A path-analytical approach to differentiate between direct and indirect drug effects on negative symptoms in schizophrenic patients

The hypothesis that differences in drug effects of risperidone and haloperidol on negative symptoms in schizophrenia are secondary to effects on positive, extrapyramidal, and depressive symptoms was investigated by means of an analysis of the data from the USA-Canada risperidone double-blind randomized clinical trial of 523 chronic schizophrenic patients. Regression analyses in the total sample and within treatment groups confirmed a strong relationship between changes in negative symptoms and the other variables studied (R²=0.50–0.51,p<0.001). Only depressive symptoms did not contribute significantly to these results (p>0.10). Path analysis showed that the greater mean change (p<0.05) of negative symptoms with risperidone compared to haloperidol could not be fully explained by correlations with favourable effects on positive and extrapyramidal symptoms. The relationship between shift in extrapyramidal symptoms and shift in negative symptoms failed to reach statistical significance; however, there was a clear tendency in the expected direction in both treatment groups.     

Ensuring data quality in a multicenter clinical trial: remote site data entry, central coordination and feedback

In an ongoing multicenter clinical trial, "Treatment Strategies in Schizophrenia," the five participating sites have the capacity to perform a variety of tasks or study functions independently. These tasks include (a) verification of diagnostic eligibility through the use of computerized decision algorithms; (b) assignment of patients to treatment based on prognostic indicators using a computerized randomization algorithm; (c) entry of data into a microcomputer using a clinical trial data management system that performs simple range and missing data item checks; and (d) regular transfer of all data to the central coordinating team. The clinical trial data management system employed allows for both independent site functioning and assurance of consistency across sites. The integration of a variety of software outside the main data management system provides the central coordinators with the tools to monitor critical data as it is collected, as well as the capacity to assess the flow, quality, and uniformity of the ongoing trial.     

The nucleophosmin-anaplastic lymphoma kinase fusion protein induces c-Myc expression in pediatric anaplastic large cell lymphomas

The majority of pediatric anaplastic large cell lymphomas (ALCLs) carry the t(2;5)(p23;q35) chromosomal translocation that juxtaposes the dimerization domain of nucleophosmin with anaplastic lymphoma kinase (ALK). The nucleophosmin-ALK fusion induces constitutive, ligand-independent activation of the ALK tyrosine kinase leading to aberrant activation of cellular signaling pathways. To study the early consequences of ectopic ALK activation, a GyrB-ALK fusion was constructed that allowed regulated dimerization with the addition of coumermycin. Expression of the fusion protein caused a coumermycin-dependent increase in cellular tyrosine phosphorylation and c-Myc immunoreactivity, which was paralleled by a rise in c-myc RNA. To assess the clinical relevance of this observation, c-Myc expression was determined in pediatric ALK-positive and -negative lymphomas. Co-expression of c-Myc and ALK was seen in tumor cells in 15 of 15 (100%) ALK-positive ALCL samples, whereas no expression of either ALK or c-Myc was seen in six of six cases of ALK-negative T-cell lymphoma. C-Myc may be a downstream target of ALK signaling and its expression a defining characteristic of ALK-positive ALCLs.     

Autonomic Correlates of Sensation Seeking and Monoamine Oxidase Activity: Using Confirmatory Factor Analysis on Psychophysiological Data

A negative relationship between platelet monoamine oxidase (MAO) activity and Sensation Seeking (SS) has been reported in several studies. This study evaluates the possible contribution of autonomic nervous system (ANS) activity to this relationship. Additionally, confirmatory factor analysis was used to create models of ANS concepts from a larger number of psychophysiological variables. Skin conductance (SC) and heart rate (HR) were recorded from 46 men and 49 women during a two-session protocol that included rest periods, a balloon stress, a series of tones, and two tasks: two-flash threshold and tachistoscopic recognition. Results showed that the best-fitting models for both rest and task periods included concepts of SC base levels (“arousal”), SC lability, and HR, and were quite similar for men and women. MAO activity correlated positively with SC concepts, most strongly for women. Women showed negative relationships between sensation seeking and both SC arousal and HR concepts. In contrast, men showed evidence of positive relationships between SC concepts and an active life style. The sex differences and response specificity in these relationships make it unlikely that ANS activity mediates the negative MAO-SS relationship.     

Family treatment for schizophrenia : the design and research application of therapist training models

The NIMH Treatment Strategies in Schizophrenia (TSS) collaborative study group investigated the efficacy of antisychotic drug maintenance strategies involving reduced medication exposure in interaction with applied and supportive family management for the long-term treatment of schizophrenia. Therapy was provided at five centers by 25 clinicians who did not participate in the development of the therapies. They were trained by two of the authors, I.R.H.F and C.W.M, in applied family management, a homebased treatment derived from the behavioral family therapy developed by them. Clinicians' characteristics, selection, and training methods, as well as patient rehospitalization rates, are reported for the two family management conditions. The TSS study represents a bridge between the development of a novel therapy and its dissemination in general clinical practice.     

Zonal differences in meniscus MR relaxation times in response to in vivo static loading in knee osteoarthritis

This study assessed the effects of static loading on MRI relaxation times of menisci in individuals with and without radiographic knee OA. High‐resolution fast spin‐echo (FSE) and T_1ρ/T₂ relaxation time MR sequences were obtained with and without loading at 50% body weight in 124 subjects. T_1ρ/T₂ relaxation times were calculated in menisci, and meniscus lesions were assessed through clinical grading. Student's t‐test compared OA and control unloaded relaxation times as well as within‐group changes with loading, Generalized Linear Models evaluated zonal variation, and ANCOVA compared loading response between groups. Unloaded T_1ρ and T₂ in the middle and inner zones of the lateral anterior horn and outer zone of the medial posterior horn were significantly higher in OA and suggest that meniscal OA change occurs unevenly. Zonal T_1ρ and T₂ showed differing patterns between anterior and posterior horns, suggesting differences in macromolecular organization. Significant increases with loading were seen largely in the T₂ of controls and less frequently in subjects with OA. In the medial posterior horn, T_1ρ and T₂ decreased with loading in OA but changed negligibly in controls; these significantly different loading responses between groups may indicate load transmission failure in OA menisci. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:249–261, 2016.     

Imaging of pediatric liver tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper

Primary hepatic malignancies are relatively rare in the pediatric population, accounting for approximately 1%–2% of all pediatric tumors. Hepatoblastoma and hepatocellular carcinoma are the most common primary liver malignancies in children under the age of 5 years and over the age of 10 years, respectively. This paper provides consensus-based imaging recommendations for evaluation of patients with primary hepatic malignancies at diagnosis and follow-up during and after therapy.     

Cigarette advertising to counter New Year's resolutions

One process through which tobacco advertising may work is by reducing rates of quitting. Theories of addiction support the notion that relapse can be prompted by environmental cues. Further, because withdrawal symptoms occur over a predictable time frame, and because the most popular time to quit smoking is the beginning of the year, as a New Year's resolution, tobacco companies can make use of advertising to remind quitters of their need to smoke. Study 1 examined advertising in 10 popular magazines. It found a higher number of ads in January and February than the rest of the year after 1984. Study 2 examined cigarette advertising on the back cover of 10 other popular magazines. This study also found a higher rate of cigarette advertisements in January and February than for the rest of the year. The results suggest that cigarette marketers may be attempting to preempt quitting by cuing smoking behavior.