A four-quadrant switched capacitor DC-DC convertor enabling power-efficient lab-grade potentiostats

This paper presents a low-power potentiostat based on a four-quadrant switched capacitor DC-DC convertor for use in lab applications. The gearbox convertor achieves a compliance voltage of ±2.5V. Through the use of frequency scaling, the convertor features output currents in the range of 1µA to 1mA, outclassing other state-of-the-art power efficient potentiostats. A hysteretic control loop and a seperate hysteretic comparator allow the potentiostat to be used for both voltammetric and ampere-metric experiments. Simulations demonstrate a peak efficiency of 87%, and a competitive overall efficiency. The system is designed and simulated in a 0.35µm process

Secondary adrenal insufficiency after treatment with budesonide for autoimmune hepatitis

Autoimmune hepatitis (AIH) is a rare cause of chronic liver disease. The backbone of treatment is immunosuppressive medication, typically prednisolone as induction therapy and azathioprine as a maintenance therapy. Side effects of the long-term use of systemic corticosteroids are well known and have led to the use of alternative induction regimens. An attractive alternative is budesonide, a nonhalogenated glucocorticosteroid characterized by a high first-pass effect in the liver (90%), resulting in a high topical anti-inflammatory activity and a low systemic activity. It should be stressed that budesonide is contraindicated in patients with established cirrhosis with portal hypertension and portocaval shunting. In this case report, we present the first case of adrenal insufficiency following treatment with budesonide for AIH

Aminotransferases During Treatment Predict Long-Term Survival in Patients With Autoimmune Hepatitis Type 1:A Landmark Analysis

Background & Aims: Biochemical remission, important treatment goal in autoimmune hepatitis (AIH), has been associated with better long-term survival. The aim of this study was to determine the independent prognostic value of aminotransferases and immunoglobulin G (IgG) during treatment on long-term transplant-free survival in AIH. Methods: In a multicenter cohort alanine aminotransferase, aspartate aminotransferase (AST), and IgG were collected at diagnosis and 6, 12, 24, and 36 months after start of therapy and related to long-term outcome using Kaplan-Meier survival and Cox regression analysis with landmark analysis at these time points, excluding patients with follow-up ending before each landmark. Results: A total of 301 AIH patients with a median follow-up of 99 (range, 7–438) months were included. During follow-up, 15 patients required liver transplantation and 33 patients died. Higher AST at 12 months was associated with worse survival (hazard ratio [HR], 1.86; P < .001), while IgG was not associated with survival (HR, 1.30; P = .53). In multivariate analysis AST at 12 months (HR, 2.13; P < .001) was predictive for survival independent of age, AST at diagnosis and cirrhosis. Multivariate analysis for AST yielded similar results at 6 months (HR, 2.61; P = .001), 24 months (HR, 2.93; P = .003), and 36 months (HR, 3.03; P = .010). There was a trend toward a worse survival in patients with mildly elevated aminotransferases (1–1.5× upper limit of normal) compared with patients with normal aminotransferases (P = .097). Conclusions: Low aminotransferases during treatment are associated with a better long-term survival in autoimmune hepatitis. IgG was not associated with survival in first 12 months of treatment. Normalization of aminotransferases should be the treatment goal for autoimmune hepatitis to improve long-term survival

Osteopontin characterizes bile duct-associated macrophages and correlates with liver fibrosis severity in primary sclerosing cholangitis

Background and Aims: Primary sclerosing cholangitis (PSC) is an immune-mediated cholestatic liver disease for which pharmacological treatment options are currently unavailable. PSC is strongly associated with colitis and a disruption of the gut-liver axis, and macrophages are involved in the pathogenesis of PSC. However, how gut-liver interactions and specific macrophage populations contribute to PSC is incompletely understood. Approach and Results: We investigated the impact of cholestasis and colitis on the hepatic and colonic microenvironment, and performed an in-depth characterization of hepatic macrophage dynamics and function in models of concomitant cholangitis and colitis. Cholestasis-induced fibrosis was characterized by depletion of resident KCs, and enrichment of monocytes and monocyte-derived macrophages (MoMFs) in the liver. These MoMFs highly express triggering-receptor-expressed-on-myeloid-cells-2 (Trem2) and osteopontin (Spp1), markers assigned to hepatic bile duct-associated macrophages, and were enriched around the portal triad, which was confirmed in human PSC. Colitis induced monocyte/macrophage infiltration in the gut and liver, and enhanced cholestasis-induced MoMF-Trem2 and Spp1 upregulation, yet did not exacerbate liver fibrosis. Bone marrow chimeras showed that knockout of Spp1 in infiltrated MoMFs exacerbates inflammation in vivo and in vitro, while monoclonal antibody–mediated neutralization of SPP1 conferred protection in experimental PSC. In human PSC patients, serum osteopontin levels are elevated compared to control, and significantly increased in advanced stage PSC and might serve as a prognostic biomarker for liver transplant-free survival. Conclusions: Our data shed light on gut-liver axis perturbations and macrophage dynamics and function in PSC and highlight SPP1/OPN as a prognostic marker and future therapeutic target in PSC.publishedVersio

