-ray Emission from Dark Matter Annihilation in the Small Magellanic Cloud with the Fermi Large Area Telescope

The Small Magellanic Cloud (SMC) is the second-largest satellite galaxy of the Milky Way and is only 60 kpc away. As a nearby, massive, and dense object with relatively low astrophysical backgrounds, it is a natural target for dark matter indirect detection searches. In this work, we use six years of Pass 8 data from the Fermi Large Area Telescope to search for gamma-ray signals of dark matter annihilation in the SMC. Using data-driven fits to the gamma-ray backgrounds, and a combination of N-body simulations and direct measurements of rotation curves to estimate the SMC DM density profile, we found that the SMC was well described by standard astrophysical sources, and no signal from dark matter annihilation was detected. We set conservative upper limits on the dark matter annihilation cross section. These constraints are in agreement with stronger constraints set by searches in the Large Magellanic Cloud and approach the canonical thermal relic cross section at dark matter masses lower than 10 GeV in the $b\bar{b}$ and $\tau^+\tau^-$ channels.Comment: 17 pages, 11 figures. Accepted by PR

Combined xIL-6R and urocortin-2 treatment restores mdx diaphragm muscle force

Introduction: Duchenne muscular dystrophy (DMD) is characterized by progressive muscle degeneration leading to immobility, respiratory failure, and premature death. As chronic inflammation and stress are implicated in DMD pathology, the efficacy of an anti-inflammatory and anti-stress intervention strategy in ameliorating diaphragm dysfunction was investigated. Methods: Diaphragm muscle contractile function was compared in wild-type and dystrophin-deficient mdx mice treated with saline, anti-interleukin-6 receptor antibodies (xIL-6R), the corticotrophin-releasing factor receptor 2 (CRFR2) agonist, urocortin 2, or both xIL-6R and urocortin 2. Results: Combined treatment with xIL-6R and urocortin 2 rescued impaired force in mdx diaphragms. Mechanical work production and muscle shortening was also improved by combined drug treatment. Conclusions: Treatment which neutralizes peripheral IL-6 signaling and stimulates CRFR2 recovers force-generating capacity and the ability to perform mechanical work in mdx diaphragm muscle. These findings may be important in the search for therapeutic targets in DMD

Increases in ‘deaths of despair’ during the COVID-19 pandemic in the United States and the United Kingdom

Objectives: The COVID-19 pandemic significantly impacted mental health, health-related behaviours such as drinking and illicit drug use and the accessibility of health and social care services. How these pandemic shocks affected ‘despair’-related mortality in different countries is less clear. This study uses public data to compare deaths from alcohol, drugs and suicide in the United States and the United Kingdom to identify similarities or differences in the impact of the pandemic on important non-COVID causes of death across countries and to consider the public health implications of these trends. Study design and methods: Data were taken from publicly available mortality figures for England and Wales, Northern Ireland, Scotland and the United States of America, 2001–2021, and analysed descriptively through age-standardised and age-specific mortality rates from suicide, alcohol and drug use. Results: Alcohol-specific deaths increased in all countries between 2019 and 2021, most notably in the United States and, to a lesser extent, England and Wales. Suicide rates did not increase markedly during the pandemic in any of the included nations. Drug-related mortality rates rose dramatically over the same period in the United States but not in other nations. Conclusions: Mortality from ‘deaths of despair’ during the pandemic has displayed divergent trends between causes and countries. Concerns about increases in deaths by suicide appear to have been unfounded, whereas deaths due to alcohol have risen across the United Kingdom and in the United States and across almost all age groups. Scotland and the United States had similarly high levels of drug-related deaths pre-pandemic, but the differing trends during the pandemic highlight the different underlying causes of these drug death epidemics and the importance of tailoring policy responses to these specific contexts

Alcohol-related suicide across Australia : a geospatial analysis

Background: The acute effects of alcohol consumption are a major risk factor for suicide. Positive blood alcohol concentrations are present in almost one-third of all suicides at time of death. These suicides are defined as alcohol-related suicides. This cross-sectional study examines the geospatial distribution/clustering of high proportions of alcohol-related suicides and reports on socioeconomic and demographic risk factors. Methods: National Coronial Information System (NCIS) data were used to calculate proportions of suicides with alcohol present at the time of death for each level 3 statistical areas (SA3) in Australia. A density analysis and hotspot cluster analysis were used to visualise and establish statistically significant clustering of areas with higher (hotspots) and lower (coldspots) proportions. Subsequently, socioeconomic and demographic risk factors for alcohol use and suicide were reported on for hot and cold spots. Results: Significant clustering of areas with higher proportions of alcohol-related suicide occurred in northern Western Australia, the Northern Territory and Queensland, as well as inland New South Wales and inland Queensland. Clustering of SA3s with significantly lower proportions occurred in major city and inner regional Sydney and Melbourne. Conclusion and implications for public health: Results from this study identify areas in which prevention strategies should target alcohol use and can be used to inform prevention strategy design. Additionally, hotspots and coldspots identified in this study can be used for further analysis to better understand contextual risk factors for alcohol-related suicide

Degradation of cognitive timing mechanisms in behavioural variant frontotemporal dementia.

The current study examined motor timing in frontotemporal dementia (FTD), which manifests as progressive deterioration in social, behavioural and cognitive functions. Twenty-patients fulfilling consensus clinical criteria for behavioural variant FTD (bvFTD), 11 patients fulfilling consensus clinical criteria for semantic-variant primary progressive aphasia (svPPA), four patients fulfilling criteria for nonfluent/agrammatic primary progressive aphasia (naPPA), eight patients fulfilling criteria for Alzheimer׳s disease (AD), and 31 controls were assessed on both an externally- and self-paced finger-tapping task requiring maintenance of a regular, 1500 ms beat over 50 taps. Grey and white matter correlates of deficits in motor timing were examined using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI). bvFTD patients exhibited significant deficits in aspects of both externally- and self-paced tapping. Increased mean inter-response interval (faster than target tap time) in the self-paced task was associated with reduced grey matter volume in the cerebellum bilaterally, right middle temporal gyrus, and with increased axial diffusivity in the right superior longitudinal fasciculus, regions and tracts which have been suggested to be involved in a subcortical-cortical network of structures underlying timing abilities. This suggests that such structures can be affected in bvFTD, and that impaired motor timing may underlie some characteristics of the bvFTD phenotype

Project #65: Reducing Door to Balloon Time in STEMI: Celebrating the EMS, ED and Cardiology QI Collaboration

Project Aim: To employ a multidisciplinary approach, engaging local emergency medical services (EMS), emergency department (ED), and cardiology teams to assure that STEMI patients in our community receive prompt, equitable, consistent, safe, and high-quality revascularization of their coronary arteries; and to deploy a variety of educational, operational and feedback tools to initiatve early prehospital EKG transmission and Cath lab activation for patients in our community suffering from ST segment elevated myocardial infarction (STEMI).https://scholarlycommons.henryford.com/qualityexpo2023/1002/thumbnail.jp

The Axial Organ and the Pharynx Are Sites of Hematopoiesis in the Sea Urchin

Background: The location of coelomocyte proliferation in adult sea urchins is unknown and speculations since the early 1800s have been based on microanatomy and tracer uptake studies. In adult sea urchins (Strongylocentrotus purpuratus) with down-regulated immune systems, coelomocyte numbers increase in response to immune challenge, and whether some or all of these cells are newly proliferated is not known. The gene regulatory network that encodes transcription factors that control hematopoiesis in embryonic and larval sea urchins has not been investigated in adults. Hence, to identify the hematopoietic tissue in adult sea urchins, cell proliferation, expression of phagocyte specific genes, and expression of genes encoding transcription factors that function in the conserved regulatory network that controls hematopoiesis in embryonic and larval sea urchins were investigated for several tissues.Results: Cell proliferation was induced in adult sea urchins either by immune challenge through injection of heat-killed Vibrio diazotrophicus or by cell depletion through aspiration of coelomic fluid. In response to either of these stimuli, newly proliferated coelomocytes constitute only about 10% of the cells in the coelomic fluid. In tissues, newly proliferated cells and cells that express SpTransformer proteins (formerly Sp185/333) that are markers for phagocytes are present in the axial organ, gonad, pharynx, esophagus, and gut with no differences among tissues. The expression level of genes encoding transcription factors that regulate hematopoiesis show that both the axial organ and the pharynx have elevated expression compared to coelomocytes, esophagus, gut, and gonad. Similarly, an RNAseq dataset shows similar results for the axial organ and pharynx, but also suggests that the axial organ may be a site for removal and recycling of cells in the coelomic cavity.Conclusions: Results presented here are consistent with previous speculations that the axial organ may be a site of coelomocyte proliferation and that it may also be a center for cellular removal and recycling. A second site, the pharynx, may also have hematopoietic activity, a tissue that has been assumed to function only as part of the intestinal tract

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey.

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management

Validation of Diffuse Correlation Spectroscopic Measurement of Cerebral Blood Flow Using Phase-Encoded Velocity Mapping Magnetic Resonance Imaging

Diffuse correlation spectroscopy (DCS) is a novel optical technique that appears to be an excellent tool for assessing cerebral blood flow in a continuous and non-invasive manner at the bedside. We present new clinical validation of the DCS methodology by demonstrating strong agreement between DCS indices of relative cerebral blood flow and indices based on phase-encoded velocity mapping magnetic resonance imaging (VENC MRI) of relative blood flow in the jugular veins and superior vena cava. Data were acquired from 46 children with single ventricle cardiac lesions during a hypercapnia intervention. Significant increases in cerebral blood flow, measured both by DCS and by VENC MRI, as well as significant increases in oxyhemoglobin concentration, and total hemoglobin concentration, were observed during hypercapnia. Comparison of blood flow changes measured by VENC MRI in the jugular veins and by DCS revealed a strong linear relationship, R = 0.88, p \u3c 0.001, slope = 0.91 ± 0.07. Similar correlations were observed between DCS and VENC MRI in the superior vena cava, R = 0.77, slope = 0.99 ± 0.12, p \u3c 0.001. The relationship between VENC MRI in the aorta and DCS, a negative control, was weakly correlated, R = 0.46, slope = 1.77 ± 0.45, p \u3c 0.001