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

Centros de acceso público a las tecnologías de información y comunicación en América Latina: características y desafíos

Incluye BibliografíaEl objetivo principal del presente estudio, fue identificar y caracterizar el mayor número posible de programas de Centros de Acceso Público a las Tecnologías de la Información y Comunicación (CAPT), existentes en los países seleccionados para el estudio. El resultado del mismo es un mapeo que debe ser entendido como una primera aproximación a la situación actual. En este sentido, el levantamiento no proclama ser exhaustivo, ni completo, o estadísticamente representativo, sino un primer paso en un terreno todavía bastante desconocido, pero de crucial importancia para el desarrollo de las Sociedades de la Información en América Latina (AL). No obstante, cabe mencionar que, de acuerdo con la literatura revisada, este estudio es el más extenso y profundo sobre esta temática realizado en la región hasta la fecha. En el marco del estudio, se realizaron un total de 70 entrevistas válidas a responsables de los programas CAPT existentes en la región, en un total de 13 países. La información coleccionada a través de este mecanismo esta definida como fuente primaria (FP). Adicionalmente se recabó información secundaria sobre 151 programas CAPT adicionales (fuente secundaria FS). El estudio está dividido en dos partes: la primera parte muestra los resultados cuantitativos sobre el fenómeno de los CAPT en 14 países de la región de América Latina. Brasil fue incluido en la muestra del estudio, aunque solo se pudo obtener información secundaria. La segunda parte presenta los análisis cualitativos realizados por los investigadores responsables de la realización de las entrevistas. Los resultados de la primera parte muestran como el fenómeno de los CAPT presenta una evolución creciente y con altas perspectivas de sostenibilidad en el tiempo. El estudio, permite tener un primer acercamiento a la realidad de los CAPT a través del análisis del centro promedio y formular algunas recomendaciones que contribuyan al mejoramiento de este tipo de iniciativas. De acuerdo con datos anteriormente disponibles (ver por ejemplo CEPAL, 2005) se estimaba que en 2004 el número de CAPT gubernamentales oscilaba entre 6.000 y 10.000 en toda América Latina. Los resultados obtenidos mediante investigaciones primarias y secundarias de este nuevo sondeo, indican que para el año 2005 el número total de CAPT, tanto gubernamentales como privados, ascendían a 139.064 y se prevee que este número se incremente en años sucesivos

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

Top research priorities in healthcare-associated infection in the UK

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

Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

p73 is required for appropriate BMP-induced mesenchymal-to-epithelial transition during somatic cell reprogramming

The generation of induced pluripotent stem cells (iPSCs) by somatic cell reprogramming holds great potential for modeling human diseases. However, the reprogramming process remains very inefficient and a better understanding of its basic biology is required. The mesenchymal-to-epithelial transition (MET) has been recognized as a crucial step for the successful reprogramming of fibroblasts into iPSCs. It has been reported that the p53 tumor suppressor gene acts as a barrier of this process, while its homolog p63 acts as an enabling factor. In this regard, the information concerning the role of the third homolog, p73, during cell reprogramming is limited. Here, we derive total Trp73 knockout mouse embryonic fibroblasts, with or without Trp53, and examine their reprogramming capacity. We show that p73 is required for effective reprogramming by the Yamanaka factors, even in the absence of p53. Lack of p73 affects the early stages of reprogramming, impairing the MET and resulting in altered maturation and stabilization phases. Accordingly, the obtained p73-deficient iPSCs have a defective epithelial phenotype and alterations in the expression of pluripotency markers. We demonstrate that p73 deficiency impairs the MET, at least in part, by hindering BMP pathway activation. We report that p73 is a positive modulator of the BMP circuit, enhancing its activation by DNp73 repression of the Smad6 promoter. Collectively, these findings provide mechanistic insight into the MET process, proposing p73 as an enhancer of MET during cellular reprogramming.Peer reviewe

Topological Defects in Nematic Droplets of Hard Spherocylinders

Using computer simulations we investigate the microscopic structure of the singular director field within a nematic droplet. As a theoretical model for nematic liquid crystals we take hard spherocylinders. To induce an overall topological charge, the particles are either confined to a two-dimensional circular cavity with homeotropic boundary or to the surface of a three-dimensional sphere. Both systems exhibit half-integer topological point defects. The isotropic defect core has a radius of the order of one particle length and is surrounded by free-standing density oscillations. The effective interaction between two defects is investigated. All results should be experimentally observable in thin sheets of colloidal liquid crystals.Comment: 13 pages, 16 figures, Phys. Rev.

Genomic adaptations to aquatic and aerial life in mayflies and the origin of insect wings

The evolution of winged insects revolutionized terrestrial ecosystems and led to the largest animal radiation on Earth. However, we still have an incomplete picture of the genomic changes that underlay this diversification. Mayflies, as one of the sister groups of all other winged insects, are key to understanding this radiation. Here, we describe the genome of the mayfly Cloeon dipterum and its gene expression throughout its aquatic and aerial life cycle and specific organs. We discover an expansion of odorant-binding-protein genes, some expressed specifically in breathing gills of aquatic nymphs, suggesting a novel sensory role for this organ. In contrast, flying adults use an enlarged opsin set in a sexually dimorphic manner, with some expressed only in males. Finally, we identify a set of wing-associated genes deeply conserved in the pterygote insects and find transcriptomic similarities between gills and wings, suggesting a common genetic program. Globally, this comprehensive genomic and transcriptomic study uncovers the genetic basis of key evolutionary adaptations in mayflies and winged insects

Optical contrast and refractive index of natural van der Waals heterostructure nanosheets of franckeite

We study mechanically exfoliated nanosheets of franckeite by quantitative optical microscopy. The analysis of transmission-mode and epi-illumination-mode optical microscopy images provides a rapid method to estimate the thickness of the exfoliated flakes at first glance. A quantitative analysis of the optical contrast spectra by means of micro-reflectance allows one to determine the refractive index of franckeite over a broad range of the visible spectrum through a fit of the acquired spectra to a model based on the Fresnel law

Distinct molecular programs regulate synapse specificity in cortical inhibitory circuits

How neuronal connections are established and organized into functional networks determines brain function. In the mammalian cerebral cortex, different classes of GABAergic interneurons exhibit specific connectivity patterns that underlie their ability to shape temporal dynamics and information processing. Much progress has been made toward parsing interneuron diversity, yet the molecular mechanisms by which interneuron-specific connectivity motifs emerge remain unclear. In this study, we investigated transcriptional dynamics in different classes of interneurons during the formation of cortical inhibitory circuits in mouse. We found that whether interneurons form synapses on the dendrites, soma, or axon initial segment of pyramidal cells is determined by synaptic molecules that are expressed in a subtype-specific manner. Thus, cell-specific molecular programs that unfold during early postnatal development underlie the connectivity patterns of cortical interneurons