Living at Higher Altitude and Incidence of Overweight/Obesity: Prospective Analysis of the SUN Cohort

BACKGROUND: Residence at high altitude has been associated with lower obesity rates probably due to hypoxia conditions. However, there is no evidence of this association in a free-living population. OBJECTIVES: We assessed the association between the altitude where each participant of a Spanish cohort (the SUN Project) was living and the incidence of overweight/obesity. METHODS: The SUN Project is a dynamic, prospective, multipurpose cohort of Spanish university graduates with a retention rate of 89%. We included in the analysis 9 365 participants free of overweight/obesity at baseline. At the baseline questionnaire, participants reported their postal code and the time they had been living in their city/village. We imputed the altitude of each postal code according to the data of the Spanish National Cartographic Institute and categorized participants in tertiles. We used Cox regression models to adjust for potential confounding variables. RESULTS: During a median follow-up of 10 years, we identified 2 156 incident cases of overweight/obesity. After adjusting for sex, age, time of residence at current city, baseline body mass index, physical activity, sedentarism and years of education (≤ 3 years, ≥ 4 years, Master/PhD), those participants in the third tertile (>456 m) exhibited a statistically significant 14% reduction in the risk of developing overweight/obesity in comparison to those in the first tertile (<124 m) (adjusted HR = 0.86; 95% CI: 0.77, 0.96). CONCLUSIONS: Living in cities of higher altitude was inversely associated with the risk of developing overweight/obesity in a cohort of Spanish university graduates

American heart association's life simple 7 and the risk of atrial fibrillation in the PREDIMED study cohort

Background and aims The American Heart Association proposed 7 ideal cardiovascular health metrics (Life's Simple 7 [LS7]) namely, not smoking, body mass index <25 kg/m2, healthy diet, moderate physical activity ≥150 min/week, total blood cholesterol <200 mg/dL, blood pressure <120/80 mmHg and fasting blood glucose <100 mg/dL. Our objective was to assess the association between these LS7 metrics and the incidence of atrial fibrillation (AF). Methods and results A total of 6,479 participants of the PREDIMED study were included. We calculated the participants’ baseline LS7 index ranging 0–7 points to categorize them according to their adherence to these LS7 health metrics. Multivariable Cox regression models were used to estimate Hazard Ratios (HR) and their 95% Confidence Intervals (95% CI). After a median follow-up of 4.8 years, we identified 250 incident cases of AF. After adjusting for potential confounders, adherence to LS7 index was not associated with the incidence of AF (adjusted HR 0.90 [95% CI: 0.56–1.45] for highest vs. lowest LS7 categories). Body mass index <25 kg/m2 was the only health metric individually associated with a lower risk of AF (HR 0.36 [95% CI: 0.16–0.78]). Conclusions In a high cardiovascular risk Spanish population, adherence to American Heart Association's LS7 metrics was not associated with the risk of incident AF

Living at a geographically higher elevation is associates with lower risk oof metabolic syndrome: prospective analysis of the SUN Cohort

Living in a geographically higher altitude affects oxygen availability. The possible connection between environmental factors and the development of metabolic syndrome (MetS) feature is not fully understood, being the available epidemiological evidence still very limited. The aim of the present study was to evaluate the longitudinal association between altitude and incidence of MetS and each of its components in a prospective Spanish cohort, The Seguimiento Universidad de Navarra (SUN) project. Our study included 6860 highly educated subjects (university graduates) free from any MetS criteria at baseline. The altitude of residence was imputed with the postal code of each individual subject residence according to the data of the Spanish National Cartographic Institute and participants were categorized into tertiles. MetS was defined according to the harmonized definition. Cox proportional hazards models were used to assess the association between the altitude of residence and the risk of MetS during follow-up. After a median follow-up period of 10 years, 462 incident cases of MetS were identified. When adjusting for potential confounders, subjects in the highest category of altitude (>456m) exhibited a significantly lower risk of developing MetS compared to those in the lowes ttertile (<122m) of altitude of residence [Model2:Hazardratio=0.75(95%Confidenceinterval:0.58–0.97);pfortrend=0.029]. Living at geographically higher altitude was associated with alower risk of developing MetS in the SUN project. Our findings suggest that geographical elevation may be an important factor linked to metabolic diseases

