Plasma adiponectin levels are associated with circulating inflammatory cytokines in autoantibody positive first-degree relatives of rheumatoid arthritis patients.

Background: Extra-articular manifestations of rheumatoid arthritis (RA), potentially due to systemic inflammation, include cardiovascular disease and sarcopenic obesity. Adiponectin, an adipose-derived cytokine, has been implicated in inflammatory processes in RA, but little is known regarding its association with inflammation in a pre-clinical period. Therefore, we investigated whether adiponectin was associated with inflammatory markers in individuals at risk for RA, and whether RA-related autoimmunity modifies these associations.

On the Use of Diversity Measures in Longitudinal Sequencing Studies of Microbial Communities.

Identification of the majority of organisms present in human-associated microbial communities is feasible with the advent of high throughput sequencing technology. As substantial variability in microbiota communities is seen across subjects, the use of longitudinal study designs is important to better understand variation of the microbiome within individual subjects. Complex study designs with longitudinal sample collection require analytic approaches to account for this additional source of variability.

Using empirical Bayes predictors from generalized linear mixed models to test and visualize associations among longitudinal outcomes.

Medical research is often designed to investigate changes in a collection of response variables that are measured repeatedly on the same subjects. The multivariate generalized linear mixed model (MGLMM) can be used to evaluate random coefficient associations (e.g.

Omega-3 fatty acids are associated with a lower prevalence of autoantibodies in shared epitope-positive subjects at risk for rheumatoid arthritis.

Objectives: Previously, we found that omega-3 fatty acids (n-3 FAs) were inversely associated with anti-cyclic citrullinated peptide (anti-CCP) positivity in participants at risk for future rheumatoid arthritis (RA). We investigated whether n-3 FAs were also associated with rheumatoid factor (RF) positivity and whether these associations were modified by shared epitope (SE) positivity.

Methods: The Studies of the Etiology of RA (SERA) cohort includes RA-free participants who are at increased risk for RA.

Perinatal Phosphatidylcholine Supplementation and Early Childhood Behavior Problems: Evidence for CHRNA7 Moderation.

Objective: α7-Nicotinic receptors are involved in the final maturation of GABA inhibitory synapses before birth. Choline at levels found in the amniotic fluid is an agonist at α7-nicotinic receptors. The authors conducted a double-blind placebo-controlled trial to assess whether high-dose oral phosphatidylcholine supplementation during pregnancy to increase maternal amniotic fluid choline levels would enhance fetal development of cerebral inhibition and, as a result, decrease childhood behavior problems associated with later mental illness.

Lower omega-3 fatty acids are associated with the presence of anti-cyclic citrullinated peptide autoantibodies in a population at risk for future rheumatoid arthritis: a nested case-control study.

Objective: The aim of this study was to investigate omega-3 fatty acid (FA) supplement use and omega-3 FAs in erythrocyte membranes [omega-3 FA % in erythrocyte membranes (RBC)] and their association with anti-CCP autoantibodies in a population without RA, but who are at genetic risk for RA.

Methods: The multicentre Studies of the Etiology of RA (SERA) cohort includes RA-free subjects who are first-degree relatives of RA probands or are enriched with the HLA-DR4 allele. In a nested case-control study, 30 SERA cases were identified who were anti-CCP2 antibody positive.

On estimating and testing associations between random coefficients from multivariate generalized linear mixed models of longitudinal outcomes.

Different types of outcomes (e.g. binary, count, continuous) can be simultaneously modeled with multivariate generalized linear mixed models by assuming: (1) same or different link functions, (2) same or different conditional distributions, and (3) conditional independence given random subject effects.

Anti-carbamylated protein antibodies are present prior to rheumatoid arthritis and are associated with its future diagnosis.

Objective: Anti-carbamylated protein (anti-CarP) antibodies could further elucidate early rheumatoid arthritis (RA) pathogenesis and predict clinical disease. We compared the diagnostic accuracy of anti-CarP antibodies for future RA to other RA-related antibodies in military personnel.

Methods: Stored pre-RA diagnosis serum samples from 76 RA cases were tested for anti-CarP fetal calf serum (FCS), anti-CarP fibrinogen (Fib), anticyclic citrullinated peptide antibodies version 2 (anti-CCP2), rheumatoid factor-nephelometry (RF-Neph), and RF isotypes [immunoglobulin M (IgM), IgG, and IgA].

Association between lifetime exposure to inorganic arsenic in drinking water and coronary heart disease in Colorado residents.

Background: Chronic diseases, including coronary heart disease (CHD), have been associated with ingestion of drinking water with high levels of inorganic arsenic (> 1,000 μg/L). However, associations have been inconclusive in populations with lower levels (< 100 μg/L) of inorganic arsenic exposure.

Objectives: We conducted a case-cohort study based on individual estimates of lifetime arsenic exposure to examine the relationship between chronic low-level arsenic exposure and risk of CHD.

B cell receptor signaling-based index as a biomarker for the loss of peripheral immune tolerance in autoreactive B cells in rheumatoid arthritis.

This study examines the loss of peripherally induced B cell immune tolerance in Rheumatoid arthritis (RA) and establishes a novel signaling-based measure of activation in a subset of autoreactive B cells--the Induced tolerance status index (ITSI). Naturally occurring naïve autoreactive B cells can escape the "classical" tolerogenic mechanisms of clonal deletion and receptor editing, but remain peripherally tolerized through B cell receptor (BCR) signaling inhibition (postdevelopmental "receptor tuning" or anergy). ITSI is a statistical index that numerically determines the level of homology between activation patterns of BCR signaling intermediaries in B cells that are either tolerized or activated by auto antigen exposure, and thus quantifies the level of peripheral immune tolerance.

Predicting arsenic concentrations in groundwater of San Luis Valley, Colorado: implications for individual-level lifetime exposure assessment.

Consumption of inorganic arsenic in drinking water at high levels has been associated with chronic diseases. Risk is less clear at lower levels of arsenic, in part due to difficulties in estimating exposure. Herein we characterize spatial and temporal variability of arsenic concentrations and develop models for predicting aquifer arsenic concentrations in the San Luis Valley, Colorado, an area of moderately elevated arsenic in groundwater.

Diminished Infant P50 Sensory Gating Predicts Increased 40-Month-Old Attention, Anxiety/Depression, and Externalizing Symptoms.

Objective: When behavioral problems resulting from attentional difficulties present, often in preschool, it is unknown whether these problems represent preexisting altered brain development or new brain changes. This study examines whether infant sensory gating of auditory evoked potentials predicts parent-reported behavior at 40 months.

Method: P50 sensory gating, an auditory evoked potential measure reflective of inhibitory processes in the brain, was measured in 50 infants around 70 days old.

Relationship between air pollution and positivity of RA-related autoantibodies in individuals without established RA: a report on SERA.

Introduction: Studies suggest that respiratory exposures including smoking, proximity to traffic and air pollution might be associated with development of rheumatoid arthritis (RA). RA-related autoantibodies are predictive of the development of RA.

Objective: We evaluated the relationship between RA-related autoantibodies and exposure to particulate matter (PM), a measure of air pollution of interest to health, in individuals without RA.

A case-cohort study examining lifetime exposure to inorganic arsenic in drinking water and diabetes mellitus.

Background: Consumption of drinking water with high levels of inorganic arsenic (over 500 μg/L) has been associated with type II diabetes mellitus (DM), but previous studies have been inconclusive about risks at lower levels (<100 μg/L). We present a case-cohort study based on individual estimates of lifetime arsenic exposure to examine the relationship between chronic low-level arsenic exposure and risk of DM.

Methods: This case-cohort study included 141 cases of DM diagnosed between 1984 and 1998 as part of the prospective San Luis Valley Diabetes Study.

Validation of estimates of past exposure to arsenic in drinking water using historical urinary arsenic concentrations.

Consumption of inorganic arsenic in drinking water at high levels has been associated with chronic diseases. Research groups have estimated historic exposure using databases and models of arsenic in drinking water supplies, along with participant residential histories. Urinary arsenic species are an established biomarker of recent exposure; we compare arsenic concentrations in historically collected urine samples with predicted estimates of arsenic exposure.

Paternal psychopathology and maternal depressive symptom trajectory during the first year postpartum.

Understanding parental psychopathology interaction is important in preventing negative family outcomes. This study investigated the effect of paternal psychiatric history on maternal depressive symptom trajectory from birth to 12 months postpartum. Maternal Edinburgh Postpartum Depression screens were collected at 1, 6 and 12 months and fathers' psychiatric diagnoses were assessed with the Structured Clinical Interview for DSM-IV from 64 families.

Multiple cytokines and chemokines are associated with rheumatoid arthritis-related autoimmunity in first-degree relatives without rheumatoid arthritis: Studies of the Aetiology of Rheumatoid Arthritis (SERA).

