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Selected AbstractsFetal sex determination using circulating cell-free fetal DNA (ccffDNA) at 11 to 13 weeks of gestationPRENATAL DIAGNOSIS, Issue 10 2010Ranjit Akolekar Abstract Objective To examine the performance of a mass spectrometry-based detection platform using three Y-chromosome sequences for fetal sex determination from circulating cell-free fetal DNA (ccffDNA) in maternal blood in the first trimester of pregnancy. Methods We extracted ccffDNA for the determination of fetal sex from stored maternal plasma obtained at 11 to 13 weeks' gestation from singleton pregnancies with documented fetal gender. Mass spectrometry was used to examine 236 specimens for the presence of three Y-chromosome sequences (SRY, DBY and TTTY2). The sample was classified as male, female or inconclusive depending on the detection of three, one/none and two sequences, respectively. Results Three (1.3%) of the 236 cases were classified as invalid due to the absence of a well-defined spectral peak for TGIF and 22 (9.3%) were reported as inconclusive. In the 211 cases with a valid result, the fetal sex was correctly identified in 90 of 91 male babies and 119 of 120 female babies giving an accuracy of 99.1% and sensitivity and specificity for prediction of male fetuses of 98.9 and 99.2%, respectively. Conclusion Fetal sex determination can be accurately determined from maternal ccffDNA in the first trimester of pregnancy using mass spectrometry analysis. Copyright © 2010 John Wiley & Sons, Ltd. [source] Comparing welfare estimates from payment card contingent valuation and discrete choice experimentsHEALTH ECONOMICS, Issue 4 2009Mandy Ryan Abstract This study presents the first comparison of willingness to pay estimates derived from the payment card (PC) contingent valuation and discrete choice experiment (DCE) methods. A within-sample experiment was used to elicit women's preferences for Chlamydia screening. The willingness to pay estimate derived from the DCE was larger than that derived from the PC. To investigate why the willingness to pay estimates were different, a range of validity tests were conducted. Both methods produced theoretically valid results, and there was no difference in the reported difficulty of completing the tasks. Evidence of a prominence effect was found in the PC responses. Responses to the DCE satisfied tests of non-satiation. Responses to both methods were compared with revealed preference data. There were significant differences between stated screening intention in both methods and actual screening uptake. Future work should address the external validity of stated preference methods. Copyright © 2008 John Wiley & Sons, Ltd. [source] Cognitive Screening Using a Tape Recorder: A Pilot StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 3 2003Peter W. Schofield MD OBJECTIVES: To determine whether a tape recorder can be used to administer cognitive tests efficiently and yield valid results. DESIGN: Convenience sample. Administration of cognitive test materials by tape recorder and conventional technique. SETTING: Outpatient clinic. PARTICIPANTS: Subjects from memory disorder clinic, hostel accommodation, and community. MEASUREMENTS: Responses to Hopkins Verbal Learning Test,revised, verbal fluency items from the controlled oral word association test, 10-item naming task, a construction task, and speed writing task. RESULTS: Performances on the tape- and clinician-administered battery of tests were highly correlated. Memory impairment was accurately detected using the tape battery. Data from 30 minutes of testing via tape were obtained at the cost to the clinician of 2 to 3 minutes of scoring time. CONCLUSION: Tape-administration of cognitive test material warrants further study as an efficient means of cognitive screening. [source] How to obtain statistically converged MM/GBSA resultsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 4 2010Samuel Genheden Abstract The molecular mechanics/generalized Born surface area (MM/GBSA) method has been investigated with the aim of achieving a statistical precision of 1 kJ/mol for the results. We studied the binding of seven biotin analogues to avidin, taking advantage of the fact that the protein is a tetramer with four independent binding sites, which should give the same estimated binding affinities. We show that it is not enough to use a single long simulation (10 ns), because the standard error of such a calculation underestimates the difference between the four binding sites. Instead, it is better to run several independent simulations and average the results. With such an approach, we obtain the same results for the four binding sites, and any desired precision can be obtained by running a proper number of simulations. We discuss how the simulations should be performed to optimize the use of computer time. The correlation time between the MM/GBSA energies is ,5 ps and an equilibration time of 100 ps is needed. For MM/GBSA, we recommend a sampling time of 20,200 ps for each separate simulation, depending on the protein. With 200 ps production time, 5,50 separate simulations are required to reach a statistical precision of 1 kJ/mol (800,8000 energy calculations or 1.5,15 ns total simulation time per ligand) for the seven avidin ligands. This is an order of magnitude more than what is normally used, but such a number of simulations is needed to obtain statistically valid results for the MM/GBSA method. © 2009 Wiley Periodicals, Inc. J Comput Chem 2010 [source] High-throughput determination of the free fraction of drugs strongly bound to plasma proteinsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2004Joachim Schuhmacher Abstract Quantification of protein binding of new chemical entities is an important early screening step during drug discovery