Cosmic Physics: The High Energy Frontier

Cosmic rays have been observed up to energies $10^8$ times larger than those of the best particle accelerators. Studies of astrophysical particles (hadrons, neutrinos and photons) at their highest observed energies have implications for fundamental physics as well as astrophysics. Thus, the cosmic high energy frontier is the nexus to new particle physics. This overview discusses recent advances being made in the physics and astrophysics of cosmic rays and cosmic gamma-rays at the highest observed energies as well as the related physics and astrophysics of very high energy cosmic neutrinos. These topics touch on questions of grand unification, violation of Lorentz invariance, as well as Planck scale physics and quantum gravity.Comment: Topical Review Paper to be published in the Journal of Physics G, 50 page

Tropical Data: Approach and Methodology as Applied to Trachoma Prevalence Surveys

PURPOSE: Population-based prevalence surveys are essential for decision-making on interventions to achieve trachoma elimination as a public health problem. This paper outlines the methodologies of Tropical Data, which supports work to undertake those surveys. METHODS: Tropical Data is a consortium of partners that supports health ministries worldwide to conduct globally standardised prevalence surveys that conform to World Health Organization recommendations. Founding principles are health ministry ownership, partnership and collaboration, and quality assurance and quality control at every step of the survey process. Support covers survey planning, survey design, training, electronic data collection and fieldwork, and data management, analysis and dissemination. Methods are adapted to meet local context and needs. Customisations, operational research and integration of other diseases into routine trachoma surveys have also been supported. RESULTS: Between 29th February 2016 and 24th April 2023, 3373 trachoma surveys across 50 countries have been supported, resulting in 10,818,502 people being examined for trachoma. CONCLUSION: This health ministry-led, standardised approach, with support from the start to the end of the survey process, has helped all trachoma elimination stakeholders to know where interventions are needed, where interventions can be stopped, and when elimination as a public health problem has been achieved. Flexibility to meet specific country contexts, adaptation to changes in global guidance and adjustments in response to user feedback have facilitated innovation in evidence-based methodologies, and supported health ministries to strive for global disease control targets

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

Work functions and surface charges at metallic facet edges

Consiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7 , Rome / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

Lifespan Versus Healthspan

International audienceLifespan is a measure of duration, not of content, and it does not provide the same information as biological markers of ageing. Therefore, one cannot rely on lifespan to infer conclusions about ageing. For example, two centenarians can die in very contrasted physiological states: as bedridden for years or during jogging. Healthspan can be measured in animal models by relying on behaviour, resistance to stress, and so on. Biogerontologists working with animal models tend to privilege the measurement of lifespan rather than that of healthspan when the animal lives for a short time (e.g. Caenorhabditis elegans, Drosophila melanogaster) because measuring lifespan is easy and studying, say, behaviour, is more difficult. Conversely, biogerontologists privilege healthspan when the animal model lives for years (e.g. rodents, non-human primates), because measuring lifespan can be out of reach. In any case, biogerontologists should try to observe both lifespan and indicators of health, whenever it is possible, and not conclude that ageing is delayed when they have simply observed longer lifespans

Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease

To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CHD, including a new T2D association at a missense variant in HLA-DRB5 (odds ratio (OR) = 1.29). We show that genetically mediated increase in T2D risk also confers higher CHD risk. Joint T2D–CHD analysis identified eight variants—two of which are coding—where T2D and CHD associations appear to colocalize, including a new joint T2D–CHD association at the CCDC92 locus that also replicated for T2D. The variants associated with both outcomes implicate new pathways as well as targets of existing drugs, including icosapent ethyl and adipocyte fatty-acid-binding protein.D.S. has received support from NHLBI, NINDS, Pfizer, Regeneron Pharmaceuticals, Genentech, and Eli Lilly. Genotyping in PROMIS was funded by the Wellcome Trust, UK, and Pfizer. Biomarker assays in PROMIS have been funded through grants awarded by the NIH (RC2HL101834 and RC1TW008485) and Fogarty International (RC1TW008485). The RACE study has been funded by NINDS (R21NS064908), Fogarty International (R21NS064908), and the Center for Non-Communicable Diseases (Karachi, Pakistan). B.F.V. was supported by funding from the American Heart Association (13SDG14330006), the W.W. Smith Charitable Trust (H1201), and the NIH/NIDDK (R01DK101478). J.D. is a British Heart Foundation Professor, European Research Council Senior Investigator, and NIHR Senior Investigator. V.S. was supported by the Finnish Foundation for Cardiovascular Research. S. Ripatti was supported by the Academy of Finland (251217 and 255847), the Center of Excellence in Complex Disease Genetics, the European Union’s Seventh Framework Programme projects ENGAGE (201413) and BioSHaRE (261433), the Finnish Foundation for Cardiovascular Research, Biocentrum Helsinki, and the Sigrid Juselius Foundation. The Mount Sinai IPM Biobank Program is supported by the Andrea and Charles Bronfman Philanthropies. S. Anand is supported by grants from the Canada Research Chair in Ethnic Diversity and CVD and from the Heart and Stroke Michael G. DeGroote Chair in Population Health, McMaster University. Data contributed by Biobank Japan were partly supported by a grant from the Leading Project of the Ministry of Education, Culture, Sports, Science and Technology, Japan. We thank the participants and staff of the Copenhagen Ischemic Heart Disease Study and the Copenhagen General Population Study for their important contributions. The CHD Exome+ Consortium was funded by the UK Medical Research Council (G0800270), the British Heart Foundation (SP/09/002), the UK NIHR Cambridge Biomedical Research Centre, the European Research Council (268834), the European Commission’s Framework Programme 7 (HEALTH-F2-2012-279233), Merck, and Pfizer. PROSPER has received funding from the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement HEALTH-F2-2009-223004