Healthy lifestyle and incidence of metabolic syndrome in the SUN cohort

We assessed the relationship between a healthy lifestyle and the subsequent risk of developing metabolic syndrome. The "Seguimiento Universidad de Navarra" (SUN) Project is a prospective cohort study, focused on nutrition, lifestyle, and chronic diseases. Participants (n = 10,807, mean age 37 years, 67% women) initially free of metabolic syndrome were followed prospectively for a minimum of 6 years. To evaluate healthy lifestyle, nine habits were used to derive a Healthy Lifestyle Score (HLS): Never smoking, moderate to high physical activity (>20 MET-h/week), Mediterranean diet (>= 4/8 adherence points), moderate alcohol consumption (women, 0.1-5.0 g/day; men, 0.1-10.0 g/day), low television exposure (1 h/day, and working at least 40 h/week. Metabolic syndrome was defined according to the harmonizing definition. The association between the baseline HLS and metabolic syndrome at follow-up was assessed with multivariable-adjusted logistic regressions. During follow-up, we observed 458 (4.24%) new cases of metabolic syndrome. Participants in the highest category of HLS adherence (7-9 points) enjoyed a significantly reduced risk of developing metabolic syndrome compared to those in the lowest category (0-3 points) (adjusted odds ratio (OR) = 0.66, 95% confidence interval (CI) = 0.47-0.93). Higher adherence to the Healthy Lifestyle Score was associated with a lower risk of developing metabolic syndrome. The HLS may be a simple metabolic health promotion tool

Guía de práctica clínica para el tratamiento farmacológico inicial de nefritis lúpica en el Seguro Social del Perú (EsSalud)

Background: This article summarizes the clinical practice guideline (CPG) for the initial pharmacological treatment of lupus nephritis in the Social Security of Peru (EsSalud). Objective: To provide evidence-based clinical recommendations for initial pharmacological treatment of non-refractory adults with class I to V lupus nephritis in EsSalud. Material and Methods: A guideline development group (GDG) was formed, which included specialist physicians and methodologists, who formulated clinical questions. Systematic searches were conducted for systematic reviews and - when deemed relevant - primary studies in PubMed during 2021. Evidence was selected to answer each of the clinical questions posed. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic working meetings, the GEG used the GRADE methodology to review the evidence and formulate recommendations. The CPG was reviewed by external experts before its approval. Results: The CPG addressed 6 clinical questions, divided into 2 topics: initial treatment of the induction and maintenance phase. Based on these questions, 11 recommendations were formulated (all conditional), 22 points of good clinical practice, and 2 flow charts. Conclusion: Evidence-based recommendations were issued for the management of patients with this pathology.Introducción: El presente artículo resume la guía de práctica clínica (GPC) para el tratamiento farmacológico inicial nefritis lúpica en el Seguro Social del Perú (EsSalud). Objetivo: Proveer recomendaciones clínicas basadas en evidencia para tratamiento farmacológico inicial de adultos con nefritis lúpica clase I a V no refractarios en EsSalud. Material y Métodos: Se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas y metodólogos, el cual formuló preguntas clínicas. Se realizaron búsquedas sistemáticas de revisiones sistemáticas y –cuando fue considerado pertinente– estudios primarios en PubMed durante el 2021. Se seleccionó la evidencia para responder cada una de las preguntas clínicas planteadas. Se evaluó la certeza de evidencia usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG usó la metodología GRADE para revisar la evidencia y formular las recomendaciones. La GPC fue revisada por expertos externos antes de su aprobación. Resultados: La GPC abordó 6 preguntas clínicas, divididas en 2 temas: tratamiento inicial de la fase de inducción y mantenimiento. En base a dichas preguntas se formularon 11 recomendaciones (todas condicionales), 22 puntos de buena práctica clínica, y 2 flujogramas. Conclusión: Se emitieron recomendaciones basadas en evidencia para el manejo de pacientes con esta patología

Risk factors for infections caused by carbapenem-resistant Enterobacterales: an international matched case-control-control study (EURECA)

