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Scheduled to launch in late 2021,the Imaging X-ray Polarimetry Explorer (IXPE) is a Small Explorer Mission designed to open up a new window of investigation --X-ray polarimetry. The IXPE observatory features 3 identical telescopes each consisting of a mirror module assembly with a polarization-sensitive imaging x-ray detector at its focus. An extending boom, deployed on orbit, provides the necessary 4 m focal length. The payload sits atop a 3-axis stabilized spacecraft which, among other things, provides power, attitude determination and control, commanding, and telemetry to the ground. During its 2-year baseline mission, IXPE will conduct precise polarimetry for samples of multiple categories of x-ray sources, with follow-on observations of selected targets. IXPE is a partnership between NASA and the Italian Space Agency (ASI).

Scheduled to launch in late 2021, the Imaging X-ray Polarimetry Explorer (IXPE) is a NASA Small Explorer Mission in collaboration with the Italian Space Agency (ASI). The mission will open a new window of investigation - imaging X-ray polarimetry. The observatory features 3 identical telescopes each consisting of a mirror module assembly with a polarization-sensitive imaging X-ray detector at the focus. A coilable boom, deployed on orbit, provides the necessary 4-m focal length. The observatory utilizes a 3-axis-stabilized spacecraft which provides services such as power, attitude determination and control, commanding, and telemetry to the ground. During its 2-year baseline mission, IXPE will conduct precise polarimetry for samples of multiple categories of X-ray sources, with follow-on observations of selected targets.

Understanding the genetic and fitness consequences of anthropogenic bottlenecks is crucial for biodiversity conservation. However, studies of bottlenecked populations combining genomic approaches with fitness data are rare. Theory predicts that severe bottlenecks deplete genetic diversity, exacerbate inbreeding depression and decrease population viability. However, actual outcomes are complex and depend on how a species’ unique demography affects its genetic load. We used population genetic and veterinary pathology data, demographic modelling, whole-genome resequencing and forward genetic simulations to investigate the genomic and fitness consequences of a near-extinction event in the northern elephant seal. We found no evidence of inbreeding depression within the contemporary population for key fitness components, including body mass, blubber thickness and susceptibility to parasites and disease. However, we detected a genomic signature of a recent extreme bottleneck (effective population size = 6; 95% confidence interval = 5.0–7.5) that will have purged much of the genetic load, potentially leading to the lack of observed inbreeding depression in our study. Our results further suggest that deleterious genetic variation strongly impacted the post-bottleneck population dynamics of the northern elephant seal. Our study provides comprehensive empirical insights into the intricate dynamics underlying species-specific responses to anthropogenic bottlenecks. Analysis of northern elephant seal populations shows no evidence of inbreeding depression, probably because a recent extreme bottleneck purged much of the genetic load.

ObjectiveTo evaluate efficacy and safety of lacosamide (up to 12 mg/kg/day or 400 mg/day) as adjunctive treatment for uncontrolled primary generalised tonic-clonic seizures (PGTCS) in patients (≥4 years) with idiopathic generalised epilepsy (IGE).MethodsPhase 3, double-blind, randomised, placebo-controlled trial (SP0982; NCT02408523) in patients with IGE and PGTCS taking 1–3 concomitant antiepileptic drugs. Primary outcome was time to second PGTCS during 24-week treatment.Results242 patients were randomised and received ≥1 dose of trial medication (lacosamide/placebo: n=121/n=121). Patients (mean age: 27.7 years; 58.7% female) had a history of generalised-onset seizures (tonic-clonic 99.6%; myoclonic 38.8%; absence 37.2%). Median treatment duration with lacosamide/placebo was 143/65 days. Risk of developing a second PGTCS during 24-week treatment was significantly lower with lacosamide than placebo (Kaplan-Meier survival estimates 55.27%/33.37%; HR 0.540, 95% CI 0.377 to 0.774; p<0.001; n=118/n=121). Median time to second PGTCS could not be estimated for lacosamide (>50% of patients did not experience a second PGTCS) and was 77.0 days for placebo. Kaplan-Meier estimated freedom from PGTCS at end of the 24-week treatment period (day 166) for lacosamide/placebo was 31.3%/17.2% (difference 14.1%; p=0.011). More patients on lacosamide than placebo had ≥50% (68.1%/46.3%) or ≥75% (57.1%/36.4%) reduction from baseline in PGTCS frequency/28 days, or observed freedom from PGTCS during treatment (27.5%/13.2%) (n=119/n=121). 96/121 (79.3%) patients on lacosamide had treatment-emergent adverse events (placebo 79/121 (65.3%)), most commonly dizziness (23.1%), somnolence (16.5%), headache (14.0%). No patients died during the trial.ConclusionsLacosamide was efficacious and generally safe as adjunctive treatment for uncontrolled PGTCS in patients with IGE.

