Pulsar-wind nebulae and magnetar outflows: observations at radio, X-ray, and gamma-ray wavelengths

We review observations of several classes of neutron-star-powered outflows: pulsar-wind nebulae (PWNe) inside shell supernova remnants (SNRs), PWNe interacting directly with interstellar medium (ISM), and magnetar-powered outflows. We describe radio, X-ray, and gamma-ray observations of PWNe, focusing first on integrated spectral-energy distributions (SEDs) and global spectral properties. High-resolution X-ray imaging of PWNe shows a bewildering array of morphologies, with jets, trails, and other structures. Several of the 23 so far identified magnetars show evidence for continuous or sporadic emission of material, sometimes associated with giant flares, and a few possible "magnetar-wind nebulae" have been recently identified.Comment: 61 pages, 44 figures (reduced in quality for size reasons). Published in Space Science Reviews, "Jets and Winds in Pulsar Wind Nebulae, Gamma-ray Bursts and Blazars: Physics of Extreme Energy Release

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Histological and morphometric lesions in the pre-clinical, developmental phase of insulin-induced laminitis in Standardbred horses

<p>Lamellar pathology in experimentally-induced equine laminitis associated with euglycaemic hyperinsulinaemia is substantial by the acute, clinical phase (∼48 h post-induction). However, lamellar pathology of the developmental, pre-clinical phase requires evaluation. The aim of this study was to analyse lamellar lesions both qualitatively and quantitatively, 6, 12 and 24 h after the commencement of hyperinsulinaemia. Histological and histomorphometrical analyses of lamellar pathology at each time-point included assessment of lamellar length and width, epidermal cell proliferation and death, basement membrane (BM) pathology and leucocyte infiltration. Archived lamellar tissue from control horses and those with acute, insulin-induced laminitis (48 h) was also assessed for cellular proliferative activity by counting the number of cells showing positive nuclear immuno labelling for TPX2.</p> <p>Decreased secondary epidermal lamellar (SEL) width and increased histomorphological evidence of SEL epidermal basal (and supra-basal) cell death occurred early in disease progression (6 h). Increased cellular proliferation in SELs, infiltration of the dermis with small numbers of leucocytes and BM damage occurred later (24 and 48 h). Some lesions, such as narrowing of the SELs, were progressive over this time period (6–48 h). Cellular pathology preceded leucocyte infiltration and BM pathology, indicating that the latter changes may be secondary or downstream events in hyperinsulinaemic laminitis.</p&gt

Intragastric acidification reduces the occurrence of false-negative urea breath test results in patients taking a proton pump inhibitor

The aim of this study was to investigate whether reducing intragastric pH, at the time of urea ingestion, decreases the likelihood of false-negative (FN) urea breath test (UBT) results in patients taking a proton pump inhibitor (PPI). Methods : Patients with active Helicobacter pylori infection underwent a baseline 14 C-UBT (UBT-1) followed by treatment with lansoprazole 30 mg/day for 14 to 16 days. On day 13, patients returned for a repeat standard UBT (UBT-2). Between days 14 to 16, patients underwent a modified UBT (UBT-3), which included consuming 200 ml of 0.1 N citrate solution 30 min before and at the time of 14 C-urea administration. Breath samples were collected 10 and 15 min after 14 C-urea ingestion. Mean 14 CO 2 excretion and the number of FN and equivocal UBT results were compared for the three UBTs. Results : A total of 20 patients completed the study. Lansoprazole caused a significant decrease in mean breath 14 CO 2 excretion (disintegrations per minute) between UBT-1 (2.96 ± 0.23) and UBT-2 (2.08 ± 0.52, p < 0.05 ). Lansoprazole caused six (30%) FN and eight (40%) equivocal UBT-2 results. Mean breath 14 CO 2 excretion for UBT-3 (677 ± 514) was greater than for UBT-2 (234 ± 327, p = 0.001 ). UBT-3 caused only two (10%) FN and three (15%) equivocal results. The 15-min breath sample caused fewer FN and equivocal results than the 10-min sample for both UBT-2 and UBT-3. Conclusions : Giving citrate before and at the time of 14 C-urea administration increases mean breath 14 CO 2 excretion and decreases FN and equivocal UBT results in patients taking a PPI. These observations suggest that it may be possible to design a UBT protocol that will remain accurate in the face of PPI therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71971/1/j.1572-0241.2001.03687.x.pd