IMPLEmenting a clinical practice guideline for acute low back pain evidence-based manageMENT in general practice (IMPLEMENT) : cluster randomised controlled trial study protocol

Background: Evidence generated from reliable research is not frequently implemented into clinical practice. Evidence-based clinical practice guidelines are a potential vehicle to achieve this. A recent systematic review of implementation strategies of guideline dissemination concluded that there was a lack of evidence regarding effective strategies to promote the uptake of guidelines. Recommendations from this review, and other studies, have suggested the use of interventions that are theoretically based because these may be more effective than those that are not. An evidencebased clinical practice guideline for the management of acute low back pain was recently developed in Australia. This provides an opportunity to develop and test a theory-based implementation intervention for a condition which is common, has a high burden, and for which there is an evidence-practice gap in the primary care setting. Aim: This study aims to test the effectiveness of a theory-based intervention for implementing a clinical practice guideline for acute low back pain in general practice in Victoria, Australia. Specifically, our primary objectives are to establish if the intervention is effective in reducing the percentage of patients who are referred for a plain x-ray, and improving mean level of disability for patients three months post-consultation. Methods/Design: This study protocol describes the details of a cluster randomised controlled trial. Ninety-two general practices (clusters), which include at least one consenting general practitioner, will be randomised to an intervention or control arm using restricted randomisation. Patients aged 18 years or older who visit a participating practitioner for acute non-specific low back pain of less than three months duration will be eligible for inclusion. An average of twenty-five patients per general practice will be recruited, providing a total of 2,300 patient participants. General practitioners in the control arm will receive access to the guideline using the existing dissemination strategy. Practitioners in the intervention arm will be invited to participate in facilitated face-to-face workshops that have been underpinned by behavioural theory. Investigators (not involved in the delivery of the intervention), patients, outcome assessors and the study statistician will be blinded to group allocation. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN012606000098538 (date registered 14/03/2006).The trial is funded by the NHMRC by way of a Primary Health Care Project Grant (334060). JF has 50% of her time funded by the Chief Scientist Office3/2006). of the Scottish Government Health Directorate and 50% by the University of Aberdeen. PK is supported by a NHMRC Health Professional Fellowship (384366) and RB by a NHMRC Practitioner Fellowship (334010). JG holds a Canada Research Chair in Health Knowledge Transfer and Uptake. All other authors are funded by their own institutions

Family medicine trainees' clinical experience of chronic disease during training: a cross-sectional analysis from the registrars' clinical encounters in training study

Background: A broad case-mix in family physicians’ (general practitioners’, GPs’) vocational trainee experience is deemed essential in producing competent independent practitioners. It is suggested that the patient-mix should include common and significant conditions and be similar to that of established GPs. But the content of contemporary GP trainees’ clinical experience in training is not well-documented. In particular, how well trainees’ experience reflects changing general practice demographics (with an increasing prevalence of chronic disease) is unknown. We aimed to establish levels of trainees’ clinical exposure to chronic disease in training (and associations of this exposure) and to establish content differences in chronic disease consultations (compared to other consultations), and differences in trainees’ actions arising from these consultations. Methods: A cross-sectional analysis from the Registrars’ Clinical Encounters in Training (ReCEnT) study, a cohort study of GP registrars’ (trainees’) consultations in four Australian GP training organisations. Trainees record detailed data from 60 consecutive consultations per six-month training term. Diagnoses/problems encountered are coded using the International Classification of Primary Care-2 PLUS (ICPC-2 PLUS). A classification system derived from ICPC-2 PLUS was used to define diagnoses/problems as chronic/non-chronic disease. The outcome factor for analyses was trainees’ consultations in which chronic disease was encountered. Independent variables were a range of patient, trainee, practice, consultation and educational factors. Results: Of 48,112 consultations (of 400 individual trainees), 29.5% included chronic disease problems/diagnoses. Associations of a consultation including chronic disease were the patient being older, male, and having consulted the trainee previously, and the practice routinely bulk-billing (not personally charging) patients. Consultations involving a chronic disease lasted longer, dealt with more problems/diagnoses, and were more likely to result in specialist referrals and trainees generating a personal learning goal. They were associated with less pathology tests being ordered. Conclusions: Trainees saw chronic disease less frequently than have established GPs in comparable studies. The longer duration and more frequent generation of learning goals in chronic disease-containing consultations suggest trainees may find these consultations particularly challenging. Our findings may inform the design of measures aimed at increasing the chronic disease component of trainees’ patient-mix.Parker Magin, Simon Morgan, Kim Henderson, Amanda Tapley, Patrick McElduff, James Pearlman, Susan Goode, Neil Spike, Caroline Laurence, John Scott, Allison Thomson and Mieke van Drie

