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Objective To investigate the role of hippocampal plasticity in the antidepressant effect of electroconvulsive therapy ( ECT). Method We used magnetic resonance ( MR) imaging including diffusion tensor imaging ( DTI) and proton MR spectroscopy (1 H- MRS) to investigate hippocampal volume, diffusivity, and metabolite changes in 19 patients receiving ECT for severe depression. Other regions of interest included the amygdala, dorsolateral prefrontal cortex ( DLPFC), orbitofrontal cortex, and hypothalamus. Patients received a 3 T MR scan before ECT ( TP1), 1 week ( TP2), and 4 weeks ( TP3) after ECT. Results Hippocampal and amygdala volume increased significantly at TP2 and continued to be increased at TP3. DLPFC exhibited a transient volume reduction at TP2. DTI revealed a reduced anisotropy and diffusivity of the hippocampus at TP2. We found no significant post- ECT changes in brain metabolite concentrations, and we were unable to identify a spectral signature at ≈1.30 ppm previously suggested to reflect neurogenesis induced by ECT. None of the brain imaging measures correlated to the clinical response. Conclusion Our findings show that ECT causes a remodeling of brain structures involved in affective regulation, but due to their lack of correlation with the antidepressant effect, this remodeling does not appear to be directly underlying the antidepressant action of ECT. [ABSTRACT FROM AUTHOR]

Aims: CCND1 and EMSY, on 11q13, are frequently amplified in breast cancer. CCND1 is implicated in cell cycle progression and EMSY is a BRCA2-associated repressor protein. The aim was to investigate gene copy numbers of CCND1 and EMSY and to determine if CCND1 amplification is associated with reduced survival of tamoxifen-treated breast cancer patients. Methods and results: Fluorescence in situ hybridization (FISH) was performed on 111 consecutive and 354 oestrogen receptor (ER)+ tamoxifen-treated breast cancers. In the consecutive set, CCND1 and EMSY were amplified in 14.8% and 7.2%, respectively, and deleted in 8.7% and 13.5%, respectively. In the ER+ set, CCND1 and EMSY were amplified in 20.6% and 9.6%, respectively, and deleted in 1.7% and 4.2%, respectively. CCND1 and EMSY gene amplifications were associated with decreased overall survival (OS) ( P = 0.03 and P = 0.04, respectively) of patients in the ER+ set. Conclusion: As hypothesized, CCND1 amplifications are associated with poor OS in ER+ patients. EMSY amplification is also associated with poor OS. However, as >70% of EMSY amplifications were CCND1 amplified, EMSY may not have any additional effect on survival of ER+ breast cancer. [ABSTRACT FROM AUTHOR]

Aim : Immunohistochemical analysis of protein expression is central to most clinical translational studies and defines patient treatment or selection criteria for novel drugs. Interobserver variation is rarely analysed despite recognition that this is a key area of potential inaccuracy. Therefore our aim was to examine observer variation and suggest the revision of current standards. Methods and results : We analysed inter- and intra-observer variation, by interclass correlation coefficient (ICCC) and κ statistics, in 8661 samples. Intra-observer assessment of nuclear, cytoplasmic and membrane staining for seven proteins in 1323 samples resulted in an ICCC of 0.94 and a κ-value of 0.787. Interobserver reproducibility, assessed on 28 proteins by seven observer pairs in 8661 carcinomas, gave an ICCC of 0.90 and a κ-value of 0.70. No significant effect of either antibody or cellular compartmentalization was observed. Conclusion : We have demonstrated that ICCC is a consistent method to assess observer variation when a continuous scoring system is used, compared with κ statistics, which depends on a categorical system. Given the importance of accurate assessment of protein expression in diagnostic and experimental medicine, we suggest raising thresholds for observer variation: ICCC of 0.7 should be regarded as the minimum acceptable standard, ICCC of 0.8 as good and ICCC of ≥ 0.9 as excellent. [ABSTRACT FROM AUTHOR]