Rapid detection of BRCA1/2 recurrent mutations in Chinese breast and ovarian cancer patients with multiplex SNaPshot genotyping panels.

BRCA1/2 mutations are significant risk factors for hereditary breast and ovarian cancer (HBOC), its mutation frequency in HBOC of Chinese ethnicity is around 9%, in which nearly half are recurrent mutations. In Hong Kong and China, genetic testing and counseling are not as common as in the West. To reduce the barrier of testing, a multiplex SNaPshot genotyping panel that targeted 25 Chinese BRCA1/2 mutation hotspots was developed, and its feasibility was evaluated in a local cohort of 441 breast and 155 ovarian cancer patients. For those who tested negative, they were then subjected to full-gene testing with next-generation sequencing (NGS). BRCA mutation prevalence in this cohort was 8.05% and the yield of the recurrent panel was 3.52%, identifying over 40% of the mutation carriers. Moreover, from 79 Chinese breast cancer cases recruited overseas, 2 recurrent mutations and one novel BRCA2 mutation were detected by the panel and NGS respectively. The developed genotyping panel showed to be an easy-to-perform and more affordable testing tool that can provide important contributions to improve the healthcare of Chinese women with cancer as well as family members that harbor high risk mutations for HBOC

A powerful and efficient multivariate approach for voxel-level connectome-wide association studies

We describe an approach to multivariate analysis, termed structured kernel principal component regression (sKPCR), to identify associations in voxel-level connectomes using resting-state functional magnetic resonance imaging (rsfMRI) data. This powerful and computationally efficient multivariate method can identify voxel-phenotype associations based on the whole-brain connectivity pattern of voxels, and it can detect linear and non-linear signals in both volume-based and surface-based rsfMRI data. For each voxel, sKPCR first extracts low-dimensional signals from the spatially smoothed connectivities by structured kernel principal component analysis, and then tests the voxel-phenotype associations by an adaptive regression model. The method's power is derived from appropriately modelling the spatial structure of the data when performing dimension reduction, and then adaptively choosing an optimal dimension for association testing using the adaptive regression strategy. Simulations based on real connectome data have shown that sKPCR can accurately control the false-positive rate and that it is more powerful than many state-of-the-art approaches, such as the connectivity-wise generalized linear model (GLM) approach, multivariate distance matrix regression (MDMR), adaptive sum of powered score (aSPU) test, and least-square kernel machine (LSKM). Moreover, since sKPCR can reduce the computational cost of non-parametric permutation tests, its computation speed is much faster. To demonstrate the utility of sKPCR for real data analysis, we have also compared sKPCR with the above methods based on the identification of voxel-wise differences between schizophrenic patients and healthy controls in four independent rsfMRI datasets. The results showed that sKPCR had better between-sites reproducibility and a larger proportion of overlap with existing schizophrenia meta-analysis findings. Code for our approach can be downloaded from https://github.com/weikanggong/sKPCR. [Abstract copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Gait Analysis From a Single Ear-Worn Sensor: Reliability and Clinical Evaluation for Orthopaedic Patients

Objective assessment of detailed gait patterns after orthopaedic surgery is important for post-surgical follow-up and rehabilitation. The purpose of this paper is to assess the use of a single ear-worn sensor for clinical gait analysis. A reliability measure is devised for indicating the confidence level of the estimated gait events, allowing it to be used in free-walking environments and for facilitating clinical assessment of orthopaedic patients after surgery. Patient groups prior to or following anterior cruciate ligament (ACL) reconstruction and knee replacement were recruited to assess the proposed method. The ability of the sensor for detailed longitudinal analysis is demonstrated with a group of patients after lower limb reconstruction by considering parameters such as temporal and force-related gait asymmetry derived from gait events. The results suggest that the ear-worn sensor can be used for objective gait assessments of orthopaedic patients without the requirement and expense of an elaborate laboratory setup for gait analysis. It significantly simplifies the monitoring protocol and opens the possibilities for home-based remote patient assessment

Bezoar in gastro-jejunostomy presenting with symptoms of gastric outlet obstruction: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Gastric outlet obstruction usually presents with non-bilious vomiting, colicky epigastric pain, loss of appetite and occasionally, upper gastrointestinal bleeding. Causes can be classified as benign or malignant, or as extra- or intraluminal. Gastrojejunostomy is a well-recognised surgical procedure performed to bypass gastric outlet obstruction. A bezoar occurs most commonly in patients with impaired gastrointestinal motility or with a history of gastric surgery. It is an intestinal concretion, which fails to pass along the alimentary canal.</p> <p>Case presentation</p> <p>A 62-year-old Asian woman with a history of gastrojejunostomy for peptic ulcer disease was admitted to hospital with epigastric pain, vomiting and dehydration. All investigations concluded gastric outlet obstruction secondary to a "stricture" at the site of gastrojejunostomy. Subsequent laparotomy revealed that the cause of the obstruction was a bezoar.</p> <p>Conclusion</p> <p>Many bezoars can be removed endoscopically, but some will require operative intervention. Once removed, emphasis must be placed upon prevention of recurrence. Surgeons must learn to recognise and classify bezoars in order to provide the most effective therapy.</p

