Gestión y liderazgos en los emprendimientos sociales: el caso del sector no lucrativo chileno

Las organizaciones sin fines de lucro han sufrido grandes cambios. Dejó de ser un sector empobrecido, donde se recibían como donaciones aquel dinero que les sobraba a los grandes empresarios, y donde sólo tenían cabida las personas voluntarias.  Hoy en día es un sector marcado por el trabajo de personas profesionales y por ser organizaciones capaces de llenar los espacios que ha dejado el Estado sin atender. Además de ser organizaciones inteligentes, con estructuras flexibles, que les permiten responder de manera ágil a los requerimientos de su entorno.  Sin embargo para que el sector sin fines de lucro pueda evolucionar de manera exitosa, no sólo necesitan de la labor de sus miembros, también necesitan del compromiso del estado, las universidades y las entidades privadas.  Un compromiso que se haga visible a través de alianzas de colaboración entre sí, y así de esta manera trabajar conjuntamente en el desarrollo humano y la inclusión social en Chile.Les organisations à but non-lucratif ont connu de grands changements. Ce secteur ne correspond plus à un secteur appauvrit recevant les donations des grands entrepreneurs, et n’incluant que des bénévoles. De nos jours, il correspond à un secteur se caractérisant par le travail de professionnels et des organisations capables de remplir les espaces délaissés par l’Etat. De plus, il s’agit d’organisations intelligentes, dotées de structures flexibles, qui leur permettent de répondre de manière adéquate aux exigences de leur milieu. Or, pour que le secteur à but non-lucratif puisse progresser avec succès, cela requiert non seulement le travail de ses membres, mais aussi l’engagement de l’Etat, des universités et des entités privées. Un engagement qui doit être visible grâce à des alliances de collaboration entre ces différents acteurs, pour ainsi travailler ensemble au développement humain et à l’intégration sociale au Chili.The not-for-profit organizations have been suffering great changes. I stopped being impoverish sector, receiving the leftover money from the big businessman, and where only volunteer’s could participate. Nowadays it is a sector characterized for hiring professionals and capable of filling those spaces the State, has left without attention. Besides being clever organizations with flexible structures that allow them to respond speedily to the environment requirements.  However, for this sector to evolve successfully, they need not only the labor of their members, but also the compromise of the State, universities and private entities. A commitment made visible through collaboration alliances, and through that work together in order to achieve social inclusion and human development in Chile.As organizações sem fins lucrativos têm sofrido grandes mudanças. Eles não estão focados exclusivamente no setor empobrecido, quando foi utilizado somente para receber o dinheiro remanescente do grande empresário, e que só tinha espaço para os voluntários. Hoje é um setor marcado pelo trabalho de profissionais e organizações para ser capaz de preencher os espaços deixados sem atenção pelo Estado. Além de ser organizações de aprendizagem, estruturas flexíveis que lhes permitam responder rapidamente às exigências do seu ambiente. No entanto, para a indústria sem fins lucrativos podem evoluir com sucesso, não só precisa do trabalho dos seus membros, também precisa do compromisso do Estado, universidades e entidades privadas. Um compromisso torna-se visível através de parcerias entre si, e assim desta forma a trabalhar juntos no desenvolvimento humano e inclusão social no Chile

Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced lung cancer

Single nucleotide polymorphisms (SNPs) may modulate individual susceptibility to carcinogens. We designed a genome-wide association study to characterize individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced non-small cell lung cancer (NSCLC), and we validated our results. We hypothesized that this strategy would enrich the frequencies of the alleles that contribute to the observed traits. We genotyped 2.37 million SNPs in 95 extreme phenotype individuals, that is: heavy smokers that either developed NSCLC at an early age (extreme cases); or did not present NSCLC at an advanced age (extreme controls), selected from a discovery set (n=3631). We validated significant SNPs in 133 additional subjects with extreme phenotypes selected from databases including >39,000 individuals. Two SNPs were validated: rs12660420 (p(combined)=5.66x10(-5); ORcombined=2.80), mapping to a noncoding transcript exon of PDE10A; and rs6835978 (p(combined)=1.02x10(-4); ORcombined=2.57), an intronic variant in ATP10D. We assessed the relevance of both proteins in early-stage NSCLC. PDE10A and ATP10D mRNA expressions correlated with survival in 821 stage I-II NSCLC patients (p=0.01 and p<0.0001). PDE10A protein expression correlated with survival in 149 patients with stage I-II NSCLC (p=0.002). In conclusion, we validated two variants associated with extreme phenotypes of high and low risk of developing tobacco-induced NSCLC. Our findings may allow to identify individuals presenting high and low risk to develop tobacco-induced NSCLC and to characterize molecular mechanisms of carcinogenesis and resistance to develop NSCLC

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

The global abundance of tree palms

Aim Palms are an iconic, diverse and often abundant component of tropical ecosystems that provide many ecosystem services. Being monocots, tree palms are evolutionarily, morphologically and physiologically distinct from other trees, and these differences have important consequences for ecosystem services (e.g., carbon sequestration and storage) and in terms of responses to climate change. We quantified global patterns of tree palm relative abundance to help improve understanding of tropical forests and reduce uncertainty about these ecosystems under climate change. Location Tropical and subtropical moist forests. Time period Current. Major taxa studied Palms (Arecaceae). Methods We assembled a pantropical dataset of 2,548 forest plots (covering 1,191 ha) and quantified tree palm (i.e., ≥10 cm diameter at breast height) abundance relative to co‐occurring non‐palm trees. We compared the relative abundance of tree palms across biogeographical realms and tested for associations with palaeoclimate stability, current climate, edaphic conditions and metrics of forest structure. Results On average, the relative abundance of tree palms was more than five times larger between Neotropical locations and other biogeographical realms. Tree palms were absent in most locations outside the Neotropics but present in >80% of Neotropical locations. The relative abundance of tree palms was more strongly associated with local conditions (e.g., higher mean annual precipitation, lower soil fertility, shallower water table and lower plot mean wood density) than metrics of long‐term climate stability. Life‐form diversity also influenced the patterns; palm assemblages outside the Neotropics comprise many non‐tree (e.g., climbing) palms. Finally, we show that tree palms can influence estimates of above‐ground biomass, but the magnitude and direction of the effect require additional work. Conclusions Tree palms are not only quintessentially tropical, but they are also overwhelmingly Neotropical. Future work to understand the contributions of tree palms to biomass estimates and carbon cycling will be particularly crucial in Neotropical forests

Mapping density, diversity and species-richness of the Amazon tree flora

Using 2.046 botanically-inventoried tree plots across the largest tropical forest on Earth, we mapped tree species-diversity and tree species-richness at 0.1-degree resolution, and investigated drivers for diversity and richness. Using only location, stratified by forest type, as predictor, our spatial model, to the best of our knowledge, provides the most accurate map of tree diversity in Amazonia to date, explaining approximately 70% of the tree diversity and species-richness. Large soil-forest combinations determine a significant percentage of the variation in tree species-richness and tree alpha-diversity in Amazonian forest-plots. We suggest that the size and fragmentation of these systems drive their large-scale diversity patterns and hence local diversity. A model not using location but cumulative water deficit, tree density, and temperature seasonality explains 47% of the tree species-richness in the terra-firme forest in Amazonia. Over large areas across Amazonia, residuals of this relationship are small and poorly spatially structured, suggesting that much of the residual variation may be local. The Guyana Shield area has consistently negative residuals, showing that this area has lower tree species-richness than expected by our models. We provide extensive plot meta-data, including tree density, tree alpha-diversity and tree species-richness results and gridded maps at 0.1-degree resolution

Mapping density, diversity and species-richness of the Amazon tree flora

Using 2.046 botanically-inventoried tree plots across the largest tropical forest on Earth, we mapped tree species-diversity and tree species-richness at 0.1-degree resolution, and investigated drivers for diversity and richness. Using only location, stratified by forest type, as predictor, our spatial model, to the best of our knowledge, provides the most accurate map of tree diversity in Amazonia to date, explaining approximately 70% of the tree diversity and species-richness. Large soil-forest combinations determine a significant percentage of the variation in tree species-richness and tree alpha-diversity in Amazonian forest-plots. We suggest that the size and fragmentation of these systems drive their large-scale diversity patterns and hence local diversity. A model not using location but cumulative water deficit, tree density, and temperature seasonality explains 47% of the tree species-richness in the terra-firme forest in Amazonia. Over large areas across Amazonia, residuals of this relationship are small and poorly spatially structured, suggesting that much of the residual variation may be local. The Guyana Shield area has consistently negative residuals, showing that this area has lower tree species-richness than expected by our models. We provide extensive plot meta-data, including tree density, tree alpha-diversity and tree species-richness results and gridded maps at 0.1-degree resolution

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

Chronic lymphocytic leukemia patients with <scp><i>IGH</i></scp> translocations are characterized by a distinct genetic landscape with prognostic implications

