Effect of Porcine circovirus 2 (PCV-2) maternally derived antibodies on performance and PCV-2 viremia in vaccinated piglets under field conditions

Background: Nowadays, the most common presentation of PCV-2 is the subclinical infection in piglets after weaning. The success of PCV-2 vaccination is associated with the control of the clinical disease as well as the improvement of production parameters. In consequence, the objective of the present study was to analyse the effect of PCV-2 maternally derived antibody (MDA) levels on vaccine efficacy in piglets vaccinated at three weeks of age with a commercial PCV-2 subunit vaccine. The study was performed analysing a database with 6112 wean-to-slaughter piglets from 4 different European regions. Results: Results showed that the use of the vaccine was able to decrease the PCV-2 viremia calculated as area under the curve (AUC = 60.29 ± 3.73), increase average daily weight gain (ADWG = 0.65 ± 0.01 kg/day) and reduce mortality (7%) in vaccinated piglets compared to non-vaccinated ones (AUC of 198.27 ± 6.14, 0.62 ± 0.01 kg/day and 11% respectively). The overall difference of ADWG between both groups was close to 30 g per day (p < 0.05), also when they were split for low and high levels of MDA titres. Moreover, the animals with the highest ADWG were observed in the group of piglets vaccinated with high or extremely high antibody titres (0.66 and 0.65 kg/day respectively). Considering only animals with extremely high antibody titres, both study groups performed similar, however there was a numerical difference of 10 g/day in favour of vaccinated piglets. Likewise, lack of correlation between ADWG and MDA was observed suggesting that no maternal antibody interference was present with the tested vaccine because the vaccinated animals grew faster compared to unvaccinated control animals, regardless of the level of maternal antibodies present at the time of vaccination. Conclusions: The results of the present study demonstrated that the MDA against PCV-2 transferred through the colostrum intake has a protective effect against this viral infection. The vaccine used in the present study (Ingelvac CircoFLEX®) was effective when applied at three weeks of age and was not affected by the level of MDA at the time of vaccination

Aplicabilidad de las herramientas de ayuda a la toma de decisiones compartidas en los servicios de Urgencias: una revisión exploratoria

Fundamentos: Las herramientas de ayuda en la toma de decisiones (HATD) han sido muy utilizadas en las enfermedades crónicas, pero existen pocos estudios sobre su utilidad en los servicios de urgencias. El objetivo de este estudio fue analizar la utilización de las HATD en los servicios de urgencias. Métodos: Se realizó una revisión exploratoria. Se realizaron búsquedas de ensayos clínicos aleatorizados y controlados, revisiones sistemáticas y otros estudios se-cundarios donde se utilizaran las HATD para la asistencia a pacientes de cualquier edad en los servicios de urgen-cias, entre el 1 de enero de 2012 y el 1 de agosto de 2019. Dos revisores examinaron y seleccionaron los estudios. Se utilizaron las siguientes bases de datos: Pubmed, Embase, Web Of Science, Cuiden, Patient Decision Aids Research Group IPDAS Collaboration, Cochrane, Centres for Reviews and Dissemination, National Guideline Clearinghouse, Guidelines International Network. Resultados: Se incluyeron doce estudios, de calidad metodológica moderada-baja. Los pacientes del Grupo de Intervención (GI) tenían mayor conocimiento de la enfer-medad (?=3, 6 frente a 3 preguntas correctas y ?=4, 2 frente a 3, 6) y más implicación en las decisiones (puntuación en OPTION: 26, 6 contra 7 y 18, 3 contra 7). El conflicto se redujo en el GI en las decisiones sobre pruebas de imagen en el traumatismo craneoencefálico (TCE) (?=14, 8 frente a 19, 2). En el GI era menos frecuente el ingreso para realizar una prueba de esfuerzo en casos de dolor torácico de bajo riesgo (58% contra 77%; IC95%=6%-31%, y 37% contra 52%; p<0, 001). Cuando se utilizaba una HATD en niños con diarrea o vómitos, en el 80% la decisión era seguir una rehidratación oral frente al 61% en el GC (p=0, 001). Conclusiones: Las HATD en los servicios de urgen-cias mejoran el conocimiento de los pacientes sobre la en-fermedad y la participación en los cuidados. Se necesitan más estudios para desarrollar HATD en los servicios de urgencias. Background: Decision aid tools (DAT) have been widely used in chronic diseases, but there are few studies on their usefulness in emergency departments. The objective of this study was to analyse the applicability of DAT in emergency services. Methods: An exploratory review was conducted. Between January 1, 2012 and August 1, 2019, searches of randomised and controlled clinical trials, systematic reviews and other secondary studies where DAT are used to assist patients of any age in emergency services were conducted. The databases used were: Pubmed, Embase, Web Of Science, Cuiden, Patient Decision Aids Research Group IPDAS Collaboration, Cochrane, Centres for Reviews and Dissemination, National Guideline Clearinghouse, Guidelines International Network. Two reviewers analysed and selected the studies. Results: Twelve studies of moderate-low quality were included. The patients in the intervention group (IG) were more aware of their illness ((X) over bar =3.6 vs 3 correct answers and (X) over bar =4.2 vs 3.6), and more involved in the decisions (score in OPTION: 26.6 vs 7 and 18.3 vs 7). The conflict was reduced in the IG regarding those imaging tests in the TBI (traumatic brain injury; (X) over bar =14.8 vs 19.2). In the IG, admittance to perform effort tests was reduced in low-risk chest pain (58% vs 77%; CI95%=6%-31%, 37% vs 52%; p<0.001). When DAT were used in children with diarrhoea or vomiting, in 80% of the cases the decision was to use oral rehydration against 61% in the control group (CG, p=0.001). Conclusions: DAT in emergency services improve patient''s knowledge about the disease and their participation in care. More studies are needed to develop DAT in emergency services

