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ImportanceAnthracyclines increase the risk for congestive heart failure (CHF); however, long-term cumulative incidence and risk factors for CHF after anthracycline therapy are not well defined in population-based studies.ObjectiveTo compare the long-term cumulative incidence of CHF in patients with breast cancer or lymphoma treated with anthracycline therapy compared with healthy controls from the same community.Design, Setting, and ParticipantsThis retrospective population-based case-control study included data from the Rochester Epidemiology Project. Participants included residents of Olmsted County, Minnesota, diagnosed with breast cancer or lymphoma from January 1985 through December 2010 matched for age, sex, and comorbidities with healthy controls, with a final ratio of 1 case to 1.5 controls. Statistical analysis was performed between July 2017 and February 2022.ExposuresCancer treatment and CHF risk factors.Main Outcomes and MeasuresThe main outcome was new-onset CHF, as defined by the modified Framingham criteria. Cox proportional hazards regression was used to estimate hazard ratios (HRs) to compare the risk of CHF in participants with cancer vs controls, adjusted for age, sex, diabetes, hypertension, hyperlipidemia, coronary artery disease, obesity, and smoking history.ResultsA total of 2196 individuals were included, with 812 patients with cancer and 1384 participants without cancer. The mean (SD) age was 52.62 (14.56) years and 1704 participants (78%) were female. Median (IQR) follow-up was 8.6 (5.2-13.4) years in the case group vs 12.5 (8.7-17.5) years in the control group. Overall, patients with cancer had higher risk of CHF compared with the control cohort even after adjusting for age, sex, diabetes, hypertension, coronary artery disease, hyperlipidemia, obesity, and smoking status (HR, 2.86 [95% CI, 1.90-4.32]; P P P = .14). Higher cumulative incidence for patients treated with anthracyclines vs comparator cohort was observed at 1 year (1.81% vs 0.09%), 5 years (2.91% vs 0.79%), 10 years (5.36% vs 1.74%), 15 years (7.42% vs 3.18%), and 20 years (10.75% vs 4.98%) (P 2 compared with those at a dose of 180 to 250 mg/m2 (HR, 0.54 [95% CI, 0.19-1.51]) or at a dose of more than 250 mg/m2 (HR, 1.23 [95% CI, 0.52-2.91]). At diagnosis, age was an independent risk factor associated with CHF (HR per 10 years, 2.77 [95% CI, 1.99-3.86]; P Conclusions and RelevanceIn this retrospective population-based case-control study, anthracyclines were associated with an increased risk of CHF early during follow-up, and the increased risk persisted over time. The cumulative incidence of CHF in patients with breast cancer or lymphoma treated with anthracyclines at 15 years was more than 2-fold that of the control group.

All naturally produced terpenes are derived from two universal C5 diphosphate precursors, dimethylallyl diphosphate (DMAPP) and isopentenyl diphosphate (IPP). Various prenyl transferases use DMAPP ...

An update of the Spanish consensus document on the diagnosis and treatment of acute tonsillopharyngitis in 2011 is presented. Clinical scores should not be used to prescribe antibiotics, unless microbiological tests are not available or there is a child at risk of rheumatic fever. There is no score better than those set out in the previous consensus. Microbiological tests are recommended in proposed cases, regardless of the result of the scores. Penicillin is the treatment of choice, prescribed twice a day for 10 days. Amoxicillin is the first alternative, prescribed once or twice a day for the same time. First-generation cephalosporins are the treatment of choice in children with non-immediate reaction to penicillin or amoxicillin. Josamycin and midecamycin are the best options for children with immediate penicillin allergic reactions, when non-beta-lactam antibiotics should be used. In microbiological treatment failure, and in streptococcal carriers, the treatments proposed in the previous consensus are still applicable. Resumen: Se presenta una actualización del documento de consenso sobre el diagnóstico y tratamiento de la faringoamigdalitis aguda, publicado en 2011. Las escalas de predicción clínica no deben ser utilizadas para iniciar antibioterapia, salvo que las pruebas microbiológicas no estén disponibles o exista riesgo de fiebre reumática. No existe ninguna escala que sea mejor que las expuestas en el consenso previo. Se proponen casos en los que se recomienda realizar pruebas microbiológicas, con independencia de los resultados de las escalas. El tratamiento de elección de la faringoamigdalitis estreptocócica es penicilina en dos dosis diarias y durante diez días. Amoxicilina, en una o dos dosis diarias y durante el mismo tiempo, es la primera alternativa terapéutica. Las cefalosporinas de primera generación son el tratamiento de elección en niños con reacción retardada no grave a penicilina o amoxicilina. En reacciones alérgicas inmediatas deben utilizarse antibióticos no betalactámicos, siendo josamicina y diacetil-midecamicina las mejores opciones. En el fracaso terapéutico bacteriológico, y en el estado de portador, los tratamientos planteados en el consenso previo siguen siendo válidos.

Background The International Classification of Diseases 10th revision (ICD10) and its clinical modification (ICD10CM) are commonly used for the identification of diseases occurrence worldwide. In Spain, diagnoses are coded with its Spanish version (ICD10ES) since 2016 regardless of the prevalence of diseases. Rare diseases (RDs) are scrambled among common diseases in ICD10 and its derivatives and many RDs dońt have a specific ICD10 code, delaying a proper identification. Orphanet developed a classification system specific for RDs called ORPHAcode. This study aims to characterize whether ICD10ES mapping to ORPHAcodes improves RDs identification and which kind of disorders would benefit the most. Methods 95% of the disorder level ORPHAcodes indexed at Orphanet was mapped to codes from 20 ICD10ES chapters by comparing the descriptors associated in both classifications. ORPHAcodes were then clustered based on their assigned ICD10ES chapter and the redundancy of each individual ICD10ES code was calculated by counting the ORPHAcodes they mapped to. 3 groups were established: Group 1 (1 ORPHAcode per ICD10ES), Group 2 (between 2-49 ORPHAcodes per ICD10ES) and Group 3 (≥50 ORPHAcodes per ICD10ES). Results 5588 ORPHAcodes were correlated to 1677 ICD10ES codes. 1051 were group 1, 3261 group 2 (615 ICD10ES) and 1276 group 3 (11 ICD10ES). Most of the Orphacodes correlated to “Q” (>40%), “G” (>14%) and “E” (>12%) chapters of ICD10ES. Regarding specificity, “G” and “Q” were also the only chapters including group 3 ORPHAcodes, while less than 10% of the ORPHAcodes linked to these chapters were in group 1. Conclusions New and improved ICD10ES codes are required because just 20% of all ORPHAcodes studied were into group 1. Especial care should be put on the two majoritarian chapters, “Q:Congenital Anomalies” and “G:Nervous System”, that show the lowest specificity for RDs. Complementary use of ORPHAcodes would improve the identification and registry of RDs either. Funded: Project RD-CODE Key messages The lack of a specific chapter for Rare Diseases in the InternationaI Classification of Diseases hinders their identification and therefore their study. Direct mapping between ICD10 and ORPHAcodes or the use of ORPHAcodes for diagnoses codification of Rare Diseases would enable better detection and epidemiological analysis.

El VIH sigue siendo un importante problema de salud pública en la Comunidad de Madrid (CM), diagnosticándose cada año unas 1000 nuevas infecciones. Desde la Dirección General de Salud Pública (DGSP),cada 1 de diciembre, Día Mundial del Sida (DMS), siguiendo las recomendaciones de la OMS, se apoya y promueve la realización de actividades para sensibilizar e informar a la población acerca de la importancia de la prevención, del diagnóstico precoz, los recursos disponibles y la lucha contra el estigma y las discriminación que aún hoy sufren las personas que viven con VIH.

Background Terpenes are industrially relevant natural compounds the biosynthesis of which relies on two well-established—mevalonic acid (MVA) and methyl erythritol phosphate (MEP)-pathways. Both pathways are widely distributed in all domains of life, the former is predominantly found in eukaryotes and archaea and the latter in eubacteria and chloroplasts. These two pathways supply isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), the universal building blocks of terpenes. Results The potential to establish a semisynthetic third pathway to access these precursors has been investigated in the present work. We have tested the ability of a collection of 93 isopentenyl phosphate kinases (IPK) from the biodiversity to catalyse the double phosphorylation of isopentenol and dimethylallyl alcohol to give, respectively IPP and DMAPP. Five IPKs selected from a preliminary in vitro screening were evaluated in vivo in an engineered chassis E. coli strain producing carotenoids. The recombinant pathway leading to the synthesis of neurosporene and lycopene, allows a simple colorimetric assay to test the potential of IPKs for the synthesis of IPP and DMAPP starting from the corresponding alcohols. The best candidate identified was the IPK from Methanococcoides burtonii (UniProt ID: Q12TH9) which improved carotenoid and neurosporene yields ~ 18-fold and > 45-fold, respectively. In our lab scale conditions, titres of neurosporene reached up to 702.1 ± 44.7 µg/g DCW and 966.2 ± 61.6 µg/L. A scale up to 4 L in-batch cultures reached to 604.8 ± 68.3 µg/g DCW and 430.5 ± 48.6 µg/L without any optimisation shown its potential for future applications. Neurosporene was almost the only carotenoid produced under these conditions, reaching ~ 90% of total carotenoids both at lab and batch scales thus offering an easy access to this sophisticated molecule. Conclusion IPK biodiversity was screened in order to identify IPKs that optimize the final carotenoid content of engineered E. coli cells expressing the lycopene biosynthesis pathway. By simply changing the IPK and without any other metabolic engineering we improved the neurosporene content by more than 45 fold offering a new biosynthetic access to this molecule of upmost importance. Electronic supplementary material The online version of this article (10.1186/s12934-019-1074-4) contains supplementary material, which is available to authorized users.

