372 research outputs found

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

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    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

    Grafitos sobre Terra Sigillata Hispánica hallados en un vertedero del siglo I en la casa de Hippolytus (Complutum)

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    Presentamos en este estudio un conjunto de materiales inéditos del yacimiento romano de "hippolytus". Estos grafitos, presentes en la mayoría de los establecimientos romanos, no han recibido, en algunas ocasiones, la debida atención por parte de los investigadores. Su análisis pormenorizado, junto a la evidente ventaja de provenir de un contexto arqueológico cerrado y bien definido, nos acerca al conocimiento de las relaciones sociales, parentesco y origen de los moradores de este nuevo enclave altoimperial complutense

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

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    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

    Winkler model for predicting the dynamic response of caisson foundations

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    The paper presents a Winkler-based numerical model for the analysis of the dynamic response of caisson foundations. The model allows the evaluation of the impedance functions and of the foundation input motion (FIM), which can be used in the framework of the substructure approach to compute inertial soil-foundation superstructure interaction analyses. In addition, kinematic stress resultants due to seismic shear waves propagating into the soil can be estimated. The caisson is modelled as a Timoshenko beam and the soil-caisson interaction forces are derived from the analyses of the plane-strain vibration problem of an annular rigid ring embedded into the soil. The problem solution is obtained in the frequency domain exploiting the finite element approach and generic soil stratigraphies can be considered in the applications. The model, which is characterised by a very low computational effort, is validated by performing a parametric investigation, comparing results with those obtained from more rigorous BEM-FEM models of the soil-caissons systems. Finally, some applications to real caisson foundations of offshore wind turbines (OWTs) are shown to demonstrate the model accuracy in capturing the seismic response of the foundations obtained from more rigorous models

    Racismo e cidadania

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    O racismo – fenómeno existente antes e depois da invenção do conceito de raça – tem marcado os debates sobre cidadania desde meados do século XX, circulando de forma marcante em todas as esferas da vida quotidiana devido às representações sociais e históricas que persistem na sociedade portuguesa, sobretudo devido ao seu passado colonial (Araújo, 2007)

    Los números de la regulación sobre igualdad. Cuantificación de la actividad normativa sobre no discriminación en España y su relación con las brechas de género en el mercado de trabajo.

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    Public policies that aim to achieve gender equality, improve work-life balance or combat harassment may have economic consequences, for example, through changes in the labour supply of women or other groups. Although there may be an increase in social awareness of these problems, a separate question is whether this increase is reflected in specific legislation in a society. The objective of this paper is to quantify for the first time when, where and at what rate these social concerns have been translated into legislation. The study covers the period 1996-2022, identifying both central government legislation and legislation in each of the autonomous regions. The analysis, therefore, organises the information in a panel format. The indicators reveal the high degree of heterogeneity in terms of the legislation in the various related areas, with non-discrimination legislation being the most developed and frequent. They also reveal the differences between autonomous regions, with Andalusia and Catalonia being those in which most legislation has been introduced. As an example of an application of this analysis, the database is then used to investigate the relationship between legislative changes and labour market inflows for women. Our estimates show a positive relationship between the volume of legislation passed in the areas of interest, such as non-discrimination policies, and indicators of both employment and female labour force participation.Las políticas públicas orientadas a lograr la igualdad de género, permitir una mayor conciliación de las actividades profesionales con la vida privada o luchar contra el acoso pueden tener consecuencias económicas; por ejemplo, a través de cambios en la oferta laboral de las mujeres u otros colectivos. Ahora bien, pese a que puede existir un aumento de la concienciación social sobre estos problemas, una cuestión diferente es si dicho aumento se ha sustanciado en medidas regulatorias concretas. Este documento tiene como objetivo cuantificar de manera exhaustiva cuándo, en qué lugares y a qué ritmo se han trasladado estas inquietudes sociales a la actividad regulatoria. El estudio abarca el período temporal 1996-2022, identificando normativa tanto estatal como para cada una de las Comunidades Autónomas (CCAA). El análisis, por tanto, organiza la información en formato panel. Los indicadores ponen de manifiesto la elevada heterogeneidad en lo que se refiere a la regulación de las distintas materias relacionadas. En lo relativo a los temas, es la normativa orientada a desarrollar políticas de no discriminación la más frecuente. En cuanto al ámbito territorial y administrativo, son Andalucía y Cataluña las CCAA en las que más normativa se ha aprobado. A modo de ejemplo de aplicación, se utiliza posteriormente la base de datos para entender la relación entre las normas aprobadas y determinados flujos de entrada en el mercado de trabajo para las mujeres. Nuestras estimaciones muestran una relación positiva entre el volumen de normas aprobadas en las materias de interés y los indicadores tanto de empleo como de participación laboral femenina

    Extensive conservation of ancient microsynteny across metazoans due to cis-regulatory constraints

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    This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date; after six months, it is available under a Creative Commons License.-- et al.The order of genes in eukaryotic genomes has generally been assumed to be neutral, since gene order is largely scrambled over evolutionary time. Only a handful of exceptional examples are known, typically involving deeply conserved clusters of tandemly duplicated genes (e.g., Hox genes and histones). Here we report the first systematic survey of microsynteny conservation across metazoans, utilizing 17 genome sequences. We identified nearly 600 pairs of unrelated genes that have remained tightly physically linked in diverse lineages across over 600 million years of evolution. Integrating sequence conservation, gene expression data, gene function, epigenetic marks, and other genomic features, we provide extensive evidence that many conserved ancient linkages involve (1) the coordinated transcription of neighboring genes, or (2) genomic regulatory blocks (GRBs) in which transcriptional enhancers controlling developmental genes are contained within nearby bystander genes. In addition, we generated ChIP-seq data for key histone modifications in zebrafish embryos, which provided further evidence of putative GRBs in embryonic development. Finally, using chromosome conformation capture (3C) assays and stable transgenic experiments, we demonstrate that enhancers within bystander genes drive the expression of genes such as Otx and Islet, critical regulators of central nervous system development across bilaterians. These results suggest that ancient genomic functional associations are far more common than previously thought—involving ∼12% of the ancestral bilaterian genome—and that cis-regulatory constraints are crucial in determining metazoan genome architecture.M.I., M.S.A., S.W.R., and H.B.F. were funded by NIH grant 1R21HG005240-01A1. H.B.F. is an Alfred P. Sloan Fellow and Pew Scholar in the Biomedical Sciences. J.J.T., A.F-M., O.B., E.C-M., and J.L.G-S. were funded by grants BFU2010-14839, CSD2007-00008, and Proyecto de Excelencia CVI-3488.Peer reviewe

    Ancient Genomic Regulatory Blocks Are a Source for Regulatory Gene Deserts in Vertebrates after Whole-Genome Duplications

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    We investigated how the two rounds of whole genome duplication that occurred at the base of the vertebrate lineage have impacted ancient microsyntenic associations involving developmental regulators (known as genomic regulatory blocks, GRBs). We showed that the majority of GRBs identified in the last common ancestor of chordates have been maintained as a single copy in humans. We found evidence that dismantling of the duplicated GRB copies occurred early in vertebrate evolution often through the differential retention of the regulatory gene but loss of the bystander gene's exonic sequences. Despite the large evolutionary scale, the presence of duplicated highly conserved non-coding regions provided unambiguous proof for this scenario for multiple ancient GRBs. Remarkably, the dismantling of ancient GRB duplicates has contributed to the creation of large gene deserts associated with regulatory genes in vertebrates, providing a potentially widespread mechanism for the origin of these enigmatic genomic traits

    Top research priorities in healthcare-associated infection in the UK

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    Background: There is a mismatch between research questions which are considered to be important by patients, carers and healthcare professionals and the research performed in many fields of medicine. No relevant studies which have assessed research priorities in healthcare-associated infection (HCAI) that have involved patients' and carers' opinions were identified in the literature. / Aim: The Healthcare-Associated Infections Priority Setting Partnership was established to identify the top research priorities in the prevention, diagnosis and treatment of HCAI in the UK, considering the opinions of all these groups. / Methods: The methods broadly followed the principles of the James Lind Alliance (JLA) priority setting activity. / Findings: In total, 259 unique valid research questions were identified from 221 valid responses to a consultation of patients, carers and healthcare professionals after seeking their opinions for research priorities. The steering committee of the priority setting partnership rationalized these to 50 unique questions. A literature review established that for these questions there were no recent high-quality systematic reviews, high-quality systematic reviews which concluded that further studies were necessary, or the steering committee considered that further research was required despite the conclusions of recent systematic reviews. An interim survey ranked the 50 questions, and the 10 main research priorities were identified from the top 32 questions by consensus at a final priority setting workshop of patients, carers and healthcare professionals using group discussions. / Conclusions: A priority setting process using JLA methods and principles involving patients, carers and healthcare professionals was used to identify the top 10 priority areas for research related to HCAI. Basic, translational, clinical and public health research would be required to address these uncertainties
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