Are quantitative trait-dependent sampling designs cost-effective for analysis of rare and common variants?

Use of trait-dependent sampling designs in whole-genome association studies of sequence data can reduce total sequencing costs with modest losses of statistical efficiency. In a quantitative trait (QT) analysis of data from the Genetic Analysis Workshop 17 mini-exome for unrelated individuals in the Asian subpopulation, we investigate alternative designs that sequence only 50% of the entire cohort. In addition to a simple random sampling design, we consider extreme-phenotype designs that are of increasing interest in genetic association analysis of QTs, especially in studies concerned with the detection of rare genetic variants. We also evaluate a novel sampling design in which all individuals have a nonzero probability of being selected into the sample but in which individuals with extreme phenotypes have a proportionately larger probability. We take differential sampling of individuals with informative trait values into account by inverse probability weighting using standard survey methods which thus generalizes to the source population. In replicate 1 data, we applied the designs in association analysis of Q1 with both rare and common variants in the FLT1 gene, based on knowledge of the generating model. Using all 200 replicate data sets, we similarly analyzed Q1 and Q4 (which is known to be free of association with FLT1) to evaluate relative efficiency, type I error, and power. Simulation study results suggest that the QT-dependent selection designs generally yield greater than 50% relative efficiency compared to using the entire cohort, implying cost-effectiveness of 50% sample selection and worthwhile reduction of sequencing costs

A brief introduction to recent developments in population-based structural health monitoring

This is the final version. Available from the publisher via the DOI in this record.One of the main problems in data-based Structural Health Monitoring (SHM), is the scarcity of measured data corresponding to damage states in the structures of interest. One approach to solving this problem is to develop methods of transferring health inferences and information between structures in an identified population—Population-based SHM (PBSHM). In the case of homogenous populations (sets of nominally-identical structures, like in a wind farm), the idea of the form has been proposed which encodes information about the ideal or typical structure together with information about variations across the population. In the case of sets of disparate structures—heterogeneous populations—transfer learning appears to be a powerful tool for sharing inferences, and is also applicable in the homogenous case. In order to assess the likelihood of transference being meaningful, it has proved useful to develop an abstract representation framework for spaces of structures, so that similarities between structures can formally be assessed; this framework exploits tools from graph theory. The current paper discusses all of these very recent developments and provides illustrative examplesEngineering and Physical Sciences Research Council (EPSRC

The cost of changing physical activity behaviour: Evidence from a "physical activity pathway" in the primary care setting

Copyright @ 2011 Boehler et al.BACKGROUND: The ‘Physical Activity Care Pathway’ (a Pilot for the ‘Let’s Get Moving’ policy) is a systematic approach to integrating physical activity promotion into the primary care setting. It combines several methods reported to support behavioural change, including brief interventions, motivational interviewing, goal setting, providing written resources, and follow-up support. This paper compares costs falling on the UK National Health Service (NHS) of implementing the care pathway using two different recruitment strategies and provides initial insights into the cost of changing physical activity behaviour. METHODS: A combination of a time driven variant of activity based costing, audit data through EMIS and a survey of practice managers provided patient-level cost data for 411 screened individuals. Self reported physical activity data of 70 people completing the care pathway at three month was compared with baseline using a regression based ‘difference in differences’ approach. Deterministic and probabilistic sensitivity analyses in combination with hypothesis testing were used to judge how robust findings are to key assumptions and to assess the uncertainty around estimates of the cost of changing physical activity behaviour. RESULTS: It cost £53 (SD 7.8) per patient completing the PACP in opportunistic centres and £191 (SD 39) at disease register sites. The completer rate was higher in disease register centres (27.3% vs. 16.2%) and the difference in differences in time spent on physical activity was 81.32 (SE 17.16) minutes/week in patients completing the PACP; so that the incremental cost of converting one sedentary adult to an ‘active state’ of 150 minutes of moderate intensity physical activity per week amounts to £ 886.50 in disease register practices, compared to opportunistic screening. CONCLUSIONS: Disease register screening is more costly than opportunistic patient recruitment. However, additional costs come with a higher completion rate and better outcomes in terms of behavioural change in patients completing the care pathway. Further research is needed to rigorously evaluate intervention efficiency and to assess the link between behavioural change and changes in quality adjusted life years (QALYs).This article is available through the Brunel Open Access Publishing Fund

Dynamics of Repeated Interviews with Children.

