Poor Response Inhibition and Symptoms of Inattentiveness Are Core Characteristics of Lifetime Illicit Substance Use among Young Adults in the General Norwegian Population: The HUNT Study.

BACKGROUND: Impairments in neurocognitive functioning are associated with substance use behavior. Previous studies in neurocognitive predictors of substance use typically use self-report measures rather than neuropsychological performance measures and suffer from low sample sizes and use of clinical diagnostic cut offs. METHODS: Crossectional data from the HUNT4 Study (Helseundersøkelsen i Trøndelag) was used to study executive neuropsychological performance and self-reported measures of neurocognitive function associated with a history of illicit substance use in a general population sample of young adults in Norway. We performed both between group comparisons and logistic regression modeling and controlled for mental health symptomatology. RESULTS: Subjects in our cohort with a self-reported use of illicit substances had significantly higher self-reported mental health and neurocognitive symptom load. A logistic regression model with substance use as response included sex, commission errors and self-reported inattentiveness and anxiety as significant predictors. After 10-fold cross-validation this model achieved a moderate area under the receiver-operator curve of 0.63. To handle the class imbalance typically found in such population data, we also calculated balanced accuracy with a optimal model cut off of 0.234 with a sensitivity of 0.50 and specificity of 0.76 as well as precision recall-area under the curve of 0.28. CONCLUSIONS: Subtle cognitive dysfunction differentiates subjects with and without a history of illicit substance use. Neurocognitive factors outperformed the effects of depressive symptoms on substance use behavior in this cohort. We highlight the need for using adequate statistical tools for evaluating the performance of models in unbalanced datasets.

Identification of novel neuroendocrine-specific tumour genes.

Neuroendocrine tumours (NETs) comprise a heterogenous group of malignancies with an often unpredictable course, and with limited treatment options. Thus, new diagnostic, prognostic, and therapeutic markers are needed. To shed new lights into the biology of NETs, we have by cDNA transcript profiling, sought to identify genes that are either up- or downregulated in NE as compared with non-NE tumour cells. A panel of six NET and four non-NET cell lines were examined, and out of 12 743 genes examined, we studied in detail the 200 most significantly differentially expressed genes in the comparison. In addition to potential new diagnostic markers (NEFM, CLDN4, PEROX2), the results point to genes that may be involved in the tumorigenesis (BEX1, TMEPAI, FOSL1, RAB32), and in the processes of invasion, progression and metastasis (MME, STAT3, DCBLD2) of NETs. Verification by real time qRT-PCR showed a high degree of consistency to the microarray results. Furthermore, the protein expression of some of the genes were examined. The results of our study has opened a window to new areas of research, by uncovering new candidate genes and proteins to be further investigated in the search for new prognostic, predictive, and therapeutic markers in NETs.

Matrix metalloproteinase 1 in pre-eclampsia and fetal growth restriction: reduced gene expression in decidual tissue and protein expression in extravillous trophoblasts.

Superficial invasion of extravillous trophoblasts (EVTs) and impaired spiral artery remodelling are characterizing phenomena in pregnancies complicated by pre-eclampsia (PE) and fetal growth restriction (FGR). However, the underlying causes remain unclear. In this study, gene expression in decidua basalis tissue from pregnancies complicated with PE and/or FGR (n = 18) and normal pregnancies (n = 17) was assessed by Affymetrix HG Focus microarray to obtain hints of mechanisms involved in the pathogenesis. A total of 200 differentially expressed transcripts were detected at a false discovery rate (FDR)

Identification of novel growth factor-responsive genes in neuroendocrine gastrointestinal tumour cells.

Targeting growth-regulatory pathways is a promising approach in cancer treatment. A prerequisite to the development of such therapies is characterisation of tumour growth regulation in the particular tumour cell type of interest. In order to gain insight into molecular mechanisms underlying proliferative responses in neuroendocrine (NE) gastrointestinal (GI) tumours, we investigated gene expression in human carcinoid BON cells after exposure to gastrin, hepatocyte growth factor (HGF), pituitary adenylate cyclase-activating polypeptide or epidermal growth factor. We particularly focused on gastrin- and HGF-induced gene expression, and identified 95 gastrin- and 101 HGF-responsive genes. The majority of these genes are known mediators of processes central in tumour biology, and a number of them have been associated with poor prognosis and metastasis in cancer patients. Furthermore, we identified 12 genes that were regulated by all four factors, indicating that they may be universally regulated during NE GI tumour cell proliferation. Our findings provide useful hypotheses for further studies aimed to search for new therapeutic targets as well as tumour markers in NE GI tumours.

Simulated likelihood methods for complex double-platform line transect surveys.

The conventional line transect approach of estimating effective search width from the perpendicular distance distribution is inappropriate in certain types of surveys, e.g., when an unknown fraction of the animals on the track line is detected, the animals can be observed only at discrete points in time, there are errors in positional measurements, and covariate heterogeneity exists in detectability. For such situations a hazard probability framework for independent observer surveys is developed. The likelihood of the data, including observed positions of both initial and subsequent observations of animals, is established under the assumption of no measurement errors. To account for measurement errors and possibly other complexities, this likelihood is modified by a function estimated from extensive simulations. This general method of simulated likelihood is explained and the methodology applied to data from a double-platform survey of minke whales in the northeastern Atlantic in 1995.