Nonintegrability of the two-body problem in constant curvature spaces

We consider the reduced two-body problem with the Newton and the oscillator potentials on the sphere ${\bf S}^{2}$ and the hyperbolic plane ${\bf H}^{2}$. For both types of interaction we prove the nonexistence of an additional meromorphic integral for the complexified dynamic systems.Comment: 20 pages, typos correcte

Pre-migration traumatic experiences, post-migration perceived discrimination and substance use among Russian and Kurdish migrants-a population-based study

Background and aims The associations between traumatic events, substance use and perceived discrimination have been rarely studied among migrants in host countries. We examined whether pre-migration potentially traumatic experiences (PTEs) or perceived discrimination (PD) are associated with substance use among migrants with voluntary (Russians) and forced (Kurds) migration backgrounds. Design Cross-sectional interview and health examination data from the Finnish Migrant Health and Wellbeing Study were used. The target sample (n = 1000 for each group) was drawn from the national population register using stratified random sampling by participants' country of birth and native language. Setting Population-based data were collected from six cities in Finland during 2010-12. Participants The participation rates were 68% (Russians) and 59% (Kurds). The analytical sample size varied (Russians n = 442-687, Kurds n = 459-613), as some participants completed only interview, health examination or short interview. The majority of Kurds had a refugee background (75%) while Russians had mainly migrated for other reasons (99%). Measurements The three main outcomes were self-reported binge drinking, daily smoking and life-time cannabis use. PTEs and PD were self-reported in the interview. Socio-demographic background, migration-related factors and current affective symptoms were adjusted for. Findings Among Kurds, PTEs were associated with binge drinking [adjusted odds ratio (aOR) = 2.65, 95% confidence interval (CI) = 1.30-5.42] and PD was associated with life-time cannabis use (aOR = 3.89, 95% CI = 1.38-10.97) after adjusting for contextual factors. Among Russians, PTEs were associated with life-time cannabis use adjusting for contextual factors (aOR = 2.17, 95% CI = 1.12-4.18). Conclusions In Finland, pre-migration traumatic experiences appear to be associated with life-time cannabis use among the Russian migrant population (voluntary migration) and binge drinking among the Kurdish migrant population (forced migration). Perceived discrimination in Finland appears to be associated with life-time cannabis use among Kurdish migrants.Peer reviewe

The Use of Molecular Analyses in Voided Urine for the Assessment of Patients with Hematuria

Introduction:Patients presenting with painless hematuria form a large part of the urological patient population. In many cases, especially in younger patients, the cause of hematuria is harmless. Nonetheless, hematuria could be a symptom of malignant disease and hence most patients will be subject to cystoscopy. In this study, we aimed to develop a prediction model based on methylation markers in combination with clinical variables, in order to stratify patients with high risk for bladder cancer.Material and Methods:Patients (n=169) presenting with painless hematuria were included. 54 patients were diagnosed with bladder cancer. In the remaining 115 patients, the cause of hematuria was non-malignant. Urine samples were collected prior to cystoscopy. Urine DNA was analyzed for methylation of OSR1, SIM2, OTX1, MEIS1 and ONECUT2. Methylation percentages were calculated and were combined with clinical variables into a logistic regression model.Results:Logistic regression analysis based on the five methylation markers, age, gender and type of hematuria resulted in an area under the curve (AUC) of 0.88 and an optimism corrected AUC of 0.84 after internal validation by bootstrapping. Using a cut-off value of 0.307 allowed stratification of patients in a low-risk and high-risk group, resulting in a sensitivity of 82% (44/54) and a specificity of 82% (94/115). Most aggressive tumors were found in patients in the high-risk group. The addition of cytology to the prediction model, improved the AUC from 0.88 to 0.89, with a sensitivity and specificity of 85% (39/46) and 87% (80/92), retrospectively.Conclusions:This newly developed prediction model could be a helpful tool in risk stratification of patients presenting with painless hematuria. Accurate risk prediction might result in less extensive examination of low risk patients and thereby, reducing patient burden and costs. Further validation in a large prospective patient cohort is necessary to prove the true clinical value of this model

