De la Cruz et al. Reply

Altres ajuts: CERCA Programme/Generalitat de Cataluny

Minimum action path theory reveals the details of stochastic transitions out of oscillatory states

Altres ajuts: CERCA Programme/Generalitat de CatalunyaCell state determination is the outcome of intrinsically stochastic biochemical reactions. Transitions between such states are studied as noise-driven escape problems in the chemical species space. Escape can occur via multiple possible multidimensional paths, with probabilities depending nonlocally on the noise. Here we characterize the escape from an oscillatory biochemical state by minimizing the Freidlin-Wentzell action, deriving from it the stochastic spiral exit path from the limit cycle. We also use the minimized action to infer the escape time probability density function

Epidemiological implications of the genetic diversification of dengue virus (DENV) serotypes and genotypes in Mexico

Variation and clade shifts in dengue virus (DENV) genotypes are responsible for numerous dengue fever outbreaks throughout Latin America in the past decade. Molecular analyses of dengue serotypes have revealed extensive genetic diversification and the emergence of new genotypes in Brazil (DENV-4 genotype I) and elsewhere in tropical and subtropical America. The goal of the present study is to assess the extent to which the adventitious introduction of DENV genotypes and their increasing genetic diversity affects dengue epidemiology in Mexico. A nuanced sequence inspection and phylogenetic analysis of the C-prM nucleotide region of DENV was performed for specimens collecting in 2009 from the Veracruz State, Mexico. Findings were contrasted with specimens collected in adjacent years and analysed based on the epidemiological patterns reported between 1990 and 2019. Additionally, the identification process of various DENV genotypes was assessed, including: (1) DENV-1, genotype V, (2) the DENV-2 Asian/American and Asian II genotypes (3) DENV-3, genotype III, and (4) DENV-4, genotype I. This resulted in the discovery of a distinct genetic cladistic pattern for serotype DENV-2. Lastly, study findings suggest that a correlation exists between the emergence of novel genotypes and genetic diversification, with the increasing incidence of DENV infections in Mexico in 2009

Проверка эффективности вспомогательной системы для маневрирования в местах слияния автомобильных потоков в режиме реального вождения автомобиля

In the latest study conducted by the National Highway Traffic Safety Administration in 2018, it was published that human error is still considered the major factor in traffic accidents, 94 %, compared with other causes such as vehicles, environment and unknown critical reasons. Some driving scenarios are especially complex, such as highways merging lanes, where the driver obtains information from the environment while making decisions on how to proceed to perform the maneuver smoothly and safely. Ignorance of the intentions of the drivers around him leads to risky situations between them caused by misunderstandings or erroneous assumptions or perceptions. For this reason, Advanced Driver Assistance Systems could provide information to obtain safer maneuvers in these critical environments. In previous works, the behavior of the driver by means of a visual tracking system while merging in a highway was studied, observing a cognitive load in those instants due to the high attentional load that the maneuver requires. For this reason, a driver assistance system for merging situations is proposed. This system uses V2V communications technology and suggests to the driver how to modify his speed in order to perform the merging manoeuver in a safe way considering the available gap and the relative speeds between vehicles. The paper presents the results of the validation of this system for assisting in the merging maneuver. For this purpose, the interface previously designed and validated in terms of usability, has been integrated into an application for a mobile device, located inside the vehicle and tests has been carried out in real driving conditions.In the latest study conducted by the National Highway Traffic Safety Administration in 2018, it was published that human error is still considered the major factor in traffic accidents, 94 %, compared with other causes such as vehicles, environment and unknown critical reasons. Some driving scenarios are especially complex, such as highways merging lanes, where the driver obtains information from the environment while making decisions on how to proceed to perform the maneuver smoothly and safely. Ignorance of the intentions of the drivers around him leads to risky situations between them caused by misunderstandings or erroneous assumptions or perceptions. For this reason, Advanced Driver Assistance Systems could provide information to obtain safer maneuvers in these critical environments. In previous works, the behavior of the driver by means of a visual tracking system while merging in a highway was studied, observing a cognitive load in those instants due to the high attentional load that the maneuver requires. For this reason, a driver assistance system for merging situations is proposed. This system uses V2V communications technology and suggests to the driver how to modify his speed in order to perform the merging manoeuver in a safe way considering the available gap and the relative speeds between vehicles. The paper presents the results of the validation of this system for assisting in the merging maneuver. For this purpose, the interface previously designed and validated in terms of usability, has been integrated into an application for a mobile device, located inside the vehicle and tests has been carried out in real driving conditions

Changes in Oxidative Stress and Inflammatory Biomarkers in Fragile Adults over Fifty Years of Age and in Elderly People Exclusively Fed Enteral Nutrition

