Remote, subsurface detection of the algal toxin domoic acid onboard the Environmental Sample Processor: Assay development and field trials

The ability to detect harmful algal bloom (HAB) species and their toxins in real- or near real-time is a critical need for researchers studying HAB/toxin dynamics, as well as for coastal resource managers charged with monitoring bloom populations in order to mitigate their wide ranging impacts. The Environmental Sample Processor (ESP), a robotic electromechanical/fluidic system, was developed for the autonomous, subsurface application of molecular diagnostic tests and has successfully detected several HAB species using DNA probe arrays during field deployments. Since toxin production and thus the potential for public health and ecosystem effects varies considerably in natural phytoplankton populations, the concurrent detection of HAB species and their toxins onboard the ESP is essential. We describe herein the development of methods for extracting the algal toxin domoic acid (DA) from Pseudonitzschia cells (extraction efficiency >90%) and testing of samples using a competitive ELISA onboard the ESP. The assay detection limit is in the low ng/mL range (in extract), which corresponds to low ng/L levels of DA in seawater for a 0.5 L sample volume acquired by the ESP. We also report the first in situ detection of both a HAB organism (i.e., Pseudo-nitzschia) and its toxin, domoic acid, via the sequential (within 2-3 h) conduct of species- and toxin-specific assays during ESP deployments in Monterey Bay, CA, USA. Efforts are now underway to further refine the assay and conduct additional calibration exercises with the aim of obtaining more reliable, accurate estimates of bloom toxicity and thus their potential impacts. Published by Elsevier B.V.

No Association of Dysbindin With Symptom Factors of Schizophrenia in an Irish Case-Control Sample

Robust associations between the dysbindin gene (DTNBP1) and schizophrenia have been demonstrated in many but not all samples, and evidence that this gene particularly predisposes to negative symptoms in this illness has been presented. The current study sought to replicate the previously reported negative symptom associations in an Irish case-control sample. Association between dysbindin and schizophrenia has been established in this cohort, and a factor analysis of the assessed symptoms yielded three factors, Positive, Negative, and Schneiderian. The sequential addition method was applied using UNPHASED to assess the relationship between these symptom factors and the high-risk haplotype. No associations were detected for any of the symptom factors indicating that the dysbindin risk haplotype does not predispose to a particular group of symptoms in this sample. Several possibilities, such as differing risk haplotypes, may explain this finding. (C) 2009 Wiley-Liss, Inc.

Replication of association between schizophrenia and ZNF804A in the Irish Case-Control Study of Schizophrenia sample

A recent genome-wide association study reported association between schizophrenia and the ZNF804A gene on chromosome 2q32.1. We attempted to replicate these findings in our Irish Case-Control Study of Schizophrenia (ICCSS) sample (N=1021 cases, 626 controls). Following consultation with the original investigators, we genotyped three of the most promising single-nucleotide polymorphisms (SNPs) from the Cardiff study. We replicate association with rs1344706 (trend test one-tailed P=0.0113 with the previously associated A allele) in ZNF804A. We detect no evidence of association with rs6490121 in NOS1 (one-tailed P=0.21), and only a trend with rs9922369 in RGRIP1L (one-tailed P=0.0515). On the basis of these results, we completed genotyping of 11 additional linkage disequilibrium-tagging SNPs in ZNF804A. Of 12 SNPs genotyped, 11 pass quality control criteria and 4 are nominally associated, with our most significant evidence of association at rs7597593 (P=0.0013) followed by rs1344706. We observe no evidence of differential association in ZNF804A on the basis of family history or sex of case. The associated SNP rs1344706 lies in approximately 30 bp of conserved mammalian sequence, and the associated A allele is predicted to maintain binding sites for the brain-expressed transcription factors MYT1l and POU3F1/OCT-6. In controls, expression is significantly increased from the A allele of rs1344706 compared with the C allele. Expression is increased in schizophrenic cases compared with controls, but this difference does not achieve statistical significance. This study replicates the original reported association of ZNF804A with schizophrenia and suggests that there is a consistent link between the A allele of rs1344706, increased expression of ZNF804A and risk for schizophrenia.

The dystrobrevin binding protein 1 (DTNBP1) gene is associated with schizophrenia in the Irish Case Control Study of Schizophrenia (ICCSS) sample

Background: DTNBP1 is associated with schizophrenia in many studies, but the associated alleles and haplotypes vary between samples.