Positive end-expiratory pressure (PEEP) may have differential hemodynamic effects according to right ventricular (RV), left ventricular (LV) function and filling pressures. We assessed the association between PEEP and outcomes in patients (pts) admitted to the cardiac intensive care unit (CICU)

The Internet of Things is created by networking many different kind of things, enabling new services and business models. However, things from different manufacturers, various domains, and a number of standards have to interact. Unfortunately, the current situation is characterized by ‘silos’ or ‘islands’ that lack interoperability. This paper gives a survey and analysis of drivers, platforms, and standards for the Internet of Things (IoT) that provide a basis for interoperability. They are considered for requirements of the VICINITY project whose goal is to offer “Interoperability as a Service”.

Nowadays vehicles have evolved from a mean of transport to something much more complex and powerful. The paradigm change that electric vehicles have brought requires new tools and methodologies for improving not only the way vehicles behave, but also all the elements that are influenced by them. Moreover, electric vehicle are also connected to the Internet, thus they are able to access to a large repository of information and also to contribute to emerging opportunities that should be exploited. The application of Internet of Things and Big Data technologies in electric vehicles enables the development of new methodologies for offering personalised energy efficiency advices. JOSPEL aims at exploiting all these possibilities making them tangible through an energy consumption reduction reached by means of the provision of different services and improving the physical elements in the vehicle. This paper presents the ICT architecture that enables the achievement of those objectives by the digitalisation and analysis of vehicle information, and also to expose existing vehicle resources for achieving other benefits in different sectors.

Resumen: La infección del tracto urinario se define como el crecimiento de microorganismos en orina recogida de forma estéril, en un paciente con síntomas clínicos compatibles. En ausencia de sintomatología el aislamiento de bacterias en urocultivo se denomina bacteriuria asintomática y no precisa tratamiento. En neonatos y lactantes el signo guía para sospechar una infección del tracto urinario es la fiebre. En niños continentes los síntomas urinarios clásicos cobran mayor importancia. El diagnóstico requiere siempre la recogida de urocultivo previo al inicio de tratamiento antibiótico. En niños continentes la muestra de orina para urocultivo se debe recoger por micción espontánea. En niños no continentes mediante sondaje vesical, pudiendo optar por punción suprapúbica en neonatos y lactantes pequeños. No se debe enviar para urocultivo una muestra recogida mediante bolsa adhesiva. No se han demostrado diferencias significativas en la evolución clínica y desarrollo de secuelas entre la administración antibiótica oral exclusiva frente a la intravenosa de corta duración seguida de administración oral. La selección de la antibioterapia empírica inicial se basará en el patrón local de susceptibilidad. En la cistitis este consenso recomienda el uso empírico de cefalosporinas de segunda generación en menores de 6 años y fosfomicina trometamol en mayores. La antibioterapia empírica recomendada en pielonefritis que no precisan ingreso son las cefalosporinas de tercera generación. En caso de precisar ingreso se recomiendan los aminoglucósidos. En menores de 3 meses se debe añadir ampicilina. Una vez conocido el resultado del cultivo se debe dirigir el tratamiento de continuación, tanto intravenoso como oral. Abstract: Urinary tract infection (UTI) is defined as the growth of microorganisms in a sterile urine culture in a patient with compatible clinical symptoms. The presence of bacteria without any symptoms is known as asymptomatic bacteriuria, and does not require any treatment. In neonates and infants, fever is the guiding sign to suspecting a UTI. Classic urinary tract symptoms become more important in older children. Urine cultures collected before starting antibiotics is always required for diagnosis. Clean-catch (midstream) specimens should be collected for urine culture. In the case of non-toilet-trained children, specimens must be obtained by urinary catheterisation, or suprapubic puncture in neonates and infants. Specimens collected by urine bag should not be used for urine culture. There are no significant differences in the clinical evolution and prognosis between oral versus short intravenous followed by oral antibiotic. Empirical antibiotic therapy should be guided by local susceptibility patterns. Second-generation cephalosporin (children under 6 years) and fosfomycin trometamol (over 6 years), are the empiric therapy recommended in this consensus. In the case of pyelonephritis, recommended antibiotic treatment are third-generation cephalosporins (outpatient care) or, if admission is required, aminoglycosides. Ampicillin should be added in infants less than 3 months old. Antibiotic de-escalation should be always practiced once the result of the urine culture is known.

[EN] Monoterpenes (C10) are isoprenoids usually employed as aromatic additives, are important components of wine aroma and some of them have antimicrobial and health beneficial properties. An efficient microbial production of these metabolites could be an inexpensive and environmentally friendly alternative to current techniques: chemical synthesis or extraction from natural sources.They are usually produced in plants from geranyl pyrophosphate (GPP), a common intermediate of isoprenoid pathway in microorganisms and higher organisms; what opens the possibility of producing them in yeasts as Saccharomyces cerevisiae, qualified as GRAS, and that has been widely employed for biotransformation and production of enzymes and metabolites of biotechnological interest.In this work, the inherent ability of this yeast for heterologous production of monoterpenes (linalool, geraniol, etc.) capable to improve organoleptic and/or functional properties of certain foods either being used as additives or produced during the elaboration process (e.g. vinification) has been characterized and improved by metabolic engineering approaches. Among the most relevant results we can find the selection of wine strain T73 because of its better ability to produce monoterpenes, and the improvement of this production by overexpressing a deregulated version of Hmg1p (catalyzes mevalonic acid synthesis, MVA) and IDI1 (encodes isopenthenyl pyrophosphate isomerase, that catalyzes the isomerization of farnesyl pyrophosphate synthase -FPPS- substrates). In addition, characterization of the FPPS role in GPP availability for the Clarkia breweri linalool synthase resulted in a 50 times increased production in yeast strains with wild-type enzyme (encoded by ERG20) replaced by one modified in its active site (K197E), encoded by erg20-2 allele; reaching a global improvement of 80 times the basal linalool production (14.51 ± 0.90 µg/L) when coexpressing IDI1 gene and erg20-2 allele in linalool producing strains lacking endogenous FPPS activity (1144.68 ± 139.39 µg/L).Geraniol producing strains (bearing Ocimum basilicum -sweet basil- GES gene that encodes geraniol synthase) derived from T73 were included in microvinification assays and geraniol concentration was over its perception threshold and a metabolic dispersion to other monoterpene (linalool, nerol and citronellol) and aromatic esters (geranyl and citronellyl acetate) was also detected. Increased monoterpene production established in IDI1 overexpressing strains under laboratory conditions was reproduced in these assays, demonstrating that the modification of key steps of MVA pathway is a valid strategy to modulate and/or improve wine aroma., [ES] Los monoterpenos (C10) son isoprenoides habitualmente utilizados como aditivos aromáticos, son componentes importantes del aroma de los vinos y algunos tienen propiedades antimicrobianas y/o beneficiosas para la salud. La producción eficiente de estos metabolitos en microorganismos podría ser una alternativa más económica y respetuosa con el medio ambiente que las técnicas empleadas en la actualidad: síntesis química y/o extracción de fuentes naturales.En las plantas los monoterpenos son producidos por monoterpeno sintasas que utilizan como sustrato geranil pirofosfato (GPP), siendo éste un intermediario común de la ruta de isoprenoides en microorganismos y organismos superiores, lo que abre la posibilidad de producirlos en la levadura Saccharomyces cerevisiae, que tiene el calificativo GRAS, y que ha sido además ampliamente utilizada para la biotransformación y producción de enzimas y metabolitos de interés biotecnológico.En este trabajo se ha caracterizado y mejorado, mediante técnicas de ingeniería metabólica, la capacidad inherente que tiene esta levadura para la producción heteróloga de monoterpenos (linalol, geraniol, etc.), que puedan mejorar las características organolépticas y/o funcionales de ciertos alimentos al ser usados como aditivos o al aumentar su concentración durante el propio proceso de elaboración (p. ej. vinificación). Entre los resultados más destacados están la selección de la cepa vínica industrial T73 por su mayor capacidad para producir monoterpenos, y la mejora de dicha producción mediante la sobreexpresión desregulada de la enzima Hmg1p (cataliza la formación del ácido mevalónico, MVA) y del gen IDI1 (codifica isopentenil pirofosfato isomerasa, que cataliza la isomerización de los sustratos de la farnesil pirofosfato sintasa, FPPS). Además, la caracterización del rol de la enzima FPPS en la disponibilidad de GPP para su aprovechamiento por la enzima linalol sintasa de Clarkia breweri, derivó en una producción de linalol 50 veces mayor en cepas en las que una versión modificada en su centro activo (K197E), codificada por el alelo erg20-2, reemplazaba a la enzima silvestre (codificada por ERG20); alcanzándose una mejora global de 80 veces respecto a la producción de linalol inicial (14,51 ± 0,90 µg/L), al sobreexpresar conjuntamente el gen IDI1 y el alelo erg20-2 en cepas productoras de linalol que carecen de la función FPPS endógena (1144,68 ± 139,39 µg/L).Las cepas productoras de geraniol (expresan el gen GES que en Ocimum basilicum -albahaca- codifica geraniol sintasa) derivadas de T73 se incluyeron en ensayos de microvinificación y la concentración de este monoterpeno en el vino final no sólo estuvo por encima de su umbral de percepción, sino que se produjo una dispersión metabólica del geraniol hacia otros monoterpenos (linalol, nerol y citronelol) y esteres (geranil y citronelil acetato) aromáticos. Además, el incremento de la producción de monoterpenos observado en condiciones de laboratorio en cepas que sobreexpresan el gen IDI1 se reprodujo en estos ensayos, demostrando que la modificación de pasos clave de la ruta MVA es una estrategia válida para modular y/o mejorar el aroma del vino., [CAT] Els monoterpens (C10) són isoprenoids habitualment utilitzats com additius aromàtics, són components importants de l'aroma dels vins i alguns tenen propietats antimicrobianes i/o beneficioses per a la salut. La producció eficient d'aquests metabòlits en microorganismes podria ser una alternativa més econòmica i respectuosa amb el medi ambient que les tècniques emprades en l'actualitat: síntesi química i/o extracció de fonts naturals.A les plantes els monoterpens són produïts per monoterpeno sintases que utilitzen com a substrat geranil pirofosfat (GPP), sent aquest un intermediari comú de la ruta dels isoprenoids en microorganismes i organismes superiors, el que obri la possibilitat de produir-los en el llevat Saccharomyces cerevisiae, amb qualificatiu GRAS, i que ha sigut a més àmpliament utilitzat per a la biotransformació i producció d'enzims i metabòlits d'interès biotecnològic.En aquest treball s'ha caracteritzat i millorat, mitjançant tècniques d'enginyeria metabòlica, la capacitat inherent que té aquest llevat per a la producció heteròloga de monoterpens (linalol, geraniol, etc.), que puguen millorar les característiques organolèptiques i/o funcionals de certs aliments en ser usats com additius o en augmentar la seua concentració durant el propi procés d'elaboració (p. ex. vinificació). Entre els resultats més destacats es troben la selecció de la soca vínica industrial T73 per la seua major capacitat per a produir monoterpens, i la millora d'aquesta producció mitjançant la sobreexpressió desregulada de l'enzim Hmg1p (catalitza la formació de l¿àcid mevalònic, MVA) i del gen IDI1 (codifica isopentenil pirofosfat isomerasa, que catalitza la isomerització dels substrats de la farnesil pirofosfat sintasa, FPPS). A més, la caracterització del rol de l'enzim FPPS en la disponibilitat de GPP per al seu aprofitament per l'enzim linalol sintasa de Clarkia breweri, va derivar en una producció de linalol 50 vegades major en soques en les que una versió modificada en el seu centre actiu (K197E), codificada per l'al¿lel erg20-2, reemplaçava a l'enzim silvestre (codificada per ERG20); aconseguint una millora global de 80 vegades respecte a la producció de linalol inicial (14,51 ± 0,90 µg/L), en sobreexpressar conjuntament el gen IDI1 i l'al¿lel erg20-2 en soques productores de linalol que no tenen la funció FPPS endògena (1144,68 ± 139,39 µg/L).Les soques productores de geraniol (expressen el gen GES que en Ocimum basilicum -alfàbrega- codifica geraniol sintasa) derivades de T73 es van incloure en assajos de microvinificació i la concentració d'aquest monoterpè en el vi final no només va estar per sobre del seu llindar de percepció, sinó que es va produir una dispersió metabòlica del geraniol cap a altres monoterpens (linalol, nerol i citronel¿lol) i èsters (geranil i citronel¿lil acetat) aromàtics. A més, l'increment de la producció de monoterpens observat en condicions de laboratori en soques que sobreexpressen el gen IDI1 es va reproduir en aquests assajos, demostrant que la modificació de passos clau de la ruta MVA és una estratègia vàlida per modular i/o millorar l'aroma del vi., Rico Molins, J. (2015). Producción heteróloga de monoterpenos en Saccharomyces cerevisiae: selección y mejora de cepas mediante técnicas de ingeniería metabólica [Tesis doctoral no publicada]. Universitat Politècnica de València. doi:10.4995/Thesis/10251/49359., TESIS

Linalool production was evaluated in different Saccharomyces cerevisiae strains expressing the Clarkia breweri linalool synthase gene ( LIS ). The wine strain T 73 was shown to produce higher levels of linalool than conventional laboratory strains (i.e., almost three times the amount). The performance of this strain was further enhanced by manipulating the endogenous mevalonate (MVA) pathway: deregulated overexpression of the rate-limiting 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) doubled linalool production. In a haploid laboratory strain, engineering of this key step also improved linalool yield.

5 pages, 3 figures.-- PMID: 19609583 [PubMed].-- Printed version published Sep 2009., The capability of Lactobacillus casei to produce the flavor-related compounds diacetyl and acetoin from whey permeate has been examined by a metabolic engineering approach. An L. casei strain in which the ilvBN genes from Lactococcus lactis, encoding acetohydroxyacid synthase, were expressed from the lactose operon was mutated in the lactate dehydrogenase gene (ldh) and in the pdhC gene, which codes for the E2 subunit of the pyruvate dehydrogenase complex. The introduction of these mutations resulted in an increased capacity to synthesize diacetyl/acetoin from lactose in whey permeate (1,400 mg/l at pH 5.5). The results showed that L. casei can be manipulated to synthesize added-value metabolites from dairy industry by-products., This work was supported by project PET2005- 0619 from the Spanish Ministerio de Ciencia e Innovación and by Corporación Alimentaria Peñasanta. J. Rico was recipient of a CSIC postgraduate fellowship partially funded by Corporación Alimentaria Peñasanta.

[Background] Monoterpenes are important contributors to grape and wine aroma. Moreover, certain monoterpenes have been shown to display health benefits with antimicrobial, anti-inflammatory, anticancer or hypotensive properties amongst others. The aim of this study was to construct self-aromatizing wine yeasts to overproduce de novo these plant metabolites in wines., [Results] Expression of the Ocimum basilicum (sweet basil) geraniol synthase (GES) gene in a Saccharomyces cerevisiae wine strain substantially changed the terpene profile of wine produced from a non-aromatic grape variety. Under microvinification conditions, and without compromising other fermentative traits, the recombinant yeast excreted geraniol de novo at an amount (~750 μg/L) well exceeding (>10-fold) its threshold for olfactory perception and also exceeding the quantities present in wines obtained from highly aromatic Muscat grapes. Interestingly, geraniol was further metabolized by yeast enzymes to additional monoterpenes and esters: citronellol, linalool, nerol, citronellyl acetate and geranyl acetate, resulting in a total monoterpene concentration (~1,558 μg/L) 230-fold greater than that of the control. We also found that monoterpene profiles of wines derived from mixed fermentations were found to be determined by the composition of the initial yeast inocula suggesting the feasibility of producing ‘à la carte’ wines having predetermined monoterpene contents., [Conclusions] Geraniol synthase-engineered yeasts demonstrate potential in the development of monoterpene enhanced wines., This work was funded by the Spanish MINECO/FEDER Grants CSD2007-0063 and AGL2011-29925. We also acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI). E. Pardo was financially supported by JCI2007-123/733 and JAEDOC086-FSE contracts. J. Rico was the recipient of a FPI (Formación de Personal de Investigador) pre-doctoral fellowship from the Comisión Interministerial de Ciencia y Tecnología (CICYT).

Los archivos históricos son instituciones que conservan los documentos al final del ciclo de vida documental con una doble función, administrativa y cultural. La función cultural busca garantizar y animar al ejercicio del derecho de acceso de los ciudadanos a los documentos mediante la organización y difusión de actividades culturales. Este proyecto analiza y compara las acciones culturales que realizan los archivos históricos nacionales cabecera de los países de España, Francia, Reino Unido y Portugal, tomando como caso de estudio el año 2013. Se concluye que los archivos históricos nacionales han integrado, como complemento de la conservación y organización de los fondos, la función cultural dentro de sus fines, como demuestra la variedad, la continuidad y la intensidad de las acciones de difusión emprendidas. Palabras clave: archivos históricos, función cultural, difusión cultural, actividades culturales, patrimonio histórico documental. Historical archives, are institutions that preserve documents at the end of the document life cycle, with a double function, administrative and cultural. Cultural function seeks to ensure and encourage the exercise of the right access of citizens through organization and diffusion of cultural activities. This project, analyzes and compare the cultural actions that made the header national archives of Spain, France, United Kingdom and Portugal, taking the year 2013 as a case study. It´s concluded that national historical archives have integrated, as a complement of the preservation and organization of the funds, the cultural function within its purposes, as evidenced by the variety, continuity and the intensity of the diffusion actions undertaken. Keywords: Historical archives, cultural function, cultural diffusion, cultural activities, documentary heritage.

Nearly 70 % of the average household utility bill could be influenced by Wireless Sensor Network (WSN) application to temperature and lighting. Home and building owners can use interactive energy management tools to create energy management profiles that are triggered by certain established consumption rates. However, security remains a critical issue. In this chapter, we will present how the new security features (both on hardware and software level) introduces improvements in the overall WSN picture, and we will explain with detail the new OTAP procedure. Furthermore, we will state all the new possibilities opened for Low Power WSN based on the enhancement of security, being a good candidate for applications restricted to much more powerful devices.

