Efficacious, effective, and embedded interventions: Implementation research in infectious disease control

Background: Research in infectious disease control is heavily skewed towards high end technology; development of new drugs, vaccines and clinical interventions. Oft ignored, is the evidence to inform the best strategies that ensure the embedding of interventions into health systems and amongst populations. In this paper we undertake an analysis of the challenge in the development of research for the sustainable implementation of disease control interventions. Results: We highlight the fundamental differences between the research paradigms associated with the development of technologies and interventions for disease control on the one hand and the research paradigms required for enhancing the sustainable uptake of those very same interventions within the communities on the other. We provide a definition for implementation research in an attempt to underscore its critical role and explore the multidisciplinary science needed to address the challenges in disease control. Conclusion: The greatest value for money in health research lies in the sustainable and effective implementation of already proven, efficacious solutions. The development of implementation research that can help provide some solutions on how this can be achieved is sorely needed

Chromosome assignment of two cloned DNA probes hybridizing predominantly to human sex chromosomes

In situ hybridization experiments were carried out with two clones, YACG 35 and 2.8, which had been selected from two genomic libraries strongly enriched for the human Y chromosome. Besides the human Y chromosome, both sequences strongly hybridized to the human X chromosome, with few minor binding sites on autosomes. In particular, on the X chromosome DNA from clone YACG 35 hybridized to the centromeric region and the distal part of the short arm (Xp2.2). On the Y chromosome, the sequence was assigned to one site situated in the border region between Yq1.1 and Yq1.2. DNA from clone 2.8 also hybridized to the centromeric region of the X and the distal part of the short arm (Xq2.2). On the Y, however, two binding sites were observed (Yp1.1 and Yq1.2). The findings indicate that sex chromosomal sequences may be localized in homologous regions (as suggested from meiotic pairing) but also at ectopic sites

Risk stratification by pre-operative cardiopulmonary exercise testing improves outcomes following elective abdominal aortic aneurysm surgery : a cohort study

Background: In 2009, the NHS evidence adoption center and National Institute for Health and Care Excellence (NICE) published a review of the use of endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs). They recommended the development of a risk-assessment tool to help identify AAA patients with greater or lesser risk of operative mortality and to contribute to mortality prediction. A low anaerobic threshold (AT), which is a reliable, objective measure of pre-operative cardiorespiratory fitness, as determined by pre-operative cardiopulmonary exercise testing (CPET) is associated with poor surgical outcomes for major abdominal surgery. We aimed to assess the impact of a CPET-based risk-stratification strategy upon perioperative mortality, length of stay and non-operative costs for elective (open and endovascular) infra-renal AAA patients. Methods: A retrospective cohort study was undertaken. Pre-operative CPET-based selection for elective surgical intervention was introduced in 2007. An anonymized cohort of 230 consecutive infra-renal AAA patients (2007 to 2011) was studied. A historical control group of 128 consecutive infra-renal AAA patients (2003 to 2007) was identified for comparison. Comparative analysis of demographic and outcome data for CPET-pass (AT ≥ 11 ml/kg/min), CPET-fail (AT < 11 ml/kg/min) and CPET-submaximal (no AT generated) subgroups with control subjects was performed. Primary outcomes included 30-day mortality, survival and length of stay (LOS); secondary outcomes were non-operative inpatient costs. Results: Of 230 subjects, 188 underwent CPET: CPET-pass n = 131, CPET-fail n = 35 and CPET-submaximal n = 22. When compared to the controls, CPET-pass patients exhibited reduced median total LOS (10 vs 13 days for open surgery, n = 74, P < 0.01 and 4 vs 6 days for EVAR, n = 29, P < 0.05), intensive therapy unit requirement (3 vs 4 days for open repair only, P < 0.001), non-operative costs (£5,387 vs £9,634 for open repair, P < 0.001) and perioperative mortality (2.7% vs 12.6% (odds ratio: 0.19) for open repair only, P < 0.05). CPET-stratified (open/endovascular) patients exhibited a mid-term survival benefit (P < 0.05). Conclusion: In this retrospective cohort study, a pre-operative AT > 11 ml/kg/min was associated with reduced perioperative mortality (open cases only), LOS, survival and inpatient costs (open and endovascular repair) for elective infra-renal AAA surgery

