RETOS Y OPORTUNIDADES EN LA INTEGRACIÓN DE SOCIEDADES COOPERATIVAS

La presente publicación contiene las actas del Curso de Verano titulado “Retos y oportunidades en la integración de cooperativas” que se celebró en la sede de la Cartuja de Sevilla de la Universidad Internacional de Andalucía (UNIA) entre los días 11 a 15 de septiembre de 2017 y que se organizó en el marco del Proyecto Investigación de Excelencia de la Junta de Andalucía "Retos y oportunidades en la concentración e integración de empresas agroalimentaria" (P12-SEJ-2555) del que el profesor Vargas Vasserot es el Investigador Principal. Una de las peculiaridades que tuvo el curso es que gran parte de los asistentes eran a su vez especialistas en las materias impartidas y miembros del proyecto de investigación de la Junta de Andalucía que organizaba el curso, por lo que con objeto de darle mayor participación se habilitó la posibilidad de presentar comunicaciones científicas, como si fuera un congreso. Una vez terminado el curso, se vio que los materiales facilitados a los alumnos por los distintos profesores del curso junto a las comunicaciones científicas presentadas por parte de los asistentes era un material que debía ser puesto a disposición de todas las personas e instituciones interesadas en los procesos de integración de cooperativas y, además, sin mucha demora por la importancia que actualmente tienen todas estas cuestiones. Además de las ponencias y comunicaciones que se presentarons, hemos includio en la publicación un anexo con legislación y normativa de interés y los resultados de una encuesta sobre los procesos de integración realizada en el sector hortofrutícola almeriense que realizamos a lo largo de 2016 en el marco del citado proyecto de investigación de la Junta de Andalucía

Comparison of different prognostic scores for patients with cirrhosis hospitalized with SARS-CoV-2 infection

Introduction and Objectives: Viral infections have been described to increase the risk of decompensation in patients with cirrhosis. We aimed to determine the effect of SARS-CoV-2 infection on outcome of hospitalized patients with cirrhosis and to compare the performance of different prognostic models for predicting mortality. Patients: We performed a prospective cohort study including 2211 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through October 1, 2020 in 38 Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters of patients with and without cirrhosis. All patients were followed until discharge or death. We evaluated the prognostic performance of different scoring systems to predict mortality in patients with cirrhosis using ROC curves. Results: Overall, 4.6% (CI 3.7–5.6) subjects had cirrhosis (n = 96). Baseline Child-Turcotte-Pugh (CTP) class was assessed: CTP-A (23%), CTP-B (45%) and CTP-C (32%); median MELD-Na score was 19 (IQR 14−25). Mortality was 47% in patients with cirrhosis and 16% in patients without cirrhosis (P 30. The areas under the ROC curves for performance evaluation in predicting 28-days mortality for Chronic Liver Failure Consortium (CLIF-C), North American Consortium for the Study of End-Stage Liver Disease (NACSELD), CTP score and MELD-Na were 0.85, 0.75, 0.69, 0.67; respectively (P < .0001). Conclusions: SARS-CoV-2 infection is associated with elevated mortality in patients with cirrhosis. CLIFC had better performance in predicting mortality than NACSELD, CTP and MELD-Na in patients with cirrhosis and SARS-CoV-2 infection. Clinicaltrials.gov:NCT04358380.Fil: Mendizabal, Manuel. Universidad Austral; Argentina. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; ArgentinaFil: Ridruejo, Ezequiel. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina. Centro de Educación Médica e Investigaciones Clínicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Piñero, Federico. Universidad Austral; Argentina. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; ArgentinaFil: Anders, Margarita. Hospital Alemán; Argentina. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; ArgentinaFil: Padilla, Martín Jesus. Hospital Nacional Guillermo Almenara Irigoyen; PerúFil: Toro, Luis G.. Fundación de Medellín y Rionegro; ColombiaFil: Torre, Aldo. Instituto Nacional de Ciencias Médicas y Nutrición; MéxicoFil: Montes, Pedro. Hospital Nacional Daniel A. Carrión; ArgentinaFil: Urzúa, Alvaro. Universidad de Chile; ChileFil: Gonzalez Ballerga, Esteban. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Silveyra, María Dolores. Sanatorio Anchorena; ArgentinaFil: Michelato, Douglas. Hospital Especializado en Enfermedades Infecciosas Instituto Couto Maia; BrasilFil: Díaz, Javier. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: Peralta, Mirta. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Pages, Josefina. Universidad Austral; Argentina. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; ArgentinaFil: García, Sandro Ruiz. Hospital de Víctor Lazarte Echegaray; PerúFil: Gutierrez Lozano, Isabel. Centro Médico ABC; MéxicoFil: Macias, Yuridia. IMSS Hospital General Regional No. 1 “Dr. Carlos Mc Gregor Sánchez”; MéxicoFil: Cocozzella, Daniel. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina. Hospital Italiano de La Plata; ArgentinaFil: Chavez Tapia, Norberto. Medica Sur Clinic & Foundation; MéxicoFil: Tagle, Martín. Clínica Anglo-Americana; PerúFil: Dominguez, Alejandra. Hospital Padre Hurtado; ChileFil: Varón, Adriana. Red Latinoamericana de Concientización y Educación en Investigación del Hígado; Argentina. Fundación Cardio Infantil; ColombiaFil: Vera Pozo, Emilia. Hospital Regional Dr. Teodoro Maldonado Carbo del IESS; EcuadorFil: Higuera de la Tijera, Fátima. Hospital General de México “Dr. Eduardo Liceaga”; MéxicoFil: Bustios, Carla. Fundación Cardio Infantil; ColombiaFil: Conte, Damián. Hospital Privado de Córdoba; ArgentinaFil: Escajadillo, Nataly. Universidad Austral; ArgentinaFil: Rubinstein, Fernando Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Especializado en Enfermedades Infecciosas Instituto Couto Maia; BrasilFil: Tenorio, Laura. Hospital Nacional Edgardo Rebagliati Martins; Per

Native American ancestry significantly contributes to neuromyelitis optica susceptibility in the admixed Mexican population

Neuromyelitis Optica (NMO) is an autoimmune disease with a higher prevalence in non-European populations. Because the Mexican population resulted from the admixture between mainly Native American and European populations, we used genome-wide microarray, HLA high-resolution typing and AQP4 gene sequencing data to analyze genetic ancestry and to seek genetic variants conferring NMO susceptibility in admixed Mexican patients. A total of 164 Mexican NMO patients and 1,208 controls were included. On average, NMO patients had a higher proportion of Native American ancestry than controls (68.1% vs 58.6%; p = 5 × 10–6). GWAS identified a HLA region associated with NMO, led by rs9272219 (OR = 2.48, P = 8 × 10–10). Class II HLA alleles HLA-DQB1*03:01, -DRB1*08:02, -DRB1*16:02, -DRB1*14:06 and -DQB1*04:02 showed the most significant associations with NMO risk. Local ancestry estimates suggest that all the NMO-associated alleles within the HLA region are of Native American origin. No novel or missense variants in the AQP4 gene were found in Mexican patients with NMO or multiple sclerosis. To our knowledge, this is the first study supporting the notion that Native American ancestry significantly contributes to NMO susceptibility in an admixed population, and is consistent with differences in NMO epidemiology in Mexico and Latin America.Fil: Romero Hidalgo, Sandra. Instituto Nacional de Medicina Genómica; MéxicoFil: Flores Rivera, José. Instituto Nacional de Neurología y Neurocirugía; MéxicoFil: Rivas Alonso, Verónica. Instituto Nacional de Neurología y Neurocirugía; MéxicoFil: Barquera, Rodrigo. Max Planck Institute For The Science Of Human History; Alemania. Instituto Nacional de Antropología e Historia; MéxicoFil: Villarreal Molina, María Teresa. Instituto Nacional de Medicina Genómica; MéxicoFil: Antuna Puente, Bárbara. Instituto Nacional de Medicina Genómica; MéxicoFil: Macias Kauffer, Luis Rodrigo. Universidad Nacional Autónoma de México; MéxicoFil: Villalobos Comparán, Marisela. Instituto Nacional de Medicina Genómica; MéxicoFil: Ortiz Maldonado, Jair. Instituto Nacional de Neurología y Neurocirugía; MéxicoFil: Yu, Neng. American Red Cross; Estados UnidosFil: Lebedeva, Tatiana V.. American Red Cross; Estados UnidosFil: Alosco, Sharon M.. American Red Cross; Estados UnidosFil: García Rodríguez, Juan Daniel. Instituto Nacional de Medicina Genómica; MéxicoFil: González Torres, Carolina. Instituto Nacional de Medicina Genómica; MéxicoFil: Rosas Madrigal, Sandra. Instituto Nacional de Medicina Genómica; MéxicoFil: Ordoñez, Graciela. Neuroimmunología, Instituto Nacional de Neurología y Neurocirugía; MéxicoFil: Guerrero Camacho, Jorge Luis. Instituto Nacional de Neurología y Neurocirugía; MéxicoFil: Treviño Frenk, Irene. American British Cowdray Medical Center; México. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Escamilla Tilch, Monica. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: García Lechuga, Maricela. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Tovar Méndez, Víctor Hugo. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Pacheco Ubaldo, Hanna. Instituto Nacional de Antropología E Historia. Escuela Nacional de Antropología E Historia; MéxicoFil: Acuña Alonzo, Victor. Instituto Nacional de Antropología E Historia. Escuela Nacional de Antropología E Historia; MéxicoFil: Bortolini, María Cátira. Universidade Federal do Rio Grande do Sul; BrasilFil: Gallo, Carla. Universidad Peruana Cayetano Heredia; PerúFil: Bedoya Berrío, Gabriel. Universidad de Antioquia; ColombiaFil: Rothhammer, Francisco. Universidad de Tarapacá; ChileFil: Gonzalez-Jose, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; ArgentinaFil: Ruiz Linares, Andrés. Colegio Universitario de Londres; Reino UnidoFil: Canizales Quinteros, Samuel. Universidad Nacional Autónoma de México; MéxicoFil: Yunis, Edmond. Dana Farber Cancer Institute; Estados UnidosFil: Granados, Julio. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Corona, Teresa. Instituto Nacional de Neurología y Neurocirugía; Méxic

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks : The GR@ACE project

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Utilization of mechanical power and associations with clinical outcomes in brain injured patients: a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial

Background: There is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes. Methods: In this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale ≤ 12 before intubation) who required mechanical ventilation (MV) ≥ 24&nbsp;h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS). Results: We included 1217 patients (mean age 51.2&nbsp;years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9&nbsp;J/min [IQR 9.2-15.1], 13&nbsp;J/min [IQR 10-17], and 14&nbsp;J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9&nbsp;J/min, aRR at 17&nbsp;J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22). Conclusions: Exposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation

Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information

Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, interrogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/

Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

Background Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. Methods We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. Findings Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16–36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10−7). Interpretation These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. Funding The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources)

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele