The Restricted Stochastic User Equilibrium with Threshold model: Large-scale application and parameter testing

This paper presents the application and calibration of the recently proposed Restricted Stochastic User Equilibrium with Threshold model (RSUET) to a large-scale case-study. The RSUET model avoids the limitations of the well-known Stochastic User Equilibrium model (SUE) and the Deterministic User Equilibrium model (DUE), by combining the strengths of the Boundedly Rational User Equilibrium model and the Restricted Stochastic User Equilibrium model (RSUE). Thereby, the RSUET model reaches an equilibrated solution in which the flow is distributed according to Random Utility Theory among a consistently equilibrated set of paths which all are within a threshold relative to the cost on the cheapest path and which do not leave any attractive paths unused. Several variants of a generic RSUET solution algorithm are tested and calibrated on a large-scale case network with 18,708 arcs and about 20 million OD-pairs, and comparisons are performed with respect to a previously proposed RSUE model as well as an existing link-based mixed Multinomial Probit (MNP) SUE model. The results show that the RSUET has very attractive computation times for large-scale applications and demonstrate that the threshold addition to the RSUE model improves the behavioural realism, especially for high congestion cases. Also, fast and well-behaved convergence to equilibrated solutions among non-universal choice sets is observed across different congestion levels, choice model scale parameters, and algorithm step sizes. Clearly, the results highlight that the RSUET outperforms the MNP SUE in terms of convergence, calculation time and behavioural realism. The choice set composition is validated by using 16,618 observed route choices collected by GPS devices in the same network and observing their reproduction within the equilibrated choice sets generated by the RSUET model. Relevantly, the RSUET model is very successful in reproducing observed link

Stochastic User Equilibrium with a Bounded Choice Model

Stochastic User Equilibrium (SUE) models allow the representation of the perceptual and preferential differences that exist when drivers compare alternative routes through a transportation network. However, as an effect of the used choice models, conventional applications of SUE are based on the assumption that all available routes have a positive probability of being chosen, however unattractive. In this paper, a novel choice model, the Bounded Choice Model (BCM), is presented along with network conditions for a corresponding Bounded SUE. The model integrates an exogenously-defined bound on the random utility of the set of paths that are used at equilibrium, within a Random Utility Theory (RUT) framework. The model predicts which routes are used and unused (the choice sets are equilibrated), while still ensuring that the distribution of flows on used routes accords to a Discrete Choice Model. Importantly, conditions to guarantee existence and uniqueness of the Bounded SUE are shown. Also, a corresponding solution algorithm is proposed and numerical results are reported by applying this to the Sioux Falls network

Path Size Logit route choice models: Issues with current models, a new internally consistent approach, and parameter estimation on a large-scale network with GPS data

Path Size Logit route choice models attempt to capture the correlation between routes by including correction terms within the route utility functions. This provides a convenient closed-form solution for implementation in traffic network models. The path size terms measure distinctiveness of routes; a route is penalised based on the number of other routes sharing its links, and the costs of those shared links. Typically, real road networks have many very long routes that should be considered unrealistic. Such unrealistic routes are problematic for the Path Size Logit (PSL) model because they negatively impact the choice probabilities of realistic routes when links are shared. The Generalised Path Size Logit (GPSL) model attempts to address this problem by weighting the contributions of routes to path size terms according to the ratio of route travel costs. However, the GPSL model is not internally consistent in how it defines routes as being unrealistic: the path size terms consider only travel cost, whereas the route choice probability relation considers disutility including the correction term. To solve these challenges, this paper formulates a new internally consistent Adaptive Path Size Logit (APSL) model wherein routes contribute to path size terms according to the ratio of route choice probabilities, ensuring that routes defined as unrealistic by the path size terms, are exactly those with very low choice probabilities. The APSL route choice probability relation is an implicit function, naturally expressed as a fixed-point problem. A proof is provided for the guaranteed existence of solutions, as well as conditions for the uniqueness of solutions. A Maximum Likelihood Estimation procedure is given for estimating the APSL model with tracked route observation data, and this procedure is investigated in a simulation study where it is shown it is generally possible to reproduce assumed true parameters. APSL is then estimated using real tracked route GPS data on a large-scale network, and results are compared with other PSL models

A Study to investigate the role of p27 and Cyclin E immunoexpression as a prognostic factor in early breast carcinoma

