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.

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.

An overall statistic for testing symmetry in social interactions

The present work focuses the attention on the skew-symmetry index as a measure of social reciprocity. This index is based on the correspondence between the amount of behaviour that each individual addresses to its partners and what it receives from them in return. Although the skew-symmetry index enables researchers to describe social groups, statistical inferential tests are required. The main aim of the present study is to propose an overall statistical technique for testing symmetry in experimental conditions, calculating the skew-symmetry statistic (Φ) at group level. Sampling distributions for the skew- symmetry statistic have been estimated by means of a Monte Carlo simulation in order to allow researchers to make statistical decisions. Furthermore, this study will allow researchers to choose the optimal experimental conditions for carrying out their research, as the power of the statistical test has been estimated. This statistical test could be used in experimental social psychology studies in which researchers may control the group size and the number of interactions within dyads.

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.

Lag-one autocorrelation in short series: Estimation and hypothesis testing

In the first part of the study, nine estimators of the first-order autoregressive parameter are reviewed and a new estimator is proposed. The relationships and discrepancies between the estimators are discussed in order to achieve a clear differentiation. In the second part of the study, the precision in the estimation of autocorrelation is studied. The performance of the ten lag-one autocorrelation estimators is compared in terms of Mean Square Error (combining bias and variance) using data series generated by Monte Carlo simulation. The results show that there is not a single optimal estimator for all conditions, suggesting that the estimator ought to be chosen according to sample size and to the information available of the possible direction of the serial dependence. Additionally, the probability of labelling an actually existing autocorrelation as statistically significant is explored using Monte Carlo sampling. The power estimates obtained are quite similar among the tests associated with the different estimators. These estimates evidence the small probability of detecting autocorrelation in series with less than 20 measurement times.

Inexperienced sonographers can successfully visualize and assess a three-dimensional image of the fetal face using a standardized ultrasound protocol.

Introduction: A standardized three-dimensional ultrasonographic (3DUS) protocol is described that allows fetal face reconstruction. Ability to identify cleft lip with 3DUS using this protocol was assessed by operators with minimal 3DUS experience. Material and Methods: 260 stored volumes of fetal face were analyzed using a standardized protocol by operators with different levels of competence in 3DUS. The outcomes studied were: (1) the performance of post-processing 3D face volumes for the detection of facial clefts; (2) the ability of a resident with minimal 3DUS experience to reconstruct the acquired facial volumes, and (3) the time needed to reconstruct each plane to allow proper diagnosis of a cleft. Results: The three orthogonal planes of the fetal face (axial, sagittal and coronal) were adequately reconstructed with similar performance when acquired by a maternal-fetal medicine specialist or by residents with minimal experience (72 vs. 76%, p = 0.629). The learning curve for manipulation of 3DUS volumes of the fetal face corresponds to 30 cases and is independent of the operator's level of experience. Discussion: The learning curve for the standardized protocol we describe is short, even for inexperienced sonographers. This technique might decrease the length of anatomy ultrasounds and improve the ability to visualize fetal face anomalies.

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.

Refinement of Rapid PCC Coarse Aggregate Testing Program, HR-1071, 1999

The characterization and categorization of coarse aggregates for use in portland cement concrete (PCC) pavements is a highly refined process at the Iowa Department of Transportation. Over the past 10 to 15 years, much effort has been directed at pursuing direct testing schemes to supplement or replace existing physical testing schemes. Direct testing refers to the process of directly measuring the chemical and mineralogical properties of an aggregate and then attempting to correlate those measured properties to historical performance information (i.e., field service record). This is in contrast to indirect measurement techniques, which generally attempt to extrapolate the performance of laboratory test specimens to expected field performance. The purpose of this research project was to investigate and refine the use of direct testing methods, such as X-ray analysis techniques and thermal analysis techniques, to categorize carbonate aggregates for use in portland cement concrete. The results of this study indicated that the general testing methods that are currently used to obtain data for estimating service life tend to be very reliable and have good to excellent repeatability. Several changes in the current techniques were recommended to enhance the long-term reliability of the carbonate database. These changes can be summarized as follows: (a) Limits that are more stringent need to be set on the maximum particle size in the samples subjected to testing. This should help to improve the reliability of all three of the test methods studied during this project. (b) X-ray diffraction testing needs to be refined to incorporate the use of an internal standard. This will help to minimize the influence of sample positioning errors and it will also allow for the calculation of the concentration of the various minerals present in the samples. (c) Thermal analysis data needs to be corrected for moisture content and clay content prior to calculating the carbonate content of the sample.

Field Testing of Asphaltic Concrete Mixes, HR-101 and R-183, 1968

The amount of asphalt cement in asphaltic concrete has a definite effect on its durability under adverse conditions. The expansion of the transportation system to more and heavier loads has also made the percentage of asphalt cement in a mix more critical. The laboratory mixer does not duplicate the mixing effect of the large pugmills; therefore, it is impossible to be completely sure of the asphalt cement needed for each mix. This percentage quite often must be varied in the field. With a central testing laboratory and the high production of mixing plants today, a large amount of asphaltic concrete is produced before a sample can be tested to determine if the asphalt content is correct. If the asphalt content lowers the durability or stability of a mix, more maintenance will be required in the future. The purpose of this project is to determine the value of a mobile laboratory in the field, the feasibility of providing adequate, early testing in the field, and correlation with the central laboratory. The major purpose was to determine as soon as possible the best percentage of asphalt.

Correlation Studies BPR Type Roughometer vs. PCE Type Road Meter, MLR-68-2, 1968

The BPR type Roughometer has been used by the Iowa State Highway Commission since 1955 for the evaluation of the relative roughness of the various Iowa road surfaces. Since the commencement of this program, standardized information about the roughness of the various Iowa roads with respect to their type, construction, location and usage has been obtained. The Roughometer has also served to improve the economics and quality of road construction by making the roughness results of various practices available to all who are interested. In 1965, the Portland Cement Association developed a device known as the PCA Road Meter for measuring road roughness. Mounted in a regular passenger car, the Road Meter is a simple electromechanical device of durable construction which can perform consistently with extremely low maintenance. In 1967, the Iowa State Highway Commission's Laboratory constructed a P.C.A. type Road Meter in order to provide an efficient and reliable method for measuring the Present Serviceability Index for the state's highways. Another possibility was that after considerable testing the Road Meter might eventually replace the Roughometer. Some advantages of the Road Meter over the Roughometer are: (1) Road Meter tests are made by the automobile driver and one assistant without the need of traffic protection. The Roughometer has a crew of four men; two operating the roughometer and two driving safety vehicles. (2) The Road Meter is able to do more miles of testing because of its faster testing speed and the fa.ct that it is the only vehicle involved in the testing. (3) Because of the faster testing speed, the Road Meter gives a better indication of how the road actually rides to the average highway traveler. (4) The cost of operating a Road Meter is less than that of a Roughometer because of the fewer number of vehicles and men needed in testing.

Freeze-Thaw Durability Testing of Oversanded Bridge Floor Concrete, MLR-95-5, 1995

Due to an equipment malfunction, too much sand was used in the concrete on the bridge floor placed on August 9, 1994, in Washington County, Project No. BRF-22-2(36)38-92. Freeze-thaw durability testing of cores taken from the concrete in question and the other two concretes not in question was performed. The experimental results indicate that the concrete in question is considered at least as durable and resistant to freeze-thaw damage as the concretes which are not in question. The concrete in question can be expected to function properly for the regular service life of the bridge.