Search

Objective: The risk of aortic dissection (AoD) is increased in Turner syndrome (TS) but predicting those at risk is difficult. Based on scarce evidence, preventive aortic surgery is recommended when aortic diameter increases >5 mm/year. To investigate the aortic growth rate in TS and TS‐related conditions associated with aortic growth. We also reported our experience of women who suffered aortic dissection (AoD), and who had preventive aortic replacement. Methods: 151 adult TS were retrospectively identified. Women who had more than one transthoracic echocardiogram (TTE) after age 16 years were included in the aortic growth study. Aortic diameters at sinuses of Valsalva (SoV) and ascending aorta (AA) were analysed by two experts. Results: 70/151 women had more than one TTE (interscan interval 4.7 years). Mean aortic growth was 0.13 ± 0.59 mm/year at SoV and 0.23 ± 0.82 mm/year at AA. Known risk factors for aortic dilatation and TS‐related conditions were not associated with aortic growth. 4/151 women experienced AoD (age 25±8 years): two had paired scans for aortic growth, which was 0.67 mm/year at both SoV and AA in the first woman, and 11 mm/year (SoV) and 4 mm/year (AA) in the second. Only 1/4 of women with AoD survived; she used a TS cardiac‐alert card to inform emergency personnel about her risk of AoD. 5/151 had a preventive aortic replacement, but one died post‐operatively. Conclusions: Mean aortic growth in our TS population was increased compared to non‐TS women and was not associated with currently known risk factors for AoD, suggesting that aortic growth rate itself could be a useful variable to stratify who is at risk for AoD. [ABSTRACT FROM AUTHOR]

In our recent paper on the clinical pharmacology of tafenoquine (Watson et al., 2022), we used all available individual patient pharmacometric data from the tafenoquine pre-registration clinical efficacy trials to characterise the determinants of anti-relapse efficacy in tropical vivax malaria. We concluded that the currently recommended dose of tafenoquine (300 mg in adults, average dose of 5 mg/kg) is insufficient for cure in all adults, and a 50% increase to 450 mg (7.5 mg/kg) would halve the risk of vivax recurrence by four months. We recommended that clinical trials of higher doses should be carried out to assess their safety and tolerability. Sharma and colleagues at the pharmaceutical company GSK defend the currently recommended adult dose of 300 mg as the optimum balance between radical curative efficacy and haemolytic toxicity (Sharma et al., 2024). We contend that the relative haemolytic risks of the 300 mg and 450 mg doses have not been sufficiently well characterised to justify this opinion. In contrast, we provided evidence that the currently recommended 300 mg dose results in sub-maximal efficacy, and that prospective clinical trials of higher doses are warranted to assess their risks and benefits. [ABSTRACT FROM AUTHOR]

For the Blue Foods economy—those sectors that gain value from the biological productivity of the oceans such as fisheries and aquaculture—climate shocks pose an existential threat. Species range shifts, harmful algal blooms, marine heatwaves, low oxygen events, coral bleaching, and hurricanes all present a serious economic risk to these industries, and yet there exist few financial tools for managing these risks. This contrasts with agriculture, where financial tools such as insurance are widely available for managing numerous weather-related shocks. Designing financial tools to aid risk management, such as insurance, for equitable resilience against marine climate shocks will give coastal communities access to the necessary means for reducing their sensitivity to climate shocks and improving their long-term adaptive capacity. We suggest that a convergence of the insurance industry and marine sectors, fostered through collaboration with governments, academics, and NGOs will help usher in new forms of insurance, such as ocean-index or parametric insurance. These new risk-management tools have the potential to help incentivize sustainable use of living marine resources, as well as strengthening the economic resilience of coastal communities to climate change. [ABSTRACT FROM AUTHOR]

In this Policy Forum article, James A. Watson and colleagues discuss recent guidelines relating to pre-referral treatment of suspected severe malaria with rectal artesunate suppositories in remote areas. [ABSTRACT FROM AUTHOR]

As anthropogenic transformation of Earth's ecology accelerates, and its impacts on the sustainability of humanity and the rest of nature become more obvious, geographers and other researchers are leveraging an abundance of spatial data to map how industrialization is transforming the biosphere. This review examines the methodologies used to create such maps and how they have enhanced our understanding of how societies can abate biodiversity loss, mitigate climate change, and achieve global sustainability goals. Although there have been great advances over the past two decades in mapping industrial transformations of ecology across the planet, the field is still in its infancy. We outline future research directions to better understand anthropogenic transformation of the biosphere and the utility of integrating global maps of socioeconomic, ecological, biodiversity, and climate data to explore and inform potential pathways of human-driven social-ecological change. [ABSTRACT FROM AUTHOR]

Healthcare services for people living with dementia (PLWD) are stretched, and government promises of increased funding remain undelivered. With the UK dementia population to surpass 1 million by 2024, and dementia care costs predicted to almost treble by 2040, it is essential we understand differences in healthcare use among PLWD. This study aimed to explore social and spatial variations in healthcare use among people diagnosed with dementia (2002–2016). Data were derived from Electronic Health Records of Clinical Practice Research Datalink GP patients in England (n = 142,302). To standardise healthcare contacts, rates of healthcare contacts per year were calculated for three primary (GP observations and medications) and three secondary healthcare types [Accident & Emergency (A&E) attendances and, emergency and elective hospital admissions]. Fully-adjusted generalised linear regression models were used to identify healthcare use variation by social and spatial groups. Twelve models were generated, one for each healthcare type in early- and late-onset populations separately. This study highlights numerous social and spatial variations in healthcare use among PLWD. Among PLWD, several groups tended to have healthcare service use more closely associated with negative outcomes, including a greater likelihood of A&E attendances and emergency and elective hospital admissions. These groups include: men, people from White ethnicity groups and people from more deprived and rural areas. Systemic and social measures are needed to reduce variations in healthcare use inequalities in PWLD. These include greater healthcare continuity, health checks and medicines reviews, culturally appropriate services, better and more accessible treatment and improved infrastructure. [ABSTRACT FROM AUTHOR]