and is of fundamental interest for the estimation of safety margins during drug development. In this publication, we describe the development of a new high-throughput assay for the determination of the free drug fraction in plasma (fu). The new technique is an enhancement of the previously published erythrocytes partition method. It is based on the distribution of drugs between plasma water, plasma proteins, and solid-supported lipid membranes (Transil®). The execution of protein binding studies by partitioning is dramatically simplified by substituting erythrocytes with commercially available Transil® beads, and makes the method particularly suitable for high-throughput studies. Eight Bayer compounds from different compound classes covering a wide range of lipophilicities (log P,=,1.9,5.6) and fu values (0.018,35%) were selected for validation of the assay. The results obtained by the new method and by either the erythrocytes partitioning technique or more conventional methods (ultrafiltration and equilibrium dialysis) are identical, confirming that the new method produces valid results even for drugs that are strongly bound to plasma proteins. Precision and accuracy of the data in the cases of very low and high fu values are comparable, indicating that the method is especially suited for highly lipophilic drugs that tend to adsorb to surfaces compared with other methods, like ultrafiltration or equilibrium dialysis, that may produce biased data. The method is also useful for the determination of binding parameters and the pH dependence of fu. In summary, this assay is well suited for high-throughput determination of protein binding during drug discovery and for extended protein binding studies during drug development. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93: 816,830, 2004 [source] Joint Assessment of Optimal Sales Force Sizes and Sales Call Guidelines: A Management-Oriented ToolCANADIAN JOURNAL OF ADMINISTRATIVE SCIENCES, Issue 3 2005René Y. Darmon Abstract Sales force sizing and sales effort allocation methods vary from simplistic rules of thumb to sophisticated analytical procedures. The former methods are easy to understand and implement, but they are typically inaccurate and probably invalid. The latter procedures may provide more accurate and valid results, but they are more difficult to explain to management and require data collection and analysis that are often quite elaborate. This paper proposes a method of optimal estimation of total sales effort level and time allocation that combines the advantages of both approaches. For each customer segment, this method accounts for the so far neglected, but relevant, optimal call effort allocation between number of calls per account during a planning period and length of sales calls. A case study illustrates this method. Résumé Les méthodes de détermination de la taille et de l'allocation des efforts de vente vont des règles empiriques les plus simples aux procédures analytiques les plus complexes. Les premières sont faciles à comprendre et à appliquer, mais elles sont imprècises et souvent non valides. Les autres méthodes peuvent donner des résultats plus exacts, mais elles sont plus difficiles à expliquer aux managers et nécessitent souvent une collecte et une analyse de données fort laborieuses. Le présent article propose une méthode d'estimation optimale de la taille et de l'allocation des efforts de vente qui combine les avantages des deux approches. Pour chaque segment de la clientèle, la méthode rend compte de l'allocation optimale (souvent négligée, mais pertinente), de l'effort de vente entre le nombre de visites à faire à un client pendant une période de planification et la longueur des visites. Un cas concret illustre la méthode. [source] An alternative design for small-scale school health experiments: does daily walking produce benefits in physical performance of school children?CHILD: CARE, HEALTH AND DEVELOPMENT, Issue 6 2009E. Mønness Abstract Background The mainstream randomized clinical trial is not always feasible in a school setting. There might be practical and ethical issues that make dividing school classes into an intervention and a control group impossible or undesirable, and there is a need to explore the validity of alternative designs and analyses. Methods An alternative to a randomized clinical trial in a physical performance experiment at a school is introduced and evaluated. The before-intervention data are utilized as control data for the intervention data in addition to adjust for pre-intervention differences. The strict class year structure of school data makes this possible. In a rural school in inland Norway, all school children joined the project of walking in a rugged terrain outside school for 20 min every school day during one school year. Measurements of low back static endurance, hamstrings flexibility, standing balance and cardiovascular fitness were made before and after the intervention. As intervention and ,aging' were confounded, the special use of the pre-intervention data, ,age-adjusted', is proposed to solve this issue. A comparison with having an independent control group is performed. Results The alternative analysing method is judged to yield valid results without having an independent control group. The age-adjusted analyses showed 11% increase in low back static endurance, 8% increase in hamstrings flexibility, 69% increase in balance and 6,13% increase in cardiovascular fitness. The effects were largest among those children who had the lowest performances before the intervention. Conclusion The introduced statistical methods display that, in a school population, evaluations from an experiment can be made without an independent control group. A 20-min walk during school time for 1 year seemed to improve physical performance. [source] |