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Cramariuc D.,University of Bergen | Rogge B.P.,University of Bergen | Lonnebakken M.T.,University of Bergen | Boman K.,Umeaa University | And 4 more authors.

Objective Women with severe aortic valve stenosis (AS) have better LV systolic function and more concentric LV geometry than their male counterparts. However, sex differences in cardiovascular (CV) outcome during progression of AS have not been reported from a longitudinal prospective study. Methods Doppler echocardiography and CV events were recorded during a median of 4.0 years in 979 men and 632 women aged 28-86 (mean 67±10) years in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study. LV systolic function was assessed by EF and midwall shortening (MWS). Study outcomes were ASrelated events, ischaemic CV events and total mortality. Results The annular cumulative incidence of AS events, ischaemic CV events and death was 8.1%, 3.4% and 2.8% in women, and 8.9%, 4.4% and 2.4% in men, respectively. Women and men had similar AS progression rate whether measured by peak jet velocity, mean gradient or valve area. In multivariate analyses, female sex independently predicted less reduction in LV MWS and EF during follow-up (both p<0.05). In time-varying Cox analyses, women had a 40% lower rate of ischaemic CV events (95% CI 21% to 54%), in particular, more than 50% lower rate of stroke and coronary artery bypass grafting, and a 31% lower allcause mortality (95% CI 1% to 51%), independent of active study treatment, age and hypertension, as well as time-varying valve area, low systolic function and abnormal LV geometry. AS event rate did not differ by sex. Conclusions In the SEAS study, women and men had similar rates of AS progression and AS-related events. However, women had lower total mortality and ischaemic CV event rate than men independent of confounders. Trial registration number ClinicalTrials.gov identi fier: NCT00092677. Funding The SEAS (Simvastatin Ezetimibe in Aortic Stenosis) Echocardiography Core Laboratory was supported by MSP Singapore Company, LLC, Singapore, a partnership between Merck Co, and the Schering-Plough Corporation. Source

Sandmann T.,Genentech | Bourgon R.,Genentech | Garcia J.,Hoffmann-La Roche | Li C.,Genentech | And 16 more authors.
Journal of Clinical Oncology

Purpose The AVAglio (Avastin in Glioblastoma) and RTOG-0825 randomized, placebo-controlled phase II trials in newly diagnosed glioblastoma reported prolonged progression-free survival (PFS), but not overall survival (OS), with the addition of bevacizumab to radiotherapy plus temozolomide. To establish whether certain patient subgroups derived an OS benefit from the addition of bevacizumab to first-line standard-of-care therapy, AVAglio patients were retrospectively evaluated for molecular subtype, and bevacizumab efficacy was assessed for each patient subgroup. Patients and Methods A total of 349 pretreatment specimens (bevacizumab arm, n = 171; placebo arm, n = 178) from AVAglio patients (total, N = 921) were available for biomarker analysis. Samples were profiled for gene expression and isocitrate dehydrogenase 1 (IDH1) mutation status and classified into previously identified molecular subtypes. PFS and OS were assessed within each subtype Results A multivariable analysis accounting for prognostic covariates revealed that bevacizumab conferred a significant OS advantage versus placebo for patients with proneural IDH1 wild-type tumors (17.1 v 12.8 months, respectively; hazard ratio, 0.43; 95% CI, 0.26 to 0.73; P = .002). This analysis also revealed an interaction between the proneural subtype biomarker and treatment arm (P = .023). The group of patients with mesenchymal and proneural tumors derived a PFS benefit from bevacizumab compared with placebo; however, this translated to an OS benefit in the proneural subset only. Conclusion Retrospective analysis of AVAglio data suggests that patients with IDH1 wild-type proneura glioblastoma may derive an OS benefit from first-line bevacizumab treatment. The predictive value of the proneural subtype observed in AVAglio should be validated in an independent data set. Copyright © 2015 American Society of Clinical Oncology. All rights reserved. Source

Lutzenkirchen J.,Karlsruhe Institute of Technology | Van Male J.,Culgi B.V. | Van Male J.,Wageningen University | Leermakers F.,Wageningen University | Sjoberg S.,Umeaa University
Journal of Chemical and Engineering Data

The charge of poly(acrylic acid) (PAA) in dilute aqueous solutions depends on pH and ionic strength. We report new experimental data and test various models to describe the deprotonation of PAA in three different NaCl concentrations. A simple surface complexation approach is found to be very successful: the constant capacitance model requires one pK a value and one capacitance for excellent fits to the data, with both parameters depending on ionic strength. The use of a self-consistent set of diffuse double layer parameters with one pK a for flat, spherical, and cylindrical geometry does not result in a satisfactory description of the data, and a number of adjustments to that model were tested to improve the fit. The basic Stern model (BSM) was tested with both plate and cylinder geometry. The cylinder geometry along with strong electrolyte binding was found to be superior to a similar approach involving weak electrolyte binding both in terms of goodness of fit and self-consistency of the parameters. The third approach, the non-ideal competitive consistent adsorption-Donnan (NICCA-Donnan) model, involving one functional group, allows an excellent description of the experimental data. Finally, the polyacid chain was modeled using a mechanistically more realistic self-consistent field (SCF) approach, which allows for radially inhomogeneous distributions of the charges and radial variations in the polymer density and electrostatic potential, while the functional groups can be in protonated, deprotonated, or complexed states. One functional group was insufficient for a satisfactory description of the data. With two segments (one monoprotic, the other diprotic) a reasonable description of the data, including the ionic strength dependence, is achieved, and the tendency of the size of the macro-ion with pH and ionic strength is as expected. This model has the fewest adjustable parameters and is considered the most realistic and comprehensive among the models tested. © 2011 American Chemical Society. Source

Rieck A.E.,University of Bergen | Cramariuc D.,University of Bergen | Boman K.,Umeaa University | Gohlke-Barwolf C.,Herz Zentrum Bad Krozingen | And 4 more authors.

The impact of hypertension on left ventricular structure and outcome during progression of aortic valve stenosis has not been reported from a large prospective study. Data from 1616 patients with asymptomatic aortic stenosis randomized to placebo-controlled treatment with combined simvastatin and ezetimibe in the Simvastatin Ezetimibe in Aortic Stenosis Study were used. The primary study end point included combined cardiovascular death, aortic valve events, and ischemic cardiovascular events. Hypertension was defined as history of hypertension or elevated baseline blood pressure. Left ventricular hypertrophy was defined as left ventricular mass/height2 7 >46.7 g/m2.7 in women and >49.2 g/m2.7 in men and concentric geometry as relative wall thickness >043. Baseline peak aortic jet velocity and aortic stenosis progression rate did not differ between hypertensive (n= 1340) and normotensive (n=276) patients. During 4.3 years of follow-up, the prevalence of concentric left ventricular hypertrophy increased 3 times in both groups. Hypertension predicted 51% higher incidence of abnormal LV geometry at final study visit independent of other confounders (P<0.01). In time-varying Cox regression, hypertension did not predict increased rate of the primary study end point. However, hypertension was associated with a 56% higher rate of ischemic cardiovascular events and a 2-fold increased mortality (both P<0.01), independent of aortic stenosis severity, abnormal left ventricular geometry, in-treatment systolic blood pressure, and randomized study treatment. No impact on aortic valve replacement was found. In conclusion, among patients with initial asymptomatic mild-to-moderate aortic stenosis, hypertension was associated with more abnormal left ventricular structure and increased cardiovascular morbidity and mortality. © 2012 American Heart Association, Inc. Source

Salovaara A.,Aalto University | Lehmuskallio A.,Aalto University | Hedman L.,Umeaa University | Valkonen P.,Idean Inc | Nasanen J.,Aalto University
International Journal of Human Computer Studies

More and more people entering the stage of retirement at around age 55-65 are healthy, active, and also very computer-literate. This trend is rapidly changing the common image of late-midlife technology users, which rests on the assumption that they find it difficult to embrace new technologies and also that their main interests are health related. Although technology use and lifestyles are changing, however, many other aspects of life remain the same. One of these aspects is that of the transitions, or life changes, that generally take place in these years. Besides retirement, these transitions include changes in health, housing, social interaction, work life, and personal finance. People develop different ways of coping with these transitions, which brings up interesting issues related to the late midlife stage. This paper presents a diary-aided interview study of late middle-age adults (N = 24) in Finland and Sweden with a focus on the interplay between technologies and transitions. Transitions were found to play a part in how the life interests of late middle-aged persons are often conflictive, forcing them to choose from among various 'possible selves'. At its best, technology can help alleviate these tensions. This finding is exemplified in the paper's discussion of two design implications associated with particular clashes of interests, related to how daily activities are organized and how contact is maintained with one's friends and family. © 2010 Elsevier Ltd. All rights reserved. Source

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