VennVax, a DNA-prime, peptide-boost multi-T-cell epitope poxvirus vaccine, induces protective immunity against vaccinia infection by T cell response alone

The potential for smallpox to be disseminated in a bioterror attack has prompted development of new, safer smallpox vaccination strategies. We designed and evaluated immunogenicity and efficacy of a T-cell epitope vaccine based on conserved and antigenic vaccinia/variola sequences, identified using bioinformatics and immunological methods. Vaccination in HLA transgenic mice using a DNA-prime/peptide-boost strategy elicited significant T cell responses to multiple epitopes. No antibody response pre-challenge was observed, neither against whole vaccinia antigens nor vaccine epitope peptides. Remarkably, 100% of vaccinated mice survived lethal vaccinia challenge, demonstrating that protective immunity to vaccinia does not require B cell priming

Acid-suppression medications and bacterial gastroenteritis:a population-based cohort study

AIMS: To investigate whether acid suppression medicines (ASMs) increase the risk of bacterial gastroenteritis. METHODS: A population-based, propensity-score matched cohort study using a record-linkage database in Tayside, Scotland. The study consisted of 188,323 exposed to ASMs [proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RA)] and 376,646 controls (a propensity-score matched cohort from the rest of population who were not exposed to ASMs) between 1999 and 2013. The main outcome measure was a positive stool test for C. difficile, Campylobacter, Salmonella, Shigella or Escherichia coli O157. The association between ASMs and risk of bacterial gastroenteritis was assessed by a Cox regression model. RESULTS: There were 22,705 positive test results (15,273 Clostridium difficile (toxin positive), 6,590 Campylobacter, 852 Salmonella, 129 Shigella and 193 Escherichia coli O157, not mutually exclusive) with a total of 5,729,743 person-years follow up time in Tayside, 1999-2013. The adjusted hazard ratios (HRs) for culture positive diarrhoea for the PPIs and H2RA exposed vs unexposed cohort were 2.72 [95% confidence interval (CI) 2.33, 3.17] during follow up time for samples submitted from the community and 1.28 (95% CI 1.08, 1.52) for samples submitted from hospitals. Compared with the unexposed cohort, patients in the exposed group had increased risks of C. difficile and Campylobacter [adjusted HRs of 1.70 (95% CI 1.28, 2.25), 3.71 (95% CI 3.04, 4.53) for community samples, and 1.42 (95% CI 1.17, 1.71), 4.53 (95% CI 1.75, 11.8) for hospital samples, respectively]. CONCLUSIONS: The results suggest that community prescribed ASMs were associated with increased rates of C. difficile and Campylobacter positive gastroenteritis in both the community and hospital settings

Spatially Correlated Cluster Populations in the Outer Disk of NGC 3184

We use deep (~27.5 mag V-band point-source limiting magnitude) V- and U-band LBT imaging to study the outer disk (beyond the optical radius R_25) of the non-interacting, face-on spiral galaxy NGC 3184 (D = 11.1 Mpc; R_25 = 11.1 kpc) and find that this outer disk contains >1000 objects (or marginally-resolved 'knots') resembling star clusters with masses ~10^2 - 10^4 M_sun and ages up to ~1 Gyr. We find statistically significant numbers of these cluster-like knots extending to ~1.4 R_25, with the redder knots outnumbering bluer at the largest radii. We measure clustering among knots and find significant correlation to galactocentric radii of 1.5 R_25 for knot separations <1 kpc. The effective integrated surface brightness of this outer disk cluster population ranges from 30 - 32 mag arcsec^-2 in V. We compare the HI extent to that of the correlated knots and find that the clusters extend at least to the damped Lyman-alpha threshold of HI column density (2e20 cm^-2; 1.62 R_25). The blue knots are correlated with HI spiral structure to 1.5 R_25, while the red knots may be correlated with the outer fringes of the HI disk to 1.7 R_25. These results suggest that outer disks are well-populated, common, and long-lasting features of many nearby disk galaxies.Comment: Accepted for publication in The Astrophysical Journal. 12 pages, 10 figure

Improved Standardization of Type II-P Supernovae: Application to an Expanded Sample

In the epoch of precise and accurate cosmology, cross-confirmation using a variety of cosmographic methods is paramount to circumvent systematic uncertainties. Owing to progenitor histories and explosion physics differing from those of Type Ia SNe (SNe Ia), Type II-plateau supernovae (SNe II-P) are unlikely to be affected by evolution in the same way. Based on a new analysis of 17 SNe II-P, and on an improved methodology, we find that SNe II-P are good standardizable candles, almost comparable to SNe Ia. We derive a tight Hubble diagram with a dispersion of 10% in distance, using the simple correlation between luminosity and photospheric velocity introduced by Hamuy & Pinto 2002. We show that the descendent method of Nugent et al. 2006 can be further simplified and that the correction for dust extinction has low statistical impact. We find that our SN sample favors, on average, a very steep dust law with total to selective extinction R_V<2. Such an extinction law has been recently inferred for many SNe Ia. Our results indicate that a distance measurement can be obtained with a single spectrum of a SN II-P during the plateau phase combined with sparse photometric measurements.Comment: ApJ accepted version. Minor change

BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

Parental attributions of control for child behaviour and their relation to discipline practices in parents of children with and without developmental delays

Children with developmental delays (DD) are at risk for developing behavior problems. Research suggests that parents’ causal attributions for child behavior are related to parenting. This study investigated this association in parents of children with DD compared to parents of typically developing (TD) children. It specifically focused on attributions of child control by separating these from attributions of responsibility, blame and intent, and from attributions of parent control and responsibility. Fifty-one parents of children with DD and 69 parents of TD children completed two questionnaires. The Written Analogue Questionnaire measured causal attributions. The Parenting Scale measured dysfunctional discipline practices. Parents of children with DD viewed the child’s role in problematic behavior more positively while also viewing misbehavior as more fixed than parents of TD children. Parents of TD children who viewed their child as more in control over misbehavior used less dysfunctional discipline, but this association was not found for parents of children with DD. The results advance understanding of how parents perceive behavior problems in children with DD and the important role these perceptions play in parental behavior management strategies. More importantly, these perceptions relate to discipline practices differently for parents of children with DD compared to parents of TD children, highlighting that parent interventions should be adapted to the specific needs of parents of children with DD

Phonological and articulation treatment approaches in Portuguese children with speech and language impairments: a randomized controlled intervention study

Background In Portugal, the routine clinical practice of speech and language therapists (SLTs) in treating children with all types of speech sound disorder (SSD) continues to be articulation therapy (AT). There is limited use of phonological therapy (PT) or phonological awareness training in Portugal. Additionally, at an international level there is a focus on collecting information on and differentiating between the effectiveness of PT and AT for children with different types of phonologically based SSD, as well as on the role of phonological awareness in remediating SSD. It is important to collect more evidence for the most effective and efficient type of intervention approach for different SSDs and for these data to be collected from diverse linguistic and cultural perspectives. Aims To evaluate the effectiveness of a PT and AT approach for treatment of 14 Portuguese children, aged 4.0–6.7 years, with a phonologically based SSD. Methods & Procedures The children were randomly assigned to one of the two treatment approaches (seven children in each group). All children were treated by the same SLT, blind to the aims of the study, over three blocks of a total of 25 weekly sessions of intervention. Outcome measures of phonological ability (percentage of consonants correct (PCC), percentage occurrence of different phonological processes and phonetic inventory) were taken before and after intervention. A qualitative assessment of intervention effectiveness from the perspective of the parents of participants was included. Outcomes & Results Both treatments were effective in improving the participants’ speech, with the children receiving PT showing a more significant improvement in PCC score than those receiving the AT. Children in the PT group also showed greater generalization to untreated words than those receiving AT. Parents reported both intervention approaches to be as effective in improving their children's speech. Conclusions & Implications The PT (combination of expressive phonological tasks, phonological awareness, listening and discrimination activities) proved to be an effective integrated method of improving phonological SSD in children. These findings provide some evidence for Portuguese SLTs to employ PT with children with phonologically based SSD

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

Physician supply forecast: better than peering in a crystal ball?

<p>Abstract</p> <p>Background</p> <p>Anticipating physician supply to tackle future health challenges is a crucial but complex task for policy planners. A number of forecasting tools are available, but the methods, advantages and shortcomings of such tools are not straightforward and not always well appraised. Therefore this paper had two objectives: to present a typology of existing forecasting approaches and to analyse the methodology-related issues.</p> <p>Methods</p> <p>A literature review was carried out in electronic databases Medline-Ovid, Embase and ERIC. Concrete examples of planning experiences in various countries were analysed.</p> <p>Results</p> <p>Four main forecasting approaches were identified. The supply projection approach defines the necessary inflow to maintain or to reach in the future an arbitrary predefined level of service offer. The demand-based approach estimates the quantity of health care services used by the population in the future to project physician requirements. The needs-based approach involves defining and predicting health care deficits so that they can be addressed by an adequate workforce. Benchmarking health systems with similar populations and health profiles is the last approach. These different methods can be combined to perform a gap analysis. The methodological challenges of such projections are numerous: most often static models are used and their uncertainty is not assessed; valid and comprehensive data to feed into the models are often lacking; and a rapidly evolving environment affects the likelihood of projection scenarios. As a result, the internal and external validity of the projections included in our review appeared limited.</p> <p>Conclusion</p> <p>There is no single accepted approach to forecasting physician requirements. The value of projections lies in their utility in identifying the current and emerging trends to which policy-makers need to respond. A genuine gap analysis, an effective monitoring of key parameters and comprehensive workforce planning are key elements to improving the usefulness of physician supply projections.</p