On reverse engineering of gene interaction networks using time course data with repeated measurements.

MOTIVATION: Gene expression measurements are the most common data source for reverse engineering gene interaction networks. When dealing with destructive sampling in time course experiments, it is common to average any available measurements for each time point and to treat this as the actual time series data for fitting the network, neglecting the variability contained in the repeated measurements. Proceeding in such a way can affect the retrieved network topology. RESULTS: We propose a fully Bayesian method for reverse engineering a gene interaction network, based on time course data with repeated measurements. The observations are treated as surrogate measurements of the underlying gene expression. As these measurements often contain outliers, we use a non-Gaussian specification for dealing with measurement error. The network interactions are assumed linear and an autoregressive model is specified, augmented with indicator variables that allow inference on the topology of the network. We analyse two in silico and one in vivo experiments, the latter dealing with the circadian clock in Arabidopsis thaliana. A systematic attenuation of the estimated regulation strengths and a concomitant overestimation of their precision is demonstrated when measurement error is disregarded. Thus, a clear improvement in the inferred topology for the synthetic datasets is demonstrated when this is included. Also, the influence of outliers in the retrieved network is demonstrated when using the in vivo data. AVAILABILITY: Matlab code and data used in the article are available from http://go.warwick.ac.uk/majuarez/home/materials.

The stress of children's births: gender differences in the impact on alcoholics.

Previously reported gender differences regarding the role of discrete life change events in the onset of alcoholism are examined through a systematic evaluation of the histories of 586 alcoholics. Several methodological features of this research distinguish it from investigations reported in the past. The use of a structured, topically organized interview protocol eliminated possible biases introduced by gender differences in the tendency to attribute the onset of alcoholism to life change. The application of an actuarial analytic procedure allowed an examination of the temporal relationship between life change (births of children) and the onset of alcoholism and a restriction of the period of risk for the onset of alcoholism following discrete life change to two years. The focus on a single type of life change event, births of children, reflects an established concern with the role of gynecological events in the onset of alcoholism among women and allows of the general comparisons. Results indicate that, among those ever at risk of first experiencing alcohol-related problems during the two year period following the birth of a child, males show a statistically significantly higher percentage with the onset of alcoholism during this time period than do females. The birth of a first child was found to be most strongly related to the development of problem drinking. Among males, but not among females, the birth of a first child was also found to follow the onset of alcoholism by two years in a significant number of cases.

The measurement of multiple drug use and its relationship to the patterning of alcohol intake.

The increasing prevalence of multiple drug use among adolescents presents researchers with complex conceptual and measurement issues. This work examines definitions of and indicators of multiple drug use involvement, as well as the interrelationships between indices of drug involvement incorporating different dimensions. Data regarding the relationship between patterns of alcohol use and illicit drug use in a population of 1473 teenagers interviewed in a northwestern metropolitan community indicate that : (1) regardless of the dimensions incorporated into four different indices of drug involvement examined, intercorrelations between indices were strong; (2) although the correlations between indices of drug involvement and overall levels of alcohol intake were uniformly weak, it was shown that levels of drug involvement vary directly with the maximum volume of alcohol used. Although the results of the current investigation must be viewed cautiously because of the concentration of heavy users of both alcohol and drugs in the population upon which the research is based, among adolescents, the spacing of drinking episodes and the patterning of alcohol intake may be more important determinants of polydrug involvement thant the quantity of alcohol consumed.

Drug abuse among alcoholic women.

Of 293 women in an alcoholic treatment center, two-thirds have received prescriptions for drugs of potential abuse, usually hypnotic and antianxiety drugs. One-third of the women admitted abusing substances; 80% of these subjects got prescriptions for potential drugs of abuse while actively abusing. These figures are alarming in light of the lack of evidence that antianxiety drugs, hypnotics, and stimulants are effective in treating alcoholics and drug abusers. Drug-misusing women in this sample reported more suicide attempts and early antisocial problems and had received more psychiatric care than nonabusers. The authors urge that hypnotics, antianxiety drugs, and stimulants almost never be prescribed to outpatient alcoholics and that analgesics be prescribed only with great care.

Psychiatric problems in women admitted to an alcoholic detoxification center.

The authors studied 293 consecutive female admissions to a public detoxification facility. One-half had a primary diagnosis of alcoholism; the rest had primary diagnosis of affective disorder (14%), antisocial personality (14%), drug abuse (6%) or did not meet the criteria for alcoholism (13%). Each subgroup had unique social backgrounds and characteristic histories of involvement with alcohol, drugs, and antisocial problems. The primary alcoholic woman in the detoxification center resembles the primary alcoholic man in the same setting. The authors underscore the importance of socioeconomic strata and primary versus secondary diagnosis in understanding the prognosis for alcoholics.

Alcohol-related problems in adolescents and women.

In the roles of student and homemaker, youthful and female problem drinkers can easily hide alcoholism. Compared with adult male alcoholics, their intake of alcohol is less but they are more likely to use other drugs concomitantly. An understanding of their unique characteristics will help the physician recognize patients in these groups with alcohol-related problems.

Stressful life events and alcohol problems among women seen at a detoxication center.

No strong temporal associations were found between the occurrence of stressful life events and the onset of alcohol problems.

Propoxyphene and Phencyclidine (PCP) use in adolescents.

Trained interviewers utilized a structured research instrument to analyze drug use patterns, personal and familial psychiatric problems, and social backgrounds of a consecutive series of 355 adolescent referred by courts to alcohol counselling and education centers in King County. Within this sample, 4% of the subjects used propoxyphene alone, 16% reported use of phencyclidine (PCP) alone, and 6% reported abuse of both substances. The data consistently reveals that the use of one of these more unusual substances is likely to occur in people with more antisocial, drug, and alcohol problems. Use of both drugs was associated with the most pervasive antisocial history, with over one-third of these subjects fulfilling strict criteria for the antisocial personality. The treatment and prognostic implications of these findings are discussed.