Concerns regarding repeat interviews with child witnesses include greater use of suggestive questions in later interviews due to bias, and that children may appear inconsistent and, therefore, be judged as less reliable in court. UK transcripts of first and second interviews with 21 child victims/witnesses (conducted by qualified interviewers) were coded for question types and child responses. Interviewers were consistent in their proportional use of question types across interviews. Furthermore, children were as informative in second interviews as in first, mostly providing new details consistent with their prior recall. Despite the apparent lack of training in conducting repeated interviews, no negative effects were found; second interviews appeared to be conducted as well as initial interviews and they provided new details without many contradictions. It is suggested that when a child’s testimony is paramount for an investigation, a well-conducted supplementary interview may be an effective way of gaining further investigative leads

Parents’ experiences of health visiting for children with Down syndrome

© MA Healthcare Limited.Children with Down syndrome have an increased likelihoodof experiencing serious health conditions. Health visitors canhave an important role in monitoring and promoting healthand development for young children with Down syndrome.This study aimed to explore parents’ experiences of healthvisiting services for children with Down syndrome. Twentyfour parents of children with Down syndrome aged 0–5 yearscompleted a brief questionnaire about the number and natureof visits from health visitors in the previous 12 months andtheir support needs. Some parents commented that otherprofessionals met the needs of their child, whereas others saidthat they would like more advice and support from healthvisitors. A further exploration of broader health serviceprovision, including health visiting, for young children withDown syndrome is needed.Peer reviewedFinal Accepted Versio

Controls on modern tributary-junction alluvial fan occurrence and morphology: High Atlas Mountains, Morocco

Modern tributary-junction alluvial fans (cone-shaped depositional landforms formed in confined valley settings) were analysed from a 20-km-long reach of the Dades River in the distal part of the fold-thrust belt region in the south-central High Atlas Mountains of Morocco. Here, a deeply dissected network of ephemeral tributary streams and a perennial trunk drainage characterised by an arid mountain desert climate are configured onto a folded and thrust faulted Mesozoic sedimentary sequence. Out of 186 tributary streams, only 29 (16%) generated alluvial fans at their tributary junctions. The fan-generating catchments possess higher relief, longer lengths, lower gradients, and larger areas than nonfan-generating catchments. Whilst geologically, fan-generating catchments are underlain by folded / steeply dipping weak bedrock conducive to high sediment yield. Tributary-junction fans are built from debris flow or fluvial processes into open or confined canyon trunk valley settings. The proximity of the perennial trunk drainage combined with the valley morphology produces lobate or foreshortened trimmed fan forms. Analysis of fan (area, gradient, process), catchment (area, relief, length, gradient), and tributary valley (width) variables reveals weak morphometric relationships, highlighted by residual plots that show dominance of smaller and lower gradient than expected fan forms. These morphometric relationships can be explained by interplay between the catchment and trunk drainage geology, morphology, climate, and flood regime that are combined into a conceptual ‘build and reset’ model. Ephemeral tributary-junction fans develop progressively during annual localised winter-spring storm events, attempting to build toward a morphological equilibrium. However, the fans never reach an equilibrium morphological form as they are reset by rare (>10 year) large floods along the River Dades that are linked to regional incursions of Atlantic low pressure troughs. The model highlights the spatial and temporal variability of tributary-junction fan building and illustrates the connectivity / coupling importance of such features in dryland mountainous terrains

Molecular screening of blue mussels indicated high mid-summer prevalence of human genogroup II Noroviruses, including the pandemic “GII.4 2012” variants in UK coastal waters during 2013

Pandemic norovirus in coastal blue mussels during summer in UK This molecular study is the first report, to the best of our knowledge, on identification of norovirus, NoV GII.4 Sydney 2012 variants, from blue mussels collected from UK coastal waters. Blue mussels (three pooled samples from twelve mussels) collected during the 2013 summer months from UK coastal sites were screened by RT-PCR assays. PCR products of RdRP gene for noroviruses were purified, sequenced and subjected to phylogenetic analysis. All the samples tested positive for NoVs. Sequencing revealed that the NoV partial RdRP gene sequences from two pooled samples clustered with the pandemic “GII.4 Sydney variants” whilst the other pooled sample clustered with the NoV GII.2 variants. This molecular study indicated mussel contamination with pathogenic NoVs even during mid-summer in UK coastal waters which posed potential risk of NoV outbreaks irrespective of season. As the detection of Sydney 2012 NoV from our preliminary study of natural coastal mussels interestingly corroborated with NoV outbreaks in nearby areas during the same period, it emphasizes the importance of environmental surveillance work for forecast of high risk zones of NoV outbreaks

Mapping Repeated Interviews

The present study introduces an adaptation of the Griffiths Question Map (GQM; Griffiths & Milne, 2006) which extends the chronological, visual map of question types used in an investigative interview to include child interviewee’s responses (through the addition of the Interview Answer Grid, IAG). Furthermore, it provides a rare evaluation of repeated interviews with children. From a sample of transcripts of Scottish repeated interviews with child victims, two ‘good’ and two ‘poor’ first interviews were chosen based on interviewer question types. First and second investigative interviews of these four children were mapped using the GQM and IAG in order to examine across the two interviews the similarity of interviewer and interviewee behaviours and the consistency and investigative-relevance of information provided. Both ‘good’ and ‘poor’ interviews were found to include practices discouraged by interviewing guidelines, which would not have been identified by examining question proportions alone. Furthermore, ‘good’ first interviews were followed by second interviews which began with poor question types, suggesting a possible impact of confirmation bias. Social support was also assessed and found to be used infrequently, mainly in response to the child being informative rather than pre-emptively by interviewers in an attempt to encourage this. Children were also found to disclose throughout their second interviews, suggesting that rapport-maintenance is vital for single and multiple interviews. The use of the GQM and IAG are encouraged as techniques for determining interview quality.N/

Fine-Grained Open Learner Models: Complexity Versus Support

Open Learner Models (OLM) show the learner model to users to assist their self-regulated learning by, for example, helping prompt reflection, facilitating planning and supporting navigation. OLMs can show different levels of detail of the underlying learner model, and can also structure the information differently. As a result, a trade-off may exist between the potential for better support for learning and the complexity of the information shown. This paper investigates students' perceptions about whether offering more and richer information in an OLM will result in more effective support for their self-regulated learning. In a first study, questionnaire responses relating to designs for six visualisations of varying complexity led to the implementation of three variations on one of the designs. A second controlled study involved students interacting with these variations. The study revealed that the most useful variation for searching for suitable learning material was a visualisation combining a basic coloured grid, an extended bar chart-like visualisation indicating related concepts, and a learning gauge

Composing individuals: ethnographic reflections on success and prestige in the British New Music Network

In contrast to established musicians, lesser-known composers have received scant attention in art music scholarship. This article, based on an ethnographic study, considers how a group of British composers construed ideas of success and prestige, which I analyse in terms of anthropological writings on exchange, Bourdieusian symbolic economies, and Foucauldian notions of disciplinary power. Prestige was ascribed to composers who created ‘interesting’ music, a category that eclipsed novelty as an aim. Individuality, enacted within a context of individualism, was key to assessing whether music was interesting. This individuality had to be tempered, structured, and embedded in the social norms of this and related ‘art worlds’. The article examines the social processes involved in creating this individuality, musical personality, and music considered interesting