231 research outputs found

    Quality target negotiation in health care : evidence from the English NHS

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    We examine how public sector third-party purchasers and hospitals negotiate quality targets when a fixed proportion of hospital revenue is required to be linked to quality. We develop a bargaining model linking the number of quality targets to purchaser and hospital characteristics. Using data extracted from 153 contracts for acute hospital services in England in 2010/11, we find that the number of quality targets is associated with the purchaser’s population health and its budget, the hospital type, whether the purchaser delegated negotiation to an agency, and the quality targets imposed by the supervising regional health authority

    Expression of endogenous putative TSH binding protein in orbit

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    Thyroid stimulating antibodies (TSAB) cause Graves’ disease and contribute to Graves’ Orbitopathy (GO) pathogenesis. We hypothesise that the presence of TSH binding proteins (truncated TSHR variants (TSHRv)) and/or nonclassical ligands such as thyrostimulin (α2β5) might provide a mechanism to protect against or exacerbate GO. We analysed primary human orbital preadipocyte-fibroblasts (OF) from GO patients and people free of GO (non-GO). Transcript (QPCR) and protein (western blot) expression levels of TSHRv were measured through an adipogenesis differentiation process. Cyclic-AMP production by TSHR activation was studied using luciferase-reporter and RIA assays. After differentiation, TSHRv levels in OF from GO were significantly higher than non-GO (p = 0.039), and confirmed in ex vivo analysis of orbital adipose samples. TSHRv western blot revealed a positive signal at 46 kDa in cell lysates and culture media (CM) from non-GO and GO-OF. Cyclic-AMP decreased from basal levels when OF were stimulated with TSH or Monoclonal TSAB (M22) before differentiation protocol, but increased in differentiated cells, and was inversely correlated with the TSHRv:TSHR ratio (Spearman correlation: TSH r = −0.55, p = 0.23, M22 r = 0.87, p = 0.03). In the bioassay, TSH/M22 induced luciferase-light was lower in CM from differentiated GO-OF than non-GO, suggesting that secreted TSHRv had neutralised their effects. α2 transcripts were present but reduced during adipogenesis (p < 0.005) with no difference observed between non-GO and GO. β5 transcripts were at the limit of detection. Our work demonstrated that TSHRv transcripts are expressed as protein, are more abundant in GO than non-GO OF and have the capacity to regulate signalling via the TSHR

    Nitric Oxide Enhances Desiccation Tolerance of Recalcitrant Antiaris toxicaria Seeds via Protein S-Nitrosylation and Carbonylation

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    The viability of recalcitrant seeds is lost following stress from either drying or freezing. Reactive oxygen species (ROS) resulting from uncontrolled metabolic activity are likely responsible for seed sensitivity to drying. Nitric oxide (NO) and the ascorbate-glutathione cycle can be used for the detoxification of ROS, but their roles in the seed response to desiccation remain poorly understood. Here, we report that desiccation induces rapid accumulation of H2O2, which blocks recalcitrant Antiaris toxicaria seed germination; however, pretreatment with NO increases the activity of antioxidant ascorbate-glutathione pathway enzymes and metabolites, diminishes H2O2 production and assuages the inhibitory effects of desiccation on seed germination. Desiccation increases the protein carbonylation levels and reduces protein S-nitrosylation of these antioxidant enzymes; these effects can be reversed with NO treatment. Antioxidant protein S-nitrosylation levels can be further increased by the application of S-nitrosoglutathione reductase inhibitors, which further enhances NO-induced seed germination rates after desiccation and reduces desiccation-induced H2O2 accumulation. These findings suggest that NO reinforces recalcitrant seed desiccation tolerance by regulating antioxidant enzyme activities to stabilize H2O2 accumulation at an appropriate concentration. During this process, protein carbonylation and S-nitrosylation patterns are used as a specific molecular switch to control antioxidant enzyme activities

    Singing the same tune? International continuities and discontinuities in how police talk about using force

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    This article focuses on a research project conducted in six jurisdictions: England, The Netherlands, Germany, Australia, Venezuela, and Brazil. These societies are very different ethnically, socially, politically, economically, historically and have wildly different levels of crime. Their policing arrangements also differ significantly: how they are organised; how their officers are equipped and trained; what routine operating procedures they employ; whether they are armed; and much else besides. Most relevant for this research, they represent policing systems with wildly different levels of police shootings, Police in the two Latin American countries represented here have a justified reputation for the frequency with which they shoot people, whereas at the other extreme the police in England do not routinely carry firearms and rarely shoot anyone. To probe whether these differences are reflected in the way that officers talk about the use of force, police officers in these different jurisdictions were invited to discuss in focus groups a scenario in which police are thwarted in their attempt to arrest two youths (one of whom is a known local criminal) by the youths driving off with the police in pursuit, and concludes with the youths crashing their car and escaping in apparent possession of a gun, It might be expected that focus groups would prove starkly different, and indeed they were, but not in the way that might be expected. There was little difference in affirmation of normative and legal standards regarding the use of force. It was in how officers in different jurisdictions envisaged the circumstances in which the scenario took place that led Latin American officers to anticipate that they would shoot the suspects, whereas officers in the other jurisdictions had little expectation that they would open fire in the conditions as they imagined them to be

