Tunneling and Metastability of continuous time Markov chains

We propose a new definition of metastability of Markov processes on countable state spaces. We obtain sufficient conditions for a sequence of processes to be metastable. In the reversible case these conditions are expressed in terms of the capacity and of the stationary measure of the metastable states

Abrupt Convergence and Escape Behavior for Birth and Death Chains

We link two phenomena concerning the asymptotical behavior of stochastic processes: (i) abrupt convergence or cut-off phenomenon, and (ii) the escape behavior usually associated to exit from metastability. The former is characterized by convergence at asymptotically deterministic times, while the convergence times for the latter are exponentially distributed. We compare and study both phenomena for discrete-time birth-and-death chains on Z with drift towards zero. In particular, this includes energy-driven evolutions with energy functions in the form of a single well. Under suitable drift hypotheses, we show that there is both an abrupt convergence towards zero and escape behavior in the other direction. Furthermore, as the evolutions are reversible, the law of the final escape trajectory coincides with the time reverse of the law of cut-off paths. Thus, for evolutions defined by one-dimensional energy wells with sufficiently steep walls, cut-off and escape behavior are related by time inversion.Comment: 2 figure

Demagnetization via Nucleation of the Nonequilibrium Metastable Phase in a Model of Disorder

We study both analytically and numerically metastability and nucleation in a two-dimensional nonequilibrium Ising ferromagnet. Canonical equilibrium is dynamically impeded by a weak random perturbation which models homogeneous disorder of undetermined source. We present a simple theoretical description, in perfect agreement with Monte Carlo simulations, assuming that the decay of the nonequilibrium metastable state is due, as in equilibrium, to the competition between the surface and the bulk. This suggests one to accept a nonequilibrium "free-energy" at a mesoscopic/cluster level, and it ensues a nonequilibrium "surface tension" with some peculiar low-T behavior. We illustrate the occurrence of intriguing nonequilibrium phenomena, including: (i) Noise-enhanced stabilization of nonequilibrium metastable states; (ii) reentrance of the limit of metastability under strong nonequilibrium conditions; and (iii) resonant propagation of domain walls. The cooperative behavior of our system may also be understood in terms of a Langevin equation with additive and multiplicative noises. We also studied metastability in the case of open boundaries as it may correspond to a magnetic nanoparticle. We then observe burst-like relaxation at low T, triggered by the additional surface randomness, with scale-free avalanches which closely resemble the type of relaxation reported for many complex systems. We show that this results from the superposition of many demagnetization events, each with a well- defined scale which is determined by the curvature of the domain wall at which it originates. This is an example of (apparent) scale invariance in a nonequilibrium setting which is not to be associated with any familiar kind of criticality.Comment: 26 pages, 22 figure

Helicobacter pylori colonization and obesity - A Mendelian randomization study

Obesity is associated with substantial morbidity, costs, and decreased life expectancy, and continues to rise worldwide. While etiological understanding is needed for prevention, epidemiological studies indicated that colonization with Helicobacter pylori (H. pylori) may affect body mass index (BMI), but with inconsistent results. Here, we examine the relationship between H. pylori colonization and BMI/obesity. Cross-sectional analyses were performed in two independent population-based cohorts of elderly from the Netherlands and Germany (n = 13,044). Genetic risk scores were conducted based on genetic loci associated with either H. pylori colonization or BMI/obesity. We performed a bi-directional Mendelian randomization. Meta-analysis of cross-sectional data revealed no association between anti-H. pylori IgG titer and BMI, nor of H. pylori positivity and BMI. Anti-H. pylori IgG titer was negatively associated with obesity (OR 0.99972; 95% CI 0.99946-0.99997, p = 0.03) and with obesity classes (Beta -6.91 •10-5; 95% CI -1.38•10-4, -5.49•10-7, p = 0.048), but the magnitude of these effects was limited. Mendelian randomization showed no causal relation between H. pylori genetic risk score and BMI/obesity, nor between BMI or obesity genetic risk scores and H. pylori positivity. This study provides no evidence for a clinically relevant association between H. pylori and BMI/obesity

Overlap of genetic loci for central serous chorioretinopathy with age-related macular degeneration

