REFERQUAL: A pilot study of a new service quality assessment instrument in the GP Exercise Referral scheme setting

Background The development of an instrument accurately assessing service quality in the GP Exercise Referral Scheme (ERS) industry could potentially inform scheme organisers of the factors that affect adherence rates leading to the implementation of strategic interventions aimed at reducing client drop-out. Methods A modified version of the SERVQUAL instrument was designed for use in the ERS setting and subsequently piloted amongst 27 ERS clients. Results Test re-test correlations were calculated via Pearson's 'r' or Spearman's 'rho', depending on whether the variables were Normally Distributed, to show a significant (mean r = 0.957, SD = 0.02, p < 0.05; mean rho = 0.934, SD = 0.03, p < 0.05) relationship between all items within the questionnaire. In addition, satisfactory internal consistency was demonstrated via Cronbach's 'α'. Furthermore, clients responded favourably towards the usability, wording and applicability of the instrument's items. Conclusion REFERQUAL is considered to represent promise as a suitable tool for future evaluation of service quality within the ERS community. Future research should further assess the validity and reliability of this instrument through the use of a confirmatory factor analysis to scrutinise the proposed dimensional structure

Novel Role of Phosphorylation-Dependent Interaction between FtsZ and FipA in Mycobacterial Cell Division

The bacterial divisome is a multiprotein complex. Specific protein-protein interactions specify whether cell division occurs optimally, or whether division is arrested. Little is known about these protein-protein interactions and their regulation in mycobacteria. We have investigated the interrelationship between the products of the Mycobacterium tuberculosis gene cluster Rv0014c-Rv0019c, namely PknA (encoded by Rv0014c) and FtsZ-interacting protein A, FipA (encoded by Rv0019c) and the products of the division cell wall (dcw) cluster, namely FtsZ and FtsQ. M. smegmatis strains depleted in components of the two gene clusters have been complemented with orthologs of the respective genes of M. tuberculosis. Here we identify FipA as an interacting partner of FtsZ and FtsQ and establish that PknA-dependent phosphorylation of FipA on T77 and FtsZ on T343 is required for cell division under oxidative stress. A fipA knockout strain of M. smegmatis is less capable of withstanding oxidative stress than the wild type and showed elongation of cells due to a defect in septum formation. Localization of FtsQ, FtsZ and FipA at mid-cell was also compromised. Growth and survival defects under oxidative stress could be functionally complemented by fipA of M. tuberculosis but not its T77A mutant. Merodiploid strains of M. smegmatis expressing the FtsZ(T343A) showed inhibition of FtsZ-FipA interaction and Z ring formation under oxidative stress. Knockdown of FipA led to elongation of M. tuberculosis cells grown in macrophages and reduced intramacrophage growth. These data reveal a novel role of phosphorylation-dependent protein-protein interactions involving FipA, in the sustenance of mycobacterial cell division under oxidative stress

An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly

Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2-ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays

What are we measuring? A critique of range of motion methods currently in use for Dupuytren's disease and recommendations for practice

Background: Range of motion is the most frequently reported measure used in practice to evaluate outcomes. A goniometer is the most reliable tool to assess range of motion yet, the lack of consistency in reporting prevents comparison between studies. The aim of this study is to identify how range of motion is currently assessed and reported in Dupuytren’s disease literature. Following analysis recommendations for practice will be made to enable consistency in future studies for comparability. This paper highlights the variation in range of motion reporting in Dupuytren’s disease. Methods: A Participants, Intervention, Comparison, Outcomes and Study design format was used for the search strategy and search terms. Surgery, needle fasciotomy or collagenase injection for primary or recurrent Dupuytren’s disease in adults were included if outcomes were monitored using range of motion to record change. A literature search was performed in May 2013 using subject heading and free-text terms to also capture electronic publications ahead of print. In total 638 publications were identified and following screening 90 articles met the inclusion criteria. Data was extracted and entered onto a spreadsheet for analysis. A thematic analysis was carried out to establish any duplication, resulting in the final range of motion measures identified. Results: Range of motion measurement lacked clarity, with goniometry reportedly used in only 43 of the 90 studies, 16 stated the use of a range of motion protocol. A total of 24 different descriptors were identified describing range of motion in the 90 studies. While some studies reported active range of motion, others reported passive or were unclear. Eight of the 24 categories were identified through thematic analysis as possibly describing the same measure, ‘lack of joint extension’ and accounted for the most frequently used. Conclusions: Published studies lacked clarity in reporting range of motion, preventing data comparison and meta-analysis. Percentage change lacks context and without access to raw data, does not allow direct comparison of baseline characteristics. A clear description of what is being measured within each study was required. It is recommended that range of motion measuring and reporting for Dupuytren’s disease requires consistency to address issues that fall into 3 main categories:- Definition of terms Protocol statement Outcome reportin

