Routine first-trimester screening for fetal trisomies in twin pregnancy: cell-free DNA test contingent on results from combined test

Objective: To report on the routine clinical implementation of cell-free (cf)DNA analysis of maternal blood for trisomies 21, 18 and 13 contingent on the results of the first-trimester combined test in twin pregnancies. Methods: Screening for trisomies 21, 18 and 13 was carried out by a combination of maternal age, fetal nuchal translucency (NT) thickness, and serum free ß-hCG and PAPP-A at 11-13 weeks’ gestation in 959 twin pregnancies in two UK NHS hospitals. Women in the high-risk group (risk >1 in 100) were offered options of invasive testing, cfDNA testing or no further testing and those in the intermediate-risk group (risk 1 in 101 to 1 in 2500 in the first phase of the study and 1 in 101 to 1 in 500 in the second phase) were offered cfDNA or no further testing. The trisomic status of the pregnancies was determined by prenatal or postnatal karyotyping or examination of the neonates. Results: In 42 (4.4%) of the 959 pregnancies there was termination, miscarriage or stillbirth with no known karyotype or there was loss to follow up. The 917 pregnancies with known trisomic status of both twins, included 6 that were discordant for trisomy 21, 4 discordant for trisomy 18 and 896 with no trisomies 21, 18 or 13. Following combined screening, 47 (5.1%), 203 (22.2%) and 667 (72.7%) of the pregnancies were classified as high-risk, intermediate-risk and low-risk, respectively. The high-risk group included 5 (83.3%) cases of trisomy 21 and 3 (75.0%) of trisomy 18. The cfDNA test was carried out in 224 pregnancies and results were provided in 214 (95.5%); this group included 6 with trisomy 21, 3 with trisomy 18 and 206 with no trisomies 21, 18 or 13. The cfDNA test correctly classified as screen positive all 6 cases of trisomy 21 and 2 of the 3 with trisomy 18 and as screen negative for each of the trisomies all 206 unaffected pregnancies. Contingent screening, led to prenatal detection of all cases of trisomy 21 and 3 of 4 with trisomy 18. Conclusions: The study has demonstrated the feasibility of introducing cfDNA testing, contingent on the results of the first-trimester combined test for major trisomies, in a routine population of twin pregnancies

Electrocardiogram Derived Respiration for Tracking Changes in Tidal Volume from a Wearable Armband

A pilot study on tracking changes in tidal volume (TV) using ECG signals acquired by a wearable armband is presented. The wearable armband provides three ECG channels by using three pairs of dry electrodes, resulting in a device that is convenient for long-term daily monitoring. An additional ECG channel was derived by computing the first principal component of the three original channels (by means of principal component analysis). Armband and spirometer signals were simultaneously recorded from five healthy subjects who were instructed to breathe with varying TV. Three electrocardiogram derived respiration (EDR) methods based on QRS complex morphology were studied: the QRS slopes range (SR), the R-wave angle (), and the R-S amplitude (RS). The peak-to-peak amplitudes of these EDR signals were estimated as surrogates for TV, and their correlations with the reference TV (estimated from the spirometer signal) were computed. In addition, a multiple linear regression model was calculated for each subject, using the peak-to-peak amplitudes from the three EDR methods from the four ECG channels. Obtained correlations between TV and EDR peak-to-peak amplitude ranged from 0.0448 up to 0.8491. For every subject, a moderate correlation (>0.5) was obtained for at least one EDR method. Furthermore, the correlations obtained for the subject-specific multiple linear regression model ranged from 0.8234 up to 0.9154, and the goodness of fit was 0.73±0.07 (median ± standard deviation). These results suggest that the peak-to-peak amplitudes of the EDR methods are linearly related to the TV. opening the possibility of estimating TV directly from an armband ECG device.Clinical Relevance - This opens the door to possible continuous monitoring of TV from the armband by using EDR

Reply: Benefit of genome-wide prenatal cfDNAtesting requires further investigation through acase–control study.

post-print50,1 K

Observational constraints on the curvaton model of inflation

Simple curvaton models can generate a mixture of of correlated primordial adiabatic and isocurvature perturbations. The baryon and cold dark matter isocurvature modes differ only by an observationally null mode in which the two perturbations almost exactly compensate, and therefore have proportional effects at linear order. We discuss the CMB anisotropy in general mixed models, and give a simple approximate analytic result for the large scale CMB anisotropy. Working numerically we use the latest WMAP observations and a variety of other data to constrain the curvaton model. We find that models with an isocurvature contribution are not favored relative to simple purely adiabatic models. However a significant primordial totally correlated baryon isocurvature perturbation is not ruled out. Certain classes of curvaton model are thereby ruled out, other classes predict enough non-Gaussianity to be detectable by the Planck satellite. In the appendices we review the relevant equations in the covariant formulation and give series solutions for the radiation dominated era.Comment: Minor changes and corrections to match version accepted by PR

The meaning of negation in the second language classroom: evidence from 'any'

This article brings together an experimental study involving L2 knowledge of negation in English and an analysis of how English language textbooks treat negation, in order to consider whether textbook explanations of negation could better exploit linguistic insights into negation. We focus on the English negative polarity item any, whose distribution is contingent on negation, whether through the explicit negator not or through lexical semantic negators (e.g. hardly). Our experiment compares Chinese-speaking learners with existing data from Arabic-speaking learners, finding lower accuracy on any with lexical semantic negators in both groups. Our textbook analysis reveals an approach to negation that is limited to form, focusing on the explicit negator not without explicit treatment of other types of negation. We propose that emphasizing the meaning of negation, with explicit treatment of the full range of negative forms could facilitate more complete acquisition across a range of grammatical properties where negation plays a role

Search for composite and exotic fermions at LEP 2

A search for unstable heavy fermions with the DELPHI detector at LEP is reported. Sequential and non-canonical leptons, as well as excited leptons and quarks, are considered. The data analysed correspond to an integrated luminosity of about 48 pb^{-1} at an e^+e^- centre-of-mass energy of 183 GeV and about 20 pb^{-1} equally shared between the centre-of-mass energies of 172 GeV and 161 GeV. The search for pair-produced new leptons establishes 95% confidence level mass limits in the region between 70 GeV/c^2 and 90 GeV/c^2, depending on the channel. The search for singly produced excited leptons and quarks establishes upper limits on the ratio of the coupling of the excited fermio

Search for lightest neutralino and stau pair production in light gravitino scenarios with stau NLSP

Promptly decaying lightest neutralinos and long-lived staus are searched for in the context of light gravitino scenarios. It is assumed that the stau is the next to lightest supersymmetric particle (NLSP) and that the lightest neutralino is the next to NLSP (NNLSP). Data collected with the Delphi detector at centre-of-mass energies from 161 to 183 \GeV are analysed. No evidence of the production of these particles is found. Hence, lower mass limits for both kinds of particles are set at 95% C.L.. The mass of gaugino-like neutralinos is found to be greater than 71.5 GeV/c^2. In the search for long-lived stau, masses less than 70.0 to 77.5 \GeVcc are excluded for gravitino masses from 10 to 150 \eVcc . Combining this search with the searches for stable heavy leptons and Minimal Supersymmetric Standard Model staus a lower limit of 68.5 \GeVcc may be set for the stau mas

Constraining the wind launching region in Herbig Ae stars: AMBER/VLTI spectroscopy of HD 104237

Astronomy and Astrophysics, 464, pp. 55-58, http://dx.doi.org./10.1051/0004-6361:20065719International audienc

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM