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Inferring Mycobacterium bovis transmission between cattle and badgers using isolates from the Randomised Badger Culling Trial
No full textMycobacterium bovis (M. bovis) is a causative agent of bovine tuberculosis, a significant source of morbidity and mortality in the global cattle industry. The Randomised Badger Culling Trial was a field experiment carried out between 1998 and 2005 in the South West of England. As part of this trial, M. bovis isolates were collected from contemporaneous and overlapping populations of badgers and cattle within ten defined trial areas. We combined whole genome sequences from 1,442 isolates with location and cattle movement data, identifying transmission clusters and inferred rates and routes of transmission of M. bovis. Most trial areas contained a single transmission cluster that had been established shortly before sampling, often contemporaneous with the expansion of bovine tuberculosis in the 1980s. The estimated rate of transmission from badger to cattle was approximately two times higher than from cattle to badger, and the rate of within-species transmission considerably exceeded these for both species. We identified long distance transmission events linked to cattle movement, recurrence of herd breakdown by infection within the same transmission clusters and superspreader events driven by cattle but not badgers. Overall, our data suggests that the transmission clusters in different parts of South West England that are still evident today were established by long-distance seeding events involving cattle movement, not by recrudescence from a long-established wildlife reservoir. Clusters are maintained primarily by within-species transmission, with less frequent spill-over both from badger to cattle and cattle to badger
Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 lineages circulating in Brazil
No full textSeveral COVID-19 vaccines have shown good efficacy in clinical trials, but there remains uncertainty about the efficacy of vaccines against different variants. Here, we investigate the efficacy of ChAdOx1 nCoV-19 (AZD1222) against symptomatic COVID-19 in a post-hoc exploratory analysis of a Phase 3 randomised trial in Brazil (trial registration ISRCTN89951424). Nose and throat swabs were tested by PCR in symptomatic participants. Sequencing and genotyping of swabs were performed to determine the lineages of SARS-CoV-2 circulating during the study. Protection against any symptomatic COVID-19 caused by the Zeta (P.2) variant was assessed in 153 cases with vaccine efficacy (VE) of 69% (95% CI 55, 78). 49 cases of B.1.1.28 occurred and VE was 73% (46, 86). The Gamma (P.1) variant arose later in the trial and fewer cases (N = 18) were available for analysis. VE was 64% (−2, 87). ChAdOx1 nCoV-19 provided 95% protection (95% CI 61%, 99%) against hospitalisation due to COVID-19. In summary, we report that ChAdOx1 nCoV-19 protects against emerging variants in Brazil despite the presence of the spike protein mutation E484K
Behavioural relevance of spontaneous, transient brain network interactions in fMRI
No full textHow spontaneously fluctuating functional magnetic resonance imaging (fMRI) signals in different brain regions relate to behaviour has been an open question for decades. Correlations in these signals, known as functional connectivity, can be averaged over several minutes of data to provide a stable representation of the functional network architecture for an individual. However, associations between these stable features and behavioural traits have been shown to be dominated by individual differences in anatomy. Here, using kernel learning tools, we propose methods to assess and compare the relation between time-varying functional connectivity, time-averaged functional connectivity, structural brain data, and non-imaging subject behavioural traits. We applied these methods to Human Connectome Project resting-state fMRI data to show that time-varying fMRI functional connectivity, detected at time-scales of a few seconds, has associations with some behavioural traits that are not dominated by anatomy. Despite time-averaged functional connectivity accounting for the largest proportion of variability in the fMRI signal between individuals, we found that some aspects of intelligence could only be explained by time-varying functional connectivity. The finding that time-varying fMRI functional connectivity has a unique relationship to population behavioural variability suggests that it might reflect transient neuronal communication fluctuating around a stable neural architecture
Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 Explanation and Elaboration: a report of the ISPOR CHEERS II Good Practices Task Force
No full textHealth economic evaluations are comparative analyses of alternative courses of action in terms of their costs and consequences. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement, published in 2013, was created to ensure health economic evaluations are identifiable, interpretable, and useful for decision making. It was intended as guidance to help authors report accurately which health interventions were being compared and in what context, how the evaluation was undertaken, what the findings were, and other details that may aid readers and reviewers in interpretation and use of the study. The new CHEERS 2022 statement replaces the previous CHEERS reporting guidance. It reflects the need for guidance that can be more easily applied to all types of health economic evaluation, new methods and developments in the field, and the increased role of stakeholder involvement including patients and the public. It is also broadly applicable to any form of intervention intended to improve the health of individuals or the population, whether simple or complex, and without regard to context (such as healthcare, public health, education, and social care). This Explanation and Elaboration Report presents the new CHEERS 2022 28-item checklist with recommendations and explanation and examples for each item. The CHEERS 2022 statement is primarily intended for researchers reporting economic evaluations for peer-reviewed journals and the peer reviewers and editors assessing them for publication. Nevertheless, we anticipate familiarity with reporting requirements will be useful for analysts when planning studies. It may also be useful for health technology assessment bodies seeking guidance on reporting, given that there is an increasing emphasis on transparency in decision making
Measurement of the CKM angle γ in B± → DK± and B± → Dπ± decays with D → K0Sh+h−
