Determinants of tuberculosis transmission and treatment abandonment in Fortaleza, Brazil

BACKGROUND: Tuberculosis (TB) remains a public health problem, despite recent achievements in reducing incidence and mortality rates. In Brazil, these achievements were above the worldwide average, but marked by large regional heterogeneities. In Fortaleza (5th largest city in Brazil), the tuberculosis cure rate has been declining and treatment abandonment has been increasing in the past decade, despite a reduction in incidence and an increase in directly observed therapy (DOT). These trends put efforts to eliminate tuberculosis at risk. We therefore sought to determine social and programmatic determinants of tuberculosis incidence and treatment abandonment in Fortaleza. METHODS: We analyzed sociodemographic and clinical data for all new tuberculosis cases notified in the Notifiable Diseases Information System (SINAN) from Fortaleza between 2007 and 2014. We calculated incidence rates for 117 neighborhoods in Fortaleza, assessed their spatial clustering, and used spatial regression models to quantify associations between neighborhood-level covariates and incidence rates. We used hierarchical logistic regression models to evaluate how individual- and neighborhood-level covariates predicted tuberculosis treatment abandonment. RESULTS: There were 12,338 new cases reported during the study period. Case rates across neighborhoods were significantly positively clustered in two low-income areas close to the city center. In an adjusted model, tuberculosis rates were significantly higher in neighborhoods with lower literacy, higher sewerage access and homicide rates, and a greater proportion of self-reported black residents. Treatment was abandoned in 1901 cases (15.4%), a rate that rose by 71% between 2007 and 2014. Abandonment was significantly associated with many individual sociodemographic and clinical factors. Notably, being recommended for DOT was protective for those who completed DOT, but associated with abandonment for those who did not. CONCLUSION: Low socioeconomic status areas have higher tuberculosis rates, and low socioeconomic individuals have higher risk of treatment abandonment, in Fortaleza. Treatment abandonment rates are growing despite the advent of universal DOT recommendations in Brazil. Proactive social policies, and active contact tracing to find missed cases, may help reduce the tuberculosis burden in this setting

Displasia Torácica

Os autores descrevem um caso clínico referente a uma criança que apresentava ao nascer uma marcada desproporção toraco-abdominal,por diminuição do diâmetro torácico. O Recém-nascido (RN) fez um Síndrome de Dificuldade Respiratória (SDR) precoce com necessidade de ventilação mecânica, tendo-se verificado dificuldade na entubação traqueal. Após a extubação manteve crises frequentes de polipneia e cianose. Na sequência da investigação etiológica, verificou-se que tinha uma estenose sub glótica importante. Associando os achados clínicos verificamos tratar-se de um síndrome de Barnes, forma rara de displasia torácica

Probabilistic Guarantees for Safe Deep Reinforcement Learning

Deep reinforcement learning has been successfully applied to many control tasks, but the application of such agents in safety-critical scenarios has been limited due to safety concerns. Rigorous testing of these controllers is challenging, particularly when they operate in probabilistic environments due to, for example, hardware faults or noisy sensors. We propose MOSAIC, an algorithm for measuring the safety of deep reinforcement learning agents in stochastic settings. Our approach is based on the iterative construction of a formal abstraction of a controller's execution in an environment, and leverages probabilistic model checking of Markov decision processes to produce probabilistic guarantees on safe behaviour over a finite time horizon. It produces bounds on the probability of safe operation of the controller for different initial configurations and identifies regions where correct behaviour can be guaranteed. We implement and evaluate our approach on agents trained for several benchmark control problems

Iguais ou diferentes? Cuidados de saúde materno-infantil a uma população de imigrantes

Os concelhos de Amadora e Sintra constituem um território de fortes características de identidade na Área Metropolitana de Lisboa que resultam, entre outros aspectos, da elevada densidade populacional (sobretudo Amadora), do marcado crescimento na última década (sobr etudo Sintra, onde a população residente aumentou cerca de 40% entre 1991 e 2001) e, principalmente, da sua diversidade social, cultural e étnica. D e facto, a proporção de imigrantes nestes concelhos atinge um dos v alores mais elevados do país. A equidade na pr estação de cuidados tem sido demonstrada como factor de r edução das disparidades na saúde que determina a morbilidade e a mortalidade decorrentes da assimetria das populações. Na Unidade de Saúde D (Hospital Fernando Fonseca e 9 Centr os de Saúde da Amadora e Sintra), não tinha ainda sido desenvolvida uma investigação científica estruturada sobre os níveis de saúde e o acesso e utilização dos serviços e que sustentem políticas ajustadas às vulnerabilidades deste grupo. Este conhecimento possibilita a reorganização dos serviços de cuidados de saúde e é fundamental para (r e)pensar processos de planeamento e modelos de inter venção que culminem numa integração de sucesso para o século XXI.info:eu-repo/semantics/publishedVersio

