42 research outputs found

    BMJ Open

    Get PDF
    OBJECTIVE: This study aims to evaluate whether the first wave of the COVID-19 pandemic resulted in a deterioration in the quality of care for socially and/or clinically vulnerable stroke and ST-segment elevation myocardial infarction (STEMI) patients. DESIGN: Two cohorts of STEMI and stroke patients in the Aquitaine neurocardiovascular registry. SETTING: Six emergency medical services, 30 emergency units, 14 hospitalisation units and 11 catheterisation laboratories in the Aquitaine region in France. PARTICIPANTS: This study involved 9218 patients (6436 stroke and 2782 STEMI patients) in the neurocardiovascular registry from January 2019 to August 2020. PRIMARY OUTCOME MEASURES: Care management times in both cohorts: first medical contact-to-procedure time for the STEMI cohort and emergency unit admission-to-imaging time for the stroke cohort. Associations between social (deprivation index) and clinical (age >65 years, neurocardiovascular history) vulnerabilities and care management times were analysed using multivariate linear mixed models, with an interaction on the time period (pre-wave, per-wave and post-first COVID-19 wave). RESULTS: The first medical contact procedure time was longer for elderly (p<0.001) and 'very socially disadvantaged' (p=0.003) STEMI patients, with no interaction regarding the COVID-19 period (age, p=0.54; neurocardiovascular history, p=0.70; deprivation, p=0.64). We found no significant association between vulnerabilities and the admission imaging time for stroke patients, and no interaction with respect to the COVID-19 period (age, p=0.81; neurocardiovascular history, p=0.34; deprivation, p=0.95). CONCLUSIONS: This study revealed pre-existing inequalities in care management times for vulnerable STEMI and stroke patients; however, these inequalities were neither accentuated nor reduced during the first COVID-19 wave. Measures implemented during the crisis did not alter the structured emergency pathway for these patients. TRIAL REGISTRATION NUMBER: NCT04979208

    Global Analysis of the Evolution and Mechanism of Echinocandin Resistance in Candida glabrata

    Get PDF
    The evolution of drug resistance has a profound impact on human health. Candida glabrata is a leading human fungal pathogen that can rapidly evolve resistance to echinocandins, which target cell wall biosynthesis and are front-line therapeutics for Candida infections. Here, we provide the first global analysis of mutations accompanying the evolution of fungal drug resistance in a human host utilizing a series of C. glabrata isolates that evolved echinocandin resistance in a patient treated with the echinocandin caspofungin for recurring bloodstream candidemia. Whole genome sequencing identified a mutation in the drug target, FKS2, accompanying a major resistance increase, and 8 additional non-synonymous mutations. The FKS2-T1987C mutation was sufficient for echinocandin resistance, and associated with a fitness cost that was mitigated with further evolution, observed in vitro and in a murine model of systemic candidemia. A CDC6-A511G(K171E) mutation acquired before FKS2-T1987C(S663P), conferred a small resistance increase. Elevated dosage of CDC55, which acquired a C463T(P155S) mutation after FKS2-T1987C(S663P), ameliorated fitness. To discover strategies to abrogate echinocandin resistance, we focused on the molecular chaperone Hsp90 and downstream effector calcineurin. Genetic or pharmacological compromise of Hsp90 or calcineurin function reduced basal tolerance and resistance. Hsp90 and calcineurin were required for caspofungin-dependent FKS2 induction, providing a mechanism governing echinocandin resistance. A mitochondrial respiration-defective petite mutant in the series revealed that the petite phenotype does not confer echinocandin resistance, but renders strains refractory to synergy between echinocandins and Hsp90 or calcineurin inhibitors. The kidneys of mice infected with the petite mutant were sterile, while those infected with the HSP90-repressible strain had reduced fungal burden. We provide the first global view of mutations accompanying the evolution of fungal drug resistance in a human host, implicate the premier compensatory mutation mitigating the cost of echinocandin resistance, and suggest a new mechanism of echinocandin resistance with broad therapeutic potential

    Exotic Grains in a Core from Cornwall, NY - Do They Have an Impact Source?

    Get PDF
    We have found seven discrete layers in a bog core from Cornwall, NY about 80 km away from the Atlantic Ocean. All but two layers contain material that is unlikely to be locally derived. In most cases, the material in the layers has been transported thousands of kilometers from its source area. Six out of the seven layers are difficult to explain except through impact processes. If all of these layers are derived from impacts that produced craters, the data imply a very high impact rate during late Holocene time. In addition, we have been able to associate two of the impact ejecta layers with dated tsunami events that span the Atlantic Ocean. If this discovery is validated by further research, it implies a much larger tsunami hazard in the Atlantic Ocean than previously reported.Мы обнаружили семь отдельных прослоек в пробах донных осадков из Корнвала, штат Нью-Йорк, расположенных около 80 км от Атлантического океана. Все прослойки пробы, кроме двух, содержали материал, который вряд ли является местным. В большинстве случаев этот материал в прослойках перенесен за тысячи километров от района их возникновения. Шесть из семи прослоек трудно объяснить, исключив импактный процесс. Если все эти прослойки получены от импактных воздействий в результате возникновения кратеров, то эти данные подразумевают очень высокие частоты импактных воздействий в период позднего голоцена. Кроме того, мы смогли связать две прослойки, содержащие частицы от импактных воздействий, с данными о цунами, которые охватывали Атлантический океан. Если это открытие подтвердится дальнейшими исследованиями, то это подразумевает гораздо большую опасность цунами в Атлантическом океане, чем сообщалось ранее

    Genetic analysis of downy mildew resistance derived from Muscadinia rotundifolia

    No full text
    International audienc

    Exotic Grains in a Core from Cornwall, NY - Do They Have an Impact Source?

    No full text
    We have found seven discrete layers in a bog core from Cornwall, NY about 80 km away from the Atlantic Ocean. All but two layers contain material that is unlikely to be locally derived. In most cases, the material in the layers has been transported thousands of kilometers from its source area. Six out of the seven layers are difficult to explain except through impact processes. If all of these layers are derived from impacts that produced craters, the data imply a very high impact rate during late Holocene time. In addition, we have been able to associate two of the impact ejecta layers with dated tsunami events that span the Atlantic Ocean. If this discovery is validated by further research, it implies a much larger tsunami hazard in the Atlantic Ocean than previously reported.Мы обнаружили семь отдельных прослоек в пробах донных осадков из Корнвала, штат Нью-Йорк, расположенных около 80 км от Атлантического океана. Все прослойки пробы, кроме двух, содержали материал, который вряд ли является местным. В большинстве случаев этот материал в прослойках перенесен за тысячи километров от района их возникновения. Шесть из семи прослоек трудно объяснить, исключив импактный процесс. Если все эти прослойки получены от импактных воздействий в результате возникновения кратеров, то эти данные подразумевают очень высокие частоты импактных воздействий в период позднего голоцена. Кроме того, мы смогли связать две прослойки, содержащие частицы от импактных воздействий, с данными о цунами, которые охватывали Атлантический океан. Если это открытие подтвердится дальнейшими исследованиями, то это подразумевает гораздо большую опасность цунами в Атлантическом океане, чем сообщалось ранее

    Detecting climate signals in populations across life histories

    Get PDF
    © The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Jenouvrier, S., Long, M. C., Coste, C. F. D., Holland, M., Gamelon, M., Yoccoz, N., & Saether, B.-E. Detecting climate signals in populations across life histories. Global Change Biology, 28, (2022): 2236– 2258, https://doi.org/10.1111/gcb.16041.Climate impacts are not always easily discerned in wild populations as detecting climate change signals in populations is challenged by stochastic noise associated with natural climate variability, variability in biotic and abiotic processes, and observation error in demographic rates. Detection of the impact of climate change on populations requires making a formal distinction between signals in the population associated with long-term climate trends from those generated by stochastic noise. The time of emergence (ToE) identifies when the signal of anthropogenic climate change can be quantitatively distinguished from natural climate variability. This concept has been applied extensively in the climate sciences, but has not been explored in the context of population dynamics. Here, we outline an approach to detecting climate-driven signals in populations based on an assessment of when climate change drives population dynamics beyond the envelope characteristic of stochastic variations in an unperturbed state. Specifically, we present a theoretical assessment of the time of emergence of climate-driven signals in population dynamics (ToEpop). We identify the dependence of (ToEpop)on the magnitude of both trends and variability in climate and also explore the effect of intrinsic demographic controls on (ToEpop). We demonstrate that different life histories (fast species vs. slow species), demographic processes (survival, reproduction), and the relationships between climate and demographic rates yield population dynamics that filter climate trends and variability differently. We illustrate empirically how to detect the point in time when anthropogenic signals in populations emerge from stochastic noise for a species threatened by climate change: the emperor penguin. Finally, we propose six testable hypotheses and a road map for future research.We acknowledge the support of NASA 80NSSC20K1289 to SJ, ML, and MH; NSF OPP 1744794 to SJ and NSF OPP 2037561 to SJ and MH
    corecore