Connections of the human orbitofrontal cortex and inferior frontal gyrus

The direct connections of the orbitofrontal cortex (OFC) were traced with diffusion tractography imaging and statistical analysis in 50 humans, to help understand better its roles in emotion and its disorders. The medial OFC and ventromedial prefrontal cortex have direct connections with the pregenual and subgenual parts of the anterior cingulate cortex; all of which are reward-related areas. The lateral OFC (OFClat) and its closely connected right inferior frontal gyrus (rIFG) have direct connections with the supracallosal anterior cingulate cortex; all of which are punishment or nonreward-related areas. The OFClat and rIFG also have direct connections with the right supramarginal gyrus and inferior parietal cortex, and with some premotor cortical areas, which may provide outputs for the OFClat and rIFG. Another key finding is that the ventromedial prefrontal cortex shares with the medial OFC especially strong outputs to the nucleus accumbens and olfactory tubercle, which comprise the ventral striatum, whereas the other regions have more widespread outputs to the striatum. Direct connections of the OFC and IFG were with especially the temporal pole part of the temporal lobe. The left IFG, which includes Broca’s area, has direct connections with the left angular and supramarginal gyri

Rotation of planet-harbouring stars

The rotation rate of a star has important implications for the detectability, characterisation and stability of any planets that may be orbiting it. This chapter gives a brief overview of stellar rotation before describing the methods used to measure the rotation periods of planet host stars, the factors affecting the evolution of a star's rotation rate, stellar age estimates based on rotation, and an overview of the observed trends in the rotation properties of stars with planets.Comment: 16 pages, 4 figures: Invited review to appear in 'Handbook of Exoplanets', Springer Reference Works, edited by Hans J. Deeg and Juan Antonio Belmont

Seeking String Theory in the Cosmos

We review the existence, formation and properties of cosmic strings in string theory, the wide variety of observational techniques that are being employed to detect them, and the constraints that current observations impose on string theory models.Comment: 25 pages; contribution for String Cosmology issue of Classical and Quantum Gravity. References added and other improvements. Matches journal versio

A Brief Mindfulness-Based Family Psychoeducation Intervention for Chinese Young Adults With First Episode Psychosis: A Study Protocol

Family psychoeducation (FPE) has been recommended as a major component in the treatment of psychosis. Many previous studies have implemented an intensive program design that often only emphasized improvements in patients’ illness outcomes but the benefits for caregivers were limited. There have been calls for a time-limited but cost-effective FPE program to mitigate the looming reality of the suffering of people with psychosis and their families. A Brief Mindfulness-Based Family Psychoeducation for psychosis program is developed to reduce caregivers’ burden and promote young adult’s recovery. A randomized controlled trial will be conducted to compare this intervention with an ordinary FPE intervention. Both arms will involve six sessions, with a total contact time of 12 h. 300 caregivers of young adults who have experienced first episode psychosis within last 3 years will be recruited. Program effectiveness will be assessed by comparing outcomes measuring the caregivers’ burden, mental health symptoms, positive well-being, and the young adult’s mental health symptoms during the study and at 9-month post-randomization. The role of expressed emotions, interpersonal mindfulness, and non-attachment in mediating these outcomes will be explored. An additional qualitative approach Photovoice is selected to explore the complex family experiences and the benefits of mindfulness from the caregivers’ personal perspectives.Trial Registration: The trial is registered with the United States Clinical Trials Registry (ClinicalTrials.gov): NCT03688009

Reward vs non-reward sensitivity of the medial vs lateral orbitofrontal cortex relates to the severity of depressive symptoms

Background: The orbitofrontal cortex (OFC) is implicated in depression. The hypothesis investigated was whether the OFC sensitivity to reward and non-reward is related to the severity of depressive symptoms. Methods: Activations in the monetary incentive delay task were measured in the IMAGEN cohort at age 14 (n=1877) and 19 (n=1140) with a longitudinal design. Clinically-relevant subgroups were compared at age 19 (high-severity group n=116; low-severity group n=206), and 14. Results: The medial OFC exhibited graded activation increases to reward; and the lateral OFC had graded activation increases to non-reward. In this general population, the medial and lateral OFC activations were associated with concurrent depressive symptoms at both age 14 and 19. In a stratified high-severity depressive symptom vs control comparison, the lateral OFC showed greater sensitivity for the magnitudes of activations related to non-reward (No-Win) in the high-severity group at age 19 (p=0.027), and the medial OFC showed decreased sensitivity to the reward magnitudes in the high-severity group at both age 14 (p=0.002) and 19 (p=0.002). In a longitudinal design, there was greater sensitivity to non-reward of the lateral OFC at age 14 for those who exhibited high depressive symptom severity later at age 19 (p=0.003). Conclusions: Activations in the lateral orbitofrontal cortex relate to sensitivity to not winning, were associated with high depressive symptom scores, and at 14 predicted the depressive symptoms at 16 and 19. Activations in the medial OFC were related to sensitivity to winning, and reduced reward sensitivity was associated with concurrent high depressive symptom scores