Methodology for Analyzing and Developing Information Management Infrastructure to Support Telerehabilitation

The proliferation of advanced technologies led researchers within the Rehabilitation Engineering Research Center on Telerehabilitation (RERC-TR) to devise an integrated infrastructure for clinical services using the University of Pittsburgh (PITT) model. This model describes five required characteristics for a telerehabilitation (TR) infrastructure: openness, extensibility, scalability, cost-effectiveness, and security. The infrastructure is to deliver clinical services over distance to improve access to health services for people living in underserved or remote areas. The methodological approach to design, develop, and employ this infrastructure is explained and detailed for the remote wheelchair prescription project, a research task within the RERC-TR. The availability of this specific clinical service and personnel outside of metropolitan areas is limited due to the lack of specialty expertise and access to resources. The infrastructure is used to deliver expertise in wheeled mobility and seating through teleconsultation to remote clinics, and has been successfully deployed to five rural clinics in Western Pennsylvania. Keywords: Telerehabilitation, Information Management, Infrastructure Development Methodology, Videoconferencing, Online Portal, Databas

Telerehabilitation Clinical and Vocational Applications for Assistive Technology: Research, Opportunities, and Challenges

Rehabilitation service providers in rural or underserved areas are often challenged in meeting the needs of their complex patients due to limited resources in their geographical area. Recruitment and retention of the rural clinical workforce are beset by the ongoing problems associated with limited continuing education opportunities, professional isolation, and the challenges inherent in coordinating rural community healthcare. People with disabilities who live in rural communities also face challenges accessing healthcare. Traveling long distances to a specialty clinic for necessary expertise may be troublesome due to inadequate or unavailable transportation, disability specific limitations, and financial limitations. Distance and lack of access are just two threats to quality of care that now being addressed by the use of videoconferencing, information exchange, and other telecommunication technologies that facilitate telerehabilitation. This white paper illustrates and summarizes clinical and vocational applications of telerehabilitation. We provide definitions related to the fields of telemedicine, telehealth, and telerehabilitation, and consider the impetus for telerehabilitation. We review the telerehabilitation literature for assistive technology applications; pressure ulcer prevention; virtual reality applications; speech-language pathology applications; seating and wheeled mobility applications; vocational rehabilitation applications; and cost effectiveness. We then discuss external telerehabilitation influencers, such as the positions of professional organizations. Finally, we summarize clinical and policy issues in a limited context appropriate to the scope of this paper. Keywords: Telerehabilitation, Telehealth, Telemedicine, Telepractic

Functional Mobility Outcomes in Telehealth and In-Person Assessments for Wheeled Mobility Devices

The purpose of this study was to compare telehealth and in-person service delivery models for wheeled mobility devices in terms of functional outcomes. We hypothesized that clinically significant improvements in functional mobility measured by the Functional Mobility Assessment (FMA) will occur in individuals receiving both telehealth and in-person clinic evaluations. A total of 27 Veterans receiving telehealth visits were compared to 27 individuals seen in clinic, selected from a database, matching for age, gender, and primary diagnosis. All mean individual item and total FMA scores in both groups increased from Time 1 to Time 2. Within the telehealth group, all changes in individual item and total FMA scores were statistically significant, with changes in 8 of 10 items meeting threshold for clinical significance (change >1.85 points). Within the clinic group, changes in 7 of 10 individual items and total FMA scores were statistically significant, and these same 7 items met threshold for clinical significance. Change scores for individual item and total FMA scores did not differ significantly between the two groups. A larger and clinically significant change in transfer score was seen in the telehealth group, suggesting telehealth visits may confer an advantage in being able to assess and address transfer issues in the home

Veteran and Provider Satisfaction with a Home-Based Telerehabilitation Assessment for Wheelchair Seating and Mobility

The objective of this project was to measure Veteran and provider satisfaction with a home-based telerehabilitation assessment for wheelchair seating and mobility. Forty-three Veterans were seen remotely at their place of residence by a provider, using a VA Video Connect synchronous videoconferencing system. Veteran and provider satisfaction were collected using the Telerehabilitation Questionnaire (TRQ). Mean individual TRQ scores for both Veterans and providers were significantly higher than the scale midpoint of 3.5. Veterans had higher scores than providers for five individual items on the TRQ. Higher scores by Veterans on the technology and quality and clarity of the video and audio likely correspond to the differences in environmental settings in which the visit occurred for the Veteran compared with the provider. High satisfaction scores with the telerehabilitation assessments are likely attributed to the positive working relationship between the provider and the rehabilitation technician, who provided in-person technical support to the Veteran in the home during the wheeled mobility evaluation. Overall, the results indicate a high level of Veteran and provider satisfaction using telerehabilitation for wheelchair seating and mobility evaluations

Complete Haplotype Sequence of the Human Immunoglobulin Heavy-Chain Variable, Diversity, and Joining Genes and Characterization of Allelic and Copy-Number Variation

The immunoglobulin heavy-chain locus (IGH) encodes variable (IGHV), diversity (IGHD), joining (IGHJ), and constant (IGHC) genes and is responsible for antibody heavy-chain biosynthesis, which is vital to the adaptive immune response. Programmed V-(D)-J somatic rearrangement and the complex duplicated nature of the locus have impeded attempts to reconcile its genomic organization based on traditional B-lymphocyte derived genetic material. As a result, sequence descriptions of germline variation within IGHV are lacking, haplotype inference using traditional linkage disequilibrium methods has been difficult, and the human genome reference assembly is missing several expressed IGHV genes. By using a hydatidiform mole BAC clone resource, we present the most complete haplotype of IGHV, IGHD, and IGHJ gene regions derived from a single chromosome, representing an alternate assembly of ∼1 Mbp of high-quality finished sequence. From this we add 101 kbp of previously uncharacterized sequence, including functional IGHV genes, and characterize four large germline copy-number variants (CNVs). In addition to this germline reference, we identify and characterize eight CNV-containing haplotypes from a panel of nine diploid genomes of diverse ethnic origin, discovering previously unmapped IGHV genes and an additional 121 kbp of insertion sequence. We genotype four of these CNVs by using PCR in 425 individuals from nine human populations. We find that all four are highly polymorphic and show considerable evidence of stratification (Fst = 0.3–0.5), with the greatest differences observed between African and Asian populations. These CNVs exhibit weak linkage disequilibrium with SNPs from two commercial arrays in most of the populations tested

A Chemistry of Organization: Combinatory Structural Analysis and Design

This paper is a response to the call for models of organization design as a science revealing the inner composition of organization and specifying the laws to be respected when crafting it. It maintains that the needed science is a chemistry of organization, addressing the combination of 'organizational elements' playing a role analogous to that of chemical elements in composing a variety of substances. Drawing both on classic organization design theory and on configurational and complementarity-based approaches, the paper specifies a set of basic organizational elements and a set of combinatory laws regulating their effective combinations. Testable propositions are derived on the necessary and sufficient conditions that the composition of organizations should have respect for achieving high levels of efficiency and innovation. These propositions are tested empirically on a sample of firms, using an innovative application of Boolean algebra

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment