Increased levels of amino acid neurotransmitters in the inferior colliculus of the genetically epilepsy-prone rat.

Previous studies have shown an increase in the number of GABAergic and total neurons in the inferior colliculus (IC) of the genetically epilepsy-prone rat (GEPR). Amino acid analysis of the central nucleus of the IC, as well as cerebellum, sensorimotor, temporal, and occipital cerebral cortices of GEPRs with high pressure liquid chromatography showed significant increases in the levels of GABA, taurine and glutamate. The IC of GEPR displayed a 2.3-fold increase in GABA as compared to that of non-epileptic rats, a 2.4-fold increase of taurine, and a 1.9-fold increase of glutamate. In addition, taurine and glutamate were increased in the sensorimotor and temporal cortex, respectively. These results are consistent with previous anatomical data on the GABAergic system in the IC and provide additional information. The increase in taurine and glutamate in the IC indicates that other neurotransmitters could be involved in the mechanism of seizure activity

A Year in the Life of the OpenECG Network

The OpenECG network formed in 2002, is a European initiative with global reach, which aims to lower the barriers for ECG interoperability and make digital ECGs available as part of the integrated electronic health record. Currently, SCP-ECG, the European standard for ECG record communication and storage, has been implemented by some manufacturers. However, these implementations are not consistent with each other, hindering ECG exchange, processing, and serial analysis. Furthermore, the presence of alternative ECG storage formats, proprietary or open, raises issues of harmonization and quality assurance. In the first year of its life, the OpenECG network numbers 105 committed members, while its portal and associated help desk have already provided valuable information and development support to several manufacturers and integrators. Recently, the OpenECG certification service has become available to members who may submit their ECG records for interoperability validation and SCP-ECG conformance testing. Still, only the first step for the OpenECG network has been taken. Future plans involve contributing to the definition of integration profiles for ECG-related examinations and addressing issues related to quality assurance of eHealth services in general

Impact of High, Low, and Non-Optimum Temperatures On Chronic Kidney Disease in a Changing Climate, 1990-2019: a Global analysis

BACKGROUND: Although a few studies have reported the relationship between high and low temperatures and chronic kidney disease (CKD), the global burden of CKD attributable to extreme heat and cold in recent decades remains unknown. METHODS: Based on the Global Burden of Disease Study (GBD) 2019, we obtained data on age-standardized mortality rates (ASMR) and age-standardized rates of disability-adjusted life years (ASDR) per 100 000 population of the CKD attributable to non-optimum temperatures from 1990 to 2019. The annual mean temperature of each country was used to divide each country into five climate zones (tropical, subtropical, warm-temperate, cool-temperate, and boreal). The locally weighted regression model was used to estimate the burden for different climate zones and Socio-demographic index (SDI) regions. RESULTS: In 1990, the ASMR and ASDR due to high temperature estimated -0.01 (95% UI, -0.74 to 0.44) and -0.32 (-21.66 to 12.66) per 100 000 population, respectively. In 2019, the ASMR and ASDR reached 0.10 (-0.28 to 0.38) and 2.71 (-8.07 to 10.46), respectively. The high-temperature burden increased most rapidly in tropical and low SDI regions. There were 0.99 (0.59 to 1.39) ASMR attributable to low-temperature in 1990, which increased to 1.05 (0.61-1.49) in 2019. While the ASDR due to low temperature declined from 22.03 (12.66 to 30.64) in 1990 to 20.43 (11.30 to 29.26) in 2019. Overall, the burden of CKD attributable to non-optimal temperatures has increased from 1990 to 2019. CKD due to hypertension and diabetes mellitus were the primary causes of CKD death attributable to non-optimum temperatures in 2019 with males and older adults being more susceptible to these temperatures. CONCLUSIONS: The CKD burden due to high, low, and non-optimum temperatures varies considerably by regions and countries. The burden of CKD attributable to high temperature has been increasing since 1990

Sensitivity of Modeled CO2 Air–Sea Flux in a Coastal Environment to Surface Temperature Gradients, Surfactants, and Satellite Data Assimilation

This work evaluates the sensitivity of CO2 air–sea gas exchange in a coastal site to four different model system configurations of the 1D coupled hydrodynamic–ecosystem model GOTM–ERSEM, towards identifying critical dynamics of relevance when specifically addressing quantification of air–sea CO2 exchange. The European Sea Regional Ecosystem Model (ERSEM) is a biomass and functional group-based biogeochemical model that includes a comprehensive carbonate system and explicitly simulates the production of dissolved organic carbon, dissolved inorganic carbon and organic matter. The model was implemented at the coastal station L4 (4 nm south of Plymouth, 50°15.00’N, 4°13.02’W, depth of 51 m). The model performance was evaluated using more than 1500 hydrological and biochemical observations routinely collected at L4 through the Western Coastal Observatory activities of 2008—2009. In addition to a reference simulation (A), we ran three distinct experiments to investigate the sensitivity of the carbonate system and modeled air–sea fluxes to (B) the sea-surface temperature (SST) diurnal cycle and thus also the near-surface verticalgradients,(C)biologicalsuppressionofgasexchangeand(D)dataassimilationusingsatellite Earth observation data. The reference simulation captures well the physical environment (simulated SST has a correlation with observations equal to 0.94 with a p > 0.95). Overall, the model captures the seasonal signal in most biogeochemical variables including the air–sea flux of CO2 and primary production and can capture some of the intra-seasonal variability and short-lived blooms. The model correctlyreproducestheseasonalityofnutrients(correlation>0.80forsilicate,nitrateandphosphate), surface chlorophyll-a (correlation > 0.43) and total biomass (correlation > 0.7) in a two year run for 2008–2009. The model simulates well the concentration of DIC, pH and in-water partial pressure of CO2 (pCO2) with correlations between 0.4–0.5. The model result suggest that L4 is a weak net source of CO2 (0.3–1.8 molCm−2 year−1). The results of the three sensitivity experiments indicate that both resolving the temperature profile near the surface and assimilation of surface chlorophyll-a significantlyimpacttheskillofsimulatingthebiogeochemistryatL4andallofthecarbonatechemistry related variables. These results indicate that our forecasting ability of CO2 air–sea flux in shelf seas environments and their impact in climate modeling should consider both model refinements as means of reducing uncertainties and errors in any future climate projections

FRA2A is a CGG repeat expansion associated with silencing of AFF3

Folate-sensitive fragile sites (FSFS) are a rare cytogenetically visible subset of dynamic mutations. Of the eight molecularly characterized FSFS, four are associated with intellectual disability (ID). Cytogenetic expression results from CGG tri-nucleotide-repeat expansion mutation associated with local CpG hypermethylation and transcriptional silencing. The best studied is the FRAXA site in the FMR1 gene, where large expansions cause fragile X syndrome, the most common inherited ID syndrome. Here we studied three families with FRA2A expression at 2q11 associated with a wide spectrum of neurodevelopmental phenotypes. We identified a polymorphic CGG repeat in a conserved, brain-active alternative promoter of the AFF3 gene, an autosomal homolog of the X-linked AFF2/FMR2 gene: Expansion of the AFF2 CGG repeat causes FRAXE ID. We found that FRA2A-expressing individuals have mosaic expansions of the AFF3 CGG repeat in the range of several hundred repeat units. Moreover, bisulfite sequencing and pyrosequencing both suggest AFF3 promoter hypermethylation. cSNP-analysis demonstrates monoallelic expression of the AFF3 gene in FRA2A carriers thus predicting that FRA2A expression results in functional haploinsufficiency for AFF3 at least in a subset of tissues. By whole-mount in situ hybridization the mouse AFF3 ortholog shows strong regional expression in the developing brain, somites and limb buds in 9.5-12.5dpc mouse embryos. Our data suggest that there may be an association between FRA2A and a delay in the acquisition of motor and language skills in the families studied here. However, additional cases are required to firmly establish a causal relationship

Learning from crowds in digital pathology using scalable variational Gaussian processes

This work was supported by the Agencia Estatal de Investigacion of the Spanish Ministerio de Ciencia e Innovacion under contract PID2019-105142RB-C22/AEI/10.13039/501100011033, and the United States National Institutes of Health National Cancer Institute Grants U01CA220401 and U24CA19436201. P.M. contribution was mostly before joining Microsoft Research, when he was supported by La Caixa Banking Foundation (ID 100010434, Barcelona, Spain) through La Caixa Fellowship for Doctoral Studies LCF/BQ/ES17/11600011.The volume of labeled data is often the primary determinant of success in developing machine learning algorithms. This has increased interest in methods for leveraging crowds to scale data labeling efforts, and methods to learn from noisy crowd-sourced labels. The need to scale labeling is acute but particularly challenging in medical applications like pathology, due to the expertise required to generate quality labels and the limited availability of qualified experts. In this paper we investigate the application of Scalable Variational Gaussian Processes for Crowdsourcing (SVGPCR) in digital pathology. We compare SVGPCR with other crowdsourcing methods using a large multi-rater dataset where pathologists, pathology residents, and medical students annotated tissue regions breast cancer. Our study shows that SVGPCR is competitive with equivalent methods trained using goldstandard pathologist generated labels, and that SVGPCR meets or exceeds the performance of other crowdsourcing methods based on deep learning. We also show how SVGPCR can effectively learn the class-conditional reliabilities of individual annotators and demonstrate that Gaussian-process classifiers have comparable performance to similar deep learning methods. These results suggest that SVGPCR can meaningfully engage non-experts in pathology labeling tasks, and that the classconditional reliabilities estimated by SVGPCR may assist in matching annotators to tasks where they perform well.Agencia Estatal de Investigacion of the Spanish Ministerio de Ciencia e Innovacion PID2019-105142RB-C22/AEI/10.13039/501100011033United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) U01CA220401 U24CA19436201La Caixa Banking Foundation (Barcelona, Spain) Barcelona, Spain) through La Caixa Fellowship 100010434 LCF/BQ/ES17/1160001

ACTIVIDAD FÍSICA Y ORIENTACIÓN NUTRICIONAL PARA NIÑOS CON SOBREPESO Y OBESIDAD

La actividad física realizada de forma regular y sistemática ha demostrado ser una práctica sumamente beneficiosa en la prevención, desarrollo y rehabilitación de la salud. Este artículo ofrece el resultado de un trabajo de investigación enmarcado dentro de un diseño experimental con mediciones pre y post intervención en un solo grupo. El objetivo del trabajo, fue evaluar un programa piloto, denominado taller balón con orientación nutricional, que promueve beneficios para niños con obesidad y sobrepeso, con la práctica de la actividad física. De una población de 234 escolares, a quienes se les midió talla, peso y nivel de actividad física, se encontraron 60 niños con diagnóstico de sobrepeso u obesidad. De este grupo, sólo 24 aceptaron participar en el taller y lo terminaron. A estos sujetos de estudio se les midió su perfil lipídico (triglicéridos, colesterol total, colesterol de HDL, colesterol de LDL). Los resultados mostraron que un porcentaje importante de la muestra tuvo al inicio valores elevados de alguno de sus lípidos sanguíneos y 85 % mantenían niveles de actividad física inferior a lo recomendado. Tras doce semanas de intervención se encontró una diferencia estadísticamente significativa para los valores de Col-LDL y ZIMC/edad

An entropy test for single-locus genetic association analysis

<p>Abstract</p> <p>Background</p> <p>The etiology of complex diseases is due to the combination of genetic and environmental factors, usually many of them, and each with a small effect. The identification of these small-effect contributing factors is still a demanding task. Clearly, there is a need for more powerful tests of genetic association, and especially for the identification of rare effects</p> <p>Results</p> <p>We introduce a new genetic association test based on symbolic dynamics and symbolic entropy. Using a freely available software, we have applied this entropy test, and a conventional test, to simulated and real datasets, to illustrate the method and estimate type I error and power. We have also compared this new entropy test to the Fisher exact test for assessment of association with low-frequency SNPs. The entropy test is generally more powerful than the conventional test, and can be significantly more powerful when the genotypic test is applied to low allele-frequency markers. We have also shown that both the Fisher and Entropy methods are optimal to test for association with low-frequency SNPs (MAF around 1-5%), and both are conservative for very rare SNPs (MAF<1%)</p> <p>Conclusions</p> <p>We have developed a new, simple, consistent and powerful test to detect genetic association of biallelic/SNP markers in case-control data, by using symbolic dynamics and symbolic entropy as a measure of gene dependence. We also provide a standard asymptotic distribution of this test statistic. Given that the test is based on entropy measures, it avoids smoothed nonparametric estimation. The entropy test is generally as good or even more powerful than the conventional and Fisher tests. Furthermore, the entropy test is more computationally efficient than the Fisher's Exact test, especially for large number of markers. Therefore, this entropy-based test has the advantage of being optimal for most SNPs, regardless of their allele frequency (Minor Allele Frequency (MAF) between 1-50%). This property is quite beneficial, since many researchers tend to discard low allele-frequency SNPs from their analysis. Now they can apply the same statistical test of association to all SNPs in a single analysis., which can be especially helpful to detect rare effects.</p

Yearly variation coupled with social interactions shape the skin microbiome in free-ranging rhesus macaques

This is the final version. Available on open access from the American Society for Microbiology via the DOI in this recordAll data analysis scripts can be found here: https://github.com/CayoBiobankResearchUnit/macaque-skin-microbiome.gitWhile skin microbes are known to mediate human health and disease, there has been minimal research on the interactions between skin microbiota, social behavior, and year-to-year effects in non-human primates—important animal models for translational biomedical research. To examine these relationships, we analyzed skin microbes from 78 rhesus macaques living on Cayo Santiago Island, Puerto Rico. We considered age, sex, and social group membership, and characterized social behavior by assessing dominance rank and patterns of grooming as compared to nonsocial behaviors. To measure the effects of a shifting environment, we sampled skin microbiota (based on sequence analysis of the 16S rRNA V4 region) and assessed weather across sampling periods between 2013 and 2015. We hypothesized that, first, monkeys with similar social behavior and/or in the same social group would possess similar skin microbial composition due, in part, to physical contact, and, second, microbial diversity would differ across sampling periods. We found significant phylum-level differences between social groups in the core microbiome as well as an association between total grooming rates and alpha diversity in the complete microbiome, but no association between microbial diversity and measures of rank or other nonsocial behaviors. We also identified alpha and beta diversity differences in microbiota and differential taxa abundance across two sampling periods. Our findings indicate that social dynamics interact with yearly environmental changes to shape the skin microbiota in rhesus macaques, with potential implications for understanding the factors affecting the microbiome in humans, which share many biological and social characteristics with these animals.National Institutes of Healt

Reliability and validity of three questionnaires measuring context-specific sedentary behaviour and associated correlates in adolescents, adults and older adults

BACKGROUND: Reliable and valid measures of total sedentary time, context-specific sedentary behaviour (SB) and its potential correlates are useful for the development of future interventions. The purpose was to examine test-retest reliability and criterion validity of three newly developed questionnaires on total sedentary time, context-specific SB and its potential correlates in adolescents, adults and older adults. METHODS: Reliability and validity was tested in six different samples of Flemish (Belgium) residents. For the reliability study, 20 adolescents, 22 adults and 20 older adults filled out the age-specific SB questionnaire twice. Test-retest reliability was analysed using Kappa coefficients, Intraclass Correlation Coefficients and/or percentage agreement, separately for the three age groups. For the validity study, data were retrieved from 62 adolescents, 33 adults and 33 older adults, with activPAL as criterion measure. Spearman correlations and Bland-Altman plots (or non-parametric approach) were used to analyse criterion validity, separately for the three age groups and for weekday, weekend day and average day. RESULTS: The test-retest reliability for self-reported total sedentary time indicated following values: ICC = 0.37-0.67 in adolescents; ICC = 0.73-0.77 in adults; ICC = 0.68-0.80 in older adults. Item-specific reliability results (e.g. context-specific SB and its potential correlates) showed good-to-excellent reliability in 67.94%, 68.90% and 66.38% of the items in adolescents, adults and older adults respectively. All items belonging to sedentary-related equipment and simultaneous SB showed good reliability. The sections of the questionnaire with lowest reliability were: context-specific SB (adolescents), potential correlates of computer use (adults) and potential correlates of motorized transport (older adults). Spearman correlations between self-reported total sedentary time and the activPAL were different for each age group: rho = 0.02-0.42 (adolescents), rho = 0.06-0.52 (adults), rho = 0.38-0.50 (older adults). Participants over-reported total sedentary time (except for weekend day in older adults) compared to the activPAL, for weekday, weekend day and average day respectively by +57.05%, +46.29%, +53.34% in adolescents; +40.40%, +19.15%, +32.89% in adults; +10.10%, -6.24%, +4.11% in older adults. CONCLUSIONS: The questionnaires showed acceptable test-retest reliability and criterion validity. However, over-reporting of total SB was noticeable in adolescents and adults. Nevertheless, these questionnaires will be useful in getting context-specific information on SB