Pooling of clodronate urinary excretion data: a new pharmacokinetic method to study drugs with highly variable gastrointestinal absorption

OBJECTIVE: Our purpose was to study effects of vibroacoustic stimuli on electrocortical activity and heart rate changes in fetal sheep in utero. STUDY DESIGN: Seven chronically instrumented near-term fetal sheep were repeatedly stimulated by an electronic artificial larynx for 32 seconds during periods of rapid-eye-movement and non-rapid-eye-movement sleep. Responses to vibroacoustic stimulation were obtained by spectral analysis of the electrocorticogram (fast Fourier transform) and by assessment of changes in fetal heart rate and fetal heart rate variability. RESULTS: During non-rapid-eye-movement sleep vibroacoustic stimulation led to electrocorticogram desynchronization that consisted of a marked reduction of delta and theta band power (p < 0.05). A concomitant fetal heart rate decrease and fetal heart rate variability increase were also noted (p < 0.05). During rapid-eye-movement sleep vibroacoustic stimulation induced a significant increase in alpha and beta band power (p < 0.05) and a slight deviation in basal fetal heart rate and fetal heart rate variability (p < 0.05). CONCLUSION: Vibroacoustic stimulation of fetal sheep provokes reproducible changes in fetal electrocortical activity and heart rate patterns. These changes, which are not easily identifiable in gross polygraphic assessments of the fetal behavioral state, are indicative of fetal arousal.     

The case of the mistaken dependent variable.

Considers that in studying self-reinforcement 2 types of research methodologies should be considered: how performance standards of self-reward are acquired and whether or not self-administered consequences affect behavior. Considerations in interpreting studies of self-reinforcement are examined in terms of recent studies of modeling influences on children's standards of performance for self-reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Panic attacks in the nonclinical population: An empirical approach to case identification.

Although self-reports of panic attacks are common among student populations, it is not clear that their panic experiences are actually comparable to those of patients with clinical anxiety disorders. An empirical approach was taken to this problem by using a cluster analysis procedure to identify Ss within 2 samples of university students who reported panic attack symptom profiles that resembled those of patients with panic disorder. Such empirically defined "clinical" panic attacks were reported by 7 and 8.1% of the 2 samples. This predominantly female group accounted for most of the increased psychopathology that has been reported in previous studies of nonclinical panic. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Psychotherapy and the twelve step approach for substance abusers: The limits of integration.

Argues that while there is potential for successful blending of 12-step approaches and psychotherapies for chemical dependency at the level of helping strategies/techniques, some basic differences in values and philosophy will make it impossible to ever fully integrate the 2 approaches without compromising one or the other approach. Some of the differences between the 2 approaches involve leadership (indigenous vs professional), individual control (increasing vs decreasing), and spirituality (enhanced vs decreased). Given that psychotherapy and the 12-step approach must remain largely independent, a model for interactions based on mutual respect, independent control, and cooperation is suggested. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Value and limits of the criteria and scale approach in clinical research in psychiatry

Interests and limitations of rating scales and diagnostic criteria are quite well figured by their psychometric qualities. Some of those qualities are described. What is being measured, the purpose of the instrument and the compatibility of those qualities are discussed. Some examples driven from clinical research are shown.     

Asymptotic confidence limits for the difference between two squared multiple correlations: A simplified approach.

This article develops equations for determining the asymptotic confidence limits for the difference between 2 squared multiple correlation coefficients. The present procedure uses the delta method described by I. Olkin and J. D. Finn (1995) but does not require the variance-covariance matrix and the partial derivatives for all the zero-order correlations that enter into the expression for the difference, as does their procedure. This simplified approach can lead to an extreme reduction in the calculations required, as well as a reduction in the mathematical complexity of the solution. This approach also demonstrates clearly that in some cases, it may be inappropriate to use the asymptotic confidence limits in tests of significance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Psychodynamic approach to the addictive personality structure specific for alcohol and hard drugs

The overconsumption of psychotropic substances is a major problem for contemporary societies. In the USA, 14.1% of the population between the age 15 and 54 have experienced addiction problems to alcohol during their lives while as 7.5% are addicted for life to other drugs (cannabis, cocaine, stimulants, etc). Many studies report that excessive consumption of alcohol, with or without illegal drug use, is associated to social conditions favoring the development of psychological distress and isolation. Although there are many studies on the differences between personality traits of alcoholics and drug users, few authors have examined the possibility to bring to the fore a specificity between the personality structures of the alcoholic and the drug user from a psychodynamic approach. This exploratory review of literature, first presents studies already conducted in order to identify common or distinct personality features for these types of addition. This article then reviews psychodynamic writings examining the possibility of a structural organization that is specific to addiction. Finally, the authors propose a few thoughts allowing to postulate on the existence of a structural organization specific to these two types of addiction.     