Levels of HIV stigma remain high, however there is a limited understanding around how different types of stigma interact to impact health. This study uses data from two time points to examine how enacted and internalized stigma lead to worse health through anticipated stigma as a mediator. We recruited 341 participants in Ontario, Canada to complete the HIV Stigma Index survey at baseline (t1) from September 2018 to August 2019 and follow up (t2) approximately two years later. Mediation models were created with enacted and internalized stigma at t1 as the antecedents, anticipated stigma at t2 as the mediator, and physical health, mental health, and overall health at t2 as the outcomes. Only the model with internalized stigma (t1) as the antecedent had anticipated stigma (t2) as a significant mediator contributing to both decreased mental and overall health. This highlights the need to address internalized stigma and the potential for anticipated stigma interventions to be effective at improving the health and wellbeing of people living with HIV. [ABSTRACT FROM AUTHOR]

CARAMAL was a large observational study which recorded mortality in children with suspected severe malaria before and after the roll-out of rectal artesunate in Nigeria, Uganda and the Democratic Republic of the Congo. The results of CARAMAL have had a huge impact on public health policy leading to a World Health Organization moratorium on the roll-out of rectal artesunate. The conclusion reported in the abstract uses strong causal language, stating that "pre-referral RAS [rectal artesunate suppositories] had no beneficial effect on child survival". We argue that this causal interpretation of the study results is not justified. Data from the CARAMAL study inform chiefly on the strengths and weaknesses of referral systems in these three countries and do not inform reliably as to the beneficial effect of providing access to a known life-saving treatment. [ABSTRACT FROM AUTHOR]

Between 2007 and 2021 we monitored adult hawks (Buteo spp.) nesting in the upper Columbia River Basin of Washington and Oregon using global positioning system (GPS) telemetry on 17 Ferruginous Hawks (B. regalis), 9 Red-tailed Hawks (B. jamaicensis), and 14 Swainson's Hawks (B. swainsoni). Our main objectives were to: (1) provide contemporary home-range estimates using fixes generated by the global positioning system to better inform protective buffers on Buteo ranges in the Columbia River Basin; and (2) describe prey analyzed from pellets collected at 47 Buteo territories. Breeding home ranges (Brownian bridge movement model, 95% isopleths) of Ferruginous Hawks (B. regalis) were substantially larger (x̄ = 378, sx = 133 km2) than those published previously, as were home ranges of Swainson's Hawks (x̄ = 276, sx = 146 km2) and Red-tailed Hawks (x̄ = 28, sx = 12 km2). Diets of Ferruginous Hawks on the study area were dominated (60%) by Northern Pocket Gophers (Thomomys talpoides), whereas Swainson's Hawks primarily (83%) ate grasshoppers (Apote notablis and Melanoplus spp.). Red-tailed Hawks ate a less-specialized diet of reptiles (40%), mammals (38%), and birds (13%). We provide models that show the probable degree of protection afforded by different-sized buffers when applied to species-specific home ranges and core areas for hawks in the Columbia River Basin. [ABSTRACT FROM AUTHOR]

Tafenoquine is a newly licensed antimalarial drug for the radical cure of Plasmodium vivax malaria. The mechanism of action and optimal dosing are uncertain. We pooled individual data from 1102 patients and 72 healthy volunteers studied in the pre-registration trials. We show that tafenoquine dose is the primary determinant of efficacy. Under an Emax model, we estimate the currently recommended 300 mg dose in a 60 kg adult (5 mg/kg) results in 70% of the maximal obtainable hypnozoiticidal effect. Increasing the dose to 7.5 mg/kg (i.e. 450 mg) would result in 90% reduction in the risk of P. vivax recurrence. After adjustment for dose, the tafenoquine terminal elimination half-life, and day 7 methaemoglobin concentration, but not the parent compound exposure, were also associated with recurrence. These results suggest that the production of oxidative metabolites is central to tafenoquine's hypnozoiticidal efficacy. Clinical trials of higher tafenoquine doses are needed to characterise their efficacy, safety and tolerability. [ABSTRACT FROM AUTHOR]

Aim: Dispersal and environmental gradients shape marine microbial communities, yet the relative importance of these factors across taxa with distinct sizes and dispersal capacity in different ocean layers is unknown. Here, we report a comparative analysis of surface and deep ocean microbial beta diversity and examine how these patterns are tied to oceanic distance and environmental gradients. Location: Tropical and subtropical oceans (30°N–40°S). Time period: 2010–2011. Major taxa studied: Prokaryotes and picoeukaryotes (eukaryotes between 0.2 and 3 μm). Methods: Beta diversity was calculated from metabarcoding data on prokaryotic and picoeukaryotic microbes collected during the Malaspina expedition across the tropical and subtropical oceans. Mantel correlations were used to determine the relative contribution of environment and oceanic distance driving community beta diversity. Results: Mean community similarity across all sites for prokaryotes was 38.9% in the surface and 51.4% in the deep ocean, compared to mean similarity of 25.8 and 12.1% in the surface and deep ocean, respectively, for picoeukaryotes. Higher dispersal rates and smaller body sizes of prokaryotes relative to picoeukaryotes likely contributed to the significantly higher community similarity for prokaryotes compared with picoeukaryotes. The ecological mechanisms determining the biogeography of microbes varied across depth. In the surface ocean, the environmental differences in space were a more important factor driving microbial distribution compared with the oceanic distance, defined as the shortest path between two sites avoiding land. In the deep ocean, picoeukaryote communities were slightly more structured by the oceanic distance, while prokaryotes were shaped by the combined action of oceanic distance and environmental filtering. Main conclusions: Horizontal gradients in microbial community assembly differed across ocean depths, as did mechanisms shaping them. In the deep ocean, the oceanic distance and environment played significant roles driving microbial spatial distribution, while in the surface the influence of the environment was stronger than oceanic distance. [ABSTRACT FROM AUTHOR]

To achieve sustainable use of our oceans globally, our ability to detect and even predict illegal maritime activities must improve. The challenge is that most vessels that commit illegal acts will not transmit their location and are in effect unobservable to enforcement agencies. To overcome this challenge, we have developed a method for inferring the location and timing of illegal maritime activities inspired by complex systems theory: by monitoring the multiscale spatial behaviour of those vessels that we can observe, we are able to monitor for anomalous spatial patterns that could be associated with the presence of illegal activities (committed by an unobserved vessel). These spatial anomalies are represented as distortions in the 'shape' or multiscale spatial organization of fleets, which can be quantified using methods from information theory. To explore this approach, we developed a spatially explicit agent‐based model of fishing vessels, where we examined the utility of several multiscale spatial anomaly indexes. We then examined the performance of these indexes in a real‐world test‐case, with a focus on illegal events that occurred on the Patagonia Shelf. Our results suggest that this method offers insight into the location and timing of illegal activities at sea, and consequently offers a promising tool for helping to improve the security and sustainability of our oceans. [ABSTRACT FROM AUTHOR]

RESULTS Intactness of Earth's coastal regions No coastal region was free from human influence (i.e., 100% intact) and 15.5% of all coastal regions had low anthropogenic pressure (80-100% intact) (Figure 1). Given the interconnectedness of coastal regions, a clear coastal region target that moves away from small, area-based percentage protection targets and focuses on large effective management targets (and utilizing OECMs and non-area-based management techniques, such as enhanced regulation of degrading activities) would likely improve outcomes for coastal regions globally. Keywords: coast; coastlines; cumulative human impact; human footprint; human pressure; restoration; wilderness; costa; huella humana; impacto humano cumulativo; litoral; presión humana; restauración; tierras vírgenes EN coast coastlines cumulative human impact human footprint human pressure restoration wilderness costa huella humana impacto humano cumulativo litoral presión humana restauración tierras vírgenes 1 12 12 08/01/22 20220801 NES 220801 INTRODUCTION Coastal regions encompass some of the most biodiverse and unique ecosystems on Earth, including coral reefs, kelp forests, seagrass, tidal flats, mangroves, estuaries, salt marshes, wetlands, and coastal wooded habitat (Ray, 1991). In contrast, conserving the remaining intact pockets of coastlines, such as those on the coastal region encompassing Collingwood Bay in Papua New Guinea, which is relied on by local communities for ecosystem services (Skewes et al., 2011), and areas in the Tambelan Archipelago in Indonesia, where the coastal ecosystems are known nurseries for fish species (Yonvitner & Fahmi, 2012), will rely on specific management actions by local communities. [Extracted from the article]

The article focuses on the June 2024 issue of Insight, highlighting the evolution and challenges in ultrasonic testing (UT) and eddy current testing (ET) within the UK civil nuclear power industry over the past 50 years.

Methaemoglobin results from the oxidation of ferrous to ferric iron in the centre of the haem moiety of haemoglobin. The production of dose‐dependent methaemoglobinaemia by 8‐aminoquinoline antimalarial drugs appears to be associated with, but is not directly linked to, therapeutic efficacy against latent Plasmodium vivax and Plasmodium ovale malarias (radical cure). Iatrogenic methaemoglobinaemia may be a useful pharmacodynamic measure in 8‐aminoquinoline drug and dose optimization. [ABSTRACT FROM AUTHOR]

Archaeological compliance is defined by state and federal legislation and the constrained, precise language in which it is written. Rules and policies operationalize the law but provide some flexibility in its interpretation and implementation. The pronounced use of "legal" and "scientific" language in archaeological compliance can be considered insensitive or offensive to some tribal members when discussing the disposition and care of the remains and belongings of their ancestors. The language we use constructs our reality and defines how we interpret our interactions of the lived experience. It is therefore necessary to revise the language employed in archaeological compliance to ensure that it reflects the values of the communities that these laws define to determine treatment and ultimate disposition of their ancestral remains and belongings. This article describes and encourages the use of a respectful terminology, developed in conjunction with compliance professionals and tribal representatives, to restructure the language we use and redefine our interactions as more considerate of tribal concerns for repatriation. [ABSTRACT FROM AUTHOR]

"Ancestral Genealogies in Modern China: A Study of Lineage Organizations in Hong Kong and Mainland China" by Masahisa Segawa is a book that explores Chinese lineage organizations in the Hong Kong New Territories and Guangdong Province. The author focuses on multi-lineage, multi-surname communities that have been overlooked by previous researchers. The book discusses how smaller lineages in these areas achieved corporate status through the efforts of descendants, rather than through the management of resources. The book also examines the reconstruction and reinvention of lineage activities in Communist-controlled regions, following the destruction of ancestral halls, tombs, and genealogies during the Cultural Revolution. The author provides detailed descriptions of the reconstruction process, making this book a valuable resource for understanding Chinese lineage organizations. [Extracted from the article]

Species ranges are shifting in response to climate change, but most predictions disregard food–web interactions and, in particular, if and how such interactions change through time. Predator–prey interactions could speed up species range shifts through enemy release or create lags through biotic resistance. Here, we developed a spatially explicit model of interacting species, each with a thermal niche and embedded in a size-structured food–web across a temperature gradient that was then exposed to warming. We also created counterfactual single species models to contrast and highlight the effect of trophic interactions on range shifts. We found that dynamic trophic interactions hampered species range shifts across 450 simulated food–webs with up to 200 species each over 200 years of warming. All species experiencing dynamic trophic interactions shifted more slowly than single-species models would predict. In addition, the trailing edges of larger bodied species ranges shifted especially slowly because of ecological subsidies from small shifting prey. Trophic interactions also reduced the numbers of locally novel species, novel interactions and productive species, thus maintaining historical community compositions for longer. Current forecasts ignoring dynamic food–web interactions and allometry may overestimate species' tendency to track climate change. [ABSTRACT FROM AUTHOR]

This article explores the shoreline industries (oysters, salt, fish, lime) that emerged along the Laufaushan coast in Hong Kong's New Territories, in the period 1667 to 1978. The shoreline in question was controlled by a local security force, staffed by young men from a nearby lineage. The study draws on ethnographic research carried out by the author and local documents (of village and government origin) gathered on site. [ABSTRACT FROM AUTHOR]

Driven by the malaria-protective effect of sickle-cell trait, balancing selection results in hemoglobin S equilibrium allele frequencies of between 15% and 20% in areas of high Plasmodium falciparum transmission in sub-Saharan Africa. From this we estimate that the malaria-attributable childhood mortality in the pretreatment era was between 15% and 24%. [ABSTRACT FROM AUTHOR]

But given the shortfalls in knowledge, technical solutions, and the current gap in our ability to concurrently meet human and biodiversity needs, we argue for more recognition of the additional challenges facing species conservation and the value of working to overcome them. LACK OF KNOWLEDGE ABOUT HOW TO SAVE THREATENED SPECIES Wiedenfeld et al. argue that "the number of extant species that cannot be recovered to a global population at greatly reduced risk of extinction is very low." Keywords: extinction prevention; knowledge shortfalls; threatened species EN extinction prevention knowledge shortfalls threatened species 1 3 3 08/01/22 20220801 NES 220801 INTRODUCTION We agree with Wiedenfeld et al. (2021) that a core mission of conservation science is to not give up on species. [Extracted from the article]

James Watson and Oscar Venter introduce the concept of wilderness and its role in conservation efforts. [ABSTRACT FROM AUTHOR]

Background: Experiences of HIV stigma remain prevalent across Canada, causing significant stress and negatively affecting the health and wellbeing of people living with HIV. While studies have consistently demonstrated that stigma negatively impacts health, there has been limited research on the mechanisms behind these effects. This study aims to identify which dimensions of stigma have significant relationships with self-rated health and examine the mechanisms by which those types of stigma impact self-rated health.Methods: We recruited 724 participants to complete the People Living with HIV Stigma Index in Ontario, designed by people living with HIV to measure nuanced changes in stigma and discrimination. The present study utilizes data from externally validated measures of stigma and health risks that were included in the survey. First, we conducted multiple regression analyses to examine which variables had a significant impact on self-rated health. Results from the multiple regression guided the mediation analysis. A parallel mediation model was created with enacted stigma as the antecedent, internalized stigma and depression as the mediators, and self-rated health as the outcome.Results: In the multiple regression analysis, internalized stigma (coefficient = -0.20, p < 0.01) and depression (coefficient = -0.07, p < 0.01) were both significant and independent predictors of health. Mediation analyses demonstrated that the relationship between enacted stigma and self-rated health is mediated in parallel by both internalized stigma [coefficient = -0.08, se = 0.03, 95% CI (-0.14, -0.02)] and depression [coefficient = -0.16, se = 0.03, 95% CI (-0.22, -0.11)].Conclusions: We developed a mediation model to explain how HIV-related stigma negatively impacts health. We found that that enacted stigma, or experiences of prejudice or discrimination, can lead to internalized stigma, or internalization of negative thoughts regarding one's HIV status and/or increased depressive symptoms which then may lead to worse overall health. Highlighting the importance of internalized stigma and depression has the potential to shape the development of targeted intervention strategies aimed at reducing the burden of stigma and improving the health and wellbeing of people living with HIV. [ABSTRACT FROM AUTHOR]

Severe falciparum malaria has substantially affected human evolution. Genetic association studies of patients with clinically defined severe malaria and matched population controls have helped characterise human genetic susceptibility to severe malaria, but phenotypic imprecision compromises discovered associations. In areas of high malaria transmission, the diagnosis of severe malaria in young children and, in particular, the distinction from bacterial sepsis are imprecise. We developed a probabilistic diagnostic model of severe malaria using platelet and white count data. Under this model, we re-analysed clinical and genetic data from 2220 Kenyan children with clinically defined severe malaria and 3940 population controls, adjusting for phenotype mis-labelling. Our model, validated by the distribution of sickle trait, estimated that approximately one-third of cases did not have severe malaria. We propose a data-tilting approach for case-control studies with phenotype mis-labelling and show that this reduces false discovery rates and improves statistical power in genome-wide association studies. [ABSTRACT FROM AUTHOR]

In 2010, Parties to the Convention on Biological Diversity (CBD) adopted the Strategic Plan for Biodiversity 2011–2020 to address the loss and degradation of nature. Subsequently, most biodiversity indicators continued to decline. Nevertheless, conservation actions can make a positive difference for biodiversity. The emerging Post‐2020 Global Biodiversity Framework has potential to catalyze efforts to "bend the curve" of biodiversity loss. Thus, the inclusion of a goal on species, articulated as Goal B in the Zero Draft of the Post‐2020 Framework, is essential. However, as currently formulated, this goal is inadequate for preventing extinctions, and reversing population declines; both of which are required to achieve the CBD's 2030 Mission. We contend it is unacceptable that Goal B could be met while most threatened species deteriorated in status and many avoidable species extinctions occurred. We examine the limitations of the current wording and propose an articulation with robust scientific basis. A goal for species that strives to end extinctions and recover populations of all species that have experienced population declines, and especially those at risk of extinction, would help to align actors toward the transformative actions and interventions needed for humans to live in harmony with nature. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this systematic review was to evaluate studies which employed routine and cohort data sets to understand inequalities in dementia care pathways. Methods: We identified 27 research papers using routine data sets to investigate inequalities in dementia care pathways through electronic and grey literature searches. Papers were independently assessed by two reviewers for inclusion based on defined criteria. Included papers were quality rated using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross‐Sectional Studies. Data was extracted based on stage(s) in dementia care pathway and socio‐economic factors investigated. Results: Inequalities were noted across dementia care pathways. Socio‐economic and protected characteristics were shown to impact the likelihood of people with dementia moving into institutional nursing care, the quality and consistency of their treatment, need for emergency and urgent healthcare, the rate of illness progression and their long‐term survival. Research was often disparate ignoring the multiple parts of the dementia care pathway, or the impact of specific factors across multiple stages. Conclusions: Our study highlights issues in dementia care pathways based on socio‐economic or protected characteristics. Equitable service provision, more culturally appropriate services, improved health literacy and increased provision for both early diagnosis and care at home can help narrow the gap in dementia care inequalities. There is greater need for research investigating dementia care pathways as something greater than the sum of its parts; exploring the influence of socio‐economic factors from a person's entrance into the system and throughout. [ABSTRACT FROM AUTHOR]

The reaction between two equivalents of {(Me3Si)2CH}(Ph)PH(BH3) (1) and Bu2Mg, followed by two equivalents of BH3·SMe2, gives the corresponding phosphido-bis(borane) complex, which may be crystallised as two distinct chemical species: the complex [{(Me3Si)2CH}(Ph)P(BH3)2]2Mg(THF)4·THF (2a), and two different THF solvates (1 : 1 and 1 : 2) of the solvent-separated ion triples [{(Me3Si)2CH}(Ph)P(BH3)2]2[Mg(THF)6]·THF (2b) and [{(Me3Si)2CH}(Ph)P(BH3)2]2[Mg(THF)6]·2THF (2c). Similar reactions between two equivalents of 1 and either (4-tBuC6H4CH2)2Ca(THF)4 or [(Me3Si)2CH]2Sr(THF)2, followed by two equivalents of BH3·SMe2, give the heavier alkali metal complexes [{(Me3Si)2CH}(Ph)P(BH3)2]2M(THF)4 [M = Ca (3), Sr (4)]. Surprisingly, compounds 2a, 3 and 4 adopt almost identical structures in the solid state, which differ only in the geometrical arrangement of the phosphido-bis(borane) ligands and the hapticity of the borane groups. [ABSTRACT FROM AUTHOR]