No full textA measurement of CP-violating observables is performed using the decays B± → DK± and B± → Dπ±, where the D meson is reconstructed in one of the self-conjugate three-body final states K0Sπ+π− and K0SK+K− (commonly denoted K0Sh+h−). The decays are analysed in bins of the D-decay phase space, leading to a measurement that is independent of the modelling of the D-decay amplitude. The observables are inter- preted in terms of the CKM angle γ. Using a data sample corresponding to an integrated luminosity of 9 fb−1 collected in proton-proton collisions at centre-of mass energies of 7, 8, and 13 TeV with the LHCb experiment, γ is measured to be (68.7+5.2−5.1)∘. The hadronic parameters rDKB,rDπB,δDKB,andδDπB, which are the ratios and strong-phase differences of the suppressed and favoured B± decays, are also reported
A sub-micron resolution, bunch-by-bunch beam trajectory feedback system and its application to reducing wakefield effects in single-pass beamlines
No full textA high-precision intra-bunch-train beam orbit feedback correction system has been developed and tested at the KEK Accelerator Test Facility, ATF2. The system uses the vertical position of the bunch measured at two beam position monitors to calculate a pair of kicks which are applied to the next bunch using two upstream kickers, thereby correcting both the vertical position and trajectory angle. Using trains of two electron bunches separated in time by 187.6ns, the system was optimised so as to stabilize the beam offset at the feedback BPMs to better than 350nm, yielding a local trajectory angle correction to within 250nrad. The quality of the correction was verified using three downstream witness BPMs and the results were found to be in agreement with the predictions of a linear lattice model used to propagate the beam trajectory from the feedback region. This same model predicts a corrected be am jitter of c.1nm at the focal point of the accelerator. Measurements with a beam size monitor at this location demonstrate that reducing the trajectory jitter of the beam by a factor of 4 also reduces the increase in the measured beam size as a function of beam charge by a factor of ~1.6
Single-cell measurements of two-dimensional binding affinity across cell contacts
No full textThe two-dimensional (2D) affinity between protein molecules across contacting cells is a key parameter regulating and initiating several cellular processes. However, measuring 2D affinity can be challenging and experimental data are limited. In addition, the obtained 2D affinities are typically averaged over the cell population. We here present a method to measure 2D affinity on single cells binding to polyhistidine-tagged fluorescent ligands anchored to a supported lipid bilayer (SLB). By decreasing the density of ligands in the SLB using imidazole a new steady-state accumulation in the contact is obtained, and from this change, both the 2D affinity and the number of receptors on the cell can be determined. The method was validated on an SLB containing rat CD2 binding to the rat CD48 mutant T92A expressed on Jurkat T cells. The addition of imidazole did not influence the average 2D affinity (1/Kd), and the spread in affinities within the cell population was low, Kd = 4.9 ± 0.9 molecules/μm2 (mean ± SD), despite an order of magnitude spread in ligand accumulation due to differences in receptor density. It was also found that cell contact size increased both with ligand density and with the number of receptors per cell, but that the contact size stayed approximately constant when lowering the ligand density, above a density of around 10 rCD2 molecules/μm2, after the contact first had formed, indicative of a heterogeneous process. In summary, this method not only allows for single-cell affinities to be measured, but it can also reduce measurement and analysis time and improve measurement accuracy. Due to the low spread in 2D Kd within the cell population, the analysis can further be restricted to the cells showing the strongest binding, paving the way for using this method to study weak binding events
Estimating the population health burden of musculoskeletal conditions using primary care electronic health records
No full textObjectives
Better indicators from affordable, sustainable data sources are needed to monitor population burden of musculoskeletal conditions. We propose five indicators of musculoskeletal health and assessed if routinely available primary care electronic health records (EHR) can estimate population levels in musculoskeletal consulters.
Methods
We collected validated patient-reported measures of pain experience, function and health status through a local survey of adults (≥35 years) presenting to English general practices over 12 months for low back pain, shoulder pain, osteoarthritis and other regional musculoskeletal disorders. Using EHR data we derived and validated models for estimating population levels of five self-reported indicators: prevalence of high impact chronic pain, overall musculoskeletal health (based on Musculoskeletal Health Questionnaire), quality of life (based on EuroQoL health utility measure), and prevalence of moderate-to-severe low back pain and moderate-to-severe shoulder pain. We applied models to a national EHR database (Clinical Practice Research Datalink) to obtain national estimates of each indicator for three successive years.
Results
The optimal models included recorded demographics, deprivation, consultation frequency, analgesic and antidepressant prescriptions, and multimorbidity. Applying models to national EHR, we estimated that 31.9% of adults (≥35 years) presenting with non-inflammatory musculoskeletal disorders in England in 2016/17 experienced high impact chronic pain. Estimated population health levels were worse in women, older aged and those in the most deprived neighbourhoods, and changed little over 3 years.
Conclusion
National and subnational estimates for a range of subjective indicators of non-inflammatory musculoskeletal health conditions can be obtained using information from routine electronic health records
The butcher, the brewer, or the baker: The role of occupations in explaining wage inequality
No full textGoogle does not pay its canteen chefs the same premium as it does its software engineers; there is heterogeneity in pay premia within a firm. To study the implications of this observation, we estimate a two-way, worker-job, fixed effect model that builds upon the canonical model by Abowd et al. (1999) by allowing for within-firm heterogeneity. Estimating our model on UK administrative data, we find that even if workers, and firms, were identical, 25% of current log-wage variance would remain, due solely to heterogeneity between occupations. We further document that worker heterogeneity accounts for a relatively small proportion of log-wage variance, and that between-firm pay heterogeneity is more important in higher-wage occupations and larger labour markets