• Jackson Klavsen posted an update 6 months, 3 weeks ago

    Early changes in biomarker levels probably occur before bloodstream infection (BSI) is diagnosed. However, this issue has not been fully addressed. We aimed at evaluating the kinetics of C-reactive protein (CRP) and plasma albumin (PA) in the 30 days before community-acquired (CA) BSI diagnosis. From a population-based BSI database we identified 658 patients with at least one measurement of CRP or PA from day -30 (D-30) through day -1 (D-1) before the day of CA-BSI (D0) and a measurement of the same biomarker at D0 or D1. Amongst these, 502 had both CRP and PA measurements which fitted these criteria. CRP and PA concentrations began to change inversely some days before CA-BSI diagnosis, CRP increasing by day -3.1 and PA decreasing by day -1.3. From D-30 to D-4, CRP kinetics (expressed as slopes – rate of concentration change per day) was -1.5 mg/l/day. From D-3 to D1, the CRP slope increased to 36.3 mg/l/day. For albumin, the slope between D-30 to D-2 was 0.1 g/l/day and changed to -1.8 g/l/day between D-1 and D1. We showed that biomarker levels begin to change some days before the CA-BSI diagnosis, CRP 3.1 days and PA 1.3 days before.BACKGROUND. Current approaches for early identification of individuals at high risk for autism spectrum disorder (ASD) in the general population are limited, and most ASD patients are not identified until after the age of 4. This is despite substantial evidence suggesting that early diagnosis and intervention improves developmental course and outcome. The aim of the current study was to test the ability of machine learning (ML) models applied to electronic medical records (EMRs) to predict ASD early in life, in a general population sample. METHODS. We used EMR data from a single Israeli Health Maintenance Organization, including EMR information for parents of 1,397 ASD children (ICD-9/10) and 94,741 non-ASD children born between January 1st, 1997 and December 31st, 2008. Routinely available parental sociodemographic information, parental medical histories, and prescribed medications data were used to generate features to train various ML algorithms, including multivariate logistic regression, artificial neural networks, and random forest. Prediction performance was evaluated with 10-fold cross-validation by computing the area under the receiver operating characteristic curve (AUC; C-statistic), sensitivity, specificity, accuracy, false positive rate, and precision (positive predictive value ). RESULTS. All ML models tested had similar performance. The average performance across all models had C-statistic of 0.709, sensitivity of 29.93%, specificity of 98.18%, accuracy of 95.62%, false positive rate of 1.81%, and PPV of 43.35% for predicting ASD in this dataset. CONCLUSIONS. We conclude that ML algorithms combined with EMR capture early life ASD risk as well as reveal previously unknown features to be associated with ASD-risk. Such approaches may be able to enhance the ability for accurate and efficient early detection of ASD in large populations of children.Estimates of the components of nutrient intake variation are needed for modeling distributions of usual intake or predicting the usual intake of individuals. Season is a potential source of variation in nutrient intakes in addition to within- and between-person variation, particularly in low- or middle-income countries. We aimed to describe seasonal variation in nutrient intakes and estimate within-person, between-person and other major components of intake variance among Zambian children. Children from rural villages and peri-urban towns in Mkushi District, Zambia aged 4 to 8 years were enrolled in the non-intervened arm of a randomized controlled trial of pro-vitamin A carotenoid biofortified maize (n=200). Up to seven 24-hour dietary recalls per child were obtained at monthly intervals over a six-month period covering the late post-harvest (August-October), early lean (November-January) and late lean (February-April) seasons (2012-2013). Nutrient intakes varied significantly by season. For energy and most nutrients, intakes were highest in the early lean season and lower in the late post-harvest and late lean seasons. Season and recall on a market day had the strongest effects on nutrient intakes among covariates examined. Unadjusted within- to between-person variance ratios ranged from 4.5 to 31.3. In components of variance models, season accounted for 3% to 20% of nutrient intake variance. Particularly in rural settings in low- and middle-income countries, where availability of locally-grown, nutrient-rich foods may vary seasonally, studies should include replicates across seasons to more precisely estimate long-term usual intakes.Digenean larvae of hermaphroditic generation – cercariae – are known to be polymorphic at genetic and behavioural levels. Cercariae arise as a result of parthenogenetic reproduction of intramolluscan stages, and represent a clone if a snail was infected with a single miracidium. Entospletinib purchase Here we investigated cercarial clones of Himasthla elongata – namely, the infectivity of cercariae with normal (negative) and deviant (positive) photoreaction. In our study, most H. elongata clones showed intraclonal variance in their response to light. The proportion of photopositive cercariae ranged between 0.2% and 60% in different H. elongata clones. Photopositive larvae demonstrated significantly reduced rates of encystment in Mytilus edulis haemolymph in vitro and in young mussels. We discuss the possible mechanisms behind intraclonal variations, such as non-specific genomic rearrangements.The only generally accepted treatment of coeliac disease (CD) is a lifelong gluten-free diet (GFD). Wheat gluten proteins include gliadins, low (LMWG) and high molecular weight glutenins (HMWG). However, we have found significant structural variations within these protein families among different cultivars. To determine which structural motifs might be less toxic than others, we assessed five variants of α-gliadin immuno-dominant CD-toxic peptides synthesised as 16mers in CD T cell stimulation assays with gluten-sensitive T cell lines generated from duodenal biopsies from CD affected individuals. The peptides harboured the overlapping T cell epitopes DQ 2.5-glia-α-2 and naturally occurring variants that differed in certain amino acids (AA). The results revealed that introduction of two selected AA substitutions in α-gliadin peptides reduced immunogenicity. A peptide with three AA substitutions involving two glutamic acids (E) and one glutamine residue (G) revealed the peptide was negative in 55 samples. We used CD small intestinal organ culture to assess CD toxicity that revealed two peptides with selected substitution of both glutamic acid (E) and proline (P) residues abrogated evidence of CD toxicity.

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