RNA interference in adult Ascaris suum - an opportunity for the development of a functional genomics platform that supports organism-, tissue- and cell-based biology in a nematode parasite

The sustainable control of animal parasitic nematodes requires the development of efficient functional genomics platforms to facilitate target validation and enhance anthelmintic discovery. Unfortunately, the utility of RNA interference (RNAi) for the validation of novel drug targets in nematode parasites remains problematic. Ascaris suum is an important veterinary parasite and a zoonotic pathogen. Here we show that adult A. suum is RNAi competent, and highlight the induction, spread and consistency of RNAi across multiple tissue types. This platform provides a new opportunity to undertake whole organism-, tissue- and cell-level gene function studies to enhance target validation processes for nematode parasites of veterinary/medical significance.

Platform Competition as Network Contestability

Recent research in industrial organisation has investigated the essential place that middlemen have in the networks that make up our global economy. In this paper we attempt to understand how such middlemen compete with each other through a game theoretic analysis using novel techniques from decision-making under ambiguity.
We model a purposely abstract and reduced model of one middleman who provides a two-sided platform, mediating surplus-creating interactions between two users. The middleman evaluates uncertain outcomes under positional ambiguity, taking into account the possibility of the emergence of an alternative middleman offering intermediary services to the two users.
Surprisingly, we find many situations in which the middleman will purposely extract maximal gains from her position. Only if there is relatively low probability of devastating loss of business under competition, the middleman will adopt a more competitive attitude and extract less from her position.

'When I Land in Islamabad I Feel Home and When I Land in Heathrow I Feel Home': Gendered Belonging and Diasporic Identities of South Asian British Citizens in London, in Leicester and in North England

According to Deleuze and Guattari (1987) ‘de-territorialization’ is followed by a moment of re-territorialization. This moment, however, has to be regarded as a continuing educational process that becomes a different spatial site of social practices. It is argued in this chapter that regional, local as well as global identification override national and mono-ethno cultural identities, while shaping particular notions of gendered belonging and creating specific diasporic practices. Based on a sample of interviews with professional and academic South Asian British citizens in London, in Leicester, and in a number of Northern English cities gendered and generational patterns in terms of local diasporic identities are explored. Apart from multiple cultural belonging, foremost, territorial bonds and notions of group loyalty collapse at a point where temporary migration and settlement alternate in individual biographies.

How Mothers Talk About Placement of Their Child With Autism Outside the Home

In this article I use insights offered by the poststructural shift and linguistic turn in social scientific inquiry, specifically discourse analysis, to explore mothers’ talk about the placement of their child with autism outside of the home. By viewing mothers’ talk as data, I bring to light the discourses and interpretive practices that mothers drew on to organize their talk of placement. In doing so, I provide insights into how mothers gave meaning to processes of placement while also expanding on commonsensical discursive notions of “good” mothering, caregiving, and family. Implications of the findings are discussed.

Social Work Home Visits to Children and Families in the UK: A Foucauldian Perspective

The home visit is at the heart of social work practice with children and families; it is what children and families' social workers do more than any other single activity (except for recording), and it is through the home visit that assessments are made on a daily basis about risk, protection and welfare of children. And yet it is, more than any other activity, an example of what Pithouse has called an ‘invisible trade’: it happens behind closed doors, in the most secret and intimate spaces of family life. Drawing on conceptual tools associated with the work of Foucault, this article sets out to provide a critical, chronological review of research, policy and practice on home visiting. We aim to explain how and in what ways changing discourses have shaped the emergence, legitimacy, research and practice of the social work home visit to children and families at significant time periods and in a UK context. We end by highlighting the importance for the social work profession of engagement and critical reflection on the identified themes as part of their daily practice.

Systematic review of the use of behaviour change techniques (BCTs) in home-based cardiac rehabilitation programmes for patients with cardiovascular disease-protocol

BACKGROUND: Cardiovascular diseases (CVDs), including myocardial infarction, heart failure, peripheral arterial disease and strokes, are highly prevalent conditions and are associated with high morbidity and mortality. Cardiac rehabilitation (CR) is an effective form of secondary prevention for CVD but there is a lack of information regarding which specific behaviour change techniques (BCTs) are included in programmes that are associated with improvements in cardiovascular risk factors. This systematic review will describe the BCTs which are utilised within home-based CR programmes that are effective at reducing a spectrum of CVD risk factors.

