IONA test for first-trimester detection of trisomies 21, 18 and 13

OBJECTIVE: To assess the potential performance of screening for fetal trisomies 21, 18 and 13 by cell-free DNA (cfDNA) analysis of maternal blood using the IONA\uae test. METHODS: This was a nested case-control study of cfDNA analysis of maternal plasma using the IONA test. Samples were obtained at 11-13 weeks' gestation, before chorionic villus sampling, from 201 euploid pregnancies, 35 with trisomy 21, four with trisomy 18 and two with trisomy 13. Laboratory personnel were blinded to the fetal karyotype. RESULTS: Probability scores for trisomies 21, 18 and 13 were given for 241/242 samples analyzed. No probability score was provided for one (0.5%) euploid pregnancy because of low fetal fraction. In all 35 cases of trisomy 21 the probability score for trisomy 21 was > 95% and the scores for trisomies 18 and 13 were 64 0.0001%. In all four cases of trisomy 18, the probability score for trisomy 18 was > 77% and the scores for trisomies 21 and 13 were 64 0.0001%. In the two cases of trisomy 13, the probability score for trisomy 13 was > 59% and the scores for trisomies 21 and 18 were 64 0.0001%. In the 200 euploid pregnancies with a test result, the probability score was < 0.08% for trisomy 21, < 0.001% for trisomy 18 and < 0.002% for trisomy 13. Therefore, the IONA test detected 100% of all three trisomies, with a false-positive rate of 0%. CONCLUSION: The IONA test successfully differentiated all cases of trisomies 21, 18 and 13 from euploid pregnancies

A topological optimization procedure applied to multiple region problems with embedded sources

The main objective of this work is the application of the topological optimization procedure to heat transfer problems considering multiple materials. The topological derivative (DT) is employed for evaluating the domain sensitivity when perturbed by inserting a small inclusion. Electronic components such as printed circuit boards (PCBs) are an important area for the application of topological optimization. Generally, geometrical optimization involving heat transfer in PCBs considers only isotropic behavior and/or a single material. Multiple domains with anisotropic characteristics take an important role on many industrial products, for instance when considering PCBs which are often connected to other components of different materials. In this sense, a methodology for solving topological optimization problems considering anisotropy and multiple regions with embedded heat sources is developed in this paper. A direct boundary element method (BEM) is employed for solving the proposed numerical problem.CNPQ – Brazil through the Science without Borders program and from Brunel University

Four methods for determining the composition of trace radioactive surface contamination of low-radioactivity metal

Four methods for determining the composition of low-level uranium- and thorium-chain surface contamination are presented. One method is the observation of Cherenkov light production in water. In two additional methods a position-sensitive proportional counter surrounding the surface is used to make both a measurement of the energy spectrum of alpha particle emissions and also coincidence measurements to derive the thorium-chain content based on the presence of short-lived isotopes in that decay chain. The fourth method is a radiochemical technique in which the surface is eluted with a weak acid, the eluate is concentrated, added to liquid scintillator and assayed by recording beta-alpha coincidences. These methods were used to characterize two `hotspots' on the outer surface of one of the He-3 proportional counters in the Neutral Current Detection array of the Sudbury Neutrino Observatory experiment. The methods have similar sensitivities, of order tens of ng, to both thorium- and uranium-chain contamination.Comment: 22 pages, 19 figure

Aspirin for evidence-based preeclampsia prevention trial: effect of aspirin in prevention of preterm preeclampsia in subgroups of women according to their characteristics and medical and obstetrical history.

Objective: To examine whether there are differences in the effect of aspirin on the incidence of preterm-PE in the ASPRE trial in subgroups defined according to maternal characteristics and medical and obstetrical history. Study design: This was a secondary analysis of data from the ASPRE trial. In ASPRE women with singleton pregnancies had screening by means of an algorithm that combines maternal factors and biomarkers at 11-13 weeks’ gestation. Those with an estimated risk for preterm-PE of >1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg/day) vs. placebo from 11 to 14 until 36 weeks’ gestation. Aspirin was associated with a significant reduction in the incidence of preterm-PE with delivery at 90% of the prescribed medication. Results are presented as forest plot with P values for the interaction effects, group sizes, event counts and estimated odds ratios. We examined whether the test of interaction was significant at the 5% level with a Bonferroni adjustment for multiple comparisons. Results: There was no evidence of heterogeneity in the aspirin effect in subgroups defined according to maternal characteristics and obstetrical history. In participants with chronic hypertension preterm-PE occurred in 10.2% (5/49) in the aspirin group and in 8.2% (5/61) in the placebo group (adjusted odds ratio 1.29, 95% confidence interval, 0.33 to 5.12); the respective values in those without chronic hypertension were 1.1% (8/749) in the aspirin group and 3.9% (30/761) in the placebo group (adjusted odds ratio 0.27, 95% confidence interval, 0.12 to 0.60). In all participants with adherence of >90% the adjusted odds ratio in the aspirin group was 0.24 (95% CI 0.09 to 0.65), in the subgroup with chronic hypertension it was 2.06 (95% CI 0.40 to 10.71) and in those without chronic hypertension it was 0.05 (95% CI 0.01 to 0.41). For the complete data set the test of interaction was not significant at the 5% level (p=0.055), but in those with adherence >90%, after adjustment for multiple comparisons, the interaction was significant at the 5% level (p=0.0019). Conclusions: The beneficial effect of aspirin in the prevention of preterm preeclampsia may not apply in pregnancies with chronic hypertension. There was no evidence of heterogeneity in the aspirin effect in subgroups defined according to maternal characteristics and obstetrical history

Screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation

Objective: To examine the performance of screening for early-, preterm- and term-preeclampsia (PE) at 11 13 weeks’ gestation by maternal factors and combinations of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PLGF) and serum pregnancy associated plasma protein A (PAPP A). Methods The data for this study were derived from three previously reported prospective non intervention screening studies at 11+0 – 13+6 weeks’ gestation in a combined total of 61,174 singleton pregnancies, including 1,770 (2.9%) that developed PE. Bayes theorem was used to combine the prior distribution of the gestational age at delivery with PE, obtained from maternal characteristics, with various combinations of biomarker multiple of the median (MoM) values to derive the p patient specific risks of delivery with PE at <37 weeks’ gestation. The performance of such screening was estimated. Results In pregnancies that develop ed PE , compared to those without PE, the MoM values of UtA-PI and MAP were increased and PAPP A and PLGF were decreased and the deviation from normal was greater for early than late PE for all four biomarkers. Combined screening by maternal factors, UtA-PI, MAP and PLGF predicted 90% of early PE, 75% of preterm PE and 4 1 % of term PE, at screen positive rate of 10%; inclusion of PAPP A did not improve the performance of screening The performance of screening depended on the racial origin of the women; in screening by a combination of maternal factors, MAP, UtA-PI and PLGF and use of the risk cut off of 1 in 10 0 for PE at <37 weeks in Caucasian women, the screen positive rate was 10% and detection rates for early --, preterm and term PE were 88%, 69% and 40%, respectively. With the same method of screening and risk cut off in women of Afro Caribbean racial origin, the screen positive rate was 34% and detection rates for early --, preterm and term PE were 100%, 92% and 75%, respectively. Conclusion Screening by maternal factors and biomarkers at 11-13 weeks’ gestation can identify a high proportion of pregnancies that develop early- and preterm-PE

Measurement of the νe and total 8B solar neutrino fluxes with the Sudbury Neutrino Observatory phase-III data set

This paper details the solar neutrino analysis of the 385.17-day phase-III data set acquired by the Sudbury Neutrino Observatory (SNO). An array of 3He proportional counters was installed in the heavy-water target to measure precisely the rate of neutrino-deuteron neutral-current interactions. This technique to determine the total active 8B solar neutrino flux was largely independent of the methods employed in previous phases. The total flux of active neutrinos was measured to be 5.54-0.31+0.33(stat.)-0.34+0.36(syst.)×106 cm-2 s-1, consistent with previous measurements and standard solar models. A global analysis of solar and reactor neutrino mixing parameters yielded the best-fit values of Δm2=7.59-0.21+0.19×10 -5eV2 and θ=34.4-1.2+1.3degrees

Src Cooperates with Oncogenic Ras in Tumourigenesis via the JNK and PI3K Pathways in Drosophila epithelial Tissue

The Ras oncogene (Rat Sarcoma oncogene, a small GTPase) is a key driver of human cancer, however alone it is insufficient to produce malignancy, due to the induction of cell cycle arrest or senescence. In a Drosophila melanogaster genetic screen for genes that cooperate with oncogenic Ras (bearing the RasV12 mutation, or RasACT), we identified the Drosophila Src (Sarcoma virus oncogene) family non-receptor tyrosine protein kinase genes, Src42A and Src64B, as promoting increased hyperplasia in a whole epithelial tissue context in the Drosophila eye. Moreover, overexpression of Src cooperated with RasACT in epithelial cell clones to drive neoplastic tumourigenesis. We found that Src overexpression alone activated the Jun N-terminal Kinase (JNK) signalling pathway to promote actin cytoskeletal and cell polarity defects and drive apoptosis, whereas, in cooperation with RasACT, JNK led to a loss of differentiation and an invasive phenotype. Src + RasACT cooperative tumourigenesis was dependent on JNK as well as Phosphoinositide 3-Kinase (PI3K) signalling, suggesting that targeting these pathways might provide novel therapeutic opportunities in cancers dependent on Src and Ras signalling