Repetibilidade em população de trabalho de cajuí via REML/BLUP em Parnaíba, Piauí.

O objetivo deste trabalho foi estimar os coeficientes de repetibilidade das variáveis agrotecnológicas de uma população de trabalho de Cajuí da Embrapa Meio-Norte, em Parnaíba, PI

Metabolic Footprint, towards Understanding Type 2 Diabetes beyond Glycemia

Type 2 diabetes (T2D) heterogeneity is a major determinant of complications risk and treatment response. Using cluster analysis, we aimed to stratify glycemia within metabolic multidimensionality and extract pathophysiological insights out of metabolic profiling. We performed a cluster analysis to stratify 974 subjects (PREVADIAB2 cohort) with normoglycemia, prediabetes, or non-treated diabetes. The algorithm was informed by age, anthropometry, and metabolic milieu (glucose, insulin, C-peptide, and free fatty acid (FFA) levels during the oral glucose tolerance test OGTT). For cluster profiling, we additionally used indexes of metabolism mechanisms (e.g., tissue-specific insulin resistance, insulin clearance, and insulin secretion), non-alcoholic fatty liver disease (NAFLD), and glomerular filtration rate (GFR). We found prominent heterogeneity within two optimal clusters, mainly representing normometabolism (Cluster-I) or insulin resistance and NAFLD (Cluster-II), at higher granularity. This was illustrated by sub-clusters showing similar NAFLD prevalence but differentiated by glycemia, FFA, and GFR (Cluster-II). Sub-clusters with similar glycemia and FFA showed dissimilar insulin clearance and secretion (Cluster-I). This work reveals that T2D heterogeneity can be captured by a thorough metabolic milieu and mechanisms profiling-metabolic footprint. It is expected that deeper phenotyping and increased pathophysiology knowledge will allow to identify subject's multidimensional profile, predict their progression, and treat them towards precision medicine.publishersversionpublishe

Immigration Rates in Fragmented Landscapes – Empirical Evidence for the Importance of Habitat Amount for Species Persistence

BACKGROUND: The total amount of native vegetation is an important property of fragmented landscapes and is known to exert a strong influence on population and metapopulation dynamics. As the relationship between habitat loss and local patch and gap characteristics is strongly non-linear, theoretical models predict that immigration rates should decrease dramatically at low levels of remaining native vegetation cover, leading to patch-area effects and the existence of species extinction thresholds across fragmented landscapes with different proportions of remaining native vegetation. Although empirical patterns of species distribution and richness give support to these models, direct measurements of immigration rates across fragmented landscapes are still lacking. METHODOLOGY/PRINCIPAL FINDINGS: Using the Brazilian Atlantic forest marsupial Gray Slender Mouse Opossum (Marmosops incanus) as a model species and estimating demographic parameters of populations in patches situated in three landscapes differing in the total amount of remaining forest, we tested the hypotheses that patch-area effects on population density are apparent only at intermediate levels of forest cover, and that immigration rates into forest patches are defined primarily by landscape context surrounding patches. As expected, we observed a positive patch-area effect on M. incanus density only within the landscape with intermediate forest cover. Density was independent of patch size in the most forested landscape and the species was absent from the most deforested landscape. Specifically, the mean estimated numbers of immigrants into small patches were lower in the landscape with intermediate forest cover compared to the most forested landscape. CONCLUSIONS/SIGNIFICANCE: Our results reveal the crucial importance of the total amount of remaining native vegetation for species persistence in fragmented landscapes, and specifically as to the role of variable immigration rates in providing the underlying mechanism that drives both patch-area effects and species extinction thresholds

Characterization and comparability of biosimilars: A filgrastim case of study and regulatory perspectives for Latin America

Background: Developing countries have an estimate of ten times more approved biosimilars than developed countries. This disparity demands the need of an objective regulation that incorporates health policies according to the technological and economical capabilities of each country. One of the challenges lies on the establishment of comparability principles based on a physicochemical and biological characterization that should determine the extent of additional non-clinical and clinical studies. This is particularly relevant for licensed biosimilars in developing countries, which have an extensive clinical experience since their approval as generics, in some cases more than a decade. To exemplify the current status of biosimilars in Mexico, a characterization exercise was conducted on licensed filgrastim biosimilars using pharmacopeial and extended characterization methodologies. Results: Most of the evaluated products complied with the pharmacopeial criteria and showed comparability in their Critical Quality Attributes (CQAs) towards the reference product. These results were expected in accordance with their equivalent performance during their licensing as generics. Accordingly, a rational approval and registration renewal scheme for biosimilars is proposed, that considers the proper identification of CQAs and its thoroughly evaluation using selected techniques. Conclusions: This approach provides support to diminish uncertainty of exhibiting different pharmacological profiles and narrows or even avoids the necessity of comparative clinical studies. Ultimately, this proposal is intended to improve the accessibility to high quality biosimilars in Latin America and other developing countries

Global Retinoblastoma Presentation and Analysis by National Income Level

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- A nd middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Acurácia do relacionamento probabilístico na avaliação da alta complexidade em cardiologia

OBJETIVO: Evaluar la viabilidad de estrategia de relación probabilística en la identificación de pacientes sometidos a procedimientos de alta complejidad en cardiología. MÉTODOS: El costo de procesamiento fue calculado con base en 1.672 registros de pacientes sometidos a cirugía de revascularización del miocardio, relacionados con todos los registros de óbito en Brasil en 2005. La precisión de la relación se basó en linkage probabilística de 99 registros de autorización de internación hospitalaria de pacientes sometidos a cirugías cardíacas en instituto de referencia en cardiología, con status vital conocido, con todos los registros de óbito del estado de Rio de Janeiro en 2005. El linkage fue realizado en cuatro etapas: estandarización de las bases, blocaje, pareamiento y clasificación de los pares. Se utilizó blocaje en cinco pasos, con claves de blocaje con combinación de variables como soundex del primero y último nombre, sexo y año de nacimiento. Las variables utilizadas en el pareamiento fueron "nombre completo", con la utilización de la distancia de Levenshtein y "fecha de nacimiento". RESULTADOS: El segundo y el quinto pasos de blocaje tuvieron los mayores números de pares formados y los mayores tiempos de procesamiento para el pareamiento. El cuarto paso demandó menor costo de procesamiento. En el estudio de precisión, posterior a cinco pasos de blocaje, la sensibilidad del linkage fue de 90,6% y la especificidad fue de 100%. CONCLUSIONES: La estrategia de relación probabilística utilizada presenta buena precisión y podrá ser utilizada en estudios sobre la efectividad de los procedimientos de alta complejidad y alto costo en cardiología.OBJECTIVE: To evaluate the viability of a probabilistic record linkage strategy to identify patients who underwent complex cardiology procedures among the total deceased population. METHODS: The processing cost was estimated based on 1,672 records of patients undergoing coronary artery bypass grafting that were compared with all death records in Brazil in 2005. The accuracy of the linkage strategy was based on the probabilistic linkage of 99 hospital admissions records of patients, with known vital status, who underwent cardiac surgery at a single cardiology institute, with the death records of the state of Rio de Janeiro, Southeastern Brazil, in 2005. Linkage was conducted in four stages: standardizing the databases, blocking, matching, and rating peers. Blocking in five steps was used, with blocking keys formed by a combination of variables such as soundex codes for the first and last names, sex, and year of birth. The variables used for matching were "full name" with the use of Levenshtein distance and "birth date". RESULTS: The second and fifth blocking steps resulted in the largest number of formed pairs and the largest processing times for the matching. The fourth step required a lower processing cost. In the accuracy study, after five blocking steps, the sensitivity of the linkage was 90.6%, and the specificity was 100%. CONCLUSIONS: The probabilistic strategy used has high accuracy and can be used in studies of the effectiveness of high-complexity, high-cost cardiology procedures.OBJETIVO: Avaliar a viabilidade de estratégia de relacionamento probabilístico de bases de dados na identificação de óbitos de pacientes submetidos a procedimentos de alta complexidade em cardiologia. MÉTODOS: O custo de processamento foi estimado com base em 1.672 registros de pacientes submetidos à cirurgia de revascularização do miocárdio, relacionados com todos os registros de óbito no Brasil em 2005. A acurácia do relacionamento baseou-se em linkage probabilístico entre 99 registros de autorização de internação hospitalar de pacientes submetidos a cirurgias cardíacas em instituto de referência em cardiologia, com status vital conhecido, e todos os registros de óbito do estado do Rio de Janeiro em 2005. O linkage foi realizado em quatro etapas: padronização das bases, blocagem, pareamento e classificação dos pares. Utilizou-se a blocagem em cinco passos, com chaves de blocagem com combinação de variáveis como soundex do primeiro e último nome, sexo e ano de nascimento. As variáveis utilizadas no pareamento foram "nome completo", com a utilização da distância de Levenshtein, e "data de nascimento". RESULTADOS: O segundo e o quinto passos de blocagem tiveram os maiores números de pares formados e os maiores tempos de processamento para o pareamento. O quarto passo demandou menor custo de processamento. No estudo de acurácia, após os cinco passos de blocagem, a sensibilidade do linkage foi de 90,6% e a especificidade foi de 100%. CONCLUSÕES: A estratégia de relacionamento probabilístico utilizada apresenta boa acurácia e poderá ser utilizada em estudos sobre a efetividade dos procedimentos de alta complexidade e alto custo em cardiologia