Thinking About the Future Cognitive Remediation Therapy—What Works and Could We Do Better?

This article reviews progress in the development of effective cognitive remediation therapy (CRT) and its translational process. There is now enough evidence that cognitive difficulties experienced by people with schizophrenia can change and that the agenda for the next generation of studies is to increase these effects systematically through cognitive remediation. We examine the necessary steps and challenges of moving CRT to treatment dissemination. Theories which have been designed to explain the effects of cognitive remediation, are important but we conclude that they are not essential for dissemination which could progress in an empirical fashion. One apparent barrier is that cognitive remediation therapies look different on the surface. However, they still tend to use many of the same training procedures. The only important marker for outcome identified in the current studies seems to be the training emphasis. Some therapies concentrate on massed practice of cognitive functions, whereas others also use direct training of strategies. These may produce differing effects as noted in the most recent meta-analyses. We recommend attention to several critical issues in the next generation of empirical studies. These include developing more complex models of the therapy effects that take into account participant characteristics, specific and broad cognitive outcomes, the study design, as well as the specific and nonspecific effects of treatment, which have rarely been investigated in this empirical programme

Mutations in PIK3CA are infrequent in neuroblastoma

BACKGROUND: Neuroblastoma is a frequently lethal pediatric cancer in which MYCN genomic amplification is highly correlated with aggressive disease. Deregulated MYC genes require co-operative lesions to foster tumourigenesis and both direct and indirect evidence support activated Ras signaling for this purpose in many cancers. Yet Ras genes and Braf, while often activated in cancer cells, are infrequent targets for activation in neuroblastoma. Recently, the Ras effector PIK3CA was shown to be activated in diverse human cancers. We therefore assessed PIK3CA for mutation in human neuroblastomas, as well as in neuroblastomas arising in transgenic mice with MYCN overexpressed in neural-crest tissues. In this murine model we additionally surveyed for Ras family and Braf mutations as these have not been previously reported. METHODS: Sixty-nine human neuroblastomas (42 primary tumors and 27 cell lines) were sequenced for PIK3CA activating mutations within the C2, helical and kinase domain "hot spots" where 80% of mutations cluster. Constitutional DNA was sequenced in cases with confirmed alterations to assess for germline or somatic acquisition. Additionally, Ras family members (Hras1, Kras2 and Nras) and the downstream effectors Pik3ca and Braf, were sequenced from twenty-five neuroblastomas arising in neuroblastoma-prone transgenic mice. RESULTS: We identified mutations in the PIK3CA gene in 2 of 69 human neuroblastomas (2.9%). Neither mutation (R524M and E982D) has been studied to date for effects on lipid kinase activity. Though both occurred in tumors with MYCN amplification the overall rate of PIK3CA mutations in MYCN amplified and single-copy tumors did not differ appreciably (2 of 31 versus 0 of 38, respectively). Further, no activating mutations were identified in a survey of Ras signal transduction genes (including Hras1, Kras2, Nras, Pik3ca, or Braf genes) in twenty-five neuroblastic tumors arising in the MYCN-initiated transgenic mouse model. CONCLUSION: These data suggest that activating mutations in the Ras/Raf-MAPK/PI3K signaling cascades occur infrequently in neuroblastoma. Further, despite compelling evidence for MYC and RAS cooperation in vitro and in vivo to promote tumourigenesis, activation of RAS signal transduction does not constitute a preferred secondary pathway in neuroblastomas with MYCN deregulation in either human tumors or murine models

Subjective response to antipsychotic treatment and compliance in schizophrenia. A naturalistic study comparing olanzapine, risperidone and haloperidol (EFESO Study)

BACKGROUND: In order to compare the effectiveness of different antipsychotic drugs in the treatment of schizophrenia it is very important to evaluate subjective response and compliance in patient cohorts treated according to routine clinical practice. METHOD: Outpatients with schizophrenia entered this prospective, naturalistic study when they received a new prescription for an antipsychotic drug. Treatment assignment was based on purely clinical criteria, as the study did not include any experimental intervention. Patients treated with olanzapine, risperidone or haloperidol were included in the analysis. Subjective response was measured using the 10-item version of the Drug Attitude Inventory (DAI-10), and treatment compliance was measured using a physician-rated 4 point categorical scale. RESULTS: A total of 2128 patients initiated treatment (as monotherapy) with olanzapine, 417 with risperidone, and 112 with haloperidol. Olanzapine-treated patients had significantly higher DAI-10 scores and significantly better treatment compliance compared to both risperidone- and haloperidol-treated patients. Risperidone-treated patients had a significantly higher DAI-10 score compared to haloperidol-treated patients. CONCLUSION: Subjective response and compliance were superior in olanzapine-treated patients, compared to patients treated with risperidone and haloperidol, in routine clinical practice. Differences in subjective response were explained largely, but not completely, by differences in incidence of EPS

Age-dependency of the prognostic impact of tumor genomics in localized resectable MYCN non-amplified neuroblastomas Report from the SIOPEN Biology Group on the LNESG Trials

BACKGROUND: Biology based treatment reduction, i.e. surgery alone also in case of not totally resected tumors, was advised in neuroblastoma patients with localized resectable disease without MYCN amplification. However, whether the genomic background of these tumors may influence outcome was unknown and therefore scrutinized in a meta-analysis comprising two prospective therapy studies and a ‘validation’ cohort. PATIENTS AND METHODS: Diagnostic samples were derived from 406 INSS stages 1/2A/2B tumors from three cohorts: LNESGI/II and COG. Genomic data were analyzed in two age groups (cut-off: 18 months) and quality controlled by the SIOPEN Biology Group. RESULTS: In both patient age groups stage 2 tumors led to similarly reduced event-free survival (5y-EFS: 83+3% versus 80+4%), but overall survival was only decreased in patients >18m (5y-OS: 97+1% versus 87+4%; p=0.001). In the latter age subgroup, only tumors with SCA led to relapses, with 11q loss as the strongest marker (5y-EFS: 40+15% versus 89+5%; p18m but not <18m. CONCLUSION: The tumor genomic make-up of resectable non-MYCN amplified stage 2 neuroblastomas has a distinct age-dependent prognostic impact in neuroblastoma patients. While in the younger age group tumors with unfavourable (SCA) and favorable genetics showed relapses, both without worsening OS, in the older age group only tumors with unfavorable genetics led to relapses and decreased OS.N/

A statistical approach to quantitative data validation focused on the assessment of students' perceptions about biotechnology

Student awareness levels are frequently used to evaluate the effectiveness of educational policies to promote scientific literacy. Over the last years several studies have been developed to assess students' perceptions towards science and technology, which usually rely on quantitative methods to achieve broad characterizations, and obtain quantifiable and comparable data. Although the usefulness of this information depends on its validity and reliability, validation is frequently neglected by researchers with limited background in statistics. In this context, we propose a guideline to implement a statistical approach to questionnaire validation, combining exploratory factor analysis and reliability analysis. The work focuses on the psychometric analysis of data provided by a questionnaire assessing 1196 elementary and high school students' perceptions about biotechnology. Procedural guidelines to enhance the efficiency of quantitative inquiry surveys are given, by discussing essential methodological aspects and relevant criteria to integrate theory into practice.The authors are grateful to all the participant teachers and students that contributed to gather the data presented and to Catarina L. Santos for useful comments and suggestions on the manuscript. Maria Joao Fonseca was supported by the FCT fellowship SFRH/BD/37389/2007 and this work was sponsored by a research grant (PTDC/AGR-PRO/111857/2009) from Fundacao para a Ciencia e Tecnologia (FCT, Portugal)

Planning and problem-solving training for patients with schizophrenia: a randomized controlled trial

BACKGROUND: The purpose of this study was to assess whether planning and problem-solving training is more effective in improving functional capacity in patients with schizophrenia than a training program addressing basic cognitive functions. METHODS: Eighty-nine patients with schizophrenia were randomly assigned either to a computer assisted training of planning and problem-solving or a training of basic cognition. Outcome variables included planning and problem-solving ability as well as functional capacity, which represents a proxy measure for functional outcome. RESULTS: Planning and problem-solving training improved one measure of planning and problem-solving more strongly than basic cognition training, while two other measures of planning did not show a differential effect. Participants in both groups improved over time in functional capacity. There was no differential effect of the interventions on functional capacity. CONCLUSION: A differential effect of targeting specific cognitive functions on functional capacity could not be established. Small differences on cognitive outcome variables indicate a potential for differential effects. This will have to be addressed in further research including longer treatment programs and other settings

A modern network approach to revisiting the positive and negative affective schedule (PANAS) construct validity

Introduction: The factor structure of the Positive and Negative Affective Schedule (PANAS) is still a topic of debate. There are several reasons why using Exploratory Graph Analysis (EGA) for scale validation is advantageous and can help understand and resolve conflicting results in the factor analytic literature. Objective: The main objective of the present study was to advance the knowledge regarding the factor structure underlying the PANAS scores by utilizing the different functionalities of the EGA method. EGA was used to (1) estimate the dimensionality of the PANAS scores, (2) establish the stability of the dimensionality estimate and of the item assignments into the dimensions, and (3) assess the impact of potential redundancies across item pairs on the dimensionality and structure of the PANAS scores. Method: This assessment was carried out across two studies that included two large samples of participants. Results and Conclusion: In sum, the results are consistent with a two-factor oblique structure.Fil: Flores Kanter, Pablo Ezequiel. Universidad Empresarial Siglo XXI; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garrido, Luis Eduardo. Pontificia Universidad Católica Madre y Maestra; República DominicanaFil: Moretti, Luciana Sofía. Universidad Empresarial Siglo XXI; Argentina. Pontificia Universidad Católica Madre y Maestra; República Dominicana. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Medrano, Leonardo. Universidad Empresarial Siglo XXI; Argentina. Pontificia Universidad Católica Madre y Maestra; República Dominicana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Working Memory Training Using Mental Calculation Impacts Regional Gray Matter of the Frontal and Parietal Regions

Training working memory (WM) improves performance on untrained cognitive tasks and alters functional activity. However, WM training's effects on gray matter morphology and a wide range of cognitive tasks are still unknown. We investigated this issue using voxel-based morphometry (VBM), various psychological measures, such as non-trained WM tasks and a creativity task, and intensive adaptive training of WM using mental calculations (IATWMMC), all of which are typical WM tasks. IATWMMC was associated with reduced regional gray matter volume in the bilateral fronto-parietal regions and the left superior temporal gyrus. It improved verbal letter span and complex arithmetic ability, but deteriorated creativity. These results confirm the training-induced plasticity in psychological mechanisms and the plasticity of gray matter structures in regions that have been assumed to be under strong genetic control