Development and validation of a prognostic score for long-term transplant-free survival in autoimmune hepatitis type 1

Background No prognostic score is currently available for long-term survival in autoimmune hepatitis (AIH) patients. Objective The aim of this study was to develop and validate such a prognostic score for AIH patients at diagnosis. Methods The prognostic score was developed using uni- & multivariate Cox regression in a 4-center Dutch cohort and validated in an independent 6-center Belgian cohort. Results In the derivation cohort of 396 patients 19 liver transplantations (LTs) and 51 deaths occurred (median follow-up 118 months; interquartile range 60-202 months). In multivariate analysis age (hazard ratio [HR] 1.045; p < 0.001), non-caucasian ethnicity (HR 1.897; p = 0.045), cirrhosis (HR 3.266; p < 0.001) and alanine aminotransferase level (HR 0.725; p = 0.003) were significant independent predictors for mortality or LT (C-statistic 0.827; 95% CI 0.790-0.864). In the validation cohort of 408 patients death or LT occurred in 78 patients during a median follow-up of 74 months (interquartile range: 25-142 months). Predicted 5-year event rate did not differ from observed event rate (high risk group 21.5% vs. 15.7% (95% CI: 6.3%-24.2%); moderate risk group 5.8% versus 4.3% (95% CI: 0.0%-9.1%); low risk group 1.9% versus 5.4% (95% CI: 0.0%-11.4%); C-statistic 0.744 [95% CI 0.644-0.844]). Conclusions A Dutch-Belgian prognostic score for long-term transplant-free survival in AIH patients at diagnosis was developed and validated

Political representation in local governance: a survey analysis of councillor attitudes and behaviour in Belgium

Recent evolutions in Western societies have sparked renewed debate on the state of political representation. This article contributes to the debate by applying a multifaceted typology developed by Andeweg and Thomassen (2005) to study political representation in Belgian local governance. The article empirically outlines the notions of 856 local councillors on political representation at the attitudinal and behavioural level. Furthermore, it searches to explain variation in the latter according to councillors' political and personal profile, their contact pattern, and the local government context. The article paints a balanced picture. The largest group of councillors prefer an all-round style, paying equal importance to authorization, accountability, delegation and responsiveness as basic styles or modes of political representation. Still we perceive a clear shift from councillors' attitudes, in which delegation takes the upper hand, to their acclaimed behaviour, which becomes more entrepreneurial as it is often hypothesized. Meanwhile, councillors' personal profile and contact pattern seem the most important determinants of political representation

Study of the optimal control problem formulation for modulating air-to-water heat pumps connected to a residential floor heating system

For implementation in low-level controllers with limited computational power, simplified optimal control formulations are highly desirable. For the case of a modulating heat pump system, however, the optimization problem is nonlinear due to the supply water temperature and load dependency of the heat pump coefficient of performance (COP). These nonlinearities do not only slow down computations but may also give rise to multiple local minima. By neglecting these nonlinearities, e.g., by assuming a constant COP value, the optimal control problem becomes convex and fast convergence to the unique and global minimum is ensured. However, a performance loss due to the simplifications is expected. In this paper this performance loss is quantified for the case of a modulating air-to-water heat pump connected to a floor heating system in a residential building. Different levels of simplification are investigated. The most detailed heat pump model takes all the nonlinearities into account, while the simplest one assumes a constant COP. A first comparison suggests a significant impact of the heat pump model on the control performance. The formulations with the nonlinear models result in continuous heat pump operation at part load while the convex approximations give rise to large heat pump power fluctuations. The latter results in an energy cost increase of 7\% to 16\%. However, by penalizing power peaks in the cost function, the control performance obtained with the convex approximations is almost identical to the one obtained with the nonlinear models. Analysis of the different control trajectories and the resulting control performance reveals that the cost function is very flat near the optimum. For the investigated case, the savings in energy consumption and energy cost compared to a conventional heating curve control strategy amount to respectively 1% and 5% (in the case of a day/night tariff structure), suggesting only a minor potential for optimization-based control strategies for the investigated application.status: publishe

A Four-Quadrant Switched Capacitor DC-DC Convertor Enabling Power-Efficient Lab-Grade Potentiostats

This paper presents a low-power potentiostat based on a four-quadrant switched capacitor DC-DC convertor for use in lab applications. The gearbox convertor achieves a compliance voltage of ±2.5V. Through the use of frequency scaling, the convertor features output currents in the range of 1µA to 1mA, outclassing other state-of-the-art power efficient potentiostats. A hysteretic control loop and a seperate hysteretic comparator allow the potentiostat to be used for both voltammetric and ampere-metric experiments. Simulations demonstrate a peak efficiency of 87%, and a competitive overall efficiency. The system is designed and simulated in a 0.35µm process.status: Published onlin