Clinical utility of a Web-enabled risk-assessment and clinical decision support program.

PURPOSE: Risk-stratified guidelines can improve quality of care and cost-effectiveness, but their uptake in primary care has been limited. MeTree, a Web-based, patient-facing risk-assessment and clinical decision support tool, is designed to facilitate uptake of risk-stratified guidelines. METHODS: A hybrid implementation-effectiveness trial of three clinics (two intervention, one control). PARTICIPANTS: consentable nonadopted adults with upcoming appointments. PRIMARY OUTCOME: agreement between patient risk level and risk management for those meeting evidence-based criteria for increased-risk risk-management strategies (increased risk) and those who do not (average risk) before MeTree and after. MEASURES: chart abstraction was used to identify risk management related to colon, breast, and ovarian cancer, hereditary cancer, and thrombosis. RESULTS: Participants = 488, female = 284 (58.2%), white = 411 (85.7%), mean age = 58.7 (SD = 12.3). Agreement between risk management and risk level for all conditions for each participant, except for colon cancer, which was limited to those <50 years of age, was (i) 1.1% (N = 2/174) for the increased-risk group before MeTree and 16.1% (N = 28/174) after and (ii) 99.2% (N = 2,125/2,142) for the average-risk group before MeTree and 99.5% (N = 2,131/2,142) after. Of those receiving increased-risk risk-management strategies at baseline, 10.5% (N = 2/19) met criteria for increased risk. After MeTree, 80.7% (N = 46/57) met criteria. CONCLUSION: MeTree integration into primary care can improve uptake of risk-stratified guidelines and potentially reduce "overuse" and "underuse" of increased-risk services.Genet Med 18 10, 1020-1028.

Utility of a molecular prescreening program in advanced colorectal cancer for enrollment on biomarker-selected clinical trials.

BACKGROUND: Incorporation of multiple enrichment biomarkers into prospective clinical trials is an active area of investigation, but the factors that determine clinical trial enrollment following a molecular prescreening program have not been assessed. PATIENTS AND METHODS: Patients with 5-fluorouracil-refractory metastatic colorectal cancer at the MD Anderson Cancer Center were offered screening in the Assessment of Targeted Therapies Against Colorectal Cancer (ATTACC) program to identify eligibility for companion phase I or II clinical trials with a therapy targeted to an aberration detected in the patient, based on testing by immunohistochemistry, targeted gene sequencing panels, and CpG island methylation phenotype assays. RESULTS: Between August 2010 and December 2013, 484 patients were enrolled, 458 (95%) had a biomarker result, and 157 (32%) were enrolled on a clinical trial (92 on biomarker-selected and 65 on nonbiomarker selected). Of the 458 patients with a biomarker result, enrollment on biomarker-selected clinical trials was ninefold higher for predefined ATTACC-companion clinical trials as opposed to nonpredefined biomarker-selected clinical trials, 17.9% versus 2%, P < 0.001. Factors that correlated positively with trial enrollment in multivariate analysis were higher performance status, older age, lack of standard of care therapy, established patient at MD Anderson, and the presence of an eligible biomarker for an ATTACC-companion study. Early molecular screening did result in a higher rate of patients with remaining standard of care therapy enrolling on ATTACC-companion clinical trials, 45.1%, in contrast to nonpredefined clinical trials, 22.7%; odds ratio 3.1, P = 0.002. CONCLUSIONS: Though early molecular prescreening for predefined clinical trials resulted in an increase rate of trial enrollment of nonrefractory patients, the majority of patients enrolled on clinical trials were refractory to standard of care therapy. Within molecular prescreening programs, tailoring screening for preidentified and open clinical trials, temporally linking screening to treatment and optimizing both patient and physician engagement are efforts likely to improve enrollment on biomarker-selected clinical trials. CLINICAL TRIALS NUMBER: The study NCT number is NCT01196130.

Analysis of the utility of QuantiFERON-TB gold in tube and measurement of IFNgamma release by peripheral mononuclear cells in response to different mycobacterium antigen in the work-up of patients with uveitis.

Evaluation Studies

A prognostic assessment method for power electronics modules

This paper describes a prognostic method which combines the physics of failure models with probability reasoning algorithm. The measured real time data (temperature vs. time) was used as the loading profile for the PoF simulations. The response surface equation of the accumulated plastic strain in the solder interconnect in terms of two variables (average temperature, and temperature amplitude) was constructed. This response surface equation was incorporated into the lifetime model of solder interconnect, and therefore the remaining life time of the solder component under current loading condition was predicted. The predictions from PoF models were also used to calculate the conditional probability table for a Bayesian Network, which was used to take into account of the impacts of the health observations of each product in lifetime prediction. The prognostic prediction in the end was expressed as the probability for the product to survive the expected future usage. As a demonstration, this method was applied to an IGBT power module used for aircraft applications.

Exploring the conditional performance of UK unit trusts

We evaluate the conditional performance of U.K. equity unit trusts using the approach of Lynch and Wachter (2007, 2008) relative to three conditional linear factor models. We find significant time variation in the conditional performance of some trust portfolios and individual trusts using the lag term spread as the information variable. The conditional performance of the trusts is countercyclical and larger trusts have more countercyclical performance than smaller trusts within certain investment sectors. These patterns in conditional trust performance cannot be fully explained by the underlying securities that the trusts hold.

Improving the performance of a Mediterranean demersal fishery towards societal objectives beyond MSY

Mediterranean demersal fisheries are highly multispecific and many of their target stocks are overexploited. In addition, rocketing fuel costs and low market prices of traditionally high-value species are challenging the viability of fisheries. Here, based on the numeric results of a simulation model, we conclude that this situation can be remedied by reducing both fishing mortality and fishing costs. According to our model results, fishing effort reductions of 48–71% would improve the health of fish stocks while increasing the economic profits of Mallorca islands bottom trawl fishery to as much as 1.9 M€ (146% higher than current profits). If all fish stocks were exploited at their MSY (or below) level, the reduction in fishing effort would have to be of 71% from current values. If equilibrium profits from the fishery were to be maximized (MEY), fishing effort would need to be reduced by 48%. These results must be taken with caution due the many sources of uncertainty of our analysis. The modeling tools used to estimate these values are conditional to the adequate treatment of two sources of uncertainty that are particularly problematic in Mediterranean fisheries: insufficiently known recruitment variability and lack of periodic evaluations of the state of many species. Our results show that fishing effort reductions would produce economic yield gains after a period of transition. Further studies on the benefits of changing the size-selection pattern of fisheries, on better estimation of stock–recruitment relationships and on better quantifications of the contribution of secondary species to these fisheries, are expected to improve the scientific recommendations for Mediterranean demersal fisheries toward sustainability principles.

Improving the performance of a Mediterranean demersal fishery toward economic objectives beyond MSY

Mediterranean demersal fisheries are highly multispecific and many of their target stocks are overexploited. In addition, rocketing fuel costs and low market prices of traditionally high-value species are challenging the viability of fisheries. Here, based on the numeric results of a simulation model, we conclude that this situation can be remedied by reducing both fishing mortality and fishing costs. According to our model results, fishing effort reductions of 48-71% would improve the health of fish stocks while increasing the economic profits of Mallorca islands bottom trawl fishery to as much as 1.9 M(sic) (146% higher than current profits). If all fish stocks were exploited at their MSY (or below) level, the reduction in fishing effort would have to be of 71% from current values. If equilibrium profits from the fishery were to be maximized (MEY), fishing effort would need to be reduced by 48%. These results must be taken with caution due the many sources of uncertainty of our analysis. The modeling tools used to estimate these values are conditional to the adequate treatment of two sources of uncertainty that are particularly problematic in Mediterranean fisheries: insufficiently known recruitment variability and lack of periodic evaluations of the state of many species. Our results show that fishing effort reductions would produce economic yield gains after a period of transition. Further studies on the benefits of changing the size-selection pattern of fisheries, on better estimation of stock recruitment relationships and on better quantifications of the contribution of secondary species to these fisheries, are expected to improve the scientific recommendations for Mediterranean demersal fisheries toward sustainability principles.

Conditional production of superpositions of coherent states with inefficient photon detection

It is shown that a linear superposition of two macroscopically distinguishable optical coherent states can be generated using a single photon source and simple all-optical operations. Weak squeezing on a single photon, beam mixing with an auxiliary coherent state, and photon detecting with imperfect threshold detectors are enough to generate a coherent state superposition in a free propagating optical field with a large coherent amplitude (alpha>2) and high fidelity (F>0.99). In contrast to all previous schemes to generate such a state, our scheme does not need photon number resolving measurements nor Kerr-type nonlinear interactions. Furthermore, it is robust to detection inefficiency and exhibits some resilience to photon production inefficiency.