Cognitive radio technology is a key enabler to reuse a finite, scarce, and expensive resource: the radio spectrum. Guaranteeing required levels of QoS to cognitive users and ensuring necessary protection to incumbent users are the two main challenges in opportunistic spectrum access. This article identifies the main requirements and challenges for QoS support in cognitive radio networks. A framework for a twofold cognitive manager is presented; one part managing spectrum availability on longer timescales and the other handling resource management on shorter timescales. This article gives particular focus to the functionalities of the latter cognitive manager related to resource management. Finally, we present a few key scenarios and describe how QoS can be managed with the proposed approach without disturbing the communications of incumbent users.

Summary Objectives To describe the population targeted for the rapid HIV testing program delivered via socio-culturally adapted services in primary care centers and to assess factors associated with uptake of first-time testing. Methods This was a descriptive cross-sectional study. We analyzed consultations between April 29, 2010 and May 31, 2012. We assessed the differences in age, origin, education, and sexual history between men who have sex with men (MSM), heterosexual men (HM), and women, using a two-sided independent t -test and Chi-square statistics. Factors associated with first-time testing were analyzed by logistic regression. Results Of 1940 consultations, 45.1% were HM, 25.4% MSM, and 29.5% women; 35.4% were immigrants, 2.5% were or had been sex workers, and 15.4% had visited one. The test was reactive in 2.1%. Up to 44.2% had never been tested. The probability of being tested for the first time increased in HM, women, populations from the Indian Subcontinent, those with no casual sexual partners, those whose partner's serostatus was unknown, and those with no history of other sexually transmitted infections. Conclusions This program managed to reach a high proportion of vulnerable people. First time HIV testing rates were high.

In the great majority of cities it is difficult and hardly expensive to create more parking spaces for vehicles since they have almost reached its full occupancy. Combining this problem with an inefficient use of parking spaces leads to congestions due to aggregation of parking seekers and regular drivers. Recent advances in low-cost, low-power embedded systems bring the opportunity to develop new applications to solve these problems. In particular, Smart Cities greatly enrich their sustainability by introducing new resource management applications that rely in those constrained devices a significant part of the functionality of the system. The proposed Smart Parking solution consists mainly in the on-site deployment of an IoT solution to monitor and signalize the state of availability of each single parking space, as well as using context information generated by the city and its citizens to provide accurate responses to driver's demands. Furthermore, this system improves the management of parking resources by public authorities, for instance handling groups of parking spaces facilitating the whole city traffic management. The integration of this deployment into an existing live test-bed implies an easy task requiring just the data collection through the available means of the parking spaces availability. At the present time there exist living test-beds which can be used to integrate these new functionalities for experimentation on IoT data level, to gain a better knowledge and understanding of the M2M world, reducing costs, resources, pollution and time.

Full Paper — This document presents a cooperative system based on GNSS (Global Navigation Satellite Systems) technologies for avalanche victims' rescue. The system includes the use of low cost user terminal comprising GNSS receivers and wireless network communications, relative navigation, and development of a control centre. System architecture and prototype is presented; an analysis of signal propagation in snow is presented, and finally results of on-site extensive test campaign in real snow conditions are discussed.

Healthy life style has increased its penetration among people in the last years. The number of licenses for practicing snow and mountain activities certificates it with an over 7% increase year by year. Due to this, expert skiers or excursionist have slightly modified traditional patterns in their activities, moving from controlled zones, such as ski resorts or typical mountain paths, to non-protected zones, thus increasing the risk of suffering an avalanche. Over 150 people die buried by snow avalanches every year, in this scenario survival probabilities are tightly related with the time employed for finding victims, being critical the first 15 minutes. Most of the existing solutions require the presence of special elements not allowing the start of the rescue once the avalanche has finished, or when allows it, they are not as quick as needed in this kind of scenarios. This work presents an alternative solution focused on accelerating the detecting process and the rescue by facilitating its use with a very intuitive set of orders. Exploiting the possibilities offered by GNSS and ICT technologies (low power low range mesh networks), the system will be capable of detecting buried victims with only the information generated by the system. Furthermore, the context information provided by a control center accelerates the rescue process and optimizes the work of professional rescue team. This paper presents the theoretical basis of signal propagation through the snow and the set of functions implemented for accomplishing the system scope.

This paper is focused on demonstrating a real testbed for managing logistics systems in hospital environment exploiting the benefits of M2M and IoT paradigms. The work presents an architecture based on low-cost devices interacting with an enterprise application server placed anywhere in the Internet following the architecture proposed by ETSI for M2M systems. Combining multiple communication technologies (NFC, UMTS, 802.11, ZigBee and 802.3) and adapting their capabilities to different functional requirements, we are capable of creating autonomous and self-managed systems. The deployed architecture integrates at end device level, a NFC reader for tracking the level of remaining stocks and multiple output interfaces for exchanging messages with the application server. The system copes with cost, availability, scalability and easy deployment requirements, being the functionality also adaptable to the requirements of potential customers.

An integrated high-resolution biostratigraphic study was conducted using calcareous nannofossils, planktonic and benthic foraminifers, and palynomorphs from two wells in the western Gulf of Mexico. Sediments range in age from early Pleistocene to middle Miocene. The early Pleistocene is represented by nannoflora of biozone NN19 and microfauna from the Globorotalia truncatulinoides truncatulinoides biozones and by the dinocyst species Spiniferites delicatus, Spiniferites membranaceous, Multispinula quanta, and Hystrichokolpoma rigaudiae. These sediments were deposited under inner to middle neritic bathymetric conditions. The Pliocene was characterized by nannofossil biozones NN18, NN17, NN16, and NN15, and the NN14–NN12 interval; foraminifera biozones of Globorotalia miocenica, Globorotalia tosaensis tosaensis, Globorotalia margaritae, and the dinoflagellate cyst species; and Polysphaeridium zoharyi, Lingulodinium machaerophorum, Melitasphaeridium choanophorum, and Operculodinium crassum. Paleobathymetry was inner neritic-upper bathyal. Late Miocene sediments produced microfossils indicating nannofossil biozones NN11, NN10, NN9, and the Globorotalia humerosa and Globorotalia acostaensis planktonic foraminiferal biozones. Dinoflagellate cysts found in these sediments were Spiniferites mirabilis, Dapsilidinium pastielsii, Sumatradinium hispidum, and Achomosphaera andalusiensis. These sediments were deposited under outer neritic-upper bathyal conditions. Middle Miocene strata are represented by calcareous nannofossil biozones NN9, NN8, NN6, and NN5, and by the planktonic foraminiferal biozones Globorotalia mayeri, Globigerinoides rubber, Globorotalia fohsi lobata-Globorotalia fohsi robusta, Globorotalia fohsi fohsi, and probably by the upper part of the Globorotalia fohsiperipheroronda biozone. These strata were deposited mainly in outer neritic-upper bathyal environments. Nannofossil diversity and abundance show notable variations throughout the two wells. A strong predominance of calcareous nannofossils and marine palynomorphs is present in outer neritic settings, and a planktonic foraminifer increase is observed mainly in the upper bathyal of well A. Continental palynomorphs are abundant in inner neritic-middle neritic settings, and a reduction is observed in the outer neritic-upper bathyal in well B.

International audience; Lactobacillus casei is a lactic acid bacterium that produces L-lactate as the main product of sugar fermentation via L-lactate dehydrogenase (Ldh1) activity. In addition, small amounts of the D-lactate isomer are produced by the activity of a D-hydroxycaproate dehydrogenase (HicD). Ldh1 is the main L-lactate producing enzyme, but mutation of its gene does not eliminate L-lactate synthesis. A survey of the L. casei BL23 draft genome sequence revealed the presence of three additional genes encoding Ldh paralogs. In order to study the contribution of these genes to the global lactate production in this organism, individual, as well as double mutants (ldh1 ldh2, ldh1 ldh3, ldh1 ldh4 and ldh1 hicD) were constructed and lactic acid production was assessed in culture supernatants. ldh2, ldh3 and ldh4 genes play a minor role in lactate production, as their single mutation or a mutation in combination with an ldh1 deletion had a low impact on L-lactate synthesis. A Deltaldh1 mutant displayed an increased production of D-lactate, which was probably synthesized via the activity of HicD, as it was abolished in a Deltaldh1 hicD double mutant. Contrarily to HicD, no Ldh1, Ldh2, Ldh3 or Ldh4 activities could be detected by zymogram assays. In addition, these assays revealed the presence of extra bands exhibiting D-/L-lactate dehydrogenase activity, which could not be attributed to any of the described genes. These results suggest that L. casei BL23 possesses a complex enzymatic system able to reduce pyruvic to lactic acid.

La Academia de Derecho Público de Santa Bárbara fue uno de los escenarios creados por la dinastía borbónica con fines reformistas. Sus posibilidades de foro intelectual y político (con las limitaciones propias del absolutismo ilustrado) fueron notablemente aprovechadas por la minoría ilustrada para debatir y plantear los problemas jurídico-políticos del Estado español del Setecientos. El presente trabajo aporta la experiencia de Juan Sempere y Guarinos en su paso por la Academia. The Public Law Academy of Santa Barbara was created by the Borbonic Dynasty with reforming purposes. Its possibilities as an intellectual and political forum (with restrictions inherent in the enlightened dictatorship) were taken advantage of by the intellectual minority to discuss and raise questions related to the Judicial Spanish State and political problems that emerged during the XVIIth Century. The present analysis brings forward the invaluable contribution of Juan Sempere to the Academy.