Transmission and dose–response experiments for social animals: a reappraisal of the colonization biology of Campylobacter jejuni in chickens

Dose-response experiments characterize the relationship between infectious agents and their hosts. These experiments are routinely used to estimate the minimum effective infectious dose for an infectious agent, which is most commonly characterized by the dose at which 50 per cent of challenged hosts become infected-the ID(50). In turn, the ID(50) is often used to compare between different agents and quantify the effect of treatment regimes. The statistical analysis of dose-response data typically makes the assumption that hosts within a given dose group are independent. For social animals, in particular avian species, hosts are routinely housed together in groups during experimental studies. For experiments with non-infectious agents, this poses no practical or theoretical problems. However, transmission of infectious agents between co-housed animals will modify the observed dose-response relationship with implications for the estimation of the ID(50) and the comparison between different agents and treatments. We derive a simple correction to the likelihood for standard dose-response models that allows us to estimate dose-response and transmission parameters simultaneously. We use this model to show that: transmission between co-housed animals reduces the apparent value of the ID(50) and increases the variability between replicates leading to a distinctive all-or-nothing response; in terms of the total number of animals used, individual housing is always the most efficient experimental design for ascertaining dose-response relationships; estimates of transmission from previously published experimental data for Campylobacter spp. in chickens suggest that considerable transmission occurred, greatly increasing the uncertainty in the estimates of dose-response parameters reported in the literature. Furthermore, we demonstrate that accounting for transmission in the analysis of dose-response data for Campylobacter spp. challenges our current understanding of the differing response of chickens with respect to host-age and in vivo passage of bacteria. Our findings suggest that the age-dependence of transmissibility between hosts-rather than their susceptibility to colonization-is the mechanism behind the 'lag-phase' reported in commercial flocks, which are typically found to be Campylobacter free for the first 14-21 days of life.A.J.K.C. is funded by DEFRA grant PU/T/WL/07/46 - SE3230, sponsored by the Veterinary Laboratories Agency. This research was developed during an earlier project funded by the Biotechnology and Biological Sciences Research Council/Defra Government Partnership Award, grants BB/500852/1 and BB/500936/1

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Analysis of Campylobacter jejuni infection in the gnotobiotic piglet and genome-wide identification of bacterial factors required for infection

To investigate how Campylobacter jejuni causes the clinical symptoms of diarrhoeal disease in humans, use of a relevant animal model is essential. Such a model should mimic the human disease closely in terms of host physiology, incubation period before onset of disease, clinical signs and a comparable outcome of disease. In this study, we used a gnotobiotic piglet model to study determinants of pathogenicity of C. jejuni. In this model, C. jejuni successfully established infection and piglets developed an increased temperature with watery diarrhoea, which was caused by a leaky epithelium and reduced bile re-absorption in the intestines. Further, we assessed the C. jejuni genes required for infection of the porcine gastrointestinal tract utilising a transposon (Tn) mutant library screen. A total of 123 genes of which Tn mutants showed attenuated piglet infection were identified. Our screen highlighted a crucial role for motility and chemotaxis, as well as central metabolism. In addition, Tn mutants of 14 genes displayed enhanced piglet infection. This study gives a unique insight into the mechanisms of C. jejuni disease in terms of host physiology and contributing bacterial factors.This work was funded by BBSRC awards BB/F020988/1 and BB/K004514/1. Moredun Research Institute receives funding via Rural and Environment Science and Analytical Services (RESAS) division of the Scottish Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

A core outcome set for future male infertility research: development of an international consensus