<p>Abstract</p> <p>Background</p> <p>Cyclin E and p27 expression is easy to assess in human tissues by standard immunohistochemical techniques. Immunohistochemistry is cost effective, relatively easy to perform and will play more of a role in the future management of cancer. The aim of this study was to investigate the role of p27 and cyclin E immunoexpression as a prognostic factor in early breast carcinoma.</p> <p>Methods</p> <p>Cyclin E and p27 immunohistochemistry was performed on sixty six cases of breast carcinoma submitted over a five year period to the Division of Anatomical Pathology, Groote Schuur hospital; Whittaker and Associates; and PathCare. All tumours included in this study were less than 5 cm in diameter (pT1 and pT2 stage) and all the patients had wide local excisions performed. Follow up information was obtained from patient folders in the Department of Radiation Oncology.</p> <p>Results</p> <p>There was no significant association of cyclin E and p27 expression with distant metastasis free survival (MFS) for all invasive carcinomas in contrast to grade, lymph node spread and vascular invasion. However, there was a statistically significant direct association of cyclin E with distant metastases in all invasive carcinomas, in the subgroup of infiltrating duct carcinomas (IDC) and in the node negative group when cyclin E was stratified as negative and positive (low/high). In this study of early breast carcinoma, only 9/66 cases showed cyclin E expression. Of these, four patients had distant metastases, one patient had a local recurrence and four patients were alive at last follow-up. Furthermore, cyclin E expression was significantly associated with grade, lymph node spread, oestrogen receptor status and histological type. None of the lobular carcinomas showed cyclin E positivity and only one case of lobular carcinoma presented with distant metastases.</p> <p>59/66 cases were positive (low/high) for p27 while seven cases were negative, 22 cases showed low expression and 37 cases demonstrated high p27 expression.</p> <p>p27 was significantly associated with oestrogen receptor status only for all invasive carcinomas and in the IDC group. There was no statistical relationship between p27 and cyclin E, but 50 (76%) tumours with positive p27 expression were negative for cyclin E. There were similar results for the invasive ductal carcinoma subgroup.</p> <p>Conclusion</p> <p>This study shows that p27 and cyclin E are not good independent prognostic markers for early breast carcinoma in contrast to grade, lymph node spread and vascular invasion for all invasive carcinomas. However, cyclin E provides some prognostic value as there is a direct statistical association with the development of distant metastases. Many previous studies have correlated overexpression of cyclin E with an aggressive course. The inverse relationship between p27 and cyclin E expression which has been reported in the literature has been highlighted, but this was not statistically significant. Most cases showed positive p27 expression and negative Cyclin E expression. This may be due to the early stage of the disease.</p

Optical biosensor differentiates signaling of endogenous PAR1 and PAR2 in A431 cells

<p>Abstract</p> <p>Background</p> <p>Protease activated receptors (PARs) consist of a family of four G protein-coupled receptors. Many types of cells express several PARs, whose physiological significance is mostly unknown.</p> <p>Results</p> <p>Here, we show that non-invasive resonant waveguide grating (RWG) biosensor differentiates signaling of endogenous protease activated receptor subtype 1 (PAR₁) and 2 (PAR₂) in human epidermoid carcinoma A431 cells. The biosensor directly measures dynamic mass redistribution (DMR) resulted from ligand-induced receptor activation in adherent cells. In A431, both PAR₁and PAR₂agonists, but neither PAR₃nor PAR₄agonists, trigger dose-dependent Ca²⁺mobilization as well as G_q-type DMR signals. Both Ca²⁺flux and DMR signals display comparable desensitization patterns upon repeated stimulation with different combinations of agonists. However, PAR₁and PAR₂exhibit distinct kinetics of receptor re-sensitization. Furthermore, both trypsin- and thrombin-induced Ca²⁺flux signals show almost identical dependence on cell surface cholesterol level, but their corresponding DMR signals present different sensitivities.</p> <p>Conclusion</p> <p>Optical biosensor provides an alternative readout for examining receptor activation under physiologically relevant conditions, and differentiates the signaling of endogenous PAR₁and PAR₂in A431.</p

Socioeconomic differences in adolescents’ smoking: a comparison between Finland and Beijing, China

Background: Various studies have demonstrated the associations between socioeconomic status (SES) and health and health behaviour among adolescents. However, few studies have compared the socioeconomic difference in adolescent smoking between countries with different stage of smoking. The purpose of this study was to examine and compare the relationship between socioeconomic status (SES) and adolescent smoking in Beijing, China and Finland through the Health Behaviour in School-aged Children (HBSC) study. Methods: The data used in this study were derived from the Chinese HBSC linked project survey 2008 in Beijing and the Finnish HBSC survey 2006. The final sample included 2005 Chinese and 1685 Finnish 15-year-old schoolchildren. The associations between Family Affluence Scale (FAS), as the SES measure, and adolescents’ smoking behaviour, including ever smoked, weekly smoking and the early onset of smoking were examined separately in two countries through binary logistic regression. Results: Compared to students from the high FAS group, Chinese boys from the low FAS group were more likely to report having ever smoked (OR = 2.12, 95 % CI = 1.49–3.01) and being early onset of smoking (OR = 2.17, 95 % CI = 1. 44–3.26). Finnish girls from the low FAS group were more likely to report being weekly smokers (OR = 1.68, 95 % CI = 1. 07–2.65). No significant difference was found for Chinese girls and Finnish boys. Conclusions: This study indicated different patterns of socioeconomic difference in smoking between Chinese and Finnish adolescents by gender and by smoking behaviour, which suggests that socioeconomic inequalities in smoking are different among adolescents in countries with different stage of smoking. Country specific policies and interventions for different target groups should be encouraged and designed for reducing the prevalence of adolescents’ smoking.peerReviewe

