1,792 research outputs found

    Incentivizing Exploration with Heterogeneous Value of Money

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    Recently, Frazier et al. proposed a natural model for crowdsourced exploration of different a priori unknown options: a principal is interested in the long-term welfare of a population of agents who arrive one by one in a multi-armed bandit setting. However, each agent is myopic, so in order to incentivize him to explore options with better long-term prospects, the principal must offer the agent money. Frazier et al. showed that a simple class of policies called time-expanded are optimal in the worst case, and characterized their budget-reward tradeoff. The previous work assumed that all agents are equally and uniformly susceptible to financial incentives. In reality, agents may have different utility for money. We therefore extend the model of Frazier et al. to allow agents that have heterogeneous and non-linear utilities for money. The principal is informed of the agent's tradeoff via a signal that could be more or less informative. Our main result is to show that a convex program can be used to derive a signal-dependent time-expanded policy which achieves the best possible Lagrangian reward in the worst case. The worst-case guarantee is matched by so-called "Diamonds in the Rough" instances; the proof that the guarantees match is based on showing that two different convex programs have the same optimal solution for these specific instances. These results also extend to the budgeted case as in Frazier et al. We also show that the optimal policy is monotone with respect to information, i.e., the approximation ratio of the optimal policy improves as the signals become more informative.Comment: WINE 201

    Dynamic sampling schemes for optimal noise learning under multiple nonsmooth constraints

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    We consider the bilevel optimisation approach proposed by De Los Reyes, Sch\"onlieb (2013) for learning the optimal parameters in a Total Variation (TV) denoising model featuring for multiple noise distributions. In applications, the use of databases (dictionaries) allows an accurate estimation of the parameters, but reflects in high computational costs due to the size of the databases and to the nonsmooth nature of the PDE constraints. To overcome this computational barrier we propose an optimisation algorithm that by sampling dynamically from the set of constraints and using a quasi-Newton method, solves the problem accurately and in an efficient way

    Computed cardiopulmonography and the idealized lung clearance index, iLCI2.5, in early-stage cystic fibrosis.

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    This study explored the use of computed cardiopulmonography (CCP) to assess lung function in early-stage cystic fibrosis (CF). CCP has two components. The first is a particularly accurate technique for measuring gas exchange. The second is a computational cardiopulmonary model where patient-specific parameters can be estimated from the measurements of gas exchange. Twenty-five participants (14 healthy controls, 11 early-stage CF) were studied with CCP. They were also studied with a standard clinical protocol to measure the lung clearance index (LCI2.5). Ventilation inhomogeneity, as quantified through CCP parameter σlnCl, was significantly greater (P < 0.005) in CF than in controls, and anatomical deadspace relative to predicted functional residual capacity (DS/FRCpred) was significantly more variable (P < 0.002). Participant-specific parameters were used with the CCP model to calculate idealized values for LCI2.5 (iLCI2.5) where extrapulmonary influences on the LCI2.5, such as breathing pattern, had all been standardized. Both LCI2.5 and iLCI2.5 distinguished clearly between CF and control participants. LCI2.5 values were mostly higher than iLCI2.5 values in a manner dependent on the participant's respiratory rate (r = 0.46, P < 0.05). The within-participant reproducibility for iLCI2.5 appeared better than for LCI2.5, but this did not reach statistical significance (F ratio = 2.2, P = 0.056). Both a sensitivity analysis on iLCI2.5 and a regression analysis on LCI2.5 revealed that these depended primarily on an interactive term between CCP parameters of the form σlnCL*(DS/FRC). In conclusion, the LCI2.5 (or iLCI2.5) probably reflects an amalgam of different underlying lung changes in early-stage CF that would require a multiparameter approach, such as potentially CCP, to resolve.NEW & NOTEWORTHY Computed cardiopulmonography is a new technique comprising a highly accurate sensor for measuring respiratory gas exchange coupled with a cardiopulmonary model that is used to identify a set of patient-specific characteristics of the lung. Here, we show that this technique can improve on a standard clinical approach for lung function testing in cystic fibrosis. Most particularly, an approach incorporating multiple model parameters can potentially separate different aspects of pathological change in this disease

    Transcriptional and functional profilling of human embryonic stem cell-derived cardiomyocytes

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    Human embryonic stemcells (hESCs) can serve as a potentially limitless source of cells that may enable regeneration of diseased tissue and organs. Here we investigate the use of human embryonic stemcell-derived cardiomyocytes (hESC-CMs) in promoting recovery from cardiac ischemia reperfusion injury in a mouse model. Using microarrays, we have described the hESC-CM transcriptome within the spectrum of changes that occur between undifferentiated hESCs and fetal heart cells. The hESC-CMs expressed cardiomyocyte genes at levels similar to those found in 20-week fetal heart cells, making this population a good source of potential replacement cells in vivo. Echocardiographic studies showed significant improvement in heart function by 8 weeks after transplantation. Finally, we demonstrate long-term engraftment of hESC-CMs by using molecular imaging to track cellular localization, survival, and proliferation in vivo. Taken together, global gene expression profiling of hESC differentiation enables a systems-based analysis of the biological processes, networks, and genes that drive hESC fate decisions, and studies such as this will serve as the foundation for future clinical applications of stem cell therapies. © 2008 Cao et al.published_or_final_versio

    Polybrominated Diphenyl Ether (PBDE) Flame Retardants and Thyroid Hormone during Pregnancy

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    BACKGROUND: Human exposure to polybrominated diphenyl ether (PBDE) flame retardants has increased exponentially over the last three decades. Animal and human studies suggest that PBDEs may disrupt thyroid function. Although thyroid hormone (TH) of maternal origin plays an essential role in normal fetal brain development, there is a paucity of human data regarding associations between exposure to PBDEs and maternal TH levels during pregnancy. OBJECTIVES: Our goal was to determine whether PBDE serum concentrations are associated with TH levels in pregnant women. METHODS: We measured the concentration of 10 PBDE congeners, free thyroxine (T4), total T4, and thyroid-stimulating hormone (TSH) in 270 pregnant women around the 27th week of gestation. RESULTS: Serum concentrations of individual PBDE congeners with detection frequencies > 50% (BDEs 28, 47, 99, 100, and 153) and their sum (ΣPBDEs) were inversely associated with TSH levels. Decreases in TSH ranged between 10.9% [95% confidence interval (CI), -20.6 to 0.0] and 18.7% (95% CI, -29.2 to -4.5) for every 10-fold increase in the concentration of individual congeners. Odds of subclinical hyperthyroidism (low TSH but normal T4) were also significantly elevated in participants in the highest quartile of ΣPBDEs and BDEs 100 and 153 relative to those in the first quartile. Associations between PBDEs and free and total T4 were not statistically significant. Results were not substantially altered after the removal of outliers and were independent of the method used to adjust for blood lipid levels and to express ΣPBDEs. CONCLUSIONS: Results suggest that exposure to PBDEs is associated with lower TSH during pregnancy. Findings may have implications for maternal health and fetal development

    The role of childhood social position in adult type 2 diabetes: Evidence from the English Longitudinal Study of Ageing

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    Copyright @ 2014 Pikhartova et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been made available through the Brunel Open Access Publishing Fund.Background: Socioeconomic circumstances in childhood and early adulthood may influence the later onset of chronic disease, although such research is limited for type 2 diabetes and its risk factors at the different stages of life. The main aim of the present study is to examine the role of childhood social position and later inflammatory markers and health behaviours in developing type 2 diabetes at older ages using a pathway analytic approach. Methods. Data on childhood and adult life circumstances of 2,994 men and 4,021 women from English Longitudinal Study of Ageing (ELSA) were used to evaluate their association with diabetes at age 50 years and more. The cases of diabetes were based on having increased blood levels of glycated haemoglobin and/or self-reported medication for diabetes and/or being diagnosed with type 2 diabetes. Father's job when ELSA participants were aged 14 years was used as the measure of childhood social position. Current social characteristics, health behaviours and inflammatory biomarkers were used as potential mediators in the statistical analysis to assess direct and indirect effects of childhood circumstances on diabetes in later life. Results: 12.6 per cent of participants were classified as having diabetes. A disadvantaged social position in childhood, as measured by father's manual occupation, was associated at conventional levels of statistical significance with an increased risk of type 2 diabetes in adulthood, both directly and indirectly through inflammation, adulthood social position and a risk score constructed from adult health behaviours including tobacco smoking and limited physical activity. The direct effect of childhood social position was reduced by mediation analysis (standardised coefficient decreased from 0.089 to 0.043) but remained statistically significant (p = 0.035). All three indirect pathways made a statistically significantly contribution to the overall effect of childhood social position on adulthood type 2 diabetes. Conclusions: Childhood social position influences adult diabetes directly and indirectly through inflammatory markers, adulthood social position and adult health behaviours. © 2014Pikhartova et al.; licensee BioMed Central Ltd.Economic and Social Research Council-funded International Centre for Life Course Studies in Society and Health (RES-596-28-0001)

    Incidental Thyroid Carcinoma by FDG-PET/CT: A Study of Clinicopathological Characteristics

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    BACKGROUND: The rising incidence of incidental thyroid carcinoma (ITC) detected during fluoro-2-deoxy-D: -glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scanning poses a challenge to clinicians. The present study aims to critically evaluate the clinicopathological characteristics of ITC detected by FDG-PET/CT. METHODS: Among the 557 patients managed at our institution, 40 (7.2%) patients were identified as having ITC. Of these, 22 patients had their tumor detected by FDG-PET/CT (PET group) and 11 by ultrasonography (USG group). Additional bedside ultrasonography +/- fine-needle aspiration (FNA) was done in all patients at their clinic visit. The clinicopathological characteristics were compared between the PET and USG groups. RESULTS: The PET group had significantly more patients with history of nonthyroidal malignancy (P < 0.001). Papillary carcinoma was the most common histological type in both groups. Despite having similar histological and prognostic features including tumor size, tumor multifocality, capsular invasion, extrathyroidal extension, and lymph node metastases, tumor bilaterality (or presence of contralateral tumor focus) was significantly more frequent in the PET than the USG group (P = 0.04). The tumors were also more advanced by the tumor-node-metastasis (TNM) staging system in the PET group (P = 0.021). None of the contralateral tumor foci were evident preoperatively. One patient in the USG group developed metastatic thyroid carcinoma in neck lymph nodes 28 months after thyroid resection. CONCLUSION: ITC by FDG-PET/CT had higher incidence of tumor bilaterality than those detected by ultrasonography. Total thyroidectomy should be considered for ITC detected by FDG-PET/CT even for tumor size <10 mm.published_or_final_versionSpringer Open Choice, 31 May 201

    The relationship between priestly motivational styles and personal wellbeing in ministry : exploring the connection between religious orientation and purpose in life among Catholic priests serving in Italy

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    This study examines the association between priestly motivation (accessed via the psychological notion of religious orientation) and personal wellbeing (accessed via the psychological notion of purpose in life) among a sample of 155 Catholic priests serving in Italy. The data confirm a positive association between intrinsic religious orientation and purpose in life, but a negative association between quest religious orientation and purpose in life. These findings are discussed in light of the expectations placed on Catholic priests by the Church and by society
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