759 research outputs found

    Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a 2023 TBnet/RESIST-TB consensus statement.

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    Drug-resistant tuberculosis is a substantial health-care concern worldwide. Despite culture-based methods being considered the gold standard for drug susceptibility testing, molecular methods provide rapid information about the Mycobacterium tuberculosis mutations associated with resistance to anti-tuberculosis drugs. This consensus document was developed on the basis of a comprehensive literature search, by the TBnet and RESIST-TB networks, about reporting standards for the clinical use of molecular drug susceptibility testing. Review and the search for evidence included hand-searching journals and searching electronic databases. The panel identified studies that linked mutations in genomic regions of M tuberculosis with treatment outcome data. Implementation of molecular testing for the prediction of drug resistance in M tuberculosis is key. Detection of mutations in clinical isolates has implications for the clinical management of patients with multidrug-resistant or rifampicin-resistant tuberculosis, especially in situations when phenotypic drug susceptibility testing is not available. A multidisciplinary team including clinicians, microbiologists, and laboratory scientists reached a consensus on key questions relevant to molecular prediction of drug susceptibility or resistance to M tuberculosis, and their implications for clinical practice. This consensus document should help clinicians in the management of patients with tuberculosis, providing guidance for the design of treatment regimens and optimising outcomes

    Maternal Relationships among Ancient and Modern Southern African Sheep: Newly Discovered Mitochondrial Haplogroups

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    We investigated the genetic diversity and historic relationships among southern African sheep as well as the relationships between them and sheep outside the continent by sourcing both archaeological and modern sheep samples. Archaeological sheep samples derived from the site Die Kelders 1, near Cape Town, date to approximately 1500 years ago. The modern samples were taken as ear snips from Damara, Namaqua Afrikaner, and Ronderib Afrikaner sheep on a farm in Prieska in the Northern Cape. Illumina sequencing libraries were constructed for both ancient and modern specimens. Ancient specimens were enriched for the mitochondrial genome using an in-solution hybridization protocol and modern specimens were subjected to shotgun sequencing. Sequences were mapped to the Ovis aries reference genome, assigned to haplogroups and subhaplogroups, and used to calculate a phylogenetic tree using previously published, geographically dispersed mitochondrial genome sheep sequences. Genetic diversity statistics show that southern African sheep have lower diversity than sheep in other regions. Phylogenetic analysis reveals that many modern southern African sheep are likely descended from prehistoric indigenous sheep populations and not from sheep imported from Europe during the historic period

    Novel Hendra Virus Variant Detected by Sentinel Surveillance of Horses in Australia

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    We identified and isolated a novel Hendra virus (HeV) variant not detected by routine testing from a horse in Queensland, Australia, that died from acute illness with signs consistent with HeV infection. Using whole-genome sequencing and phylogenetic analysis, we determined the variant had ≈83% nt identity with prototypic HeV. In silico and in vitro comparisons of the receptor-binding protein with prototypic HeV support that the human monoclonal antibody m102.4 used for postexposure prophylaxis and current equine vaccine will be effective against this variant. An updated quantitative PCR developed for routine surveillance resulted in subsequent case detection. Genetic sequence consistency with virus detected in grey-headed flying foxes suggests the variant circulates at least among this species. Studies are needed to determine infection kinetics, pathogenicity, reservoir-species associations, viral-host coevolution, and spillover dynamics for this virus. Surveillance and biosecurity practices should be updated to acknowledge HeV spillover risk across all regions frequented by flying foxes. © 2022 Centers for Disease Control and Prevention (CDC). All rights reserved

    Novel Hendra Virus Variant Detected by Sentinel Surveillance of Horses in Australia

    No full text
    We identified and isolated a novel Hendra virus (HeV) variant not detected by routine testing from a horse in Queensland, Australia, that died from acute illness with signs consistent with HeV infection. Using whole-genome sequencing and phylogenetic analysis, we determined the variant had ≈83% nt identity with prototypic HeV. In silico and in vitro comparisons of the receptor-binding protein with prototypic HeV support that the human monoclonal antibody m102.4 used for postexposure prophylaxis and current equine vaccine will be effective against this variant. An updated quantitative PCR developed for routine surveillance resulted in subsequent case detection. Genetic sequence consistency with virus detected in grey-headed flying foxes suggests the variant circulates at least among this species. Studies are needed to determine infection kinetics, pathogenicity, reservoir-species associations, viral-host coevolution, and spillover dynamics for this virus. Surveillance and biosecurity practices should be updated to acknowledge HeV spillover risk across all regions frequented by flying foxes

    The sources of sea‐level changes in the Mediterranean Sea since 1960

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    Past sea-level changes in the Mediterranean Sea are highly non-uniform and can deviate significantly from both the global average sea-level rise and changes in the nearby Atlantic. Understanding the causes of this spatial non-uniformity is crucial to the success of coastal adaptation strategies. This, however, remains a challenge owing to the lack of long sea-level records in the Mediterranean. Previous studies have addressed this challenge by reconstructing past sea levels through objective analysis of sea-level observations. Such reconstructions have enabled significant progress toward quantifying sea-level changes, however, they have difficulty capturing long-term changes and provide little insight into the causes of the changes. Here, we combine data from tide gauges and altimetry with sea-level fingerprints of contemporary land-mass changes using spatial Bayesian methods to estimate the sources of sea-level changes in the Mediterranean Sea since 1960. We find that, between 1960 and 1989, sea level in the Mediterranean fell at an average rate of −0.3 ± 0.5 mm yr−1, due to an increase in atmospheric pressure over the basin and opposing sterodynamic and land-mass contributions. After 1989, Mediterranean sea level started accelerating rapidly, driven by both sterodynamic changes and land-ice loss, reaching an average rate of 3.6 ± 0.3 mm yr−1 in the period 2000–2018. The rate of sea-level rise shows considerable spatial variation in the Mediterranean Sea, primarily reflecting changes in the large-scale circulation of the basin. Since 2000, sea level has been rising faster in the Adriatic, Aegean, and Levantine Seas than anywhere else in the Mediterranean Sea

    Development of targeted indicators and their uncertainties for demonstrators and Forecasts

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    This deliverable reports on the achievements of the EuroSea project in developing targeted indicators co-designed with demonstrators (WPs 5–7) and forecasts (WP4). For this, the indicators implemented are expressed in term of Essential Ocean/Climate Variables (EOVs/ECVs) together with their requirements. The co-development undertaken address ocean indicators for all range of scales: from the large, basin scale to the regional and local scales. Such approach as well as the proposed solution to focus, at regional/local scales, on EEZs, represent one of the innovative results of EuroSea that will help to rationalize risks assessments and guide environmental management approaches in European Seas

    Impaired Glymphatic Function and Pulsation Alterations in a Mouse Model of Vascular Cognitive Impairment

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    ACKNOWLEDGMENTS Schematic diagrams in Figures 2, 8 are created withBiorender.com. FUNDING We gratefully acknowledge the grant support from the Alzheimer’s Society (152 (PG-157); 290 (AS-PG-15b-018); 228 (AS-DTC-2014-017), 314 (AS –PhD-16-006), and Alzheimer’s Research United Kingdom (ART-PG2010-3; ARUK-PG2013- 22; ARUK-PG2016B-6), and The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (G0700704/84698). ML and JB are funded by an Alzheimer’s Society Scotland Doctoral Training Programme and RS Macdonald Trust. ML was also funded by a China Scholarship Council (CSC)/University of Edinburgh scholarship.Peer reviewedPublisher PD

    The impact of Covid-19 on Professional Identity Formation: An international qualitative study of medical students’ reflective entries in a Global Creative Competition

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    Introduction: The Covid-19 pandemic, which affected medical students globally, could be viewed as a disorientating dilemma with the potential to offer opportunities for transformative learning. In 2021 the Medical Education Innovation and Research Centre at Imperial College London launched a Global Creative Competition as a platform for medical students to reflect on their experiences during the pandemic. Methods: 648 creative pieces with written reflections were submitted by medical students from 52 countries. 155 students from 28 countries consented for their entries to be included in this study. The reflections were analysed thematically and independently by three reviewers to explore how the pandemic impacted students’ professional identity formation (PIF). Results: The pandemic increased students’ awareness of the social and global role of doctors in addressing health inequities. Students felt part of a wider healthcare community and showed greater appreciation towards person-centred care. Students also became more aware of their personal needs, priorities, and the importance of self-care. Discussion: In agreement with Mezirow’s theory of transformative learning (2003), the pandemic led students to re-examine pre-existing epistemic and sociocultural assumptions concerning the role of doctors and explore new perspectives of what it means to be a doctor. In accordance with Cheng’s theory of coping flexibility (2021), students developed both emotion-focused coping strategies (e.g., arts engagement) and problem-solving strategies (e.g., volunteering), suggesting they were able to adjust psychologically and develop agency. However, students experienced tension between their sense of duty and sense of wellbeing, highlighting the need for medical educators to design into programmes formal support systems where medical students have the space and time they need to reflect on their emergent identities as a doctor. Conclusion: Medical educators should encourage students to reflect on their identity formation while encountering disorientating dilemmas. The inclusion of arts and humanities within the medical curriculum is strongly recommended to provide an avenue for students to access and express complex emotions and experiences
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