The reliability-based stochastic transit assignment problem with elastic demand

This paper examines the reliability-based stochastic transit assignment problem with elastic demand. A Variational Inequality (VI) model for this problem is developed. The VI model considers capacity, waiting time and in-vehicle travel time as stochastic variables, and includes Spiess and Florian’s (1989) and de Cea and Fernández’s (1993) models as special cases. A reliability-based stochastic user equilibrium condition is defined to capture the route choice behavior of passengers. To illustrate the properties of the VI model, numerical studies were conducted on de Cea and Fernández’s (1993) network. The studies also show that Spiess and Florian’s and de Cea and Fernández’s models can overestimate the system performance substantially.postprin

Efficacy of a progressive walking program and glucosamine sulphate supplementation on osteoarthritic symptoms of the hip and knee: a feasibility trial

Introduction: Management of osteoarthritis (OA) includes the use of non-pharmacological and pharmacological therapies. Although walking is commonly recommended for reducing pain and increasing physical function in people with OA, glucosamine sulphate has also been used to alleviate pain and slow the progression of OA. This study evaluated the effects of a progressive walking program and glucosamine sulphate intake on OA symptoms and physical activity participation in people with mild to moderate hip or knee OA. Methods: Thirty-six low active participants (aged 42 to 73 years) were provided with 1500 mg glucosamine sulphate per day for 6 weeks, after which they began a 12-week progressive walking program, while continuing to take glucosamine. They were randomized to walk 3 or 5 days per week and given a pedometer to monitor step counts. For both groups, step level of walking was gradually increased to 3000 steps/day during the first 6 weeks of walking, and to 6000 steps/day for the next 6 weeks. Primary outcomes included physical activity levels, physical function (self-paced step test), and the WOMAC Osteoarthritis Index for pain, stiffness and physical function. Assessments were conducted at baseline and at 6-, 12-, 18-, and 24-week follow-ups. The Mann Whitney Test was used to examine differences in outcome measures between groups at each assessment, and the Wilcoxon Signed Ranks Test was used to examine differences in outcome measures between assessments. Results: During the first 6 weeks of the study (glucosamine supplementation only), physical activity levels, physical function, and total WOMAC scores improved (P<0.05). Between the start of the walking program (Week 6) and the final follow-up (Week 24), further improvements were seen in these outcomes (P<0.05) although most improvements were seen between Weeks 6 and 12. No significant differences were found between walking groups. Conclusions: In people with hip or knee OA, walking a minimum of 3000 steps (~30 minutes), at least 3 days/week, in combination with glucosamine sulphate, may reduce OA symptoms. A more robust study with a larger sample is needed to support these preliminary findings. Trial Registration: Australian Clinical Trials Registry ACTRN012607000159459

Frozen-thawed embryo transfer cycles

Objective: To review the outcomes of frozen-thawed embryo transfer cycles. Design: Retrospective review. Setting: Tertiary assisted reproduction centre, Hong Kong. Patients: Subfertile patients undergoing frozen-thawed embryo transfer between July 2005 and December 2007. Main outcome measures: Clinical and ongoing pregnancy rates. Results: A total of 983 frozen-thawed embryo transfer cycles performed during the study period were reviewed. The clinical pregnancy and ongoing pregnancy rates were 35% and 30%, respectively. Factors associated with successful outcome included younger maternal age (≤35 years) and 4 or more blastomeres at replacement, but not the method of insemination, the cause of subfertility, or the type of frozen-thawed embryo transfer cycle. The overall multiple pregnancy rate was 18%. For cycles with a single embryo replaced, embryos having 4-cell or higher stages at replacement gave an ongoing pregnancy rate of 25%, whereas those with less than 4 cells had a significantly lower ongoing pregnancy rate of 5% only. Blastomere lysis after thawing significantly reduced the clinical pregnancy and ongoing pregnancy rates of cycles with one embryo replaced. Conclusions Clinical pregnancy and ongoing pregnancy rates of frozen-thawed embryo transfer cycles were 35% and 30%, respectively. Higher pregnancy rates were associated with younger maternal age (≤35 years), blastomere numbers of 4 or more, and no blastomere lysis after thawing.published_or_final_versio

Vac-and-fill: A micromoulding technique for fabricating microneedle arrays with vacuum-activated, hands-free mould-filling

We report a simple and reproducible micromoulding technique that dynamically fills microneedle moulds with a liquid formulation, using a plastic syringe, triggered by the application of vacuum (‘vac-and-fill’). As pressure around the syringe drops, air inside the syringe pushes the plunger to uncover an opening in the syringe and fill the microneedle mould without manual intervention, therefore removing inter-operator variability. The technique was validated by monitoring the plunger movement and pressure at which the mould would be filled over 10 vacuum cycles for various liquid formulation of varying viscosity (water, glycerol, 20% polyvinylpyrrolidone (PVP) solution or 40% PVP solution). Additionally, the impact of re-using the disposable syringes on plunger movement, and thus the fill pressure, was investigated using a 20% PVP solution. The fill pressure was consistent at 300–450 mbar. It produced well-formed and mechanically robust PVP, poly(methylvinylether/maleic anhydride) and hydroxyethylcellulose microneedles from liquid formulations. This simple and inexpensive technique of micromoulding eliminated the air entrapment and bubble formation, which prevent reproducible microneedle formation, in the resultant microneedle arrays. It provides a cost-effective alternative to the conventional micromoulding techniques, where the application of vacuum (‘fill-and-vac’) or centrifugation following mould-filling may be unsuitable, ineffective or have poor reproducibility

Justice at Sea: Fishers’ politics and marine conservation in coastal Odisha, India

This is a paper about the politics of fishing rights in and around the Gahirmatha marine sanctuary in coastal Odisha, in eastern India. Claims to the resources of this sanctuary are politicised through the creation of a particularly damaging narrative by influential Odiya environmental actors about Bengalis, as illegal immigrants who have hurt the ecosystem through their fishing practices. Anchored within a theoretical framework of justice as recognition, the paper considers the making of a regional Odiya environmentalism that is, potentially, deeply exclusionary. It details how an argument about ‘illegal Bengalis’ depriving ‘indigenous Odiyas’ of their legitimate ‘traditional fishing rights’ derives from particular notions of indigeneity and territory. But the paper also shows that such environmentalism is tenuous, and fits uneasily with the everyday social landscape of fishing in coastal Odisha. It concludes that a wider class conflict between small fishers and the state over a sanctuary sets the context in which questions about legitimate resource rights are raised, sometimes with important effects, like when out at sea

ANXA3/JNK Signaling Promotes Self-Renewal and Tumor Growth, and Its Blockade Provides a Therapeutic Target for Hepatocellular Carcinoma

Frequent tumor relapse in hepatocellular carcinoma (HCC) has been commonly attributed to the presence of residual cancer stem cells (CSCs) after conventional treatments. We have previously identified and characterized CD133 to mark a specific CSC subset in HCC. In the present study, we found endogenous and secretory annexin A3 (ANXA3) to play pivotal roles in promoting cancer and stem cell-like features in CD133+ liver CSCs through a dysregulated JNK pathway. Blockade of ANXA3 with an anti-ANXA3 monoclonal antibody in vitro as well as in human HCC xenograft models resulted in a significant reduction in tumor growth and self-renewal. Clinically, ANXA3 expression in HCC patient sera closely associated with aggressive clinical features. Our results suggest that ANXA3 can serve as a novel diagnostic biomarker and that the inhibition of ANXA3 may be a viable therapeutic option for the treatment of CD133+ liver-CSC-driven HCC. © 2015 The Authors.published_or_final_versio

Regulatory role of miR-142-3p on the functional hepatic cancer stem cell marker CD133

Tumor relapse after therapy typifies hepatocellular carcinoma (HCC) and is believed to be attributable to residual cancer stem cells (CSCs) that survive treatment. We have previously identified a CSC population derived from HCC that is characterized by CD133. Despite our growing knowledge of the importance of this subset of cells in driving HCC, the regulatory mechanism of CD133 is not known. Epigenetic changes are believed to be essential in the control of cancer and stem cells. Here, we report the epigenetic regulation of CD133 by miR-142-3p. The interaction between CD133 and miR-142-3p was identified by in silico prediction and substantiated by luciferase reporter analysis. Expression of CD133 was found to be inversely correlated with miR-142-3p in HCC clinical samples as well as in cell lines. Importantly, lower miR-142-3p expression in HCC was significantly associated with worst survival. Functional studies with miR-142-3p stably transduced in HCC cells demonstrated a diminished ability to self-renew, initiate tumor growth, invade, migrate, induce angiogenesis and resist chemotherapy. Rescue experiments whereby CD133 and miR-142-3p is simultaneously overexpressed compensated the deregulated ability of the cells to confer these features. Thus, miR-142-3p directly targets CD133 to regulate its ability to confer cancer and stem cell-like features in HCC.published_or_final_versio

Optimal leverage from non-ergodicity

In modern portfolio theory, the balancing of expected returns on investments against uncertainties in those returns is aided by the use of utility functions. The Kelly criterion offers another approach, rooted in information theory, that always implies logarithmic utility. The two approaches seem incompatible, too loosely or too tightly constraining investors' risk preferences, from their respective perspectives. The conflict can be understood on the basis that the multiplicative models used in both approaches are non-ergodic which leads to ensemble-average returns differing from time-average returns in single realizations. The classic treatments, from the very beginning of probability theory, use ensemble-averages, whereas the Kelly-result is obtained by considering time-averages. Maximizing the time-average growth rates for an investment defines an optimal leverage, whereas growth rates derived from ensemble-average returns depend linearly on leverage. The latter measure can thus incentivize investors to maximize leverage, which is detrimental to time-average growth and overall market stability. The Sharpe ratio is insensitive to leverage. Its relation to optimal leverage is discussed. A better understanding of the significance of time-irreversibility and non-ergodicity and the resulting bounds on leverage may help policy makers in reshaping financial risk controls.Comment: 17 pages, 3 figures. Updated figures and extended discussion of ergodicit