Stoichiometry of Base Excision Repair Proteins Correlates with Increased Somatic CAG Instability in Striatum over Cerebellum in Huntington's Disease Transgenic Mice

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by expansion of an unstable CAG repeat in the coding sequence of the Huntingtin (HTT) gene. Instability affects both germline and somatic cells. Somatic instability increases with age and is tissue-specific. In particular, the CAG repeat sequence in the striatum, the brain region that preferentially degenerates in HD, is highly unstable, whereas it is rather stable in the disease-spared cerebellum. The mechanisms underlying the age-dependence and tissue-specificity of somatic CAG instability remain obscure. Recent studies have suggested that DNA oxidation and OGG1, a glycosylase involved in the repair of 8-oxoguanine lesions, contribute to this process. We show that in HD mice oxidative DNA damage abnormally accumulates at CAG repeats in a length-dependent, but age- and tissue-independent manner, indicating that oxidative DNA damage alone is not sufficient to trigger somatic instability. Protein levels and activities of major base excision repair (BER) enzymes were compared between striatum and cerebellum of HD mice. Strikingly, 5′-flap endonuclease activity was much lower in the striatum than in the cerebellum of HD mice. Accordingly, Flap Endonuclease-1 (FEN1), the main enzyme responsible for 5′-flap endonuclease activity, and the BER cofactor HMGB1, both of which participate in long-patch BER (LP–BER), were also significantly lower in the striatum compared to the cerebellum. Finally, chromatin immunoprecipitation experiments revealed that POLβ was specifically enriched at CAG expansions in the striatum, but not in the cerebellum of HD mice. These in vivo data fit a model in which POLβ strand displacement activity during LP–BER promotes the formation of stable 5′-flap structures at CAG repeats representing pre-expanded intermediate structures, which are not efficiently removed when FEN1 activity is constitutively low. We propose that the stoichiometry of BER enzymes is one critical factor underlying the tissue selectivity of somatic CAG expansion

CMB Telescopes and Optical Systems

The cosmic microwave background radiation (CMB) is now firmly established as a fundamental and essential probe of the geometry, constituents, and birth of the Universe. The CMB is a potent observable because it can be measured with precision and accuracy. Just as importantly, theoretical models of the Universe can predict the characteristics of the CMB to high accuracy, and those predictions can be directly compared to observations. There are multiple aspects associated with making a precise measurement. In this review, we focus on optical components for the instrumentation used to measure the CMB polarization and temperature anisotropy. We begin with an overview of general considerations for CMB observations and discuss common concepts used in the community. We next consider a variety of alternatives available for a designer of a CMB telescope. Our discussion is guided by the ground and balloon-based instruments that have been implemented over the years. In the same vein, we compare the arc-minute resolution Atacama Cosmology Telescope (ACT) and the South Pole Telescope (SPT). CMB interferometers are presented briefly. We conclude with a comparison of the four CMB satellites, Relikt, COBE, WMAP, and Planck, to demonstrate a remarkable evolution in design, sensitivity, resolution, and complexity over the past thirty years.Comment: To appear in: Planets, Stars and Stellar Systems (PSSS), Volume 1: Telescopes and Instrumentatio

Enhanced Luminescence of Eu-Doped TiO2Nanodots

Monodisperse and spherical Eu-doped TiO2nanodots were prepared on substrate by phase-separation-induced self-assembly. The average diameters of the nanodots can be 50 and 70 nm by changing the preparation condition. The calcined nanodots consist of an amorphous TiO2matrix with Eu3+ions highly dispersed in it. The Eu-doped TiO2nanodots exhibit intense luminescence due to effective energy transfer from amorphous TiO2matrix to Eu3+ions. The luminescence intensity is about 12.5 times of that of Eu-doped TiO2film and the luminescence lifetime can be as long as 960 μs

Quality of care associated with number of cases seen and self-reports of clinical competence for Japanese physicians-in-training in internal medicine

BACKGROUND: The extent of clinical exposure needed to ensure quality care has not been well determined during internal medicine training. We aimed to determine the association between clinical exposure (number of cases seen), self- reports of clinical competence, and type of institution (predictor variables) and quality of care (outcome variable) as measured by clinical vignettes. METHODS: Cross-sectional study using univariate and multivariate linear analyses in 11 teaching hospitals in Japan. Participants were physicians-in-training in internal medicine departments. Main outcome measure was standardized t-scores (quality of care) derived from responses to five clinical vignettes. RESULTS: Of the 375 eligible participants, 263 (70.1%) completed the vignettes. Most were in their first (57.8%) and second year (28.5%) of training; on average, the participants were 1.8 years (range = 1–8) after graduation. Two thirds of the participants (68.8%) worked in university-affiliated teaching hospitals. The median number of cases seen was 210 (range = 10–11400). Greater exposure to cases (p = 0.0005), higher self-reports of clinical competence (p = 0.0095), and type of institution (p < 0.0001) were significantly associated with higher quality of care, using a multivariate linear model and adjusting for the remaining factors. Quality of care rapidly increased for the first 100 to 200 cases seen and tapered thereafter. CONCLUSION: The amount of clinical exposure and levels of self-reports of clinical competence, not years after graduation, were positively associated with quality of care, adjusting for the remaining factors. The learning curve tapered after about 200 cases

A spectroscopy approach to the study of virus infection in the endophytic fungus Epichloë festucae

<p>Abstract</p> <p>Background</p> <p>In this work we propose a rapid method based on visible and near-infrared (Vis-NIR) spectroscopy to determine the occurrence of double-stranded RNA (dsRNA) viruses in <it>Epichloë festucae </it>strains isolated from <it>Festuca rubra </it>plants. In addition, we examined the incidence of infections by <it>E. festucae </it>in populations of <it>F. rubra </it>collected in natural grasslands of Western Spain.</p> <p>Methods</p> <p>Vis-NIR spectra (400-2498 nm) from 124 virus-infected and virus-free <it>E. festucae </it>isolates were recorded directly from ground and freeze-dried mycelium. To estimate how well the spectra for uninfected and infected fungal samples could be differentiated, we used partial least-squares discriminant analysis (PLS1-DA) and several data pre-treatments to develop calibration models.</p> <p>Results</p> <p>Applying the best regression model, obtained with two sampling years and using standard normal variate (SNV) combined with first derivative transformation to a new validating data set (42 samples), we obtained a correct classification for 75% of the uninfected isolates and up to 86% of the infected isolates.</p> <p>Conclusions</p> <p>The results obtained suggest that Vis-NIR spectroscopy is a promising technology for detection of viral infections in fungal samples when an alternative faster approach is desirable. It provides a tool adequately exact and more time- and cost-saving than the conventional reference analysis.</p

First observations of separated atmospheric nu_mu and bar{nu-mu} events in the MINOS detector

The complete 5.4 kton MINOS far detector has been taking data since the beginning of August 2003 at a depth of 2070 meters water-equivalent in the Soudan mine, Minnesota. This paper presents the first MINOS observations of nuµ and [overline nu ]µ charged-current atmospheric neutrino interactions based on an exposure of 418 days. The ratio of upward- to downward-going events in the data is compared to the Monte Carlo expectation in the absence of neutrino oscillations, giving Rup/downdata/Rup/downMC=0.62-0.14+0.19(stat.)±0.02(sys.). An extended maximum likelihood analysis of the observed L/E distributions excludes the null hypothesis of no neutrino oscillations at the 98% confidence level. Using the curvature of the observed muons in the 1.3 T MINOS magnetic field nuµ and [overline nu ]µ interactions are separated. The ratio of [overline nu ]µ to nuµ events in the data is compared to the Monte Carlo expectation assuming neutrinos and antineutrinos oscillate in the same manner, giving R[overline nu ][sub mu]/nu[sub mu]data/R[overline nu ][sub mu]/nu[sub mu]MC=0.96-0.27+0.38(stat.)±0.15(sys.), where the errors are the statistical and systematic uncertainties. Although the statistics are limited, this is the first direct observation of atmospheric neutrino interactions separately for nuµ and [overline nu ]µ