Copy number variation and expression of exportin-4 associates with severity of fibrosis in metabolic associated fatty liver disease

Background: Liver fibrosis risk is a heritable trait, the outcome of which is the net deposition of extracellular matrix by hepatic stellate cell-derived myofibroblasts. Whereas nucleotide sequence variations have been extensively studied in liver fibrosis, the role of copy number variations (CNV) in which genes exist in abnormal numbers of copies (mostly due to duplication or deletion) has had limited exploration. Methods: The impact of the XPO4 CNV on histological liver damage was examined in a cohort comprised 646 Caucasian patients with biopsy-proven MAFLD and 170 healthy controls. XPO4 expression was modulated and function was examined in human and animal models. Findings: Here we demonstrate in a cohort of 816 subjects, 646 with biopsy-proven metabolic associated liver disease (MAFLD) and 170 controls, that duplication in the exportin 4 (XPO4) CNV is associated with the severity of liver fibrosis. Functionally, this occurs via reduced expression of hepatic XPO4 that maintains sustained activation of SMAD3/SMAD4 and promotes TGF-β1-mediated HSC activation and fibrosis. This effect was mediated through termination of nuclear SMAD3 signalling. XPO4 demonstrated preferential binding to SMAD3 compared to other SMADs and led to reduced SMAD3-mediated responses as shown by attenuation of TGFβ1 induced SMAD transcriptional activity, reductions in the recruitment of SMAD3 to target gene promoters following TGF-β1, as well as attenuation of SMAD3 phosphorylation and disturbed SMAD3/SMAD4 complex formation. Interpretation: We conclude that a CNV in XPO4 is a critical mediator of fibrosis severity and can be exploited as a therapeutic target for liver fibrosis. Funding: ME and JG are supported by the Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney; a National Health and Medical Research Council of Australia (NHMRC) Program Grant (APP1053206) and Project and ideas grants (APP2001692, APP1107178 and APP1108422). AB is supported by an Australian Government Research Training Program (RTP) scholarship. EB is supported by Horizon 2020 under grant 634413 for the project EPoS

The highly prevalent BRCA2 mutation c.2808_2811del (3036delACAA) is located in a mutational hotspot and has multiple origins

