Trust-Based Mechanisms for Robust and Efficient Task Allocation in the Presence of Execution Uncertainty

Vickrey-Clarke-Groves (VCG) mechanisms are often used to allocate tasks to selfish and rational agents. VCG mechanisms are incentive-compatible, direct mechanisms that are efficient (i.e. maximise social utility) and individually rational (i.e. agents prefer to join rather than opt out). However, an important assumption of these mechanisms is that the agents will always successfully complete their allocated tasks. Clearly, this assumption is unrealistic in many real-world applications where agents can, and often do, fail in their endeavours. Moreover, whether an agent is deemed to have failed may be perceived differently by different agents. Such subjective perceptions about an agent’s probability of succeeding at a given task are often captured and reasoned about using the notion of trust. Given this background, in this paper, we investigate the design of novel mechanisms that take into account the trust between agents when allocating tasks. Specifically, we develop a new class of mechanisms, called trust-based mechanisms, that can take into account multiple subjective measures of the probability of an agent succeeding at a given task and produce allocations that maximise social utility, whilst ensuring that no agent obtains a negative utility. We then show that such mechanisms pose a challenging new combinatorial optimisation problem (that is NP-complete), devise a novel representation for solving the problem, and develop an effective integer programming solution (that can solve instances with about 2×105 possible allocations in 40 seconds).

Body weight and colorectal cancer risk in a cohort of Swedish women: relation varies by age and cancer site

The relation between relative body weight and colorectal cancer among women is unclear. In a large prospective cohort study, we found a positive association only for distal cancers among younger women that became attenuated at older ages. These results support previous reports in which results were stratified by age or colorectal cancer site. © 2001 Cancer Research Campaign http://www.bjcancer.co

Metabolomic Biomarkers of Prostate Cancer: Prediction, Diagnosis, Progression, Prognosis, and Recurrence

Metabolite profiling is being increasing employed in the study of prostate cancer as a means of identifying predictive, diagnostic, and prognostic biomarkers. This review provides a summary and critique of the current literature. Thirty-three human case-control studies of prostate cancer exploring disease prediction, diagnosis, progression, or treatment response were identified. All but one demonstrated the ability of metabolite profiling to distinguish cancer from benign, tumor aggressiveness, cases who recurred, and those who responded well to therapy. In the subset of studies where biomarker discriminatory ability was quantified, high AUCs were reported that would potentially outperform the current gold standards in diagnosis, prognosis, and disease recurrence, including PSA testing. There were substantial similarities between the metabolites and the associated pathways reported as significant by independent studies, and important roles for abnormal cell growth, intensive cell proliferation, and dysregulation of lipid metabolism were highlighted. The weight of the evidence therefore suggests metabolic alterations specific to prostate carcinogenesis and progression that may represent potential metabolic biomarkers. However, replication and validation of the most promising biomarkers is currently lacking and a number of outstanding methodologic issues remain to be addressed to maximize the utility of metabolomics in the study of prostate cancer.National Institutes of Health (U.S.) (Grant P01 CA055075)National Institutes of Health (U.S.) (Grant CA133891)National Institutes of Health (U.S.) (Grant CA141298)National Institutes of Health (U.S.) (Grant CA136578)National Institutes of Health (U.S.) (Grant UM1 CA167552

Benefit-risk assessment of vitamin D supplementation

Summary: Current intake recommendations of 200 to 600IU vitamin D per day may be insufficient for important disease outcomes reduced by vitamin D. Introduction: This study assessed the benefit of higher-dose and higher achieved 25-hydroxyvitamin D levels [25(OH)D] versus any associated risk. Methods and results: Based on double-blind randomized control trials (RCTs), eight for falls (n = 2426) and 12 for non-vertebral fractures (n = 42,279), there was a significant dose-response relationship between higher-dose and higher achieved 25(OH)D and greater fall and fracture prevention. Optimal benefits were observed at the highest dose tested to date for 700 to 1000IU vitamin D per day or mean 25(OH)D between 75 and 110nmol/l (30-44ng/ml). Prospective cohort data on cardiovascular health and colorectal cancer prevention suggested increased benefits with the highest categories of 25(OH)D evaluated (median between 75 and 110nmol/l). In 25 RCTs, mean serum calcium levels were not related to oral vitamin D up to 100,000IU per day or achieved 25(OH)D up to 643nmol/l. Mean levels of 75 to 110nmol/l were reached in most RCTs with 1,800 to 4,000IU vitamin D per day without risk. Conclusion: Our analysis suggests that mean serum 25(OH)D levels of about 75 to 110nmol/l provide optimal benefits for all investigated endpoints without increasing health risks. These levels can be best obtained with oral doses in the range of 1,800 to 4,000IU vitamin D per day; further work is needed, including subject and environment factors, to better define the doses that will achieve optimal blood levels in the large majority of the populatio

Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer

Background Selective cyclooxygenase inhibitors may retard the progression of cancer, but they have enhanced thrombotic potential. We report on cardiovascular adverse events in patients receiving rofecoxib to reduce rates of recurrence of colorectal cancer. Methods All serious adverse events that were cardiovascular thrombotic events were reviewed in 2434 patients with stage II or III colorectal cancer participating in a randomized, placebo-controlled trial of rofecoxib, 25 mg daily, started after potentially curative tumor resection and chemotherapy or radiotherapy as indicated. The trial was terminated prematurely owing to worldwide withdrawal of rofecoxib. To examine possible persistent risks, we examined cardiovascular thrombotic events reported up to 24 months after the trial was closed. Results The median duration of active treatment was 7.4 months. The 1167 patients receiving rofecoxib and the 1160 patients receiving placebo were well matched, with a median follow-up period of 33.0 months (interquartile range, 27.6 to 40.1) and 33.4 months (27.7 to 40.4), respectively. Of the 23 confirmed cardiovascular thrombotic events, 16 occurred in the rofecoxib group during or within 14 days after the treatment period, with an estimated relative risk of 2.66 (from the Cox proportional-hazards model; 95% confidence interval [CI], 1.03 to 6.86; P = 0.04). Analysis of the Antiplatelet Trialists’ Collaboration end point (the combined incidence of death from cardiovascular, hemorrhagic, and unknown causes; of nonfatal myocardial infarction; and of nonfatal ischemic and hemorrhagic stroke) gave an unadjusted relative risk of 1.60 (95% CI, 0.57 to 4.51; P = 0.37). Fourteen more cardiovascular thrombotic events, six in the rofecoxib group, were reported within the 2 years after trial closure, with an overall unadjusted relative risk of 1.50 (95% CI, 0.76 to 2.94; P = 0.24). Four patients in the rofecoxib group and two in the placebo group died from thrombotic causes during or within 14 days after the treatment period, and during the follow-up period, one patient in the rofecoxib group and five patients in the placebo group died from cardiovascular causes. Conclusions Rofecoxib therapy was associated with an increased frequency of adverse cardiovascular events among patients with a median study treatment of 7.4 months’ duration. (Current Controlled Trials number, ISRCTN98278138.

Long-term use of antibiotics and risk of colorectal adenoma

Objective—Recent evidence suggests that antibiotic use, which alters the gut microbiome, is associated with an increased risk of colorectal cancer. However, the association between antibiotic use and risk of colorectal adenoma, the precursor for the majority of colorectal cancers, has not been investigated. Design—We prospectively evaluated the association between antibiotic use at age 20–39 and 40–59 (assessed in 2004) and recent antibiotic use (assessed in 2008) with risk of subsequent colorectal adenoma among 16,642 women aged ≥60 enrolled in the Nurses’ Health Study who underwent at least one colonoscopy through 2010. We used multivariate logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results—We documented 1,195 cases of adenoma. Increasing duration of antibiotic use at age 20–39 (Ptrend=0.002) and 40–59 (Ptrend=0.001) was significantly associated with an increased risk of colorectal adenoma. Compared to non-users, women who used antibiotics for ≥2 months between age 20–39 had a multivariable OR of 1.36 (95% CI: 1.03–1.79). Women who used ≥2 months of antibiotics between age 40–59 had a multivariable OR of 1.69 (95% CI: 1.24–2.31). The associations were similar for low-risk vs. high-risk adenomas (size ≥1 cm, or with tubulovillous/villous histology, or ≥3 detected lesions), but appeared modestly stronger for proximal compared with distal adenomas. In contrast, recent antibiotic use within the past 4 years was not associated with risk of adenoma (Ptrend=0.44). Conclusions—Long-term antibiotic use in early to middle adulthood was associated with increased risk of colorectal adenoma

A prospective study of plasma inflammatory markers and risk of colorectal cancer in men

Background: Chronic inflammation may mediate risk of colorectal cancer (CRC); however, the association between circulating inflammatory markers and risk of CRC has been inconsistent. Methods: We prospectively evaluated the association of plasma C-reactive protein (CRP), interleukin-6 (IL-6), and the soluble tumour necrosis factor receptor 2 (sTNFR-2) with incident CRC among 274 cases and 532 matched controls nested in the Health Professionals Follow-up Study. Results: Multivariate relative risk (RR) of CRC comparing the extreme quartiles of plasma IL-6 was 1.54 (95% confidence interval (CI), 0.99–2.40; Ptrend=0.02). However, after excluding cases diagnosed within 2 years of blood draw, this association was not statistically significant (RR=1.26, 95% CI, 0.78–2.05; Ptrend=0.21). In analyses restricted to cases diagnosed at least 2 years after blood draw, the association of IL-6 with CRC appeared to differ by body mass index such that the significantly positive association was only present among lean individuals (Pinteraction=0.03). We did not observe any significant association between CRP or sTNFR-2 and CRC. Conclusion: Plasma inflammatory markers are not generally associated with risk of CRC among men. However, the possibility that plasma IL-6 is associated with increased risk of CRC among lean men requires further investigation