Patient Perspectives on Osseointegration: A National Survey of Veterans with Upper Limb Amputation

INTRODUCTION: Osseointegrated (OI) prostheses have a unique benefit-risk profile among prosthetic alternatives and have been marketed in the United States under a Humanitarian Device Exemption since 2015. Information about upper limb prosthesis user perspectives on benefits and risks, prosthesis-user subpopulations for whom OI is most acceptable, and outcomes that matter most to patients could help inform clinical and regulatory decision-making. Recent 21st Century Cures legislation expanded the role of patient experience data in the decision-making process of the U.S. Food and Drug Administration, recognizing that patient perspectives may be informative to regulators. OBJECTIVE: To better understand prosthesis user perspectives about the benefits and risks associated with upper limb OI prostheses. DESIGN: Patient perspective survey. SETTING: Telephone administration. PARTICIPANTS: National sample of veterans with upper limb loss. INTERVENTIONS: NA MAIN OUTCOME MEASURES: Benefit-risk survey developed for this study. RESULTS: Twenty-eight percent of unilateral and 13% of bilateral amputees were willing to consider osseointegration surgery. Multivariate logistic regression models [OR; 95% CI] showed that transhumeral amputation level [OR 1.40; 1.01-1.98] was associated with greater willingness to consider surgery, whereas older age [OR 0.17; 0.09-0.32] and higher VR-12 Mental Component Summary [OR 0.53; 0.35-0.81] were associated with less willingness. Having a durable/reliable device, the ability to do more activities, and having a comfortable device were rated as very important or somewhat important by 98% or more for every risk condition. CONCLUSIONS: Persons who were older, had transradial amputation (compared to transhumeral), and those who had better mental functioning were less willing to consider this surgery. Respondents who were willing to consider surgery indicated that the most important potential benefits were obtaining a durable/reliable device, the ability to do more activities, and having a comfortable device. Most were willing to accept one or more risks of surgery, with long-term risks including chronic pain, loss of nerve function, or device failure considered the most unacceptable. LEVEL OF EVIDENCE: III. has been contributed to by US Government employees and their work is in the public domain in the USA

Stellar Coronal Spectroscopy with the Chandra HETGS

Spectroscopy with the Chandra High Energy Transmission Grating Spectrometer provides details on X-ray emission and activity from young and cool stars through resolution of emission lines from a variety of ions. We are beginning to see trends in activity regarding abundances, emission measures, and variability. Here we contrast spectra of TV Crt, a weak-lined T Tauri star, with TW Hya, a Classical T Tauri star. TV Crt has a spectrum more like magnetic activity driven coronae, relative to the TW Hya spectrum, which we have interpreted as due to accretion-produced X-rays. We have also observed the long period system, IM Pegasi to search for rotational modulation, and to compare activity in a long period active binary to shorter period systems and to the pre-main sequence stars. We detected no rotational modulation, but did see long-duration flares.Comment: 5 pages, 2 figures; to be published in IAU Symposium 219: "Stars as Suns: Activity, Evolution, Planets" (Ed. A. Dupree and A. O. Benz

Mitochondrial DNA Copy Number Is Associated with Breast Cancer Risk

Mitochondrial DNA (mtDNA) copy number in peripheral blood is associated with increased risk of several cancers. However, data from prospective studies on mtDNA copy number and breast cancer risk are lacking. We evaluated the association between mtDNA copy number in peripheral blood and breast cancer risk in a nested case-control study of 183 breast cancer cases with pre-diagnostic blood samples and 529 individually matched controls among participants of the Singapore Chinese Health Study. The mtDNA copy number was measured using real time PCR. Conditional logistic regression analyses showed that there was an overall positive association between mtDNA copy number and breast cancer risk (Ptrend = 0.01). The elevated risk for higher mtDNA copy numbers was primarily seen for women with <3 years between blood draw and cancer diagnosis; ORs (95% CIs) for 2nd, 3rd, 4th, and 5th quintile of mtDNA copy number were 1.52 (0.61, 3.82), 2.52 (1.03, 6.12), 3.12 (1.31, 7.43), and 3.06 (1.25, 7.47), respectively, compared with the 1st quintile (Ptrend = 0.004). There was no association between mtDNA copy number and breast cancer risk among women who donated a blood sample ≥3 years before breast cancer diagnosis (Ptrend = 0.41). This study supports a prospective association between increased mtDNA copy number and breast cancer risk that is dependent on the time interval between blood collection and breast cancer diagnosis. Future studies are warranted to confirm these findings and to elucidate the biological role of mtDNA copy number in breast cancer risk. © 2013 Thyagarajan et al

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 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

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

A modified Delphi study of screening for fetal alcohol spectrum disorders in Australia

Background: There is little reliable information on the prevalence of fetal alcohol spectrum disorders (FASD) in Australia and no coordinated national approach to facilitate case detection. The aim of this study was to identify health professionals’ perceptions about screening for FASD in Australia. Method: A modified Delphi process was used to assess perceptions of the need for, and the process of, screening for FASD in Australia. We recruited a panel of 130 Australian health professionals with experience or expertise in FASD screening or diagnosis. A systematic review of the literature was used to develop Likert statements on screening coverage, components and assessment methods which were administered using an online survey over two survey rounds. Results: Of the panel members surveyed, 95 (73%) responded to the questions on screening in the first survey round and, of these, 81 (85%) responded to the second round. Following two rounds there was consensus agreement on the need for targeted screening at birth (76%) and in childhood (84%). Participants did not reach consensus agreement on the need for universal screening at birth (55%) or in childhood (40%). Support for targeted screening was linked to perceived constraints on service provision and the need to examine the performance, costs and benefits of screening. For targeted screening of high risk groups, we found highest agreement for siblings of known cases of FASD (96%) and children of mothers attending alcohol treatment services (93%). Participants agreed that screening for FASD primarily requires assessment of prenatal alcohol exposure at birth (86%) and in childhood (88%), and that a checklist is needed to identify the components of screening and criteria for referral at birth (84%) and in childhood (90%). Conclusions: There is an agreed need for targeted but not universal screening for FASD in Australia, and sufficient consensus among health professionals to warrant development and evaluation of standardised methods for targeted screening and referral in the Australian context. Participants emphasised the need for locally-appropriate, evidence-based approaches to facilitate case detection, and the importance of ensuring that screening and referral programs are supported by adequate diagnostic and management capacity

Gas generation and wind power: A review of unlikely allies in the United Kingdom and Ireland

No single solution currently exists to achieve the utopian desire of zero fossil fuel electricity generation. Until such time, it is evident that the energy mix will contain a large variation in stochastic and intermittent sources of renewable energy such as wind power. The increasing prominence of wind power in pursuit of legally binding European energy targets enables policy makers and conventional generating companies to plan for the unique challenges such a natural resource presents. This drive for wind has been highly beneficial in terms of security of energy supply and reducing greenhouse gas emissions. However, it has created an unusual ally in natural gas. This paper outlines the suitability and challenges faced by gas generating units in their utilisation as key assets for renewable energy integration and the transition to a low carbon future. The Single Electricity Market of the Republic of Ireland and Northern Ireland and the British Electricity Transmission Trading Agreement Market are the backdrop to this analysis. Both of these energy markets have a reliance on gas generation matching the proliferation of wind power. The unlikely and mostly ignored relationship between natural gas generation and wind power due to policy decisions and market forces is the necessity of gas to act as a bridging fuel. This review finds gas generation to be crucially important to the continued growth of renewable energy. Additionally, it is suggested that power market design should adequately reward the flexibility required to securely operate a power system with high penetrations of renewable energy, which in most cases is provided by gas generation

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types