Risk model for prostate cancer using environmental and genetic factors in the spanish multi-case-control (MCC) study

Prostate cancer (PCa) is the second most common cancer among men worldwide. Its etiology remains largely unknown compared to other common cancers. We have developed a risk stratification model combining environmental factors with family history and genetic susceptibility. 818 PCa cases and 1,006 healthy controls were compared. Subjects were interviewed on major lifestyle factors and family history. Fifty-six PCa susceptibility SNPs were genotyped. Risk models based on logistic regression were developed to combine environmental factors, family history and a genetic risk score. In the whole model, compared with subjects with low risk (reference category, decile 1), those carrying an intermediate risk (decile 5) had a 265% increase in PCa risk (OR = 3.65, 95% CI 2.26 to 5.91). The genetic risk score had an area under the ROC curve (AUROC) of 0.66 (95% CI 0.63 to 0.68). When adding the environmental score and family history to the genetic risk score, the AUROC increased by 0.05, reaching 0.71 (95% CI 0.69 to 0.74). Genetic susceptibility has a stronger risk value of the prediction that modifiable risk factors. While the added value of each SNP is small, the combination of 56 SNPs adds to the predictive ability of the risk model

A systems pharmacology model for inflammatory bowel disease

Motivation The literature on complex diseases is abundant but not always quantitative. This is particularly so for Inflammatory Bowel Disease (IBD), where many molecular pathways are qualitatively well described but this information cannot be used in traditional quantitative mathematical models employed in drug development. We propose the elaboration and validation of a logic network for IBD able to capture the information available in the literature that will facilitate the identification/validation of therapeutic targets. Results In this article, we propose a logic model for Inflammatory Bowel Disease (IBD) which consists of 43 nodes and 298 qualitative interactions. The model presented is able to describe the pathogenic mechanisms of the disorder and qualitatively describes the characteristic chronic inflammation. A perturbation analysis performed on the IBD network indicates that the model is robust. Also, as described in clinical trials, a simulation of anti-TNFα, anti-IL2 and Granulocyte and Monocyte Apheresis showed a decrease in the Metalloproteinases node (MMPs), which means a decrease in tissue damage. In contrast, as clinical trials have demonstrated, a simulation of anti-IL17 and anti-IFNγ or IL10 overexpression therapy did not show any major change in MMPs expression, as corresponds to a failed therapy. The model proved to be a promising in silico tool for the evaluation of potential therapeutic targets, the identification of new IBD biomarkers, the integration of IBD polymorphisms to anticipate responders and non-responders and can be reduced and transformed in quantitative model/s

Prevalence of urinary incontinence and oberactive bladder in spanish population: results from EPICC study

Introducción: A pesar del creciente interés que despiertan en nuestro país la Incontinencia Urinaria (IU), la enuresis nocturna y la Vejiga Hiperactiva (VH), no existe ningún estudio epidemiológico que evalúe la prevalencia de estas patologías en los diferentes grupos sobre los que se asientan, de la población general de España. Material y Métodos: Estudio epidemiológico, observacional, multicéntrico y de ámbito nacional. Se recogieron datos, a través de encuestas en 5 áreas representativas de todo el ámbito nacional y en cuatro grupos de la población: 1) Mujeres, laboralmente activas (entre 25 y 64 años); 2) Varones, laboralmente activos (entre 50 y 64 años); 3) Niños en enseñanza primaria (entre 6 y 11 años); y 4) Personas mayores de 65 años nstitucionalizadas con nivel cognitivo conservado. La encuesta a población adulta y ancianos incluía dos partes: 1) variables socio-demográficas y antecedentes de la historia clínica; y 2) sobre síntomas de VH e IU. La encuesta a niños incluía variables socio-demográficas y sobre ingesta de líquidos y control de la orina. Resultados: El porcentaje de respuesta en los diferentes grupos del estudio osciló entre el 79,7% y el 98%. La prevalencia de VH y de IU aisladas en mujeres laboralmente activas fue de 2,69% y 4,01% respectivamente; en varones fue de 3,55% y 0,56%; en personas de más de 65 años fue de 9,14% y 15,16%. En conjunto el 9,94% (95% IC= 8,9–11,04) de las mujeres estudiadas padecían una o las dos patologías, porcentaje que fue de 5,14% (95% IC= 3,89–6,63) para varones y de 53,71% (95% IC= 50,56–56,85) para personas de más de 65 años. La prevalencia de enuresis nocturna en niños fue de 7,82% (95% IC= 6,62–9,17). Conclusión: La prevalencia de VH y/o IU en España se acerca al 10% en mujeres entre 25 y 64 años, está alrededor del 5% en varones entre 50 y 65 años y es superior al 50% en personas de más de 65 años de ambos sexos; la prevalencia de enuresis nocturna en niños entre 6 y 11 años está alrededor del 8%

Expansion of Signal Transduction Pathways in Fungi by Extensive Genome Duplication

[EN] Plants and fungi use light and other signals to regulate development, growth, and metabolism. The fruiting bodies of the fungus Phycomyces blakesleeanus are single cells that react to environmental cues, including light, but the mechanisms are largely unknown [1]. The related fungus Mucor circinelloides is an opportunistic human pathogen that changes its mode of growth upon receipt of signals from the environment to facilitate pathogenesis [2]. Understanding how these organisms respond to environmental cues should provide insights into the mechanisms of sensory perception and signal transduction by a single eukaryotic cell, and their role in pathogenesis. We sequenced the genomes of P. blakesleeanus and M. circinelloides and show that they have been shaped by an extensive genome duplication or, most likely, a whole-genome duplication (WGD), which is rarely observed in fungi [3-6]. We show that the genome duplication has expanded gene families, including those involved in signal transduction, and that duplicated genes have specialized, as evidenced by differences in their regulation by light. The transcriptional response to light varies with the developmental stage and is still observed in a photoreceptor mutant of P. blakesleeanus. A phototropic mutant of P. blakesleeanus with a heterozygous mutation in the photoreceptor gene madA demonstrates that photosensor dosage is important for the magnitude of signal transduction. We conclude that the genome duplication provided the means to improve signal transduction for enhanced perception of environmental signals. Our results will help to understand the role of genome dynamics in the evolution of sensory perception in eukaryotes.European funds (European Regional Development Fund, ERDF); Spanish Ministerio de Economı´a y Competitividad; Junta de Andalucí

Black holes, gravitational waves and fundamental physics:a roadmap

The grand challenges of contemporary fundamental physics---dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem---all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level