Coordinated optimization of visual cortical maps (II) Numerical studies

It is an attractive hypothesis that the spatial structure of visual cortical architecture can be explained by the coordinated optimization of multiple visual cortical maps representing orientation preference (OP), ocular dominance (OD), spatial frequency, or direction preference. In part (I) of this study we defined a class of analytically tractable coordinated optimization models and solved representative examples in which a spatially complex organization of the orientation preference map is induced by inter-map interactions. We found that attractor solutions near symmetry breaking threshold predict a highly ordered map layout and require a substantial OD bias for OP pinwheel stabilization. Here we examine in numerical simulations whether such models exhibit biologically more realistic spatially irregular solutions at a finite distance from threshold and when transients towards attractor states are considered. We also examine whether model behavior qualitatively changes when the spatial periodicities of the two maps are detuned and when considering more than 2 feature dimensions. Our numerical results support the view that neither minimal energy states nor intermediate transient states of our coordinated optimization models successfully explain the spatially irregular architecture of the visual cortex. We discuss several alternative scenarios and additional factors that may improve the agreement between model solutions and biological observations.Comment: 55 pages, 11 figures. arXiv admin note: substantial text overlap with arXiv:1102.335

De Novo Mutations in PDE10A Cause Childhood-Onset Chorea with Bilateral Striatal Lesions.

Chorea is a hyperkinetic movement disorder resulting from dysfunction of striatal medium spiny neurons (MSNs), which form the main output projections from the basal ganglia. Here, we used whole-exome sequencing to unravel the underlying genetic cause in three unrelated individuals with a very similar and unique clinical presentation of childhood-onset chorea and characteristic brain MRI showing symmetrical bilateral striatal lesions. All individuals were identified to carry a de novo heterozygous mutation in PDE10A (c.898T>C [p.Phe300Leu] in two individuals and c.1000T>C [p.Phe334Leu] in one individual), encoding a phosphodiesterase highly and selectively present in MSNs. PDE10A contributes to the regulation of the intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Both substitutions affect highly conserved amino acids located in the regulatory GAF-B domain, which, by binding to cAMP, stimulates the activity of the PDE10A catalytic domain. In silico modeling showed that the altered residues are located deep in the binding pocket, where they are likely to alter cAMP binding properties. In vitro functional studies showed that neither substitution affects the basal PDE10A activity, but they severely disrupt the stimulatory effect mediated by cAMP binding to the GAF-B domain. The identification of PDE10A mutations as a cause of chorea further motivates the study of cAMP signaling in MSNs and highlights the crucial role of striatal cAMP signaling in the regulation of basal ganglia circuitry. Pharmacological modulation of this pathway could offer promising etiologically targeted treatments for chorea and other hyperkinetic movement disorders

Adolescent gambling behaviour, a single latent construct and indicators of risk: findings from a national survey of New Zealand high school students

This study explores underlying latent construct/s of gambling behaviour, and identifies indicators of “unhealthy gambling”. Data were collected from Youth’07 a nationally representative sample of New Zealand secondary school students (N = 9107). Exploratory factor analyses, item-response theory analyses, multiple indicators-multiple causes, and differential item functioning analyses were used to assess dimensionality of gambling behaviour, underlying factors, and indicators of unhealthy gambling. A single underlying continuum of gambling behaviour was identified. Gambling frequency and ‘gambling because I can’t stop’ were most strongly associated with unhealthy gambling. Gambling to ‘feel better about myself’ and to ‘forget about things’ provided the most precise discriminants of unhealthy gambling. Multivariable analyses found that school connectedness was associated with lower levels of unhealthy gambling

Oral cancer awareness amongst hospital nursing staff: a pilot study

<p>Abstract</p> <p>Background</p> <p>Oral cancer is as prevalent as cervical and testicular cancer in the United Kingdom. Nursing staff provide the oral health care for the patient population in hospital. Admission to hospital provides a 'window of opportunity' for oral cancer 'screening' via an oral health check during nursing clerking. This study aimed to investigate whether nursing staff are aware of risk factors for oral cancer, its clinical signs, and could therefore provide a 'screening' service for oral cancer.</p> <p>Method</p> <p>Through the use of a questionnaire we assessed 121 nursing staff on oral health check behaviour and attitudes; their knowledge of risk factors for oral cancer; their understanding of common clinical signs of oral cancer; and their undergraduate and postgraduate training in oral health and oral cancer.</p> <p>Results</p> <p>Over 80% thought oral health checks were important although only 49% performed this task regularly; approximately 70% identified smoking as a risk factor but less than 30% identified alcohol. Awareness of the clinical signs of oral cancer was low with 21% identifying white patches, 15% identifying ulceration and only 2% identifying red patches despite their malignant potential. Nurses within 3 years of qualification were significantly better at recognising risk factors for oral cancer than their colleagues, identifying a need for continuing postgraduate education on oral health and oral cancer. Sixty-one percent of nursing staff received oral healthcare as an undergraduate with 34 percent receiving postgraduate training.</p> <p>Conclusion</p> <p>An oral health check upon admission to hospital provides an opportunity for nurses to 'screen' for oral diseases including oral cancer and allows nurses a greater role in total patient care. Nurses' awareness of oral cancer risk factors and clinical signs was, however, poor. This study highlights a need for improved education of nurses on oral cancer to make the oral health check on admission viable for oral cancer screening.</p

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH

Attracting and retaining health workers in rural areas: investigating nurses’ views on rural posts and policy interventions

<p>Abstract</p> <p>Background</p> <p>Kenya has bold plans for scaling up priority interventions nationwide, but faces major human resource challenges, with a lack of skilled workers especially in the most disadvantaged rural areas.</p> <p>Methods</p> <p>We investigated reasons for poor recruitment and retention in rural areas and potential policy interventions through quantitative and qualitative data collection with nursing trainees. We interviewed 345 trainees from four purposively selected Medical Training Colleges (MTCs) (166 pre-service and 179 upgrading trainees with prior work experience). Each interviewee completed a self-administered questionnaire including likert scale responses to statements about rural areas and interventions, and focus group discussions (FGDs) were conducted at each MTC.</p> <p>Results</p> <p>Likert scale responses indicated mixed perceptions of both living and working in rural areas, with a range of positive, negative and indifferent views expressed on average across different statements. The analysis showed that attitudes to working in rural areas were significantly positively affected by being older, but negatively affected by being an upgrading student. Attitudes to living in rural areas were significantly positively affected by being a student at the MTC furthest from Nairobi.</p> <p>During FGDs trainees raised both positive and negative aspects of rural life. Positive aspects included lower costs of living and more autonomy at work. Negative issues included poor infrastructure, inadequate education facilities and opportunities, higher workloads, and inadequate supplies and supervision. Particular concern was expressed about working in communities dominated by other tribes, reflecting Kenya’s recent election-related violence.</p> <p>Quantitative and qualitative data indicated that students believed several strategies could improve rural recruitment and retention, with particular emphasis on substantial rural allowances and the ability to choose their rural location. Other interventions highlighted included provision of decent housing, and more rapid career advancement. However, recently introduced short term contracts in named locations were not favoured due to their lack of pension plans and job security.</p> <p>Conclusions</p> <p>This study identified a range of potential interventions to increase rural recruitment and retention, with those most favored by nursing students being additional rural allowances, and allowing choice of rural location. Greater investment is needed in information systems to evaluate the impact of such policies.</p