Detection and identification of 700 drugs by multi-target screening with a 3200 Q TRAP LC-MS/MS system and library searching

The multi-target screening method described in this work allows the simultaneous detection and identification of 700 drugs and metabolites in biological fluids using a hybrid triple-quadrupole linear ion trap mass spectrometer in a single analytical run. After standardization of the method, the retention times of 700 compounds were determined and transitions for each compound were selected by a "scheduled" survey MRM scan, followed by an information-dependent acquisition using the sensitive enhanced product ion scan of a Q TRAP hybrid instrument. The identification of the compounds in the samples analyzed was accomplished by searching the tandem mass spectrometry (MS/MS) spectra against the library we developed, which contains electrospray ionization-MS/MS spectra of over 1,250 compounds. The multi-target screening method together with the library was included in a software program for routine screening and quantitation to achieve automated acquisition and library searching. With the help of this software application, the time for evaluation and interpretation of the results could be drastically reduced. This new multi-target screening method has been successfully applied for the analysis of postmortem and traffic offense samples as well as proficiency testing, and complements screening with immunoassays, gas chromatography-mass spectrometry, and liquid chromatography-diode-array detection. Other possible applications are analysis in clinical toxicology (for intoxication cases), in psychiatry (antidepressants and other psychoactive drugs), and in forensic toxicology (drugs and driving, workplace drug testing, oral fluid analysis, drug-facilitated sexual assault).

Selección de métodos estadísticos para la interpretación de intercomparaciones en ensayos de áridos para hormigón, mortero y balasto

El objeto del proyecto es determinar los métodos estadísticos adecuados para la evaluación de los resultados de un ejercicio de intercomparación entre laboratorios para ensayos de aptitud de áridos para hormigón, mortero y balasto. Los ensayos estudiados son los aludidos en la norma UNE-EN 12620:2002 de áridos para hormigón, UNE-EN 13139:2003 para mortero, y UNE-EN 13450:2003 para balasto, que pueden clasificarse según las propiedades a determinar: - Geométricas - Mecánicas y Físicas - Térmicas y de Alteración - Químicas Los criterios aplicables para el desarrollo de los trabajos son los exigidos por la Entidad Nacional de Acreditación (ENAC) para laboratorios acreditados conforme a la Norma UNE-EN ISO/IEC 17025 y para proveedores acreditados conforme a la Norma UNE-EN ISO/IEC 17043. ABSTRACT The purpose of the project is to determine the appropriate statistical methods to evaluate the results of an intercomparison exercise among laboratories for proficiency testing of aggregates for concrete, mortar and ballast. The studied assays are mentioned in the UNE-EN 12620:2002 standard of aggregates for concrete, UNE-EN 13139:2003 for mortar, and UNE-EN 13450:2003 for ballast, which can be classified according to the properties to determine: - Geometric - Mechanical and Physical - Thermal and Alteration - Chemical The criteria for the development of the work are those required by the National Accreditation Body (ENAC) for laboratories accredited according to the UNE-EN ISO / IEC 17025 and for suppliers according to the UNE-EN ISO / IEC 17043.

Variation in pre-PCR processing of FFPE samples leads to discrepancies in BRAF and EGFR mutation detection: a diagnostic RING trial.

AIMS: Mutation detection accuracy has been described extensively; however, it is surprising that pre-PCR processing of formalin-fixed paraffin-embedded (FFPE) samples has not been systematically assessed in clinical context. We designed a RING trial to (i) investigate pre-PCR variability, (ii) correlate pre-PCR variation with EGFR/BRAF mutation testing accuracy and (iii) investigate causes for observed variation. METHODS: 13 molecular pathology laboratories were recruited. 104 blinded FFPE curls including engineered FFPE curls, cell-negative FFPE curls and control FFPE tissue samples were distributed to participants for pre-PCR processing and mutation detection. Follow-up analysis was performed to assess sample purity, DNA integrity and DNA quantitation. RESULTS: Rate of mutation detection failure was 11.9%. Of these failures, 80% were attributed to pre-PCR error. Significant differences in DNA yields across all samples were seen using analysis of variance (p

Position paper on passive sampling techniques for the monitoring of contaminants in the aquatic environment - Achievements to date and perspectives

This paper, based on the outcome of discussions at a NORMAN Network-supported workshop in Lyon (France) in November 2014 aims to provide a common position of passive sampling community experts regarding concrete actions required to foster the use of passive sampling techniques in support of contaminant risk assessment and management and for routine monitoring of contaminants in aquatic systems. The brief roadmap presented here focusses on the identification of robust passive sampling methodology, technology that requires further development or that has yet to be developed, our current knowledge of the evaluation of uncertainties when calculating a freely dissolved concentration, the relationship between data from PS and that obtained through biomonitoring. A tiered approach to identifying areas of potential environmental quality standard (EQS) exceedances is also shown. Finally, we propose a list of recommended actions to improve the acceptance of passive sampling by policy-makers. These include the drafting of guidelines, quality assurance and control procedures, developing demonstration projects where biomonitoring and passive sampling are undertaken alongside, organising proficiency testing schemes and interlaboratory comparison and, finally, establishing passive sampler-based assessment criteria in relation to existing EQS.

Large-scale testing of proficiency in English: Back to multiple choice?

The paper analyses whether that a properly designed multiple choice test can discriminate with a high level of accuracy if a student in our context has reached a B2 level according to the CEFRL.

Testing motor fitness in karate

Background and Study Aim: Evaluation of sport skills test can be very useful tool for coach practice. The aim of the present paper was: (a) to evaluate the reliability and accuracy of the Specific Physical Fitness Tests (SPFT) (b) to review the results of karate athletes who represent different weight categories, and who are at different stages of schooling; (c) to establish grading criteria of physical fitness preparation. Material/Methods: The reseach was conducted among 219 Kyokushin karate players, whose profiles were presented as (chi) over bar +/- SD and their main characteristics were the following: age 26.8 +/- 4.67 (19-39) years, body mass 75.2 +/- 8.35 (50-97) kg and body height 176.4 +/- 5.67 (160-196) cm. The value of the BMI amounted to 24.1 +/- 2.17 (17.9-29.4) kg/m(2). All the subjects of the research had training experience of 10.5 +/- 3.71 (4-20) years and their degree of proficiency ranged from 4(th) kyu to 3(rd) dan. The physical fitness trials proposed by Story (1989) included: hip turning speed, speed punches, flexibility, rapid kicks, agility, and evasion actions. It was supplemented by a test of local strength endurance, composing a battery of the SPFT, which was implemented by first of the authors between 1991 and 2006. Results: SPFT is characterized by high reliability and it can be used to diagnose the physical fitness preparation and monitor the individual results of training. It discriminates accurately competitors with different sports level and it is characterized by very high accuracy, it is correlated with the test results of motor general physical fitness abilities and coordination abilities as well as it is connected with the somatic build of the athlete. The performance classification table was developed on the basis of our research. Discussion: Results obtained in SPFT were shortly discussed. Conclusions: The collected results of our research allowed us to come to, the conclusion: The table can be applied not only to assess karate fighters, but also adepts in taekwondo, kick-boxing, ju-jitsu, hapkido or other mixed martial arts.

KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program.

Novel therapeutic agents targeting the epidermal growth factor receptor (EGFR) have improved outcomes for patients with colorectal carcinoma. However, these therapies are effective only in a subset of patients. Activating mutations in the KRAS gene are found in 30-40% of colorectal tumors and are associated with poor response to anti-EGFR therapies. Thus, KRAS mutation status can predict which patient may or may not benefit from anti-EGFR therapy. Although many diagnostic tools have been developed for KRAS mutation analysis, validated methods and standardized testing procedures are lacking. This poses a challenge for the optimal use of anti-EGFR therapies in the management of colorectal carcinoma. Here we review the molecular basis of EGFR-targeted therapies and the resistance to treatment conferred by KRAS mutations. We also present guideline recommendations and a proposal for a European quality assurance program to help ensure accuracy and proficiency in KRAS mutation testing across the European Union.

Results and harmonization guidelines from two large-scale international Elispot proficiency panels conducted by the Cancer Vaccine Consortium (CVC/SVI).

The Cancer Vaccine Consortium of the Sabin Vaccine Institute (CVC/SVI) is conducting an ongoing large-scale immune monitoring harmonization program through its members and affiliated associations. This effort was brought to life as an external validation program by conducting an international Elispot proficiency panel with 36 laboratories in 2005, and was followed by a second panel with 29 participating laboratories in 2006 allowing for application of learnings from the first panel. Critical protocol choices, as well as standardization and validation practices among laboratories were assessed through detailed surveys. Although panel participants had to follow general guidelines in order to allow comparison of results, each laboratory was able to use its own protocols, materials and reagents. The second panel recorded an overall significantly improved performance, as measured by the ability to detect all predefined responses correctly. Protocol choices and laboratory practices, which can have a dramatic effect on the overall assay outcome, were identified and lead to the following recommendations: (A) Establish a laboratory SOP for Elispot testing procedures including (A1) a counting method for apoptotic cells for determining adequate cell dilution for plating, and (A2) overnight rest of cells prior to plating and incubation, (B) Use only pre-tested serum optimized for low background: high signal ratio, (C) Establish a laboratory SOP for plate reading including (C1) human auditing during the reading process and (C2) adequate adjustments for technical artifacts, and (D) Only allow trained personnel, which is certified per laboratory SOPs to conduct assays. Recommendations described under (A) were found to make a statistically significant difference in assay performance, while the remaining recommendations are based on practical experiences confirmed by the panel results, which could not be statistically tested. These results provide initial harmonization guidelines to optimize Elispot assay performance to the immunotherapy community. Further optimization is in process with ongoing panels.

Testing the Revised Hierarchical Model: evidence from word associations

The main purpose of the work described in this paper is to examine the extent to which the L2 developmental changes predicted by Kroll and Stewart's (1994) Revised Hierarchical Model (RHM) can be understood by word association response behaviour. The RHM attempts to account for the relative “strength of the links between words and concepts in each of the bilingual's languages” (Kroll, Van Hell, Tokowicz & Green, 2010, p. 373). It proposes that bilinguals with higher L2 proficiency tend to rely less on mediation, while less proficient L2 learners tend to rely on mediation and access L2 words by translating from L1 equivalents. In this paper, I present findings from a simple word association task. More proficient learners provided a greater proportion of collocational links, suggesting that they mediate less when compared to less proficient learners. The results provide tentative support for Kroll and Stewart's model

Large-scale assessment of language proficiency: theoretical and pedagogical reflections on the use of multiple-choice tests

The new requirement placed on students in tertiary settings in Spain to demonstrate a B1 or a B2 proficiency level of English, in accordance with the Common European Framework of Reference for Languages (CEFRL), has led most Spanish universities to develop a program of certification or accreditation of the required level. The first part of this paper aims to provide a rationale for the type of test that has been developed at the Universidad Politécnica de Madrid for the accreditation of a B2 level, a multiple choice version, and to describe how it was constructed and validated. Then, in the second part of the paper, the results from its application to 924 students enrolled in different degree courses at a variety of schools and faculties at the university are analyzed based on a final test version item analysis. To conclude, some theoretical as well as practical conclusions about testing grammar that affect the teaching and learning process are drawn. RESUMEN. Las nuevas exigencias sobre niveles de competencia B1 y B2 en inglés según el Marco Común Europeo de Referencia para las Lenguas (MCERL) que se imponen sobre los estudiantes de grado y posgrado han llevado a la mayoría de las universidades españolas a desarrollar programas de acreditación o de certificación de estos niveles. La primera parte de este trabajo trata sobre las razones que fundamentan la elección de un tipo concreto de examen para la acreditación del nivel B2 de lengua inglesa en la Universidad Politécnica de Madrid. Se trata de un test de opción múltiple y en esta parte del trabajo se describe cómo fue diseñado y validado. En la segunda parte, se analizan los resultados de la aplicación del test a gran escala a un total de 924 estudiantes matriculados en varias escuelas y Facultades de la Universidad. Para terminar, se apuntan una serie de conclusiones teóricas y prácticas sobre la evaluación de la gramática y de qué modo influye en los procesos de enseñanza y aprendizaje.

