Mitral valve prolapse syndrome and MASS phenotype: stability of aortic dilatation but progression of mitral valve prolapse

AbstractBackgroundMitral valve prolapse syndrome (MVPS) and MASS phenotype (MASS) are Marfan-like syndromes that exhibit aortic dilatation and mitral valve prolapse. Unlike in Marfan syndrome (MFS), the presence of ectopia lentis and aortic aneurysm preclude diagnosis of MVPS and MASS. However, it is unclear whether aortic dilatation and mitral valve prolapse remain stable in MVPS or MASS or whether they progress like in MFS.MethodsThis retrospective longitudinal observational study examines clinical characteristics and long-term prognosis of 44 adults with MVPS or MASS (18 men, 26 women aged 38±17years) as compared with 81 adults with Marfan syndrome (MFS) with similar age and sex distribution. The age at final contact was 42±15years with mean follow-up of 66±49months.ResultsAt baseline, ectopia lentis and aortic sinus aneurysm were absent in MVPS and MASS, and systemic scores defined by the revised Ghent nosology were lower than in MFS (all P<.001). Unlike in MFS, no individual with MVPS and MASS developed aortic complications (P<.001). In contrast, the incidence of endocarditis (P=.292), heart failure (P=.644), and mitral valve surgery (P=.140) was similar in all syndromes. Cox regression analysis identified increased LV end-diastolic (P=.013), moderate MVR (P=.019) and flail MV leaflet (P=.017) as independent predictors of mitral valve surgery.ConclusionsThe study provides evidence that MVPS and MASS are Marfan-like syndromes with stability of aortic dilatation but with progression of mitral valve prolapse. Echocardiographic characteristics of mitral valve disease rather than the type of syndrome, predict clinical progression of mitral valve prolapse

The effects of heuristic rule training on operator performance in a simulated process control environment

In complex work environments, the occurrence of novel system states represents a particular challenge for the design of training. This article is concerned with the use of heuristic rules to prepare operators for the management of unfamiliar fault states. An experiment was carried out to examine the effects of heuristic rule training on operator performance and system management behaviour

Untangling dislocation and grain boundary mediated plasticity in nanocrystalline nickel

Nanocrystalline (nc) materials possess unique mechanical properties, such as very high strength. However, an understanding of the deformation mechanisms and the succession of related microscopic processes that occur during deformation is still incomplete. We used synchrotron-based in situ compression testing to investigate the sequence of deformation mechanisms emerging in bulk nc nickel with a grain size of 30 nm. The study was accompanied by high-resolution grain size analysis and crystal orientation mapping using transmission electron microscopy. Regardless of the initial microstructure, the deformation behavior of electrodeposited nc Ni is initiated by inhomogeneous elastic lattice straining and its accommodation within the grain boundary network, followed by the onset of dislocation plasticity, which was inferred from texture evolution, and stress-driven grain growth. This observation indicates that deformation in nc metals is governed by a succession of different, partly overlapping mechanisms. It is estimated that intragranular dislocation plasticity contributes only about 40% to the overall deformation. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved

Patient derived renal cell carcinoma xenografts exhibit distinct sensitivity patterns in response to antiangiogenic therapy and constitute a suitable tool for biomarker development

Systemic treatment is necessary for one third of patients with renal cell carcinoma. No valid biomarker is currently available to tailor personalized therapy. In this study we established a representative panel of patient derived xenograft (PDX) mouse models from patients with renal cell carcinomas and determined serum levels of high mobility group B1 (HMGB1) protein under treatment with sunitinib, pazopanib, sorafenib, axitinib, temsirolimus and bevacizumab. Serum HMGB1 levels were significantly higher in a subset of the PDX collection, which exhibited slower tumor growth during subsequent passages than tumors with low HMGB1 serum levels. Pre-treatment PDX serum HMGB1 levels also correlated with response to systemic treatment: PDX models with high HMGB1 levels predicted response to bevacizumab. Taken together, we provide for the first time evidence that the damage associated molecular pattern biomarker HMGB1 can predict response to systemic treatment with bevacizumab. Our data support the future evaluation of HMGB1 as a predictive biomarker for bevacizumab sensitivity in patients with renal cell carcinoma