We aim to evaluate whether exclusive feeding of an enteral formula enriched with n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA) affects oxidative stress and the antioxidant defence system and may improve the levels of some relevant inflammatory, and cardiovascular biomarkers in frail adults over fifty years of age and in elderly subjects. Fifty-five patients were divided into two groups and were exclusively fed a newly designed normoproteic and isocaloric enteral formula enriched with eicosapentaenoic (98 mg/d) and docosahexaenoic acids (46 mg/d) (n=26) or a reference enteral diet (n=29). Oxidative, inflammatory and cardiovascular risk biomarkers and red blood cell fatty acid profiles were determined at the beginning and after 90 and 180 days of feeding. The n-3 LC-PUFA percentage tended to be higher (P=0.053) in the experimental group than in the reference group. Administration of the n-3 LC-PUFA diet did not increase oxidative stress or modify plasma antioxidant capacity but decreased antioxidant enzymatic activities. MMP-9 plasma concentration decreased with both formulae, whereas tPAI-1 tended to decrease (P=0.116) with the administration of the experimental formula. In conclusion, administration of the new n-3 LC-PUFA-enriched product for 6 months did not negatively alter the oxidative status and improved some cardiovascular risk biomarkers

Validation of a Novel, Sensitive, and Specific Urine-Based Test for Recurrence Surveillance of Patients With Non-Muscle-Invasive Bladder Cancer in a Comprehensive Multicenter Study

Bladder cancer (BC), the most frequent malignancy of the urinary system, is ranked the sixth most prevalent cancer worldwide. Of all newly diagnosed patients with BC, 70-75% will present disease confined to the mucosa or submucosa, the non-muscle-invasive BC (NMIBC) subtype. Of those, approximately 70% will recur after transurethral resection (TUR). Due to high rate of recurrence, patients are submitted to an intensive follow-up program maintained throughout many years, or even throughout life, resulting in an expensive follow-up, with cystoscopy being the most cost-effective procedure for NMIBC screening. Currently, the gold standard procedure for detection and follow-up of NMIBC is based on the association of cystoscopy and urine cytology. As cystoscopy is a very invasive approach, over the years, many different noninvasive assays (both based in serum and urine samples) have been developed in order to search genetic and protein alterations related to the development, progression, and recurrence of BC. TERT promoter mutations and FGFR3 hotspot mutations are the most frequent somatic alterations in BC and constitute the most reliable biomarkers for BC. Based on these, we developed an ultra-sensitive, urine-based assay called Uromonitor®, capable of detecting trace amounts of TERT promoter (c.1-124C > T and c.1-146C > T) and FGFR3 (p.R248C and p.S249C) hotspot mutations, in tumor cells exfoliated to urine samples. Cells present in urine were concentrated by the filtration of urine through filters where tumor cells are trapped and stored until analysis, presenting long-term stability. Detection of the alterations was achieved through a custom-made, robust, and highly sensitive multiplex competitive allele-specific discrimination PCR allowing clear interpretation of results. In this study, we validate a test for NMIBC recurrence detection, using for technical validation a total of 331 urine samples and 41 formalin-fixed paraffin-embedded tissues of the primary tumor and recurrence lesions from a large cluster of urology centers. In the clinical validation, we used 185 samples to assess sensitivity/specificity in the detection of NMIBC recurrence vs. cystoscopy/cytology and in a smaller cohort its potential as a primary diagnostic tool for NMIBC. Our results show this test to be highly sensitive (73.5%) and specific (93.2%) in detecting recurrence of BC in patients under surveillance of NMIBC.info:eu-repo/semantics/publishedVersio

The Sensitivity of HAWC to High-Mass Dark Matter Annihilations

The High Altitude Water Cherenkov (HAWC) observatory is a wide field-of-view detector sensitive to gamma rays of 100 GeV to a few hundred TeV. Located in central Mexico at 19 degrees North latitude and 4100 m above sea level, HAWC will observe gamma rays and cosmic rays with an array of water Cherenkov detectors. The full HAWC array is scheduled to be operational in Spring 2015. In this paper, we study the HAWC sensitivity to the gamma-ray signatures of high-mass (multi- TeV) dark matter annihilation. The HAWC observatory will be sensitive to diverse searches for dark matter annihilation, including annihilation from extended dark matter sources, the diffuse gamma-ray emission from dark matter annihilation, and gamma-ray emission from non-luminous dark matter subhalos. Here we consider the HAWC sensitivity to a subset of these sources, including dwarf galaxies, the M31 galaxy, the Virgo cluster, and the Galactic center. We simulate the HAWC response to gamma rays from these sources in several well-motivated dark matter annihilation channels. If no gamma-ray excess is observed, we show the limits HAWC can place on the dark matter cross-section from these sources. In particular, in the case of dark matter annihilation into gauge bosons, HAWC will be able to detect a narrow range of dark matter masses to cross-sections below thermal. HAWC should also be sensitive to non-thermal cross-sections for masses up to nearly 1000 TeV. The constraints placed by HAWC on the dark matter cross-section from known sources should be competitive with current limits in the mass range where HAWC has similar sensitivity. HAWC can additionally explore higher dark matter masses than are currently constrained.Comment: 15 pages, 4 figures, version to be published in PR

Ibero-American Consensus on Low- and No-Calorie Sweeteners: Safety, Nutritional Aspects and Benefits in Food and Beverages

International scientific experts in food, nutrition, dietetics, endocrinology, physical activity, paediatrics, nursing, toxicology and public health met in Lisbon on 2-4 July 2017 to develop a Consensus on the use of low- and no-calorie sweeteners (LNCS) as substitutes for sugars and other caloric sweeteners. LNCS are food additives that are broadly used as sugar substitutes to sweeten foods and beverages with the addition of fewer or no calories. They are also used in medicines, health-care products, such as toothpaste, and food supplements. The goal of this Consensus was to provide a useful, evidence-based, point of reference to assist in efforts to reduce free sugars consumption in line with current international public health recommendations. Participating experts in the Lisbon Consensus analysed and evaluated the evidence in relation to the role of LNCS in food safety, their regulation and the nutritional and dietary aspects of their use in foods and beverages. The conclusions of this Consensus were: (1) LNCS are some of the most extensively evaluated dietary constituents, and their safety has been reviewed and confirmed by regulatory bodies globally including the World Health Organisation, the US Food and Drug Administration and the European Food Safety Authority; (2) Consumer education, which is based on the most robust scientific evidence and regulatory processes, on the use of products containing LNCS should be strengthened in a comprehensive and objective way; (3) The use of LNCS in weight reduction programmes that involve replacing caloric sweeteners with LNCS in the context of structured diet plans may favour sustainable weight reduction. Furthermore, their use in diabetes management programmes may contribute to a better glycaemic control in patients, albeit with modest results. LNCS also provide dental health benefits when used in place of free sugars; (4) It is proposed that foods and beverages with LNCS could be included in dietary guidelines as alternative options to products sweetened with free sugars; (5) Continued education of health professionals is required, since they are a key source of information on issues related to food and health for both the general population and patients. With this in mind, the publication of position statements and consensus documents in the academic literature are extremely desirable

Trends in the epidemiology of catheter-related bloodstream infections; towards a paradigm shift, Spain, 2007 to 2019

Altres ajuts: Departament de Salut. Generalitat de Catalunya ("Pla estratègic de recerca i innovació en salut (PERIS) 2019-2021"); Ministerio de Asuntos Económicos y Transformación Digital; Red Española de Investigación en Patología Infecciosa (REIPI).Background: Catheter-related bloodstream infections (CRBSI) are frequent healthcare-associated infections and an important cause of death. Aim: To analyse changes in CRBSI epidemiology observed by the Infection Control Catalan Programme (VINCat). Methods: A cohort study including all hospital-acquired CRBSI episodes diagnosed at 55 hospitals (2007-2019) in Catalonia, Spain, was prospectively conducted. CRBSI incidence rates were adjusted per 1,000patientdays. To assess the CRBSI rate trend per year, negative binomial models were used, with the number of events as the dependent variable, and the year as the main independent variable. From each model, the annual rate of CRBSI diagnosed per 1,000patientdays and the incidence rate ratio (IRR) with its 95% confidence intervals (CI) were reported. Results: During the study, 9,290 CRBSI episodes were diagnosed (mean annual incidence rate:0.20episodes/1,000patientdays). Patients' median age was 64.1years; 36.6% (3,403/9,290) were female. In total, 73.7% (n=6,845) of CRBSI occurred in non-intensive care unit (ICU) wards, 62.7% (n=5,822) were related to central venous catheter (CVC), 24.1% (n=2,236) to peripheral venous catheters (PVC) and 13.3% (n=1,232) to peripherally-inserted central venous catheters (PICVC). Incidence rate fell over the study period (IRR:0.94;95%CI:0.93-0.96), especially in the ICU (IRR:0.88;95%CI:0.87-0.89). As a whole, while episodes of CVC CRBSI fell significantly (IRR:0.88;95%CI:0.87-0.91), peripherally-inserted catheter CRBSI (PVC and PICVC) rose, especially in medical wards (IRR PICVC:1.08;95%CI:1.05-1.11; IRR PVC: 1.03; 95% 1.00-1.05). Conclusions: Over the study, CRBSIs associated with CVC and diagnosed in ICUs decreased while episodes in conventional wards involving peripherally-inserted catheters increased. Hospitals should implement preventive measures in conventional wards

Compressed representation of a partially defined integer function over multiple arguments

In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one