The clinical relevance and newsworthiness of NIHR HTA-funded research: a cohort study

ObjectiveTo assess the clinical relevance and newsworthiness of the UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme funded reports.Study designRetrospective cohort study.SettingThe cohort included 311 NIHR HTA Programme funded reports publishing in HTA in the period 1 January 2007–31 December 2012. The McMaster Online Rating of Evidence (MORE) system independently identified the clinical relevance and newsworthiness of NIHR HTA publications and non-NIHR HTA publications. The MORE system involves over 4000 physicians rating publications on a scale of relevance (the extent to which articles are relevant to practice) and a scale of newsworthiness (the extent to which articles contain news or something clinicians are unlikely to know).Main outcome measuresThe proportion of reports published in HTA meeting MORE inclusion criteria and mean average relevance and newsworthiness ratings were calculated and compared with publications from the same studies publishing outside HTA and non-NIHR HTA funded publications.Results286/311 (92.0%) of NIHR HTA reports were assessed by MORE, of which 192 (67.1%) passed MORE criteria. The average clinical relevance rating for NIHR HTA reports was 5.48, statistically higher than the 5.32 rating for non-NIHR HTA publications (mean difference=0.16, 95% CI 0.04 to 0.29, p=0.01). Average newsworthiness ratings were similar between NIHR HTA reports and non-NIHR HTA publications (4.75 and 4.70, respectively; mean difference=0.05, 95% CI ?0.18 to 0.07, p=0.402). NIHR HTA-funded original research reports were statistically higher for newsworthiness than reviews (5.05 compared with 4.64) (mean difference=0.41, 95% CI 0.18 to 0.64, p=0.001).ConclusionsFunding research of clinical relevance is important in maximising the value of research investment. The NIHR HTA Programme is successful in funding projects that generate outputs of clinical relevance

On soil-structure interaction in large non-slender partially buried structures

This paper addresses the seismic analysis of a deeply embedded non-slender structure hosting the pumping unit of a reservoir. The dynamic response in this type of problems is usually studied under the assumption of a perfectly rigid structure using a sub-structuring procedure (three-step solution) proposed specifically for this hypothesis. Such an approach enables a relatively simple assessment of the importance of some key factors influencing the structural response. In this work, the problem is also solved in a single step using a direct approach in which the structure and surrounding soil are modelled as a coupled system with its actual geometry and flexibility. Results indicate that, quite surprisingly, there are significant differences among prediction using both methods. Furthermore, neglecting the flexibility of the structure leads to a significant underestimation of the spectral accelerations at certain points of the structure

A proposal for normalized impedance functions of inclined piles in non-homogeneous media

10th International Conference on Structural Dynamics (EURODYN). Sapienza University Rome, September, 10-13, 2017.This work presents impedance functions for inclined pile groups embedded in different half spaces whose stiffness continuously increases with depth. The results are obtained through a three-dimensional harmonic model where the soil response is modelled through the reciprocity theorem in elastodynamics and the use of Green’s functions for the layered half space, while the piles are represented by finite elements as Timoshenko’s beams. Linear behaviour of soil and piles is assumed. The use of several normalization schemes for the representation of the impedance functions is discussed, highlighting the benefits and drawbacks of each choice and their effects on the interpretation of the obtained results. As a result, expressions for the dimensionless impedance functions and frequency are proposed in order to synthesize the results of the different soil profiles into the same curves. The final objective of the proposed normalization is to transform the well-known impedance functions for the homogeneous halfspace into the corresponding curves for a specific non-homogeneous profile that can be used, e.g., in a substructuring methodology. Despite the fact that the presence of soil non-homogeneity increases the dependence of the impedance functions on the frequency, good agreements between the homogeneous and non-homogeneous profiles can be achieved for a range of frequency of interest.This work was supported by Subdirección General de Proyectos de Investigación of the Ministerio de Economía y Competitividad (MINECO) of Spain and FEDER through research project BIA2014-57640-R. G.M. Álamo is a recipient of FPU research fellowship FPU14/06115 from the Ministerio de Educación, Cultura y Deporte of Spain

First report of Solanum sisymbriifolium and S. americanum as Natural weed hosts of Tomato chlorosis virus (Genus Crinivirus) in South America.

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Complete genome sequence of a novel recombinant Citrus tristeza virus, a resistance-breaking isolate from Uruguay

We report here the complete genome sequence of a Citrus tristeza virus (CTV) from Uruguay, sequenced by using Illumina and Sanger sequencing technology. This CTV DSST-17 genome clustered within genotype resistance breaking (RB) and presents two recombination events

His452Tyr polymorphism in the human 5-HT2A receptor affects clozapine-induced signaling networks revealed by quantitative phosphoproteomics

Antipsychotic drugs remain the current standard for schizophrenia treatment. Although they directly recognize the orthosteric binding site of numerous monoaminergic G protein-coupled receptors (GPCRs), these drugs, and particularly second-generation antipsychotics such as clozapine, all have in common a very high affinity for the serotonin 5-HT receptor (5-HTR). Using classical pharmacology and targeted signaling pathway assays, previous findings suggest that clozapine and other atypical antipsychotics behave principally as 5-HTR neutral antagonists and/or inverse agonists. However, more recent findings showed that antipsychotics may also behave as pathway-specific agonists. Reversible phosphorylation is a common element in multiple signaling networks. Combining a quantitative phosphoproteomic method with signaling network analysis, we tested the effect of clozapine treatment on the overall level of protein phosphorylation and signal transduction cascades in vitro in mammalian cell lines induced to express either the human 5-HTR or the H452Y variant of the gene encoding the 5-HTR receptor. This naturally occurring variation within the 5-HTR gene was selected because it has been repeatedly associated with schizophrenia patients who do not respond to clozapine treatment. Our data show that short time exposure (5 or 10 min) to clozapine (10 M) led to phosphorylation of numerous signaling components of pathways involved in processes such as endocytosis, ErbB signaling, insulin signaling or estrogen signaling. Cells induced to express the H452Y variant showed a different basal phosphoproteome, with increases in the phosphorylation of mTOR signaling components as a translationally relevant example. However, the effect of clozapine on the functional landscape of the phosphoproteome was significantly reduced in cells expressing the 5-HTR-H452Y construct. Together, these findings suggest that clozapine behaves as an agonist inducing phosphorylation of numerous pathways downstream of the 5-HTR, and that the single nucleotide polymorphism encoding 5-HTR-H452Y affects these clozapine-induced phosphorylation-dependent signaling networks