Three-phase traffic theory and two-phase models with a fundamental diagram in the light of empirical stylized facts

Despite the availability of large empirical data sets and the long history of traffic modeling, the theory of traffic congestion on freeways is still highly controversial. In this contribution, we compare Kerner's three-phase traffic theory with the phase diagram approach for traffic models with a fundamental diagram. We discuss the inconsistent use of the term "traffic phase" and show that patterns demanded by three-phase traffic theory can be reproduced with simple two-phase models, if the model parameters are suitably specified and factors characteristic for real traffic flows are considered, such as effects of noise or heterogeneity or the actual freeway design (e.g. combinations of off- and on-ramps). Conversely, we demonstrate that models created to reproduce three-phase traffic theory create similar spatiotemporal traffic states and associated phase diagrams, no matter whether the parameters imply a fundamental diagram in equilibrium or non-unique flow- density relationships. In conclusion, there are different ways of reproducing the empirical stylized facts of spatiotemporal congestion patterns summarized in this contribution, and it appears possible to overcome the controversy by a more precise definition of the scientific terms and a more careful comparison of models and data, considering effects of the measurement process and the right level of detail in the traffic model used.Comment: 18 pages in the published article, 13 figures, 2 table

Psychometric properties of the quality of life scale Child Health and Illness Profile-Child Edition in a combined analysis of five atomoxetine trials

Our aim was to evaluate the psychometric properties of the generic quality of life (QoL) scale Child Health and Illness Profile-Child Edition (CHIP-CE) by means of a combined analysis of atomoxetine clinical trials in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Individual patient-level data from five clinical trials were included in the combined analysis. Psychometric properties of the CHIP-CE were explored in terms of internal consistency and structure. Patients (n = 794) aged between 6 and 15 years (mean 9.7) with mean baseline ADHD Rating Scale of 41.8 ± 8.04 were included. On average, 0.7 (SD 2.23) items were missing for the whole CHIP-CE. The internal consistency of the CHIP-CE assessed by Cronbach’s alpha was good for all sub-domains at baseline and at endpoint. Considerable ceiling effects were only observed for the “restricted activity” sub-domain. No considerable floor effects were seen. The factor analysis supported the 12-factor solution for the sub-domains, but not the 5-factor solution for the domains. Our analyses were based on a large sample of non-US patients which allowed the measurement of clear changes in QoL over time. The results support that the CHIP-CE scale is psychometrically robust over time in terms of internal consistency and structure

Functional cartography of complex metabolic networks

High-throughput techniques are leading to an explosive growth in the size of biological databases and creating the opportunity to revolutionize our understanding of life and disease. Interpretation of these data remains, however, a major scientific challenge. Here, we propose a methodology that enables us to extract and display information contained in complex networks. Specifically, we demonstrate that one can (i) find functional modules in complex networks, and (ii) classify nodes into universal roles according to their pattern of intra- and inter-module connections. The method thus yields a ``cartographic representation'' of complex networks. Metabolic networks are among the most challenging biological networks and, arguably, the ones with more potential for immediate applicability. We use our method to analyze the metabolic networks of twelve organisms from three different super-kingdoms. We find that, typically, 80% of the nodes are only connected to other nodes within their respective modules, and that nodes with different roles are affected by different evolutionary constraints and pressures. Remarkably, we find that low-degree metabolites that connect different modules are more conserved than hubs whose links are mostly within a single module.Comment: 17 pages, 4 figures. Go to http://amaral.northwestern.edu for the PDF file of the reprin

Training emergency services’ dispatchers to recognise stroke: an interrupted time-series analysis

Background: Stroke is a time-dependent medical emergency in which early presentation to specialist care reduces death and dependency. Up to 70% of all stroke patients obtain first medical contact from the Emergency Medical Services (EMS). Identifying ‘true stroke’ from an EMS call is challenging, with over 50% of strokes being misclassified. The aim of this study was to evaluate the impact of the training package on the recognition of stroke by Emergency Medical Dispatchers (EMDs). Methods: This study took place in an ambulance service and a hospital in England using an interrupted time-series design. Suspected stroke patients were identified in one week blocks, every three weeks over an 18 month period, during which time the training was implemented. Patients were included if they had a diagnosis of stroke (EMS or hospital). The effect of the intervention on the accuracy of dispatch diagnosis was investigated using binomial (grouped) logistic regression. Results: In the Pre-implementation period EMDs correctly identified 63% of stroke patients; this increased to 80% Post-implementation. This change was significant (p=0.003), reflecting an improvement in identifying stroke patients relative to the Pre-implementation period both the During-implementation (OR=4.10 [95% CI 1.58 to 10.66]) and Post-implementation (OR=2.30 [95% CI 1.07 to 4.92]) periods. For patients with a final diagnosis of stroke who had been dispatched as stroke there was a marginally non-significant 2.8 minutes (95% CI −0.2 to 5.9 minutes, p=0.068)reduction between Pre- and Post-implementation periods from call to arrival of the ambulance at scene. Conclusions: This is the first study to develop, implement and evaluate the impact of a training package for EMDs with the aim of improving the recognition of stroke. Training led to a significant increase in the proportion of stroke patients dispatched as such by EMDs; a small reduction in time from call to arrival at scene by the ambulance also appeared likely. The training package has been endorsed by the UK Stroke Forum Education and Training, and is free to access on-line

Prognostic value of nuclear morphometry in patients with TNM stage T1 ovarian clear cell adenocarcinoma

In 40 patients with TNM stage T1 ovarian clear cell adenocarcinoma, we used nuclear morphometry to study the relations among morphometric variables, clinical prognostic factors and outcome. The presence of one or more giant nuclear cells was positively associated with death (OR = 10.6, P = 0.02) and tended to be associated with disease recurrence (OR = 5.1, P = 0.07). Nuclear irregularity (expressed in terms of the nuclear roundness factor) was positively associated with both death (OR = 8.6, P = 0.02) and disease recurrence (OR = 8.2, P = 0.02). A combination of giant nuclear cell presence or nuclear irregularity proved to be a useful prognostic indicator, with a sensitivity and specificity of 83% and 71% in the prediction of death, and 75% and 71% in the prediction of disease recurrence. Patients' age and substage were of no prognostic value. We conclude that the nuclear morphometric characteristics, especially the presence of giant nuclear cells and nuclear irregularity, may be useful in predicting outcome in patients with early stage ovarian clear cell adenocarcinoma. © 1999 Cancer Research Campaig

A mathematical model for breath gas analysis of volatile organic compounds with special emphasis on acetone

Recommended standardized procedures for determining exhaled lower respiratory nitric oxide and nasal nitric oxide have been developed by task forces of the European Respiratory Society and the American Thoracic Society. These recommendations have paved the way for the measurement of nitric oxide to become a diagnostic tool for specific clinical applications. It would be desirable to develop similar guidelines for the sampling of other trace gases in exhaled breath, especially volatile organic compounds (VOCs) which reflect ongoing metabolism. The concentrations of water-soluble, blood-borne substances in exhaled breath are influenced by: (i) breathing patterns affecting gas exchange in the conducting airways; (ii) the concentrations in the tracheo-bronchial lining fluid; (iii) the alveolar and systemic concentrations of the compound. The classical Farhi equation takes only the alveolar concentrations into account. Real-time measurements of acetone in end-tidal breath under an ergometer challenge show characteristics which cannot be explained within the Farhi setting. Here we develop a compartment model that reliably captures these profiles and is capable of relating breath to the systemic concentrations of acetone. By comparison with experimental data it is inferred that the major part of variability in breath acetone concentrations (e.g., in response to moderate exercise or altered breathing patterns) can be attributed to airway gas exchange, with minimal changes of the underlying blood and tissue concentrations. Moreover, it is deduced that measured end-tidal breath concentrations of acetone determined during resting conditions and free breathing will be rather poor indicators for endogenous levels. Particularly, the current formulation includes the classical Farhi and the Scheid series inhomogeneity model as special limiting cases.Comment: 38 page

The hypoactive corpora cavernosa with degenerative erectile dysfunction: a new syndrome

BACKGROUND: In a group of 22 patients with erectile dysfunction, vasculogenic, neurogenic, endocrinologic or psychogenic investigations failed to find a cause for their erectile dysfunction. The electro-cavernosograms of these patients recorded a diminished activity. We investigated the hypothesis that diminished corpus cavernosum electromyography activity was the cause of erectile dysfunction in these patients. METHODS: The study comprised the above mentioned 22 patients (study group, 43.8 ± 5.9 SD years) and 15 healthy volunteers (control group, 41.8 ± 5.1 SD years). The electro-cavernosograms were recorded in the flaccid, erectile and detumescent phases by 2 electrodes inserted into the corpus cavernosum. RESULTS: The electro-cavernosogram of the healthy volunteers registered in the flaccid phase regular slow waves and random action potentials. The wave variables declined significantly in the erectile phase (p < 0.01). In the study group, the slow wave variables in the flaccid phase exhibited a significant decrease (p < 0.05) compared to the healthy volunteers, and the rhythm was irregular. Erection did not occur with sildenafil administration or intracavernosal papaverine injection, and penile implant was performed. Biopsy examination showed degenerated muscle fibers, and fragmented collagen and elastic fibers with areas of fibrosis. CONCLUSION: A novel concept of the cause of erectile dysfunction was presented. Corpora cavernosa showed degenerative changes on histopathologic examination and exhibited diminished electromyography activity. They did not respond to sildenafil administration or intracavernosal papaverine injection. Penile implants were the only treatment. The condition is given the name 'hypoactive corpus cavernosum'. The cause of corpus cavernosum degenerative changes needs further study

Galectin-9 Controls CD40 Signaling through a Tim-3 Independent Mechanism and Redirects the Cytokine Profile of Pathogenic T Cells in Autoimmunity

While it has long been understood that CD40 plays a critical role in the etiology of autoimmunity, glycobiology is emerging as an important contributor. CD40 signaling is also gaining further interest in transplantation and cancer therapies. Work on CD40 signaling has focused on signaling outcomes and blocking of its ligand, CD154, while little is known about the actual receptor itself and its control. We demonstrated that CD40 is in fact several receptors occurring as constellations of differentially glycosylated forms of the protein that can sometimes form hybrid receptors with other proteins. An enticing area of autoimmunity is differential glycosylation of immune molecules leading to altered signaling. Galectins interact with carbohydrates on proteins to effect such signaling alterations. Studying autoimmune prone NOD and non-autoimmune BALB/c mice, here we reveal that in-vivo CD40 signals alter the glycosylation status of non-autoimmune derived CD4 T cells to resemble that of autoimmune derived CD4 T cells. Galectin-9 interacts with CD40 and, at higher concentrations, prevents CD40 induced proliferative responses of CD4loCD40+ effector T cells and induces cell death through a Tim-3 independent mechanism. Interestingly, galectin-9, at lower concentrations, alters the surface expression of CD3, CD4, and TCR, regulating access to those molecules and thereby redirects the inflammatory cytokine phenotype and CD3 induced proliferation of autoimmune CD4loCD40+ T cells. Understanding the dynamics of the CD40 receptor(s) and the impact of glycosylation status in immunity will gain insight into how to maintain useful CD40 signals while shutting down detrimental ones