The costs of preventing and treating chagas disease in Colombia

Background: The objective of this study is to report the costs of Chagas disease in Colombia, in terms of vector disease control programmes and the costs of providing care to chronic Chagas disease patients with cardiomyopathy. Methods: Data were collected from Colombia in 2004. A retrospective review of costs for vector control programmes carried out in rural areas included 3,084 houses surveyed for infestation with triatomine bugs and 3,305 houses sprayed with insecticide. A total of 63 patient records from 3 different hospitals were selected for a retrospective review of resource use. Consensus methodology with local experts was used to estimate care seeking behaviour and to complement observed data on utilisation. Findings: The mean cost per house per entomological survey was $4.4 (in US$ of 2004), whereas the mean cost of spraying a house with insecticide was $27. The main cost driver of spraying was the price of the insecticide, which varied greatly. Treatment of a chronic Chagas disease patient costs between$46.4 and $7,981 per year in Colombia, depending on severity and the level of care used. Combining cost and utilisation estimates the expected cost of treatment per patient-year is$1,028, whereas lifetime costs averaged $11,619 per patient. Chronic Chagas disease patients have limited access to healthcare, with an estimated 22% of patients never seeking care. Conclusion: Chagas disease is a preventable condition that affects mostly poor populations living in rural areas. The mean costs of surveying houses for infestation and spraying infested houses were low in comparison to other studies and in line with treatment costs. Care seeking behaviour and the type of insurance affiliation seem to play a role in the facilities and type of care that patients use, thus raising concerns about equitable access to care. Preventing Chagas disease in Colombia would be cost-effective and could contribute to prevent inequalities in health and healthcare.Wellcome Trus

Signatures of arithmetic simplicity in metabolic network architecture

Metabolic networks perform some of the most fundamental functions in living cells, including energy transduction and building block biosynthesis. While these are the best characterized networks in living systems, understanding their evolutionary history and complex wiring constitutes one of the most fascinating open questions in biology, intimately related to the enigma of life's origin itself. Is the evolution of metabolism subject to general principles, beyond the unpredictable accumulation of multiple historical accidents? Here we search for such principles by applying to an artificial chemical universe some of the methodologies developed for the study of genome scale models of cellular metabolism. In particular, we use metabolic flux constraint-based models to exhaustively search for artificial chemistry pathways that can optimally perform an array of elementary metabolic functions. Despite the simplicity of the model employed, we find that the ensuing pathways display a surprisingly rich set of properties, including the existence of autocatalytic cycles and hierarchical modules, the appearance of universally preferable metabolites and reactions, and a logarithmic trend of pathway length as a function of input/output molecule size. Some of these properties can be derived analytically, borrowing methods previously used in cryptography. In addition, by mapping biochemical networks onto a simplified carbon atom reaction backbone, we find that several of the properties predicted by the artificial chemistry model hold for real metabolic networks. These findings suggest that optimality principles and arithmetic simplicity might lie beneath some aspects of biochemical complexity

Positive Interspecific Relationship between Temporal Occurrence and Abundance in Insects

One of the most studied macroecological patterns is the interspecific abundance–occupancy relationship, which relates species distribution and abundance across space. Interspecific relationships between temporal distribution and abundance, however, remain largely unexplored. Using data for a natural assemblage of tabanid flies measured daily during spring and summer in Nova Scotia, we found that temporal occurrence (proportion of sampling dates in which a species occurred in an experimental trap) was positively related to temporal mean abundance (number of individuals collected for a species during the study period divided by the total number of sampling dates). Moreover, two models that often describe spatial abundance–occupancy relationships well, the He–Gaston and negative binomial models, explained a high amount of the variation in our temporal data. As for the spatial abundance–occupancy relationship, the (temporal) aggregation parameter, k, emerged as an important component of the hereby named interspecific temporal abundance–occurrence relationship. This may be another case in which a macroecological pattern shows similarities across space and time, and it deserves further research because it may improve our ability to forecast colonization dynamics and biological impacts

Functional Polymorphisms in IL13 Are Protective against High Schistosoma mansoni Infection Intensity in a Brazilian Population