BRCA2-c.2808_2811del (3036delACAA) is one of the most reported germ line mutations in non-Ashkenazi breast cancer patients. We investigated its genetic origin in 51 Spanish carrier families that were genotyped with 11 13q polymorphic markers. Three independent associated haplotypes were clearly distinguished accounting for 23 [west Castilla y León (WCL)], 20 [east Castilla y León (ECL)] and 6 (South of Spain) families. Mutation age was estimated with the Disequilibrium Mapping using Likelihood Estimation software in a range of 45–68 and 45–71 generations for WCL and ECL haplotypes, respectively. The most prevalent variants, c.2808_2811del and c.2803G > A, were located in a double-hairpin loop structure (c.2794–c.2825) predicted by Quikfold that was proposed as a mutational hotspot. To check this hypothesis, random mutagenesis was performed over a 923 bp fragment of BRCA2, and 86 DNA variants were characterized. Interestingly, three mutations reported in the mutation databases (c.2680G > A, c.2944del and c.2957dup) were replicated and 20 affected the same position with different nucleotide changes. Moreover, five variants were placed in the same hairpin loop of c.2808_2811del, and one affected the same position (c.2808A > G). In conclusion, our results support that at least three different mutational events occurred to generate c.2808_2811del. Other highly prevalent DNA variants, such as BRCA1-c.68_69delAG, BRCA2- c.5946delT and c.8537delAG, are concentrated in hairpin loops, suggesting that these structures may represent mutational hotspots

Mistranslation Drives Alterations in Protein Levels and the Effects of a Synonymous Variant at the Fibroblast Growth Factor 21 Locus

Fibroblast growth factor 21 (FGF21) is a liver-derived hormone with pleiotropic beneficial effects on metabolism. Paradoxically, FGF21 levels are elevated in metabolic diseases. Interventions that restore metabolic homeostasis reduce FGF21. Whether abnormalities in FGF21 secretion or resistance in peripheral tissues is the initiating factor in altering FGF21 levels and function in humans is unknown. A genetic approach is used to help resolve this paradox. The authors demonstrate that the primary event in dysmetabolic phenotypes is the elevation of FGF21 secretion. The latter is regulated by translational reprogramming in a genotype- and context-dependent manner. To relate the findings to tissues outcomes, the minor (A) allele of rs838133 is shown to be associated with increased hepatic inflammation in patients with metabolic associated fatty liver disease. The results here highlight a dominant role for translation of the FGF21 protein to explain variations in blood levels that is at least partially inherited. These results provide a framework for translational reprogramming of FGF21 to treat metabolic diseases

The emergence of a new source of X-rays from the binary neutron star merger GW170817

The binary neutron-star (BNS) merger GW170817 is the first celestial object from which both gravitational waves (GWs) and light have been detected enabling critical insight on the pre-merger (GWs) and post-merger (light) physical properties of these phenomena. For the first $\sim 3$ years after the merger the detected radio and X-ray radiation has been dominated by emission from a structured relativistic jet initially pointing $\sim 15-25$ degrees away from our line of sight and propagating into a low-density medium. Here we report on observational evidence for the emergence of a new X-ray emission component at $\delta t>900$ days after the merger. The new component has luminosity $L_x \approx 5\times 10^{38}\rm{erg s^{-1}}$ at 1234 days, and represents a $\sim 3.5\sigma$ - $4.3\sigma$ excess compared to the expectations from the off-axis jet model that best fits the multi-wavelength afterglow of GW170817 at earlier times. A lack of detectable radio emission at 3 GHz around the same time suggests a harder broadband spectrum than the jet afterglow. These properties are consistent with synchrotron emission from a mildly relativistic shock generated by the expanding merger ejecta, i.e. a kilonova afterglow. In this context our simulations show that the X-ray excess supports the presence of a high-velocity tail in the merger ejecta, and argues against the prompt collapse of the merger remnant into a black hole. However, radiation from accretion processes on the compact-object remnant represents a viable alternative to the kilonova afterglow. Neither a kilonova afterglow nor accretion-powered emission have been observed before.Comment: 66 pages, 12 figures, Submitte

Towards the high-accuracy determination of the 238U fission cross section at the threshold region at CERN - N-TOF

The 238U fission cross section is an international standard beyond 2 MeV where the fission plateau starts. However, due to its importance in fission reactors, this cross-section should be very accurately known also in the threshold region below 2 MeV. The 238U fission cross section has been measured relative to the 235U fission cross section at CERN - n-TOF with different detection systems. These datasets have been collected and suitably combined to increase the counting statistics in the threshold region from about 300 keV up to 3 MeV. The results are compared with other experimental data, evaluated libraries, and the IAEA standards

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson