CD14 C-159T and Toll-Like Receptor 4 Asp299Gly Polymorphisms in Surviving Meningococcal Disease Patients

BACKGROUND: Carriage of Neisseria meningitidis occurs approximately in 10% of the population, onset of invasive meningococcal disease (IMD) cannot be predicted and differs between ages. It remains unclear, which host factors determine invasion of the bloodstream by the bacteria. Innate immunity has a very important role in the first recognition of invading pathogens. The functional single nucleotide polymorphisms (SNPs) CD14 C-159T and toll-like receptor 4 (TLR4) Asp299Gly have been associated with the risk of gram-negative infections. However, their role in development of IMD still remains unclear. Our aim was to investigate the influence of CD14 C-159T and TLR4 Asp299Gly polymorphisms on the risk of IMD. METHODOLOGY/PRINCIPAL FINDINGS: It was a retrospective case control study. Surviving Austrian meningococcal disease patients were enrolled by sending buccal swabs for DNA analysis. 185 cases with a proven meningococcal infection and 770 healthy controls were enrolled. In surviving meningococcal disease patients DNA analysis of CD14 C-159T and TLR 4 Asp299Gly polymorphisms was performed, as they are part of the innate immune response to bacterial determinants. CD14 C-159T and TLR4 Asp299Gly SNPs were not significantly associated with the presence of IMD when compared to healthy controls. The odds ratio for CD14 C-159T SNP was 1.14 (95% confidence interval (CI) 0.91-1.43; p = 0.266). In TLR4 Asp 299 Gly SNP the odds ratio was 0.78 (CI 0.47-1.43; p = 0.359). CONCLUSION/SIGNIFICANCE: We could not observe a significant influence of CD14 C-159T and TLR4 Asp299Gly polymorphisms on the risk of developing IMD in surviving meningococcal disease patients. To our knowledge, this is the first study investigating the influence of the CD14 C-159T SNP on the susceptibility to IMD

Evaluation of Glycine max mRNA clusters

BACKGROUND: Clustering the ESTs from a large dataset representing a single species is a convenient starting point for a number of investigations into gene discovery, genome evolution, expression patterns, and alternatively spliced transcripts. Several methods have been developed to accomplish this, the most widely available being UniGene, a public domain collection of gene-oriented clusters for over 45 different species created and maintained by NCBI. The goal is for each cluster to represent a unique gene, but currently it is not known how closely the overall results represent that reality. UniGene's build procedure begins with initial mRNA clusters before joining ESTs. UniGene's results for soybean indicate a significant amount of redundancy among some sequences reported to be unique mRNAs. To establish a valid non-redundant known gene set for Glycine max we applied our algorithm to the clustering of only mRNA sequences. The mRNA dataset was run through the algorithm using two different matching stringencies. The resulting cluster compositions were compared to each other and to UniGene. Clusters exhibiting differences among the three methods were analyzed by 1) nucleotide and amino acid alignment and 2) submitting authors conclusions to determine whether members of a single cluster represented the same gene or not. RESULTS: Of the 12 clusters that were examined closely most contained examples of sequences that did not belong in the same cluster. However, neither the two stringencies of PECT nor UniGene had a significantly greater record of accuracy in placing paralogs into separate clusters. CONCLUSION: Our results reveal that, although each method produces some errors, using multiple stringencies for matching or a sequential hierarchical method of increasing stringencies can provide more reliable results and therefore allow greater confidence in the vast majority of clusters that contain only ESTs and no mRNA sequences

High Quality Care and Ethical Pay-for-Performance: A Society of General Internal Medicine Policy Analysis

BACKGROUND: Pay-for-performance is proliferating, yet its impact on key stakeholders remains uncertain. OBJECTIVE: The Society of General Internal Medicine systematically evaluated ethical issues raised by performance-based physician compensation. RESULTS: We conclude that current arrangements are based on fundamentally acceptable ethical principles, but are guided by an incomplete understanding of health-care quality. Furthermore, their implementation without evidence of safety and efficacy is ethically precarious because of potential risks to stakeholders, especially vulnerable patients. CONCLUSION: We propose four major strategies to transition from risky pay-for-performance systems to ethical performance-based physician compensation and high quality care. These include implementing safeguards within current pay-for-performance systems, reaching consensus regarding the obligations of key stakeholders in improving health-care quality, developing valid and comprehensive measures of health-care quality, and utilizing a cautious evaluative approach in creating the next generation of compensation systems that reward genuine quality

Availability and structure of primary medical care services and population health and health care indicators in England

BACKGROUND: It has been proposed that greater availability of primary medical care practitioners (GPs) contributes to better population health. We evaluated whether measures of the supply and structure of primary medical services are associated with health and health care indicators after adjusting for confounding. METHODS: Data for the supply and structure of primary medical services and the characteristics of registered patients were analysed for 99 health authorities in England in 1999. Health and health care indicators as dependent variables included standardised mortality ratios (SMR), standardised hospital admission rates, and conceptions under the age of 18 years. Linear regression analyses were adjusted for Townsend score, proportion of ethnic minorities and proportion of social class IV/ V. RESULTS: Higher proportions of registered rural patients and patients ≥ 75 years were associated with lower Townsend deprivation scores, with larger partnership sizes and with better health outcomes. A unit increase in partnership size was associated with a 4.2 (95% confidence interval 1.7 to 6.7) unit decrease in SMR for all-cause mortality at 15–64 years (P = 0.001). A 10% increase in single-handed practices was associated with a 1.5 (0.2 to 2.9) unit increase in SMR (P = 0.027). After additional adjustment for percent of rural and elderly patients, partnership size and proportion of single-handed practices, GP supply was not associated with SMR (-2.8, -6.9 to 1.3, P = 0.183). CONCLUSIONS: After adjusting for confounding with health needs of populations, mortality is weakly associated with the degree of organisation of practices as represented by the partnership size but not with the supply of GPs