A three-step procedure for assessing bioequivalence in the general mixed model framework

Bioavailability data arising from a standard two-period cross-over study are routinely analysed to establish bioequivalence between test and reference formulations. Current regulatory guidelines only require evidence of equivalence in average bioavailability for the assessment of bioequivalence. Under normality assumptions, this is achieved by demonstrating equivalence between the formulation means (step 1). However, the equivalence of formulation variances should also be assessed to get evidence of population bioequivalence (step 2), since a difference in variability of bioavailability may also pose significant problems in drug safety and efficacy. On the other hand, even population bioequivalence does not ensure that an individual subject could be expected to respond similarly to the two formulations. Therefore, whenever individual bioequivalence is the ultimate goal, the magnitude of intra-subject correlation should always be examined as the final stage (step 3). In this paper, these three successive concepts of bioequivalence are cast into the general mixed model framework and a stepwise testing procedure for the global assessment of bioequivalence is proposed. In addition to this, important issues addressed in the regulatory guidelines, such as verification of the model assumptions and application of the log-transformation, are discussed. Lastly, an example is presented to illustrate the proposed three-step procedure on the original and log-transformed scale of measurement.     

An adaptive finite-element approach for the analysis of dental restorations

The present paper deals with the problem of stresses generated during the setting process of polymer tooth fillings. A finite element procedure capable of accurately predicting the stresses along an interface between two different materials is presented. Adaptation of the finite element mesh is carried out based on a simple error estimator. The procedure is tested against benchmark problems and then applied to polymer tooth fillings. The results of the study are relevant in understanding and improving the behaviour of dental restorations.     

Surgical widening of strictures in the small intestine in Crohn disease

Twenty-two stricture plasties were performed in five patients with multiple stenosis of the small intestine due to Crohn's disease. Immediate post-operative results were satisfactory but progressive degradation followed. These findings are similar to those reported in the literature on this technique which does not give better results than other methods since none have an effect on the clinical course of the disease. The only advantage is to decrease the amount of intestinal mutilation.     

Use of the repeated cross-over designs in assessing bioequivalence

We consider applications of the repeated 2 x 2 cross-over design to evaluating bioequivalence between the two formulations. The repeated 2 x 2 cross-over design allows us not only to assess bioequivalence on average bioavailability and to examine the subject-by-formulation interaction but also to obtain independent unbiased estimates of intrasubject variability. One consequence of unequal intrasubject variabilities is that the sum of squares of intersubject residuals and the sum of squares of subject-by-formulation residuals are not independent. We also discuss the relative merits of this design as compared to the standard 2 x 2 cross-over design without repeated measurements in terms of precision and sample size with respect to the ratio of the number of subjects to the repeated measurements per subject. We investigate other uses of the 2 x 2 cross-over in examining the bioequivalence between the two different dosing regimens. Possible applications of other repeated cross-over designs to bioequivalence for more than two formulations are explored. A numerical example illustrates the proposed procedure.     

Presentation of the intrasubject coefficient of variation for sample size planning in bioequivalence studies

Bioequivalence studies are generally performed as crossover studies and, therefore, information on the intrasubject coefficient of variation is needed for sample size planning. Unfortunately, this information is usually not presented in publications on bioequivalence studies, and only the pooled inter- and intrasubject coefficient of variation for either test or reference formulation is reported. Thus, the essential information for sample size planning of future studies is not made available to other researchers. In order to overcome such shortcomings, the presentation of results from bioequivalence studies should routinely include the intrasubject coefficient of variation. For the relevant coefficients of variation, theoretical background together with modes of calculation and presentation are given in this communication with particular emphasis on the multiplicative model.     

Double-strand conformation polymorphism (DSCP) analysis of the mitochondrial control region generates highly variable markers for population studies in a social insect

Genetic markers were obtained for the termite Nasutitermes corniger by DSCP (double-strand conformation polymorphism) analysis of PCR-amplified mitochondrial control region DNA. This procedure revealed twenty-one haplotypes in forty-four colonies, whereas a restriction fragment length polymorphism analysis detected only nine haplotypes. Sequence analysis of DSCP fragments of contrasting mobilities suggests that the electrophoretic haplotypes are caused by DNA curvature in this highly AT-rich region. DSCP markers showed that some termite colonies contained maternally unrelated queens, each of which produced worker offspring. This pattern is consistent with nest founding by unrelated queens. Due to the availability of conserved primers for the mtDNA control region, DSCP analysis may readily reveal comparatively high levels of variation in a wide variety of organisms.