Objective: We investigated whether rheumatoid arthritis (RA)-related autoantibodies were associated with systemic inflammation in a prospective cohort of first-degree relatives (FDRs) of RA probands, a population without RA but at increased risk for its future development.

Methods: We studied 44 autoantibody positive FDRs, of whom 29 were rheumatoid factor (RF) positive, 25 were positive for the high risk autoantibody profile (HRP), that is, positive for anti-cyclic citrullinated peptide and/or for at least two RF IgM, IgG or IgA isotypes, and nine FDRs who were positive for both; and 62 FDRs who were never autoantibody positive. Twenty-five cytokines/chemokines were measured using a bead-based assay in serum.

Mothers and fathers do not accurately report each other's psychopathology.

It is unclear whether information obtained from a one parent can be used to infer the other parent's history of psychopathology. Two hundred and one parental dyads were asked to complete psychiatric interviews. Based on maternal report, non-participating husbands/ fathers had higher rates than participating fathers of psychiatric illness.

Antidepressants may mitigate the effects of prenatal maternal anxiety on infant auditory sensory gating.

Objective: Prenatal maternal anxiety has detrimental effects on the offspring's neurocognitive development, including impaired attentional function. Antidepressants are commonly used during pregnancy, yet their impact on offspring attention and their interaction with maternal anxiety has not been assessed. The authors used P50 auditory sensory gating, a putative marker of early attentional processes measurable in young infants, to assess the impact of maternal anxiety and antidepressant use.

Acculturation, maternal cortisol, and birth outcomes in women of Mexican descent.

Objective: This study investigated the effects of acculturation on cortisol, a biological correlate of maternal psychological distress, and perinatal infant outcomes, specifically gestational age at birth and birth weight.

Methods: Fifty-five pregnant women of Mexican descent were recruited from a community hospital, and their saliva samples were collected at home for 3 days during pregnancy at 15 to 18 weeks (early), 26 to 32 weeks (mid), and more than 32 weeks (late) of gestation and once in the postpartum period (4-12 weeks). These values were used to determine the diurnal cortisol slope at each phase of pregnancy.

Solutions for Determining the Significance Region Using the Johnson-Neyman Type Procedure in Generalized Linear (Mixed) Models.

Researchers often compare the relationship between an outcome and covariate for two or more groups by evaluating whether the fitted regression curves differ significantly. When they do, researchers need to determine the "significance region," or the values of the covariate where the curves significantly differ. In analysis of covariance (ANCOVA), the Johnson-Neyman procedure can be used to determine the significance region; for the hierarchical linear model (HLM), the Miyazaki and Maier (M-M) procedure has been suggested.

Influence of age and nature of primary infection on varicella-zoster virus-specific cell-mediated immune responses.

Background: Varicella-zoster virus (VZV)-specific cell-mediated immunity is important for protection against VZV disease. We studied the relationship between VZV cell-mediated immunity and age after varicella or VZV vaccination in healthy and human immunodeficiency virus (HIV)-infected individuals.

Methods: VZV responder cell frequency (RCF) determinations from 752 healthy and 200 HIV-infected subjects were used to identify group-specific regression curves on age.

Initial phase 2 trial of a nicotinic agonist in schizophrenia.

Objective: Nicotinic acetylcholine receptors are possible therapeutic targets for schizophrenia, as shown by neurobiological and molecular evidence for deficiencies in expression of alpha(7)-nicotinic receptors. Patients' heavy smoking suggests attempted self-medication through this mechanism. The agent 3-(2,4-dimethoxybenzylidene) anabaseine (DMXB-A) is a partial alpha(7)-nicotinic agonist and can be taken orally.

The stability of inhibitory and working memory deficits in children and adolescents who are children of parents with schizophrenia.

Cognitive deficits are a central feature of schizophrenia and occur in first-degree relatives of schizophrenic probands, even in the absence of psychotic symptoms. A number of cognitive domains have been implicated including measures of response inhibition and working memory. While the stability of cognitive deficits has been demonstrated in individuals with schizophrenia, stability of deficits has not been explored in first-degree relatives.

Permutation-based adjustments for the significance of partial regression coefficients in microarray data analysis.

The aim of this paper is to generalize permutation methods for multiple testing adjustment of significant partial regression coefficients in a linear regression model used for microarray data. Using a permutation method outlined by Anderson and Legendre [1999] and the permutation P-value adjustment from Simon et al. [2004], the significance of disease related gene expression will be determined and adjusted after accounting for the effects of covariates, which are not restricted to be categorical.