Jet substructure at the Large Hadron Collider

Jet substructure has emerged to play a central role at the Large Hadron Collider, where it has provided numerous innovative ways to search for new physics and to probe the standard model, particularly in extreme regions of phase space. This review focuses on the development and use of state-of-the-art jet substructure techniques by the ATLAS and CMS experiments

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Prospective, multicentre study of screening, investigation and management of hyponatraemia after subarachnoid haemorrhage in the UK and Ireland

Background: Hyponatraemia often occurs after subarachnoid haemorrhage (SAH). However, its clinical significance and optimal management are uncertain. We audited the screening, investigation and management of hyponatraemia after SAH. Methods: We prospectively identified consecutive patients with spontaneous SAH admitted to neurosurgical units in the United Kingdom or Ireland. We reviewed medical records daily from admission to discharge, 21 days or death and extracted all measurements of serum sodium to identify hyponatraemia (<135 mmol/L). Main outcomes were death/dependency at discharge or 21 days and admission duration >10 days. Associations of hyponatraemia with outcome were assessed using logistic regression with adjustment for predictors of outcome after SAH and admission duration. We assessed hyponatraemia-free survival using multivariable Cox regression. Results: 175/407 (43%) patients admitted to 24 neurosurgical units developed hyponatraemia. 5976 serum sodium measurements were made. Serum osmolality, urine osmolality and urine sodium were measured in 30/166 (18%) hyponatraemic patients with complete data. The most frequently target daily fluid intake was >3 L and this did not differ during hyponatraemic or non-hyponatraemic episodes. 26% (n/N=42/164) patients with hyponatraemia received sodium supplementation. 133 (35%) patients were dead or dependent within the study period and 240 (68%) patients had hospital admission for over 10 days. In the multivariable analyses, hyponatraemia was associated with less dependency (adjusted OR (aOR)=0.35 (95% CI 0.17 to 0.69)) but longer admissions (aOR=3.2 (1.8 to 5.7)). World Federation of Neurosurgical Societies grade I–III, modified Fisher 2–4 and posterior circulation aneurysms were associated with greater hazards of hyponatraemia. Conclusions: In this comprehensive multicentre prospective-adjusted analysis of patients with SAH, hyponatraemia was investigated inconsistently and, for most patients, was not associated with changes in management or clinical outcome. This work establishes a basis for the development of evidence-based SAH-specific guidance for targeted screening, investigation and management of high-risk patients to minimise the impact of hyponatraemia on admission duration and to improve consistency of patient care

The contribution of X-linked coding variation to severe developmental disorders

Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Distribution patterns of zoochlorellae and zooxanthellae hosted by two Pacific Northeast anemones, Anthopleura elegantissima and A. xanthogrammica

This study investigated patterns in the relative abundance of two photosynthetic algal symbionts, zoochlorellae (ZC) and zooxanthellae (ZX), hosted by two temperate anemones, Anthopleura elegantissima and A. xanthogrammica. Previous studies have documented varying proportions of each symbiont along environmental gradients, presumably determined by their respective physiological capabilities. To test for differences in the algal type between the two host species, we sampled anemone tissues (tentacle or tentacle and body column) of similarly sized polyps that were located close together in multiple habitats: tidepools, crevices, underneath rock ledges, and along natural light gradients in caves. The ZC-A. elegantissima symbiosis was rare on the west coast of Vancouver Island, British Columbia, Canada. Even in low-irradiance habitats, ZC were the dominant algae hosted by A. xanthogrammica, while nearby A. elegantissima hosted ZX or was algae-free. As a first step in determining whether symbiont growth rates differed between the two host species, we quantified mitotic index (MI), the percentage of cells with division furrows, under artificial light and in the field by simultaneously sampling tentacles from both species. MI was more stable in A. elegantissima: the MI of ZX isolated from the tentacles of A. xanthogrammica was slightly higher at a light level of 80 micromol quanta m(-2) s(-1) than it was for ZX from A. elegantissima (respectively, 7.3 vs. 6.2) and relatively lower at 40 micromol quanta m(-2) s(-1) (3.9 vs. 5.6). Our data indicate host-specific differences in symbiont distributions and MI when extrinsic physical parameters were similar

Structural mass spectrometry analysis of lipid changes in a Drosophila epilepsy model brain

Phosphatidylethanolamine (PtdEtn) is one of the most abundant phospholipids in many animal cell types. The Drosophila easily shocked (eas(2)) mutant, used as an epilepsy model, is null for the PtdEtn biosynthetic enzyme, ethanolamine kinase. This mutant displays bang sensitive paralysis, and was previously shown to have decreased levels of PtdEtn. We have developed a highly selective and sensitive measurement strategy using ion mobility-mass spectrometry for the relative quantitation of intact phospholipid species directly from isolated brain tissue of eas mutants. Over 1200 distinct lipid signals are observed and within this population 38, including PtdEtn, phosphatidylinositol (PtdIns) and phosphatidylcholine (PtdCho) species are identified to have changed significantly (p < 0.03) between mutant and control tissue. This method has revealed for the first time the structural complexity and biosynthetic interconnectedness of specific PtdEtn and PtdIns lipid species within tissue, and provides great molecular detail compared to traditionally used detection techniques