INTERPRETATION : La pasteurisation du lait maternel a l'aide de la methode de Holder (a 62,5 degreesC pendant 30 min) inactive le SRAS-CoV-2. Ainsi, si du lait maternel provenant de donneuses ...contenait le virus a la suite d'une transmission par la glande mammaire ou d'une contamination, cette methode de pasteurisation rendrait le lait sans danger pour la consommation par le nourrisson et la manipulation par les travailleurs de la sante.
Left ventricular ejection fraction (LVEF) has been the central parameter used for diagnosis and management in patients with heart failure. A good predictor of adverse outcomes in heart failure when ...below ∼45%, LVEF is less useful as a marker of risk as it approaches normal. As a measure of cardiac function, ejection fraction has several important limitations. Calculated as the stroke volume divided by end-diastolic volume, the estimation of ejection fraction is generally based on geometric assumptions that allow for assessment of volumes based on linear or two-dimensional measurements. Left ventricular ejection fraction is both preload- and afterload-dependent, can change substantially based on loading conditions, is only moderately reproducible, and represents only a single measure of risk in patients with heart failure. Moreover, the relationship between ejection fraction and risk in patients with heart failure is modified by factors such as hypertension, diabetes, and renal function. A more complete evaluation and understanding of left ventricular function in patients with heart failure requires a more comprehensive assessment: we conceptualize an integrative approach that incorporates measures of left and right ventricular function, left ventricular geometry, left atrial size, and valvular function, as well as non-imaging factors (such as clinical parameters and biomarkers), providing a comprehensive and accurate prediction of risk in heart failure.
Markov Chain Monte–Carlo (MCMC) is an increasingly popular method for obtaining information about distributions, especially for estimating posterior distributions in Bayesian inference. This article ...provides a very basic introduction to MCMC sampling. It describes what MCMC is, and what it can be used for, with simple illustrative examples. Highlighted are some of the benefits and limitations of MCMC sampling, as well as different approaches to circumventing the limitations most likely to trouble cognitive scientists.
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Proteolysis targeting chimeras (PROTACs) are heterobifunctional compounds with molecular weights and other properties that lie outside the classic ‘rule-of-five’ space. Consequently, ...PROTACs have unique challenges associated with their development as potential therapeutic agents. This review summarizes and analyzes a representative set of recent PROTACs and highlights some of the potential future challenges facing this promising modality.
In the mining sector, local communities have emerged as particularly important governance actors. Conventional approaches to mineral development no longer suffice for these communities, which have ...demanded a greater share of benefits and increased involvement in decision making. These trends have been spurred by the growth of the sustainable development paradigm and governance shifts that have increasingly transferred governing authority towards non-state actors. Accordingly, there is now widespread recognition that mineral developers need to gain a ‘social license to operate’ (SLO) from local communities in order to avoid potentially costly conflict and exposure to social risks. A social license can be considered to exist when a mining project is seen as having the ongoing approval and broad acceptance of society to conduct its activities. Due to the concept's relatively recent emergence, however, only a limited body of scholarship has developed around SLO. Drawing on examples from northern Canada, this paper uses governance and sustainability theories to conceptualize the origins of SLO in the mining sector and describe some of the associated implications. Further research is needed to determine governance arrangements which help facilitate establishment of SLO in different mineral development contexts.
► We review the origins of the ‘social license to operate’ (SLO) in the mining sector. ► Northern Canada is used to demonstrate the context-specific nature of SLO. ► Shifts in governance and a focus on sustainability have enabled SLO to emerge. ► Complex configurations of state, market and civil society actors and institutions are additional influences on SLO. ► Further research is needed to determine governance arrangements that facilitate SLO.
Natural abundance nitrogen and oxygen isotopes of nitrate (δ15NNO3 and δ18ONO3) provide an important tool for evaluating sources and transformations of natural and contaminant nitrate (NO₃⁻) in the ...environment. Nevertheless, conventional interpretations of NO₃⁻ isotope distributions appear at odds with patterns emerging from studies of nitrifying and denitrifying bacterial cultures. To resolve this conundrum, we present results from a numerical model of NO₃⁻ isotope dynamics, demonstrating that deviations in δ18ONO3 vs. δ15NNO3 from a trajectory of 1 expected for denitrification are explained by isotopic over-printing from coincident NO₃⁻ production by nitrification and/or anammox. The analysis highlights two driving parameters: (i) the δ18O of ambient water and (ii) the relative flux of NO₃⁻ production under net denitrifying conditions, whether catalyzed aerobically or anaerobically. In agreement with existing analyses, dual isotopic trajectories >1, characteristic of marine denitrifying systems, arise predominantly under elevated rates of NO₂⁻ reoxidation relative to NO₃⁻ reduction (>50%) and in association with the elevated δ18O of seawater. This result specifically implicates aerobic nitrification as the dominant NO₃⁻ producing term in marine denitrifying systems, as stoichiometric constraints indicate anammox-based NO₃⁻ production cannot account for trajectories >1. In contrast, trajectories <1 comprise the majority of model solutions, with those representative of aquifer conditions requiring lower NO₂⁻ reoxidation fluxes (<15%) and the influence of the lower δ18O of freshwater. Accordingly, we suggest that widely observed δ18ONO3 vs. δ15NNO3 trends in freshwater systems (<1) must result from concurrent NO₃⁻ production by anammox in anoxic aquifers, a process that has been largely overlooked.
Antibodies, and the B cell and plasma cell populations responsible for their production, are key components of the human immune system’s response to SARS-CoV-2, which has caused the coronavirus ...disease 2019 (COVID-19) pandemic. Here, we review findings addressing the nature of antibody responses against SARS-CoV-2 and their role in protecting from infection or modulating COVID-19 disease severity. In just over a year, much has been learned, and replicated in independent studies, about human immune responses to this pathogen, contributing to the development of effective vaccines. Nevertheless, important questions remain about the duration and effectiveness of antibody responses, differences between immunity derived from infection compared to vaccination, the cellular basis for serological findings, and the extent to which viral variants will escape from current immunity.
Röltgen and Boyd review research in the past year that has analyzed antibody and B cell responses to SARS-CoV-2 infection and vaccination, and their ability to prevent subsequent infection. The duration of immunity and the impact of new SARS-CoV-2 variants are major questions for the pandemic’s next phase.
The emergency use authorization of two mRNA vaccines in less than a year from the emergence of SARS-CoV-2 represents a landmark in vaccinology
. Yet, how mRNA vaccines stimulate the immune system to ...elicit protective immune responses is unknown. Here we used a systems vaccinology approach to comprehensively profile the innate and adaptive immune responses of 56 healthy volunteers who were vaccinated with the Pfizer-BioNTech mRNA vaccine (BNT162b2). Vaccination resulted in the robust production of neutralizing antibodies against the wild-type SARS-CoV-2 (derived from 2019-nCOV/USA_WA1/2020) and, to a lesser extent, the B.1.351 strain, as well as significant increases in antigen-specific polyfunctional CD4 and CD8 T cells after the second dose. Booster vaccination stimulated a notably enhanced innate immune response as compared to primary vaccination, evidenced by (1) a greater frequency of CD14
CD16
inflammatory monocytes; (2) a higher concentration of plasma IFNγ; and (3) a transcriptional signature of innate antiviral immunity. Consistent with these observations, our single-cell transcriptomics analysis demonstrated an approximately 100-fold increase in the frequency of a myeloid cell cluster enriched in interferon-response transcription factors and reduced in AP-1 transcription factors, after secondary immunization. Finally, we identified distinct innate pathways associated with CD8 T cell and neutralizing antibody responses, and show that a monocyte-related signature correlates with the neutralizing antibody response against the B.1.351 variant. Collectively, these data provide insights into the immune responses induced by mRNA vaccination and demonstrate its capacity to prime the innate immune system to mount a more potent response after booster immunization.
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