Wave intensity analysis: A novel non-invasive method for determining arterial wave transmission

Wave intensity analysis is a novel technique for assessing wavelet transmission in the cardiovascular system. Using this tool, we have developed non-invasive techniques to study wave transmission in both central & peripheral arteries in man. The aim of this study was to determine the reproducibility of various haemodynamic measures in the carotid, brachial and radial arteries. 12 treated hypertensive men underwent applanation tonometry and pulsed Doppler ultrasound studies of the carotid, brachial and radial arteries on 2 occasions. Coefficients of variation for the local wave speed, cardiac compression wave intensity and main reflected wave intensity ranged between 3.7-6.6%, 8.2-11.4% and 12.5-19.6% respectively. We conclude that non-invasive methods used for wave intensity analysis are reproducible & provide additional information regarding the complex phenomenon of arterial wave transmission in man

Limitations of augmentation index in the assessment of wave reflection in normotensive healthy individuals

Objectives Augmentation index (AIx) is widely used as a measure of wave reflection. We compared the relationship between AIx and age, height and sex with ‘gold standard’ measures of wave reflection derived from measurements of pressure and flow to establish how well AIx measures wave reflection. Materials and Methods Measurements of carotid pressure and flow velocity were made in the carotid artery of 65 healthy normotensive individuals (age 21–78 yr; 43 male) and pulse wave analysis, wave intensity analysis and wave separation was performed; waveforms were classified into type A, B or C. AIx, the time of the first shoulder (Ts), wave reflection index (WRI) and the ratio of backward to forward pressure (Pb/Pf) were calculated. Results AIx did not correlate with log WRI or Pb/Pf. When AIx was restricted to positive values AIx and log WRI were positively correlated (r = 0.33; p = 0.04). In contrast log WRI and Pb/Pf were closely correlated (r = 0.66; p<0.001). There was no correlation between the Ts and the timing of Pb or the reflected wave identified by wave intensity analysis. Wave intensity analysis showed that the morphology of type C waveforms (negative AIx) was principally due to a forward travelling (re-reflected) decompression wave in mid-systole. AIx correlated positively with age, inversely with height and was higher in women. In contrast log WRI and Pb/Pf showed negative associations with age, were unrelated to height and did not differ significantly by gender. Conclusions AIx has serious limitations as a measure of wave reflection. Negative AIx values derived from Type C waves should not be used as estimates of wave reflection magnitude

Are bisphosphonates effective in the treatment of osteoarthritis pain? A meta-analysis and systematic review.

Osteoarthritis (OA) is the most common form of arthritis worldwide. Pain and reduced function are the main symptoms in this prevalent disease. There are currently no treatments for OA that modify disease progression; therefore analgesic drugs and joint replacement for larger joints are the standard of care. In light of several recent studies reporting the use of bisphosphonates for OA treatment, our work aimed to evaluate published literature to assess the effectiveness of bisphosphonates in OA treatment

Reconstruction and quantification of the carotid artery bifurcation from 3D ultrasound images

Three-dimensional (3-D) ultrasound is a relatively new technique, which is well suited to imaging superficial blood vessels, and potentially provides a useful, noninvasive method for generating anatomically realistic 3-D models of the peripheral vasculature. Such models are essential for accurate simulation of blood flow using computational fluid dynamics (CFD), but may also be used to quantify atherosclerotic plaque more comprehensively than routine clinical methods. In this paper, we present a spline-based method for reconstructing the normal and diseased carotid artery bifurcation from images acquired using a freehand 3-D ultrasound system. The vessel wall (intima-media interface) and lumen surfaces are represented by a geometric model defined using smoothing splines. Using this coupled wall-lumen model, we demonstrate how plaque may be analyzed automatically to provide a comprehensive set of quantitative measures of size and shape, including established clinical measures, such as degree of (diameter) stenosis. The geometric accuracy of 3-D ultrasound reconstruction is assessed using pulsatile phantoms of the carotid bifurcation, and we conclude by demonstrating the in vivo application of the algorithms outlined to 3-D ultrasound scans from a series of patient carotid arteries

Drawing to Remember: External Support of Older Adults’ Eyewitness Performance

Although healthy aging is accompanied by a general decline in memory functioning, environmental support at retrieval can improve older adults’ (+65 years) episodic remembering. Despite those over the age of 65years representing a growing proportion of the population, few environmental retrieval support methods have been empirically evaluated for use with older witnesses and victims of crime. Here, the efficacy of a novel retrieval technique, the Sketch Mental Reinstatement of Context, is compared with a standard Mental Reinstatement of Context and a no support control (Control). Fifty-one participants witnessed an unexpected live event, and 48 hours later were interviewed using one of three aforementioned techniques. In line with predictions emanating from cognitive theories of aging and the environmental support hypothesis, participants in the Sketch Mental Reinstatement of Context condition recalled significantly more correct information and fewer inaccurate items. The Sketch Mental Reinstatement of Context technique appears to scaffold memory retrieval in an age-appropriate manner during a post-event interview, possibly by encouraging more effortful retrieval and reducing dual-task load. As such, this procedure offers an effective alternative to current approaches, adding to the toolbox of techniques available to forensic and other interviewers

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

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente