Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine immunogenicity varies between individuals, and immune responses correlate with vaccine efficacy. Using data from 1,076 participants enrolled in ChAdOx1 nCov-19 vaccine efficacy trials in the United Kingdom, we found that inter-individual variation in normalized antibody responses against SARS-CoV-2 spike and its receptor-binding domain (RBD) at 28 days after first vaccination shows genome-wide significant association with major histocompatibility complex (MHC) class II alleles. The most statistically significant association with higher levels of anti-RBD antibody was HLA-DQB1*06 (P = 3.2 × 10−9), which we replicated in 1,677 additional vaccinees. Individuals carrying HLA-DQB1*06 alleles were less likely to experience PCR-confirmed breakthrough infection during the ancestral SARS-CoV-2 virus and subsequent Alpha variant waves compared to non-carriers (hazard ratio = 0.63, 0.42–0.93, P = 0.02). We identified a distinct spike-derived peptide that is predicted to bind differentially to HLA-DQB1*06 compared to other similar alleles, and we found evidence of increased spike-specific memory B cell responses in HLA-DQB1*06 carriers at 84 days after first vaccination. Our results demonstrate association of HLA type with Coronavirus Disease 2019 (COVID-19) vaccine antibody response and risk of breakthrough infection, with implications for future vaccine design and implementation

Saturn Atmospheric Structure and Dynamics

2 Saturn inhabits a dynamical regime of rapidly rotating, internally heated atmospheres similar to Jupiter. Zonal winds have remained fairly steady since the time of Voyager except in the equatorial zone and slightly stronger winds occur at deeper levels. Eddies supply energy to the jets at a rate somewhat less than on Jupiter and mix potential vorticity near westward jets. Convective clouds exist preferentially in cyclonic shear regions as on Jupiter but also near jets, including major outbreaks near 35°S associated with Saturn electrostatic discharges, and in sporadic giant equatorial storms perhaps generated from frequent events at depth. The implied meridional circulation at and below the visible cloud tops consists of upwelling (downwelling) at cyclonic (anti-cyclonic) shear latitudes. Thermal winds decay upward above the clouds, implying a reversal of the circulation there. Warm-core vortices with associated cyclonic circulations exist at both poles, including surrounding thick high clouds at the south pole. Disequilibrium gas concentrations in the tropical upper troposphere imply rising motion there. The radiative-convective boundary and tropopause occur at higher pressure in the southern (summer) hemisphere due to greater penetration of solar heating there. A temperature “knee ” of warm air below the tropopause, perhaps due to haze heating, is stronger in the summer hemisphere as well. Saturn’s south polar stratosphere is warmer than predicted by radiative models and enhanced in ethane, suggesting subsidence-driven adiabatic warming there. Recent modeling advances suggest that shallow weather laye

Charismatic marine mega-fauna

The whale shark (Rhincodon typus, Smith, 1828) is a migratory species (classed as Vulnerable by the IUCN) with genetic and circumstantial evidence for inter-ocean connectivity. Given this migratory behaviour, populationwide occurrence trends can only be contextualized by examining the synchrony in occurrence patterns among locations where they occur. We present a two-step modelling approach of whale shark spatial and temporal probability of occurrence in the Atlantic and Pacific Oceans using generalized linear mixed-effects models. To test the hypothesis that the probability of whale shark occurrence is asynchronous across oceans, as expected if inter-ocean migration occurs, we used long-term datasets of whale shark sightings derived from tuna purseseine logbooks covering most of the central-east Atlantic (19802010) and western Pacific (20002010). We predicted seasonal habitat suitability to produce maps in each area, and then evaluated the relative effect of time (year) on the probability of occurrence to test whether it changed over the study period. We also applied fast Fourier transforms to determine if any periodicity was apparent in whale shark occurrences in each ocean. After partialling out the effects of seasonal patterns in spatial distribution and sampling effort, we found no evidence for a temporal trend inwhale shark occurrence in the Atlantic, but therewas aweak trend of increasing probability of occurrence in the Pacific. The highest-ranked model for the latter included a spatial predictor of occurrence along with fishing effort, a linear term for time, and a random temporal effect (year), explaining 15% of deviance in whale shark probability of occurrence. Fast Fourier transforms revealed a prominent 15.5-year cycle in the Atlantic. The increase in the probability of occurrence in the Pacific is concurrent with a decrease previously detected in the Indian Ocean. Cyclic patterns driven by migratory behaviour would better explain temporal trends in whale shark occurrence at the oceanic scale. However, despite cycles partially explaining observations of fewer sharks in some years, overall reported sighting rate has been decreasing. As a result, we suggest that the current IUCN status of the species should be re-assessed, but more data are needed to examine the flow of individuals across oceans and to identify possible reasons for asynchronous occurrences