IL-13 is a signature cytokine of the helper T cell type 2 (TH2) pathway which underlies host defense to helminthic infection and activates production of IgE in both parasitized populations and in urban settings after allergen exposure.Two functional polymorphisms in IL13, rs1800925 (or c.1-1111C>T) and rs20541 (or R130Q) were previously found to be associated with Schistosoma hematobium infection intensity. They have not been thoroughly explored in S. mansoni-endemic populations, however, and were selected along with 5 tagging SNPs for genotyping in 812 individuals in 318 nuclear families from a schistosomiasis-endemic area of Conde, Bahia, in Brazil. Regression models using GEE to account for family membership and family-based quantitative transmission disequilibrium tests (QTDT) were used to evaluate associations with total serum IgE (tIgE) levels and S. mansoni fecal egg counts adjusted for non-genetic covariates. We identified a protective effect for the T allele at rs20541 (P = 0.005) against high S. mansoni egg counts, corroborated by QTDT (P = 0.014). Our findings also suggested evidence for protective effects for the T allele at rs1800925 and A allele at rs2066960 after GEE analysis only (P = 0.050, 0.0002).The two functional variants in IL13 are protective against high S. mansoni egg counts. These markers showed no evidence of association with tIgE levels, unlike tIgE levels previously studied in non-parasitized or atopic study populations

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Two-Year Longitudinal Analysis of a Cluster Randomized Trial of Physical Activity Promotion by General Practitioners

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Low frequency of TERT promoter mutations in gastrointestinal stromal tumors (GISTs).

Somatic mutations in the promoter region of telomerase reverse transcriptase (TERT) gene, mainly at positions c. − 124 and c. − 146 bp, are frequent in several human cancers; yet its presence in gastrointestinal stromal tumor (GIST) has not been reported to date. Herein, we searched for the presence and clinicopathological association of TERT promoter mutations in genomic DNA from 130 bona fide GISTs. We found TERT promoter mutations in 3.8% (5/130) of GISTs. The c. − 124C4T mutation was the most common event, present in 2.3% (3/130), and the c. − 146C4T mutation in 1.5% (2/130) of GISTs. No significant association was observed between TERT promoter mutation and patient’s clinicopathological features. The present study establishes the low frequency (4%) of TERT promoter mutations in GISTs. Further studies are required to confirm our findings and to elucidate the hypothetical biological and clinical impact of TERT promoter mutation in GIST pathogenesis.This project was partially supported by Barretos Cancer Hospital internal research funds (PAIP) and CNPq Universal Grant (476192/2013-7) to RMR. NCC is a recipient of an FAPESP Doctoral Fellowship (2013/25787-3). Further funding from the project ‘Microenvironment, metabolism and cancer’ that was partially supported by Programa Operacional Regional do Norte (ON.2—O Novo Norte) under the Quadro de Referência Estratégico Nacional (QREN) and the Fundo Europeu de Desenvolvimento Regional (FEDER). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education that is partially supported by the FCT

Allele-Specific Gene Expression Is Widespread Across the Genome and Biological Processes

Allelic specific gene expression (ASGE) appears to be an important factor in human phenotypic variability and as a consequence, for the development of complex traits and diseases. In order to study ASGE across the human genome, we have performed a study in which genotyping was coupled with an analysis of ASGE by screening 11,500 SNPs using the Mapping 10 K Array to identify differential allelic expression. We found that from the 5,133 SNPs that were suitable for analysis (heterozygous in our sample and expressed in peripheral blood mononuclear cells), 2,934 (57%) SNPs had differential allelic expression. Such SNPs were equally distributed along human chromosomes and biological processes. We validated the presence or absence of ASGE in 18 out 20 SNPs (90%) randomly selected by real time PCR in 48 human subjects. In addition, we observed that SNPs close to -but not included in- segmental duplications had increased levels of ASGE. Finally, we found that transcripts of unknown function or non-coding RNAs, also display ASGE: from a total of 2,308 intronic SNPs, 1510 (65%) SNPs underwent differential allelic expression. In summary, ASGE is a widespread mechanism in the human genome whose regulation seems to be far more complex than expected