Hospitalization of Children with Rotavirus Infection

Introdução. A infecção por rotavírus é a principal causa de diarreia aguda em todo o mundo. Nos países desenvolvidos não constitui uma causa importante de morte, mas cursa com uma alta morbilidade. Objectivo. Caracterizar a infecção por rotavírus em crianças hospitalizadas em dois Departamentos de Pediatria de Lisboa. Material e métodos. Revisão casuística dos internamentos com o diagnóstico de infecção por rotavírus, num hospital central especializado e num hospital geral na Zona Metropolitana de Lisboa, entre Janeiro e Dezembro de 2005. O diagnóstico foi efectuado através da identificação de antigénios virais nas fezes por “enzyme immunoassay”. Resultados. Foram analisados 92 casos; 82% ocorreram entre Dezembro e Março e 52,8% em crianças entre os três e os doze meses. Em metade dos casos registou-se bom nível socio-económico. Os factores de risco epidemiológicos encontrados foram: frequência de instituição de ensino ou ama em 21/38 (55%), contacto com pessoas com sintomatologia semelhante em 10/53 (19%) e irmãos com idade inferior a cinco anos em 25/76 (33%) das crianças. As infecções nosocomiais foram responsáveis por 26% dos casos estudados. A clínica cursou com: diarreia aquosa (96%), vómitos (87%) e febre (69%). Ocorreram complicações em 19/92 (21%) crianças e estas foram mais frequentes em lactentes com menos de seis meses de idade (35% vs. 16%, p=0,058). A mediana da duração de internamento foi cinco dias e o custo hospitalar directo variou entre 629,63 e 2342,38 euros. Discussão. O número de internamentos por infecção por rotavírus, especialmente em lactentes, a frequência de infecções nosocomiais por este agente, as complicações inerentes e os elevados custos, reflectem a importância da infecção por este agente em países desenvolvidos como Portugal

The value of subtraction MRI in detection of amyloid-related imaging abnormalities with oedema or effusion in Alzheimer's patients: An interobserver study

BACKGROUND: Immunotherapeutic treatments targeting amyloid-β plaques in Alzheimer's disease (AD) are associated with the presence of amyloid-related imaging abnormalities with oedema or effusion (ARIA-E), whose detection and classification is crucial to evaluate subjects enrolled in clinical trials. PURPOSE: To investigate the applicability of subtraction MRI in the ARIA-E detection using an established ARIA-E-rating scale. METHODS: We included 75 AD patients receiving bapineuzumab treatment, including 29 ARIA-E cases. Five neuroradiologists rated their brain MRI-scans with and without subtraction images. The accuracy of evaluating the presence of ARIA-E, intraclass correlation coefficient (ICC) and specific agreement was calculated. RESULTS: Subtraction resulted in higher sensitivity (0.966) and lower specificity (0.970) than native images (0.959, 0.991, respectively). Individual rater detection was excellent. ICC scores ranged from excellent to good, except for gyral swelling (moderate). Excellent negative and good positive specific agreement among all ARIA-E imaging features was reported in both groups. Combining sulcal hyperintensity and gyral swelling significantly increased positive agreement for subtraction images. CONCLUSION: Subtraction MRI has potential as a visual aid increasing the sensitivity of ARIA-E assessment. However, in order to improve its usefulness isotropic acquisition and enhanced training are required. The ARIA-E rating scale may benefit from combining sulcal hyperintensity and swelling. KEY POINTS: • Subtraction technique can improve detection amyloid-related imaging-abnormalities with edema/effusion in Alzheimer's patients. • The value of ARIA-E detection, classification and monitoring using subtraction was assessed. • Validation of an established ARIA-E rating scale, recommendations for improvement are reported. • Complementary statistical methods were employed to measure accuracy, inter-rater-reliability and specific agreement

The influence of semantic and phonological factors on syntactic decisions: An event-related brain potential study

During language production and comprehension, information about a word's syntactic properties is sometimes needed. While the decision about the grammatical gender of a word requires access to syntactic knowledge, it has also been hypothesized that semantic (i.e., biological gender) or phonological information (i.e., sound regularities) may influence this decision. Event-related potentials (ERPs) were measured while native speakers of German processed written words that were or were not semantically and/or phonologically marked for gender. Behavioral and ERP results showed that participants were faster in making a gender decision when words were semantically and/or phonologically gender marked than when this was not the case, although the phonological effects were less clear. In conclusion, our data provide evidence that even though participants performed a grammatical gender decision, this task can be influenced by semantic and phonological factors

Haploinsufficiency of the NOTCH1 Receptor as a Cause of Adams-Oliver Syndrome With Variable Cardiac Anomalies.

BACKGROUND: Adams-Oliver syndrome (AOS) is a rare disorder characterized by congenital limb defects and scalp cutis aplasia. In a proportion of cases, notable cardiac involvement is also apparent. Despite recent advances in the understanding of the genetic basis of AOS, for the majority of affected subjects, the underlying molecular defect remains unresolved. This study aimed to identify novel genetic determinants of AOS. METHODS AND RESULTS: Whole-exome sequencing was performed for 12 probands, each with a clinical diagnosis of AOS. Analyses led to the identification of novel heterozygous truncating NOTCH1 mutations (c.1649dupA and c.6049_6050delTC) in 2 kindreds in which AOS was segregating as an autosomal dominant trait. Screening a cohort of 52 unrelated AOS subjects, we detected 8 additional unique NOTCH1 mutations, including 3 de novo amino acid substitutions, all within the ligand-binding domain. Congenital heart anomalies were noted in 47% (8/17) of NOTCH1-positive probands and affected family members. In leukocyte-derived RNA from subjects harboring NOTCH1 extracellular domain mutations, we observed significant reduction of NOTCH1 expression, suggesting instability and degradation of mutant mRNA transcripts by the cellular machinery. Transient transfection of mutagenized NOTCH1 missense constructs also revealed significant reduction in gene expression. Mutant NOTCH1 expression was associated with downregulation of the Notch target genes HEY1 and HES1, indicating that NOTCH1-related AOS arises through dysregulation of the Notch signaling pathway. CONCLUSIONS: These findings highlight a key role for NOTCH1 across a range of developmental anomalies that include cardiac defects and implicate NOTCH1 haploinsufficiency as a likely molecular mechanism for this group of disorders

Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world

[No abstract available

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH