Estimating the relative rate of recombination to mutation in bacteria from single-locus variants using composite likelihood methods

A number of studies have suggested using comparisons between DNA sequences of closely related bacterial isolates to estimate the relative rate of recombination to mutation for that bacterial species. We consider such an approach which uses single-locus variants: pairs of isolates whose DNA differ at a single gene locus. One way of deriving point estimates for the relative rate of recombination to mutation from such data is to use composite likelihood methods. We extend recent work in this area so as to be able to construct confidence intervals for our estimates, without needing to resort to computationally-intensive bootstrap procedures, and to develop a test for whether the relative rate varies across loci. Both our test and method for constructing confidence intervals are obtained by modeling the dependence structure in the data, and then applying asymptotic theory regarding the distribution of estimators obtained using a composite likelihood. We applied these methods to multi-locus sequence typing (MLST) data from eight bacteria, finding strong evidence for considerable rate variation in three of these: Bacillus cereus, Enterococcus faecium and Klebsiella pneumoniae.Comment: Published at http://dx.doi.org/10.1214/14-AOAS795 in the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Clustering of equine grass sickness cases in the United Kingdom: a study considering the effect of position-dependent reporting on the space-time K-function

Equine grass sickness (EGS) is a largely fatal, pasture-associated dysautonomia. Although the aetiology of this disease is unknown, there is increasing evidence that Clostridium botulinum type C plays an important role in this condition. The disease is widespread in the United Kingdom, with the highest incidence believed to occur in Scotland. EGS also shows strong seasonal variation (most cases are reported between April and July). Data from histologically confirmed cases of EGS from England and Wales in 1999 and 2000 were collected from UK veterinary diagnostic centres. The data did not represent a complete census of cases, and the proportion of all cases reported to the centres would have varied in space and, independently, in time. We consider the variable reporting of this condition and the appropriateness of the space–time K-function when exploring the spatial-temporal properties of a ‘thinned’ point process. We conclude that such position-dependent under-reporting of EGS does not invalidate the Monte Carlo test for space–time interaction, and find strong evidence for space–time clustering of EGS cases (P<0.001). This may be attributed to contagious or other spatially and temporally localized processes such as local climate and/or pasture management practices

Semi-automatic selection of summary statistics for ABC model choice

A central statistical goal is to choose between alternative explanatory models of data. In many modern applications, such as population genetics, it is not possible to apply standard methods based on evaluating the likelihood functions of the models, as these are numerically intractable. Approximate Bayesian computation (ABC) is a commonly used alternative for such situations. ABC simulates data x for many parameter values under each model, which is compared to the observed data xobs. More weight is placed on models under which S(x) is close to S(xobs), where S maps data to a vector of summary statistics. Previous work has shown the choice of S is crucial to the efficiency and accuracy of ABC. This paper provides a method to select good summary statistics for model choice. It uses a preliminary step, simulating many x values from all models and fitting regressions to this with the model as response. The resulting model weight estimators are used as S in an ABC analysis. Theoretical results are given to justify this as approximating low dimensional sufficient statistics. A substantive application is presented: choosing between competing coalescent models of demographic growth for Campylobacter jejuni in New Zealand using multi-locus sequence typing data

A cluster randomised controlled trial of the efficacy of a brief walking intervention delivered in primary care : study protocol

Background: The aim of the present research is to conduct a fully powered explanatory trial to evaluate the efficacy of a brief self-regulation intervention to increase walking. The intervention will be delivered in primary care by practice nurses (PNs) and Healthcare Assistants (HCAs) to patients for whom increasing physical activity is a particular priority. The intervention has previously demonstrated efficacy with a volunteer population, and subsequently went through an iterative process of refinement in primary care, to maximise acceptability to both providers and recipients. Methods/ Design: This two arm cluster randomised controlled trial set in UK general practices will compare two strategies for increasing walking, assessed by pedometer, over six months. Patients attending practices randomised to the self-regulation intervention arm will receive an intervention consisting of behaviour change techniques designed to increase walking self-efficacy (confidence in ability to perform the behaviour), and to help people translate their “good” intentions into behaviour change by making plans. Patients attending practices randomised to the information provision arm will receive written materials promoting walking, and a short unstructured discussion about increasing their walking. The trial will recruit 20 PN/HCAs (10 per arm), who will be trained by the research team to deliver the selfregulation intervention or information provision control intervention, to 400 patients registered at their practices (20 patients per PN/HCA). This will provide 85% power to detect a mean difference of five minutes/day walking between the self-regulation intervention group and the information provision control group. Secondary outcomes include health services costs, and intervention effects in sub-groups defined by age, ethnicity, gender, socioeconomic status, and clinical condition. A mediation analysis will investigate the extent to which changes in constructs specified by the Theory of Planned Behaviour lead to changes in objectively assessed walking behaviour. Discussion: This trial addresses the current lack of evidence for interventions that are effective at increasing walking and that can be offered to patients in primary care. The intervention being evaluated has demonstrated efficacy, and has been through an extensive process of adaptation to ensure acceptability to both provider and recipient, thus optimising fidelity of intervention delivery and treatment receipt. It therefore provides a strong test of the hypothesis that a self-regulation intervention can help primary care patients increase their walking

Leveraging affect: mobilizing enthusiasm and the co-production of the musical economy

This chapter considers the promises and problems of fandom and enthusiasm within capitalism, with particular reference to rise of crowdsourcing as a means of mobilising fan enthusiasm to fund new creative projects, with a particular focus on the music industry. Crowdfunding has emerged as an alternative way of funding projects caused by the more cautious investments of record companies, and is the latest development here firms and companies have sought to harness the affect and emotions of fans. However, although crowdfunding may tap new sources of money, the process is not without its costs, both in terms of the demands placed on its users and of being able to navigate a system that requires reserves of social, cultural and financial capital

A photodiode for detection within molecular diagnostics

A photodiode (200), for instance a PN or a PIN photodiode, is disclosed. The photodiode receives incident radiation having first and second spectral distributions, where the first spectral distribution is spectrally shifted from the second spectral distribution. The photodiode has a first semiconductor layer (211) capable of absorbing incident radiation (231) having a first spectral distribution without generating a photocurrent, while simultaneously transmitting incident radiation having a second spectral distribution to the intrinsic layer (212) for generating a photocurrent (213). The photodiode may be used in connection with detecting the presence of target molecules that has been labeled with labeling agents, such as fluorophores or quantum dots. The labeling agents are characterized by the Stokes shift and, therefore, they emit fluorescent radiation having the second spectral distribution that is spectrally shifted from the illumination radiation having the first spectral distribution

Ecological assessment of the direct and indirect effects of routine rotavirus vaccination in Merseyside, UK using data from multiple health systems: a study protocol

INTRODUCTION: Rotavirus is the most common cause of severe gastroenteritis in infants and young children worldwide. Currently 67 countries include rotavirus vaccine in childhood immunisation programmes, but uptake in Western Europe has been slow. In July 2013, rotavirus vaccine was introduced into the UK's routine childhood immunisation programme. Prior to vaccine introduction in the UK, rotavirus was estimated to result in 750 000 diarrhoea episodes and 80 000 general practice (GP) consultations each year, together with 45% and 20% of hospital admissions and emergency department attendances for acute gastroenteritis, in children under 5 years of age. This paper describes a protocol for an ecological study that will assess rotavirus vaccine impact in the UK, to inform rotavirus immunisation policy in the UK and in other Western European countries. METHODS AND ANALYSIS: In Merseyside, UK, we will conduct an ecological study using a ‘before and after’ approach to examine changes in gastroenteritis and rotavirus incidence following the introduction of rotavirus vaccination. Data will be collected on mortality, hospital admissions, nosocomial infection, emergency department attendances, GP consultations and community health consultations to capture all healthcare providers in the region. We will assess both the direct and indirect effects of the vaccine on the study population. Comparisons of outcome indicator rates will be made in relation to vaccine uptake and socioeconomic status. ETHICS AND DISSEMINATION: The study has been approved by NHS Research Ethics Committee, South Central-Berkshire REC Reference: 14/SC/1140. Study outputs will be disseminated through scientific conferences and peer-reviewed publications. The study will demonstrate the impact of rotavirus vaccination on the burden of disease from a complete health system perspective. It will identify key areas that require improved data collection tools to maximise the usefulness of this surveillance approach and will provide a template for vaccine evaluations using ecological methods in the UK