Decentralization and Electoral Accountability : Incentives, Separation, and Voter Welfare

This paper studies the relationship between fiscal decentralization and electoral accountability, by analyzing how decentralization impacts upon incentive and selection effects, and thus on voter welfare. The model abstracts from features such as public good spillovers or economies of scale, so that absent elections, voters are indifferent about the fiscal regime. The effect of fiscal centralization on voter welfare works through two channels : (i) via its effect on the probability of pooling by the bad incumbent; (ii) conditional on the probability of pooling, the extent to which, with centralization, the incumbent can divert rents in some regions without this being detected by voters in other regions (selective rent diversion). Both these effects depend on the information structure ; whether voters only observe fiscal policy in their own region, in all regions, or an intermediate case with a uniform tax across all regions. More voter information does not necessarily raise voter welfare, and under some conditions, voter would choose uniform over differentiated taxes ex ante to constrain selective rent diversion

Borderline Aggregation Kinetics in ``Dry'' and ``Wet'' Environments

We investigate the kinetics of constant-kernel aggregation which is augmented by either: (a) evaporation of monomers from finite-mass clusters, or (b) continuous cluster growth -- \ie, condensation. The rate equations for these two processes are analyzed using both exact and asymptotic methods. In aggregation-evaporation, if the evaporation is mass conserving, \ie, the monomers which evaporate remain in the system and continue to be reactive, the competition between evaporation and aggregation leads to several asymptotic outcomes. For weak evaporation, the kinetics is similar to that of aggregation with no evaporation, while equilibrium is quickly reached in the opposite case. At a critical evaporation rate, the cluster mass distribution decays as $k^{-5/2}$, where $k$ is the mass, while the typical cluster mass grows with time as $t^{2/3}$. In aggregation-condensation, we consider the process with a growth rate for clusters of mass $k$, $L_k$, which is: (i) independent of $k$, (ii) proportional to $k$, and (iii) proportional to $k^\mu$, with $0<\mu<1$. In the first case, the mass distribution attains a conventional scaling form, but with the typical cluster mass growing as $t\ln t$. When $L_k\propto k$, the typical mass grows exponentially in time, while the mass distribution again scales. In the intermediate case of $L_k\propto k^\mu$, scaling generally applies, with the typical mass growing as $t^{1/(1-\mu)}$. We also give an exact solution for the linear growth model, $L_k\propto k$, in one dimension.Comment: plain TeX, 17 pages, no figures, macro file prepende

Unicyclic Components in Random Graphs

The distribution of unicyclic components in a random graph is obtained analytically. The number of unicyclic components of a given size approaches a self-similar form in the vicinity of the gelation transition. At the gelation point, this distribution decays algebraically, U_k ~ 1/(4k) for k>>1. As a result, the total number of unicyclic components grows logarithmically with the system size.Comment: 4 pages, 2 figure

Atherosclerosis and liver inflammation induced by increased dietary cholesterol intake: a combined transcriptomics and metabolomics analysis

With increasing dietary cholesterol intake the liver switches from a mainly resilient to a predominantly inflammatory state, which is associated with early lesion formation

Effect of body fat distribution on the transcription response to dietary fat interventions

Combination of decreased energy expenditure and increased food intake results in fat accumulation either in the abdominal site (upper body obesity, UBO) or on the hips (lower body obesity, LBO). In this study, we used microarray gene expression profiling of adipose tissue biopsies to investigate the effect of body fat distribution on the physiological response to two dietary fat interventions. Mildly obese UBO and LBO male subjects (n = 12, waist-to-hip ratio range 0.93–1.12) were subjected to consumption of diets containing predominantly either long-chain fatty acids (PUFA) or medium-chain fatty acids (MCT). The results revealed (1) a large variation in transcription response to MCT and PUFA diets between UBO and LBO subjects, (2) higher sensitivity of UBO subjects to MCT/PUFA dietary intervention and (3) the upregulation of immune and apoptotic pathways and downregulation of metabolic pathways (oxidative, lipid, carbohydrate and amino acid metabolism) in UBO subjects when consuming MCT compared with PUFA diet. In conclusion, we report that despite the recommendation of MCT-based diet for improving obesity phenotype, this diet may have adverse effect on inflammatory and metabolic status of UBO subjects. The body fat distribution is, therefore, an important parameter to consider when providing personalized dietary recommendation

Supplementation with Lactobacillus plantarum WCFS1 Prevents Decline of Mucus Barrier in Colon of Accelerated Aging Ercc1−/Δ7 Mice

textabstractAlthough it is clear that probiotics improve intestinal barrier function, little is known about the effects of probiotics on the aging intestine. We investigated effects of 10-week bacterial supplementation of Lactobacillus plantarum WCFS1, Lactobacillus casei BL23, or Bifidobacterium breve DSM20213 on gut barrier and immunity in 16-week-old accelerated aging Ercc1-/Δ7 mice, which have a median lifespan of ~20 weeks, and their wild-type littermates. The colonic barrier in Ercc1-/Δ7 mice was characterized by a thin (< 10 μm) mucus layer. L. plantarum prevented this decline in mucus integrity in Ercc1-/Δ7 mice, whereas B. breve exacerbated it. Bacterial supplementations affected the expression of immune-related genes, including Toll-like receptor 4. Regulatory T cell frequencies were increased in the mesenteric lymph nodes of L. plantarum- and L. casei-treated Ercc1-/Δ7 mice. L. plantarum- and L. casei-treated Ercc1-/Δ7 mice showed increased specific antibody production in a T cell-dependent immune response in vivo. By contrast, the effects of bacterial supplementation on wild-type control mice were negligible. Thus, supplementation with L. plantarum - but not with L. casei and B. breve - prevented the decline in the mucus barrier in Ercc1-/Δ7 mice. Our data indicate that age is an important factor influencing beneficial or detrimental effects of candidate probiotics. These findings also highlight the need for caution in translating beneficial effects of probiotics observed in young animals or humans to the elderly

