Myeloid cell deficiency of p38γ/p38δ protects against candidiasis and regulates antifungal immunity

Fundació la Marató de TV3 (GrantNumber(s): 20133431; Grant recipient(s): Ana Cuenda) Wellcome Trust (GrantNumber(s): 97377, 102705; Grant recipient(s): GORDON D. BROWN) Ministerio de Economía y Competitividad (GrantNumber(s): SAF2016-79792-R, SAF2014- 52009-R, SAF2013-45331-R; Grant recipient(s): Ana Cuenda, SUSANA ALEMANY) Medical Research Council (GrantNumber(s): MR/N006364/1; Grant recipient(s): GORDON D. BROWN) ERC Consolidator Grant (GrantNumber(s): 310372; Grant recipient(s): Mihai Netea)Peer reviewedPublisher PD

Avance en el diseño de un péptido bloqueador del receptor opioide kappa 2 humano

Se evaluó la posibilidad de predecir una probable estructura secundaria para el Receptor Opioide Kappa 2 humano tomando como base la secuencia de aminoácidos del Receptor Opioide Kappa 1 humano. La estructura predicha mostró ser compatible con los datos que se poseen acerca de este tipo de receptores. Con esta prueba inicial, el proyecto que tiene como objetivo principal diseñar un análogo proteico para el Receptor Opioide Kappa 2 humano, ha mostrado el nivel mínimo de viabilidad necesario para ser continuado

Plant diversity patterns in neotropical dry forests and their conservation implications

This is the author accepted manuscript. The final version is available from American Association for the Advancement of Science via the DOI in this record.Seasonally dry tropical forests are distributed across Latin America and the Caribbean and are highly threatened, with less than 10% of their original extent remaining in many countries. Using 835 inventories covering 4660 species of woody plants, we show marked floristic turnover among inventories and regions, which may be higher than in other neotropical biomes, such as savanna. Such high floristic turnover indicates that numerous conservation areas across many countries will be needed to protect the full diversity of tropical dry forests. Our results provide a scientific framework within which national decision-makers can contextualize the floristic significance of their dry forest at a regional and continental scale.This paper is the result of the Latin American and Caribbean Seasonally Dry Tropical Forest Floristic Network (DRYFLOR), which has been supported at the Royal Botanic Garden Edinburgh by a Leverhulme Trust International Network Grant (IN-074). This work was also supported by the U.K. Natural Environment Research Council grant NE/I028122/1; Colciencias Ph.D. scholarship 529; Synthesys Programme GBTAF-2824; the NSF (NSF 1118340 and 1118369); the Instituto Humboldt (IAvH)–Red colombiana de investigación y monitoreo en bosque seco; the Inter-American Institute for Global Change Research (IAI; Tropi-Dry, CRN2-021, funded by NSF GEO 0452325); Universidad Nacional de Rosario (UNR); and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). The data reported in this paper are available at www.dryflor.info. R.T.P. conceived the study. M.P., A.O.-F., K.B.-R., R.T.P., and J.W. designed the DRYFLOR database system. K.B.-R. and K.G.D. carried out most analyses. K.B.-R. R.T.P., and K.G.D. wrote the manuscript with substantial input from A.D.-S., R.L.-P., A.O.-F., D.P., C.Q., and R.R. All the authors contributed data, discussed further analyses, and commented on various versions of the manuscript. K.B.-R. thanks G. Galeano who introduced her to dry forest research. We thank J. L. Marcelo, I. Huamantupa, C. Reynel, S. Palacios, and A. Daza for help with fieldwork and data entry in Peru

Naturaleza y cultura en Ámerica Latina

La concreción del XVIII Foro de Estudiantes Latinoamericanos de Antrología y Arqueología: Cultura y naturaleza en América Latina: escenarios para un modelo de desarrollo no civilizatorio, efectuado en Quito desde el 17 al 23 de julio del 2011, se constituyó en un acontecimiento sumamente significativo para la antropología latinoamericana debido a dos motivos. Primero porque coincidió con la emergencia del movimiento universitario estudiantil latinoamericano que expresaba sus tendencias, propuestas y exigencias de cambios tanto de las prácticas académicas como de los patrones civilizatorios que rigen las relaciones actuales. Segundo, porque se inscribía en un contexto de consolidación de las nuevas democracias de los países andinos, de carácter antineoliberal y basadas en los sujetos de derecho entre los cuales se incluye la naturaleza. Estos contextos determinaron que el Foro no ponga en escena certidumbres teóricas o metodológicas, ni se preste al exhibicionismo estéril de los avances disciplinares. Más bien, la convocatoria de la antropología y la arqueología fue apenas un pretexto para hablar, con su lenguaje, de nosotros mismos, de lo que somos, de lo que pensamos, de lo que aspiramos y sentimos sobre nuestra Latinoamérica. Lo que hemos visto, oído y compartido, en realidad, no han sido solamente ideas o conceptos sino opciones y toma de posiciones respecto a múltiples encrucijadas. Posición ante situaciones que amenazan la vida, la justicia y los derechos de todos, un desafío epistemológico todavía en ciernes y que no termina de cuajar aún en nuestras prácticas académicas

The DUNE far detector vertical drift technology. Technical design report

DUNE is an international experiment dedicated to addressing some of the questions at the forefront of particle physics and astrophysics, including the mystifying preponderance of matter over antimatter in the early universe. The dual-site experiment will employ an intense neutrino beam focused on a near and a far detector as it aims to determine the neutrino mass hierarchy and to make high-precision measurements of the PMNS matrix parameters, including the CP-violating phase. It will also stand ready to observe supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector implements liquid argon time-projection chamber (LArTPC) technology, and combines the many tens-of-kiloton fiducial mass necessary for rare event searches with the sub-centimeter spatial resolution required to image those events with high precision. The addition of a photon detection system enhances physics capabilities for all DUNE physics drivers and opens prospects for further physics explorations. Given its size, the far detector will be implemented as a set of modules, with LArTPC designs that differ from one another as newer technologies arise. In the vertical drift LArTPC design, a horizontal cathode bisects the detector, creating two stacked drift volumes in which ionization charges drift towards anodes at either the top or bottom. The anodes are composed of perforated PCB layers with conductive strips, enabling reconstruction in 3D. Light-trap-style photon detection modules are placed both on the cryostat's side walls and on the central cathode where they are optically powered. This Technical Design Report describes in detail the technical implementations of each subsystem of this LArTPC that, together with the other far detector modules and the near detector, will enable DUNE to achieve its physics goals

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

A Discussion about the Rod Position in the Splitting Tensile Tests on Hollow Concrete Blocks

Different loading conditions cause different tensile stress patterns in masonry structures. Several studies related to masonry behavior use indirect tensile tests to obtain that value, where the splitting test from ASTM-C-1006 is usually employed. In this paper, an experimental analysis of the tensile strength of hollow concrete blocks is reported. Different locations of the rod from the ASTM-C-1006 splitting test were analyzed. The tensile strength was evaluated in four different ways, placing the rod: (1) in the transversal direction over the gross area, (2) in the transversal direction over the net area, (3) in the longitudinal direction, and (4) 200 mm from the central region of the block in the longitudinal direction. The obtained results were compared with the tensile strength values measured from the direct tensile test in the longitudinal direction. In addition, an axial compressive test was performed to characterize the blocks, and a discussion about the tensile/compression ratio is shown. The experimental results from the splitting tests show that for each configuration setup, the tensile stress is different. The main result was that the splitting test over the net area with the rod positioned in the longitudinal direction can overestimate the tensile strength by more than 21% of the one over the gross area