METHODS/DESIGN: The review will be reported in line with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidance. Randomised and quasi-randomised controlled trials of home-based CR initiated following a vascular event (myocardial infarction, heart failure, peripheral arterial disease and stroke patients) will be included. Articles will be identified through a comprehensive search of MEDLINE, Embase, PsycINFO, Web of Science and Cochrane Database guided by a medical librarian. Two review authors will independently screen articles retrieved from the search for eligibility and extract relevant data, identifying which specific BCTs are included in programmes that are associated with improvements in particular modifiable vascular risk factors.

DISCUSSION: This review will be of value to clinicians and healthcare professionals working with cardiovascular patients by identifying specific BCTs which are used within effective home-based CR. It will also inform the future design and evaluation of complex health service interventions aimed at secondary prevention in CVD.

Home-range size in juveniles of the temperate reef fish, the common triplefin (Forsterygion lapillum)

An organism’s home range dictates the spatial scale on which important processes occur (e.g. competition and predation) and directly affects the relationship between individual fitness and local habitat quality. Many reef fish species have very restricted home ranges after settlement and, here, we quantify home-range size in juveniles of a widespread and abundant reef fish in New Zealand, the common triplefin (Forsterygion lapillum). We conducted visual observations on 49 juveniles (mean size = 35-mm total length) within the Wellington harbour, New Zealand. Home ranges were extremely small, 0.053 m2 ± 0.029 (mean ± s.d.) and were unaffected by adult density, body size or substrate composition. A regression tree indicated that home-range size sharply decreased ~4.5 juveniles m–2 and a linear mixed model confirmed that home-range sizes in high-density areas (>4.5 juveniles m–2) were significantly smaller (34%) than those in low-density areas (after accounting for a significant effect of fish movement on our home-range estimates). Our results suggest that conspecific density may have negative and non-linear effects on home-range size, which could shape the spatial distribution of juveniles within a population, as well as influence individual fitness across local density gradients.

Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

BACKGROUND: Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone.

METHODS: Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544).

FINDINGS: 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc.

INTERPRETATION: Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy.

FUNDING: Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research.

Temperament test for re-homed dogs validated through direct behavioral observation in shelter and home environment

This study was the first attempt to carry out a validation of a temperament test (TT) for shelter dogs that addressed the topics of inter- and intra-raters agreements, test-retest reliability, and validity. The TT consisted of 22 subtests. Each dog was approached and handled by an unfamiliar person and made to interact with a same- and an opposite-gender conspecific. Dogs were tested twice in the shelter and once in their new homes 4 months after adoption to evaluate consistency in behavioral assessment. Playfulness, trainability, problem solving abilities, food possessiveness, and reactivity to sudden stimuli were also evaluated. Testers scored dogs' responses in terms of confidence, fearfulness, and aggressiveness. Results highlighted strengths and limits of this TT that was devised to help shelter staff in matching dogs' personality and owners' expectations. Methodological constraints when working with sheltered dogs are unavoidable; however, the test proved to be overall feasible, reliable, and valid although further studies are needed to address the critical issues that emerged. © 2011 Elsevier Inc.

The Impact of Multimedia Education on Uptake of Comprehensive Eye Examinations in Rural China: A Randomized, Controlled Trial

PURPOSE: To study the effect of multimedia education on acceptance of comprehensive eye examinations (CEEs), critical for detecting glaucoma and diabetic eye disease, among rural Chinese patients using a randomized, controlled design.
METHODS: Patients aged ≥40 years were recruited from 52 routine clinic sessions (26 intervention, 26 control) conducted at seven rural hospitals in Guangdong, China. Subjects answered demographic questionnaires, were tested on knowledge about CEEs and chronic eye disease, and were told the cost of examination (range US$0-8). At intervention sessions, subjects were cluster-randomized to view a 10-minute video on the value of CEEs and retested. Control subjects were not retested. Trial outcomes were acceptance of CEEs (primary outcome) and final knowledge scores (secondary outcome).
RESULTS: At baseline, >70% (p = 0.70) of both intervention (n = 241, 61.2 ± 12.3 years) and control (n = 218, 58.4 ± 11.7 years) subjects answered no knowledge questions correctly, but mean scores on the test (maximum 5 points) increased by 1.39 (standard deviation 0.12) points (p < 0.001) after viewing the video. Intervention (73.0%) and control (72.9%) subjects did not differ in acceptance of CEEs (p > 0.50). In mixed-effect logistic regression models, acceptance of CEEs was associated with availability of free CEEs (odds ratio 18.3, 95% confidence interval 1.32-253.0), but not group assignment or knowledge score. Acceptance was 97.5% (79/81) when free exams were offered.
CONCLUSIONS: Education increased knowledge about but not acceptance of CEEs, which was generally high. Making CEEs free could further increase acceptance.