The Dysexecutive Questionnaire Revised (DEX-R): An extended measure of everyday dysexecutive problems after acquired brain injury.

The Dysexecutive Questionnaire (DEX) is a tool for measuring everyday problems experienced with the dysexecutive syndrome. This study investigated the psychometric properties of a revised version of the measure (DEX-R), a comprehensive tool, grounded in current theoretical conceptualisations of frontal lobe function and dysexecutive problems. The aim was to improve measurement of dysexecutive problems following acquired brain injury (ABI). Responses to the DEX-R were collected from 136 men and women who had experienced an ABI (the majority of whom had experienced a stroke or subarachnoid haemorrhage) and where possible, one of their carers or family members (n = 71), who acted as an informant. Rasch analysis techniques were employed to explore the psychometric properties of four newly developed, theoretically distinct subscales based on Stuss model of frontal lobe function and to evaluate the comparative validity and reliability of self and informant ratings of these four subscales. The newly developed subscales were well targeted to the range of dysexecutive problems reported by the current sample and each displayed a good level of internal validity. Both self- and independent-ratings were found to be performing reliably as outcome measures for at least a group-level. This new version of the tool could help guide selection of interventions for different types of dysexecutive problems and provide accurate measurement in neurorehabilitation services.National Institute for Health ResearchThis is the author accepted manuscript. The final version is available from Taylor & Francis via http://dx.doi.org/10.1080/09602011.2015.112188

Identification of Small Molecule Inhibitors of the Staphylococcus aureus Sortase A Enzyme

The Sortase A (SrtA) enzyme is a potential target for a new class of anti-infective drugs because it is responsible for anchoring virulence factors to the surface of pathogenic, Gram-positive bacteria such as Staphylococcus aureus. High throughput screening yielded low molecular weight compounds that inhibit purified SrtA from S. aureus. The efficacy of these compounds at targeting SrtA in live bacteria was successfully determined by developing sensitive biological assays that measure inhibition of sortasedependent surface protein expression in S. aureus. Fibrinogen-clumping and fibrinogenbinding assays were developed to determine the presence of clumping factors (ClfA and B), a fibronectin-binding assay was used to determine the presence of fibrinogen-binding proteins (FnBPA and B), and dot blots were developed to measure protein A on the cell surface. Fifty-six compounds were identified that inhibit surface protein expression in at least one of the biological assays. The effectiveness of these compounds at treating infection will soon be tested in vivo using the S. aureus septic arthritis model in mice

SarS, a SarA Homolog Repressible by agr, Is an Activator of Protein A Synthesis in Staphylococcus aureus

The expression of protein A (spa) is repressed by global regulatory loci sarA and agr. Although SarA may directly bind to the spa promoter to downregulate spa expression, the mechanism by which agr represses spa expression is not clearly understood. In searching for SarA homologs in the partially released genome, we found a SarA homolog, encoding a 250-amino-acid protein designated SarS, upstream of the spa gene. The expression of sarS was almost undetectable in parental strain RN6390 but was highly expressed in agr and sarA mutants, strains normally expressing high level of protein A. Interestingly, protein A expression was decreased in a sarS mutant as detected in an immunoblot but returned to near-parental levels in a complemented sarS mutant. Transcriptional fusion studies with a 158- and a 491-bp spa promoter fragment linked to the xylE reporter gene disclosed that the transcription of the spa promoter was also downregulated in the sarS mutant compared with the parental strain. Interestingly, the enhancement in spa expression in an agr mutant returned to a near-parental level in the agr sarS double mutant but not in the sarA sarS double mutant. Correlating with this divergent finding is the observation that enhanced sarS expression in an agr mutant was repressed by the sarA locus supplied in trans but not in a sarA mutant expressing RNAIII from a plasmid. Gel shift studies also revealed the specific binding of SarS to the 158-bp spa promoter. Taken together, these data indicated that the agr locus probably mediates spa repression by suppressing the transcription of sarS, an activator of spa expression. However, the pathway by which the sarA locus downregulates spa expression is sarS independent

Thermal behaviour of high amylose cornstarch studied by DSC

The thermal behaviour of high amylose cornstarches (80% amylose content) was studied by DSC using high pressure stainless steel pans in the temperature range between 0-350 degrees C. The number of endotherms and the enthalpy of gelatinization were found to depend on moisture content. Up to four endotherms and one exotherm were determined when the moisture content was above 40%. The meaning of each endotherm has been discussed. The enthalpy of gelatinization was calculated based on the summation of all the gelatinization endotherms and found to increase with increasing water content

The value of statistical life for adults and children: Comparisons of the contingent valuation and chained approaches

Estimates of the Value of Statistical Life (VSL) provide a vital input to a variety of policy decisions ranging from health provision to transportation planning. However, the bulk of VSL research has focussed on estimating average values rather than taking account of the potential variation in VSL across groups. Policymakers are particularly concerned that using estimates based on data concerning adults might provide poor proxies of the values associated with preventing child fatalities. We investigate this empirical problem while also addressing methodological critiques of standard contingent valuation (CV) approaches to VSL estimation which ask survey respondents to value an outcome described in terms of both the probability of occurrence and the health impact of an event. A prior lab experiment confirms fundamental problems in subjects’ abilities to provide internally consistent valuations of such compound goods. Given this we compare CV approaches with the ‘chaining method’ of Carthy et al. (1999) which splits the valuation task in two, assessing the probability of an event and the disutility of that event separately and then ‘chaining’ responses together to obtain a VSL estimate. We provide a first application of this method to the estimation of the VSL for children and contrast this with values for adults. Results confirm prior expectations that VSL values for preventing child fatalities significantly exceed those for adults. Finally, we carry out the first replication of the chaining approach in a large and nationally representative sample of parents. We identify many advantages of chaining over CV approaches, however, through a novel variant of a validation test suggested by Carthy et al., we reveal anomalies in the estimates produced by the chaining method suggesting that a robust method for VSL calculation is yet to be refined