Continuity of midwifery care and gestational weight gain in obese women: a randomised controlled trial

Background: The increased prevalence of obesity in pregnant women in Australia and other developed countries is a significant public health concern. Obese women are at increased risk of serious perinatal complications and guidelines recommend weight gain restriction and additional care. There is limited evidence to support the effectiveness of dietary and physical activity lifestyle interventions in preventing adverse perinatal outcomes and new strategies need to be evaluated. The primary aim of this project is to evaluate the effect of continuity of midwifery care on restricting gestational weight gain in obese women to the recommended range. The secondary aims of the study are to assess the impact of continuity of midwifery care on: women&rsquo;s experience of pregnancy care; women&rsquo;s satisfaction with care and a range of psychological factors.Methods/Design: A two arm randomised controlled trial (RCT) will be conducted with primigravid women recruited from maternity services in Victoria, Australia. Participants will be primigravid women, with a BMI&ge;30 who are less than 17 weeks gestation. Women allocated to the intervention arm will be cared for in a midwifery continuity of care model and receive an informational leaflet on managing weight gain in pregnancy. Women allocated to the control group will receive routine care in addition to the same informational leaflet. Weight gain during pregnancy, standards of care, medical and obstetric information will be extracted from medical records. Data collected at recruitment (self administered survey) and at 36 weeks by postal survey will include sociodemographic information and the use of validated scales to measure secondary outcomes.Discussion: Continuity of midwifery care models are well aligned with current Victorian, Australian and many international government policies on maternity care. Increasingly, midwifery continuity models of care are being introduced in low risk maternity care, and information on their application in high risk populations is required. There is an identified need to trial alternative antenatal interventions to reduce perinatal risk factors for women who are obese and the findings from this project may have application in other maternity services. In addition this study will inform a larger trial that will focus on birth and postnatal outcomes.<br /

Phosphodiesterase Inhibition Increases CREB Phosphorylation and Restores Orientation Selectivity in a Model of Fetal Alcohol Spectrum Disorders

Background: Fetal alcohol spectrum disorders (FASD) are the leading cause of mental retardation in the western world and children with FASD present altered somatosensory, auditory and visual processing. There is growing evidence that some of these sensory processing problems may be related to altered cortical maps caused by impaired developmental neuronal plasticity. Methodology/Principal Findings: Here we show that the primary visual cortex of ferrets exposed to alcohol during the third trimester equivalent of human gestation have decreased CREB phosphorylation and poor orientation selectivity revealed by western blotting, optical imaging of intrinsic signals and single-unit extracellular recording techniques. Treating animals several days after the period of alcohol exposure with a phosphodiesterase type 1 inhibitor (Vinpocetine) increased CREB phosphorylation and restored orientation selectivity columns and neuronal orientation tuning. Conclusions/Significance: These findings suggest that CREB function is important for the maturation of orientation selectivity and that plasticity enhancement by vinpocetine may play a role in the treatment of sensory problems in FASD

Inhibition of glucose metabolism selectively targets autoreactive follicular helper T cells.

Follicular helper T (TFH) cells are expanded in systemic lupus erythematosus, where they are required to produce high affinity autoantibodies. Eliminating TFH cells would, however compromise the production of protective antibodies against viral and bacterial pathogens. Here we show that inhibiting glucose metabolism results in a drastic reduction of the frequency and number of TFH cells in lupus-prone mice. However, this inhibition has little effect on the production of T-cell-dependent antibodies following immunization with an exogenous antigen or on the frequency of virus-specific TFH cells induced by infection with influenza. In contrast, glutaminolysis inhibition reduces both immunization-induced and autoimmune TFH cells and humoral responses. Solute transporter gene signature suggests different glucose and amino acid fluxes between autoimmune TFH cells and exogenous antigen-specific TFH cells. Thus, blocking glucose metabolism may provide an effective therapeutic approach to treat systemic autoimmunity by eliminating autoreactive TFH cells while preserving protective immunity against pathogens