Syntactic complexity measures and their relation to oral proficiency in Japanese as a foreign language

The study reported in this article is a part of a large-scale study investigating syntactic complexity in second language (L2) oral data in commonly taught foreign languages (English, German, Japanese, and Spanish; Ortega, Iwashita, Rabie, & Norris, in preparation). In this article, preliminary findings of the analysis of the Japanese data are reported. Syntactic complexity, which is referred to as syntactic maturity or the use of a range of forms with degrees of sophistication (Ortega, 2003), has long been of interest to researchers in L2 writing. In L2 speaking, researchers have examined syntactic complexity in learner speech in the context of pedagogic intervention (e.g., task type, planning time) and the validation of rating scales. In these studies complexity is examined using measures commonly employed in L2 writing studies. It is assumed that these measures are valid and reliable, but few studies explain what syntactic complexity measures actually examine. The language studied is predominantly English, and little is known about whether the findings of such studies can be applied to languages that are typologically different from English. This study examines how syntactic complexity measures relate to oral proficiency in Japanese as a foreign language. An in-depth analysis of speech samples from 33 learners of Japanese is presented. The results of the analysis are compared across proficiency levels and cross-referenced with 3 other proficiency measures used in the study. As in past studies, the length of T-units and the number of clauses per T-unit is found to be the best way to predict learner proficiency; the measure also had a significant linear relation with independent oral proficiency measures. These results are discussed in light of the notion of syntactic complexity and the interfaces between second language acquisition and language testing. Adapted from the source document

English language learners and standardized testing in an urban senior high school

The primary purpose of this study was to examine the influences of literacy variables on high-stakes test performance including: (a) student achievement on the Metropolitan Achievement Test, Seventh Edition (MAT-7) as correlated to the high-stakes test such as the FCAT examination and (b) the English language proficiency attained by English Language Learners (ELL) students when participating in, or exiting from English Speakers of Other Languages (ESOL) program as determined by the Limited English Proficient (LEP) committee. ^ Two one-sample Chi-square tests were conducted to investigate the relationship between passing the MAT-7 Reading and Language examinations and the FCAT-SSS Reading Comprehension and FCAT-NRT examinations. In addition, 2x2 Analyses of Variance (ANOVAs) were conducted to address the relationship between the time ELL students spent in the ESOL program and the level of achievement on MAT-7 Reading and Language examinations and the FCAT-SSS Reading Comprehension and FCAT-NRT. ^ Findings of this study indicated that more ELL students exit the program based on the LEP committee decisions than by passing the MAT-7. The majority of ELL students failed the 10th grade FCAT, the passing of which is needed for graduation. A significant number of ELL students failed, even when passing the MAT-7 or being duly exited through the decision of the LEP committee. The data also indicated that ELL students who exited the ESOL program in six semesters or fewer had higher FCAT scores than those who exited the program in seven semesters or more. The MAT-7 and the decision of the LEP committee were shown to be ineffective as predictors of success on the FCAT. ^ Further research to determine the length of time a student in the ESOL program uses English to read, write, and speak should be conducted. Additionally, the development of a new assessment instrument to better predict student success should be considered. However, it should be noted that the results of this study are limited to the context in which it was conducted and does not warrant generalizations beyond that context. ^

Correlates of voluntary HIV testing and counseling among middle aged and older Latinas

This study identifies and describes HIV Voluntary Counseling and Testing (VCT) of middle aged and older Latinas. The rate of new cases of HIV in people age 45 and older is rapidly increasing, with a 40.6% increase in the numbers of older Latinas infected with HIV between 1998 and 2002. Despite this increase, there is paucity of research on this population. This research seeks to address the gap through a secondary data analysis of Latina women. The aim of this study is twofold: (1) Develop and empirically test a multivariate model of VCT utilization for middle aged and older Latinas; (2) To test how the three individual components of the Andersen Behavioral Model impact VCT for middle aged and older Latinas. The study is organized around the three major domains of the Andersen Behavioral Model of service use that include: (a) predisposing factors; (b) enabling characteristics and (c) need. Logistic regression using structural equation modeling techniques were used to test multivariate relationships of variables on VCT for a sample of 135 middle age and older Latinas residing in Miami-Dade County, Florida. Over 60% of participants had been tested for HIV. Provider endorsement was found to he the strongest predictor of VCT (odds ration [OR] 6.38), followed by having a clinic as a regular source of healthcare (OR=3.88). Significant negative associations with VCT included self rated health status (OR=.592); Age (OR=.927); Spanish proficiency (OR=.927); number of sexual partners (OR=.613) and consumption of alcohol during sexual activity (.549). As this line of inquiry provides a critical glimpse into the VCT of older Latinas, recommendations for enhanced service provision and research will he offered.

Retention and special education referral practices before and after the implementation of high -stakes testing

The rewards and sanctions associated with high-stakes testing may induce educators to participate in practices that will ensure the elimination of the scores of low-achieving students from the testing pool. Two ways in which scores may be eliminated is through retention or referral to special education. ^ This study examined the use of these practices at 179 elementary schools in Miami-Dade County Public Schools, the 4th largest school district in the country. Between- and within-subjects designs were analyzed using repeated measures analysis of variance to compare retention and referral to special education practices over a five-year period of time, two years prior to and two years after the implementation of Florida's high-stakes test, the Florida Comprehensive Assessment Test, FCAT. ^ Significant main effects for referral and retention over time were demonstrated. The use of retention steadily increased over the first three years, with its usage maintained during the fourth year. While the use of referral actually decreased from the first to second years, a significant change occurred after the implementation of the FCAT. ^ Examination of the use of these practices according to student and school characteristics revealed significant differences. Increases in the use of referral across time was significant for Black, non-Hispanic and Hispanic students, all limited English proficiency population categories, medium and low socioeconomic status category schools, all grade levels, and for schools with accountability grades of A. C, D and F with the most striking absolute increase occurring for F schools. Increases in the use of retention across time were significant for all ethnic groups, limited English proficiency categories, and socioeconomic status categories, for grades kindergarten through four and by gender. Significant increases occurred for schools with accountability performance grades of C, D and F; however the most dramatic increase occurred for the F schools. A direct relationship between performance category grade of school and their use of retention was demonstrated. The results suggest that schools changed their use of referral and retention in response to the implementation of the FCAT. ^

Retention and special education referral practices before and after the implementation of high-stakes testing

The rewards and sanctions associated with high-stakes testing may induce educators to participate in practices that will ensure the elimination of the scores of low-achieving students from the testing pool. Two ways in which scores may be eliminated is through retention or referral to special education. This study examined the use of these practices at 179 elementary schools in Miami-Dade County Public Schools, the 4th largest school district in the country. Between- and within-subjects designs were analyzed using repeated measures analysis of variance to compare retention and referral to special education practices over a five-year period of time, two years prior to and two years after the implementation of Florida's high-stakes test, the Florida Comprehensive Assessment Test, FCAT. Significant main effects for referral and retention over time were demonstrated. The use of retention steadily increased over the first three years, with its usage maintained during the fourth year. While the use of referral actually decreased from the first to second years, a significant change occurred after the implementation of the FCAT. Examination of the use of these practices according to student and school characteristics revealed significant differences. Increases in the use of referral across time was significant for Black, non-Hispanic and Hispanic students, all limited English proficiency population categories, medium and low socioeconomic status category schools, all grade levels, and for schools with accountability grades of A, C, D and F with the most striking absolute increase occurring for F schools. Increases in the use of retention across time were significant for all ethnic groups, limited English proficiency categories, and socioeconomic status categories, for grades kindergarten through four and by gender. Significant increases occurred for schools with accountability performance grades of C, D and F; however the most dramatic increase occurred for the F schools. A direct relationship between performance category grade of school and their use of retention was demonstrated. The results suggest that schools changed their use of referral and retention in response to the implementation of the FCAT.