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Non-invasive prenatal testing (NIPT) for the detection of foetal aneuploidy through analysis of cell-free DNA (cfDNA) in maternal blood is offered routinely by many healthcare providers across the developed world. This testing has recently been recommended for evaluative implementation in the UK National Health Service (NHS) foetal anomaly screening pathway as a contingent screen following an increased risk of trisomy 21, 18 or 13. In preparation for delivering a national service, we have implemented cfDNA-based NIPT in our Regional Genetics Laboratory. Here, we describe our validation and verification processes and initial experiences of the technology prior to rollout of a national screening service.
Data are presented from more than 1000 patients (215 retrospective and 840 prospective) from ‘high- and low-risk pregnancies’ with outcome data following birth or confirmatory invasive prenatal sampling. NIPT was by the Illumina Verifi® test.
Our data confirm a high-fidelity service with a failure rate of ~0.24% and a high sensitivity and specificity for the detection of foetal trisomy 13, 18 and 21. Secondly, the data show that a significant proportion of patients continue their pregnancies without prenatal invasive testing or intervention after receiving a high-risk cfDNA-based result. A total of 46.5% of patients referred to date were referred for reasons other than high screen risk. Ten percent (76/840 clinical service referrals) of patients were referred with ultrasonographic finding of a foetal structural anomaly, and data analysis indicates high- and low-risk scan indications for NIPT.
NIPT can be successfully implemented into NHS regional genetics laboratories to provide high-quality services. NHS provision of NIPT in patients with high-risk screen results will allow for a reduction of invasive testing and partially improve equality of access to cfDNA-based NIPT in the pregnant population. Patients at low risk for a classic trisomy or with other clinical indications are likely to continue to access cfDNA-based NIPT as a private test.
We derive a mathematical model for the drawing of a two-dimensional thin sheet of viscous fluid in the direction of gravity. If the gravitational field is sufficiently strong, then a portion of the sheet experiences a compressive stress and is thus unstable to transverse buckling. We analyse the dependence of the instability and the subsequent evolution on the process parameters, and the mutual coupling between the weakly nonlinear buckling and the stress profile in the sheet. Over long time scales, the sheet centreline ultimately adopts a universal profile, with the bulk of the sheet under tension and a single large bulge caused by a small compressive region near the bottom, and we derive a canonical inner problem that describes this behaviour. The large-time analysis involves a logarithmic asymptotic expansion, and we devise a hybrid asymptotic–numerical scheme that effectively sums the logarithmic series.
The conservation of threatened species requires information on how management activities influence habitat quality. The Critically Endangered black rhinoceros Diceros bicornis is restricted to savannahs representing c. 5% of its historical range. Fire is used extensively in savannahs but little is known about how rhinos respond to burning. Our aim was to understand rhino responses to fire by studying habitat selection and foraging at multiple scales. We used resource selection functions and locations of 31 rhinos during 2014–2016 to study rhino habitat use in Serengeti National Park, Tanzania. Rhino selectivity was quantified by comparing forage consumption to plant species availability in randomly sampled vegetation plots; rhino diets were subsequently verified through DNA metabarcoding analysis of faecal samples. Rhino habitat use was a unimodal function of fire history, with highly occupied sites having fire frequencies of < 0.6 fires/year and maximum occupancy occurring at a fire frequency of 0.1 fires/year. Foraging stations had characteristic plant communities, with 17 species associated with rhino foraging. Rhinos were associated with, and disproportionately consumed, woody plants, forbs and legumes, all of which decreased in abundance with increasing fire frequency. In contrast to common management practices, multiple lines of evidence suggest that the current fire regime in the Serengeti negatively influences rhino habitat use and foraging and that frequent fire limits access of rhinos to preferred forage. We outline a conceptual model to guide managers and conservationists in the use of fire under variable habitat conditions.
Adolescence is a critical time point in the lifecourse. LifeLab is an educational intervention engaging adolescents in understanding Developmental Origins of Health and Disease (DOHaD) concepts and the impact of the early life environment on future health, benefitting both their long-term health and that of the next generation. We aimed to assess whether engaging adolescents with DOHaD concepts improves scientific literacy and whether engagement alone improves health behaviours.
Six schools were randomized, three to intervention and three to control. Outcome measures were changed in knowledge, and intended and actual behaviour in relation to diet and lifestyle. A total of 333 students completed baseline and follow-up questionnaires. At 12 months, intervention students showed greater understanding of DOHaD concepts. No sustained changes in behaviours were identified.
Adolescents’ engagement with DOHaD concepts can be improved and maintained over 12 months. Such engagement does not itself translate into behaviour change. The intervention has consequently been revised to include additional components beyond engagement alone.
We describe the performance of the Boolardy Engineering Test Array, the prototype for the Australian Square Kilometre Array Pathfinder telescope. Boolardy Engineering Test Array is the first aperture synthesis radio telescope to use phased array feed technology, giving it the ability to electronically form up to nine dual-polarisation beams. We report the methods developed for forming and measuring the beams, and the adaptations that have been made to the traditional calibration and imaging procedures in order to allow BETA to function as a multi-beam aperture synthesis telescope. We describe the commissioning of the instrument and present details of Boolardy Engineering Test Array’s performance: sensitivity, beam characteristics, polarimetric properties, and image quality. We summarise the astronomical science that it has produced and draw lessons from operating Boolardy Engineering Test Array that will be relevant to the commissioning and operation of the final Australian Square Kilometre Array Path telescope.
The Cycadales are a group of significant global conservation concern and have the highest extinction risk of all seed plants. Understanding the synchronisation of reproductive phenology of Cycadales may be useful for conservation by enabling the targeting of pollen and seed collection from wild populations and identifying the window of fertilisation to aid in the cultivation of Cycadales. Phenological data for 11 species of Zamia were gathered from herbarium specimens. Four phenological characters were coded with monthly character states. DNA was isolated and sequenced for 26S, CAB, NEEDLY, matK and rbcL, and a simultaneous phylogenetic analysis of phenology and DNA sequence data was carried out. Three major clades were recovered: a Caribbean clade, a Central American clade and a South American clade. Eight species showed statistically significant synchronisation in microsporangiate and ovulate phenological phases, indicating the time of fertilisation. Close reproductive synchronisation was consistently observed throughout the Caribbean clade (statistically significant in four of five species) but was less consistent in the Central American clade (statistically significant in one of two species) and South American clade (statistically significant in three of four species). Ultimately, phenology is shown to be a potential driver of speciation in some clades of Zamia and in others to be a potential barrier to hybridisation.
During 1990 we surveyed the southern sky using a multi-beam receiver at frequencies of 4850 and 843 MHz. The half-power beamwidths were 4 and 25 arcmin respectively. The finished surveys cover the declination range between +10 and −90 degrees declination, essentially complete in right ascension, an area of 7.30 steradians. Preliminary analysis of the 4850 MHz data indicates that we will achieve a five sigma flux density limit of about 30 mJy. We estimate that we will find between 80 000 and 90 000 new sources above this limit. This is a revised version of the paper presented at the Regional Meeting by the first four authors; the surveys now have been completed.
Within the framework of shallow-water magnetohydrodynamics, we investigate the linear instability of horizontal shear flows, influenced by an aligned magnetic field and stratification. Various classical instability results, such as Høiland’s growth-rate bound and Howard’s semi-circle theorem, are extended to this shallow-water system for quite general flow and field profiles. In the limit of long-wavelength disturbances, a generalisation of the asymptotic analysis of Drazin & Howard (J. Fluid Mech., vol. 14, 1962, pp. 257–283) is performed, establishing that flows can be distinguished as either shear layers or jets. These possess contrasting instabilities, which are shown to be analogous to those of certain piecewise-constant velocity profiles (the vortex sheet and the rectangular jet). In both cases it is found that the magnetic field and stratification (as measured by the Froude number) are generally each stabilising, but weak instabilities can be found at arbitrarily large Froude number. With this distinction between shear layers and jets in mind, the results are extended numerically to finite wavenumber for two particular flows: the hyperbolic-tangent shear layer and the Bickley jet. For the shear layer, the instability mechanism is interpreted in terms of counter-propagating Rossby waves, thereby allowing an explication of the stabilising effects of the magnetic field and stratification. For the jet, the competition between even and odd modes is discussed, together with the existence at large Froude number of multiple modes of instability.
Thin glass sheets may be manufactured using a two-part process in which a sheet is first cast and then subsequently reheated and drawn to a required thickness. The latter redrawing process typically results in a sheet with non-uniform thickness and with smaller width than the cast glass block. Experiments suggest that the loss of width can be minimized and the non-uniformities can be essentially confined to thickening at the sheet edges if the heater zone through which the glass is drawn is made very short. We present a three-dimensional mathematical model for the redraw process and consider the limits in which (i) the heater zone is short compared with the sheet width, and (ii) the sheet thickness is small compared with both of these length scales. We show that, in the majority of the sheet, the properties vary only in the direction of drawing and the sheet motion is one-dimensional, with two-dimensional behaviour and the corresponding thick edges confined to boundary layers at the sheet extremities. We present numerical solutions to this boundary-layer problem and demonstrate good agreement with experiment, as well as with numerical solutions to the full three-dimensional problem. We show that the final thickness at the sheet edge scales with the inverse square root of the draw ratio, and explore the effect of tapering of the ends to identify a shape for the initial preform that results in a uniform rectangular final product.
Injecting drug use is often associated with deep-seated infection. In Lothian in Scotland there has been a recent increase in the use of injected new psychoactive substances (NPS). Patients who have injected NPS have presented with Staphylococcus aureus bacteraemia (SAB) with life-threatening complications. We describe a unique case-series of 14 episodes of SAB in ten patients. Users of injected NPS had a significantly higher incidence of endocarditis and cavitating pulmonary lesions (P < 0·05) compared to those who inject only opiates. Cases of SAB in people who inject NPS have contributed to a significant rise in the overall incidence of SAB in people who inject drugs (P < 0·05) which has in turn impacted on the ability of Lothian to meet national targets for reducing the incidence of SAB.
In this paper, we consider the straining flow of a weakly interacting polymer–surfactant solution below a free surface, with the bulk surfactant concentration above the critical micelle concentration. We formulate a set of coupled differential equations describing the concentration of monomers, micelles, polymer, and polymer–micelle aggregates in the flow. We analyse the model in several asymptotic limits, and make predictions about the distribution of each of the species. In particular, in the large-reaction-rate limit we find that the model predicts a region near the free surface where no micelles or aggregates are present, and beneath this a region where the concentration of surfactant is constant, across which the concentration of aggregates increases until all the free polymer is consumed. For certain parameter regimes, a maximum in the concentration of the polymer–micelle complex occurs within the bulk fluid. In the finite-reaction-rate limit, micelles, and aggregates are present right up to the free surface, and the plateau in the concentration of surfactant in the bulk is no longer present. Results from the asymptotic theory compare favorably with full numerical solutions.
It is well known that web-based interventions can be effective treatments for depression. However, dropout rates in web-based interventions are typically high, especially in self-guided web-based interventions. Rigorous empirical evidence regarding factors influencing dropout in self-guided web-based interventions is lacking due to small study sample sizes. In this paper we examined predictors of dropout in an individual patient data meta-analysis to gain a better understanding of who may benefit from these interventions.
A comprehensive literature search for all randomized controlled trials (RCTs) of psychotherapy for adults with depression from 2006 to January 2013 was conducted. Next, we approached authors to collect the primary data of the selected studies. Predictors of dropout, such as socio-demographic, clinical, and intervention characteristics were examined.
Data from 2705 participants across ten RCTs of self-guided web-based interventions for depression were analysed. The multivariate analysis indicated that male gender [relative risk (RR) 1.08], lower educational level (primary education, RR 1.26) and co-morbid anxiety symptoms (RR 1.18) significantly increased the risk of dropping out, while for every additional 4 years of age, the risk of dropping out significantly decreased (RR 0.94).
Dropout can be predicted by several variables and is not randomly distributed. This knowledge may inform tailoring of online self-help interventions to prevent dropout in identified groups at risk.
This paper describes the system architecture of a newly constructed radio telescope – the Boolardy engineering test array, which is a prototype of the Australian square kilometre array pathfinder telescope. Phased array feed technology is used to form multiple simultaneous beams per antenna, providing astronomers with unprecedented survey speed. The test array described here is a six-antenna interferometer, fitted with prototype signal processing hardware capable of forming at least nine dual-polarisation beams simultaneously, allowing several square degrees to be imaged in a single pointed observation. The main purpose of the test array is to develop beamforming and wide-field calibration methods for use with the full telescope, but it will also be capable of limited early science demonstrations.
The future of centimetre and metre-wave astronomy lies with the Square Kilometre Array (SKA), a telescope under development by a consortium of 17 countries that will be 50 times more sensitive than any existing radio facility. Most of the key science for the SKA will be addressed through large-area imaging of the Universe at frequencies from a few hundred MHz to a few GHz. The Australian SKA Pathfinder (ASKAP) is a technology demonstrator aimed in the mid-frequency range, and achieves instantaneous wide-area imaging through the development and deployment of phased-array feed systems on parabolic reflectors. The large field-of-view makes ASKAP an unprecedented synoptic telescope that will make substantial advances in SKA key science. ASKAP will be located at the Murchison Radio Observatory in inland Western Australia, one of the most radio-quiet locations on the Earth and one of two sites selected by the international community as a potential location for the SKA. In this paper, we outline an ambitious science program for ASKAP, examining key science such as understanding the evolution, formation and population of galaxies including our own, understanding the magnetic Universe, revealing the transient radio sky and searching for gravitational waves.
A survey of the Milky Way disk and the Magellanic System at the wavelengths of the 21-cm atomic hydrogen (H i) line and three 18-cm lines of the OH molecule will be carried out with the Australian Square Kilometre Array Pathfinder telescope. The survey will study the distribution of H i emission and absorption with unprecedented angular and velocity resolution, as well as molecular line thermal emission, absorption, and maser lines. The area to be covered includes the Galactic plane (|b| < 10°) at all declinations south of δ = +40°, spanning longitudes 167° through 360°to 79° at b = 0°, plus the entire area of the Magellanic Stream and Clouds, a total of 13 020 deg2. The brightness temperature sensitivity will be very good, typically σT≃ 1 K at resolution 30 arcsec and 1 km s−1. The survey has a wide spectrum of scientific goals, from studies of galaxy evolution to star formation, with particular contributions to understanding stellar wind kinematics, the thermal phases of the interstellar medium, the interaction between gas in the disk and halo, and the dynamical and thermal states of gas at various positions along the Magellanic Stream.
We describe nine patients (eight aged <1 year) clinically diagnosed with pertussis yet laboratory-confirmed with Bordetella holmesii infections, a human pathogen normally isolated from blood. Most patients reported cough and cold symptoms. No death was reported. We report B. holmesii isolation in infants with respiratory symptoms in Argentina.