Forage fermentation patterns and their implications for herbivore ingesta retention times

1. Differences in digestive physiology between browsing and grazing ruminant feeding types have been discussed extensively. The potentially underlying differences in fermentative behaviour of forage plants have received much less attention. 2. In this study, different groups of temperate forage plants (grasses, browse leaves and twigs, herbs and legumes) were compared in their chemical composition and fementative behaviour. They were evaluated via an in vitro fermentation system (modified Hohenheim gas test), and relevant fermentation parameters such as maximal gas production and relative gas production rate were calculated. 3. Grasses generally had a higher NDF (neutral detergent fibre = total cell wall) content than browse leaves, herbs and legumes, while browse leaf cell wall was more lignified than that of herbs, legumes and grass. 4. With respect to fermentation parameters, grass had the highest maximal gas production, followed by herbs and legumes, and the lowest maximal gas production in browse leaves and twigs. Relative gas production rate was highest in herbs and legumes, while that of grass and browse was lower. As expected, browse twigs had the lowest nutritional value. 5. Dicot material reached given setpoints of absolute gas production rate like 1.0 or 0.5 mL gas/(200 mg dry matter x h) faster than grass material. Based on these results, a longer passage time of food particles seems to be adaptive for grazing ruminants, as over a wide range of fermentation times, absolute gas production rate is higher in grass compared with dicots. Especially for browse leaves, a higher intake level should be expected to balance energy requirements of animals relying on this forage type

A likelihood ratio approach for utilizing case-control data in the clinical classification of rare sequence variants:Application to BRCA1 and BRCA2

A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance