Purpose To investigate the performance of two microwave ablation (MWA) systems regarding ablation volume, ablation shape and variability. Materials and Methods In this ex vivo study, the Emprint... Show morePurpose To investigate the performance of two microwave ablation (MWA) systems regarding ablation volume, ablation shape and variability. Materials and Methods In this ex vivo study, the Emprint and Amica MWA systems were used to ablate porcine livers at 4 different settings of time and power (3 and 5 minutes at 60 and 80 Watt). In total, 48 ablations were analysed for ablation size and shape using Vitrea Advanced Visualization software after acquisition of a 7T MRI scan. Results Emprint ablations were smaller (11,1 vs. 21,1 mL p < 0.001), more spherical (sphericity index of 0.89 vs. 0.59 p < 0.001) and showed less variability than Amica ablations. In both systems, longer ablation time and higher power resulted in significantly larger ablation volumes. Conclusion Emprint ablations were more spherical, and the results showed a lower variability than those of Amica ablations. This comes at the price of smaller ablation volumes. Show less
Background Glycemic variation has been suggested to be a risk factor for diabetes-related complications. Previous studies did not address confounding of diabetes duration, number of visits and... Show moreBackground Glycemic variation has been suggested to be a risk factor for diabetes-related complications. Previous studies did not address confounding of diabetes duration, number of visits and length of follow-up. Here, we characterize glycemic variability over time and whether its relation to diabetes-related complications and mortality is independent from diabetes- and follow-up duration. Materials and methods Individuals with type 2 diabetes (n = 6770) from the Hoorn Diabetes Care System cohort were included in this study. The coefficient of variation (CV) was calculated over 5-year sliding intervals. People divided in quintiles based on their CV. Cox proportional hazard models were used to investigate the role of glycemic CV as risk factor in diabetes-related complications and mortality. Results The coefficient of variation of glucose (FG-CV) increased with time, in contrast to HbA1c (HbA1c-CV). People with a high FG-CV were those with an early age of diabetes onset (Delta(Q5-Q1) = - 2.39 years), a higher BMI (Delta(Q5-Q1) = + 0.92 kg/m(2)), an unfavorable lipid profile, i.e. lower levels of HDL-C (Delta(Q5-Q1) = - 0.06 mmol/mol) and higher triglycerides (Delta(Q5-Q1) =+ 1.20 mmol/mol). People with the highest FG-CV in the first 5-year interval showed an increased risk of insulin initiation, retinopathy, macrovascular complications and mortality independent of mean glycemia, classical risk factors and medication use. For HbA1c, the associations were weaker and less consistent. Conclusions Individuals with a higher FG-CV have an unfavorable metabolic profile and have an increased risk of developing micro- and macrovascular complications and mortality. The association of HbA1c-CV with metabolic outcomes and complications was less consistent in comparison to FG-CV. Show less
Bottcher, S.; Velden, V.H.J. van der; Villamor, N.; Ritgen, M.; Flores-Montero, J.; Escobar, H.M.; ... ; Orfao, A. 2019
The fluorescence detected using fluorochrome-labelled monoclonal antibodies depends not only on the abundance of the target antigen, but amongst many other factors also on the effective... Show moreThe fluorescence detected using fluorochrome-labelled monoclonal antibodies depends not only on the abundance of the target antigen, but amongst many other factors also on the effective fluorochrome-to-antibody ratio. The diagnostic approach of the EuroFlow consortium relies on reproducible fluorescence intensities over time.A capture bead system for mouse immunoglobulin light chains was utilized to compare the mean fluorescence intensity of 1323 consecutive antibody lots to the currently used lot of the same monoclonal antibody. In total, 157 different monoclonal antibodies were assessed over seven years. Median relative difference between consecutive lots was 3.8% (range: 0.01% to 164.7%, interquartile range: 1.3% to 10.1%). The relative difference exceeded 20% in 8.8% of all comparisons. F1TC labelled monoclonal antibodies (median relative difference: 2.1%) showed a significantly smaller variation between lots than antibodies conjugated to PE (3.5%), PECy7 (3.9%), PerCPCy5.5 (5.8%), APC (5.8%),APCH7 ( 7.4%), and APCC750 (14.5%). Reagents labelled with Pacific Blue (1.4%), Pacific Orange (2.4%), HV450 (0.7%), and HV500 (1.7%) demonstrated more consistent results compared to conjugates of BV421 (4.1%) and BV510 (16.2%). Additionally, significant differences in lot-to-lot fluorescence stability amongst antibodies labelled with the same fluorochrome were observed between manufacturers.These observations might guide future quality recommendations for the production and application of fluorescence-labelled monoclonal antibodies in multicolor flow cytometry. (C) 2017 Published by Elsevier B.V. Show less