    Magnet therapy for the relief of pain and inflammation in rheumatoid arthritis (CAMBRA): A randomised placebo-controlled crossover trial

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    <p>Abstract</p> <p>Background</p> <p>Rheumatoid arthritis is a common inflammatory autoimmune disease. Although disease activity may be managed effectively with prescription drugs, unproven treatments such as magnet therapy are sometimes used as an adjunct for pain control. Therapeutic devices incorporating permanent magnets are widely available and easy to use. Magnets may also be perceived as a more natural and less harmful alternative to analgesic compounds. Of interest to health service researchers is the possibility that magnet therapy might help to reduce the economic burden of managing chronic musculoskeletal disorders. Magnets are extremely cheap to manufacture and prolonged treatment involves a single cost. Despite this, good quality scientific evidence concerning the safety, effectiveness and cost-effectiveness of magnet therapy is scarce. The primary aim of the CAMBRA trial is to investigate the effectiveness of magnet therapy for relieving pain and inflammation in rheumatoid arthritis.</p> <p>Methods/Design</p> <p>The CAMBRA trial employs a randomised double-blind placebo-controlled crossover design. Participant will each wear four devices: a commercially available magnetic wrist strap; an attenuated wrist strap; a demagnetised wrist strap; and a copper bracelet. Device will be allocated in a randomised sequence and each worn for five weeks. The four treatment phases will be separated by wash out periods lasting one week. Both participants and researchers will be blind, as far as feasible, to the allocation of experimental and control devices. In total 69 participants will be recruited from general practices within the UK. Eligible patients will have a verified diagnosis of rheumatoid arthritis that is being managed using drugs, and will be experiencing chronic pain. Outcomes measured will include pain, inflammation, disease activity, physical function, medication use, affect, and health related costs. Data will be collected using questionnaires, diaries, manual pill counts and blood tests.</p> <p>Discussion</p> <p>Magnetism is an inherent property of experimental devices which is hard to conceal. The use of multiple control devices, including a copper bracelet, represents a concerted attempt to overcome methodological limitations associated with trials in this field. The trial began in July 2007. At the time of submission (August 2008) recruitment has finished, with 70 trial participants, and data collection is almost complete.</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN51459023</p

    Putative DHHC-Cysteine-Rich Domain S-Acyltransferase in Plants

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    Protein S-acyltransferases (PATs) containing Asp-His-His-Cys within a Cys-rich domain (DHHC-CRD) are polytopic transmembrane proteins that are found in eukaryotic cells and mediate the S-acylation of target proteins. S-acylation is an important secondary and reversible modification that regulates the membrane association, trafficking and function of target proteins. However, little is known about the characteristics of PATs in plants. Here, we identified 804 PATs from 31 species with complete genomes. The analysis of the phylogenetic relationships suggested that all of the PATs fell into 8 groups. In addition, we analysed the phylogeny, genomic organization, chromosome localisation and expression pattern of PATs in Arabidopsis, Oryza sative, Zea mays and Glycine max. The microarray data revealed that PATs genes were expressed in different tissues and during different life stages. The preferential expression of the ZmPATs in specific tissues and the response of Zea mays to treatments with phytohormones and abiotic stress demonstrated that the PATs play roles in plant growth and development as well as in stress responses. Our data provide a useful reference for the identification and functional analysis of the members of this protein family

    Transcriptomic and metabolomic shifts in rice roots in response to Cr (VI) stress

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    <p>Abstract</p> <p>Background</p> <p>Widespread use of chromium (Cr) contaminated fields due to careless and inappropriate management practices of effluent discharge, mostly from industries related to metallurgy, electroplating, production of paints and pigments, tanning, and wood preservation elevates its concentration in surface soil and eventually into rice plants and grains. In spite of many previous studies having been conducted on the effects of chromium stress, the precise molecular mechanisms related to both the effects of chromium phytotoxicity, the defense reactions of plants against chromium exposure as well as translocation and accumulation in rice remain poorly understood.</p> <p>Results</p> <p>Detailed analysis of genome-wide transcriptome profiling in rice root is reported here, following Cr-plant interaction. Such studies are important for the identification of genes responsible for tolerance, accumulation and defense response in plants with respect to Cr stress. Rice root metabolome analysis was also carried out to relate differential transcriptome data to biological processes affected by Cr (VI) stress in rice. To check whether the Cr-specific motifs were indeed significantly over represented in the promoter regions of Cr-responsive genes, occurrence of these motifs in whole genome sequence was carried out. In the background of whole genome, the lift value for these 14 and 13 motifs was significantly high in the test dataset. Though no functional role has been assigned to any of the motifs, but all of these are present as promoter motifs in the Database of orthologus promoters.</p> <p>Conclusion</p> <p>These findings clearly suggest that a complex network of regulatory pathways modulates Cr-response of rice. The integrated matrix of both transcriptome and metabolome data after suitable normalization and initial calculations provided us a visual picture of the correlations between components. Predominance of different motifs in the subsets of genes suggests the involvement of motif-specific transcription modulating proteins in Cr stress response of rice.</p
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