66 research outputs found

    Reoptimisation strategies for dynamic vehicle routing problems with proximity-dependent nodes

    Get PDF
    Autonomous vehicles create new opportunities as well as new challenges to dynamic vehicle routing. The introduction of autonomous vehicles as information-collecting agents results in scenarios, where dynamic nodes are found by proximity. This paper presents a novel dynamic vehicle-routing problem variant with proximity-dependent nodes. Here, we introduced a novel variable, detectability, which determines whether a proximal dynamic node will be detected, based on the sight radius of the vehicle. The problem considered is motivated by autonomous weed-spraying vehicles in large agricultural operations. This work is generalisable to many other autonomous vehicle applications. The first step to crafting a solution approach for the problem is to decide when reoptimisation should be triggered. Two reoptimisation trigger strategies are considered—exogenous and endogenous. Computational experiments compared the strategies for both the classical dynamic vehicle routing problem as well as the introduced variant. Experiments used extensive standardised vehicle-routing problem benchmarks with varying degrees of dynamism and geographical node distributions. The results showed that for both the classical problem and the novel variant, an endogenous trigger strategy is better in most cases, while an exogenous trigger strategy is only suitable when both detectability and dynamism are low. Furthermore, the optimal level of detectability was shown to be dependent on the combination of trigger, degree of dynamism, and geographical node distribution, meaning practitioners may determine the required detectability based on the attributes of their specific problem

    Assessing Asset Data on Low-Income Households

    Get PDF
    Assessing Asset Data on Low-Income Household

    An N-terminal splice variant of human Stat5a that interacts with different transcription factors is the dominant form expressed in invasive ductal carcinoma

    Get PDF
    AbstractWe have identified a new variant of human Stat5a, found at higher ratios to full-length Stat5a in invasive ductal carcinoma versus contiguous normal tissue. The variant, missing exon 5, inhibits p21 and Bax production and increases cell number. After prolactin stimulation, only full-length Stat5a interacts with the vitamin D and retinoid X receptors, whereas only Δ5 Stat5a interacts with activating protein 1–2 and specificity protein 1. Prolactin also oppositely regulates interaction of the two Stat5a forms with β-catenin. We propose that a change in splicing leading to upregulation of this new isoform is a pathogenic aspect of invasive ductal carcinoma

    Chinese medicine treatment for menopausal symptoms in the UK health service: Is a clinical trial warranted?

    Get PDF
    Objectives The aims of this pilot study were to evaluate treatment effects, ascertain safety and formulate best practice Chinese medicine protocols relevant for London women suffering from menopausal symptoms. Study design This clinical pilot study employed a case series design within a wider action-based research project. 117 perimenopausal women between 45 and 55 years of age recruited from the general population were treated for menopausal symptoms by six experienced practitioners of Chinese medicine at the Polyclinic of the University of Westminster. Practitioners were instructed to treat as near to their usual practice style as possible. This involved using Chinese herbal medicine and/or acupuncture along with dietary and lifestyle advice. A maximum of 12 treatments over 6 months was allowed per patient. Outcome measures The menopause specific quality of life questionnaire (MenQoL), the Greene climacteric scale, and flushing diaries were used to evaluate treatment outcomes. Liver and kidney function tests were carried out at intake and after 1, 6 and 12 treatments to evaluate the safety particularly in relation to the use of herbal medicines. Results Patients showed significant improvement across all domains measured by the MenQoL and Greene climacteric scales. Reduction on the MenQoL scale between first and last visit was from 4.31 to 3.27 (p < 0.001) and on the Green climacteric scale from 21.01 to 13.00 (p < 0.001). Study participants did not reliably complete their flushing diaries. No adverse events or abnormal liver or kidney function values were observed during the course of the study. Conclusions Further research that seeks to investigate the effects observed in more detail and to evaluate them against other forms of treatment and/or no-treatment controls is warranted. This could be achieved by way of a pragmatic randomized controlled trial that evaluated Chinese medicine against orthodox medical care

    A study of a culturally focused psychiatric consultation service for Asian American and Latino American primary care patients with depression

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Ethnic minorities with depression are more likely to seek mental health care through primary care providers (PCPs) than mental health specialists. However, both provider and patient-specific challenges exist. PCP-specific challenges include unfamiliarity with depressive symptom profiles in diverse patient populations, limited time to address mental health, and limited referral options for mental health care. Patient-specific challenges include stigma around mental health issues and reluctance to seek mental health treatment. To address these issues, we implemented a multi-component intervention for Asian American and Latino American primary care patients with depression at Massachusetts General Hospital (MGH).</p> <p>Methods/Design</p> <p>We propose a randomized controlled trial to evaluate a culturally appropriate intervention to improve the diagnosis and treatment of depression in our target population. Our goals are to facilitate a) primary care providers' ability to provide appropriate, culturally informed care of depression, and b) patients' knowledge of and resources for receiving treatment for depression. Our two-year long intervention targets Asian American and Latino American adult (18 years of age or older) primary care patients at MGH screening positive for symptoms of depression. All eligible patients in the intervention arm of the study who screen positive will be offered a culturally focused psychiatric (CFP) consultation. Patients will meet with a study clinician and receive toolkits that include psychoeducational booklets, worksheets and community resources. Within two weeks of the initial consultation, patients will attend a follow-up visit with the CFP clinicians. Primary outcomes will determine the feasibility and cost associated with implementation of the service, and evaluate patient and provider satisfaction with the CFP service. Exploratory aims will describe the study population at screening, recruitment, and enrollment and identify which variables influenced patient participation in the program.</p> <p>Discussion</p> <p>The study involves an innovative yet practical intervention that builds on existing resources and strives to improve quality of care for depression for minorities. Additionally, it complements the current movement in psychiatry to enhance the treatment of depression in primary care settings. If found beneficial, the intervention will serve as a model for care of Asian American and Latino American patients.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01239407">NCT01239407</a></p

    Complement C1 Esterase Inhibitor Levels Linked to Infections and Contaminated Heparin-Associated Adverse Events

    Get PDF
    Activation of kinin-kallikrein and complement pathways by oversulfated-chondroitin-sulfate (OSCS) has been linked with recent heparin-associated adverse clinical events. Given the fact that the majority of patients who received contaminated heparin did not experience an adverse event, it is of particular importance to determine the circumstances that increase the risk of a clinical reaction. In this study, we demonstrated by both the addition and affinity depletion of C1inh from normal human plasma, that the level of C1inh in the plasma has a great impact on the OSCS-induced kallikrein activity and its kinetics. OSCS-induced kallikrein activity was dramatically increased after C1inh was depleted, while the addition of C1inh completely attenuated kallikrein activity. In addition, actual clinical infection can lead to increased C1inh levels. Plasma from patients with sepsis had higher average levels of functional C1inh and decreased OSCS-induced kallikrein activity. Lastly, descriptive data on adverse event reports suggest cases likely to be associated with contaminated heparin are inversely correlated with infection. Our data suggest that low C1inh levels can be a risk factor and high levels can be protective. The identification of risk factors for contact system-mediated adverse events may allow for patient screening and clinical development of prophylaxis and treatments

    Enhanced Fusion Pore Expansion Mediated by the Trans-Acting Endodomain of the Reovirus FAST Proteins

    Get PDF
    The reovirus fusion-associated small transmembrane (FAST) proteins are virus-encoded membrane fusion proteins that function as dedicated cell–cell fusogens. The topology of these small, single-pass membrane proteins orients the majority of the protein on the distal side of the membrane (i.e., inside the cell). We now show that ectopic expression of the endodomains of the p10, p14, and p15 FAST proteins enhances syncytiogenesis induced by the full-length FAST proteins, both homotypically and heterotypically. Results further indicate that the 68-residue cytoplasmic endodomain of the p14 FAST protein (1) is endogenously generated from full-length p14 protein expressed in virus-infected or transfected cells; (2) enhances syncytiogenesis subsequent to stable pore formation; (3) increases the syncytiogenic activity of heterologous fusion proteins, including the differentiation-dependent fusion of murine myoblasts; (4) exerts its enhancing activity from the cytosol, independent of direct interactions with either the fusogen or the membranes being fused; and (5) contains several regions with protein–protein interaction motifs that influence enhancing activity. We propose that the unique evolution of the FAST proteins as virus-encoded cellular fusogens has allowed them to generate a trans-acting, soluble endodomain peptide to harness a cellular pathway or process involved in the poorly understood process that facilitates the transition from microfusion pores to macrofusion and syncytiogenesis
    corecore