Translation across species and from in vitro to in vivo is a central tenet in drug discovery pharmacology. Successful implementation requires proper assessment of both in vivo potency and efficacy.... Show moreTranslation across species and from in vitro to in vivo is a central tenet in drug discovery pharmacology. Successful implementation requires proper assessment of both in vivo potency and efficacy. This notwith- standing, in vivo data is typically defined mostly in terms of ligand-to-target binding affinity, similar to in vitrostudies. As in vivo potency and efficacy involve a combination not only of drug, but also partitioning, target, and drug-target-complex events and processes, ignoring some of the central differences between in vivo and in vitromay result in serious miscalculations of in vivo efficacious exposure for translational predictions.We compare potency measures derived from two basic pharmacodynamic model situations: A ‘closed’ in vitrosystem defining target binding of a ligand when both concentrations remain essentially static, and an ‘open’ in vivo system where target turnover dynamics and elimination of the drug-target complex are also included. Corresponding equilibrium (steady-state) expressions in the central pharmacokinetic compartment are derived and presented. Three representative variants of ‘open’ in vivo systems are discussed, showing relationships for ligand-target complex and ligand for each of the systems and graphically illustrating corresponding shapes. The examples include i) two ligands competing for one target, ii) two targets competing for one ligand (/drug), andiii) target-ligand (/drug) interactions in a peripheral PK compartment. The expanded in vivo potency EC50 ex- pression emphasises the contribution from target-related biology parameters that need accounting for, and particularly that ‘closed’ system (in vitro) properties should not be first choice when ranking compounds in vivo(‘open’ system). Show less
Slieker, R.C.; Iterson, M. van; Luijk, R.; Beekman, M.; Zhernakova, D.V.; Moed, M.H.; ... ; BIOS Consortium 2016
With increasing age, incidence and prevalence of cardiovascular disease increase. Many physicians face the dilemma whether or not to start preventive treatment in old age. To help physicians decide... Show moreWith increasing age, incidence and prevalence of cardiovascular disease increase. Many physicians face the dilemma whether or not to start preventive treatment in old age. To help physicians decide whether to advise preventive medication to their older patients, prediction of those at highest or lowest (relative) risk using (preferably) inexpensive and easy to use cardiovascular risk factors is important. However, in old age there is a lack of good cardiovascular risk predictors. This thesis shows that the use of multiple blood pressure measurements expressed in the variability (in diastolic blood pressure) or trends in blood pressure can identify older persons with high cardiovascular risk. It also shows that in the oldest old, the absence or presence of heart failure does not influence the prognostic value of low systolic blood pressure regarding risk of death. The serological biomarker N-terminal pro-B-type natriuretic peptide (NT-proBNP) is found to be an interesting candidate in cardiovascular risk prediction in old age, especially in secondary prevention. In the oldest old, an increase in NT-proBNP still reflects increased risk of (cardiovascular) death, independent of decreasing renal function and is associated with incident heart failure and atrial fibrillation. Show less
Caljouw, M.A.A.; Cools, H.J.M.; Gussekloo, J. 2014
Throughout this research the focus has been on unraveling of the factors and relations that link different aspects of collaborative workflow to strategic performance management. However, the same... Show moreThroughout this research the focus has been on unraveling of the factors and relations that link different aspects of collaborative workflow to strategic performance management. However, the same issues that applied to strategic performance management of supply chains also apply to other areas of strategic performance in business. The following (to be - tested) recommendations, organized along the lines of the "expected managerial contributions" therefore apply both to strategic performance management of supply chains and other strategic business processes. a) The SPI (Strategic Performance Inhibitor) Model will enable an integrated approach to (i) Problem structuring (ii) Problem solving and (iii) Learning for managers on potential threats and problem to strategic performance of supply chains. b) The SPI classification will provide a systematic and structured manner of communicating and addressing potential problems and risk to strategic performance of supply chains. Once classified, each class will have its own type of impact on strategic performance of supply chains and consequently the resolution for it. c) Collaborative Workflow will enable inventory (i.e. right quantity at the right time and right place) to be substitutes by Information (i.e. the right information at the right time and the right place) resulting in cost reduction. Show less
