ATENÇÃO PRIMÁRIA À SAÚDE: ORDENADORA DA INTEGRAÇÃO ASSISTENCIAL NA REDE DE URGÊNCIA E EMERGÊNCIA

RESUMO A atenção primária à saúde (APS) é considerada a principal porta de entrada na rede assistencial à saúde, no entanto, apresentam-se dificuldades para efetivá-la como tal. Portanto, o objetivo do artigo é analisar a integração entre unidade de saúde (US) e unidade de pronto-atendimento (UPA), tendo a APS como ordenadora da rede de urgência e emergência (RUE). Trata-se de pesquisa qualitativa, descritiva e exploratória. Na coleta de dados foram realizadas 49 entrevistas com médicos, enfermeiros e gestores de saúde, entre fevereiro e junho de 2015, em uma capital da região Sul do Brasil. Do processamento dos dados para a análise textual realizado pelo software IRAMUTEQ resultaram quatro classes: comunicação formal e informal na organização de saúde; acesso da população aos serviços de saúde; integração entre a US e a UPA; funções da US e da UPA na rede de atenção à saúde. A pesquisa revelou que a integração do cuidado entre a APS e a UPA mostra-se frágil e desarticulada com os outros serviços que compõem a rede assistencial à saúde, potencializado pela indefinição das atribuições de cada componente da RUE pelos gestores do sistema e profissionais assistenciais e a sobreposição de funções entre a US e a UPA

Monotonicity of Fitness Landscapes and Mutation Rate Control

A common view in evolutionary biology is that mutation rates are minimised. However, studies in combinatorial optimisation and search have shown a clear advantage of using variable mutation rates as a control parameter to optimise the performance of evolutionary algorithms. Much biological theory in this area is based on Ronald Fisher's work, who used Euclidean geometry to study the relation between mutation size and expected fitness of the offspring in infinite phenotypic spaces. Here we reconsider this theory based on the alternative geometry of discrete and finite spaces of DNA sequences. First, we consider the geometric case of fitness being isomorphic to distance from an optimum, and show how problems of optimal mutation rate control can be solved exactly or approximately depending on additional constraints of the problem. Then we consider the general case of fitness communicating only partial information about the distance. We define weak monotonicity of fitness landscapes and prove that this property holds in all landscapes that are continuous and open at the optimum. This theoretical result motivates our hypothesis that optimal mutation rate functions in such landscapes will increase when fitness decreases in some neighbourhood of an optimum, resembling the control functions derived in the geometric case. We test this hypothesis experimentally by analysing approximately optimal mutation rate control functions in 115 complete landscapes of binding scores between DNA sequences and transcription factors. Our findings support the hypothesis and find that the increase of mutation rate is more rapid in landscapes that are less monotonic (more rugged). We discuss the relevance of these findings to living organisms

Ship-based contributions to global ocean, weather, and climate observing systems

The role ships play in atmospheric, oceanic, and biogeochemical observations is described with a focus on measurements made within 100 m of the ocean surface. Ships include merchant and research vessels, cruise liners and ferries, fishing vessels, coast guard, military, and other government-operated ships, yachts, and a growing fleet of automated surface vessels. The present capabilities of ships to measure essential climate/ocean variables and the requirements from a broad community to address operational, commercial, and scientific needs are described. Following the guidance from the OceanObs'19 organizing committee, the authors provide a vision to expand observations needed from ships to understand and forecast the exchanges across the ocean-atmosphere interface. The vision addresses (1) recruiting vessels to improve both spatial and temporal sampling, (2) conducting multi-variate sampling on ships, (3) raising technology readiness levels of automated shipboard sensors and ship-to-shore data communications, (4) advancing quality evaluation of observations, and (5) developing a unified data management approach for observations and metadata that meets the needs of a diverse user community. Recommendations are made focusing on integrating private and autonomous vessels into the observing system, investing in sensor and communications technology development, developing an integrated data management structure that includes all types of ships, and moving towards a quality evaluation process that will result in a subset of ships being defined as mobile reference ships that will support climate studies. We envision a future where commercial, research, and privately-owned vessels are making multivariate observations using a combination of automated and human-observed measurements. All data and metadata will be documented, tracked, evaluated, distributed, and archived to benefit users of marine data. This vision looks at ships as a holistic network, not a set of disparate commercial, research, and/or third-party activities working in isolation, to bring these communities together for the mutual benefit of all

The lived experience of psychosis: a bottom-up review co-written by experts by experience and academics

: Psychosis is the most ineffable experience of mental disorder. We provide here the first co-written bottom-up review of the lived experience of psychosis, whereby experts by experience primarily selected the subjective themes, that were subsequently enriched by phenomenologically-informed perspectives. First-person accounts within and outside the medical field were screened and discussed in collaborative workshops involving numerous individuals with lived experience of psychosis as well as family members and carers, representing a global network of organizations. The material was complemented by semantic analyses and shared across all collaborators in a cloud-based system. The early phases of psychosis (i.e., premorbid and prodromal stages) were found to be characterized by core existential themes including loss of common sense, perplexity and lack of immersion in the world with compromised vital contact with reality, heightened salience and a feeling that something important is about to happen, perturbation of the sense of self, and need to hide the tumultuous inner experiences. The first episode stage was found to be denoted by some transitory relief associated with the onset of delusions, intense self-referentiality and permeated self-world boundaries, tumultuous internal noise, and dissolution of the sense of self with social withdrawal. Core lived experiences of the later stages (i.e., relapsing and chronic) involved grieving personal losses, feeling split, and struggling to accept the constant inner chaos, the new self, the diagnosis and an uncertain future. The experience of receiving psychiatric treatments, such as inpatient and outpatient care, social interventions, psychological treatments and medications, included both positive and negative aspects, and was determined by the hope of achieving recovery, understood as an enduring journey of reconstructing the sense of personhood and re-establishing the lost bonds with others towards meaningful goals. These findings can inform clinical practice, research and education. Psychosis is one of the most painful and upsetting existential experiences, so dizzyingly alien to our usual patterns of life and so unspeakably enigmatic and human

Frontal lobe changes occur early in the course of affective disorders in young people

<p>Abstract</p> <p>Background</p> <p>More severe and persistent forms of affective disorders are accompanied by grey matter loss in key frontal and temporal structures. It is unclear whether such changes precede the onset of illness, occur early in the course or develop gradually with persistence or recurrence of illness. A total of 47 young people presenting with admixtures of depressive and psychotic symptoms were recruited from specialist early intervention services along with 33 age matched healthy control subjects. All participants underwent magnetic resonance imaging and patients were rated clinically as to current stage of illness. Twenty-three patients were identified as being at an early 'attenuated syndrome' stage, while the remaining were rated as having already reached the 'discrete disorder' or 'persistent or recurrent illness' stage. Contrasts were carried out between controls subjects and patients cohorts with attenuated syndromes and discrete disorders, separately.</p> <p>Results</p> <p>The patients that were identified as having a discrete or persisting disorder demonstrated decreased grey matter volumes within distributed frontal brain regions when contrasted to both the control subjects as well as those patients in the attenuated syndrome stage. Overall, patients who were diagnosed as more advanced in terms of the clinical stage of their illness, exhibited the greatest grey matter volume loss of all groups.</p> <p>Conclusions</p> <p>This study suggests that, in terms of frontal grey matter changes, a major transition point may occur in the course of affective illness between early attenuated syndromes and later discrete illness stages.</p

Absent B Cells, agammaglobulinemia, and Hypertrophic Cardiomyopathy in Folliculin-interacting Protein 1 Deficiency

Agammaglobulinemia is the most profound primary antibody deficiency that can occur due to an early termination of B-cell development. We here investigated 3 novel patients, including the first known adult, from unrelated families with agammaglobulinemia, recurrent infections, and hypertrophic cardiomyopathy (HCM). Two of them also presented with intermittent or severe chronic neutropenia. We identified homozygous or compound-heterozygous variants in the gene for folliculin interacting protein 1 (FNIP1), leading to loss of the FNIP1 protein. B-cell metabolism, including mitochondrial numbers and activity and phosphatidylinositol 3-kinase/AKT pathway, was impaired. These defects recapitulated the Fnip1-/- animal model. Moreover, we identified either uniparental disomy or copy-number variants (CNVs) in 2 patients, expanding the variant spectrum of this novel inborn error of immunity. The results indicate that FNIP1 deficiency can be caused by complex genetic mechanisms and support the clinical utility of exome sequencing and CNV analysis in patients with broad phenotypes, including agammaglobulinemia and HCM. FNIP1 deficiency is a novel inborn error of immunity characterized by early and severe B-cell development defect, agammaglobulinemia, variable neutropenia, and HCM. Our findings elucidate a functional and relevant role of FNIP1 in B-cell development and metabolism and potentially neutrophil activity

Sex-dependent associations between maternal prenatal cortisol and child callous-unemotional traits: findings from the Wirral Child Health and Development Study

Elevated maternal glucocorticoids during pregnancy may impact on fetal development in a sex-dependent way, leading to increased amygdala activation and increased risk for internalising disorders in females. Based on evidence implicating reduced amygdala activation in callous-unemotional (CU) traits, we predicted that elevated maternal cortisol in pregnancy would be associated with lower CU traits and elevated anxious-depressed symptoms, only in girls. Participants were 225 members of a stratified subsample within an epidemiological longitudinal cohort (WCHADS). Salivary cortisol was measured over two days at 32 weeks gestation (on waking, 30-min post-waking and during the evening) and the log of the area under the curve (LogAUC) was calculated as an index of diurnal cortisol. Mothers reported on child CU traits and anxious-depressed symptoms at 2.5, 3.5 and 5.0 years of age. As predicted there was a sex of child by cortisol interaction (p < .001) whereby elevated maternal cortisol was associated with lower child CU traits, explaining 25% of the variance, in girls, but not in boys. This effect remained when controlling for relevant confounders and anxious-depressed symptoms. By contrast, elevated maternal cortisol did not predict higher anxious-depressed symptoms in girls. The study adds to growing evidence for sex-dependent effects of elevated maternal cortisol during pregnancy on early child psychopathology, consistent with mediation by elevated amygdala activation. The conditions under which, in girls, this is associated with heightened responsiveness to others' distress characteristic of low CU traits, or with increased affective symptoms, require further study