Investigation of the added value of CT-based radiomics in predicting the development of brain metastases in patients with radically treated stage III NSCLC

Introduction: Despite radical intent therapy for patients with stage III non-small-cell lung cancer (NSCLC), cumulative incidence of brain metastases (BM) reaches 30%. Current risk stratification methods fail to accurately identify these patients. As radiomics features have been shown to have predictive value, this study aims to develop a model combining clinical risk factors with radiomics features for BM development in patients with radically treated stage III NSCLC. Methods: Retrospective analysis of two prospective multicentre studies. Inclusion criteria: adequately staged [18F-fluorodeoxyglucose positron emission tomography-computed tomography (18-FDG-PET-CT), contrast-enhanced chest CT, contrast-enhanced brain magnetic resonance imaging/CT] and radically treated stage III NSCLC, exclusion criteria: second primary within 2 years of NSCLC diagnosis and prior prophylactic cranial irradiation. Primary endpoint was BM development any time during follow-up (FU). CT-based radiomics features (N = 530) were extracted from the primary lung tumour on 18-FDG-PET-CT images, and a list of clinical features (N = 8) was collected. Univariate feature selection based on the area under the curve (AUC) of the receiver operating characteristic was performed to identify relevant features. Generalized linear models were trained using the selected features, and multivariate predictive performance was assessed through the AUC. Results: In total, 219 patients were eligible for analysis. Median FU was 59.4 months for the training cohort and 67.3 months for the validation cohort; 21 (15%) and 17 (22%) patients developed BM in the training and validation cohort, respectively. Two relevant clinical features (age and adenocarcinoma histology) and four relevant radiomics features were identified as predictive. The clinical model yielded the highest AUC value of 0.71 (95% CI: 0.58–0.84), better than radiomics or a combination of clinical parameters and radiomics (both an AUC of 0.62, 95% CIs of 0.47–076 and 0.48–0.76, respectively). Conclusion: CT-based radiomics features of primary NSCLC in the current setup could not improve on a model based on clinical predictors (age and adenocarcinoma histology) of BM development in radically treated stage III NSCLC patients

Comparison of Outcome After Percutaneous Mitral Valve Repair With the MitraClip in Patients With Versus Without Atrial Fibrillation

Percutaneous mitral valve repair with the MitraClip is an established treatment for patients with mitral regurgitation (MR) who are inoperable or at high risk for surgery. Atrial Fibrillation (AF) frequently coincides with MR, but only scarce data of the influence of AF on outcome after MitraClip is available. The aim of the current study was to compare the clinical outcome after MitraClip treatment in patients with versus without atrial fibrillation. Between January 2009 and January 2016, all consecutive patients treated with a MitraClip in 5 Dutch centers were included. Outcome measures were survival, symptoms, MR grade, and stroke incidence. In total, 618 patients were treated with a MitraClip. Patients with AF were older, had higher N-terminal B-type natriuretic peptide levels, more tricuspid regurgitation, less often coronary artery disease and a better left ventricular function. Survival of patients treated with the MitraClip was similar for patients with AF (82%) and without AF (non-AF; 85%) after 1 year (p = 0.30), but significantly different after 5-year follow-up (AF 34%; non-AF 47%; p = 0.006). After 1 month, 64% of the patients with AF were in New York Heart Association class I or II, in contrast to 77% of the patients without AF (p = 0.001). The stroke incidence appeared not to be significantly different (AF 1.8%; non-AF 1.0%; p = 0.40). In conclusion, patients with AF had similar 1-year survival, MR reduction, and stroke incidence compared with non-AF patients. However, MitraClip patients with AF had reduced long-term survival and remained more symptomatic compared with those without AF.</p

Nonlinear pharmacokinetics of therapeutic proteins resulting from receptor mediated endocytosis

Receptor mediated endocytosis (RME) plays a major role in the disposition of therapeutic protein drugs in the body. It is suspected to be a major source of nonlinear pharmacokinetic behavior observed in clinical pharmacokinetic data. So far, mostly empirical or semi-mechanistic approaches have been used to represent RME. A thorough understanding of the impact of the properties of the drug and of the receptor system on the resulting nonlinear disposition is still missing, as is how to best represent RME in pharmacokinetic models. In this article, we present a detailed mechanistic model of RME that explicitly takes into account receptor binding and trafficking inside the cell and that is used to derive reduced models of RME which retain a mechanistic interpretation. We find that RME can be described by an extended Michaelis–Menten model that accounts for both the distribution and the elimination aspect of RME. If the amount of drug in the receptor system is negligible a standard Michaelis–Menten model is capable of describing the elimination by RME. Notably, a receptor system can efficiently eliminate drug from the extracellular space even if the total number of receptors is small. We find that drug elimination by RME can result in substantial nonlinear pharmacokinetics. The extent of nonlinearity is higher for drug/receptor systems with higher receptor availability at the membrane, or faster internalization and degradation of extracellular drug. Our approach is exemplified for the epidermal growth factor receptor system