CV4 Impact of Short Periods with Improved or Worsened INR Control on Life Expectancy and QALYs in Patients with Atrial Fibrillation

ObjectivesWarfarin-treated patients with poor international normalized ratio (INR) control, measured with time in therapeutic range (TTR) or the standard deviation of transformed INR (SDTINR), have an increased risk for clinical events. To what extent only a short period with an altered INR control may influence outcomes remains unknown. This study assessed the impact of transient periods of improved or worsened INR control on life expectancy and quality-adjusted life years (QALYs) among warfarin-treated patients with atrial fibrillation (AF) using both metrics.MethodsWarfarin-treated patients with AF, registered in the patient record system Journalia during years 1985-2000, were included. Information on all-cause mortality was collected from the Cause of Death Register. Scenarios where patients were assumed to have a transiently altered INR control during 30 days were modeled statistically using hazard functions, and the impact on remaining life expectancy and QALYs was assessed.ResultsWhen using SDTINR, a 70-year old man within the 2.5th worst INR control percentile was estimated to gain 10.8 days of life or 0.0168 QALYs from a 30-day improvement in INR control to that of an average 70-year old man. Correspondingly, 15.5 days of life or 0.0196 QALYs would be lost if a 70-year old man within the 2.5th best INR control percentile would have an average INR control during 30 days. The magnitudes were smaller when TTR was used to determine INR control.ConclusionsEven short periods of altered INR control is expected to have impact on life expectancy and QALYs among patients with AF

T cells that cannot respond to TGF-β escape control by CD4+CD25+ regulatory T cells

CD4+CD25+ regulatory T (T reg) cells play a pivotal role in control of the immune response. Transforming growth factor-β (TGF-β) has been shown to be required for T reg cell activity; however, precisely how it is involved in the mechanism of suppression is poorly understood. Using the T cell transfer model of colitis, we show here that CD4+CD45RBhigh T cells that express a dominant negative TGF-β receptor type II (dnTβRII) and therefore cannot respond to TGF-β, escape control by T reg cells in vivo. CD4+CD25+ T reg cells from the thymus of dnTβRII mice retain the ability to inhibit colitis, suggesting that T cell responsiveness to TGF-β is not required for the development or peripheral function of thymic-derived T reg cells. In contrast, T reg cell activity among the peripheral dnTβRII CD4+CD25+ population is masked by the presence of colitogenic effector cells that cannot be suppressed. Finally, we show that CD4+CD25+ T reg cells develop normally in the absence of TGF-β1 and retain the ability to suppress colitis in vivo. Importantly, the function of TGF-β1−/− T reg cells was abrogated by anti–TGF-β monoclonal antibody, indicating that functional TGF-β can be provided by a non–T reg cell source

A Reflection on Economic Uncertainty and Fertility in Europe: The Narrative Framework

none5openVignoli, Daniele; Guetto, Raffaele; Bazzani, Giacomo; Pirani, Elena; Minello, AlessandraVignoli, Daniele; Guetto, Raffaele; Bazzani, Giacomo; Pirani, Elena; Minello, Alessandr

Beyond What Meets the Eye: Imaging and Imagining Wood Mechanical–Structural Properties

Abstract: Wood presents a hierarchical structure, containing features at all length scales: from the tracheids or vessels that make up its cellular structure, through to the microfibrils within the cell walls, down to the molecular architecture of the cellulose, lignin, and hemicelluloses that comprise its chemical makeup. This structure renders it with high mechanical (e.g., modulus and strength) and interesting physical (e.g., optical) properties. A better understanding of this structure, and how it plays a role in governing mechanical and other physical parameters, will help to better exploit this sustainable resource. Here, recent developments on the use of advanced imaging techniques for studying the structural properties of wood in relation to its mechanical properties are explored. The focus is on synchrotron nuclear magnetic resonance spectroscopy, X‐ray diffraction, X‐ray tomographical imaging, Raman and infrared spectroscopies, confocal microscopy, electron microscopy, and atomic force microscopy. Critical discussion on the role of imaging techniques and how fields are developing rapidly to incorporate both spatial and temporal ranges of analysis is presented