Exploring the similarities and differences between medical assessments of competence and criminal responsibility

The medical assessments of criminal responsibility and competence to consent to treatment are performed, developed and debated in distinct domains. In this paper I try to connect these domains by exploring the similarities and differences between both assessments. In my view, in both assessments a decision-making process is evaluated in relation to the possible influence of a mental disorder on this process. I will argue that, in spite of the relevance of the differences, both practices could benefit from the recognition of this similarity. For cooperative research could be developed directed at elucidating exactly how various mental disturbances can affect decision-making processes

Multitrophic Interaction in the Rhizosphere of Maize: Root Feeding of Western Corn Rootworm Larvae Alters the Microbial Community Composition

BACKGROUND: Larvae of the Western Corn Rootworm (WCR) feeding on maize roots cause heavy economical losses in the US and in Europe. New or adapted pest management strategies urgently require a better understanding of the multitrophic interaction in the rhizosphere. This study aimed to investigate the effect of WCR root feeding on the microbial communities colonizing the maize rhizosphere. METHODOLOGY/PRINCIPAL FINDINGS: In a greenhouse experiment, maize lines KWS13, KWS14, KWS15 and MON88017 were grown in three different soil types in presence and in absence of WCR larvae. Bacterial and fungal community structures were analyzed by denaturing gradient gel electrophoresis (DGGE) of the 16S rRNA gene and ITS fragments, PCR amplified from the total rhizosphere community DNA. DGGE bands with increased intensity were excised from the gel, cloned and sequenced in order to identify specific bacteria responding to WCR larval feeding. DGGE fingerprints showed that the soil type and the maize line influenced the fungal and bacterial communities inhabiting the maize rhizosphere. WCR larval feeding affected the rhiyosphere microbial populations in a soil type and maize line dependent manner. DGGE band sequencing revealed an increased abundance of Acinetobacter calcoaceticus in the rhizosphere of several maize lines in all soil types upon WCR larval feeding. CONCLUSION/SIGNIFICANCE: The effects of both rhizosphere and WCR larval feeding seemed to be stronger on bacterial communities than on fungi. Bacterial and fungal community shifts in response to larval feeding were most likely due to changes of root exudation patterns. The increased abundance of A. calcoaceticus suggested that phenolic compounds were released upon WCR wounding

Rethinking therapeutic strategies in cancer: wars, fields, anomalies and monsters

This article argues that the excessive focus on cancer as an insidious living defect that needs to be destroyed has obscured the fact that cancer develops inside human beings. Therefore, in order to contribute to debates about new cancer therapies, we argue that it is important to gain a broader understanding of what cancer is and how it might be otherwise. First, in order to reframe the debate, we utilize Pierre Bourdieu’s field analysis in order to gain a stronger understanding of the structure of the (sub)field of cancer research. In doing so, we are able to see that those in a dominant position in the field, with high levels of scientific capital at their disposal, are in the strongest position to determine the type of research that is carried out and, more significantly, how cancer is perceived. Field analysis enables us to gain a greater understanding of the complex interplay between the field of science (and, more specifically, the subfield of cancer research) and broader sources of power. Second, we draw attention to new possible ways of understanding cancer in its evolutionary context. One of the problems facing cancer research is the narrow time frame within which cancer is perceived: the lives of cancer cells are considered from the moment the cells initially change. In contrast, the approach put forward here requires a different way of thinking: we take a longer view and consider cancer as a living entity, with cancer perceived as anomalous rather than abnormal. Third, we theorize the possibility of therapeutic strategies that might involve the redirection (rather than the eradication) of cancer cells. This approach also necessitates new ways of perceiving cancer

Regulatory elements and transcriptional control of chicken vasa homologue (CVH) promoter in chicken primordial germ cells

BACKGROUND: Primordial germ cells (PGCs), the precursors of functional gametes, have distinct characteristics and exhibit several unique molecular mechanisms to maintain pluripotency and germness in comparison to somatic cells. They express germ cell-specific RNA binding proteins (RBPs) by modulating tissue-specific cis- and trans-regulatory elements. Studies on gene structures of chicken vasa homologue (CVH), a chicken RNA binding protein, involved in temporal and spatial regulation are thus important not only for understanding the molecular mechanisms that regulate germ cell fate, but also for practical applications of primordial germ cells. However, very limited studies are available on regulatory elements that control germ cell-specific expression in chicken. Therefore, we investigated the intricate regulatory mechanism(s) that governs transcriptional control of CVH. RESULTS: We constructed green fluorescence protein (GFP) or luciferase reporter vectors containing the various 5′ flanking regions of CVH gene. From the 5′ deletion and fragmented assays in chicken PGCs, we have identified a CVH promoter that locates at −316 to +275 base pair fragment with the highest luciferase activity. Additionally, we confirmed for the first time that the 5′ untranslated region (UTR) containing intron 1 is required for promoter activity of the CVH gene in chicken PGCs. Furthermore, using a transcription factor binding prediction, transcriptome analysis and siRNA-mediated knockdown, we have identified that a set of transcription factors play a role in the PGC-specific CVH gene expression. CONCLUSIONS: These results demonstrate that cis-elements and transcription factors localizing in the 5′ flanking region including the 5′ UTR and an intron are important for transcriptional regulation of the CVH gene in chicken PGCs. Finally, this information will contribute to research studies in areas of reproductive biology, constructing of germ cell-specific synthetic promoter for tracing primordial germ cells as well as understanding the transcriptional regulation for maintaining germness in PGCs

A global threats overview for Numeniini populations: synthesising expert knowledge for a group of declining migratory birds

The Numeniini is a tribe of thirteen wader species (Scolopacidae, Charadriiformes) of which seven are near-threatened or globally threatened, including two critically endangered. To help inform conservation management and policy responses, we present the results of an expert assessment of the threats that members of this taxonomic group face across migratory flyways. Most threats are increasing in intensity, particularly in non-breeding areas, where habitat loss resulting from residential and commercial development, aquaculture, mining, transport, disturbance, problematic invasive species, pollution and climate change were regarded as having the greatest detrimental impact. Fewer threats (mining, disturbance, problematic native species and climate change) were identified as widely affecting breeding areas. Numeniini populations face the greatest number of non-breeding threats in the East Asian-Australasian Flyway, especially those associated with coastal reclamation; related threats were also identified across the Central and Atlantic Americas, and East Atlantic flyways. Threats on the breeding grounds were greatest in Central and Atlantic Americas, East Atlantic and West Asian flyways. Three priority actions were associated with monitoring and research: to monitor breeding population trends (which for species breeding in remote areas may best be achieved through surveys at key non-breeding sites), to deploy tracking technologies to identify migratory connectivity, and to monitor land-cover change across breeding and non-breeding areas. Two priority actions were focused on conservation and policy responses: to identify and effectively protect key non-breeding sites across all flyways (particularly in the East Asian - Australasian Flyway), and to implement successful conservation interventions at a sufficient scale across human-dominated landscapes for species’ recovery to be achieved. If implemented urgently, these measures in combination have the potential to alter the current population declines of many Numeniini species and provide a template for the conservation of other groups of threatened species

Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain long-term plasticity in the embryonic mammary gland.

Recent lineage tracing studies have revealed that mammary gland homeostasis relies on unipotent stem cells. However, whether and when lineage restriction occurs during embryonic mammary development, and which signals orchestrate cell fate specification, remain unknown. Using a combination of in vivo clonal analysis with whole mount immunofluorescence and mathematical modelling of clonal dynamics, we found that embryonic multipotent mammary cells become lineage-restricted surprisingly early in development, with evidence for unipotency as early as E12.5 and no statistically discernable bipotency after E15.5. To gain insights into the mechanisms governing the switch from multipotency to unipotency, we used gain-of-function Notch1 mice and demonstrated that Notch activation cell autonomously dictates luminal cell fate specification to both embryonic and basally committed mammary cells. These functional studies have important implications for understanding the signals underlying cell plasticity and serve to clarify how reactivation of embryonic programs in adult cells can lead to cancer.Wellcome Trus