Hannu Oja

The role of acute and chronic stress in asthma attacks in children

BACKGROUND High levels of stress have been shown to predict the onset of asthma in children genetically at risk, and to correlate with higher asthma morbidity. Our study set out to examine whether stressful experiences actually provoke new exacerbations in children who already have asthma. METHODS A group of child patients with verified chronic asthma were prospectively followed up for 18 months. We used continuous monitoring of asthma by the use of diaries and daily peak-flow values, accompanied by repeated interview assessments of life events and long-term psychosocial experiences. The key measures included asthma exacerbations, severely negative life events, and chronic stressors. FINDINGS Severe events, both on their own and in conjunction with high chronic stress, significantly increased the risk of new asthma attacks. The effect of severe events without accompanying chronic stress involved a small delay; they had no effect within the first 2 weeks, but significantly increased the risk in the subsequent 4 weeks (odds ratio 1.71 [95% CI 1.04-2.82], p < or = 0.05 for weeks 2-4 and 2.17 [1.32-3.57], p < or = 0.01 for weeks 4-6). When severe events occurred against the backdrop of high chronic stress, the risk increased sharply and almost immediately within the first fortnight (2.98 [1.20-7.38], p < or = 0.05). The overall attack frequency was affected by several factors, some related to asthma and some to child characteristics. Female sex, higher baseline illness severity, three or more attacks within 6 months, autumn to winter season, and parental smoking were all related to increased risk of new exacerbations; social class and chronic stress were not. INTERPRETATION Severely negative life events increase the risk of childrens asthma attacks over the coming few weeks. This risk is magnified and brought forward in time if the childs life situation is also characterised by multiple chronic stressors.

Descriptive Statistics for Multivariate Distributions

The purpose of this paper is to study the concepts location, scatter, skewness and kurtosis of multivariate distributions. Measures of these properties are introduced which include some new generalizations of well-known univariate statistics. Previous work is briefly reviewed.

Characterisation of human dental stem cells and buccal mucosa fibroblasts

Human craniofacial stem cells are recently discovered sources of putative mesenchymal stem cells that hold great promise for autogenic or allogenic cell therapy and tissue engineering. Prior to employing these cells in clinical applications, they must be thoroughly investigated and characterized. In this study, the surface marker expression was investigated on dental pulp stem cells (DPSCs), dental follicle cells (DFCs), periodontal ligament stem cells (PDLSCs), and buccal mucosa fibroblasts (BMFs) utilising surface markers for flow cytometry. The osteogenic potential was also examined by bone-associated markers alkaline phosphatase, Runx2, collagen type I, osteocalcin, and osteopontin. The results from our study demonstrate that the dental cell sources exhibit comparable surface marker and bone-associated marker profiles parallel to those of other mesenchymal stem cell sources, yet distinct from the buccal mucosa fibroblasts. Our data support evidence towards clinical applicability of dental stem cells in hard tissue regeneration.

Early developmental milestones in adult schizophrenia and other psychoses. A 31-year follow-up of the Northern Finland 1966 Birth Cohort.

Delayed childhood development may precede adult psychoses. We tested this hypothesis in a large, general population birth cohort (n=12058) followed to age 31 years. The ages at which individuals learned to stand, walk, speak, and became potty-trained (bowel control) and dry (bladder control), were recorded at a 1-year examination. Psychiatric outcome was ascertained through linkage to a national hospital discharge register. Cumulative incidence of DSM-III-R schizophrenia, other psychoses and non-psychotic disorders were stratified according to the timing of milestones and compared within the cohort using internal standardization. 100 cases of DSM-III-R schizophrenia, 55 other psychoses, and 315 non-psychotic disorders were identified. The ages at learning to stand, walk and become potty-trained were each related to subsequent incidence of schizophrenia and other psychoses. Compared with the whole cohort, earlier milestones reduced, and later milestones increased, the risk in a linear manner. These developmental effects were not seen for non-psychotic outcomes. The findings support hypotheses regarding psychosis as having a developmental dimension with precursors apparent in early life.

Multivariate spatial sign and rank methods

Rotation invariant multivariate spatial sign and rank tests and corresponding rotation equivariant estimates based on L1 type objective function with Euclidean distance are considered. Multivariate spatial analogues of sign and rank concepts, one- and two-sample sign tests, Wilcoxon rank sum and signed rank tests, median and Hodges-Lehmann estimates are reviewed and discussed. Connections with other generalization are considered. The testing theory is illustrated by two examples.

miR-193b is an epigenetically regulated putative tumor suppressor in prostate cancer.

miRNAs have proven to be key regulators of gene expression and are differentially expressed in various diseases, including cancer. Our aim was to identify epigenetically dysregulated genes in prostate cancer. We performed miRNA expression profiling after relieving epigenetic modifications in 6 prostate cancer cell lines and nonmalignant prostate epithelial cells. Thirty‐eight miRNAs showed increased expression in any prostate cancer cell line after 5‐aza‐2′‐deoxycytidine (5azadC) and trichostatin A (TSA) treatments. Six of these also had decreased expression in clinical prostate cancer samples compared to benign prostatic hyperplasia. Among these, miR‐193b was methylated in 22Rv1 cell line at a CpG island ∼1 kb upstream of the miRNA locus. Expressing miR‐193b in 22Rv1 cells using pre‐miR‐193b oligonucleotides caused a significant growth reduction (p < 0.001) resulting from a decrease of cells in S‐phase of the cell cycle (p < 0.01). In addition, the anchorage independent growth was partially inhibited in transiently miR‐193b‐expressing 22Rv1 cells (p < 0.01). Altogether, our data suggest that miR‐193b is an epigenetically silenced putative tumor suppressor in prostate cancer.

Sign and rank covariance matrices

The robust estimation of multivariate location and shape is one of the most challenging problems in statistics and crucial in many application areas. The objective is to find highly efficient, robust, computable and affine equivariant location and covariance matrix estimates. In this paper, three different concepts of multivariate sign and rank are considered and their ability to carry information about the geometry of the underlying distribution (or data cloud) are discussed. New techniques for robust covariance matrix estimation based on different sign and rank concepts are proposed and algorithms for computing them outlined. In addition, new tools for evaluating the qualitative and quantitative robustness of a covariance estimator are proposed. The use of these tools is demonstrated on two rank-based covariance matrix estimates. Finally, to illustrate the practical importance of the problem, a signal processing example where robust covariance matrix estimates are needed is given.

Multivariate Nonparametric Tests

Multivariate nonparametric statistical tests of hypotheses are described for the one-sample location problem, the several-sample location problem and the problem of testing independence between pairs of vectors. These methods are based on affine-invariant spatial sign and spatial rank vectors. They provide affine-invariant multivariate generalizations of the univariate sign test, signed-rank test, Wilcoxon rank sum test, Kruskal-Wallis test, and the Kendall and Spearman correlation tests. While the emphasis is on tests of hypotheses, certain references to associated affine-equivariant estimators are included. Pitman asymptotic efficiencies demonstrate the excellent performance of these methods, particularly in heavy-tailed population settings. Moreover, these methods are easy to compute for data in common dimensions.

Perinatal outcome of pregnancies complicated by vaginal bleeding

Objective To examine the effect of first and/or second trimester vaginal bleeding on pregnancy outcome.

Is a child's risk of early onset schizophrenia increased in the highest social class?

In a sample from the unselected, general population Northern Finland 1966 Birth Cohort, 11017 individuals alive at the age of 16 years were studied until the age of 27. The cumulative incidence of early onset schizophrenia until 23 years was higher (1.14%; 9/792) among young persons from the highest social class or class I (determined according to fathers occupation) than among children from lower social classes (0.47%; 48/10225), the difference being statistically significant (p < 0.05). The incidence of schizophrenia in the highest social class was higher than expected among girls, firstborns, children of young mothers under 30 and urban residents (p < 0.05) compared with lower social classes. When cases from the highest and other social classes were compared, there was no clear difference in background factors or clinical course. Four alcoholics, one of them also schizophrenic, were found among nine social class I fathers. The results suggest that in some families in Northern Finland, a fathers professional advancement, often linked to mental disorder, may be one determinant of an increased risk of schizophrenia in the child.