Tetra-allelic SNPs: Informative forensic markers compiled from public whole-genome sequence data

Multiple-allele single nucleotide polymorphisms (SNPs) are potentially useful for forensic DNA analysis as they can provide more discrimination power than normal binary SNPs. In addition, the presence in a profile of more than two alleles per marker provides a clearer indication of mixed DNA than assessments of imbalanced signals in the peak pairs of binary SNPs. Using the 1000 Genomes Phase III human variant data release of 2014 as the starting point, this study collated 961 tetra-allelic SNPs that pass minimum sequence quality thresholds and where four separate nucleotide substitution alleles were detected. Although most of these loci had three of the four alleles in combined frequencies of 2% or less, 160 had high heterozygosities with 50 exceeding those of ‘ideal’ 0.5:0.5 binary SNPs. From this set of most polymorphic tetra-allelic SNPs, we identified markers most informative for forensic purposes and explored these loci in detail. Subsets of the most polymorphic tetra-allelic SNPs will make useful additions to current panels of forensic identification SNPs and ancestry-informative SNPs. The 24 most discriminatory tetra-allelic SNPs were estimated to detect more than two alleles in at least one marker per profile in 99.9% of mixtures of African contributors. In European contributor mixtures 99.4% of profiles would show multiple allele patterns, but this drops to 92.6% of East Asian contributor mixtures due to reduced levels of polymorphism for the 24 SNPs in this population group.     

Real-time modulation of visual feedback on human full-body movements in a virtual mirror: development and proof-of-concept

Background

Virtual reality (VR) provides interactive multimodal sensory stimuli and biofeedback, and can be a powerful tool for physical and cognitive rehabilitation. However, existing systems have generally not implemented realistic full-body avatars and/or a scaling of visual movement feedback. We developed a “virtual mirror” that displays a realistic full-body avatar that responds to full-body movements in all movement planes in real-time, and that allows for the scaling of visual feedback on movements in real-time. The primary objective of this proof-of-concept study was to assess the ability of healthy subjects to detect scaled feedback on trunk flexion movements.

Methods

The “virtual mirror” was developed by integrating motion capture, virtual reality and projection systems. A protocol was developed to provide both augmented and reduced feedback on trunk flexion movements while sitting and standing. The task required reliance on both visual and proprioceptive feedback. The ability to detect scaled feedback was assessed in healthy subjects (n = 10) using a two-alternative forced choice paradigm. Additionally, immersion in the VR environment and task adherence (flexion angles, velocity, and fluency) were assessed.

Results

The ability to detect scaled feedback could be modelled using a sigmoid curve with a high goodness of fit (R² range 89-98%). The point of subjective equivalence was not significantly different from 0 (i.e. not shifted), indicating an unbiased perception. The just noticeable difference was 0.035 ± 0.007, indicating that subjects were able to discriminate different scaling levels consistently. VR immersion was reported to be good, despite some perceived delays between movements and VR projections. Movement kinematic analysis confirmed task adherence.

Conclusions

The new “virtual mirror” extends existing VR systems for motor and pain rehabilitation by enabling the use of realistic full-body avatars and scaled feedback. Proof-of-concept was demonstrated for the assessment of body perception during active movement in healthy controls. The next step will be to apply this system to assessment of body perception disturbances in patients with chronic pain.     

Feasibility study of the BrightBrainer™ integrative cognitive rehabilitation system for elderly with dementia

Purpose: To describe the development of BrightBrainer? integrative cognitive rehabilitation system and determine clinical feasibility with nursing home-bound dementia patients. Method: BrightBrainer cognitive rehabilitation simulations were first played uni-manually, then bimanually. Participants sat in front of a laptop and interacted through a game controller that measured hand movements in 3D, as well as flexion of both index fingers. Interactive serious games were designed to improve basic and complex attention (concentration, short-term memory, dual tasking), memory recall, executive functioning and emotional well-being. Individual simulations adapted automatically to each participant’s level of motor functioning. The system underwent feasibility trials spanning 16 sessions over 8 weeks. Participants were evaluated pre- and post-intervention, using standardized neuropsychological measures. Computerized measures of movement repetitions and task performance were stored on a remote server. Results: Group analysis for 10 participants showed statistically significant improvement in decision making (p?p?p?p?p?Conclusions: Preliminary findings demonstrate utility within an advanced dementia population, suggesting that it will be beneficial to evaluate BrightBrainer through controlled clinical trials and to investigate its application in other clinical populations.

• Implications for Rehabilitation

• It is possible to improve cognitive function in older low-functioning patients. Integrative rehabilitation through games combining cognitive (memory, focusing, executive function) and physical (bimanual whole arm movement, grasping, task sequencing) elements is enjoyable for this population.

• The severity of depression in these elderly can be reduced through virtual reality bimanual games.

• The number of upper extremity active repetitions performed in the process of solving cognitive problems with the BrightBrainer? system is 600. This number is 18 times (1875%) larger than those observed by other researchers in conventional physical or occupational rehabilitation sessions.

     

Myoepithelial Neoplasms of Soft Tissue: An Updated Review of the Clinicopathologic,Immunophenotypic, and Genetic Features

Myoepithelial tumors in skin and soft tissue are uncommon but have been increasingly characterized over the past decade. Men and women are equally affected across all age groups and lesions arise most frequently on the extremities and limb girdles. Approximately 20 % of cases occur in pediatric patients, in whom they are frequently malignant. Similar to their salivary gland counterparts, myoepithelial tumors of soft tissue demonstrate heterogeneous morphologic and immunophenotypic features. Tumors are classified as mixed tumor/chondroid syringoma, myoepithelioma, and myoepithelial carcinoma; in soft tissue, tumors having at least moderate cytologic atypia are classified as malignant. Mixed tumor and myoepithelioma show a benign clinical course, with recurrence in up to 20 % (typically secondary to incomplete excision), and do not metastasize. In contrast, myoepithelial carcinoma shows more aggressive behavior with recurrence and metastasis in up to 40–50 % of cases. The majority of myoepithelial neoplasms typically coexpress epithelial antigens (cytokeratin and/or EMA) and S-100 protein; GFAP and p63 are frequently positive and a subset of malignant neoplasms lose INI1 expression. Up to 45 % of myoepitheliomas and myoepithelial carcinomas harbor EWSR1 gene rearrangements, unlike mixed tumor/chondroid syringoma which is characterized by PLAG1 gene rearrangement. While mixed tumor/chondroid syringoma are likely related to primary salivary myoepithelial tumors, soft tissue myoepithelioma and myoepithelial carcinoma appear to be pathologically distinct neoplasms.     

Mixed connective tissue disease with interstitial pneumonia in HTLV-1 carrier: case report and review of the literature

We report on a carrier of human T-lymphotropic virus type 1 (HTLV-1) who developed mixed connective tissue disease (MCTD). This patient suddenly manifested clinical symptoms and interstitial pneumonia ascribable to MCTD following long-term infection with HTLV-1. After initiation of oral prednisolone all manifestations quickly improved in parallel with a decrease in inflammatory reactions. In this patient HTLV-1 infection might have played an important role in the pathogenesis of MCTD. Since HTLV-1 can cause adult T-cell leukemia and HTLV-1-associated myelopathy, and also collagen diseases including MCTD, careful observation is necessary even in a carrier, particularly when autoantibodies are detectable in serum.     

A novel motion tracking system for evaluation of functional rehabilitation of the upper limbs

Upper limb function impairment is one of the most common sequelae of central nervous system in jury, especially in stroke patients and when spinal cord injury produces tetraplegia. Conventional assessment methods cannot provide objective evaluation of patient performance and the effec tiveness of therapies. The most common assessment tools are based on rating scales, which are inefficient when measuring small changes and can yield subjective bias. In this study, we designed an inertial sensorbased monitoring system composed of five sensors to measure and analyze the complex movements of the upper limbs, which are common in activities of daily living. We devel oped a kinematic model with nine degrees of freedom to analyze upper limb and head movements in three dimensions. This system was then validated using a commercial optoelectronic system. These findings suggest that an inertial sensorbased motion tracking system can be used in patients who have upper limb impairment through data integration with a virtual realitybased neurorehabili tation system.     

Virtual reality-based paediatric interactive therapy system (PITS) for improvement of arm and hand function in children with motor impairment—a pilot study

Objective: Rehabilitation of upper-limb sensorimotor function in children with motor dysfunctions is primarily based on movement training. This study developed a virtual-reality based, paediatric interactive therapy system (PITS) that allows children to practice specific movements of the upper limbs with immediate feedback about their motor performance.

Methods: The system was tested on five children with motor dysfunctions over 3 weeks of training. Pre- and post-assessment was conducted before and after the training period.

Results: Results of the pilot study show improvements of hand function in the test scores (except one patient). Patient motivation was high and maintained over the course of the therapy sessions.

Conclusion: PITS is an applicable VR-system which can be feasibly applied during the rehabilitation of children with upper limb motor dysfunctions. Further investigation is necessary to determine if the system provides significantly improved results compared to conventional therapies, both in terms of motor function outcomes and patient motivation.