Linkage of Type I Interferon Activity and TNF-Alpha Levels in Serum with Sarcoidosis Manifestations and Ancestry

BACKGROUND: Both type I interferon (IFN), also known as IFN-α and tumor necrosis factor alpha (TNF-α) have been implicated in the pathogenesis of sarcoidosis. We investigated serum levels of these cytokines in a large multi-ancestral sarcoidosis population to determine correlations between cytokine levels and disease phenotypes. METHODS: We studied serum samples from 98 patients with sarcoidosis, including 71 patients of African-American ancestry and 27 patients of European-American ancestry. Serum type I IFN was measured using a sensitive reporter cell assay and serum TNF-α was measured using a commercial ELISA kit. Clinical data including presence or absence of neurologic, cardiac, and severe pulmonary manifestations of sarcoidosis were abstracted from medical records. Twenty age-matched non-autoimmune controls were also studied from each ancestral background. Differences in cytokine levels between groups were analyzed with Mann-Whitney U test, and correlations were assessed using Spearman's rho. Multivariate logistic regression models were used to detect associations between cytokines and clinical manifestations. RESULTS: Significant differences in cytokine levels were observed between African- and European-American patients with sarcoidosis. In African-Americans, serum TNF-α levels were significantly higher relative to matched controls (P = 0.039), and patients with neurologic disease had significantly higher TNF-α than patients lacking this manifestation (P = 0.022). In European-Americans, serum type I IFN activity was higher in sarcoidosis cases as compared to matched controls, and patients with extra-pulmonary disease represented a high serum IFN subgroup (P = 0.0032). None of the associations observed were shared between the two ancestral groups. CONCLUSIONS: Our data indicate that significant associations between serum levels of TNF-α and type I IFN and clinical manifestations exist in a sarcoidosis cohort that differ significantly by self-reported ancestry. In each ancestral background, the cytokine elevated in patients with sarcoidosis was also associated with a particular disease phenotype. These findings may relate to ancestral differences in the molecular pathogenesis of this heterogeneous disease

Bayesian Dynamical Systems Modelling in the Social Sciences

Data arising from social systems is often highly complex, involving non-linear relationships between the macro-level variables that characterize these systems. We present a method for analyzing this type of longitudinal or panel data using differential equations. We identify the best non-linear functions that capture interactions between variables, employing Bayes factor to decide how many interaction terms should be included in the model. This method punishes overly complicated models and identifies models with the most explanatory power. We illustrate our approach on the classic example of relating democracy and economic growth, identifying non-linear relationships between these two variables. We show how multiple variables and variable lags can be accounted for and provide a toolbox in R to implement our approach

Developmental milestones of vertically HIV infected and seroreverters children: follow up of 83 children Desenvolvimento psicomotor de crianças verticalmente infectadas pelo HIV e sororevertidas: seguimento de 83 crianças

The aim of the study was to detect neurological abnormalities in human immunodeficiency virus (HIV) infected children. This was achieved by a prospective evaluation, from November/1995 to April/2000, of 43 HIV infected children (group I) and 40 HIV seroreverters children (group II) through neurological exam and neurodevelopmental tests: Denver Developmental Screening Test (DDST) and Clinical Adaptive Test / Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS). A control group (III), of 67 children, were evaluated by CAT/CLAMS. Hyperactivity, irritability and hypotonia were the findings on neurological examination, without statistical differences between group I and II. On CAT/CLAMS, the group I developmental quotient (DQ) was significantly lower than the other groups. The same occurred in DDST, with group I presenting significantly more failures than group II. Nineteen HIV children of group I had brain computed tomographic scan, with abnormalities in three of them (basal ganglia calcification, white matter hypodensity and asymmetry of lateral ventricles). We conclude that in HIV infected children a neurodevelopment delay occur early in the disease, and it can be detected by screening tests.<br>Objetivou-se com o presente estudo detectar anormalidades neurológicas em crianças infectadas pelo vírus da imunodeficiência humana (HIV). Avaliou-se prospectivamente, de novembro de 1995 a abril de 2000, 43 crianças infectadas pelo HIV (grupo I) e 40 crianças sororevertidas (grupo II), por meio de exame neurológico, testes de screening de neurodesenvolvimento: Teste Denver de Triagem de Desenvolvimento (DDST) e Teste de Adaptação Clínica / Escala Linguística e Desenvolvimento Auditivo (CAT/CLAMS). Como grupo controle (III), foram avaliadas 67 crianças pelo CAT/CLAMS. Hiperatividade, irritabilidade e hipotonia foram as alterações encontradas ao exame neurológico, não ocorrendo diferenças estatísticas entre as crianças infectadas ou sororevertidas. No CAT/CLAMS o quociente de desenvolvimento (QD) do grupo I foi significativamente mais baixo que dos outros . O mesmo ocorreu no DDST, com o grupo I apresentando reprovações mais frequentes que o grupo II. Tomografia axial computadorizada de crânio foi realizada em 19 crianças do grupo I, sendo anormal em três delas (calcificação de gânglios da base, hipodensidade de substância branca e assimetria de ventrículos laterais). Conclui-se que, nas crianças infectadas, o atraso do neurodesenvolvimento ocorre precocemente e pode ser detectado por testes de screening