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

Telephone and face to face methods of assessment of veteran's community reintegration yield equivalent results

<p>Abstract</p> <p>Background</p> <p>The Community Reintegration of Service Members (CRIS) is a new measure of community reintegration developed to measure veteran's participation in life roles. It consists of three sub-scales: Extent of Participation (Extent), Perceived Limitations with Participation (Perceived), and Satisfaction with Participation (Satisfaction). Testing of the CRIS measure to date has utilized in-person administration. Administration of the CRIS measure by telephone, if equivalent to in-person administration, would be desirable to lower cost and decrease administrative burden. The purpose of this study was to test the equivalence of telephone and in-person mode of CRIS administration.</p> <p>Methods</p> <p>A convenience sample of 102 subjects (76% male, 24% female, age mean = 49 years, standard deviation = 8.3) were randomly assigned to received either telephone interview at Visit 1 and in-person interview at Visit 2, or in-person interview at Visit 1 and telephone interview a Visit 2. Both Visits were conducted within one week. Intraclass correlation coefficients, ICC (2,1), were used to evaluate correspondence between modes for both item scores and summary scores. ANOVAs with mode order as a covariate were used to test for presence of an ordering effect.</p> <p>Results</p> <p>ICCs (95%CI) for the subscales were 0.92 (0.88-0.94) for Extent, 0.85 (0.80-0.90) for Perceived, and 0.89 (0.84-0.93) for Satisfaction. No ordering effect was observed.</p> <p>Conclusion</p> <p>Telephone administration of the CRIS measure yielded equivalent results to in-person administration. Telephone administration of the CRIS may enable lower costs of administration and greater adoption.</p

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

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

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

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies

Angular analysis of the B-0 -&gt; K*(0) e(+) e(-) decay in the low-q(2) region

An angular analysis of the $B^0 \rightarrow K^{*0} e^+ e^-$ decay is performed using a data sample, corresponding to an integrated luminosity of 3.0 {\mbox{fb}^{-1}}, collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of 7 and 8 TeV during 2011 and 2012. For the first time several observables are measured in the dielectron mass squared ($q^2$) interval between 0.002 and 1.120${\mathrm{\,Ge\kern -0.1em V^2\!/}c^4}$. The angular observables $F_{\mathrm{L}}$ and $A_{\mathrm{T}}^{\mathrm{Re}}$ which are related to the $K^{*0}$ polarisation and to the lepton forward-backward asymmetry, are measured to be $F_{\mathrm{L}}= 0.16 \pm 0.06 \pm0.03$ and $A_{\mathrm{T}}^{\mathrm{Re}} = 0.10 \pm 0.18 \pm 0.05$, where the first uncertainty is statistical and the second systematic. The angular observables $A_{\mathrm{T}}^{(2)}$ and $A_{\mathrm{T}}^{\mathrm{Im}}$ which are sensitive to the photon polarisation in this $q^2$ range, are found to be $A_{\mathrm{T}}^{(2)} = -0.23 \pm 0.23 \pm 0.05$ and $A_{\mathrm{T}}^{\mathrm{Im}} =0.14 \pm 0.22 \pm 0.05$. The results are consistent with Standard Model predictions.An angular analysis of the B$^{0}$ → K^{*}^{0} e$^{+}$ e$^{−}$ decay is performed using a data sample, corresponding to an integrated luminosity of 3.0 fb$^{−1}$, collected by the LHCb experiment in pp collisions at centre-of-mass energies of 7 and 8 TeV during 2011 and 2012. For the first time several observables are measured in the dielectron mass squared (q$^{2}$) interval between 0.002 and 1.120 GeV$^{2}$ /c$^{4}$. The angular observables F$_{L}$ and A$_{T}^{Re}$ which are related to the K^{*}^{0} polarisation and to the lepton forward-backward asymmetry, are measured to be F$_{L}$ = 0.16 ± 0.06 ± 0.03 and A$_{T}^{Re}$  = 0.10 ± 0.18 ± 0.05, where the first uncertainty is statistical and the second systematic. The angular observables A$_{T}^{(2)}$ and A$_{T}^{Im}$ which are sensitive to the photon polarisation in this q$^{2}$ range, are found to be A$_{T}^{(2)}$  = − 0.23 ± 0.23 ± 0.05 and A$_{T}^{Im}$  = 0.14 ± 0.22 ± 0.05. The results are consistent with Standard Model predictions.An angular analysis of the $B^0 \rightarrow K^{*0} e^+ e^-$ decay is performed using a data sample, corresponding to an integrated luminosity of 3.0 {\mbox{fb}^{-1}}, collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of 7 and 8 TeV during 2011 and 2012. For the first time several observables are measured in the dielectron mass squared ($q^2$) interval between 0.002 and 1.120${\mathrm{\,Ge\kern -0.1em V^2\!/}c^4}$. The angular observables $F_{\mathrm{L}}$ and $A_{\mathrm{T}}^{\mathrm{Re}}$ which are related to the $K^{*0}$ polarisation and to the lepton forward-backward asymmetry, are measured to be $F_{\mathrm{L}}= 0.16 \pm 0.06 \pm0.03$ and $A_{\mathrm{T}}^{\mathrm{Re}} = 0.10 \pm 0.18 \pm 0.05$, where the first uncertainty is statistical and the second systematic. The angular observables $A_{\mathrm{T}}^{(2)}$ and $A_{\mathrm{T}}^{\mathrm{Im}}$ which are sensitive to the photon polarisation in this $q^2$ range, are found to be $A_{\mathrm{T}}^{(2)} = -0.23 \pm 0.23 \pm 0.05$ and $A_{\mathrm{T}}^{\mathrm{Im}} =0.14 \pm 0.22 \pm 0.05$. The results are consistent with Standard Model predictions

Measurement of CPCP asymmetries and polarisation fractions in Bs0→K∗0Kˉ∗0B_s^0 \rightarrow K^{*0}\bar{K}{}^{*0} decays

An angular analysis of the decay $B_s^0 \rightarrow K^{*0}\overline{K}{}^{*0}$ is performed using $pp$ collisions corresponding to an integrated luminosity of $1.0$ ${fb}^{-1}$ collected by the LHCb experiment at a centre-of-mass energy $\sqrt{s} = 7$ TeV. A combined angular and mass analysis separates six helicity amplitudes and allows the measurement of the longitudinal polarisation fraction $f_L = 0.201 \pm 0.057 {(stat.)} \pm 0.040{(syst.)}$ for the $B_s^0 \rightarrow K^*(892)^0 \overline{K}{}^*(892)^0$ decay. A large scalar contribution from the $K^{*}_{0}(1430)$ and $K^{*}_{0}(800)$ resonances is found, allowing the determination of additional $CP$ asymmetries. Triple product and direct $CP$ asymmetries are determined to be compatible with the Standard Model expectations. The branching fraction $\mathcal{B}(B_s^0 \rightarrow K^*(892)^0 \overline{K}^*(892)^0)$ is measured to be $(10.8 \pm 2.1 {(stat.)} \pm 1.4 {(syst.)} \pm 0.6 (f_d/f_s) ) \times 10^{-6}$