\ua9 The Author(s). Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.STUDY QUESTION: Can a core outcome set be developed through a global consensus to standardize outcome selection, collection, comparison, and reporting in future male infertility trials? SUMMARY ANSWER: A minimum dataset, known as a \u27core outcome set\u27, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential interventions for male infertility. WHAT IS KNOWN ALREADY: Numerous factors, including a failure to consider the perspectives of men with lived experiences of infertility or their partners when developing and conducting RCTs can limit their clinical utility. Selection of outcomes, variations in outcome definitions, and the selective reporting of outcomes based on statistical analysis make the results of infertility research challenging to interpret, compare, and implement. For male infertility, this is further compounded by there being potentially three participants, the male, their female partner, and any offspring born, all with outcomes to be reported. This has led to significant heterogeneity in trial design and reporting. While a core outcome set for general infertility trials has been developed, there is no such outcome set for male infertility trials. STUDY DESIGN, SIZE, DURATION: A two-round Delphi survey (334 participants from 39 countries) and consensus development workshops (44 participants from 21 countries). PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers, and men and women with infertility were brought together in a transparent process using formal consensus science methods. MAIN RESULTS AND THE ROLE OF CHANCE: The core outcome set for male infertility trials has been developed by the inclusion of specific male-factor outcomes in addition to the general infertility core outcome set. These outcomes include assessment of semen using the World Health Organization recommendations for semen analysis; viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin, and higher multiple pregnancies); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth, and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Although not a requirement as part of the core outcome set, other outcomes were identified as potentially useful in certain study settings. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods in this work, which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition, and an arbitrary consensus threshold. WIDER IMPLICATIONS OF THE FINDINGS: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection, and reporting of core outcomes, which are inconsistently reported at present. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set for male infertility trials

Diffractive Dijet Production at s = 630 and 1800 GeV at the Fermilab Tevatron

We report a measurement of the diffractive structure function F-jj(D) of the antiproton obtained from a study of dijet events produced in association with a leading antiproton in (p) over barp collisions at roots = 630 GeV at the Fermilab Tevatron. The ratio of F-jj(D) at roots = 630 GeV to F-jj(D) obtained from a similar measurement at roots = 1800 GeV is compared with expectations from QCD factorization and other theoretical predictions. We also report a measurement of the xi (x-Pomeron) and beta (x of parton in Pomeron) dependence of F-jj(D) at roots = 1800 GeV . In the region 0.035 < &xi; < 0.095 , \t\ < 1 GeV2 , and &beta; < 0.5 , F-jj(D)(beta, xi) is found to be of the form beta(-1.0+/-0.1) xi(-0.9+/-0. 1) , which obeys beta-xi factorization

Persistent Place-Making in Prehistory: the Creation, Maintenance, and Transformation of an Epipalaeolithic Landscape

Most archaeological projects today integrate, at least to some degree, how past people engaged with their surroundings, including both how they strategized resource use, organized technological production, or scheduled movements within a physical environment, as well as how they constructed cosmologies around or created symbolic connections to places in the landscape. However, there are a multitude of ways in which archaeologists approach the creation, maintenance, and transformation of human-landscape interrelationships. This paper explores some of these approaches for reconstructing the Epipalaeolithic (ca. 23,000–11,500&nbsp;years BP) landscape of Southwest Asia, using macro- and microscale geoarchaeological approaches to examine how everyday practices leave traces of human-landscape interactions in northern and eastern Jordan. The case studies presented here demonstrate that these Epipalaeolithic groups engaged in complex and far-reaching social landscapes. Examination of the Early and Middle Epipalaeolithic (EP) highlights that the notion of “Neolithization” is somewhat misleading as many of the features we use to define this transition were already well-established patterns of behavior by the Neolithic. Instead, these features and practices were enacted within a hunter-gatherer world and worldview

Measurement of the Ratio of b Quark Production Cross Sections in Antiproton-Proton Collisions at 630 GeV and 1800 GeV

We report a measurement of the ratio of the bottom quark production cross section in antiproton-proton collisions at 630 GeV to 1800 GeV using bottom quarks with transverse momenta greater than 10.75 GeV identified through their semileptonic decays and long lifetimes. The measured ratio sigma(630)/sigma(1800) = 0.171 +/- .024 +/- .012 is in good agreement with next-to-leading order (NLO) quantum chromodynamics (QCD)

Erratum: "Searches for Gravitational Waves from Known Pulsars at Two Harmonics in 2015–2017 LIGO Data" (2019, ApJ, 879, 10)

This is a correction for 2019 ApJ 879 1

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO’s second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h95%0=3.47×10−25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering