Unfolding-Based Process Discovery

This paper presents a novel technique for process discovery. In contrast to the current trend, which only considers an event log for discovering a process model, we assume two additional inputs: an independence relation on the set of logged activities, and a collection of negative traces. After deriving an intermediate net unfolding from them, we perform a controlled folding giving rise to a Petri net which contains both the input log and all independence-equivalent traces arising from it. Remarkably, the derived Petri net cannot execute any trace from the negative collection. The entire chain of transformations is fully automated. A tool has been developed and experimental results are provided that witness the significance of the contribution of this paper.Comment: This is the unabridged version of a paper with the same title appearead at the proceedings of ATVA 201

Infective endocarditis in the Netherlands:current epidemiological profile and mortality An analysis based on partial ESC EORP collected data

Introduction: Infective endocarditis (IE) is associated with a high in-hospital and long term mortality. Although progress has been made in diagnostic approach and management of IE, morbidity and mortality of IE remain high. In the latest European guidelines, the importance of the multi-modality imaging in diagnosis and follow up of IE is emphasized. Aim: The aim was to provide information regarding mortality and adverse events of IE, to determine IE characteristics and to assess current use of imaging in the diagnostic workup of IE. Methods: This is a prospective observational cohort study. We used data from the EURO-ENDO registry. Seven hospitals in the Netherlands have participated and included patients with IE between April 2016 and April 2018. Results: A total of 139 IE patients were included. Prosthetic valve endocarditis constituted 32.4% of the cases, cardiac device related IE 7.2% and aortic root prosthesis IE 3.6%. In-hospital mortality was 14.4% (20 patients) and one-year mortality was 21.6% (30 patients). The incidence of embolic events under treatment was 16.5%, while congestive heart failure or cardiogenic shock occurred in 15.1% of the patients. Transthoracic and transoesophageal echocardiography were performed most frequently (97.8%; 81.3%) and within 3 days after IE suspicion, followed by 18F‑fluorodeoxyglucose positron emission tomography/computed tomography (45.3%) within 6 days and multi-slice computed tomography (42.4%) within 7 days. Conclusion: We observed a high percentage of prosthetic valve endocarditis, rapid and extensive use of imaging and a relatively low in-hospital and one-year mortality of IE in the Netherlands. Limitations include possible selection bias

The aldehyde dehydrogenase enzyme 7A1 is functionally involved in prostate cancer bone metastasis

High aldehyde dehydrogenase (ALDH) activity can be used to identify tumor-initiating and metastasis-initiating cells in various human carcinomas, including prostate cancer. To date, the functional importance of ALDH enzymes in prostate carcinogenesis, progression and metastasis has remained elusive. Previously we identified strong expression of ALDH7A1 in human prostate cancer cell lines, primary tumors and matched bone metastases. In this study, we evaluated whether ALDH7A1 is required for the acquisition of a metastatic stem/progenitor cell phenotype in human prostate cancer. Knockdown of ALDH7A1 expression resulted in a decrease of the α2hi/αvhi/CD44+ stem/progenitor cell subpopulation in the human prostate cancer cell line PC-3M-Pro4. In addition, ALDH7A1 knockdown significantly inhibited the clonogenic and migratory ability of human prostate cancer cells in vitro. Furthermore, a number of genes/factors involved in migration, invasion and metastasis were affected including transcription factors (snail, snail2, and twist) and osteopontin, an ECM molecule involved in metastasis. Knockdown of ALDH7A1 resulted in decreased intra-bone growth and inhibited experimentally induced (bone) metastasis, while intra-prostatic growth was not affected. In line with these observations, evidence is presented that TGF-β, a key player in cancer invasiveness and bone metastasis, strongly induced ALDH activity while BMP7 (an antagonist of TGF-β signaling) down-regulated ALDH activity. Our findings show, for the first time, that the ALDH7A1 enzyme is functionally involved in the formation of bone metastases and that the effect appeared dependent on the microenvironment, i.e., bone versus prostate

Differences in school environment, school policy and actions regarding overweight prevention between Dutch schools. A nationwide survey

<p>Abstract</p> <p>Background</p> <p>Schools are regarded as an important setting for the prevention of overweight. This study presents a nationally representative picture of the obesogenity of the school environment, the awareness of schools regarding overweight, and actions taken by the schools aiming at overweight prevention. In addition, differences between school levels were studied.</p> <p>Methods</p> <p>In 2006-2007, questionnaires were sent to all Dutch secondary schools (age group 12-18 years). Prevalences of the outcome variables were calculated for the schools in total and by school level. The association between school level and outcome variables were analysed by a log linear regression.</p> <p>Results</p> <p>Unhealthy foods and drinks are widely available at secondary schools. One third of the schools indicated that overweight has increased among students and half of the schools agreed that schools were (co)responsible for the prevention of overweight. Only 3% of the schools have a policy on overweight prevention. Small differences were observed between vocational education schools and higher education schools. The presence of vending machines did not differ by school level, but at vocational education schools, the content of the vending machines was less healthy.</p> <p>Conclusion</p> <p>This study describes the current situation at schools which is essential for the development and evaluation of future overweight prevention policies and interventions. In general, secondary schools are not actively involved in overweight prevention and the nutritional environment at most schools could be improved. The small differences between school levels do not give reason for a differential approach for a certain school level for overweight prevention.</p

