Regional Geographies of Extreme Heat

Shaped by countless influences from the atmosphere, biosphere, hydrosphere, and anthroposphere acting across a wide spectrum of spatiotemporal scales, spatial variations in climate are ubiquitous. Meanwhile, the warming signal from anthropogenically elevated greenhouse-gas concentrations is emerging as an overriding determinant for more and more aspects of the climate system, extreme heat among them. In this dissertation, I explore the interaction of these two effects, and the implications of the patterns they create. A key finding is that rapid increases in extreme heat are already occurring, by some metrics having already doubled in the past 40 years, and further nonlinear increases are expected. Another is the strong dependence of extreme heat-humidity combinations on atmospheric moisture, creating subseasonal and interannual patterns dictated by the principal source of regional warm-season moisture — pre-monsoonal advection in some cases, local evapotranspiration in others. These relationships lead to the demonstrated potential for improvements in predictive power, on the basis of sea-surface temperatures and other canonical modes of large-scale climate variability. In contrast to this overall confidence in current temporal patterns and long-term projections, I show that extreme heat at small spatial scales is much more poorly characterized in gridded products, and that these biases are especially acute along coastlines. While summer daytime temperature differences between the shoreline of the Northeast U.S. and locations 60 km inland are often 5°C or more, I find that recent high-resolution downscaled Earth-system models typically represent no more than 25% of this difference. Across the globe, ERA-Interim reanalysis similarly underestimates extreme humid heat by >3°C, a highly significant margin given the large sensitivity of health and economic impacts to marginal changes in the most extreme conditions. I find that these biases propagate into projections, and their importance is also amplified by the large populations living in the affected areas. Rapid mean warming is pushing the climate system to more and more frequently include extreme heat-humidity combinations beyond that which the human species has likely ever experienced. Such conditions, which had not been previously reported in weather-station data, are described in detail and some of the associated characteristics examined. Several channels of analysis highlight that these events are driven primarily by rising sea-surface temperatures in shallow subtropical gulfs, and the subsequent impingement of marine air on the coastline. Given the severity of potential impacts on infrastructure and agriculture, and the size of the populations exposed, this result underscores that major research and adaptation efforts are needed to avoid calamitous outcomes from the emergence of extreme heat-humidity combinations too severe to tolerate in the absence of artificial cooling. This dissertation discusses strategies for advancing knowledge of extreme heat’s natural variations and its behavior under climate change, in order to design metrics, models, methodologies, and presentation types such that essential findings are translated into tangible action in the most effective way possible. Sustained and integrated efforts are necessary to transition to a climate-system management style encompassing more foresight than the effectively unplanned experiment which has been pursued so far, and which has already exacerbated extreme heat events so much

Recent Increases in Exposure to Extreme Humid-Heat Events Disproportionately Affect Populated Regions

Extreme heat research has largely focused on dry-heat, while humid-heat that poses a substantial threat to human-health remains relatively understudied. Using hourly high-resolution ERA5 reanalysis and HadISD station data, we provide the first spatially comprehensive, global-scale characterization of the magnitude, seasonal timing, and frequency of dry- and wet-bulb temperature extremes and their trends. While the peak dry- and humid-heat extreme occurrences often coincide, their timing differs in climatologically wet regions. Since 1979, dry- and humid-heat extremes have become more frequent over most land regions, with the greatest increases in the tropics and Arctic. Humid-heat extremes have increased disproportionately over populated regions (∼5.0 days per-person per-decade) relative to global land-areas (∼3.6 days per-unit-land-area per-decade) and population exposure to humidheat has increased at a faster rate than to dry-heat. Our study highlights the need for a multivariate approach to understand and mitigate future harm from heat stress in a warming world

Assay platform for clinically relevant metallo-beta-lactamases

Metallo-β-lactamases (MBLs) are a growing threat to the use of almost all clinically used β-lactam antibiotics. The identification of broad-spectrum MBL inhibitors is hampered by the lack of a suitable screening platform, consisting of appropriate substrates and a set of clinically relevant MBLs. We report procedures for the preparation of a set of clinically relevant metallo-β-lactamases (i.e., NDM-1 (New Delhi MBL), IMP-1 (Imipenemase), SPM-1 (São Paulo MBL), and VIM-2 (Verona integron-encoded MBL)) and the identification of suitable fluorogenic substrates (umbelliferone-derived cephalosporins). The fluorogenic substrates were compared to chromogenic substrates (CENTA, nitrocefin, and imipenem), showing improved sensitivity and kinetic parameters. The efficiency of the fluorogenic substrates was exemplified by inhibitor screening, identifying 4-chloroisoquinolinols as potential pan MBL inhibitors

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Search for supersymmetry in events with one lepton and multiple jets in proton-proton collisions at root s=13 TeV

Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Search for anomalous couplings in boosted WW/WZ -> l nu q(q)over-bar production in proton-proton collisions at root s=8TeV

Peer reviewe