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Previous literature has focused on predicting a diagnostic label from structural brain imaging. Since subtle changes in the brain precede a cognitive decline in healthy and pathological aging, our study predicts future decline as a continuous trajectory instead. Here, we tested whether baseline multimodal neuroimaging data improve the prediction of future cognitive decline in healthy and pathological aging. Nonbrain data (demographics, clinical, and neuropsychological scores), structural MRI, and functional connectivity data from OASIS-3 (N = 662; age = 46-96 years) were entered into cross-validated multitarget random forest models to predict future cognitive decline (measured by CDR and MMSE), on average 5.8 years into the future. The analysis was preregistered, and all analysis code is publicly available. Combining non-brain with structural data improved the continuous prediction of future cognitive decline (best test-set performance: R2 = 0.42). Cognitive performance, daily functioning, and subcortical volume drove the performance of our model. Including functional connectivity did not improve predictive accuracy. In the future, the prognosis of age-related cognitive decline may enable earlier and more effective individualized cognitive, pharmacological, and behavioral interventions., Competing Interests: Disclosure statement The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Bilateral in-phase (IP) and anti-phase (AP) movements represent two fundamental modes of bilateral coordination that are essential for daily living. Although previous studies have shown that aging is behaviorally associated with decline in bilateral coordination, especially in AP movements, the underlying neural mechanisms remain unclear. Here, we use kinematic measurements and electroencephalography to compare motor performance of young and older adults executing bilateral IP and AP hand movements. On the behavioral level, inter-limb synchronization was reduced during AP movements compared to IP and this reduction was stronger in the older adults. On the neural level, we found interactions between group and condition for task-related power change in different frequency bands. The interaction was driven by smaller alpha power decreases over the non-dominant cortical motor area in young adults during IP movements and larger beta power decreases over the midline region in older adults during AP movements. In addition, the decrease in inter-limb synchronization during AP movements was predicted by stronger directional connectivity in the beta-band: an effect more pronounced in older adults. Our results therefore show that age-related differences in the two bilateral coordination modes are reflected on the neural level by differences in alpha and beta oscillatory power as well as interhemispheric directional connectivity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Radiotherapy is an effective treatment of intermediate/high-risk locally advanced prostate cancer, however, >30% of patients relapse within 5 years. Clinicopathological parameters currently fail to identify patients prone to systemic relapse and those whom treatment intensification may be beneficial. The purpose of this study was to independently validate the performance of a 70-gene Metastatic Assay in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy., Patients and Methods: A bridging cohort of prostate cancer diagnostic biopsy specimens was profiled to enable optimization of the Metastatic Assay threshold before further independent clinical validation in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy. Multivariable Cox proportional hazard regression analysis was used to assess assay performance in predicting biochemical failure-free survival (BFFS) and metastasis-free survival (MFS)., Results: Gene expression analysis was carried out in 248 patients from the independent validation cohort and the Metastatic Assay applied. Ten-year MFS was 72% for Metastatic Assay positive patients and 94% for Metastatic Assay negative patients [HR = 3.21 (1.35-7.67); P = 0.003]. On multivariable analysis the Metastatic Assay remained predictive for development of distant metastases [HR = 2.71 (1.11-6.63); P = 0.030]. The assay retained independent prognostic performance for MFS when assessed with the Cancer of the Prostate Assessment Score (CAPRA) [HR = 3.23 (1.22-8.59); P = 0.019] whilst CAPRA itself was not significant [HR = 1.88, (0.52-6.77); P = 0.332]. A high concordance [100% (61.5-100)] for the assay result was noted between two separate foci taken from 11 tumours, whilst Gleason score had low concordance., Conclusions: The Metastatic Assay demonstrated significant prognostic performance in patients treated with radical radiotherapy both alone and independent of standard clinical and pathological variables. The Metastatic Assay could have clinical utility when deciding upon treatment intensification in high-risk patients. Genomic and clinical data are available as a public resource., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

Objective: The aim of the study was to investigate the effects of facilitatory anodal tDCS (a-tDCS) applied over the leg area of the primary motor cortex on learning a complex whole-body dynamic balancing task (DBT). We hypothesized that a-tDCS during DBT enhances learning performance compared to sham tDCS (s-tDCS)., Methods: In a randomized, parallel design, we applied either a-tDCS (n=13) or s-tDCS (n=13) in a total of 26 young subjects while they perform the DBT. Task performance and error rates were compared between groups. Additionally, we investigated the effect of tDCS on the relationship between performance and kinematic variables capturing different aspects of task execution., Results: A-tDCS over M1 leg area promotes balance performance in a DBT relative to s-tDCS, indicated by higher performance and smaller error scores. Furthermore, a-tDCS seems to mediate the relationship between DBT performance and the kinematic variable velocity., Conclusions: Our findings provide novel evidence for the ability of tDCS to improve dynamic balance learning, a fact, particularly important in the context of treating balance and gait disorders., Significance: TDCS facilitates dynamic balance performance by strengthening the inverse relationship of performance and velocity, thus making tDCS one potential technique to improve walking ability or help to prevent falls in patients in the future., (Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: We have reported genetic linkage between bipolar disorder and markers on chromosome 6q16.3-22.1 in the National Institute of Mental Health Genetics Initiative wave 3 pedigrees. Here we test for: 1) robustness of the linkage to differing analysis methods, genotyping error, and gender-specific maps; 2) parent-of-origin effects; and 3) interaction with markers within the schizophrenia linkage region on chromosome 6p., Methods: Members of 245 families ascertained through a sibling pair affected with bipolar I or schizoaffective-bipolar disorder were genotyped with 18 markers spanning chromosome 6. Nonparametric linkage analysis was performed., Results: Linkage to 6q is robust to analysis method, gender-specific map differences, and genotyping error. The locus confers a 1.4-fold increased risk. Affected siblings share the maternal more often than the paternal chromosome (p =.006), which could reflect a maternal parent-of-origin effect. There is a positive correlation between family-specific linkage scores on 6q and those on 6p22.2 (r =.26; p <.0001). Linkage analysis for each locus conditioned on evidence of linkage to the other increases the evidence for linkage at both loci (p <.0005). Logarithm of the odds (LOD) scores increased from 2.26 to 5.42 on 6q and from.35 to 2.26 on 6p22.2., Conclusions: These results support linkage of bipolar disorder to 6q, uncover a maternal parent-of-origin effect, and demonstrate an interaction of this locus with one on chromosome 6p22.2, previously linked only to schizophrenia.

A rapid enzyme linked immunoassay for pregnancy specific beta 1-glycoprotein is described. The method is sensitive and precise (within batch C.V. = 6.5-7.4%) and should be suitable for the biochemical monitoring of pregnancy and the investigation of patients suffering from various malignancies.