Objective: This study examined whether informal caregiver psychologic distress decreases the likelihood of influenza vaccination for community-dwelling elderly with dementia. A secondary aim was to determine whether psychologic distress mediates the relationship between other predisposing, enabling, and medical need variables and vaccination. Methods: Data were drawn from the 1998 National Longitudinal Caregiver Survey. The final sample consisted of 1406 communitydwelling male veterans with dementia and their coresiding female informal caregivers. Presence of caregiver psychologic distress was measured using the Boston Short Form of the Center for Epidemiologic Studies Depression Scale. Vaccination was identified by examining Veteran Administration Outpatient Data Files for visits indicating influenza vaccine administration during the 1998 influenza vaccine season (September 1 to December 31). Multivariate path analysis with observed variables was used to estimate direct and indirect probit path coefficients between independent variables, caregiver psychologic distress, and veteran vaccination. Results: As hypothesized, caregiver distress was significantly associated with a decreased likelihood of care-recipient vaccination (unstandardized coefficient [b] = -0.023, P < 0.01). Adjusted for other variables, the predicted probability of vaccination was 37.7% for care-recipients with nondistressed caregivers compared with 29.4% for care-recipients with distressed caregivers. Furthermore, a number of factors significantly influenced vaccination via their influence on psychologic distress. Conclusion: We conclude that caregiver psychologic distress may interfere with access to influenza vaccination in persons with dementia. Access to vaccination may be improved directly by detecting and treating emotional health problems in caregivers and indirectly by addressing precursors to caregiver distress.

INTRODUCTION:Left ventricular assist device (LVAD) therapy is a form of mechanical support for patients with advanced heart failure as either a bridge to heart transplant or destination therapy. The association between gastrointestinal bleeding (GIB) and LVAD recipients is well established. There has been reported literature comparing demographics and clinical associations between patients with and without GIB. The aim of this study was to further investigate these characteristics, identify associations with GIB, and further understand endoscopic management of GIB among LVAD recipients.METHODS:This was a single-center retrospective study analyzing randomly selected patients from a population of 425 Heartmate (HMII) and 193 Heartware recipients from 2007 to 2018. Chart review was performed and data pertaining to demographics, LVAD therapy intention and settings, endoscopic reports, home medications, and echocardiogram reports was collected. Univariate analysis was performed.RESULTS:A total of 188 HMII and 134 Heartware patients were included in this study. Patients that developed GIB tended to be older (56.4 vs. 61.7 years; P = 0.0002). No differences were found in race and gender. Patients that developed a GIB had a higher baseline Cr (1.2 vs. 1.4; P = 0.0284) and lower baseline Hg (10 vs. 11; <0.001). A supratherapeutic INR was associated with GIB (14.7% vs. 26.7%; P = 0.0075). Patients prescribed angiotensin II receptor blockers had less occurrence of GIB (Table 1). Melena was the most common presenting sign. Bleeding lesions were most frequent in the small bowel (42.6%). Of all bleeding lesions identified, 73% were found with EGD and 80.4% were found with push enteroscopy. Arteriovenous malformations were the predominant etiology (Table 2).CONCLUSION:This is one of the largest single-center studies of GIB among patients with LVADs. Small bowel gastric arteriovenous malformations were the most common etiology. The majority of upper GI bleeds were within reach of a push enteroscope (proximal small bowel), which had an incremental diagnostic yield over EGD. There was a protective association with reduced occurrence of GIB among patients taking angiotensin II receptor blockers. The use of proton pump inhibitors showed no association in GIB occurrence and may be overused in this population. Further development of the association between angiotensin II receptor blockers and GIB effect in LVADs are warranted. Multivariate analyses to validate these associations are in progress.Table 1.Baseline Characteristics of Non-Bleeding vs. Bleeding Left Ventricular Assist Device RecipientsTable 2.Description of Gastrointestinal Bleeding Characteristics, Findings, and Interventions Among Left Ventricular Assist Device Recipients