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

SMARTphone-based, early cardiac REHABilitation in patients with acute coronary syndromes [SMART-REHAB Trial]: A randomized controlled trial protocol

© 2016 The Author(s). Background: There are well-documented treatment gaps in secondary prevention of coronary heart disease and no clear guidelines to assist early physical activity after acute coronary syndromes (ACS). Smartphone technology may provide an innovative platform to close these gaps. This paper describes the study design of a randomized controlled trial assessing whether a smartphone-based secondary prevention program can facilitate early physical activity and improve cardiovascular health in patients with ACS. Methods: We have developed a multi-faceted, patient-centred smartphone-based secondary prevention program emphasizing early physical activity with a graduated walking program initiated on discharge from ACS admission. The program incorporates; physical activity tracking through the smartphone's accelerometer with interactive feedback and goal setting; a dynamic dashboard to review and optimize cardiovascular risk factors; educational messages delivered twice weekly; a photographic food diary; pharmacotherapy review; and support through a short message service. The primary endpoint of the trial is change in exercise capacity, as measured by the change in six-minute walk test distance at 8-weeks when compared to baseline. Secondary endpoints include improvements in cardiovascular risk factor status, psychological well-being and quality of life, medication adherence, uptake of cardiac rehabilitation and re-hospitalizations. Discussion: This randomized controlled trial will use a smartphone-phone based secondary prevention program to emphasize early physical activity post-ACS. It will provide evidence regarding the feasibility and utility of this innovative platform in closing the treatment gaps in secondary prevention. Trial registration: The trial was retrospectively registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) on April 4, 2016. The registration number is ACTRN12616000426482

Effectiveness of a new model of primary care management on knee pain and function in patients with knee osteoarthritis: Protocol for THE PARTNER STUDY

© 2018 The Author(s). Background: To increase the uptake of key clinical recommendations for non-surgical management of knee osteoarthritis (OA) and improve patient outcomes, we developed a new model of service delivery (PARTNER model) and an intervention to implement the model in the Australian primary care setting. We will evaluate the effectiveness and cost-effectiveness of this model compared to usual general practice care. Methods: We will conduct a mixed-methods study, including a two-arm, cluster randomised controlled trial, with quantitative, qualitative and economic evaluations. We will recruit 44 general practices and 572 patients with knee OA in urban and regional practices in Victoria and New South Wales. The interventions will target both general practitioners (GPs) and their patients at the practice level. Practices will be randomised at a 1:1 ratio. Patients will be recruited if they are aged =45 years and have experienced knee pain =4/10 on a numerical rating scale for more than three months. Outcomes are self-reported, patient-level validated measures with the primary outcomes being change in pain and function at 12 months. Secondary outcomes will be assessed at 6 and 12 months. The implementation intervention will support and provide education to intervention group GPs to deliver effective management for patients with knee OA using tailored online training and electronic medical record support. Participants with knee OA will have an initial GP visit to confirm their diagnosis and receive management according to GP intervention or control group allocation. As part of the intervention group GP management, participants with knee OA will be referred to a centralised multidisciplinary service: the PARTNER Care Support Team (CST). The CST will be trained in behaviour change support and evidence-based knee OA management. They will work with patients to develop a collaborative action plan focussed on key self-management behaviours, and communicate with the patients' GPs. Patients receiving care by intervention group GPs will receive tailored OA educational materials, a leg muscle strengthening program, and access to a weight-loss program as appropriate and agreed. GPs in the control group will receive no additional training and their patients will receive usual care. Discussion: This project aims to address a major evidence-to-practice gap in primary care management of OA by evaluating a new service delivery model implemented with an intervention targeting GP practice behaviours to improve the health of people with knee OA. Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12617001595303, date of registration 1/12/2017

Nr2e3 is a Genetic Modifier That Rescues Retinal Degeneration and Promotes Homeostasis in Multiple Models of Retinitis Pigmentosa

Recent advances in viral vector engineering, as well as an increased understanding of the cellular and molecular mechanism of retinal diseases, have led to the development of novel gene therapy approaches. Furthermore, ease of accessibility and ocular immune privilege makes the retina an ideal target for gene therapies. In this study, the nuclear hormone receptor gene Nr2e3 was evaluated for efficacy as broad-spectrum therapy to attenuate early to intermediate stages of retinal degeneration in five unique mouse models of retinitis pigmentosa (RP). RP is a group of heterogenic inherited retinal diseases associated with over 150 gene mutations, affecting over 1.5 million individuals worldwide. RP varies in age of onset, severity, and rate of progression. In addition, ~40% of RP patients cannot be genetically diagnosed, confounding the ability to develop personalized RP therapies. Remarkably, Nr2e3 administered therapy resulted in reduced retinal degeneration as observed by increase in photoreceptor cells, improved electroretinogram, and a dramatic molecular reset of key transcription factors and associated gene networks. These therapeutic effects improved retinal homeostasis in diseased tissue. Results of this study provide evidence that Nr2e3 can serve as a broad-spectrum therapy to treat multiple forms of RP