Public Awareness and Perception of Ionizing Radiation

Introduction. Exposure to ionizing radiation has potential for acute and chronic health effects. Within the general public, there is discrepancy between perceived and actual health risks. It is vital to assess existing knowledge and perceptions about ionizing radiation among Vermonters.https://scholarworks.uvm.edu/comphp_gallery/1188/thumbnail.jp

Feasibility and acceptability of integrated psychological therapy versus treatment as usual for people with bipolar disorder and co-morbid alcohol use:A single blind randomised controlled trial

Background Alcohol use is a common problem in bipolar disorder (BD) and evidence indicates more promising outcomes for alcohol use than other substances. No trials have evaluated individual integrated motivational interviewing and cognitive behaviour therapy (MI-CBT) for problematic alcohol use in BD. We therefore assessed the feasibility and acceptability of a novel MI-CBT intervention for alcohol use in BD. Methods A single blind RCT was conducted to compare MI-CBT plus treatment as usual (TAU) with TAU only. MI-CBT was delivered over 20 sessions with participants followed up at 3, 6, 9 and 12 months post-randomisation. Primary outcomes were the feasibility and acceptability of MI-CBT (recruitment to target, retention to follow-up and therapy, acceptability of therapy and absence of adverse events). We also conducted preliminary analyses of alcohol and mood outcomes (frequency and severity of alcohol use and time to mood relapse). Results 44 participants were recruited with 75% retention to 6 and 12 months follow-up. Therapy participants attended a mean of 17.6 (SD 4.5) sessions. Therapy alliance and treatment fidelity were acceptable. Qualitative interviews indicated the intervention was experienced as collaborative, and helpful, in addressing mood and alcohol issues, although risk of overconfidence following therapy was also identified. Clinical outcomes did not differ between arms at 12 months follow-up. Limitations As a feasibility and acceptability trial any secondary results should be treated with caution. Conclusions Integrated MI-CBT is feasible and acceptable, but lack of clinical impact, albeit in a feasibility study, suggests need for further development. Potential adaptations are discussed

Post hoc depression analysis from a pharmacist-led diabetes trial

Introduction: Diabetes and depression may present concurrently, and clinical pharmacists are well equipped to manage these conditions. Clinical pharmacists were grant funded to implement a diabetes-focused randomized controlled trial in a Federally Qualified Health Center. The objective of this analysis is to evaluate if glycemic control and depressive symptoms improve for patients with diabetes and depression with additional management from clinical pharmacists compared with those receiving the standard of care. Methods: This is a post hoc subgroup analysis of a diabetes-focused randomized controlled trial. Pharmacists enrolled patients with type 2 diabetes mellitus (T2DM) and a glycated hemoglobin (A1C) greater than 8% and randomly assigned them to 1 of 2 cohorts, one managed by the primary care provider alone and one with additional care from the pharmacist. Pharmacists completed encounters with patients who have T2DM with or without depression to comprehensively optimize pharmacotherapy while tracking glycemic and depressive outcomes throughout the study. Results: A1C improved from baseline to 6 months in patients with depressive symptoms who received additional care from pharmacists by -2.4 percentage points (SD, 2.41) compared with a -0.1 percentage point (SD, 1.78) reduction in the control arm (P .0081), and there was no change in depressive symptoms. Discussion: Patients with T2DM and depressive symptoms experienced better diabetes outcomes with additional pharmacist management compared with a similar cohort of patients with depressive symptoms, managed independently by primary care providers. These patients with diabetes and comorbid depression received a higher level of engagement and care from the pharmacists, which led to more therapeutic interventions

Comparison of plasma and CSF biomarkers in predicting cognitive decline

OBJECTIVES: Concentrations of amyloid-β peptides (Aβ42/Aβ40) and neurofilament light (NfL) can be measured in plasma or cerebrospinal fluid (CSF) and are associated with Alzheimer\u27s disease brain pathology and cognitive impairment. This study directly compared plasma and CSF measures of Aβ42/Aβ40 and NfL as predictors of cognitive decline. METHODS: Participants were 65 years or older and cognitively normal at baseline with at least one follow-up cognitive assessment. Analytes were measured with the following types of assays: plasma Aβ42/Aβ40, immunoprecipitation-mass spectrometry; plasma NfL, Simoa; CSF Aβ42/Aβ40, automated immunoassay; CSF NfL plate-based immunoassay. Mixed effects models evaluated the global cognitive composite score over a maximum of 6 years as predicted by the fluid biomarkers. RESULTS: Analyses included 371 cognitively normal participants, aged 72.7 ± 5.2 years (mean ± standard deviation) with an average length of follow-up of 3.9 ± 1.6 years. Standardized concentrations of biomarkers were associated with annualized cognitive change: plasma Aβ42/Aβ40, 0.014 standard deviations (95% confidence intervals 0.002 to 0.026); CSF Aβ42/Aβ40, 0.020 (0.008 to 0.032); plasma Nfl, -0.018 (-0.030 to -0.005); and CSF NfL, -0.024 (-0.036 to -0.012). Power analyses estimated that 266 individuals in each treatment arm would be needed to detect a 50% slowing of decline if identified by abnormal plasma measures versus 229 for CSF measures. INTERPRETATION: Both plasma and CSF measures of Aβ42/Aβ40 and NfL predicted cognitive decline. A clinical trial that enrolled individuals based on abnormal plasma Aβ42/Aβ40 and NfL levels would require only a marginally larger cohort than if CSF measures were used