Cases were patients with complicated urinary tract infection (cUTI), complicated intraabdominal (cIAI), pneumonia or bacteraemia from other sources (BSI-OS) due to CRE; control groups were patients with infection caused by carbapenem-susceptible Enterobacterales (CSE), and by non-infected patients, respectively. Matching criteria included type of infection for CSE group, ward and duration of hospital admission. Conditional logistic regression was used to identify risk factors. Findings Overall, 235 CRE case patients, 235 CSE controls and 705 non-infected controls were included. The CRE infections were cUTI (133, 56.7%), pneumonia (44, 18.7%), cIAI and BSI-OS (29, 12.3% each). Carbapenemase genes were found in 228 isolates: OXA-48/like, 112 (47.6%), KPC, 84 (35.7%), and metallo-beta-lactamases, 44 (18.7%); 13 produced two. The risk factors for CRE infection in both type of controls were (adjusted OR for CSE controls; 95% CI; p value) previous colonisation/infection by CRE (6.94; 2.74-15.53; <0.001), urinary catheter (1.78; 1.03-3.07; 0.038) and exposure to broad spectrum antibiotics, as categorical (2.20; 1.25-3.88; 0.006) and time-dependent (1.04 per day; 1.00-1.07; 0.014); chronic renal failure (2.81; 1.40-5.64; 0.004) and admission from home (0.44; 0.23-0.85; 0.014) were significant only for CSE controls. Subgroup analyses provided similar results. Interpretation The main risk factors for CRE infections in hospitals with high incidence included previous coloni-zation, urinary catheter and exposure to broad spectrum antibiotics

Low exposure long-baseline neutrino oscillation sensitivity of the DUNE experiment

The Deep Underground Neutrino Experiment (DUNE) will produce world-leading neutrino oscillation measurements over the lifetime of the experiment. In this work, we explore DUNE's sensitivity to observe charge-parity violation (CPV) in the neutrino sector, and to resolve the mass ordering, for exposures of up to 100 kiloton-megawatt-years (kt-MW-yr). The analysis includes detailed uncertainties on the flux prediction, the neutrino interaction model, and detector effects. We demonstrate that DUNE will be able to unambiguously resolve the neutrino mass ordering at a 3$\sigma$ (5$\sigma$) level, with a 66 (100) kt-MW-yr far detector exposure, and has the ability to make strong statements at significantly shorter exposures depending on the true value of other oscillation parameters. We also show that DUNE has the potential to make a robust measurement of CPV at a 3$\sigma$ level with a 100 kt-MW-yr exposure for the maximally CP-violating values \delta_{\rm CP}} = \pm\pi/2. Additionally, the dependence of DUNE's sensitivity on the exposure taken in neutrino-enhanced and antineutrino-enhanced running is discussed. An equal fraction of exposure taken in each beam mode is found to be close to optimal when considered over the entire space of interest

Impact of cross-section uncertainties on supernova neutrino spectral parameter fitting in the Deep Underground Neutrino Experiment

A primary goal of the upcoming Deep Underground Neutrino Experiment (DUNE) is to measure the $\mathcal{O}(10)$ MeV neutrinos produced by a Galactic core-collapse supernova if one should occur during the lifetime of the experiment. The liquid-argon-based detectors planned for DUNE are expected to be uniquely sensitive to the $\nu_e$ component of the supernova flux, enabling a wide variety of physics and astrophysics measurements. A key requirement for a correct interpretation of these measurements is a good understanding of the energy-dependent total cross section $\sigma(E_\nu)$ for charged-current $\nu_e$ absorption on argon. In the context of a simulated extraction of supernova $\nu_e$ spectral parameters from a toy analysis, we investigate the impact of $\sigma(E_\nu)$ modeling uncertainties on DUNE's supernova neutrino physics sensitivity for the first time. We find that the currently large theoretical uncertainties on $\sigma(E_\nu)$ must be substantially reduced before the $\nu_e$ flux parameters can be extracted reliably: in the absence of external constraints, a measurement of the integrated neutrino luminosity with less than 10\% bias with DUNE requires $\sigma(E_\nu)$ to be known to about 5%. The neutrino spectral shape parameters can be known to better than 10% for a 20% uncertainty on the cross-section scale, although they will be sensitive to uncertainties on the shape of $\sigma(E_\nu)$. A direct measurement of low-energy $\nu_e$-argon scattering would be invaluable for improving the theoretical precision to the needed level.Comment: 25 pages, 21 figure

Volume I. Introduction to DUNE

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture 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 technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. This TDR is intended to justify the technical choices for the far detector that flow down from the high-level physics goals through requirements at all levels of the Project. Volume I contains an executive summary that introduces the DUNE science program, the far detector and the strategy for its modular designs, and the organization and management of the Project. The remainder of Volume I provides more detail on the science program that drives the choice of detector technologies and on the technologies themselves. It also introduces the designs for the DUNE near detector and the DUNE computing model, for which DUNE is planning design reports. Volume II of this TDR describes DUNE\u27s physics program in detail. Volume III describes the technical coordination required for the far detector design, construction, installation, and integration, and its organizational structure. Volume IV describes the single-phase far detector technology. A planned Volume V will describe the dual-phase technology