A hybrid radiation detector for simultaneous spatial and temporal dosimetry

In this feasibility study an organic plastic scintillator is calibrated against ionisation chamber measurements and then embedded in a polymer gel dosimeter to obtain a quasi-4D experimental measurement of a radiation field. This hybrid dosimeter was irradiated with a linear accelerator, with temporal measurements of the dose rate being acquired by the scintillator and spatial measurements acquired with the gel dosimeter. The detectors employed in this work are radiologically equivalent; and we show that neither detector perturbs the intensity of the radiation field of the other. By employing these detectors in concert, spatial and temporal variations in the radiation intensity can now be detected and gel dosimeters can be calibrated for absolute dose from a single irradiation

The effectiveness of the Liverpool care pathway in improving end of life care for dying cancer patients in hospital. A cluster randomised trial

<p>Abstract</p> <p>Background</p> <p>Most cancer patients still die in hospital, mainly in medical wards. Many studies in different countries have shown the poor quality of end-of-life care delivery in hospitals. The Program "Liverpool Care Pathway for the dying patient" (LCP), developed in the UK to transfer the hospice model of care into hospitals and other care settings, is a complex intervention to improve the quality of end-of-life care. The results from qualitative and quantitative studies suggest that the LCP Program can improve significantly the quality of end-of-life care delivery in hospitals, but no randomised trial has been conducted till now.</p> <p>Methods and design</p> <p>This is a randomized cluster trial, stratified by regions and matched for assessment period. Pairs of eligible medical wards from different hospitals will be randomized to receive the LCP-I Program or no intervention until the end of the trial. The LCP-I Program will be implemented by a Palliative Care Unit.</p> <p>The assessment of the end-points will be performed for all cancer deaths occurred in the six months after the end of the LCP-I implementation in the experimental wards and, in the same period of time, in the matched control wards. The primary end-point is the overall quality of end-of-life care provided on the ward to dying cancer patients and their families, assessed using the Global Scale of the Italian version of the Toolkit <it>"After-death Bereaved Family Member Interview</it>".</p> <p>Discussion</p> <p>This study can be interpreted as a Phase III trial according to the Medical Research Council Framework. In this study, the effectiveness of a fully defined intervention is assessed by comparing the distribution of the endpoints in the experimental and in the control arm.</p> <p>Research ID</p> <p>RFPS-2006-6-341619</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01081899">NCT01081899</a></p

Statistical significance of cis-regulatory modules

BACKGROUND: It is becoming increasingly important for researchers to be able to scan through large genomic regions for transcription factor binding sites or clusters of binding sites forming cis-regulatory modules. Correspondingly, there has been a push to develop algorithms for the rapid detection and assessment of cis-regulatory modules. While various algorithms for this purpose have been introduced, most are not well suited for rapid, genome scale scanning. RESULTS: We introduce methods designed for the detection and statistical evaluation of cis-regulatory modules, modeled as either clusters of individual binding sites or as combinations of sites with constrained organization. In order to determine the statistical significance of module sites, we first need a method to determine the statistical significance of single transcription factor binding site matches. We introduce a straightforward method of estimating the statistical significance of single site matches using a database of known promoters to produce data structures that can be used to estimate p-values for binding site matches. We next introduce a technique to calculate the statistical significance of the arrangement of binding sites within a module using a max-gap model. If the module scanned for has defined organizational parameters, the probability of the module is corrected to account for organizational constraints. The statistical significance of single site matches and the architecture of sites within the module can be combined to provide an overall estimation of statistical significance of cis-regulatory module sites. CONCLUSION: The methods introduced in this paper allow for the detection and statistical evaluation of single transcription factor binding sites and cis-regulatory modules. The features described are implemented in the Search Tool for Occurrences of Regulatory Motifs (STORM) and MODSTORM software

High-growth firms and productivity:evidence from the United Kingdom

Abstract There is considerable evidence that high-growth firms (HGFs) contribute significantly to employment and economic growth. However, the literature so far does not adequately explore the link between HGFs and productivity. This paper investigates the empirical link between total factor productivity (TFP) growth and HGFs, defined in terms of sales growth, in the United Kingdom over the period 2001-2010, by examining two related research questions. Firstly, does higher TFP growth lead to HGF status and secondly, does HGF experience help firms achieve faster TFP growth? Our findings reveal that firms in both the manufacturing and services sectors are more likely to become HGFs when they exhibit higher TFP growth. In addition, firms that have had HGF experience tend to enjoy faster TFP growth following the high-growth episodes. Policy implications are drawn based on the self-reinforcing process of the high-growth phenomenon that is revealed by our results

Inferring Visuomotor Priors for Sensorimotor Learning

Sensorimotor learning has been shown to depend on both prior expectations and sensory evidence in a way that is consistent with Bayesian integration. Thus, prior beliefs play a key role during the learning process, especially when only ambiguous sensory information is available. Here we develop a novel technique to estimate the covariance structure of the prior over visuomotor transformations – the mapping between actual and visual location of the hand – during a learning task. Subjects performed reaching movements under multiple visuomotor transformations in which they received visual feedback of their hand position only at the end of the movement. After experiencing a particular transformation for one reach, subjects have insufficient information to determine the exact transformation, and so their second reach reflects a combination of their prior over visuomotor transformations and the sensory evidence from the first reach. We developed a Bayesian observer model in order to infer the covariance structure of the subjects' prior, which was found to give high probability to parameter settings consistent with visuomotor rotations. Therefore, although the set of visuomotor transformations experienced had little structure, the subjects had a strong tendency to interpret ambiguous sensory evidence as arising from rotation-like transformations. We then exposed the same subjects to a highly-structured set of visuomotor transformations, designed to be very different from the set of visuomotor rotations. During this exposure the prior was found to have changed significantly to have a covariance structure that no longer favored rotation-like transformations. In summary, we have developed a technique which can estimate the full covariance structure of a prior in a sensorimotor task and have shown that the prior over visuomotor transformations favor a rotation-like structure. Moreover, through experience of a novel task structure, participants can appropriately alter the covariance structure of their prior

Elimination of Rhodnius prolixus in Central America

Rhodnius prolixus is one of the main vectors of Trypanosoma cruzi, causative agent of Chagas disease. In Central America, it was first discovered in 1915 in El Salvador, from where it spread northwest to Guatemala and Mexico, and southeast to Nicaragua and Costa Rica, arriving also in Honduras in the late 1950s. Indoor residual spraying (IRS) by the antimalaria services of Costa Rica prevented its spread southwards, and similar IRS programmes appear to have eliminated it from El Salvador by the late 1970s. In 1997, by resolution of the Ministers of Health of the seven Central American countries, a multinational initiative against Chagas disease (IPCA) was launched with one of the specific objectives being the elimination of R. prolixus from the region. As a result, more and more infested areas were encountered, and progressively sprayed using an IRS strategy already deployed against Triatoma infestans in the southern cone countries of South America. In 2008, Guatemala became the first of these countries to be formally certified as free of Chagas disease transmission due to R. prolixus. The other infested countries have since been similarly certified, and none of these has reported the presence of R. prolixus since June 2010. Further surveillance is required, but current evidence suggests that R. prolixus may now been eliminated from throughout the mesoamerican region, with a corresponding decline in the incidence of T. cruzi infections

Kynurenine–3–monooxygenase inhibition prevents multiple organ failure in rodent models of acute pancreatitis

Acute pancreatitis (AP) is a common and devastating inflammatory condition of the pancreas that is considered to be a paradigm of sterile inflammation leading to systemic multiple organ dysfunction syndrome (MODS) and death1,2 Acute mortality from AP-MODS exceeds 20%3 and for those who survive the initial episode, their lifespan is typically shorter than the general population4. There are no specific therapies available that protect individuals against AP-MODS. Here, we show that kynurenine-3-monooxygenase (KMO), a key enzyme of tryptophan metabolism5, is central to the pathogenesis of AP-MODS. We created a mouse strain deficient for Kmo with a robust biochemical phenotype that protected against extrapancreatic tissue injury to lung, kidney and liver in experimental AP-MODS. A medicinal chemistry strategy based on modifications of the kynurenine substrate led to the discovery of GSK180 as a potent and specific inhibitor of KMO. The binding mode of the inhibitor in the active site was confirmed by X-ray co-crystallography at 3.2 Å resolution. Treatment with GSK180 resulted in rapid changes in levels of kynurenine pathway metabolites in vivo and afforded therapeutic protection against AP-MODS in a rat model of AP. Our findings establish KMO inhibition as a novel therapeutic strategy in the treatment of AP-MODS and open up a new area for drug discovery in critical illness