Acinetobacter baumannii is an important nosocomial pathogen that displays high antibiotic resistance. It causes a variety of infections including pneumonias and sepsis which may result in disseminated intravascular coagulation. In this work, we identify and characterize a novel secreted, zinc-dependent, metallo-endopeptidase CpaA (coagulation targeting metallo-endopeptidase of Acinetobacter baumannii) which deregulates human blood coagulation in vitro and thus is likely to contribute to A. baumannii virulence. Three quarters of the clinical isolates tested (n = 16) had the cpaA gene; however, it was absent from two type strains, A. baumannii ATCC 17978 and A. baumannii ATCC 19606. The CpaA protein was purified from one clinical isolate and was able to cleave purified factor (F) V and fibrinogen and reduce the coagulation activity of FV in human plasma. CpaA-treated plasma showed reduced clotting activity in contact pathway-activated partial thromboplastin time (aPTT) assays, but increased clotting activity in tissue factor pathway prothrombin time (PT) assays. A significant portion of clinically relevant A. baumannii isolates secrete a protease which targets and deregulates the coagulation system.
The World Health Organization endorses molecular subclassification of endometrial endometrioid carcinomas (EECs). Our objectives were to test the sensitivity of tumor morphology in capturing p53 abnormal (p53abn) cases and to model the impact of p53abn on changes to ESGO/ESTRO/ESP (European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology) risk stratification. A total of 292 consecutive endometrial carcinoma resections received at Foothills Medical Centre, Calgary, Canada (2019-2021) were retrieved and assigned to ESGO risk groups with and without p53 status. Three pathologists reviewed the representative H&E-stained slides, predicted the p53 status, and indicated whether p53 immunohistochemistry (IHC) would be ordered. Population-based survival for endometrial carcinomas diagnosed during 2008-2016 in Alberta was obtained from the Alberta Cancer Registry. The cohort consisted mostly of grade 1/2 endometrioid carcinomas (EEC1/2; N = 218, 74.6%). One hundred and fifty-two EEC1/2 (52.1% overall) were stage IA and 147 (50.3%) were low risk by ESGO. The overall prevalence of p53abn and subclonal p53 was 14.5 and 8.3%, respectively. The average sensitivity of predicting p53abn among observers was 83.6%. Observers requested p53 IHC for 39.4% with 98.5% sensitivity to detect p53abn (99.6% negative predictive value). Nuclear features including smudged chromatin, pleomorphism, atypical mitoses, and tumor giant cells accurately predicted p53abn. In 7/292 (2.4%), p53abn upgraded ESGO risk groups (2 to intermediate risk, 5 to high risk). EEC1/2/stage IA patients had an excellent disease-specific 5-year survival of 98.5%. Pathologists can select cases for p53 testing with high sensitivity and low risk of false negativity. Molecular characterization of endometrial carcinomas has great potential to refine ESGO risk classification for a small subset but offers little value for approximately half of endometrial carcinomas, namely, EEC1/2/stage IA cases.
The suction dynamics of axial piston pumps become more critical if the pump is to be used at high speeds. In order to prevent air-release and cavitation from occurring within the pump it is necessary to pressurise the pump inlet. As the speed of a pump is increased, higher boost pressures are required, due to the extra losses incurred through the suction line and portplate at the higher flowrates. However, the lack of data regarding axial piston pump behavior at high speeds creates problems for the system designer in selecting suitable boost conditions and for the pump designer in selecting the portplate configuration that is required to reduce fluid-borne-noise levels. This paper discusses the suction performance of piston pumps, and presents experimental and simulation results exploring the behavior of a high-speed axial-piston pump. Different air-release and cavitation models that are suitable for simulation studies are investigated.
Previous work on car-trailer stability has been largely limited to theoretical studies with some reference to practical experience or accident statistics. In this study, extensive and systematic experimental investigations were carried out on a combined car-adjustable-trailer system. The influence of different trailer parameters on the system high-speed stability was examined by changing the mass, dimensions, and inertial characteristics of a fully adjustable trailer. It was found that the dominant factors affecting stability were the trailer yaw inertia, nose mass (mass distribution), and trailer axle position. The tyre pressure also affects the stability, although this effect is less significant. It is interesting to see that the trailer mass alone does not dramatically affect the high-speed stability, as this runs contrary to current guidelines relating to limits on the relative mass of the car and trailer. Experimental tests on a friction stabilizer and on car electronic stability programs demonstrate that both of these improve the high-speed stability and help to delay the onset of 'snaking'.
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