Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma

Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes

Prácticas del enfermero en el contexto de la atención básica: scoping review

Objective: to identify and categorize the practices performed by nurses working in Primary Health Care and Family Health Strategy Units in light of responsibilities established by the profession’s legal and programmatic frameworks and by the Brazilian Unified Health System. Method: a scoping review was conducted in the following databases: LILACS, IBECS, BDENF, CINAHL and MEDLINE, and the Cochrane and SciELO libraries. Original research papers written by nurses addressing nursing practices in the primary health care context were included. Results: the review comprised 30 studies published between 2005 and 2014. Three categories emerged from the analysis: practices in the service; practices in the community; and management and education practices. Conclusion: the challenges faced by nurses are complex, as care should be centered on the population’s health needs, which requires actions at other levels of clinical and health responsibility. Brazilian nursing has achieved important advancements since the implementation of policies intended to reorganize work. There is, however, a need to shift work processes from being focused on individual procedures to being focused on patients so that an enlarged clinic is the ethical-political imperative guiding the organization of services and professional intervention.Objetivo: identificar e categorizar as práticas exercidas pelos enfermeiros junto às Unidades Básicas e às Equipes de Saúde da Família, à luz das atribuições previstas pelos marcos legais e programáticos da profissão e do Sistema Único de Saúde. Método: realizou-se uma revisão da literatura com o método scoping review, nas bases LILACS, IBECS, BDENF, CINAHL e MEDLINE, e nas bibliotecas Cochrane e SciELO. Incluíram-se artigos de pesquisa original, produzidos com enfermeiros, sobre as práticas de enfermagem no contexto dos cuidados de saúde primários. Resultados: a revisão abrangeu trinta estudos publicados entre 2005 e 2014. Da análise, resultaram três categorias: práticas no serviço, práticas na comunidade e práticas de gestão e formação. Conclusão: os desafios dos enfermeiros são complexos, posto que o cuidado deve estar centrado nas necessidades de saúde da população, o que remete à ação para outros níveis de responsabilidade clínica e sanitária. A enfermagem brasileira mostra importantes avanços desde a implantação das políticas de reorganização do trabalho. Necessita, entretanto, avançar no que se refere ao deslocamento dos processos de trabalho, focados em procedimentos individuais, para um processo mais voltado aos usuários, onde a clínica ampliada seja o imperativo ético-político da organização dos serviços e da intervenção profissional.Objetivo: identificar y categorizar las prácticas ejercidas por los enfermeros en las Unidades Básicas y los Equipos de Salud de la Familia, desde el punto de vista de las atribuciones previstas por los marcos legales y programáticos de la profesión y del Sistema Único de la Salud. Método: se realizó una revisión de la literatura con el método scoping review, en las bases LILACS, IBECS, BDENF, CINAHL y MEDLINE, y en las bibliotecas Cochrane y SciELO. Se incluyeron artículos de investigación original, producidos con enfermeros, sobre las prácticas de enfermería en el contexto de los cuidados de salud primarios. Resultados: la revisión abarcó treinta estudios publicados entre 2005 y 2014. Del análisis, resultaron tres categorías: prácticas en el servicio; prácticas en la comunidad; y, prácticas de administración y formación. Conclusión: los desafíos de los enfermeros son complejos, ya que el cuidado debe estar centrado en las necesidades de salud de la población, lo que conduce a la acción para otros niveles de responsabilidad clínica y sanitaria. La enfermería brasileña muestra importantes avances a partir de la implantación de las políticas de reorganización del trabajo. Necesita, entre tanto, avanzar en lo que se refiere al desplazamiento de los procesos de trabajo, enfocados en procedimientos individuales, para un proceso más dirigido a los usuarios, en donde la clínica ampliada sea el imperativo ético político de la organización de los servicios y de la intervención profesional.info:eu-repo/semantics/publishedVersio

Longitudinal Molecular Trajectories of Diffuse Glioma in Adults

The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear ¹² . Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of difuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specifc gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at diferent rates across the glioma subtypes, and hypermutation was not associated with diferences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar over time, but the presence of subclonal selection was associated with decreased survival. Finally, there were no differences in the levels of immunoediting between initial and recurrent gliomas. Collectively, our results suggest that the strongest selective pressures occur during early glioma development and that current therapies shape this evolution in a largely stochastic manner

Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.

BACKGROUND: Lower respiratory infections are a leading cause of morbidity and mortality around the world. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, provides an up-to-date analysis of the burden of lower respiratory infections in 195 countries. This study assesses cases, deaths, and aetiologies spanning the past 26 years and shows how the burden of lower respiratory infection has changed in people of all ages. METHODS: We used three separate modelling strategies for lower respiratory infections in GBD 2016: a Bayesian hierarchical ensemble modelling platform (Cause of Death Ensemble model), which uses vital registration, verbal autopsy data, and surveillance system data to predict mortality due to lower respiratory infections; a compartmental meta-regression tool (DisMod-MR), which uses scientific literature, population representative surveys, and health-care data to predict incidence, prevalence, and mortality; and modelling of counterfactual estimates of the population attributable fraction of lower respiratory infection episodes due to Streptococcus pneumoniae, Haemophilus influenzae type b, influenza, and respiratory syncytial virus. We calculated each modelled estimate for each age, sex, year, and location. We modelled the exposure level in a population for a given risk factor using DisMod-MR and a spatio-temporal Gaussian process regression, and assessed the effectiveness of targeted interventions for each risk factor in children younger than 5 years. We also did a decomposition analysis of the change in LRI deaths from 2000-16 using the risk factors associated with LRI in GBD 2016. FINDINGS: In 2016, lower respiratory infections caused 652 572 deaths (95% uncertainty interval [UI] 586 475-720 612) in children younger than 5 years (under-5s), 1 080 958 deaths (943 749-1 170 638) in adults older than 70 years, and 2 377 697 deaths (2 145 584-2 512 809) in people of all ages, worldwide. Streptococcus pneumoniae was the leading cause of lower respiratory infection morbidity and mortality globally, contributing to more deaths than all other aetiologies combined in 2016 (1 189 937 deaths, 95% UI 690 445-1 770 660). Childhood wasting remains the leading risk factor for lower respiratory infection mortality among children younger than 5 years, responsible for 61·4% of lower respiratory infection deaths in 2016 (95% UI 45·7-69·6). Interventions to improve wasting, household air pollution, ambient particulate matter pollution, and expanded antibiotic use could avert one under-5 death due to lower respiratory infection for every 4000 children treated in the countries with the highest lower respiratory infection burden. INTERPRETATION: Our findings show substantial progress in the reduction of lower respiratory infection burden, but this progress has not been equal across locations, has been driven by decreases in several primary risk factors, and might require more effort among elderly adults. By highlighting regions and populations with the highest burden, and the risk factors that could have the greatest effect, funders, policy makers, and programme implementers can more effectively reduce lower respiratory infections among the world's most susceptible populations. FUNDING: Bill & Melinda Gates Foundation