Chromosome 14q32 rearrangements/translocations involving the immunoglobulinheavy chain (IGH) are rarely detected in chronic lymphocytic leukemia (CLL). Theprognostic significance of the IGH translocation is controversial and its mutational profile remains unknown. Here, we present for the first time a comprehensive next-generation sequencing (NGS) analysis of 46 CLL patients with IGH rearrangement(IGHR-CLLs) and we demonstrate that IGHR-CLLs have a distinct mutational profilewith recurrent mutations in BRAF and HIST1H1E genes. Interestingly, BCL2 and FBXW7mutations were significantly associated with this subgroup and almost half of BCL2, IGLL5 and HISTH1E mutations reported were previously identified in non-Hodgkin lymphomas. Notably, IGH/BCL2 rearrangements were associated with a lower mutation frequency and carried BCL2 and IGLL5 mutations, while the other IGHR-CLLs had mutations in genesrelated to poor prognosis (NOTCH1, SF3B1 and TP53) and shorter time to first treat-ment (TFT). Moreover, IGHR-CLLs patients showed a shorter TFT than CLL patients carrying 13q−, normal fluorescence in situ hybridization (FISH) and +12 CLL, NOTCH1, SF3B1, TP53, BIRC3 and BRAF werealso mutated. The presence of these mutations not only was an independent risk fac-tor within IGHR-CLLs, but also refined the prognosis of low-risk cytogenetic patients(13q−/normal FISH). Hence, our study demonstrates that IGHR-CLLs have a distinct mutational profile from the majority of CLLs and highlights the relevance of incorporating NGS and the status ofIGHby FISH analysis to refine the risk-stratification CLL model.Instituto de Salud Carlos III'El Fondo Social Europeo invierte en tu futuroEuropean Regional Development FundSpanish Fondo de Investigaciones SanitariasDepto. de Bioquímica y Biología MolecularFac. de FarmaciaFALSEpu

Chronic lymphocytic leukemia patients with IGH translocations are characterized by a distinct genetic landscape with prognostic implications

Chromosome 14q32 rearrangements/translocations involving the immunoglobulin heavy chain (IGH) are rarely detected in chronic lymphocytic leukemia (CLL). The prognostic significance of the IGH translocation is controversial and its mutational profile remains unknown. Here, we present for the first time a comprehensive next‐generation sequencing (NGS) analysis of 46 CLL patients with IGH rearrangement (IGHR‐CLLs) and we demonstrate that IGHR‐CLLs have a distinct mutational profile with recurrent mutations in NOTCH1, IGLL5, POT1, BCL2, FBXW7, ZMYM3, MGA, BRAF and HIST1H1E genes. Interestingly, BCL2 and FBXW7 mutations were significantly associated with this subgroup and almost half of BCL2, IGLL5 and HISTH1E mutations reported were previously identified in non‐Hodgkin lymphomas. Notably, IGH/BCL2 rearrangements were associated with a lower mutation frequency and carried BCL2 and IGLL5 mutations, while the other IGHR‐CLLs had mutations in genes related to poor prognosis (NOTCH1, SF3B1 and TP53) and shorter time to first treatment (TFT). Moreover, IGHR‐CLLs patients showed a shorter TFT than CLL patients carrying 13q−, normal fluorescence in situ hybridization (FISH) and +12 CLL, being this prognosis particularly poor when NOTCH1, SF3B1, TP53, BIRC3 and BRAF were also mutated. The presence of these mutations not only was an independent risk factor within IGHR‐CLLs, but also refined the prognosis of low‐risk cytogenetic patients (13q−/normal FISH). Hence, our study demonstrates that IGHR‐CLLs have a distinct mutational profile from the majority of CLLs and highlights the relevance of incorporating NGS and the status of IGH by FISH analysis to refine the risk‐stratification CLL model.This work was supported by grants from the Spanish Fondo de Investigaciones Sanitarias, PI15/01471, PI18/01500, Instituto de Salud Carlos III (ISCIII), European Regional Development Fund (ERDF) “Una manera de hacer Europa”, “Consejería de Educación, Junta de Castilla y León” (SA271P18), “Proyectos de Investigación del SACYL”, Spain: GRS 1847/A/18, GRS1653/A17, “Fundación Memoria Don Samuel Solórzano Barruso”, by grants (RD12/0036/0069) from Red Temática de Investigación Cooperativa en Cáncer (RTICC) and Centro de Investigación Biomédica en Red de Cáncer (CIBERONC CB16/12/00233). Claudia Pérez‐Carretero was supported by an “Ayuda predoctoral en Oncología” (AECC) and is a recipient of a PFIS grant (FI19/00191) from Instituto de Salud Carlos III; María Hernández‐Sánchez was supported by a grant from FEHH/Janssen (“Sociedad Española de Hematología y Hemoterapia”) and now holds a Sara Borrell post‐doctoral contract (CD19/00222) from the Instituto de Salud Carlos III (ISCIII). PFIS grant and Sara Borrell post‐doctoral contrat is co‐founded by Fondo Social Europeo (FSE) “El Fondo Social Europeo invierte en tu futuro”; Miguel Quijada‐Álamo is supported by an “Ayuda Predoctoral de la Junta de Castilla y León” (JCYL‐EDU/529/2017); Jesús‐María Hernández‐Sánchez and Ana E. Rodríguez‐Vicente are supported by research grants of FEHH (“Fundación Española de Hematología y Hemoterapia”).Peer reviewe