Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17 : analysis for the Global Burden of Disease Study 2017

Background Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. Findings The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1–65·8), 17·4% (7·7–28·4), and 59·5% (34·2–86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. Interpretation By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health

Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine

Development of Nuclear Analysis Capabilities for DOE Waste Management Activities

The objective of this project is to develop and demonstrate prototypical analysis capabilities that can be used by nuclear safety analysis practitioners to: (1) demonstrate a more thorough understanding of the underlying physics phenomena that can lead to improved reliability and defensibility of safety evaluations; and (2) optimize operations related to the handling, storage, transportation, and disposal of fissile material and DOE spent fuel. To address these problems, this project has been investigating the implementation of sensitivity and uncertainty methods within existing Monte Carlo codes used for criticality safety analyses. It is also investigating the use of a new deterministic code that allows for specification of arbitrary grids to accurately model geometric details required in a criticality safety analysis. This capability can facilitate improved estimations of the required subcritical margin and potentially enable the use of a broader range of experiments in the validation process. The new arbitrary grid radiation transport code will also enable detailed geometric modeling valuable for improved accuracy in application to a myriad of other problems related to waste characterization. Application to these problems will also be explored. RESEARCH PROGRESS AND IMPLICATION

EMSP project summary (Project ID: 60077): Development of nuclear analysis capabilities for DOE waste management activities

The objective of this project is to develop and demonstrate prototypical analysis capabilities that can be used by nuclear safety analysis practitioners to: (1) demonstrate a more thorough understanding of the underlying physics phenomena that can lead to improved reliability and defensibility of safety evaluations; and (2) optimize operations related to the handling, storage, transportation, and disposal of fissile material and DOE spent fuel. To address these problems, this project has been investigating the implementation of sensitivity and uncertainty methods within existing Monte Carlo codes used for criticality safety analyses. It is also investigating the use of a new deterministic code that allows for specification of arbitrary grids to accurately model geometric details required in a criticality safety analysis. This capability can facilitate improved estimations of the required subcritical margin and potentially enable the use of a broader range of experiments in the validation process. The new arbitrary-grid radiation transport code will also enable detailed geometric modeling valuable for improved accuracy in application to a myriad of other problems related to waste characterization. Application to these problems will also be explored

Quantifying phenotypic plasticity of berry traits using an allometric-type approach: A case study on anthocyanins and sugars in berries of Cabernet Sauvignon

The definitive version is available at www.blackwell-synergy.comIn this paper we advance a novel allometric-type approach to quantify the stability of key berry traits viz. anthocyanins and sugars. To test the concept, we used data from Cabernet Sauvignon grown in a hot environment of South Australia. Sources of variation in berry traits included water supply, fruit load, seasonal conditions and their interactions. Anthocyanins and sugars were measured in berry samples taken 7–8 times between veraison and harvest. Rates and durations of accumulation of anthocyanins and sugars per berry were derived from a bi-linear model between amount of compound and thermal time. We develop a framework based on ‘α’ a parameter representing the slope of the regression between rate and duration in a log-log scale. This relationship accommodates three conditions viz. (a) potentially plastic, rate-driven trait (α –1), (b) potentially plastic, duration-driven trait (α < –1), and (c) a stable trait, whereby variation in rate and variation in duration cancel each other (α = –1). Under our experimental conditions, amount of anthocyanins (range of variation 148%) was more plastic than amount of sugars per berry (range of variation 37%). The slope α captured the differential plasticity of these traits: α was significantly greater than –1 for anthocyanins and statistically undistinguishable from –1 for sugars. The rate-dominated accumulation of anthocyanins explained the relatively large variation in this constituent whereas the tightly coupled, inverse relationship between duration and rate (α –1) explained the relative stability of sugars per berry. We conclude that our allometric-type relationship between rate and duration allows for the quantification of cultivar-environment specific plasticity of important berry traits.V.O. Sadras, R.M. Stevens, J.M. Pech, E.J. Taylor, P.R. Nicholas, M.G. McCarth

A Holocene record of human induced and natural environmental change from Lake Forsyth (Te Wairewa), New Zealand

A 1.2 m sediment core from Lake Forsyth, Canterbury, New Zealand, records the development of the catchment/lake system over the last 7000 years, and its response to anthropogenic disturbance following European settlement c. 1840 AD. Pollen was used to reconstruct catchment vegetation history, while foraminifera, chironomids, Trichoptera, and the abundance of Pediastrum simplex colonies were used to infer past environmental conditions within the lake. The basal 30 cm of core records the transition of the Lake Forsyth Basin from a tidal embayment to a brackish coastal lake. Timing of closure of the lake mouth could not be accurately determined, but it appears that Lake Forsyth had stabilised as a slightly brackish, oligo-mesotrophic shallow lake by about 500 years BP. Major deforestation occurred on Banks Peninsula between 1860 AD and 1890 AD. This deforestation is marked by the rapid decline in the main canopy trees (Prumnopitys taxifolia (matai) and Podocarpus totara/hallii (totara/mountain totara), an increase in charcoal, and the appearance of grasses. At around 1895 AD, pine appears in the record while a willow (Salix spp.) appears somewhat later. Redundancy analysis (RDA) of the pollen and aquatic species data revealed a significant relationship between regional vegetation and the abundance of aquatic taxa, with the percentage if disturbance pollen explaining most (14.8%) of the constrained variation in the aquatic species data. Principle components analysis (PCA) of aquatic species data revealed that the most significant period of rapid biological change in the lakes history corresponded to the main period of human disturbance in the catchment. Deforestation led to increased sediment and nutrient input into the lake which was accompanied by a major reduction in salinity. These changes are inferred from the appearance and proliferation of freshwater algae (Pediastrum simplex), an increase in abundance and diversity of chironomids, and the abundance of cases and remains from the larvae of the caddisfly, Oecetis unicolor. Eutrophication accompanied by increasing salinity of the lake is inferred from a significant peak and then decline of P. simplex, and a reduction in the abundance and diversity of aquatic invertebrates. The artificial opening of the lake to the Pacific Ocean, which began in the late 1800s, is the likely cause of the recent increase in salinity. An increase in salinity may have also encouraged blooms of the halotolerant and hepatotoxic cyanobacteria Nodularia spumigena