Integration of local-scale hydrological and regional-scale geophysical based on a nonlinear Bayesian sequential simulation approach

Significant progress has been made with regard to the quantitative integration of geophysical and hydrological data at the local scale. However, extending the corresponding approaches to the regional scale represents a major, and as-of-yet largely unresolved, challenge. To address this problem, we have developed a downscaling procedure based on a non-linear Bayesian sequential simulation approach. The basic objective of this algorithm is to estimate the value of the sparsely sampled hydraulic conductivity at non-sampled locations based on its relation to the electrical conductivity, which is available throughout the model space. The in situ relationship between the hydraulic and electrical conductivities is described through a non-parametric multivariate kernel density function. This method is then applied to the stochastic integration of low-resolution, re- gional-scale electrical resistivity tomography (ERT) data in combination with high-resolution, local-scale downhole measurements of the hydraulic and electrical conductivities. Finally, the overall viability of this downscaling approach is tested and verified by performing and comparing flow and transport simulation through the original and the downscaled hydraulic conductivity fields. Our results indicate that the proposed procedure does indeed allow for obtaining remarkably faithful estimates of the regional-scale hydraulic conductivity structure and correspondingly reliable predictions of the transport characteristics over relatively long distances.

Screening for gestational diabetes: variation in guidelines.

OBJECTIVE: To compare published guidelines concerning screening for gestational diabetes. STUDY DESIGN: Systematic search and comparative analysis of published guidelines. Appraisal of guidelines quality. Simulation analysis. RESULTS: Ten published guidelines proposed either universal screening (5), selective screening (3) or screening when clinically indicated (2). Variations of testing schedules and blood glucose thresholds were observed. The quality of the published guidelines was low, on average 22 (8-51) percentage points on the assessment scale. These differences would have led to large variations in the number of patients to be screened. CONCLUSIONS: Large variations between guidelines have been observed which would translate in large practice variations, if the guidelines were systematically applied. These variations are partially explained by the absence of definite evidence that universal or selective screening for gestational diabetes do more good than harm on infant and maternal health. The methodology of developing guidelines should be more evidence based, systematic and explicit.

Personalized care in neuro-oncology coming of age: why we need MGMT and 1p/19q testing for malignant glioma patients in clinical practice.

Histological subtyping and grading by malignancy are the cornerstones of the World Health Organization (WHO) classification of tumors of the central nervous system. They shall provide clinicians with guidance as to the course of disease to be expected and the choices of treatment to be made. Nonetheless, patients with histologically identical tumors may have very different outcomes, notably in patients with astrocytic and oligodendroglial gliomas of WHO grades II and III. In gliomas of adulthood, 3 molecular markers have undergone extensive studies in recent years: 1p/19q chromosomal codeletion, O(6)-methylguanine methyltransferase (MGMT) promoter methylation, and mutations of isocitrate dehydrogenase (IDH) 1 and 2. However, the assessment of these molecular markers has so far not been implemented in clinical routine because of the lack of therapeutic implications. In fact, these markers were considered to be prognostic irrespective of whether patients were receiving radiotherapy (RT), chemotherapy, or both (1p/19q, IDH1/2), or of limited value because testing is too complex and no chemotherapy alternative to temozolomide was available (MGMT). In 2012, this situation has changed: long-term follow-up of the Radiation Therapy Oncology Group 9402 and European Organisation for Research and Treatment of Cancer 26951 trials demonstrated an overall survival benefit from the addition to RT of chemotherapy with procarbazine/CCNU/vincristine confined to patients with anaplastic oligodendroglial tumors with (vs without) 1p/19q codeletion. Furthermore, in elderly glioblastoma patients, the NOA-08 and the Nordic trial of RT alone versus temozolomide alone demonstrated a profound impact of MGMT promoter methylation on outcome by therapy and thus established MGMT as a predictive biomarker in this patient population. These recent results call for the routine implementation of 1p/19q and MGMT testing at least in subpopulations of malignant glioma patients and represent an encouraging step toward the development of personalized therapeutic approaches in neuro-oncology.

Designing and testing of a sensor based on a magnetoresistive manganese perovskite thick film

In this paper we report on the growth of thick films of magnetoresistive La2/3Sr1/3MnO3 by using spray and screen printing techniques on various substrates (Al2O3 and ZrO2). The growth conditions are explored in order to optimize the microstructure of the films. The films display a room-temperature magnetoresistance of 0.0012%/Oe in the 1 kOe field region. A magnetic sensor is described and tested.

MMPBSA decomposition of the binding energy throughout a molecular dynamics simulation of Amyloid-Beta (Aß10-35) aggregation

Recent experiments with amyloid-beta (Aß) peptides indicate that the formation of toxic oligomers may be an important contribution to the onset of Alzheimer's disease. The toxicity of Aß oligomers depend on their structure, which is governed by assembly dynamics. However, a detailed knowledge of the structure of at the atomic level has not been achieved yet due to limitations of current experimental techniques. In this study, replica exchange molecular dynamics simulations are used to identify the expected diversity of dimer conformations of Aß10-35 monomers. The most representative dimer conformation has been used to track the dimer formation process between both monomers. The process has been characterized by means of the evolution of the decomposition of the binding free energy, which provides an energetic profile of the interaction. Dimers undergo a process of reorganization driven basically by inter-chain hydrophobic and hydrophilic interactions and also solvation/desolvation processes.

HIV testing in Switzerland.

OBJECTIVES: To obtain information about the prevalence of, reasons for, and adequacy of HIV testing in the general population in Switzerland in 1992. DESIGN: Telephone survey (n = 2800). RESULTS: Some 47% of the sample underwent one HIV test performed through blood donation (24%), voluntary testing (17%) or both (6%). Of the sample, 46% considered themselves well or very well informed about the HIV test. Patients reported unsystematic pre-test screening by doctors for the main HIV risks. People having been in situations of potential exposure to risk were more likely to have had the test than others. Overall, 85% of those HIV-tested had a relevant, generally risk-related reason for having it performed. CONCLUSIONS: HIV testing is widespread in Switzerland. Testing is mostly performed for relevant reasons. Pre-test counselling is poor and an opportunity for prevention is thus lost.

Looking for Validity or Testing It? The Perils of Stepwise Regression, Extreme-Scores Analysis, Heteroscedasticity, and Measurement Error

When researchers introduce a new test they have to demonstrate that it is valid, using unbiased designs and suitable statistical procedures. In this article we use Monte Carlo analyses to highlight how incorrect statistical procedures (i.e., stepwise regression, extreme scores analyses) or ignoring regression assumptions (e.g., heteroscedasticity) contribute to wrong validity estimates. Beyond these demonstrations, and as an example, we re-examined the results reported by Warwick, Nettelbeck, and Ward (2010) concerning the validity of the Ability Emotional Intelligence Measure (AEIM). Warwick et al. used the wrong statistical procedures to conclude that the AEIM was incrementally valid beyond intelligence and personality traits in predicting various outcomes. In our re-analysis, we found that the reliability-corrected multiple correlation of their measures with personality and intelligence was up to .69. Using robust statistical procedures and appropriate controls, we also found that the AEIM did not predict incremental variance in GPA, stress, loneliness, or well-being, demonstrating the importance for testing validity instead of looking for it.

Dosage optimization of treatments using population pharmacokinetic modeling and simulation.

Pharmacokinetic variability in drug levels represent for some drugs a major determinant of treatment success, since sub-therapeutic concentrations might lead to toxic reactions, treatment discontinuation or inefficacy. This is true for most antiretroviral drugs, which exhibit high inter-patient variability in their pharmacokinetics that has been partially explained by some genetic and non-genetic factors. The population pharmacokinetic approach represents a very useful tool for the description of the dose-concentration relationship, the quantification of variability in the target population of patients and the identification of influencing factors. It can thus be used to make predictions and dosage adjustment optimization based on Bayesian therapeutic drug monitoring (TDM). This approach has been used to characterize the pharmacokinetics of nevirapine (NVP) in 137 HIV-positive patients followed within the frame of a TDM program. Among tested covariates, body weight, co-administration of a cytochrome (CYP) 3A4 inducer or boosted atazanavir as well as elevated aspartate transaminases showed an effect on NVP elimination. In addition, genetic polymorphism in the CYP2B6 was associated with reduced NVP clearance. Altogether, these factors could explain 26% in NVP variability. Model-based simulations were used to compare the adequacy of different dosage regimens in relation to the therapeutic target associated with treatment efficacy. In conclusion, the population approach is very useful to characterize the pharmacokinetic profile of drugs in a population of interest. The quantification and the identification of the sources of variability is a rational approach to making optimal dosage decision for certain drugs administered chronically.

Laboratory Testing of SHRP SPS-2 P.C.C. Mixes, MLR-94-5, 1995

This research evaluated the concrete strength of two mixes which were used in the Polk County project NHS-500-1(3)--10-77 and were developed to meet a contract requirement of 900 psi third-point 28-day flexural strength. Two concrete mixes, the Proposed Mix and the Enhanced Mix, were tested for strength. Based on the experimental results, it was found that the addition of 50 lb of cementitious materials did not significantly increase concrete strength. The requirement of 900 psi 28-day third-point flexural strength (MOR-TPL) was not achieved by this amount of addition of cementitious materials.

Testing of Old Reinforced Concrete Bridges, HR-390, 1997

The objective of this research project was to service load test a representative sample of old reinforced concrete bridges (some of them historic and some of them scheduled for demolition) with the results being used to create a database so the performance of similar bridges could be predicted. The types of bridges tested included two reinforced concrete open spandrel arches, two reinforced concrete filled spandrel arches, one reinforced concrete slab bridge, and one two span reinforced concrete stringer bridge. The testing of each bridge consisted of applying a static load at various locations on the bridges and monitoring strains and deflections in critical members. The load was applied by means of a tandem axle dump truck with varying magnitudes of load. At each load increment, the truck was stopped at predetermined transverse and longitudinal locations and strain and deflection data were obtained. The strain data obtained were then evaluated in relation to the strain values predicted by traditional analytical procedures and a carrying capacity of the bridges was determined based on the experimental data. The response of a majority of the bridges tested was considerably lower than that predicted by analysis. Thus, the safe load carrying capacities of the bridges were greater than those predicted by the analytical models, and in a few cases, the load carrying capacities were found to be three or four times greater than calculated values. However, the test results of one bridge were lower than those predicted by analysis and thus resulted in the analytical rating being reduced. The results of the testing verified that traditional analytical methods, in most instances, are conservative and that the safe load carrying capacities of a majority of the reinforced concrete bridges are considerably greater than what one would determine on the basis of analytical analysis alone. In extrapolating the results obtained from diagnostic load tests to levels greater than those placed on the bridge during the load test, care must be taken to ensure safe bridge performance at the higher load levels. To extrapolate the load test results from the bridges tested in this investigation, the method developed by Lichtenstein in NCHRP Project 12-28(13)A was used.