WMO Assessment of Weather and Climate Mortality Extremes: Lightning, Tropical Cyclones, Tornadoes, and Hail

A World Meteorological Organization (WMO) Commission for Climatology international panel was convened to examine and assess the available evidence associated with five weather-related mortality extremes: 1) lightning (indirect), 2) lightning (direct), 3) tropical cyclones, 4) tornadoes, and 5) hail. After recommending for acceptance of only events after 1873 (the formation of the predecessor of the WMO), the committee evaluated and accepted the following mortality extremes: 1) “highest mortality (indirect strike) associated with lightning” as the 469 people killed in a lightning-caused oil tank fire in Dronka, Egypt, on 2 November 1994; 2) “highest mortality directly associated with a single lightning flash” as the lightning flash that killed 21 people in a hut in Manica Tribal Trust Lands, Zimbabwe (at time of incident, eastern Rhodesia), on 23 December 1975; 3) “highest mortality associated with a tropical cyclone” as the Bangladesh (at time of incident, East Pakistan) cyclone of 12–13 November 1970 with an estimated death toll of 300 000 people; 4) “highest mortality associated with a tornado” as the 26 April 1989 tornado that destroyed the Manikganj district, Bangladesh, with an estimated death toll of 1300 individuals; and 5) “highest mortality associated with a hailstorm” as the storm occurring near Moradabad, India, on 30 April 1888 that killed 246 people. These mortality extremes serve to further atmospheric science by giving baseline mortality values for comparison to future weather-related catastrophes and also allow for adjudication of new meteorological information as it becomes available

WMO assessment of weather and climate mortality extremes : lightning, tropical cyclones, tornadoes, and hail

A World Meteorological Organization (WMO) Commission for Climatology international panel was convened to examine and assess the available evidence associated with five weather-related mortality extremes: 1) lightning (indirect), 2) lightning (direct), 3) tropical cyclones, 4) tornadoes, and 5) hail. After recommending for acceptance of only events after 1873 (the formation of the predecessor of the WMO), the committee evaluated and accepted the following mortality extremes: 1) ''highest mortality (indirect strike) associated with lightning'' as the 469 people killed in a lightning-caused oil tank fire in Dronka, Egypt, on 2 November 1994; 2) ''highest mortality directly associated with a single lightning flash'' as the lightning flash that killed 21 people in a hut in Manica Tribal Trust Lands, Zimbabwe (at time of incident, eastern Rhodesia), on 23 December 1975; 3) ''highest mortality associated with a tropical cyclone'' as the Bangladesh (at time of incident, East Pakistan) cyclone of 12-13 November 1970 with an estimated death toll of 300 000 people| 4) ''highest mortality associated with a tornado'' as the 26 April 1989 tornado that destroyed the Manikganj district, Bangladesh, with an estimated death toll of 1300 individuals| and 5) ''highest mortality associated with a hailstorm'' as the storm occurring near Moradabad, India, on 30 April 1888 that killed 246 people. These mortality extremes serve to further atmospheric science by giving baseline mortality values for comparison to future weather-related catastrophes and also allow for adjudication of new meteorological information as it becomes available.https://www.ametsoc.org/ams/index.cfm/publications/journals/weather-climate-and-society2018-01-30hj2017Geography, Geoinformatics and Meteorolog

Imetelstat-mediated alterations in fatty acid metabolism to induce ferroptosis as a therapeutic strategy for acute myeloid leukemia

Telomerase enables replicative immortality in most cancers including acute myeloid leukemia (AML). Imetelstat is a first-in-class telomerase inhibitor with clinical efficacy in myelofibrosis and myelodysplastic syndromes. Here, we develop an AML patient-derived xenograft resource and perform integrated genomics, transcriptomics and lipidomics analyses combined with functional genetics to identify key mediators of imetelstat efficacy. In a randomized phase II-like preclinical trial in patient-derived xenografts, imetelstat effectively diminishes AML burden and preferentially targets subgroups containing mutant NRAS and oxidative stress-associated gene expression signatures. Unbiased, genome-wide CRISPR/Cas9 editing identifies ferroptosis regulators as key mediators of imetelstat efficacy. Imetelstat promotes the formation of polyunsaturated fatty acid-containing phospholipids, causing excessive levels of lipid peroxidation and oxidative stress. Pharmacological inhibition of ferroptosis diminishes imetelstat efficacy. We leverage these mechanistic insights to develop an optimized therapeutic strategy using oxidative stress-inducing chemotherapy to sensitize patient samples to imetelstat causing substantial disease control in AML

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Preliminary study of factors affecting the superovulatory response of high producing dairy cows superstimulated regardless of the stage of estrous cycle in Egypt

This work was conducted as a first time commercial production of embryos from lactating Holstein and Brown Swiss cows using multiple ovulation embryo transfer (MOET) technology in Egypt. We studied factors affecting the superovulatory response (SR) in superovulated cows and effects of propylene glycol (PG) on embryo quality. Daily milk production at flushing had significantly negative effects on SR and embryo yields in superovulated cows. In addition, Brown Swiss cows had better SR than Holstein cows. Moreover, cows having more than 3 parities yielded better response, compared to cows in the first three parities. However, factors such as body weight at flushing, body condition score (BCS) at flushing and days in milk (DIM) at flushing did not have any association with SR in cows. In addition, drenching of PG prior to and during the superovulatory treatment improved SR (Right CL number, P < 0.05; Left CL number, P < 0.05), total embryos per flush (P < 0.05), first grade embryos per flush (P < 0.01) and tended to improve transferable embryos (P = 0.13) and second grade embryos per flush (P = 0.11). However, it tended to increase the number of degenerated embryos per flush (0.06). In conclusion, commercial production of embryos from lactating Holstein and Brown Swiss cows regardless of stage of estrous cycle by MOET proved successful under Egyptian conditions. Milk yield was negatively associated with SR and embryo yields in superovulated cows. Moreover, drenching of PG prior to and during the superovulatory treatment improved SR and embryo yields