Minimum founding populations for the first peopling of Sahul

The timing, context and nature of the first people to enter Sahul is still poorly understood owing to a fragmented archaeological record. However, quantifying the plausible demographic context of this founding population is essential to determine how and why the initial peopling of Sahul occurred. We developed a stochastic, age-structured model using demographic rates from hunter-gatherer societies, and relative carrying capacity hindcasted with LOVECLIM's net primary productivity for northern Sahul. We projected these populations to determine the resilience and minimum sizes required to avoid extinction. A census founding population of between 1,300 and 1,550 individuals was necessary to maintain a quasi-extinction threshold of ≲0.1. This minimum founding population could have arrived at a single point in time, or through multiple voyages of ≥130 people over ~700-900 years. This result shows that substantial population amalgamation in Sunda and Wallacea in Marine Isotope Stages 3-4 provided the conditions for the successful, large-scale and probably planned peopling of Sahul.Corey J.A. Bradshaw, Sean Ulm, Alan N. Williams, Michael I. Bird, Richard G. Roberts, Zenobia Jacobs, Fiona Laviano, Laura S. Weyrich, Tobias Friedrich, Kasih Norman, and Frédérik Saltr

Evidence-based medicine: the time has come to set standards for staging.

Contains fulltext : 88652.pdf (publisher's version ) (Closed access)For international communication in cancer, staging systems such as TNM are essential; however, the principles and processes used to decide about changes in every new edition of TNM need to be subject to debate. Changes with major impact for patient treatment are introduced without evidence. We think that TNM should be a continual reactive process, rather than a proactive process. Changes should only occur after extensive discussion within the community, and before the introduction of any changes these should be tested for reproducibility and compared to the currently used gold standard. TNM should not be used to test hypotheses. It should introduce established facts that are beneficial to predicting patient prognosis. TNM should thus be restructured on a basis equivalent to evidence-based guidelines. The strength of the evidence should be explicitly stated and the evidence base given. It is time for the principles of staging to be widely debated and new principles and processes to be introduced to ensure that we are not in the same situation in the future. The disparity between therapeutic decision making and TNM staging is marked and we would appeal for the radical overhaul of TNM staging to make it fit for the twenty-first century. TNM is central to the management of cancer patients and we must protect and enhance its reputation.1 augustus 201

Stochastic models support rapid peopling of Late Pleistocene Sahul

The peopling of Sahul (the combined continent of Australia and New Guinea) represents the earliest continental migration and settlement event of solely anatomically modern humans, but its patterns and ecological drivers remain largely conceptual in the current literature. We present an advanced stochastic-ecological model to test the relative support for scenarios describing where and when the first humans entered Sahul, and their most probable routes of early settlement. The model supports a dominant entry via the northwest Sahul Shelf first, potentially followed by a second entry through New Guinea, with initial entry most consistent with 50,000 or 75,000 years ago based on comparison with bias-corrected archaeological map layers. The model's emergent properties predict that peopling of the entire continent occurred rapidly across all ecological environments within 156-208 human generations (4368-5599 years) and at a plausible rate of 0.71-0.92 km year-1. More broadly, our methods and approaches can readily inform other global migration debates, with results supporting an exit of anatomically modern humans from Africa 63,000-90,000 years ago, and the peopling of Eurasia in as little as 12,000-15,000 years via inland routes.Corey J. A. Bradshaw, Kasih Norman, Sean Ulm, Alan N. Williams, Chris Clarkson, Joël Chadœuf ... et al

Pines

Pinus is the most important genus within the Family Pinaceae and also within the gymnosperms by the number of species (109 species recognized by Farjon 2001) and by its contribution to forest ecosystems. All pine species are evergreen trees or shrubs. They are widely distributed in the northern hemisphere, from tropical areas to northern areas in America and Eurasia. Their natural range reaches the equator only in Southeast Asia. In Africa, natural occurrences are confined to the Mediterranean basin. Pines grow at various elevations from sea level (not usual in tropical areas) to highlands. Two main regions of diversity are recorded, the most important one in Central America (43 species found in Mexico) and a secondary one in China. Some species have a very wide natural range (e.g., P. ponderosa, P. sylvestris). Pines are adapted to a wide range of ecological conditions: from tropical (e.g., P. merkusii, P. kesiya, P. tropicalis), temperate (e.g., P. pungens, P. thunbergii), and subalpine (e.g., P. albicaulis, P. cembra) to boreal (e.g., P. pumila) climates (Richardson and Rundel 1998, Burdon 2002). They can grow in quite pure stands or in mixed forest with other conifers or broadleaved trees. Some species are especially adapted to forest fires, e.g., P. banksiana, in which fire is virtually essential for cone opening and seed dispersal. They can grow in arid conditions, on alluvial plain soils, on sandy soils, on rocky soils, or on marsh soils. Trees of some species can have a very long life as in P. longaeva (more than 3,000 years)