For most antivenoms there is little information from clinical studies to infer the relationship between dose and efficacy or dose and toxicity. Antivenom dose-finding studies usually recruit too few patients (e.g. fewer than 20) relative to clinically significant event rates (e.g. 5%). Model based adaptive dose-finding studies make efficient use of accrued patient data by using information across dosing levels, and converge rapidly to the contextually defined 'optimal dose'. Adequate sample sizes for adaptive dose-finding trials can be determined by simulation. We propose a model based, Bayesian phase 2 type, adaptive clinical trial design for the characterisation of optimal initial antivenom doses in contexts where both efficacy and toxicity are measured as binary endpoints. This design is illustrated in the context of dose-finding for Daboia siamensis (Eastern Russell's viper) envenoming in Myanmar. The design formalises the optimal initial dose of antivenom as the dose closest to that giving a pre-specified desired efficacy, but resulting in less than a pre-specified maximum toxicity. For Daboia siamensis envenoming, efficacy is defined as the restoration of blood coagulability within six hours, and toxicity is defined as anaphylaxis. Comprehensive simulation studies compared the expected behaviour of the model based design to a simpler rule based design (a modified '3+3' design). The model based design can identify an optimal dose after fewer patients relative to the rule based design. Open source code for the simulations is made available in order to determine adequate sample sizes for future adaptive snakebite trials. Antivenom dose-finding trials would benefit from using standard model based adaptive designs. Dose-finding trials where rare events (e.g. 5% occurrence) are of clinical importance necessitate larger sample sizes than current practice. We will apply the model based design to determine a safe and efficacious dose for a novel lyophilised antivenom to treat Daboia siamensis envenoming in Myanmar. Author summary: Snakebite envenoming is one of the most neglected tropical diseases considering its burden of mortality and morbidity. Antivenoms are the only known effective treatment for snake-bite envenoming but are frequently responsible for high rates of adverse reactions. Clinical development of antivenoms rarely follows the iterative phases of clinical development applied to other drugs. Dosing is typically based on pre-clinical testing. Here we propose a Bayesian model based adaptive design for phase 2 clinical trials aiming to determine the optimal dose of antivenom needed for treatment of snakebite envenoming. Optimality is defined using safety and efficacy thresholds contextual to the study. This design can be applied to all antivenoms which have binary efficacy and toxicity endpoints. Our design formally specifies a desired efficacy and a maximum tolerated toxicity. We use simulation studies to characterise adequate sample sizes to determine an approximately optimal dose under different scenarios. The simulation studies highlight the advantages of a model based design over simpler rule based alternatives. This design will be used to determine an effective and safe dose of the new lyophilised viper antivenom currently in use to treat Russell's viper envenoming in Myanmar. [ABSTRACT FROM AUTHOR]

The article provides an anthropological study on female hunters of the early Americas. It mentions Sexual division of labor with females as gatherers and males as hunters is a major empirical regularity of hunter-gatherer ethnography, suggesting an ancestral behavioral pattern. It further present an archeological discovery and meta-analysis that challenge the man-the-hunter hypothesis.

Genetic surveillance of malaria parasites supports malaria control programmes, treatment guidelines and elimination strategies. Surveillance studies often pose questions about malaria parasite ancestry (e.g. how antimalarial resistance has spread) and employ statistical methods that characterise parasite population structure. Many of the methods used to characterise structure are unsupervised machine learning algorithms which depend on a genetic distance matrix, notably principal coordinates analysis (PCoA) and hierarchical agglomerative clustering (HAC). PCoA and HAC are sensitive to both the definition of genetic distance and algorithmic specification. Importantly, neither algorithm infers malaria parasite ancestry. As such, PCoA and HAC can inform (e.g. via exploratory data visualisation and hypothesis generation), but not answer comprehensively, key questions about malaria parasite ancestry. We illustrate the sensitivity of PCoA and HAC using 393 Plasmodium falciparum whole genome sequences collected from Cambodia and neighbouring regions (where antimalarial resistance has emerged and spread recently) and we provide tentative guidance for the use and interpretation of PCoA and HAC in malaria parasite genetic epidemiology. This guidance includes a call for fully transparent and reproducible analysis pipelines that feature (i) a clearly outlined scientific question; (ii) a clear justification of analytical methods used to answer the scientific question along with discussion of any inferential limitations; (iii) publicly available genetic distance matrices when downstream analyses depend on them; and (iv) sensitivity analyses. To bridge the inferential disconnect between the output of non-inferential unsupervised learning algorithms and the scientific questions of interest, tailor-made statistical models are needed to infer malaria parasite ancestry. In the absence of such models speculative reasoning should feature only as discussion but not as results. Author summary: Genetic epidemiology studies of malaria attempt to characterise what is happening in malaria parasite populations. In particular, they are an important tool to track the spread of drug resistance and to validate genetic makers of drug resistance. To make sense of parasite genetic data, researchers usually characterise the population structure using statistical methods. This is most often done as a two step process. The first is a data reduction step, whereby the data are summarised into a distance matrix (each entry represents the genetic distance between two isolates). The distance matrix is then input into an unsupervised machine learning algorithm. Principal coordinates analysis and hierarchical agglomerative clustering are the two most popular unsupervised machine learning algorithms used for this purpose in malaria genetic epidemiology. We highlight that this procedure is sensitive to the choice of genetic distance and to the specification of the algorithms. These unsupervised methods are useful for exploratory data analysis but cannot be used to infer historical events. We provide some guidance on how to make genetic epidemiology analyses more transparent and reproducible. [ABSTRACT FROM AUTHOR]

Nicholas White and coauthors discuss chloroquine and hydroxychloroquine pharmacology in the context of possible treatment of SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Beginning in 1977 the Washington Department of Fish and Wildlife conducted annual surveys to determine statewide golden eagle (Aquila chrysaetos) occupancy and productivity. Current interest in the regional and national status of the species prompted our investigation to determine utility of historical data in assessing trends in reproduction, and to test efficacy of a sampling protocol that surveyed randomly selected territories and also accounted for detection probability. We found evidence indicating poor reproduction from 38 annual surveys conducted at 301 known territories statewide between 1977 and 2014. At 256 territories in eastern Washington, USA, apparent occupancy was low (x¯ = 50.9%) and nesting success declined by 22%. All reproductive parameters were higher than at 45 territories in western Washington. We tested efficacy of a sampling protocol in 2013 and 2014 by surveying 108 randomly selected eastern territories. Probability of detecting eagles for these years from ground (x̂= 89%) was greater than from air (x̂= 66%). Our estimate of territory occupancy, corrected by probability of detection, was lower in 2013 (x̂= 56.7%, 95% CI = 46.3–66.7%) than in 2014 (x̂= 73.7%, 95% CI = 64.8–81.7%), as was the estimated number of breeding pairs (2013: x̂= 158, 95% CI = 151–164; 2014: x̂= 187, 95% CI = 182–192). Higher productivity (young/occupied territory) in 2013 (x̂= 0.59, 95% CI = 0.40–0.82) than in 2014 (x̂= 0.41, 95% CI = 0.27–0.59) and lower proportions of ≥1 immature eagle among nesting pairs in 2013 (16%) than in 2014 (31%), suggested higher immature pairing among sampled pairs contributed to inter‐year differences in these reproductive parameters. Current and historical evidence for depressed golden eagle nesting in Washington is consistent with documented effects from habitat conversion, prey declines, lead contamination, and wind power development. We recommend future surveys in eastern Washington adhere to the random sampling protocol and conduct surveys at regular intervals to allow for trend analysis of reproductive parameters to better monitor golden eagle status. Surveys in western Washington, conducted exclusively from ground at all nests, will improve detection and cost efficiency. © 2020 The Wildlife Society. Historical and recent surveys provide evidence for depressed golden eagle nesting in Washington that is consistent with several current stressors and threats. We recommend future surveys in eastern Washington adhere to a random sampling protocol to allow for trend analysis of reproductive parameters to monitor golden eagle status. [ABSTRACT FROM AUTHOR]

Background: Exploration and modelling of heterogeneous treatment effects as a function of baseline covariates is an important aspect of precision medicine in randomised controlled trials (RCTs). Randomisation generally guarantees the internal validity of an RCT, but heterogeneity in treatment effect can reduce external validity. Estimation of heterogeneous treatment effects is usually done via a predictive model for individual outcomes, where one searches for interactions between treatment allocation and important patient baseline covariates. However, such models are prone to overfitting and multiple testing and typically demand a transformation of the outcome measurement, for example, from the absolute risk in the original RCT to log-odds of risk in the predictive model.Methods: We show how reference classes derived from baseline covariates can be used to explore heterogeneous treatment effects via a two-stage approach. We first estimate a risk score which captures on a single dimension some of the heterogeneity in outcomes of the trial population. Heterogeneity in the treatment effect can then be explored via reweighting schemes along this axis of variation. This two-stage approach bypasses the search for interactions with multiple covariates, thus protecting against multiple testing. It also allows for exploration of heterogeneous treatment effects on the original outcome scale of the RCT. This approach would typically be applied to multivariable models of baseline risk to assess the stability of average treatment effects with respect to the distribution of risk in the population studied.Case Study: We illustrate this approach using the single largest randomised treatment trial in severe falciparum malaria and demonstrate how the estimated treatment effect in terms of absolute mortality risk reduction increases considerably in higher risk strata.Conclusions: 'Local' and 'tilting' reweighting schemes based on ranking patients by baseline risk can be used as a general approach for exploring, graphing and reporting heterogeneity of treatment effect in RCTs.Trial Registration: ISRCTN clinical trials registry: ISRCTN50258054. Prospectively registered on 22 July 2005. [ABSTRACT FROM AUTHOR]

Nest predation is considered a major cause of population decline for the Endangered Alwal Psephotellus chrysopterygius (Golden-shouldered parrot) in Cape York Peninsula, Australia. Camera-traps were installed at 28 Alwal nests across two breeding seasons in four important refuges for the parrot, to confirm nest predator identities and their impact on nesting success. Nest predators were more common at Alwal nests prior to fledging. The feral cat Felis catus and yellow-spotted monitor Varanus panoptes were the most common predators detected at nests, but the Black-backed butcherbird Cracticus mentalis, Pied butcherbird C. nigrogularis and Brown goshawk Acciptier fasciatus were also documented predating nests. Predators were significantly more common at nests in the days prior to fledging, possibly due to increased nest site activity. Nest success was higher amongst denser vegetation, indicating that cover may inhibit detection of nests by predators, particularly at fledging time. As with many threatened species globally, further monitoring is needed to disentangle knowledge of Alwal nest predation, including refined nest-monitoring techniques to document elusive predation events. [ABSTRACT FROM AUTHOR]

Transitioning from fossil fuels to renewable energy is fundamental for halting anthropogenic climate change. However, renewable energy facilities can be land‐use intensive and impact conservation areas, and little attention has been given to whether the aggregated effect of energy transitions poses a substantial threat to global biodiversity. Here, we assess the extent of current and likely future renewable energy infrastructure associated with onshore wind, hydropower and solar photovoltaic generation, within three important conservation areas: protected areas (PAs), Key Biodiversity Areas (KBAs) and Earth's remaining wilderness. We identified 2,206 fully operational renewable energy facilities within the boundaries of these conservation areas, with another 922 facilities under development. Combined, these facilities span and are degrading 886 PAs, 749 KBAs and 40 distinct wilderness areas. Two trends are particularly concerning. First, while the majority of historical overlap occurs in Western Europe, the renewable electricity facilities under development increasingly overlap with conservation areas in Southeast Asia, a globally important region for biodiversity. Second, this next wave of renewable energy infrastructure represents a ~30% increase in the number of PAs and KBAs impacted and could increase the number of compromised wilderness areas by ~60%. If the world continues to rapidly transition towards renewable energy these areas will face increasing pressure to allow infrastructure expansion. Coordinated planning of renewable energy expansion and biodiversity conservation is essential to avoid conflicts that compromise their respective objectives. [ABSTRACT FROM AUTHOR]

We present algorithms and results for a robotic manipulation system that was designed to be easily programable and adaptable to various tasks common to industrial setting, which is inspired by the Industrial Assembly Challenge at the 2018 World Robotics Summit in Tokyo. This challenge included assembly of standard, commercially available industrial parts into 2D and 3D assemblies. We demonstrate three tasks that can be classified into 'peg-in-hole' and 'hole-on-peg' tasks and identify two canonical algorithms: spiral-based search and tilting insertion. Both algorithms use hand-coded thresholds in the force and torque domains to detect critical points in the assembly. After briefly summarizing the state of the art in research, we describe the strategy and approach utilized by the tested system, how it's design bears on its performance, statistics on 20 experimental trials for each task, lessons learned during the development of the system, and open research challenges that still remain. [ABSTRACT FROM AUTHOR]

Background: Retrospective exploratory analyses of randomised controlled trials (RCTs) seeking to identify treatment effect heterogeneity (TEH) are prone to bias and false positives. Yet the desire to learn all we can from exhaustive data measurements on trial participants motivates the inclusion of such analyses within RCTs. Moreover, widespread advances in machine learning (ML) methods hold potential to utilise such data to identify subjects exhibiting heterogeneous treatment response.Methods: We present a novel analysis strategy for detecting TEH in randomised data using ML methods, whilst ensuring proper control of the false positive discovery rate. Our approach uses random data partitioning with statistical or ML-based prediction on held-out data. This method can test for both crossover TEH (switch in optimal treatment) and non-crossover TEH (systematic variation in benefit across patients). The former is done via a two-sample hypothesis test measuring overall predictive performance. The latter is done via 'stacking' the ML predictors alongside a classical statistical model to formally test the added benefit of the ML algorithm. An adaptation of recent statistical theory allows for the construction of a valid aggregate p value. This testing strategy is independent of the choice of ML method.Results: We demonstrate our approach with a re-analysis of the SEAQUAMAT trial, which compared quinine to artesunate for the treatment of severe malaria in Asian adults. We find no evidence for any subgroup who would benefit from a change in treatment from the current standard of care, artesunate, but strong evidence for significant TEH within the artesunate treatment group. In particular, we find that artesunate provides a differential benefit to patients with high numbers of circulating ring stage parasites.Conclusions: ML analysis plans using computational notebooks (documents linked to a programming language that capture the model parameter settings, data processing choices, and evaluation criteria) along with version control can improve the robustness and transparency of RCT exploratory analyses. A data-partitioning algorithm allows researchers to apply the latest ML techniques safe in the knowledge that any declared associations are statistically significant at a user-defined level. [ABSTRACT FROM AUTHOR]

We examine the changes in funerary rituals from the Early Agricultural period (2100 BC–AD 50) to the Early Preclassic period (AD 475–750) and how these changes concurrently reflect changes in social relationships between the dead, their families, and the community. The predominant mortuary ritual in the Early Agricultural period was inhumation, possibly emphasizing a variety of identity intersections of the dead and the mourners in the treatment of the body while creating collective memories and remembrances through shared ways of commemorating the dead. An innovation in funerary practices in the form of secondary cremation appeared in the Early Agricultural period and was slowly but broadly adopted, representing new social dynamics within the society. Thereafter, secondary cremation became the main funeral custom. During the Early Preclassic period, the variation in body position and the type and quantity of objects found with individuals decreased. It is possible that the vehicle for displaying different identity intersections changed and was not placed in the body, per se, as much as in previous periods. However, the transformation characteristics of these funeral rituals and the increase in community investment could have fostered the building or reinforcing of stronger social ties that highlighted a “collective identity.” [ABSTRACT FROM AUTHOR]

Habitat destruction is among the greatest threats facing biodiversity, and it affects common and threatened species alike. However, metrics for communicating its impacts typically overlook the nonthreatened component of assemblages. This risks the loss of habitat going unreported for species that comprise the majority of assemblages. We adapted a widely used measure for summarizing researcher output (the h index) to provide a metric that describes natural habitat loss for entire assemblages, inclusive of threatened and nonthreatened species. For each of 447 Australian native terrestrial bird species, we combined information on their association with broad vegetation groups with distributional range maps to identify the difference between the estimated pre‐European and current extents of potential habitat, defined as vegetation groups most closely associated with each species. From this, we calculated the loss index (LI), which revealed that 30% of native birds have each lost at least 30% of their potential natural habitat (LI = 30). At the subcontinental scale, LIs ranged from 15 in arid Australia to 61 in the highly transformed southeastern part of the country. Different subcomponents of the assemblage had different LI values. For example, Australia's parrots (n = 52 species) had an LI of 38, whereas raptors (n = 32 species) had an LI of 25. The LI is simple to calculate and can be determined using readily available spatial information on species distributions, native vegetation associations, and human impacts on natural land cover. This metric, including the curves used to deduce it, could complement other biodiversity indices if it is used for regional and global biodiversity assessments that compare the status of natural habitat extent for assemblages within and among nations, monitor changes through time, and forecast future changes to guide strategic land‐use planning. The LI is an intuitive tool that can be used to summarize and communicate how human actions affect whole assemblages, not just threatened species. Article impact statement: The habitat loss index allows for effect of habitat removal on multispecies assemblages to be easily described and systematically tracked. [ABSTRACT FROM AUTHOR]

Understanding the behavioral ecology of species of conservation concern can help to inform better management. During winters 2011 through 2017, we placed camera traps at stations baited with carrion to investigate characteristics of winter scavenging by golden eagles (Aquila chrysaetos) and bald eagles (Haliaeetus leucocephalus) in eastern Washington and Oregon, USA. Our objectives were to better understand exposure risk of individual eagles to lead contaminants and evaluate factors that affect eagle visitation to carrion to inform measures that reduce lead exposure. We studied photo sequences from 108 traps (x¯ = 2,725 ± 306 [SE] images/trap) and used plumage and physical characteristics to track visitation of 183 individual golden eagles and 90 bald eagles at deer (Odocoileus spp.) carrion until it was totally consumed. At least 1 eagle visited 76% of traps (x¯ = 2.5 ± 0.3 unique eagles/trap). On average, an eagle visited a trap 3.4 ± 0.2 times (range = 1–19 visits) over 1.9 ± 0.1 days (range = 1–9 days). We used general linear mixed models to identify influences on number of eagle visits and pooled visit duration. Individual golden eagles visited carrion about 25% more often and 50% longer than bald eagles, and individual juvenile eagles visited carrion more often and longer than immature and adult eagles. On average, an eagle made an additional visit to carrion for every golden eagle that came to the same trap. Eagles spent less time at offal (x¯ = 26.2 ± 6.4 min) than at a whole carcass (x¯ = 92.9 ± 7.5 min), and understory vegetation immediately surrounding carrion was associated with a 30% reduction in visitation time. In the Pacific Northwest during winter, adult and juvenile golden eagles, by virtue of their abundance and visitation to carrion compared to the immature age class and bald eagles of all ages, have the highest potential for exposure to anthropogenic effects from carrion visitation. Concealment of offal piles in vegetation may reduce, but not eliminate, eagle use because of competing scavengers that expose carrion locations. We found no evidence that carrion proximity to nearest known nests, topography, or snow cover affect visitation by eagles. Thus, short of using alternative ammunition to lead, we recommend burial or removal of offal from hunter‐killed ungulates. © 2019 The Wildlife Society. Eagle visitation to deer carrion varied by eagle species and age, carrion type, and other factors including ground cover. Results identify opportunities to reduce potential exposure to lead and provide information on eagle scavenging rates useful to mitigation models. [ABSTRACT FROM AUTHOR]

From 1999 to 2014 we used satellite telemetry to address knowledge gaps in the migration of juvenile Ferruginous Hawks (Buteo regalis) related to their migration independence from adults, migration patterns, and locations of settlement ranges. Nine fledgling hawks migrated independently from their radio-tagged parents, left natal areas at different times and directions, and settled on summer ranges separated from parents by an average of 592 km. Juvenile hawks that we followed through their entire first year (n = 12) travelled about three times farther and twice as long as adults during annual migrations, and arrived an average of 11 to 38 d later on summer, winter, and spring ranges. Hawks that hatched west of the Continental Divide (n = 14) migrated northeast in summer to ranges in the northern grasslands and to winter ranges in California and the Great Plains. Hawks that hatched east of the divide (n = 17) also migrated north to summer ranges, but wintered south from the Central Plains to Mexico. At the end of their first year, hawks (n = 14) settled on spring ranges within their natal regions, an average of 350 km from their hatch locations. In their third spring, hawks (n = 6) settled an average of 123 km from hatch locations and two females nested. We ascribe differences in migration distance and timing of juvenile hawks relative to adults to juveniles' inexperience in locating suitable feeding areas and range prospecting independently from parents. Because migration patterns and regional fidelity of juvenile Ferruginous Hawks to settlement ranges were similar to those exhibited by adult hawks, the protection of fossorial prey and their habitats on seasonal ranges that promote survival of adult hawks will afford the same benefits to the juvenile cohorts. [ABSTRACT FROM AUTHOR]

Nomadism in birds is characterized by inconsistent and unpredictable migrations to breeding or nonbreeding areas often related to changing prey conditions. The Ferruginous Hawk (Buteo regalis) has been described as nomadic in studies that documented fluctuations in breeding territory occupancy and synchronous changes in prey abundance. However, documentation of tracked individuals engaged in nomadic movements is lacking and is important for evaluating population status. Between 1999 and 2014 we studied repeatability in patterns of interannual range occupancy and migration of radio-tagged, breeding adult Ferruginous Hawks (n = 33). We computed repeatability coefficients to test individual fidelity to seasonal ranges and migration paths, and timing of migrations among range-wide populations over multiple years (range = 2–6 yr). Hawks exhibited dramatic seasonal differences in annual repeatability of individual movements. During the post-breeding period in late summer, repeatability coefficients for annual range occupancy and migration path fidelity were low (r = 0.37), only 50% of hawks showed range fidelity, and hawks occupied multiple ranges (x̄ = 1.5 ± 0.2 ranges/yr). In contrast, repeatability was moderate to high (r ≥ 0.65) in the breeding season and winter, 83% and 87% of hawks showed range fidelity to respective ranges, and hawks occupied an average of one range each season. All hawks returned to the same breeding region each year. Variation attributed to differences between individuals was significant for most migration characteristics, providing evidence for flexibility within the species for individuals to adapt to different situations and conditions, but with each individual tending to follow the same patterns over multiple years. Seasonal nomadism in Ferruginous Hawks was limited to the post-breeding period in late summer, and we found no evidence for systematic nomadism in spring migration of Ferruginous Hawks that would confound interpretation of breeding population trends. However, we recommend further telemetry studies to simultaneously document migration repeatability for this species prior to and during dramatic prey declines. [ABSTRACT FROM AUTHOR]

Background: Severe falciparum malaria is a medical emergency characterised by potentially lethal vital organ dysfunction. Patient fatality rates even with parenteral artesunate treatment remain high. Despite considerable research into adjuvant therapies targeting organ and tissue dysfunction, none have shown efficacy apart from renal replacement therapy. Understanding the causal contributions of clinical and laboratory abnormalities to mortality is essential for the design and evaluation of novel therapeutic interventions.Methods and Findings: We used a structural model causal inference approach to investigate causal relationships between epidemiological, laboratory, and clinical variables in patients with severe falciparum malaria enrolled in clinical trials and their in-hospital mortality. Under this causal model, we analysed records from 9,040 hospitalised children (0-12 years, n = 5,635) and adults (n = 3,405, 12-87 years) with severe falciparum malaria from 15 countries in Africa and Asia who were studied prospectively over the past 35 years. On admission, patient covariates associated with increased in-hospital mortality were severity of acidosis (odds ratio [OR] 2.10 for a 7-mEq/L increase in base deficit [95% CI 1.93-2.28]), renal impairment (OR 1.71 for a 2-fold increase in blood urea nitrogen [95% CI 1.58, 1.86]), coma (OR 3.59 [95% CI 3.07-4.21]), seizures (OR 1.40 [95% CI 1.16-1.68]), shock (OR 1.51 [95% CI 1.14-1.99]), and presumed pulmonary oedema (OR 1.58 [95% CI 1.04-2.39]). Lower in-hospital mortality was associated with moderate anaemia (OR 0.87 for a decrease of 10 percentage points in haematocrit [95% CI 0.80-0.95]). Circulating parasite density was not associated with mortality (OR 1.02 for a 6-fold increase [95% CI 0.94-1.11]), so the pathological effects of parasitaemia appear to be mediated entirely by the downstream effects of sequestration. Treatment with an artemisinin derivative decreased mortality compared with quinine (OR 0.64 [95% CI 0.56-0.74]). These estimates were consistent across children and adults (mainly representing African and Asian patients, respectively). Using inverse probability weighting, transfusion was not estimated to be beneficial in children with admission haematocrit values between 15% and 25% (OR 0.99 [95% CI 0.97-1.02]). Except for the effects of artemisinin treatment and transfusion, causal interpretations of these estimates could be biased by unmeasured confounding from severe bacterial sepsis, immunity, and duration of illness.Conclusion: These data suggest that moderate anaemia is associated with a reduced risk of death in severe falciparum malaria. This is possibly a direct causal association. The severe anaemia threshold criteria for a definition of severe falciparum malaria should be reconsidered. [ABSTRACT FROM AUTHOR]