Genetic Variation in the Serotonin 2A Receptor and Suicidal Ideation in a Sample of 270 Irish High-Density Schizophrenia Families

Genetic variation in the serotonin 2A receptor (HTR2A) has been associated with both schizophrenia and suicidal behavior. Our sample comprised 270 Irish high-density schizophrenia families (n = 1,408 subjects, including 755 with psychotic illness). Diagnoses were generated using a modified SCID. All patients who had at least one episode of psychosis were rated on the Operation Criteria Checklist for Psychotic Illness (OPCRIT). Lifetime history of suicidal ideation was determined from medical records and psychiatric interviews and was scored in the OPCRIT. Twelve SNPs were selected for study. Ten of these were tagSNPs derived from HapMap data, along with His452Tyr and T102C. We tested for association with psychotic illness as a whole, as well as stratified by the presence of suicidal ideation, using FBAT and PDTPHASE. Single-marker as well as haplotype-based tests using a

The trace amine associated receptor (TAAR6) gene is not associated with schizophrenia in the Irish Case-Control Study of Schizophrenia (ICCSS) sample

To replicate previous association between TAAR6 and schizophrenia, including our own finding in the Irish Study of High Density Schizophrenia Families (ISHDSF) sample, we genotyped 12 single nucleotide polymorphisms (SNPs) in the Irish Case-Control Study of Schizophrenia (ICCSS) sample. Only rs9389020 provided nominal evidence for association (p

Impact of Sample Heterogeneity on Methylation Analysis

The recent emergence of high-throughput arrays for methylation analysis has made the influence of tumor content on the interpretation of methylation levels increasingly pertinent. However, to what degree does tumor content have an influence, and what degree of tumor content makes a specimen acceptable for accurate analysis remains unclear. Taking a systematic approach, we analyzed 98 unselected formalin-fixed and paraffin-embedded gastric tumors and matched normal tissue samples using the Illumina GoldenGate methylation assay. Unsupervised hierarchical clustering showed 2 separate clusters with a significant difference in average tumor content levels. The probes identified to be significantly differentially methylated between the tumors and normals also differed according to the tumor content of the samples included, with the sensitivity of identifying the

Factor structure and validity of the Alcohol Use Disorders Identification Test (AUDIT) in a sample of mentally disordered offenders

Investigations of the factor structure of the Alcohol Use Disorders Identification Test (AUDIT) have produced conflicting results. The current study assessed the factor structure of the AUDIT for a group of Mentally Disordered Offenders (MDOs) and examined the pattern of scoring in specific subgroups. The sample comprised 2005 MDOs who completed a battery of tests including the AUDIT. Confirmatory factor analyses revealed that a two-factor solution – alcohol consumption and alcohol-related consequences – provided the best data fit for AUDIT scores. A three-factor solution provided an equally good fit, but the second and third factors were highly correlated and a measure of parsimony also favoured the two-factor solution. This study provides useful information on the factor structure of the AUDIT amongst a large MDO population, while also highlighting the difficulties associated with the presence of people with mental health problems in the criminal justice system.

Self-esteem and self-efficacy: Associations with alcohol consumption in a sample of adolescents in Northern Ireland

Cross-sectional and longitudinal studies have reported equivocal findings regarding the association between self-esteem, self-efficacy and adolescent alcohol use. Data were collected from a sample of 11-16-year olds in Northern Ireland (n = 4088) over two consecutive academic years measuring global self-esteem, academic, social and emotional self-efficacy and alcohol involvement. Results showed a domain-specific association between alcohol involvement and self-efficacy, with more problematic alcohol use associated with higher social self-efficacy but lower emotional and academic self-efficacy. Additionally, regression analyses revealed that all self-concept measures significantly predicted drinking group membership. The results are discussed in terms of reported drinking behaviour, interventions with adolescent groups and general development.

Effort-reward imbalance at work and the co-occurrence of lifestyle risk factors: cross-sectional survey in a sample of 36,127 public sector employees

Background: In occupational life, a mismatch between high expenditure of effort and receiving few rewards may promote the co-occurrence of lifestyle risk factors, however, there is insufficient evidence to support or refute this hypothesis. The aim of this study is to examine the extent to which the dimensions of the Effort-Reward Imbalance (ERI) model - effort, rewards and ERI - are associated with the co-occurrence of lifestyle risk factors.