Use of Hy's law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury.

BACKGROUND & AIMS Hy's Law, which states that hepatocellular drug-induced liver injury (DILI) with jaundice indicates a serious reaction, is used widely to determine risk for acute liver failure (ALF). We aimed to optimize the definition of Hy's Law and to develop a model for predicting ALF in patients with DILI. METHODS We collected data from 771 patients with DILI (805 episodes) from the Spanish DILI registry, from April 1994 through August 2012. We analyzed data collected at DILI recognition and at the time of peak levels of alanine aminotransferase (ALT) and total bilirubin (TBL). RESULTS Of the 771 patients with DILI, 32 developed ALF. Hepatocellular injury, female sex, high levels of TBL, and a high ratio of aspartate aminotransferase (AST):ALT were independent risk factors for ALF. We compared 3 ways to use Hy's Law to predict which patients would develop ALF; all included TBL greater than 2-fold the upper limit of normal (×ULN) and either ALT level greater than 3 × ULN, a ratio (R) value (ALT × ULN/alkaline phosphatase × ULN) of 5 or greater, or a new ratio (nR) value (ALT or AST, whichever produced the highest ×ULN/ alkaline phosphatase × ULN value) of 5 or greater. At recognition of DILI, the R- and nR-based models identified patients who developed ALF with 67% and 63% specificity, respectively, whereas use of only ALT level identified them with 44% specificity. However, the level of ALT and the nR model each identified patients who developed ALF with 90% sensitivity, whereas the R criteria identified them with 83% sensitivity. An equal number of patients who did and did not develop ALF had alkaline phosphatase levels greater than 2 × ULN. An algorithm based on AST level greater than 17.3 × ULN, TBL greater than 6.6 × ULN, and AST:ALT greater than 1.5 identified patients who developed ALF with 82% specificity and 80% sensitivity. CONCLUSIONS When applied at DILI recognition, the nR criteria for Hy's Law provides the best balance of sensitivity and specificity whereas our new composite algorithm provides additional specificity in predicting the ultimate development of ALF.

Transpalpebral proton beam radiotherapy of choroidal melanoma.

BACKGROUND: Collateral damage to upper eyelid margin during proton beam radiotherapy (PBR) for choroidal melanoma may cause squamous metaplasia of the tarsal conjunctiva with keratinisation, corneal irritation, discomfort and, rarely, corneal perforation. We evaluated transpalpebral PBR as a means of avoiding collateral damage to the upper eyelid margin without increasing the risk of failure of local tumour control. METHODS: Retrospective study of consecutive patients who underwent PBR for choroidal melanoma between 1992 and 2007 at the Royal Liverpool University Hospital and the Douglas Cyclotron at Clatterbridge Cancer Centre, UK. RESULTS: Sixty-three patients were included in this study. Mean basal tumour diameter and tumour thickness were 11.8 mm and 3.6 mm, respectively. PBR mean beam range and modulation were 26.5 mm and 16.9 mm respectively. The eyelid margin was included in the radiation field in 15 (24%) eyes. The median follow-up was 2.5 years. Local tumour recurrence developed in 2 (3.2%) patients. In these two cases that developed tumour recurrence the transpalpebral treatment did not involve the eyelid margin. Six (9.5%) patients died of metastatic disease. No eyelid or ocular surface problems developed in any of the 48 patients who were treated without eyelid rim involvement, while 7 of the 15 patients with unavoidable irradiation of the eyelid rim developed some degree of madarosis. These seven patients all received more than 26.55 proton Gy to the eyelid margin. Symptoms, such as grittiness occurred in 12% of 48 patients without eyelid margin irradiation as compared with 53% of 15 patients whose lid margin was irradiated. CONCLUSIONS: Transpalpebral PBR of choroidal melanoma avoids eyelid and ocular surface complications without increasing failure of local tumour control.

Investigation of the Modified Beam-in-Slab Bridge System, Technical Report, 2004, Vol. 1

Technical Report

Investigation of the Modified Beam-in-Slab Bridge System, Design Guide, 2004, Vol. 3

Design guide

Investigation of the Modified Beam-in-Slab Bridge System, Design Manual, 2004, Vol. 2

Design Manual

Evaluation of Composite Pavement Unbonded Overlays: Phases I and II, April 2003

In recent years, thin whitetopping has evolved as a viable rehabilitation technique for deteriorated asphalt cement concrete (ACC) pavements. Numerous projects have been constructed and tested; these projects allow researchers to identify the important elements contributing to the projects’ successes. These elements include surface preparation, overlay thickness, synthetic fiber reinforcement usage, joint spacing, and joint sealing. Although the main factors affecting thin whitetopping performance have been identified by previous research, questions still existed as to the optimum design incorporating these variables. The objective of this research is to investigate the interaction between these variables over time. Laboratory testing and field-testing were planned in order to accomplish the research objective. Laboratory testing involved shear testing of the bond between the portland cement concrete (PCC) overlay and the ACC surface. Field-testing involved falling weight deflectometer deflection responses, measurement of joint faulting and joint opening, and visual distress surveys on the 9.6-mile project. The project was located on Iowa Highway 13 extending north from the city of Manchester, Iowa, to Iowa Highway 3 in Delaware County. Variables investigated included ACC surface preparation, PCC thickness, synthetic fiber reinforcement usage, and joint spacing. This report documents the planning, equipment selection, construction, field changes, and construction concerns of the project built in 2002. The data from this research could be combined with historical data to develop a design specification for the construction of thin, unbonded overlays.

[Recueil composite].

Contient : Job, cum commentariis ; Fridegisus, Tractatus de grammatica (34-36). - S. Bonifatius, Ars grammatica (36v-47v, 58-70). - Tatuinus, Ars grammatica (48, 57, 49-56v, 79-86, 71-78v)

Evaluation of Composite Pavement Unbonded Overlays: Phase III, August 2006

In recent years, thin whitetopping has evolved as a viable rehabilitation technique for deteriorated asphalt cement concrete (ACC) pavements. Numerous projects have been constructed and tested, allowing researchers to identify the important elements contributing to the projects’ successes. These elements include surface preparation, overlay thickness, synthetic fiber reinforcement usage, joint spacing, and joint sealing. Although the main factors affecting thin whitetopping performance have been identified by previous research, questions still existed as to the optimum design incorporating these variables. The objective of this research is to investigate the interaction between these variables over time. Laboratory testing and field testing were conducted to achieve the research objectives. Laboratory testing involved shear testing of the bond between the portland cement concrete (PCC) overlay and the ACC surface. Field testing involved falling weight deflectometer deflection responses, measurement of joint faulting and joint opening, and visual distress surveys on the 9.6-mile project. The project was located on Iowa Highway 13 extending north from the city of Manchester, Iowa, to Iowa Highway 3 in Delaware County. Variables investigated include ACC surface preparation, PCC thickness, slab size, synthetic fiber reinforcement usage, and joint spacing. This report documents the planning, construction, and performance of each variable in the time period from summer 2002 through spring 2006. The project has performed well with only minor distress identification since its construction.

European French-speaking study from the GEMO group on bone metastases management: a special focus on external beam radiotherapy practice survey.

This study seeks to perform a survey of patterns of practice among the different physicians involved in the bone metastases management, with special focus on external beam radiotherapy (EBRT).A questionnaire about bone metastases based on clinical cases and supplemented with general questions, including medical therapies, EBRT and metabolic radiotherapy strategies, surgery, and supportive care approaches, was sent to 4,706 French-speaking physicians in Belgium, France, Luxemburg, and Switzerland.Overall, 644 questionnaires were analyzed. Twenty-eight percent concerned the radiotherapy approach and were judged adequate to respond to the part dedicated to EBRT. Sixty-nine percent of physicians used a total dose irradiation of 30 Gy delivered in ten fractions. A large majority (75%) used two opposed fields prescribed at mid-depth (30%), or with non-equally weighted fields (45%). Seventy percent irradiated also above and below the concerned vertebra. A dosimetry planning treatment was done in 85% and high-energy megavoltage photons were used in 42%. Moreover, 54% physicians used short course radiotherapy in routine.Radiotherapy remains the mainstay of treatment of bone metastases, but there is substantial heterogeneity in clinical practice. Guidelines and treatment protocols are required to improve the treatment quality.

An assessment of empirical Bayes and composite estimators for small areas

We compare a set of empirical Bayes and composite estimators of the population means of the districts (small areas) of a country, and show that the natural modelling strategy of searching for a well fitting empirical Bayes model and using it for estimation of the area-level means can be inefficient.

Using composite estimators to improve both domain and total area estimation

In this article we propose using small area estimators to improve the estimatesof both the small and large area parameters. When the objective is to estimateparameters at both levels accurately, optimality is achieved by a mixed sampledesign of fixed and proportional allocations. In the mixed sample design, oncea sample size has been determined, one fraction of it is distributedproportionally among the different small areas while the rest is evenlydistributed among them. We use Monte Carlo simulations to assess theperformance of the direct estimator and two composite covariant-freesmall area estimators, for different sample sizes and different sampledistributions. Performance is measured in terms of Mean Squared Errors(MSE) of both small and large area parameters. It is found that the adoptionof small area composite estimators open the possibility of 1) reducingsample size when precision is given, or 2) improving precision for a givensample size.

Whole brain radiotherapy with a conformational external beam radiation boost for lung cancer patients with 1-3 brain metastasis: a multi institutional study.

BACKGROUND: To determine the outcome of patients with brain metastasis (BM) from lung cancer treated with an external beam radiotherapy boost (RTB) after whole brain radiotherapy (WBRT). METHODS: A total of 53 BM patients with lung cancer were treated sequentially with WBRT and RTB between 1996 and 2008 according to our institutional protocol. Mean age was 58.8 years. The median KPS was 90. Median recursive partitioning analysis (RPA) and graded prognostic assessment (GPA) grouping were 2 and 2.5, respectively. Surgery was performed on 38 (71%) patients. The median number of BM was 1 (range, 1-3). Median WBRT and RTB combined dose was 39 Gy (range, 37.5-54). Median follow-up was 12.0 months. RESULTS: During the period of follow-up, 37 (70%) patients died. The median overall survival (OS) was 14.5 months. Only 13 patients failed in the brain. The majority of patients (n = 29) failed distantly. The 1-year OS, -local control, extracranial failure rates were 61.2%, 75.2% and 60.8%, respectively. On univariate analysis, improved OS was found to be significantly associated with total dose (< or = 39 Gy vs. > 39 Gy; p < 0.01), age < 65 (p < 0.01), absence of extracranial metastasis (p < 0.01), GPA > or = 2.5 (p = 0.01), KPS > or = 90 (p = 0.01), and RPA < 2 (p = 0.04). On multivariate analysis, total dose (p < 0.01) and the absence of extracranial metastasis (p = 0.03) retained statistical significance. CONCLUSIONS: The majority of lung cancer patients treated with WBRT and RTB progressed extracranially. There might be a subgroup of younger patients with good performance status and no extracranial disease who may benefit from dose escalation after WBRT to the metastatic site.