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The process of identifying suitable genome-wide association (GWA) studies and formatting the data to calculate multiple polygenic risk scores on a single genome can be laborious. Here, we present a centralized polygenic risk score calculator currently containing over 250,000 genetic variant associations from the NHGRI-EBI GWAS Catalog for users to easily calculate sample-specific polygenic risk scores with comparable results to other available tools. Polygenic risk scores are calculated either online through the Polygenic Risk Score Knowledge Base (PRSKB; https://prs.byu.edu ) or via a command-line interface. We report study-specific polygenic risk scores across the UK Biobank, 1000 Genomes, and the Alzheimer's Disease Neuroimaging Initiative (ADNI), contextualize computed scores, and identify potentially confounding genetic risk factors in ADNI. We introduce a streamlined analysis tool and web interface to calculate and contextualize polygenic risk scores across various studies, which we anticipate will facilitate a wider adaptation of polygenic risk scores in future disease research.

Background: We compared dissociative seizure specific cognitive behavior therapy (DS-CBT) plus standardized medical care (SMC) to SMC alone in a randomized controlled trial. DS-CBT resulted in better outcomes on several secondary trial outcome measures at the 12-month follow-up point. The purpose of this paper is to evaluate putative treatment mechanisms. Methods: We carried out a secondary mediation analysis of the CODES trial. 368 participants were recruited from the National Health Service in secondary / tertiary care in England, Scotland, and Wales. Sixteen mediation hypotheses corresponding to combinations of important trial outcomes and putative mediators were assessed. Twelve-month trial outcomes considered were final-month seizure frequency, Work and Social Adjustment Scale (WSAS), and the SF-12v2, a quality-of-life measure providing physical (PCS) and mental component summary (MCS) scores. Mediators chosen for analysis at six months (broadly corresponding to completion of DS-CBT) included: (a) beliefs about emotions, (b) a measure of avoidance behavior, (c) anxiety and (d) depression. Results: All putative mediator variables except beliefs about emotions were found to be improved by DS-CBT. We found evidence for DS-CBT effect mediation for the outcome variables dissociative seizures (DS), WSAS and SF-12v2 MCS scores by improvements in target variables avoidance behavior, anxiety, and depression. The only variable to mediate the DS-CBT effect on the SF-12v2 PCS score was avoidance behavior. Conclusions: Our findings largely confirmed the logic model underlying the development of CBT for patients with DS. Interventions could be additionally developed to specifically address beliefs about emotions to assess whether it improves outcomes. [ABSTRACT FROM AUTHOR]

An ecologically sound approach to the problem of brush encroachment onto Israeli rangeland might be their utilization by goats, but better knowledge of the feeding selectivity and ability of goats to thrive in encroached areas is required to devise viable production systems. Direct observation of bites could provide precise and accurate estimates of diet selection, but construction of a sufficiently large database would require too much time. The present study describes the first attempt to construct fecal near-infrared reflectance spectroscopy (NIRS) calibrations of the botanical and nutritional composition of the diet, and of the total intake of free-ranging goats, based on reference values determined with bite-count procedures. Calibration of fecal NIRS was based on 43 observations encompassing 3 goat breeds and 4 periods (spring, summer, and fall of 2004, and spring of 2005). Each observation comprised 242 min of continuous recording of the species and bite-type category selected by a single animal, on each of 2 consecutive days. The mass and chemical quality of each species and bite-type category--a total of more than 200,000 bites--were determined by using the simulated bite technique. Associated feces were scanned in the 1,100- to 2,500-nm range with a reflectance monochromator. Fecal NIRS calibrations had reasonable precision for dietary percentages of the 3 main botanical components: herbaceous vegetation (as one category; [R.sup.2] = 0.85), Phillyrea latifolia ([R.sup.2] = 0.89), and tannin-rich Pistacia lentiscus ([R.sup.2] = 0.77), with SE of cross-validation (SECV) of 7.8, 6.3, and 5.6% of DM, respectively. The [R.sup.2] values for dietary percentages of CP, NDF, IVDMD, and polyethylene glycol-binding tannins were 0.93, 0.88, 0.91, and 0.74, respectively, with SECV values of 0.9, 2.1, 4.3, and 0.9% of DM, respectively. The [R.sup.2] values for intakes of herbaceous vegetation, P. latifolia, and P. lentiscus were 0.80, 0.75, and 0.65, with SECV values of 71, 64, and 46 g of DM/d, respectively. The [R.sup.2] values for the daily nutrient intakes were below 0.60. Fecal NIRS data can be used to expand the databases of botanical and nutritional dietary composition when observed and resident animals graze simultaneously, but intakes should be calculated from fecal NIRS-predicted dietary DM composition and an independent evaluation of DMI. Key words: browse, diet composition, feces, goat, near-infrared reflectance spectroscopy

Since Dirac stated his Large Number Hypothesis the space-time variation of fundamental constants has been an active subject of research. Here we analyze the possible spatial variation of two fundamental constants: the fine structure constant and the speed of light . We study the effects of such variations on the luminosity distance and on the peak luminosity of Type Ia supernovae (SNe Ia). For this, we consider the change of each fundamental constant separately and discuss a dipole model for its variation. Elaborating upon our previous work, we take into account the variation of the peak luminosity of Type Ia supernovae resulting from the variation of each of these fundamental constants. Furthermore, we also include the change of the energy release during the explosion, which was not studied before in the literature. We perform a statistical analysis to compare the predictions of the dipole model for and variation with the Union 2.1 and JLA compilations of SNe Ia. Allowing the nuisance parameters of the distance estimator and the cosmological density matter to vary. As a result of our analysis, we obtain a first estimate of the possible spatial variation of the speed of light . On the other hand, we find that there is no significant difference between the several phenomenological models studied here and the standard cosmological model, in which fundamental constants do not vary at all. Thus, we conclude that the actual set of data of Type Ia supernovae does not allow to verify the hypothetical spatial variation of fundamental constants. [ABSTRACT FROM AUTHOR]

In the context of determining the sustainable carrying capacity of dry-Mediterranean herbaceous rangelands, we examined the effect of animal density on cattle nutrition, which is fundamental to animal performance and welfare. The effects on dietary components of low (0.56 cows/ha; L) and high (1.11 cows/ha; H) animal densities were monitored for three consecutive years in grazing beef cows. In the dry season (summer and early autumn), cows had free access to N-rich poultry litter (PL) given as a dietary supplement. In each season, near-IR spectroscopy (NIRS) was used to predict the chemical composition of herbage samples (ash, NDF, CP, in vitro dry matter digestibility (IVDMD) and metabolizable energy (ME) content from IVDMD). Near-IR spectroscopy was applied also to faecal samples to determine the chemical composition of the diet selected by the animal, as well as the contents of ash, NDF and CP in the faeces themselves. A faecal-NIRS equation was applied to estimate the dietary proportion of PL. Seasonal categories were green, dry without PL supplementation and dry with it. We found no effects of animal density on nutrition during the green season but effects were apparent when cows consumed dry pasture. Ash content predicted by faecal NIRS was higher in the diet than in plant samples clipped from pasture, which infers that cows ingested soil. Dietary and faecal ash contents were higher (P<0.05) at the H, implying greater soil intake in these animals. During the dry period, dietary contents of ME were higher in L than in H (P<0.05). Poultry litter supplementation was associated with a marked increase (P<0.01) in dietary and faecal CP contents. Poultry litter represented 0.45 and 0.59 of the diet in treatments L and H, respectively (P<0.05). Consequently, treatment H had higher faecal protein (P<0.05). A tendency of higher dietary protein (P=0.08) and lower dietary NDF (P=0.10) in treatment H was probably related to greater PL ingestion. Given that high and sustained rates of poultry litter consumption are detrimental to animal health, the above results cast doubts on the long-term sustainability of the higher of the animal densities tested. Although it may be sustainable vis-à-vis the vegetation, treatment H may have exceeded the boundaries of what is acceptable for cow health. Chemical information revealed with NIRS can be used to evaluate whether animal densities are compatible with animal health and welfare standards and can play a role in determining the carrying capacity of Mediterranean rangelands. [ABSTRACT FROM PUBLISHER]

• Silage was made from willow trees irrigated with saline (EC 4) water. • Feeding willow silage at 200 g/kg DM did not affect goat milk yield or composition. • Milk from willow-fed goats contained more phenolic acids than controls. • Milk from both groups contained salicylic acid and saligenin but no flavonoids. • Milk from willow-fed goats contained more sulfated derivatives of phenolics. Willow trees irrigated with recycled water yields fodder of good nutritional value that can be ensiled to provide feed year-round for dairy goats. We investigated the nutritional value of silage from willow irrigated with saline water (Electrical Conductivity 4.0) in a cross-over experiment (twenty eight goats, two periods). We compared total dry matter intake (TDMI), milking performance and milk composition, with a focus on plant phenolic compounds, of Damascus goats fed oats and vetch hays as the sole source of roughage (all-hay) or oats hay with willow silage, with 470 g/kg DM concentrates. Willow silage represented 175 and 205 g/kg of TDMI in the last five days of periods 1 and 2, respectively. Individual TDMI tended (P <0.06) to be 3.7% lower in the willow-fed goats. Milk yield, and the milk contents and daily yields of fat, protein and lactose did not differ between treatments. However, willow consumption was associated with lower contents of milk urea (P <0.02) and 59% higher anti-oxidative capacity (P <0.04). Consumption of willow silage was associated with higher levels of plasma malondialdehyde, but did not affect leucocyte clustering. We assessed the contents of plant specialized metabolites (PSMs) in the feeds and in the milk of five goats of each treatment at the end of period 2 by liquid chromatography / time-of-flight / mass spectrometry (LC-TOF-MS), with exact or tentative compound identification, depending on availability of appropriate standards. Although many flavonoids were present in feeds, they were not found in the milk of either treatment. Major phenolic compounds, including the salicinoids salicin, esculetin and chaenomeloidin found in feeds, were not recovered in milk but salicylic acid, found in all feeds, was present equally in the milk of both control and treated goats. Only two compounds directly related to the metabolism of salicin, i.e., salicylic acid and saligenin, were found in milk. Overall, milk from willow silage-fed goats contained more phenolic compounds, including benzyl alcohol, hydroquinone, methyl-syringate (P <0.001), and a saligenin derivative (P <0.005), and tended to contain more 4-hydroxybenzoic acid and hippuric acid (P <0.10) than milk from all-hay fed goats. Volcano plot-to-target changes in milk metabolites related to willow (untargeted LC-TOF-MS) showed intense upregulation of sulfated derivatives of phenolics. Growing willow for silage for dairy goats is an appropriate way to produce feed where saline water irrigation is available. [ABSTRACT FROM AUTHOR]