A 0.8V, 7μA, rail-to-rail input/output, constant Gm operational amplifier in standard digital 0.18μm CMOS

A two-stage amplifier, operational at 0.8V and drawing 7/spl mu/A, has been integrated in a standard digital 0.18/spl mu/m CMOS process. Rail-to-rail operations at the input are enabled by complementary transistor pairs with g/sub m/ control. The efficient rail-to-rail output stage is biased in class AB. The measured DC gain of the amplifier is 75dB, and the unity-gain frequency is 870kHz with a 12pF, 100k/spl Omega/load. Both input and output stage transistors are biased in weak inversion

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes.

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs

CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

Funder: Breast Cancer Now (BCN); doi: https://doi.org/10.13039/100009794Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265Funder: U.S. Department of Health & Human Services | National Institutes of Health (NIH)Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): HEALTH-F2-2009-223175, HEALTH-F2-2009-223175Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada); doi: https://doi.org/10.13039/501100000024Funder: Quebec Breast cancer Foundation Genome QuebecFunder: U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM); doi: https://doi.org/10.13039/100000092Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))Funder: European Union’s Horizon 2020Funder: Deutsche Krebshilfe (German Cancer Aid); doi: https://doi.org/10.13039/501100005972Funder: BCAST - European Union’s Horizon 2020Funder: Breast Cancer Now; doi: https://doi.org/10.13039/501100007913Abstract: Background: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Methods: We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. Results: For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (−49.2%, 95% CI −56.1% to −41.1%, P = 3.1 × 10–18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (−26.7%, 95% CI −39.4% to −11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82–0.91, P = 6.9 × 10–8). Conclusions: The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women

Aantasten van peulvruchten door insekten, schimmels, breuk en dergelijke

The enzymatic digestibility of organic matter (EDOM) method is an in vitro multi-enzymatic method for estimating the organic matter (OM) digestibility of feeds. The EDOM method previously showed high accuracy with in vivo values for compound feeds. The aim of this study was to evaluate the precision of the EDOM method and determine its additivity, compared with the long-assumed additive property of the chemical components of compound feeds. 149 feed samples, 70 commercial compound feeds and 79 associated ingredients, were analyzed in a laboratory (lab1) for OM digestibility measured by EDOM (OMDEDOM) with 2 repetitions separated in time to estimate repeatability. Of the total samples, 49 compound feeds were further analyzed in a commercial laboratory (lab2) for OMDEDOM to determine reproducibility. The 49 compounds and their 69 associated ingredients were also analyzed by lab2 for dry matter (DM), ash, crude protein (CP), neutral detergent fiber (NDF), and starch. The EDOM method resulted in an intralaboratory correlation of 98.9% and an interlaboratory correlation of 92.6%, with no significant mean bias between the 2 laboratories tested. The formulation of compound feeds, total mixed rations, and mixtures in general assumes that their nutrient content can be calculated by adding together the nutrient supply of individual ingredients. This is of great importance in the feed industry for the creation of compound feeds. Additivity of OMDEDOM for the compound feed samples was evaluated by comparing the sum of the digestible OM (DOMEDOM) of the ingredients (predicted) with DOMEDOM estimated directly in the compound feed (observed). The regression of predicted versus observed showed a coefficient of determination (R2) of 0.93 and root mean square error (RMSE) of 1.07% of total DM, with no linear bias but with a mean bias (0.83% of DM). Additivity of CP, starch, crude fat, and NDF showed an R2 of 0.95, 0.98, 0.95, and 0.93, and RMSE of 1.56, 1.90, 0.39, and 1.46% of DM, respectively, all presenting linear bias. Crude fat also presented mean bias. Although significant, all linear and mean bias for DOMEDOM and chemical components were within the acceptable error limits for declaration of feeds. The results demonstrate the high precision of the EDOM method and its additive property, which is an advantage for the estimation of OM digestibility in compound feeds. Moreover, results of the tests of chemical components confirm their additive property