Mixed-Valve Disease: Management of Patients with Aortic Stenosis and Mitral Regurgitation: Thresholds for Surgery Versus Percutaneous Therapies

Significant mitral regurgitation (MR), frequently seen in the presence of severe aortic stenosis (AS), results in an association that negatively affects prognosis and imposes particular challenges for both the assessment of the severity of valvular lesions and decisions regarding treatment allocation. This article reviews the available literature with regards to the assessment of MR and AS in the presence of both; surgical management and results in patients with concomitant AS and MR; the effect of MR on outcomes in patients undergoing transcatheter aortic valve replacement; the effect of transcatheter aortic valve replacement on MR severity; and percutaneous treatment for MR after transcatheter aortic valve implantation. The authors aim to provide assistance in the decision-making process to treat patients with either a higher-risk double-valve procedure or a simpler, but perhaps incomplete, single-valve option

Semaine d'Etude Mathématiques et Entreprises 1 : Géométrie des matrices de covariance pour le traitement de signaux radars

Les radars Doppler permettent de détecter des objets volants petits ou de faible signature radar. Thalès propose ici de réfléchir aux techniques permettant de faire ressortir de la masse des données radar celles qui sont "aberrantes" afin de repérer parmi le bruit de fond dû aux milieux environnants (nuages de pluie,...) la trace d'un objet volant

Comparison of the Hemodynamic Performance of Percutaneous and Surgical Bioprostheses for the Treatment of Severe Aortic Stenosis

ObjectivesThis study was undertaken to compare the hemodynamic performance of a percutaneous bioprosthesis to that of surgically implanted (stented and stentless) bioprostheses for the treatment of severe aortic stenosis.MethodsFifty patients who underwent percutaneous aortic valve implantation (PAVI) with the Cribier-Edwards or Edwards SAPIEN bioprosthetic valve (Edwards Lifesciences, Inc., Irvine, California) were matched 1:1 for sex, aortic annulus diameter, left ventricular ejection fraction, body surface area, and body mass index, with 2 groups of 50 patients who underwent surgical aortic valve replacement (SAVR) with a stented valve (Edwards Perimount Magna [SAVR-ST group]), or a stentless valve (Medtronic Freestyle, Medtronic, Minneapolis, Minnesota [SAVR-SL group]). Doppler echocardiographic data were prospectively obtained before the intervention, at discharge, and at 6- to 12-month follow-up.ResultsMean transprosthetic gradient at discharge was lower (p < 0.001) in the PAVI group (10 ± 4 mm Hg) compared with the SAVR-ST (13 ± 5 mm Hg) and SAVR-SL (14 ± 6 mm Hg) groups. Aortic regurgitation (AR) occurred more frequently in the PAVI group (mild: 42%, moderate: 8%) compared with the SAVR-ST (mild: 10%, moderate: 0%) and SAVR-SL (mild: 12%, moderate: 0%) groups (p < 0.0001). At follow-up, the mean gradient in the PAVI group remained lower (p < 0.001) than that of the SAVR-ST group, but was similar to that of the SAVR-SL group. The incidence of severe prosthesis-patient mismatch was significantly lower (p = 0.007) in the PAVI group (6%) compared with the SAVR-ST (28%) and SAVR-SL (20%) groups. However, the incidence of AR remained higher (p < 0.0001) in the PAVI group compared with the 2 other groups.ConclusionsPAVI provided superior hemodynamic performance compared with the surgical bioprostheses in terms of transprosthetic gradient and prevention of severe prosthesis-patient mismatch, but was associated with a higher incidence of AR

Test 1157: John Deere 2630 and 2640 Diesel

EXPLANATION OF TEST REPORT GENERAL CONDITIONS East tractor is a production model equipped for common usage. Power consuming accessories can be disconnected only when it is convenient for the operator to do so in practice. Additional weight can be added as ballast if the manufacturer regularly supplies it for sale. The static tire loads and the inflation pressures muse conform to recommendations in the Tire Standards published by the Society of Automotive Engineers. PREPARATION FOR PERFORMANCE RUNS The engine crank case is drained and refilled with a measured amount of new oil conforming to specifications in the operator’s manual. The fuel used and the maintenance operations must also conform to the published information delivered with the tractor. The tractor is then limbered-up for 1 hour on drawbar work in accordance with the manufacturers published recommendations. The manufacturer’s representative is present to make appropriate decisions regarding mechanical adjustments. The tractor is equipped with approximately the amount of added ballast that is used during maximum drawbar tests. The tire tread-bar height must be at least 65% of new tread height prior to the maximum power run. BELT OR POWER TAKE-OFF PERFORMANCE Maximum Power and Fuel Consumption. The manufacturer’s representative makes carburetor, fuel pump, ignition and governor control settings which remain unchanged throughout tall subsequent runs. The governor and the manually operated governor control lever is set to provide the high-idle speed specified by the manufacturer for maximum power. Maximum power is measured by connecting the belt pulley or the power take-off to a dynamometer. The dynamometer load is then gradually increased until the engine is operating at the rated speed specified by the manufacturer for maximum power. The corresponding fuel consumption is measured. Varying Power and Fuel Consumption. Six different horsepower levels are used to show corresponding fuel consumption rates and how the governor causes the engine to react to the following changes in dynamometer load: 85% of the dynamometer torque at maximum power; minimum dynamometer torque, ½ the 85% torque; maximum power; ¼ and ¾ of the 85% torque. Since at tractor is generally subjected to varying loads the average of the results in this test serve well for predicting the fuel consumption of a tractor in general usage. DRAWBAR PERFORMANCE All engine adjustments are the same as those used in the belt or power take-off tests. If the manufacturer specifies a different rated crankshaft speed for drawbar operations, then the position of the manually operated governor control is changed to provide the high-idle speed specified by the manufacturer in the operating instructions. Varying Power and Fuel Consumption With Ballast. The varying power runs are made to show the effect of speed-control devices (engine governor, automatic transmissions, etc.) on horsepower, speed and fuel consumption. These runs are made around the entire test course with has two 180 degree turns with a minimum radius of 50 feet. The drawbar pull is set at 3 different levels as follows: (1) as near to the pull a maximum power as possible and still have the tractor maintain the travel speed at maximum horsepower on the straight sections of the test course; (2) 75% of the pull at maximum power; and (3) 50% of the pull at maximum power. Prior to 1958, fuel consumption data (10 hour test) were shown only for the pull obtained at maximum power for tractors having torque converters and at 75% of the pull obtained at maximum power for gear-type tractors. Maximum Power With Ballast. Maximum power is measured on straight level sections of the test course. Data are shown for not more that 12 different gears or travel speeds. Some gears or travel speeds may be omitted because of high slippage of the traction members or because the travel speed may exceed the safe-limit for the test course. The maximum safe speed for the Nebraska Test course has been set at 15 miles per hour. The slippage limits have been set at 15% and 7% for pneumatic tires and steel tracks or lugs, respectively. Higher slippage gives widely varying results. Maximum Power Without Ballast. All added ballast is removed from the tractor. The maximum drawbar power of the tractor is determined by the same procedure used for getting maximum power with ballast. The gear (or travel speed) is the same as that used in the 10-hours test. Varying Power and Travel Speed With Ballast. Travel speeds corresponding to drawbar pulls beyond the maximum power range are obtained to show the “lugging ability” of the tractor. The run starts with the pull at maximum power; then additional drawbar pull is applied to cause decreasing speeds. The run is ended by one of three conditions; (1) maximum pull is obtained, (2) the maximum slippage limit is reached, or (3) some other operating limit is reached

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

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

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