38 research outputs found

    Identifying groundwater fluoride source in a weathered basement aquifer in central Malawi : human health and policy implications

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    Consumption of groundwater containing fluoride exceeding World Health Organization (WHO) 1.5 mg/L standard leaves people vulnerable to fluorosis: a vulnerability not well characterised in Malawi. To evaluate geogenic fluoride source and concentration, groundwater fluoride and geology was documented in central Malawi where groundwater supplies are mainly sourced from the weathered basement aquifer. Lithological composition was shown as the main control on fluoride occurrence. Augen gneiss of granitic composition posed the greatest geological fluoride risk. The weathered basement aquifer profile was the main factor controlling fluoride distributions. These results and fluoride-lithology statistical analysis allowed the development of a graded map of geological fluoride risk. A direct link to human health risk (dental fluorosis) from geological fluoride was quantified to support science-led policy change for fluoride in rural drinking water in Malawi. Hazard quotient (HQ) values were calculated and assigned to specific water points, depending on user age group; in this case, 74% of children under six were shown to be vulnerable to dental fluorosis. Results are contrary to current standard for fluoride in Malawi groundwater of 6 mg/L, highlighting the need for policy change. Detailed policy recommendations are presented based on the results of this stud

    Buccal, intranasal or intravenous lorazepam for the treatment of acute convulsions in children in Malawi: An open randomized trial

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    IntroductionAcute convulsions in children are a common emergency worldwide. Benzodiazepines are the recommended first line treatment. Intravenous lorazepam is inexpensive, long acting and the first line drug in resource-rich settings. However, comparable efficacy by other routes of administration is unknown. We wished to compare the efficacy of lorazepam by the buccal, intranasal or intravenous route in the treatment of acute seizures in Malawian children.MethodsA prospective, open-label, randomised, non-inferiority trial was performed in children aged 2months to 14years presenting to the Queen Elizabeth Central Hospital in Blantyre, Malawi with acute seizures lasting longer than 5min. Children were randomly assigned to receive lorazepam, 0.1mg/kg, by the buccal, intranasal or intravenous route. The primary endpoint was seizure cessation within 10min of drug administration.ResultsThere were 761 seizures analysed, with 252 patients in the buccal, 245 in the intranasal and 264 in the intravenous groups. Intravenous lorazepam stopped seizures within 10min in 83%, intranasal lorazepam in 57% (RR 2.46, CI 1.82–3.34), and the buccal route in 46% (RR 3.14, CI 2.35–4.20; p=0.001) of children. There were no significant cardio-respiratory events and no difference in mortality or neurological deficits. The study was halted after an interim analysis showed that the primary endpoint had exceeded the protocol-stopping rule.ConclusionsIntravenous lorazepam effectively treats most childhood seizures in this setting. Intranasal and buccal routes are less effective but may be useful in pre-hospital care or when intravenous access cannot be obtained. Further studies comparing intranasal lorazepam to other benzodiazepines, or alternative doses by a non-intravenous route are warranted

    Genomic analysis of the population structure of Paenibacillus larvae in New Zealand

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    New Zealand is a remote country in the South Pacific Ocean. The isolation and relatively late arrival of humans into New Zealand has meant there is a recorded history of the introduction of domestic species. Honey bees (Apis mellifera) were introduced to New Zealand in 1839, and the disease American foulbrood was subsequently found in the 1870s. Paenibacillus larvae, the causative agent of American foulbrood, has been genome sequenced in other countries. We sequenced the genomes of P. larvae obtained from 164 New Zealand apiaries where American foulbrood was identified in symptomatic hives during visual inspection. Multi-locus sequencing typing (MLST) revealed the dominant sequence type to be ST18, with this clonal cluster accounting for 90.2% of isolates. Only two other sequence types (with variants) were identified, ST5 and ST23. ST23 was only observed in the Otago area, whereas ST5 was limited to two geographically non-contiguous areas. The sequence types are all from the enterobacterial repetitive intergenic consensus I (ERIC I) genogroup. The ST18 and ST5 from New Zealand and international P. larvae all clustered by sequence type. Based on core genome MLST and SNP analysis, localized regional clusters were observed within New Zealand, but some closely related genomes were also geographically dispersed, presumably due to hive movements by beekeepers

    The coincidence of ecological opportunity with hybridization explains rapid adaptive radiation in Lake Mweru cichlid fishes

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    Abstract: The process of adaptive radiation was classically hypothesized to require isolation of a lineage from its source (no gene flow) and from related species (no competition). Alternatively, hybridization between species may generate genetic variation that facilitates adaptive radiation. Here we study haplochromine cichlid assemblages in two African Great Lakes to test these hypotheses. Greater biotic isolation (fewer lineages) predicts fewer constraints by competition and hence more ecological opportunity in Lake Bangweulu, whereas opportunity for hybridization predicts increased genetic potential in Lake Mweru. In Lake Bangweulu, we find no evidence for hybridization but also no adaptive radiation. We show that the Bangweulu lineages also colonized Lake Mweru, where they hybridized with Congolese lineages and then underwent multiple adaptive radiations that are strikingly complementary in ecology and morphology. Our data suggest that the presence of several related lineages does not necessarily prevent adaptive radiation, although it constrains the trajectories of morphological diversification. It might instead facilitate adaptive radiation when hybridization generates genetic variation, without which radiation may start much later, progress more slowly or never occur

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

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    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

    Future-ai:International consensus guideline for trustworthy and deployable artificial intelligence in healthcare

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    Despite major advances in artificial intelligence (AI) for medicine and healthcare, the deployment and adoption of AI technologies remain limited in real-world clinical practice. In recent years, concerns have been raised about the technical, clinical, ethical and legal risks associated with medical AI. To increase real world adoption, it is essential that medical AI tools are trusted and accepted by patients, clinicians, health organisations and authorities. This work describes the FUTURE-AI guideline as the first international consensus framework for guiding the development and deployment of trustworthy AI tools in healthcare. The FUTURE-AI consortium was founded in 2021 and currently comprises 118 inter-disciplinary experts from 51 countries representing all continents, including AI scientists, clinicians, ethicists, and social scientists. Over a two-year period, the consortium defined guiding principles and best practices for trustworthy AI through an iterative process comprising an in-depth literature review, a modified Delphi survey, and online consensus meetings. The FUTURE-AI framework was established based on 6 guiding principles for trustworthy AI in healthcare, i.e. Fairness, Universality, Traceability, Usability, Robustness and Explainability. Through consensus, a set of 28 best practices were defined, addressing technical, clinical, legal and socio-ethical dimensions. The recommendations cover the entire lifecycle of medical AI, from design, development and validation to regulation, deployment, and monitoring. FUTURE-AI is a risk-informed, assumption-free guideline which provides a structured approach for constructing medical AI tools that will be trusted, deployed and adopted in real-world practice. Researchers are encouraged to take the recommendations into account in proof-of-concept stages to facilitate future translation towards clinical practice of medical AI
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