Lack of clinically significant improvement of patients with tardive dyskinesia following phosphatidylcholine therapy

A double-blind controlled study was undertaken to examine the value of phosphatidylcholine as a treatment for tardive dyskinesia (TD) in 19 psychiatric patients. All patients were maintained on their usual psychotropic medication throughout the entire study. In addition, they were given either phosphatidylcholine (30 g/day) or placebo for 6 weeks. Thirteen of the patients received the crossover treatment for 6 weeks, after which 10 of the 13 were continued on the crossover medication for an additional 6 weeks. At the end of the study, 5 patients had received phosphatidylcholine for 12 weeks and another 12 patients had received the drug for only 6 weeks. Plasma and red blood cell choline levels were monitored every 3 weeks as a measure of compliance. Although some patients showed clinical improvement of their TD, the results did not differ significantly between active drug and placebo. This was in spite of a marked elevation of plasma and red blood cell choline (up to 300% for the Lafayette Clinic patients and up to 400% for the patients from the Ypsilanti Regional Psychiatric Hospital) during treatment with phosphatidylcholine. Side effects of the drug included occasional gastrointestinal upsets and diarrhea but, in general, the medication was tolerated very well. The results indicate that large doses of phosphatidylcholine of soya origin are of no clinical value in treating symptoms of TD in spite of very large increases in blood choline.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25523/1/0000064.pd

Machine learning prediction of progressive subclinical myocardial dysfunction in moderate aortic stenosis

BackgroundModerate severity aortic stenosis (AS) is poorly understood, is associated with subclinical myocardial dysfunction, and can lead to adverse outcome rates that are comparable to severe AS. Factors associated with progressive myocardial dysfunction in moderate AS are not well described. Artificial neural networks (ANNs) can identify patterns, inform clinical risk, and identify features of importance in clinical datasets.MethodsWe conducted ANN analyses on longitudinal echocardiographic data collected from 66 individuals with moderate AS who underwent serial echocardiography at our institution. Image phenotyping involved left ventricular global longitudinal strain (GLS) and valve stenosis severity (including energetics) analysis. ANNs were constructed using two multilayer perceptron models. The first model was developed to predict change in GLS from baseline echocardiography alone and the second to predict change in GLS using data from baseline and serial echocardiography. ANNs used a single hidden layer architecture and a 70%:30% training/testing split.ResultsOver a median follow-up interval of 1.3 years, change in GLS (≤ or >median change) could be predicted with accuracy rates of 95% in training and 93% in testing using ANN with inputs from baseline echocardiogram data alone (AUC: 0.997). The four most important predictive baseline features (reported as normalized % importance relative to most important feature) were peak gradient (100%), energy loss (93%), GLS (80%), and DI < 0.25 (50%). When a further model was run including inputs from both baseline and serial echocardiography (AUC 0.844), the top four features of importance were change in dimensionless index between index and follow-up studies (100%), baseline peak gradient (79%), baseline energy loss (72%), and baseline GLS (63%).ConclusionsArtificial neural networks can predict progressive subclinical myocardial dysfunction with high accuracy in moderate AS and identify features of importance. Key features associated with classifying progression in subclinical myocardial dysfunction included peak gradient, dimensionless index, GLS, and hydraulic load (energy loss), suggesting that these features should be closely evaluated and monitored in AS

The effect of multiple vitrectomies and its indications on intraocular pressure

Background: To assess the relationship between different indications for trans pars plana vitrectomies (PPV's) and the intraocular pressure (IOP), and the effect of multiple PPV's on the IOP. We also examined whether there were differences in the number of IOP-lowering medications or surgeries before and after PPV. Methods: A retrospective study including all patients that underwent at least one PPV in the period from 2001 till 2014 at our clinic. Medical records of all patients were reviewed and clinically relevant data were entered in a database. Generalized estimating equations models for repeated measurements were used to examine the effect of the number of PPV's on the IOP and on the risk of undergoing glaucoma surgery, for each of the indications for PPV. Results: Of 1072 PPV's 447 eyes fulfilled the inclusion criteria. The IOP increased with 3.0 mmHg after a PPV with indication retinal detachment (p < 0.001), but remained stable after PPV for epiretinal membrane (p = 0.555), macular hole (p = 0.695), and vitreous hemorrhage (p = 0.787). At the end of the follow-up period the number of IOP-lowering medications was significantly higher compared to baseline, except in the macular hole group (p = 0.103). Also, the number of eyes that underwent glaucoma surgery was significantly higher compared to the fellow (not-operated) eyes (p < 0.001). There was a significant association between the number of PPV's and the final IOP for the indication retinal detachment (p = 0.009), and between the number of PPV's and glaucoma surgery (odds ratio [95% confidence interval]: 2.60 [1.62-4.15]). Conclusions: The IOP rises significantly after PPV with indication retinal detachment. This association was not found for other indications for PPV. Also, the risk of IOP-lowering surgeries was higher after PPV, but not different between the PPV indications. The IOP should be monitored carefully after PPV, since there may be a higher risk of secondary glaucoma

The Effects of Cocaine on Different Redox Forms of Cysteine and Homocysteine, and on Labile, Reduced Sulfur in the Rat Plasma Following Active versus Passive Drug Injections

Received: 28 November 2012 / Revised: 19 April 2013 / Accepted: 6 May 2013 / Published online: 16 May 2013 The Author(s) 2013. This article is published with open access at Springerlink.comThe aim of the present studies was to evaluate cocaine-induced changes in the concentrations of different redox forms of cysteine (Cys) and homocysteine (Hcy), and products of anaerobic Cys metabolism, i.e., labile, reduced sulfur (LS) in the rat plasma. The above-mentioned parameters were determined after i.p. acute and subchronic cocaine treatment as well as following i.v. cocaine self-administration using the yoked procedure. Additionally, Cys, Hcy, and LS levels were measured during the 10-day extinction training in rats that underwent i.v. cocaine administration. Acute i.p. cocaine treatment increased the total and protein-bound Hcy contents, decreased LS, and did not change the concentrations of Cys fractions in the rat plasma. In turn, subchronic i.p. cocaine administration significantly increased free Hcy and lowered the total and protein-bound Cys concentrations while LS level was unchanged. Cocaine self-administration enhanced the total and protein-bound Hcy levels, decreased LS content, and did not affect the Cys fractions. On the other hand, yoked cocaine infusions did not alter the concentration of Hcy fractions while decreased the total and protein-bound Cys and LS content. This extinction training resulted in the lack of changes in the examined parameters in rats with a history of cocaine self-administration while in the yoked cocaine group an increase in the plasma free Cys fraction and LS was seen. Our results demonstrate for the first time that cocaine does evoke significant changes in homeostasis of thiol amino acids Cys and Hcy, and in some products of anaerobic Cys metabolism, which are dependent on the way of cocaine administration

Integrative single-cell meta-analysis reveals disease-relevant vascular cell states and markers in human atherosclerosis

Coronary artery disease (CAD) is characterized by atherosclerotic plaque formation in the arterial wall. CAD progression involves complex interactions and phenotypic plasticity among vascular and immune cell lineages. Single-cell RNA-seq (scRNA-seq) studies have highlighted lineage-specific transcriptomic signatures, but human cell phenotypes remain controversial. Here, we perform an integrated meta-analysis of 22 scRNA-seq libraries to generate a comprehensive map of human atherosclerosis with 118,578 cells. Besides characterizing granular cell-type diversity and communication, we leverage this atlas to provide insights into smooth muscle cell (SMC) modulation. We integrate genome-wide association study data and uncover a critical role for modulated SMC phenotypes in CAD, myocardial infarction, and coronary calcification. Finally, we identify fibromyocyte/fibrochondrogenic SMC markers (LTBP1 and CRTAC1) as proxies of atherosclerosis progression and validate these through omics and spatial imaging analyses. Altogether, we create a unified atlas of human atherosclerosis informing cell state-specific mechanistic and translational studies of cardiovascular diseases.</p