IMPORTANCE Central serous chorioretinopathy (CSC) is a serous maculopathy of unknown etiology. Two of 3 previously reported CSC genetic risk loci are also associated with AMD. Improved understanding of CSC genetics may broaden our understanding of this genetic overlap and unveil mechanisms in both diseases.OBJECTIVE To identify novel genetic risk factors for CSC and compare genetic risk factors for CSC and AMD.DESIGN, SETTING, AND PARTICIPANTS Using International Classification of Diseases, Ninth (ICD-9) and Tenth (ICD-10) Revision code-based inclusion and exclusion criteria, patients with CSC and controls were identified in both the FinnGen study and the Estonian Biobank (EstBB). Also included in ameta-analysis were previously reported patients with chronic CSC and controls. Data were analyzed from March 1 to September 31, 2022.MAIN OUTCOMES AND MEASURES Genome-wide association studies (GWASs) were performed in the biobank-based cohorts followed by ameta-analysis of all cohorts. The expression of genes prioritized by the polygenic priority score and nearest-gene methods were assessed in cultured choroidal endothelial cells and public ocular single-cell RNA sequencing data sets. The predictive utility of polygenic scores (PGSs) for CSC and AMD were evaluated in the FinnGen study.RESULTS A total of 1176 patients with CSC and 526 787 controls (312 162 female [59.3%]) were included in this analysis: 552 patients with CSC and 343 461 controls were identified in the FinnGen study, 103 patients with CSC and 178 573 controls were identified in the EstBB, and 521 patients with chronic CSC and 3577 controls were included in ameta-analysis. Two previously reported CSC risk loci were replicated (near CFH and GATA5) and 3 novel loci were identified (near CD34/46, NOTCH4, and PREX1). The CFH and NOTCH4 loci were associated with AMD but in the opposite direction. Prioritized genes showed increased expression in cultured choroidal endothelial cells compared with other genes in the loci (median [IQR] of log 2 [counts per million], 7.3 [0.6] vs 4.7 [3.7]; P =.004) and were differentially expressed in choroidal vascular endothelial cells in single-cell RNA sequencing data (mean [SD] fold change, 2.05 [0.38] compared with other cell types; P < 7.1 x 10(-20)). A PGS for AMD was predictive of reduced CSC risk (odds ratio, 0.76; 95% CI, 0.70-0.83 per +1 SD in AMD-PGS; P = 7.4 x 10(-10)). This association may have been mediated by loci containing complement genes.CONCLUSIONS AND RELEVANCE In this 3-cohort genetic association study, 5 genetic risk loci for CSC were identified, highlighting a likely role for genes involved in choroidal vascular function and complement regulation. Results suggest that polygenic AMD risk was associated with reduced risk of CSC and that this genetic overlap was largely due to loci containing complement genes.Ophthalmic researc

Accuracy of upper endoscopies with random biopsies to identify patients with gastric premalignant lesions who can safely be exempt from surveillance

Introduction: Guidelines recommend endoscopy with biopsies to stratify patients with gastric premalignant lesions (GPL) to high and low progression risk. High-risk patients are recommended to undergo surveillance. We aimed to assess the accuracy of guideline recommendations to identify low-risk patients, who can safely be discharged from surveillance. Methods: This study includes patients with GPL. Patients underwent at least two endoscopies with an interval of 1–6 years. Patients were defined ‘low risk’ if they fulfilled requirements for discharge, and ‘high risk’ if they fulfilled requirements for surveillance, according to European guidelines (MAPS-2012, updated MAPS-2019, BSG). Patients defined ‘low risk’ with progression of disease during follow-up (FU) were considered ‘misclassified’ as low risk. Results: 334 patients (median age 60 years IQR11; 48.7% ma

Contribuição ao estudo da interrelação flúor-manganês em ratos

Devido a numerosas discrepâncias nos resultados de estudos experimentais relativos à interação flúor-manganês, propusemo-nos a verificar se a adição de manganês 5 água fluoretada (1 ppm), em diferentes proporções fluor-manganês, levaria a uma diferente fixaçao do halogênio. Para tanto, 24 ratos Wistar, recém-desmamados, foram mantidos em dieta padrão de caseína a 27%, recebendo na sua água de consumo: 1) H2O destilada (controle); 2) 1,0 ppm de flúor: 3) 1,0 ppm de flúor + 0,5 ppm de manganês (F:Mn = 2,0); 4) 1,0 ppm de flúor +1,0 ppm de manganês (F: Mn = 1,0). Foram anotados o peso ganho e o consumo de alimento e água, durante os 60 dias de experimento, após o qual as patas traseiras, dos animais sacrificados, foram autoclavadas e desossadas, e os femures retirados. Posteriormente, foram estes submetidos à secagem, extração da gordura, pulverização e analise do flúor fixado. Também foram efetuadas analises da composição centesimal da ração e de flúor e manganês nesta e nas diferentes águas de consumo. Os resultados de percentagem do flúor ingerido fixado nos femures, foram analisados estatisticamente pelo teste não-paramétrico de Kruskal-Wallis (níveis de 1% e 5%) mostrando que, para as proporções consideradas, o flúor na taxa de 1 ppm, o manganês, quando administrado após o desmame, parece não afetar a fixaçao do flúor. Contudo, faz-se necessário dar continuidade aos estudos com novas proporções e taxas mais elevadas de flúor e manganês.An experiment to determine the effects of varying the manganese concentration of the diet on the fluorine retention in the femur of rats was made. Four groups of weaning rats were fed ad libitum a 27% casein synthetic diet and were provided with water as follows: 1) distilled (control); 2) containing 1 ppm of fluorine (F); 3) 1,0 ppm F + 0,5 ppm Mn; 4) 1 ppm F + 1 ppm Mn. The weight gain and food and water consumption were measured during 60 days. The results indicated that manganese does not seem to affect the proportional fixation of fluorine in the femur. The authors think that more data should be available before a definite conclusion on the influence of the ratio F:Mn on the fluorine retention could be drawn

A strategic knowledge and research agenda on polycentric metropolitan areas

Urban StudiesOTB Research Institute for the Built Environmen

The structure and dimensionality of the Inventory of Depressive Symptomatology Self Report (IDS-SR) in patients with depressive disorders and healthy controls

Background: The Inventory of Depressive Symptomatology Self Report (IDS-SR) is a widely used but heterogeneous measure of depression severity. Insight in its factor structure and dimensionality could help to develop more homogeneous IDS-SR subscales. However previous factoranalytical studies have found mixed results. Therefore, the present study tested which factor structure underlies the IDS-SR and, in addition, if the factors can be used as unidimensional subscales. Methods: Confirmatory factor analysis (CFA) was done to identify the best-fitting factor structure. The study sample consisted of 2600 individuals (mean age 40.5 ± 12.1). We assessed model fit in 4 groups: 957 Major Depressive Disorder (MDD) patients, 450 remitted MDD patients, 570 patients with an anxiety disorder and 623 healthy controls to test the consistency of model fit. Rasch analyses in the full sample were used to evaluate and optimize the unidimensionality and psychometric quality of the factors. Results: CFA indicated that a 3-factor model fits the IDS-SR data best and is consistent across groups, with a 'mood/cognition' factor, an 'anxiety/arousal' factor and a 'sleep' factor. In addition, Rasch analyses indicated that the 'mood/cognition' and 'anxiety/arousal' factors could be optimized to be used as unidimensional subscales. Limitations: The fit of only 4 models was tested, ranging from a 1-to 4-factor model. Conclusions: The IDS-SR is a heterogeneous instrument with a multifactorial underlying structure. It is possible to measure more homogeneous symptomatology with IDS-SR subscales, which could be useful in clinical practice and scientific research. © 2010 Elsevier B.V. All rights reserved

Vitality predicts level of guideline-concordant care in routine treatment of mood, anxiety and somatoform disorders

Objective  To examine the clinical and psychosocial correlates of adherence to treatment guidelines among outpatients with common mental disorders in a routine clinical setting. Methods  In this retrospective cohort study, we analysed 192 patients who were treated for a mood, anxiety or somatoform disorder with pharmacotherapy, psychotherapy or a combination of both treatment modalities. Guideline adherence was assessed with a disorder independent set of quality indicators during up to 3 years of follow-up. At baseline, a standardized diagnostic interview, the Brief Symptom Inventory (BSI), the Short Form 36 (SF-36) and demographic variables were assessed. Using multivariable regression analysis we identified independent predictors associated with guideline adherence. Results  Patients were aged 36.8 years (SD 11.6) on average. The majority of patients were treated with psychotherapy (47.4%), followed by pharmacotherapy (37.5%) and a combination of pharmacotherapy and psychotherapy (15.1%). Three adherence groups were defined: low (29.7%), intermediate (43.2%) and high (27.1%). Univariate predictors of low adherence were low scores on the subscales vitality and social functioning of the SF-36. In the multivariable model, low adherence was independently predicted by a score lower than 50 on the subscale vitality of the SF-36 (odds ratio per 10 units increase in vitality = 1.34, 95% confidence interval: 1.06-1.71). No significant differences were found within socio-demographic variables, co-morbidity and the scores on the BSI subscales between the adherence groups. Conclusions  We found that patients with low scores on the vitality subscale of the SF-36 were at the highest risk to receive low guideline-concordant care. Understanding factors that affect treatment adherence may help to prevent non-adherence and increase the quality of care as well as cost-effectiveness.Stress-related psychiatric disorders across the life spa