Determining in vivo ruminal stability of three ruminally protected nutrients in lactating Jersey cows

Current methods to determine rumen escape (as stability) of rumen protected nutrients(RPNU), such as ruminal in situ evaluation, only estimate the rate at which nutrients leavethe in situ bag (rather than the rumen) and thus can provide only a rough estimate ofactual rumen stability, which is also impacted by actual ruminal RPNU release rate, rateof ruminal passage of the RPNU, as well as impacts of ruminative chewing on the RPNUproduct; all of which can only be estimated. The aim of our study was to use a novel invivo dual liquid phase marker technique to measure actual ruminal stability of three fatcoated RPNU products, and to determine if a common in situ incubation time could matchthe in vivo values determined among products. The three RPNU products were RP ascorbicacid, RP lysine and RP niacin, which were manufactured to contain Co-EDTA, and pulsedosed into the rumen at a single time for each experimental period, concomitant with anequal weight of Cr which was pulse dosed as free Cr-EDTA. The study was a 4 × 4 Latinsquare with 14 d periods using 4 multiparous ruminally cannulated lactating Jersey cows.Rumen instability of the RPNU products was measured as the proportion of the area underthe curve from ruminal in vivo clearance of Co (manufactured into each RPNU product asCo-EDTA) relative to the clearance of Cr (simultaneously rumen dosed as free crystalline Cr-EDTA). The measured rumen payload of the three RPNU products differed despite having thesame fat matrix coating and general characteristics, likely due to differences in the chemicalinteractions of the nutrients with the fat covering, with the in vivo measured payload of RPniacin highest at 656 g/kg, relative to RP lysine at 527 (P<0.05) and to RP ascorbic acid at558 g/kg (P<0.10). In situ incubations of the RPNU products in the same cows, at the sametime, suggested that in situ 30 h dry matter stability was the best predictor of their in vivomeasured rumen stability. This novel in vivo dual liquid phase marker technique can beused to determine the actual rumen stability of any ruminally protected product under anytarget feeding scenario.QualiTech Inc. (Chaska, MN, USA)http://www.elsevier.com/locate/anifeedscihb201

Multi-Donor longitudinal antibody repertoire sequencing reveals the existence of public antibody clonotypes in HIV-1 infection

Characterization of single antibody lineages within infected individuals has provided insights into the development of Env-specific antibodies. However, a systems-level understanding of the humoral response against HIV-1 is limited. Here, we interrogated the antibody repertoires of multiple HIV-infected donors from an infection-naive state through acute and chronic infection using next-generation sequencing. This analysis revealed the existence of “public” antibody clonotypes that were shared among multiple HIV-infected individuals. The HIV-1 reactivity for representative antibodies from an identified public clonotype shared by three donors was confirmed. Furthermore, a meta-analysis of publicly available antibody repertoire sequencing datasets revealed antibodies with high sequence identity to known HIV-reactive antibodies, even in repertoires that were reported to be HIV naive. The discovery of public antibody clonotypes in HIV-infected individuals represents an avenue of significant potential for better understanding antibody responses to HIV-1 infection, as well as for clonotype-specific vaccine development

The Typhoid Vaccine Acceleration Consortium (TyVAC): Vaccine effectiveness study designs: Accelerating the introduction of typhoid conjugate vaccines and reducing the global burden of enteric fever. Report from a meeting held on 26-27 October 2016, Oxford, UK

Typhoid fever is estimated to cause between 11.9–26.9 million infections globally each year with 129,000–216,510 deaths. Access to improved water sources have reduced disease incidence in parts of the world but the use of efficacious vaccines is seen as an important public health tool for countries with a high disease burden. A new generation of Vi typhoid conjugate vaccines (TCVs), licensed for use in young children and expected to provide longer lasting protection than previous vaccines, are now available. The WHO Strategic Advisory Group of Experts on Immunization (SAGE) has convened a working group to review the evidence on TCVs and produce an updated WHO position paper for all typhoid vaccines in 2018 that will inform Gavi, the Vaccine Alliance's future vaccine investment strategies for TCVs. The Typhoid Vaccine Acceleration Consortium (TyVAC) has been formed through a $36.9 million funding program from the Bill & Melinda Gates Foundation to accelerate the introduction of TCVs into Gavi-eligible countries. In October 2016, a meeting was held to initiate planning of TCV effectiveness studies that will provide the data required by policy makers and stakeholders to support decisions on TCV use in countries with a high typhoid burden. Discussion topics included (1) the latest evidence and data gaps in typhoid epidemiology; (2) WHO and Gavi methods and data requirements; (3) data on TCV efficacy; (4) cost effectiveness analysis for TCVs from mathematical models; (5) TCV delivery and effectiveness study design. Specifically, participants were asked to comment on study design in 3 sites for which population-based typhoid surveillance is underway. The conclusion of the meeting was that country-level decision making would best be informed by the respective selected sites in Africa and Asia vaccinating children aged from 9-months to 15-years-old, employing either an individual or cluster randomized design with design influenced by population characteristics, transmission dynamics, and statistical considerations

Demographic reconstruction from ancient DNA supports rapid extinction of the great auk

The great auk was once abundant and distributed across the North Atlantic. It is now extinct, having been heavily exploited for its eggs, meat, and feathers. We investigated the impact of human hunting on its demise by integrating genetic data, GPS-based ocean current data, and analyses of population viability. We sequenced complete mitochondrial genomes of 41 individuals from across the species’ geographic range and reconstructed population structure and population dynamics throughout the Holocene. Taken together, our data do not provide any evidence that great auks were at risk of extinction prior to the onset of intensive human hunting in the early 16th century. In addition, our population viability analyses reveal that even if the great auk had not been under threat by environmental change, human hunting alone could have been sufficient to cause its extinction. Our results emphasise the vulnerability of even abundant and widespread species to intense and localised exploitation

Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h 2 SNP) for European-American females of 29% that is similar to h 2 SNP for schizophrenia and is substantially higher than h 2 SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD - for both European- and African-American individuals - and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for 1/410 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci

A putative causal relationship between genetically determined female body shape and posttraumatic stress disorder

Background: The nature and underlying mechanisms of the observed increased vulnerability to posttraumatic stress disorder (PTSD) in women are unclear. Methods: We investigated the genetic overlap of PTSD with anthropometric traits and reproductive behaviors and functions in women. The analysis was conducted using female-specific summary statistics from large genome-wide association studies (GWAS) and a cohort of 3577 European American women (966 PTSD cases and 2611 trauma-exposed controls). We applied a high-resolution polygenic score approach and Mendelian randomization analysis to investigate genetic correlations and causal relationships. Results: We observed an inverse association of PTSD with genetically determined anthropometric traits related to body shape, independent of body mass index (BMI). The top association was related to BMI-adjusted waist circumference (WCadj; R = -0.079, P &lt; 0.001, Q = 0.011). We estimated a relative decrease of 64.6% (95% confidence interval = 27.5-82.7) in the risk of PTSD per 1-SD increase in WCadj. MR-Egger regression intercept analysis showed no evidence of pleiotropic effects in this association (Ppleiotropy = 0.979). We also observed associations of genetically determined WCadj with age at first sexual intercourse and number of sexual partners (P = 0.013 and P &lt; 0.001, respectively). Conclusions: There is a putative causal relationship between genetically determined female body shape and PTSD, which could be mediated by evolutionary mechanisms involved in human sexual behaviors

Sub-arcsecond imaging with the International LOFAR Telescope I. Foundational calibration strategy and pipeline

The International LOFAR Telescope is an interferometer with stations spread across Europe. With baselines of up to ~2000 km, LOFAR has the unique capability of achieving sub-arcsecond resolution at frequencies below 200 MHz. However, it is technically and logistically challenging to process LOFAR data at this resolution. To date only a handful of publications have exploited this capability. Here we present a calibration strategy that builds on previous high-resolution work with LOFAR. It is implemented in a pipeline using mostly dedicated LOFAR software tools and the same processing framework as the LOFAR Two-metre Sky Survey (LoTSS). We give an overview of the calibration strategy and discuss the special challenges inherent to enacting high-resolution imaging with LOFAR, and describe the pipeline, which is publicly available, in detail. We demonstrate the calibration strategy by using the pipeline on P205+55, a typical LoTSS pointing with an 8 h observation and 13 international stations. We perform in-field delay calibration, solution referencing to other calibrators in the field, self-calibration of these calibrators, and imaging of example directions of interest in the field. We find that for this specific field and these ionospheric conditions, dispersive delay solutions can be transferred between calibrators up to ~1.5° away, while phase solution transferral works well over ~1°. We also demonstrate a check of the astrometry and flux density scale with the in-field delay calibrator source. Imaging in 17 directions, we find the restoring beam is typically ~0.3′′ ×0.2′′ although this varies slightly over the entire 5 deg2 field of view. We find we can achieve ~80–300 μJy bm−1 image rms noise, which is dependent on the distance from the phase centre; typical values are ~90 μJy bm−1 for the 8 h observation with 48 MHz of bandwidth. Seventy percent of processed sources are detected, and from this we estimate that we should be able to image roughly 900 sources per LoTSS pointing. This equates to ~ 3 million sources in the northern sky, which LoTSS will entirely cover in the next several years. Future optimisation of the calibration strategy for efficient post-processing of LoTSS at high resolution makes this estimate a lower limit

Subluminal to superluminal propagation in a left-handed medium

In this paper we report large group delays in the propagation of narrow-band pulses through a dispersive medium with both dielectric function and magnetic permeability negative. We show how the numerical results can be understood in terms of the phase time as calculated from the complex transmission amplitude. We also demonstrate superluminal passage and saturation of phase time in the same material albeit in a different spectral region.Peer reviewedPhysic