Previous studies by our group have demonstrated the feasibility of noninvasive imaging of alpha(v) integrin to assess temporal and spatial changes in peripheral and myocardial angiogenesis. In this study, we validate the reproducibility, accuracy, and applicability of a new semiautomated noninvasive approach for serial quantitative evaluation of targeted micro-SPECT/CT images of peripheral angiogenesis in wild-type and endothelial nitric oxide sythase (eNOS)-deficient (eNOS-/-) mice subjected to hindlimb ischemia. Mice (n = 15) underwent surgical ligation of the right femoral artery to induce unilateral hindlimb ischemia. One week after ligation, a (99m)Tc-labeled cyclic-Arg-Gly-Asp peptide targeted at alpha(v) integrin (NC100692, n = 10) or a (99m)Tc-labeled negative control (AH-111744, n = 5) was injected, and 60 min later in vivo micro-SPECT/CT images were acquired. Mice were euthanized, tissue from proximal and distal hindlimb was excised for gamma-well counting (GWC) of radiotracer activity, and ischemic-to-nonischemic (I/NI) ratio was calculated. Micro-SPECT/CT images were analyzed using a new semiautomated approach that applies complex volumes of interest (VOIs) derived from segmentation of the micro-CT images onto micro-SPECT images to calculate I/NI activity ratios for the proximal and distal hindlimb. Studies were reprocessed for determination of intra- and interobserver variability. To compare 3-dimensional (3D) VOI analysis with traditional manual 2-dimensional region-of-interest (ROI) analysis of maximum-intensity-projection images, micro-SPECT images were summed onto a single anterior-posterior projection. Rectangular ROIs were manually drawn and I/NI ratio calculated. Our new 3D analysis approach was applied to additional groups of mice (eNOS-/-, n = 5; wild-type, n = 3) imaged before and 1 and 4 wk after femoral artery resection. Our new semiautomated approach for the evaluation of images of alpha(v) integrin targeted with micro-SPECT/CT demonstrated both a high intra- and interobserver variability (R(2) = 0.997) and an accuracy (R(2) = 0.780) for estimation of relative radiotracer activity relative to GWC. Analysis of serial micro-SPECT/CT images demonstrated a significant increase in relative NC100692 retention in the ischemic hindlimb of both wild-type and eNOS-/- mice at 1 wk after surgery. There was a significant (approximately 25%) decrease in radiotracer uptake in eNOS-/- mice relative to wild-type animals, which was not observed at baseline or 4 wk after ligation. A new semiautomated analysis of images of alpha(v) integrin targeted with micro-SPECT/CT provides a noninvasive approach for serial quantitative evaluation of peripheral angiogenesis. The reproducibility and accuracy of this approach allows for quantitative analysis of serial targeted molecular images of lower extremities, has applicability to other targeted SPECT or PET radiotracers, and may have implications for clinical imaging in patients with peripheral arterial disease.

Previous studies by our group have demonstrated the feasibility of non-invasive imaging of αv integrin to assess temporal and spatial changes in peripheral and myocardial angiogenesis. In this study we validate the reproducibility, accuracy, and applicability of a new semi-automated non-invasive approach for serial quantitative evaluation of targeted microSPECT-CT images of peripheral angiogenesis in wild-type and eNOS-deficient mice subjected to hindlimb ischemia.

Vocation is most often linked with a specific calling for those in professional ministry. Doing More with Life explores the way higher education can expand this limited understanding of vocation. Specifically, this volume shows that higher education can clarify how God calls all people, allow mentoring across specific vocations, and inspire future generations to think of their lives as vocations.

Abstract Insofar as methane was the predominant greenhouse gas of the Archean and early Proterozoic eons, its wax and wane in Earth’s atmosphere would have contributed to climate change and the relative flux of harmful UV radiation to surface environments. If correct, understanding the first-order environmental controls (e.g., O2 or resource concentration) of the biological methane cycle might shed light on the repetition of biological, atmospheric and climatic events preserved in the sedimentary rock record between ~2.8 and 2.0 billion years ago. Environmental controls on the dynamics of methane cycling may further explain other repetitious events in deep time, as well as the present-day increase in the methane flux to the atmosphere from wetland environments. In this study, we developed an ecological interaction model to predict the conditions in which methane is preferentially released to the atmosphere, and found that the interplay of resource and O2 availability can cause complex cyclic patterns in methane dynamics that are unrelated to the size and efficiency of any of the microbial communities, to initial conditions, or to other model constraints. Based on these model results, we propose that the cyclicity of methane haze events and glacial episodes in the late Archean and early Proterozoic may have been linked to the progressive increase in oceanic and atmospheric O2 through the interval. Competing Interest Statement The authors have declared no competing interest.