Scaling of Particle and Transverse Energy Production in 208Pb+208Pb collisions at 158 A GeV

Transverse energy, charged particle pseudorapidity distributions and photon transverse momentum spectra have been studied as a function of the number of participants (N_{part}) and the number of binary nucleon-nucleon collisions (N_{coll}) in 158 A GeV Pb+Pb collisions over a wide impact parameter range. A scaling of the transverse energy pseudorapidity density at midrapidity as N_{part}^{1.08 \pm 0.06} and N_{coll}^{0.83 \pm 0.05} is observed. For the charged particle pseudorapidity density at midrapidity we find a scaling as N_{part}^{1.07 \pm 0.04} and N_{coll}^{0.82 \pm 0.03}. This faster than linear scaling with N_{part} indicates a violation of the naive Wounded Nucleon Model.Comment: 13 pages, 16 figures, submitted to European Physical Journal C (revised results for scaling exponents

Telomere Length Trajectory and Its Determinants in Persons with Coronary Artery Disease: Longitudinal Findings from the Heart and Soul Study

Background: Leukocyte telomere length, an emerging marker of biological age, has been shown to predict cardiovascular morbidity and mortality. However, the natural history of telomere length in patients with coronary artery disease has not been studied. We sought to investigate the longitudinal trajectory of telomere length, and to identify the independent predictors of telomere shortening, in persons with coronary artery disease. Methodology/Principal Findings: In a prospective cohort study of 608 individuals with stable coronary artery disease, we measured leukocyte telomere length at baseline, and again after five years of follow-up. We used multivariable linear and logistic regression models to identify the independent predictors of leukocyte telomere trajectory. Baseline and follow-up telomere lengths were normally distributed. Mean telomere length decreased by 42 base pairs per year (p,0.001). Three distinct telomere trajectories were observed: shortening in 45%, maintenance in 32%, and lengthening in 23 % of participants. The most powerful predictor of telomere shortening was baseline telomere length (OR per SD increase = 7.6; 95 % CI 5.5, 10.6). Other independent predictors of telomere shortening were age (OR per 10 years = 1.6; 95 % CI 1.3, 2.1), male sex (OR = 2.4; 95 % CI 1.3, 4.7), and waist-to-hip ratio (OR per 0.1 increase = 1.4; 95 % CI 1.0, 2.0). Conclusions/Significance: Leukocyte telomere length may increase as well as decrease in persons with coronary arter

The Influence of Education and Socialization on Radicalization: An Exploration of Theoretical Presumptions and Empirical Research

Background and Objective: Research into radicalization does not pay much attention to education. This is remarkable and possibly misses an important influence on the process of radicalization. Therefore this article sets out to explore the relation between education on the one hand and the onset or prevention of radicalization on the other hand. Method: This article is a theoretical literature review. It has analyzed empirical studies-mainly from European countries-about the educational aims, content and style of Muslim parents and parents with (extreme) right-wing sympathies. Results: Research examining similarity in right-wing sympathies between parents and children yields mixed results, but studies among adolescents point to a significant concordance. Research also showed that authoritarian parenting may play a significant role. Similar research among Muslim families was not found. While raising children with distrust and an authoritarian style are prevalent, the impact on adolescents has not been investigated. The empirical literature we reviewed does not give sufficient evidence to conclude that democratic ideal in and an authoritative style of education are conducive to the development of a democratic attitude. Conclusion: There is a knowledge gap with regard to the influence of education on the onset or the prevention of radicalization. Schools and families are underappreciated sources of informal social control and social capital and therefore the gap should be closed. If there is a better understanding of the effect of education, policy as well as interventions can be developed to assist parents and teachers in preventing radicalization. © 2011 The Author(s)

Chronic Helminth Infections Protect Against Allergic Diseases by Active Regulatory Processes

Developed countries are suffering from an epidemic rise in immunologic disorders, such as allergy-related diseases and certain autoimmunities. Several studies have demonstrated a negative association between helminth infections and inflammatory diseases (eg, allergy), providing a strong case for the involvement of helminth infections in this respect. However, some studies point in the opposite direction. The discrepancy may be explained by differences in frequency, dose, time, and type of helminth. In this review, new studies are discussed that may support the concept that chronic helminth infections in particular—but not acute infections—are associated with the expression of regulatory networks necessary for downmodulating allergic immune responses to harmless antigens. Furthermore, different components of regulatory networks are highlighted, such as the role of regulatory T and B cells, modulation of dendritic cells, early innate signals from structural cells (eg, epithelial cells), and their individual contributions to protection against allergic diseases. It is of great interest to define and characterize specific helminth molecules that have profound immunomodulatory capacities as targets for therapeutic application in the treatment or prophylaxis of allergic manifestations