Cost-effectiveness of programs to eliminate disparities in elderly vaccination rates in the United States

Background: There are disparities in influenza and pneumococcal vaccination rates among elderly minority groups and little guidance as to which intervention or combination of interventions to eliminate these disparities is likely to be most cost-effective. Here, we evaluate the cost-effectiveness of four hypothetical vaccination programs designed to eliminate disparities in elderly vaccination rates and differing in the number of interventions. Methods. We developed a Markov model in which we assumed a healthcare system perspective, 10-year vaccination program and lifetime time horizon. The cohort was the combined African-American and Hispanic 65 year-old birth cohort in the United States in 2009. We evaluated five different vaccination strategies: no vaccination program and four vaccination programs that varied from "low intensity" to "very high intensity" based on the number of interventions deployed in each program, their cumulative cost and their cumulative impact on elderly minority influenza and pneumococcal vaccination rates. Results: The very high intensity vaccination program ($24,479/ quality-adjusted life year; QALY) was preferred at willingness-to-pay-thresholds of$50,000 and $100,000/QALY and prevented 37,178 influenza cases, 342 influenza deaths, 1,158 invasive pneumococcal disease (IPD) cases and 174 IPD deaths over the birth cohort's lifetime. In one-way sensitivity analyses, the very high intensity program only became cost-prohibitive (>$100,000/QALY) at less likely values for the influenza vaccination rates achieved in year 10 of the high intensity (>73.5%) or very high intensity (<76.8%) vaccination programs. Conclusions: A practice-based vaccination program designed to eliminate disparities in elderly minority vaccination rates and including four interventions would be cost-effective. © 2014 Michaelidis et al.; licensee BioMed Central Ltd

Transcriptional signatures of Itk-deficient CD3+, CD4+ and CD8+ T-cells

<p>Abstract</p> <p>Background</p> <p>The Tec-family kinase Itk plays an important role during T-cell activation and function, and controls also conventional versus innate-like T-cell development. We have characterized the transcriptome of Itk-deficient CD3⁺T-cells, including CD4⁺and CD8⁺subsets, using Affymetrix microarrays.</p> <p>Results</p> <p>The largest difference between Itk^-/-and Wt CD3⁺T-cells was found in unstimulated cells, e.g. for killer cell lectin-like receptors. Compared to anti-CD3-stimulation, anti-CD3/CD28 significantly decreased the number of transcripts suggesting that the CD28 co-stimulatory pathway is mainly independent of Itk. The signatures of CD4⁺and CD8⁺T-cell subsets identified a greater differential expression than in total CD3⁺cells. Cyclosporin A (CsA)-treatment had a stronger effect on transcriptional regulation than Itk-deficiency, suggesting that only a fraction of TCR-mediated calcineurin/NFAT-activation is dependent on Itk. Bioinformatic analysis of NFAT-sites of the group of transcripts similarly regulated by Itk-deficiency and CsA-treatment, followed by chromatin-immunoprecipitation, revealed NFATc1-binding to the <it>Bub1</it>, <it>IL7R, Ctla2a</it>, <it>Ctla2b</it>, and <it>Schlafen1 </it>genes. Finally, to identify transcripts that are regulated by Tec-family kinases in general, we compared the expression profile of Itk-deficient T-cells with that of Btk-deficient B-cells and a common set of transcripts was found.</p> <p>Conclusion</p> <p>Taken together, our study provides a general overview about the global transcriptional changes in the absence of Itk.</p

Gastrocnemius medialis muscle architecture and physiological cross sectional area in adult males with Duchenne muscular dystrophy

Objectives: To describe muscle size and architecture of the gastrocnemius medialis (GM) muscle in eleven adult males with Duchenne Muscular Dystrophy (DMD, age 24.5±5.4 years), and a control group of eleven males without DMD (CTRL, age 22.1±0.9 years). Methods: GM anatomical cross sectional area (ACSA), volume (VOL), physiological cross sectional area (PCSA), fascicle length (Lf) and pennation angle (θ) were assessed using B-Mode Ultrasonography. GM ACSA was measured at 25, 50 and 75% of muscle length (Lm), from which VOL was calculated. At 50% of Lm, sagittal plane images were analysed to determine GM Lf and θ. GM PCSA was calculated as: VOL/Lf. The ratio of Lf and Lm was also calculated. Results: GM ACSA at 50% Lm, VOL and PCSA were smaller in DMD males compared to CTRL males by 36, 47 and 43%, respectively (P<0.01). There were no differences in Lf and θ. GM Lm was 29% shorter in DMD compared to CTRL. Lf/Lm was 29% longer in DMD (P<0.01). Conclusions: Unlike previous data in children with DMD, our results show significant atrophy in adult males with DMD, and no change in Lf or θ. The shorter Lm may have implications for joint flexibility

Effect of arsenic-phosphorus interaction on arsenic-induced oxidative stress in chickpea plants

Arsenic-induced oxidative stress in chickpea was investigated under glasshouse conditions in response to application of arsenic and phosphorus. Three levels of arsenic (0, 30 and 60 mg kg−1) and four levels of P (50, 100, 200, and 400 mg kg−1) were applied to soil-grown plants. Increasing levels of both arsenic and P significantly increased arsenic concentrations in the plants. Shoot growth was reduced with increased arsenic supply regardless of applied P levels. Applied arsenic induced oxidative stress in the plants, and the concentrations of H2O2 and lipid peroxidation were increased. Activity of superoxide dismutase (SOD) and concentrations of non-enzymatic antioxidants decreased in these plants, but activities of catalase (CAT) and ascorbate peroxidase (APX) were significantly increased under arsenic phytotoxicity. Increased supply of P decreased activities of CAT and APX, and decreased concentrations of non-enzymatic antioxidants, but the high-P plants had lowered lipid peroxidation. It can be concluded that P increased uptake of arsenic from the soil, probably by making it more available, but although plant growth was inhibited by arsenic the P may have partially protected the membranes from arsenic-induced oxidative stress

Contribution of the cyclic nucleotide gated channel subunit, CNG-3, to olfactory plasticity in Caenorhabditis elegans.

In Caenorhabditis elegans, the AWC neurons are thought to deploy a cGMP signaling cascade in the detection of and response to AWC sensed odors. Prolonged exposure to an AWC sensed odor in the absence of food leads to reversible decreases in the animal's attraction to that odor. This adaptation exhibits two stages referred to as short-term and long-term adaptation. Previously, the protein kinase G (PKG), EGL-4/PKG-1, was shown necessary for both stages of adaptation and phosphorylation of its target, the beta-type cyclic nucleotide gated (CNG) channel subunit, TAX-2, was implicated in the short term stage. Here we uncover a novel role for the CNG channel subunit, CNG-3, in short term adaptation. We demonstrate that CNG-3 is required in the AWC for adaptation to short (thirty minute) exposures of odor, and contains a candidate PKG phosphorylation site required to tune odor sensitivity. We also provide in vivo data suggesting that CNG-3 forms a complex with both TAX-2 and TAX-4 CNG channel subunits in AWC. Finally, we examine the physiology of different CNG channel subunit combinations

Using palaeoenvironmental DNA to reconstruct past environments: progress and prospects

Palaeoenvironmental DNA (PalEnDNA) is defined as ancient DNA (aDNA) originating from disseminated genetic material within palaeoenvironmental samples. Sources of PalEnDNA include marine and lake sediments, peat, loess, till, ice, permafrost, palaeosols, coprolites, preserved gut contents, dental calculus, tephras, and soils as well as deposits in caves/rockshelters and at archaeological sites. PalEnDNA analysis provides a relatively new tool for Quaternary and archaeological sciences and its applications have included palaeoenvironmental and palaeodietary reconstructions, testing hypotheses regarding megafaunal extinctions, human–environment interactions, taxonomic studies and studies of DNA damage. Because PalEnDNA samples comprise markedly different materials, and represent wide-ranging depositional and taphonomic contexts, various issues must be addressed to achieve robust, reproducible findings. Such issues include climatic and temporal limitations, the biological origin and state (free versus bound) of PalEnDNA, stratigraphic reliability, sterile sampling, ability to distinguish modern from aDNA signals, DNA damage and PCR amplification, DNA extraction methods, and taxonomic resolution. In this review, we provide a non-specialist introduction to the use of PalEnDNA for Quaternary and archaeological researchers, assess attributes and limitations of this palaeoenvironmental tool, and discuss future prospects of using PalEnDNA to reconstruct past environments

The Effects of Resistance Exercise Training on Strength and Functional Tasks in Adults With Limb-Girdle, Becker, and Facioscapulohumeral Dystrophies

© Copyright © 2019 Bostock, O'Dowd, Payton, Smith, Orme, Edwards and Morse. Background: The inclusion of resistance training in the treatment and management of muscular dystrophy has previously been discouraged, based on mainly anecdotal evidence. There remains a lack of experimental investigation into resistance training in individuals with muscular dystrophy. The aim of the current study was therefore, to determine the effect of a 12-week resistance training programme on muscle strength and functional tasks in ambulatory adults with muscular dystrophy. Methods: Seventeen ambulatory adults with muscular dystrophy (Facioscapulohumeral muscular dystrophy: n = 6, Limb-Girdle muscular dystrophy: n = 6, Becker muscular dystrophy: n = 5) were recruited for this study. Participants attended three testing sessions: one session at baseline, one session after a 12-week control period and one session after a 12-week resistance training period. Each testing session consisted of measurements of isometric knee extensor and knee flexor maximum voluntary contraction (MVC) torque (Cybex dynamometer). Participants also completed a timed sit-to-stand, a four steps-stair ascent, and a four steps-stair decent. The 12-week resistance training period consisted of two supervised sessions a week. Each training session included a 5-min warm-up, a step-up exercise, free-standing or assisted squats, knee flexion and knee extension exercises, and an additional 6 single-joint exercises specific to each individual's needs. Results: Knee flexor MVC torque increased by 13% after the 12-week resistance training programme (p < 0.05), with no change over the control period. Knee extensor MVC torque did not significantly change after the training programme or the control period. Time taken to complete sit-to-stand, stair ascent and stair descent all decreased (improved) following the 12-week training programme (p < 0.05). Conclusions: A twice-a-week, 12-week, resistance training programme resulted in increased knee flexion strength and improvements in functional tasks in ambulatory adults with muscular dystrophy. This provides support for the inclusion of resistance training in the treatment programmes for these forms of muscular dystrophy