Bayesian Identification of Nonseparable Hamiltonian Systems Using Stochastic Dynamic Models

This paper proposes a probabilistic Bayesian formulation for system identification (ID) and estimation of nonseparable Hamiltonian systems using stochastic dynamic models. Nonseparable Hamiltonian systems arise in models from diverse science and engineering applications such as astrophysics, robotics, vortex dynamics, charged particle dynamics, and quantum mechanics. The numerical experiments demonstrate that the proposed method recovers dynamical systems with higher accuracy and reduced predictive uncertainty compared to state-of-the-art approaches. The results further show that accurate predictions far outside the training time interval in the presence of sparse and noisy measurements are possible, which lends robustness and generalizability to the proposed approach. A quantitative benefit is prediction accuracy with less than 10% relative error for more than 12 times longer than a comparable least-squares-based method on a benchmark problem

Exercise capacity and incidence of myocardial perfusion defects after Kawasaki disease in children and adolescents

Objectives.This study evaluated exercise performance and myocardial perfusion during exercise in patients with Kawasaki disease who had a broad spectrum of residual coronary abnormalities.Background.Reports of exercise performance after Kawasaki disease have generally included a small number of patients evaluated by various protocols, frequently with incomplete data. Myocardial perfusion studies have usually been limited to those using pharmacologically induced coronary vasodilation. Therefore, to our knowledge there has not been a large study directly correlating exercise performance, electrocardiographic (ECG) changes and myocardial perfusion imaging.Methods.Forty-six patients were classified into three groups on the basis of coronary artery status: group 1 (n = 27) had no objective evidence of coronary artery lesions; group 2 (n = 11) had resolved aneurysms; group 3 (n = 8) had persistent coronary aneurysms. All patients underwent exercise testing with monitor ing of ECG changes and oxygen consumption. Single-photon emission computed tomographic imaging was performed at rest and during peak exercise using technetium-99m sestamibi.Results.Maximal oxygen consumption was within normal limits and was similar for all three groups. Five patients had mild ST segment changes at peak exercise. Two of these patients had stress-induced perfusion defects. Myocardial perfusion defects were present in 37% of patients in group 1, 63% in group 2 and 100% in group 3. Perfusion defects corresponded to the coronary artery lesion site in all but three patients.Conclusions.Maximal oxygen consumption is normal after Kawasaki disease regardless of coronary artery status. Stressinduced perfusion defects are frequent even in the absence of coronary abnormalities and are common in the absence of ST segment changes suggestive of ischemia

LRRK2 affects vesicle trafficking, neurotransmitter extracellular level and membrane receptor localization

The leucine-rich repeat kinase 2 (LRRK2) gene was found to play a role in the pathogenesis of both familial and sporadic Parkinson's disease (PD). LRRK2 encodes a large multi-domain protein that is expressed in different tissues. To date, the physiological and pathological functions of LRRK2 are not clearly defined. In this study we have explored the role of LRRK2 in controlling vesicle trafficking in different cellular or animal models and using various readouts. In neuronal cells, the presence of LRRK2(G2019S) pathological mutant determines increased extracellular dopamine levels either under basal conditions or upon nicotine stimulation. Moreover, mutant LRRK2 affects the levels of dopamine receptor D1 on the membrane surface in neuronal cells or animal models. Ultrastructural analysis of PC12-derived cells expressing mutant LRRK2(G2019S) shows an altered intracellular vesicle distribution. Taken together, our results point to the key role of LRRK2 to control vesicle trafficking in neuronal cells

Acute Colonic Diverticulitis: CT Findings, Classifications, and a Proposal of a Structured Reporting Template

Acute colonic diverticulitis (ACD) is the most common complication of diverticular disease and represents an abdominal emergency. It includes a variety of conditions, extending from localized diverticular inflammation to fecal peritonitis, hence the importance of an accurate diagnosis. Contrast-enhanced computed tomography (CE-CT) plays a pivotal role in the diagnosis due to its high sensitivity, specificity, accuracy, and interobserver agreement. In fact, CE-CT allows alternative diagnoses to be excluded, the inflamed diverticulum to be localized, and complications to be identified. Imaging findings have been reviewed, dividing them into bowel and extra-intestinal wall findings. Moreover, CE-CT allows staging of the disease; the most used classifications of ACD severity are Hinchey’s modified and WSES classifications. Differential diagnoses include colon carcinoma, epiploic appendagitis, ischemic colitis, appendicitis, infectious enterocolitis, and inflammatory bowel disease. We propose a structured reporting template to standardize the terminology and improve communication between specialists involved in patient care

Bacterial adherence to mucosal epithelium in the upper airways has less significance than believed

BACKGROUND: Bacterial adherence to the upper airway epithelium is considered to be an important phenomenon in the pathogenesis of infections. However, the evidence for the hypothesis that bacterial adherence to mucosal epithelial cells has significance for pathogenesis of mucosal infections is based on studies using indirect techniques. We could find no biopsy studies with direct ocular observations of significant numbers of bacteria adhering to upper airway mucosal epithelial cells either in health or during disease. RESULTS: We studied specimens from healthy and infected tonsillar epithelium and specimens from the soft palate epithelium obtained by surgery. The specimens were examined by TEM. In the vast majority of specimens, we found no bacteria adhering to the epithelial cells in the mucosal line regardless of whether the patient was infected or not. Bacteria adhering to shed epithelial cells were seen in higher numbers. Furthermore, as bacteria are small compared to epithelial cells, we calculated the risk of overlooking every adhered bacteria in a section if bacterial adherence was such a significant phenomenon as earlier suggested. We found this risk to be very small. CONCLUSION: We conclude that bacterial adherence to mucosal surface epithelial cells is not a significant phenomenon, either in healthy mucosa in the upper airways or during infection. This is also in line with our earlier results, where we have shown that the site for the infectious process in pharyngotonsillitis is in the secretion on the tonsillar mucosal surface

Eosinophils Are Important for Protection, Immunoregulation and Pathology during Infection with Nematode Microfilariae

Eosinophil responses typify both allergic and parasitic helminth disease. In helminthic disease, the role of eosinophils can be both protective in immune responses and destructive in pathological responses. To investigate whether eosinophils are involved in both protection and pathology during filarial nematode infection, we explored the role of eosinophils and their granule proteins, eosinophil peroxidase (EPO) and major basic protein-1 (MBP-1), during infection with Brugia malayi microfilariae. Using eosinophil-deficient mice (PHIL), we further clarify the role of eosinophils in clearance of microfilariae during primary, but not challenge infection in vivo. Deletion of EPO or MBP-1 alone was insufficient to abrogate parasite clearance suggesting that either these molecules are redundant or eosinophils act indirectly in parasite clearance via augmentation of other protective responses. Absence of eosinophils increased mast cell recruitment, but not other cell types, into the broncho-alveolar lavage fluid during challenge infection. In addition absence of eosinophils or EPO alone, augmented parasite-induced IgE responses, as measured by ELISA, demonstrating that eosinophils are involved in regulation of IgE. Whole body plethysmography indicated that nematode-induced changes in airway physiology were reduced in challenge infection in the absence of eosinophils and also during primary infection in the absence of EPO alone. However lack of eosinophils or MBP-1 actually increased goblet cell mucus production. We did not find any major differences in cytokine responses in the absence of eosinophils, EPO or MBP-1. These results reveal that eosinophils actively participate in regulation of IgE and goblet cell mucus production via granule secretion during nematode-induced pathology and highlight their importance both as effector cells, as damage-inducing cells and as supervisory cells that shape both innate and adaptive immunity

Alcoholism and Strongyloides stercoralis: Daily Ethanol Ingestion Has a Positive Correlation with the Frequency of Strongyloides Larvae in the Stools

It has been reported that Strongyloides stercoralis infection is more prevalent in chronic alcoholic patients than in non alcoholics living in the same country. In a retrospective study on the prevalence of S. stercoralis infection in a large sample of alcoholic patients, we demonstrate that this prevalence is significantly higher than in non-alcoholic patients admitted at the same hospital. Moreover, the frequency of the parasite was in close relationship with the daily amount of ingested ethanol, even in the absence of liver cirrhosis, reinforcing the idea that chronic alcoholism is associated with increased susceptibility to Strongyloides infection. Beside the bad hygiene profile of alcoholic patients, which explains high risk for acquisition of the parasite, the high prevalence of S. stercoralis in alcoholics may be in relationship with other effects of ethanol on the intestinal motility, steroid metabolism and immune system, which could enhance the chance of autoinfection and the survival and fecundity of females in duodenum. In this way, the number of larvae in the stools is higher in alcoholic patients, increasing the chance of a positive result in a stool examination by sedimentation method