Effect of changes over time in the performance of a customized SAPS-II model on the quality of care assessment

Purpose: The aim of our study was to explore, using an innovative method, the effect of temporal changes in the mortality prediction performance of an existing model on the quality of care assessment. The prognostic model (rSAPS-II) was a recalibrated Simplified Acute Physiology Score-II model developed for very elderly Intensive Care Unit (ICU) patients. Methods: The study population comprised all 12,143 consecutive patients aged 80 years and older admitted between January 2004 and July 2009 to one of the ICUs of 21 Dutch hospitals. The prospective dataset was split into 30 equally sized consecutive subsets. Per subset, we measured the model's discrimination [area under the curve (AUC)], accuracy (Brier score), and standardized mortality ratio (SMR), both without and after repeated recalibration. All performance measures were considered to be stable if 1 without and after repeated recalibration for the year 2009. Results: For all subsets, the AUCs were stable, but the Brier scores and SMRs were not. The SMR was downtrending, achieving levels significantly below 1. Repeated recalibration rendered it stable again. The proportions of hospitals with SMR>1 and SMR <1 changed from 15 versus 85% to 35 versus 65%. Conclusions: Variability over time may markedly vary among different performance measures, and infrequent model recalibration can result in improper assessment of the quality of care in many hospitals. We stress the importance of the timely recalibration and repeated validation of prognostic models over tim

Bone marrow mesenchymal stem cells do not enhance intra-synovial tendon healing despite engraftment and homing to niches within the synovium

Intra-synovial tendon injuries display poor healing, which often results in reduced functionality and pain. A lack of effective therapeutic options has led to experimental approaches to augment natural tendon repair with autologous mesenchymal stem cells (MSCs) although the effects of the intra-synovial environment on the distribution, engraftment and functionality of implanted MSCs is not known. This study utilised a novel sheep model which, although in an anatomically different location, more accurately mimics the mechanical and synovial environment of the human rotator cuff, to determine the effects of intra-synovial implantation of MSCs

Utilization of livers donated after circulatory death for transplantation - An international comparison.

BACKGROUND AND AIM Liver graft utilization rates are a hot topic due to the worldwide organ shortage and an increasing number of transplant candidates on waiting lists. Liver perfusion techniques have been introduced in several countries, and may help to increase the organ supply, as they potentially allow the assessment of livers before use. METHODS Liver offers were counted from donation after circulatory death (DCD) donors (Maastricht-type-III) arising during the past decade in eight countries, including Belgium, France, Italy, the Netherlands, Spain, Switzerland, UK, and US. Initial DCD-type-III liver offers were correlated with accepted, recovered and implanted livers. RESULTS A total number of 34`269 DCD livers were offered, resulting in 9`780 liver transplants (28.5%). The discard rates were highest in UK and US, ranging between 70 and 80%. In contrast, much lower DCD liver discard rates, e.g., between 30-40%, were found in Belgium, France, Italy, Spain and Switzerland. In addition, large differences were recognized in the use of various machine perfusion techniques, and in terms of risk factors in the cohorts of implanted livers. For example, the median donor age and functional donor warm ischemia were highest in Italy, e.g., >40minutes, followed by Switzerland, France, and the Netherlands. Importantly, such varying risk profiles of accepted DCD livers between countries did not translate into large differences in five-year graft survival rates, which ranged between 60-82% in this analysis. CONCLUSIONS We highlight a significant number of discarded and consequently unused DCD liver offers. Countries with more routine use of in- and ex-situ machine perfusion strategies showed better DCD utilization rates without compromised outcome. IMPACT AND IMPLICATIONS A significant number of Maastricht type III DCD livers are discarded across Europe and North America today. The overall utilization rate among eight Western countries is 28.5%, but varies significantly between 18.9% and 74.2%. For example, the median DCD III liver utilization in five countries, e.g., Belgium, France, Italy, Switzerland, and Spain is 65%, in contrast to 24% in the Netherlands, UK and US. Despite this, and despite different rules and strategies for organ acceptance and preservation, the one and five-year graft survival remains currently relatively comparable among all participating countries. Factors which impact on DCD liver acceptance rates include the national pre-selections of donors, before the offer is made, as well as cutoffs for key risk factors, including donor age and donor warm ischemia time. In addition, a highly varying experience with modern machine perfusion technology is noticed. In situ and ex situ liver perfusion concepts, and assessment tools for type III DCD livers before transplantation may be one key part for the observed differences in better DCD III utilization

Elucidating the real-time Ag nanoparticle growth on a-Ag2WO4 during electron beam irradiation: experimental evidence and theoretical insights

Why and how Ag is formed when electron beam irradiation takes place on α-Ag2WO4 in a vacuum transmission electron microscopy chamber? To find an answer, the atomic-scale mechanisms underlying the formation and growth of Ag on α-Ag2WO4 have been investigated by detailed in situ transmission electron microscopy (TEM) and field emission scanning electron microscopy (FE-SEM) studies, density functional theory based calculations and ab initio molecular dynamics simulations. The growth process at different times, chemical composition, size distribution and element distribution were analyzed in depth at the nanoscale level using FE-SEM, operated at different voltages (5, 10, 15, and 20 kV), and TEM with energy dispersive spectroscopy (EDS) characterization. The size of Ag nanoparticles covers a wide range of values. Most of the Ag particles are in the 20–40 nm range. The nucleation and formation of Ag on α-Ag2WO4 is a result of structural and electronic changes in the AgOx (x = 2,4, 6, and 7) clusters used as constituent building blocks of this material, consistent with metallic Ag formation. First principle calculations point out that Ag-3 and Ag-4-fold coordinated centers, located in the sub-surface of the (100) surface, are the most energetically favorable to undergo the diffusion process to form metallic Ag. Ab initio molecular dynamics simulations and the nudged elastic band (NEB) method were used to investigate the minimum energy pathways of these Ag atoms from positions in the first slab layer to outward sites on the (100) surface of α-Ag2WO4. The results point out that the injection of electrons decreases the activation barrier for this diffusion step and this unusual behavior results from the presence of a lower energy barrier process.Generalitat-Valenciana: Prometeo/2009/053 Ministerio de Economia y Competitividad (Spain): CTQ2012-36253-C03-02 Spanish Brazilian program: PHB2009-0065-PC FAPESP : 2013/07296-2, 2012/14468-1, 2010/16970-0, 2013/02032-7. CAPES CNPq : 573636/2008-7, 150753/2013-6. CAPES : 088/201

Farmer seed networks make a limited contribution to agriculture? Four common misconceptions

The importance of seed provisioning in food security and nutrition, agricultural development and rural livelihoods, and agrobiodiversity and germplasm conservation is well accepted by policy makers, practitioners and researchers. The role of farmer seed networks is less well understood and yet is central to debates on current issues ranging from seed sovereignty and rights for farmers to GMOs and the conservation of crop germplasm. In this paper we identify four common misconceptions regarding the nature and importance of farmer seed networks today. (1) Farmer seed networks are inefficient for seed dissemination. (2) Farmer seed networks are closed, conservative systems. (3) Farmer seed networks provide ready, egalitarian access to seed. (4) Farmer seed networks are destined to weaken and disappear. We challenge these misconceptions by drawing upon recent research findings and the authors’ collective field experience in studying farmer seed systems in Africa, Europe, Latin America and Oceania. Priorities for future research are suggested that would advance our understanding of seed networks and better inform agricultural and food policy

A new ultrafast and high-throughput mass spectrometric approach for the therapeutic drug monitoring of the multi-targeted anti-folate pemetrexed in plasma from lung cancer patients

An analytical assay has been developed and validated for ultrafast and high-throughput mass spectrometric determination of pemetrexed concentrations in plasma using matrix assisted laser desorption/ionization–triple quadrupole–tandem mass spectrometry. Patient plasma samples spiked with the internal standard methotrexate were measured by multiple reaction monitoring. The detection limit was 0.4 fmol/μL, lower limit of quantification was 0.9 fmol/μL, and upper limit of quantification was 60 fmol/μL, respectively. Overall observed pemetrexed concentrations in patient samples ranged between 8.7 (1.4) and 142.7 (20.3) pmol/μL (SD). The newly developed mass spectrometric assay is applicable for (routine) therapeutic drug monitoring of pemetrexed concentrations in plasma from non-small cell lung cancer patients