An evaluation of the appropriateness of advice and healthcare contacts made following calls to NHS Direct Wales

Background: An evaluation of NHS Direct Wales (NHSDW), a national telephone-based healthcare advice and information service, was undertaken. A key objective was to describe the actions of callers and assess the appropriateness of advice and healthcare contacts made following calls, results of which are reported here. Methods: Postal questionnaires were sent to consecutive callers to NHSDW in May 2002 and February 2004 to determine 1) callers' actions following calls and 2) their views about the appropriateness of: advice given; and when to seek further care. An independent clinical panel agreed and applied a set of rules about healthcare sites where examinations, investigations, treatments and referrals could be obtained. The rules were then applied to the subsequent contacts to healthcare services reported by respondents and actions were classified in terms of whether they had been necessary and sufficient for the care received. Results: Response rates were similar in each survey: 1033/1897 (54.5%); 606/1204 (50.3%), with 75% reporting contacting NHSDW. In both surveys, nearly half of all callers reported making no further healthcare contact after their call to NHSDW. The most frequent subsequent contacts made were with GPs. More than four fifths of callers rated the advice given - concerning any further care needed and when to seek it - as appropriate (further care needed: survey 1: 673/729, 82.3%; survey 2: 389/421, 92.4%; when to seek further care - survey 1: 462/555, 83.2%; survey 2: n = 295/346, 85.3%). A similar proportion of cases was also rated through the rule set and backed up by the clinical panel as having taken necessary and sufficient actions following their calls to NHSDW (survey 1: 624/729, 80.6%; survey 2: 362/421, 84.4%), with more unnecessary than insufficient actions identified at each survey (survey 1: unnecessary 132/729, 17.1% versus insufficient 11/729, 1.4%; survey 2: unnecessary 47/421, 11.0% versus insufficient 14/421, 3.3%). Conclusion: Based on NHSDW caller surveys responses and applying a transparent rule set to caller actions a large majority of subsequent actions were assessed as appropriate, with insufficient contacts particularly infrequent. The challenge for NHSDW is to reduce the number of unnecessary contacts made following calls to the service, whilst maintaining safety.</p

Predicting the Effect of Surface Texture on the Qualitative Form of Prehension

Reach-to-grasp movements change quantitatively in a lawful (i.e. predictable) manner with changes in object properties. We explored whether altering object texture would produce qualitative changes in the form of the precontact movement patterns. Twelve participants reached to lift objects from a tabletop. Nine objects were produced, each with one of three grip surface textures (high-friction, medium-friction and low-friction) and one of three widths (50 mm, 70 mm and 90 mm). Each object was placed at three distances (100 mm, 300 mm and 500 mm), representing a total of 27 trial conditions. We observed two distinct movement patterns across all trials—participants either: (i) brought their arm to a stop, secured the object and lifted it from the tabletop; or (ii) grasped the object ‘on-the-fly’, so it was secured in the hand while the arm was moving. A majority of grasps were on-the-fly when the texture was high-friction and none when the object was low-friction, with medium-friction producing an intermediate proportion. Previous research has shown that the probability of on-the-fly behaviour is a function of grasp surface accuracy constraints. A finger friction rig was used to calculate the coefficients of friction for the objects and these calculations showed that the area available for a stable grasp (the ‘functional grasp surface size’) increased with surface friction coefficient. Thus, knowledge of functional grasp surface size is required to predict the probability of observing a given qualitative form of grasping in human prehensile behaviour

Conserved community structure and simultaneous divergence events in the fig wasps associated with Ficus benjamina in Australia and China

Localised patterns of species diversity can be influenced by many factors, including regional species pools, biogeographic features and interspecific interactions. Despite recognition of these issues, we still know surprisingly little about how invertebrate biodiversity is structured across geographic scales. In particular, there have been few studies of how insect communities vary geographically while using the same plant host. We compared the composition (species, genera) and functional structure (guilds) of the chalcid wasp communities associated with the widespread fig tree, Ficus benjamina, towards the northern (Hainan province, China) and southern (Queensland, Australia) edges of its natural range. Sequence data were generated for nuclear and mtDNA markers and used to delimit species, and Bayesian divergence analyses were used to test patterns of community cohesion through evolutionary time. Both communities host at least 14 fig wasp species, but no species are shared across continents. Community composition is similar at the genus level, with six genera shared although some differ in species diversity between China and Australia; a further three genera occur in only China or Australia. Community functional structure remains very similar in terms of numbers of species in each ecological guild despite community composition differing a little (genera) or a lot (species), depending on taxonomic level. Bayesian clustering analyses favour a single community divergence event across continents over multiple events for different ecological guilds. Molecular dating estimates of lineage splits between nearest inter-continental species pairs are broadly consistent with a scenario of synchronous community divergence from a shared "ancestral community". Fig wasp community structure and genus-level composition are largely conserved in a wide geographic comparison between China and Australia. Moreover, dating analyses suggest that the functional community structure has remained stable for long periods during historic range expansions. This suggests that ecological interactions between species may play a persistent role in shaping these communities, in contrast to findings in some comparable temperate systems

Efficacy and tolerability of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder: sex and age effects and effect size across the day

<p>Abstract</p> <p>Background</p> <p>Efficacy and safety profiles by sex and age (6-9 vs 10-12 years) and magnitude and duration of effect by effect size overall and across the day of lisdexamfetamine dimesylate (LDX) vs placebo were assessed.</p> <p>Methods</p> <p>This study enrolled children (6-12 years) with attention-deficit/hyperactivity disorder (ADHD) in an open-label dose optimization with LDX (30-70 mg/d) followed by a randomized, double-blind, placebo-controlled, 2-way crossover phase. Post hoc analyses assessed interaction between sex or age and treatment and assessed effect sizes for Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) and Permanent Product Measure of Performance (PERMP) scales and ADHD Rating Scale IV measures. No corrections for multiple testing were applied on time points and subgroup statistical comparisons.</p> <p>Results</p> <p>129 participants enrolled; 117 randomized. Both sexes showed improvement on all assessments at postdose time points; females showed less impairment than males for SKAMP and PERMP scores in treatment and placebo groups at nearly all times. Both age groups improved on all assessments at postdose time points. Children 10-12 years had less impairment in SKAMP ratings than those 6-9 years. Treatment-by-sex interactions were observed at time points for SKAMP-D, SKAMP total, and PERMP scores; no consistent pattern across scales or time points was observed. LDX demonstrated significant improvement vs placebo, by effect size, on SKAMP-D from 1.5-13 hours postdose. The overall LS mean (SE) SKAMP-D effect size was -1.73 (0.18). In the dose-optimization phase, common (≥2%) treatment-emergent adverse events (TEAEs) in males were upper abdominal pain, headache, affect lability, initial insomnia, and insomnia; in females were nausea and decreased weight. During the crossover phase for those taking LDX, higher incidence (≥2% greater) was observed in males for upper abdominal pain and insomnia and in females for nausea and headache. Overall incidence of TEAEs in age groups was similar.</p> <p>Conclusion</p> <p>Apparent differences in impairment level between sex and age groups were noted. However, these results support the efficacy of LDX from 1.5 hours to 13 hours postdose in boys and girls with medium to large effect sizes across the day with some variability in TEAE incidence by sex.</p> <p>Trial Registration Number</p> <p>ClinicalTrials.gov Identifier: <a href="http://clinicaltrials.gov/ct2/show/NCT00500149">NCT00500149</a>.</p

Trajectories of dementia-related cognitive decline in a large mental health records derived patient cohort

Background: Modeling trajectories of decline can help describe the variability in progression of cognitive impairment in dementia. Better characterisation of these trajectories has significant implications for understanding disease progression, trial design and care planning. Methods: Patients with at least three Mini-mental State Examination (MMSE) scores recorded in the South London and Maudsley NHS Foundation Trust Electronic Health Records, UK were selected (N = 3441) to form a retrospective cohort. Trajectories of cognitive decline were identified through latent class growth analysis of longitudinal MMSE scores. Demographics, Health of Nation Outcome Scales and medications were compared across trajectories identified. Results: Four of the six trajectories showed increased rate of decline with lower baseline MMSE. Two trajectories had similar initial MMSE scores but different rates of decline. In the faster declining trajectory of the two, a higher incidence of both behavioral problems and sertraline prescription were present. Conclusions: We find suggestive evidence for association of behavioral problems and sertraline prescription with rate of decline. Further work is needed to determine whether trajectories replicate in other datasets

Dissecting the transcriptional networks underlying breast cancer: NR4A1 reduces the migration of normal and breast cancer cell lines

Introduction: Breast cancer currently accounts for more than one-quarter of all female cancers and, despite the great progress in treatment observed in the past few years, the need for identification of new gene targets that can be used for diagnosis, prognosis and therapy is evident. A previous study identified the transcription factor NR4A1 as a gene upregulated in primary breast cancer compared with normal tissue by microarray analysis and sequencing technologies. The purpose of the study was to identify the role of NR4A1 in normal mammary epithelial and breast cancer cell biology.Methods: NR4A1 expression in breast tumours was assessed by semiquantitative and real-time PCR using RNA from normal and tumour samples or breast cancer cell lines. Immunohistochemistry on tissue microarrays was performed to check NR4A1 protein expression in breast tumours. MCF-10A and 226L normal mammary epithelial cells as well as the tumour lines PMC42, ZR-75-1 and MDA-MB-231 were transduced with full-length NR4A1, and the ability of NR4A1-overexpressing cells to migrate was tested using scratch wound or transwell migration assays. Proliferation was measured using the MTT and BrdU assays, while apoptosis was determined by the Annexin V assay. The ability of the cells to adhere to extracellular matrix was tested by adhesion assays and integrin cell surface expression was measured by flow cytometry. Activation of the FAK as well as ERK1/2 and PI3K pathways was checked by western blotting.Results: Breast tissue microarray analysis showed NR4A1 expression in primary tumours, which was reduced in higher grade and metastatic tumours. Ectopic expression of NR4A1 in MCF-10A, 226L, PMC42 and ZR-75-1 cells led to reduced ability of the cells to migrate, while no differences were observed in their proliferation and apoptotic index. NR4A1 expression altered the ability of the MCF-10A cells to adhere to the extracellular matrix and affected cell surface expression of integrins.Conclusions: NR4A1 acts as an antimigratory factor in two normal mammary epithelial and two breast cancer cell lines tested. It is therefore possible that NR4A1 acts as an antimigratory factor in breast tumours, and further studies should be conducted to understand the mechanisms involved

Role of HDAC3 on p53 Expression and Apoptosis in T Cells of Patients with Multiple Sclerosis

Background: Histone deacetylase 3 (HDAC3) belongs to a family of proteins which plays an important role in protein acetylation, chromatin remodeling and transcription of genes, including those that are involved in cell proliferation and cell death. While increased expression of HDAC3 is seen in neoplastic cells, the role of HDAC3 in T cells and their role in autoimmune disease is not known. Methodology/Principal Findings: Applying Affymetrix GeneChip Human Gene 1.0 ST Array and the mixed effects model for gene set analysis, we compared gene expression profiles between multiple sclerosis (MS) patients and healthy controls (HC). Within the Apoptosis_GO gene set, the constitutive expression level of HDAC3 in peripheral blood mononuclear cell (PBMC) was significantly increased in MS patients when compared to controls. Following addition of trichostatin A (TSA), an inhibitor of HDAC3, we examined the expression of p53 by flow cytometry and p53 targeted genes by real time RT-PCR in MS and HC. Culture of PBMC with TSA resulted in increased expression of p53 in HC but not in MS patients. TSA treated T cells from MS patients also showed reduced sensitivity to apoptosis when compared to HC, which was independent of activation of p53 targeted pro-apoptotic genes. Conclusion/Significance: MS patients, when compared to controls, show an increased expression of HDAC3 and relative resistance to TSA induced apoptosis in T cells. Increased expression of HDAC3 in PBMC of MS patients may render putativ

Fishery-Independent Data Reveal Negative Effect of Human Population Density on Caribbean Predatory Fish Communities

BACKGROUND: Understanding the current status of predatory fish communities, and the effects fishing has on them, is vitally important information for management. However, data are often insufficient at region-wide scales to assess the effects of extraction in coral reef ecosystems of developing nations. METHODOLOGY/PRINCIPAL FINDINGS: Here, I overcome this difficulty by using a publicly accessible, fisheries-independent database to provide a broad scale, comprehensive analysis of human impacts on predatory reef fish communities across the greater Caribbean region. Specifically, this study analyzed presence and diversity of predatory reef fishes over a gradient of human population density. Across the region, as human population density increases, presence of large-bodied fishes declines, and fish communities become dominated by a few smaller-bodied species. CONCLUSIONS/SIGNIFICANCE: Complete disappearance of several large-bodied fishes indicates ecological and local extinctions have occurred in some densely populated areas. These findings fill a fundamentally important gap in our knowledge of the ecosystem effects of artisanal fisheries in developing nations, and provide support for multiple approaches to data collection where they are commonly unavailable

Social navigation

In this chapter we present one of the pioneer approaches in supporting users in navigating the complex information spaces, social navigation support. Social navigation support is inspired by natural tendencies of individuals to follow traces of each other in exploring the world, especially when dealing with uncertainties. In this chapter, we cover details on various approaches in implementing social navigation support in the information space as we also connect the concept to supporting theories. The first part of this chapter reviews related theories and introduces the design space of social navigation support through a series of example applications. The second part of the chapter discusses the common challenges in design and implementation of social navigation support, demonstrates how these challenges have been addressed, and reviews more recent direction of social navigation support. Furthermore, as social navigation support has been an inspirational approach to various other social information access approaches we discuss how social navigation support can be integrated with those approaches. We conclude with a review of evaluation methods for social navigation support and remarks about its current state

Oral health and social and emotional well-being in a birth cohort of Aboriginal Australian young adults

Background: Social and emotional well-being is an important component of overall health. In the Indigenous Australian context, risk indicators of poor social and emotional well-being include social determinants such as poor education, employment, income and housing as well as substance use, racial discrimination and cultural knowledge. This study sought to investigate associations between oral health-related factors and social and emotional well-being in a birth cohort of young Aboriginal adults residing in the northern region of Australia's Northern Territory. Methods: Data were collected on five validated domains of social and emotional well-being: anxiety, resilience, depression, suicide and overall mental health. Independent variables included socio-demographics, dental health behaviour, dental disease experience, oral health-related quality of life, substance use, racial discrimination and cultural knowledge. Results: After adjusting for other covariates, poor oral health-related items were associated with each of the social and emotional well-being domains. Specifically, anxiety was associated with being female, having one or more decayed teeth and racial discrimination. Resilience was associated with being male, having a job, owning a toothbrush, having one or more filled teeth and knowing a lot about Indigenous culture; while being female, having experienced dental pain in the past year, use of alcohol, use of marijuana and racial discrimination were associated with depression. Suicide was associated with being female, having experience of untreated dental decay and racial discrimination; while being female, having experience of dental disease in one or more teeth, being dissatisfied about dental appearance and racial discrimination were associated with poor mental health. Conclusion: The results suggest there may be value in including oral health-related initiatives when exploring the role of physical conditions on Indigenous social and emotional well-being.Lisa M Jamieson, Yin C Paradies, Wendy Gunthorpe, Sheree J Cairney and Susan M Sayer