Objective Ultrasound has been reported to be greater than 90% sensitive for the diagnosis of accreta. Prior studies may be subject to bias because of single expert observers, suspicion for accreta, ...and knowledge of risk factors. We aimed to assess the accuracy of ultrasound for the prediction of accreta. Study Design Patients with accreta at a single academic center were matched to patients with placenta previa, but no accreta, by year of delivery. Ultrasound studies with views of the placenta were collected, deidentified, blinded to clinical history, and placed in random sequence. Six investigators prospectively interpreted each study for the presence of accreta and findings reported to be associated with its diagnosis. Sensitivity, specificity, positive predictive, negative predictive value, and accuracy were calculated. Characteristics of accurate findings were compared using univariate and multivariate analyses. Results Six investigators examined 229 ultrasound studies from 55 patients with accreta and 56 controls for 1374 independent observations. 1205/1374 (87.7% overall, 90% controls, 84.9% cases) studies were given a diagnosis. There were 371 (27.0%) true positives; 81 (5.9%) false positives; 533 (38.8%) true negatives, 220 (16.0%) false negatives, and 169 (12.3%) with uncertain diagnosis. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 53.5%, 88.0%, 82.1%, 64.8%, and 64.8%, respectively. In multivariate analysis, true positives were more likely to have placental lacunae (odds ratio OR, 1.5; 95% confidence interval CI, 1.4–1.6), loss of retroplacental clear space (OR, 2.4; 95% CI, 1.1–4.9), or abnormalities on color Doppler (OR, 2.1; 95% CI, 1.8–2.4). Conclusion Ultrasound for the prediction of placenta accreta may not be as sensitive as previously described.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary Background We sought to improve outcome in patients with childhood acute myeloid leukaemia (AML) by applying risk-directed therapy that was based on genetic abnormalities of the leukaemic ...cells and measurements of minimal residual disease (MRD) done by flow cytometry during treatment. Methods From Oct 13, 2002, to June 19, 2008, 232 patients with de-novo AML (n=206), therapy-related or myelodysplasia-related AML (n=12), or mixed-lineage leukaemia (n=14) were enrolled at eight centres. 230 patients were assigned by block, non-blinded randomisation, stratified by cytogenetic or morphological subtype, to high-dose (18 g/m2 , n=113) or low-dose (2 g/m2 , n=117) cytarabine given with daunorubicin and etoposide (ADE; induction 1). The primary aim of the study was to compare the incidence of MRD positivity of the high-dose group and the low-dose group at day 22 of induction 1. Induction 2 consisted of ADE with or without gemtuzumab ozogamicin (GO anti-CD33 monoclonal antibody); consolidation therapy included three additional courses of chemotherapy or haematopoietic stem-cell transplantation (HSCT). Levels of MRD were used to allocate GO and to determine the timing of induction 2. Both MRD and genetic abnormalities at diagnosis were used to determine the final risk classification. Low-risk patients (n=68) received five courses of chemotherapy, whereas high-risk patients (n=79), and standard-risk patients (n=69) with matched sibling donors, were eligible for HSCT (done for 48 high-risk and eight standard-risk patients). All 230 randomised patients were analysed for the primary endpoint. Other analyses were limited to the 216 patients with AML, excluding those with mixed-lineage leukaemia. This trial is closed to accrual and is registered with ClinicalTrials.gov , number NCT00136084. Findings Complete remission was achieved in 80% (173 of 216 patients) after induction 1 and 94% (203 of 216) after induction 2. Induction failures included two deaths from toxic effects and ten cases of resistant leukaemia. The introduction of high-dose versus low-dose cytarabine did not significantly lower the rate of MRD-positivity after induction 1 (34% vs 42%, p=0·17). The 6-month cumulative incidence of grade 3 or higher infection was 79·3% (SE 4·0) for patients in the high-dose group and 75·5% (4·2) for the low-dose group. 3-year event-free survival and overall survival were 63·0% (SE 4·1) and 71·1% (3·8), respectively. 80% (155 of 193) of patients achieved MRD of less than 0·1% after induction 2, and the cumulative incidence of relapse for this group was 17% (SE 3). MRD of 1% or higher after induction 1 was the only significant independent adverse prognostic factor for both event-free (hazard ratio 2·41, 95% CI 1·36–4·26; p=0·003) and overall survival (2·11, 1·09–4·11; p=0·028). Interpretation Our findings suggest that the use of targeted chemotherapy and HSCT, in the context of a comprehensive risk-stratification strategy based on genetic features and MRD findings, can improve outcome in patients with childhood AML. Funding National Institutes of Health and American Lebanese Syrian Associated Charities (ALSAC).
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Context.
The intriguing binary
LS V +22 25
(LB-1) has drawn much attention following claims of it being a single-lined spectroscopic binary with a 79-day orbit comprising a B-type star and a ≈70
M
⊙
...black hole – the most massive stellar black hole reported to date. Subsequent studies demonstrated a lack of evidence for a companion of such great mass. Recent analyses have implied that the primary star is a stripped He-rich star with peculiar sub-solar abundances of heavy elements, such as Mg and Fe. However, the nature of the secondary, which was proposed to be a black hole, a neutron star, or a main sequence star, remains unknown.
Aims.
Based on 26 newly acquired spectroscopic observations secured with the HERMES and FEROS spectrographs covering the orbit of the system, we perform an orbital analysis and spectral disentangling of LB-1 to elucidate the nature of the system.
Methods.
To derive the radial velocity semi-amplitude
K
2
of the secondary and extract the spectra of the two components, we used two independent disentangling methods: the shift-and-add technique and Fourier disentangling with FDBinary. We used atmosphere models to constrain the surface properties and abundances.
Results.
Our disentangling and spectral analysis shows that LB-1 contains two components of comparable brightness in the optical. The narrow-lined primary, which we estimate to contribute ≈55% in the optical, has spectral properties that suggest that it is a stripped star: it has a small spectroscopic mass (≈1
M
⊙
) for a B-type star and it is He- and N-rich. Unlike previous reports, the abundances of heavy elements are found to be solar. The “hidden” secondary, which contributes about 45% of the optical flux, is a rapidly rotating (
v
sin
i
≈ 300 km s
−1
) B3 V star with a decretion disk – a Be star. As a result of its rapid rotation and dilution, the photospheric absorption lines of the secondary are not readily apparent in the individual observations. We measure a semi-amplitude for this star of
K
2
= 11.2 ± 1.0 km s
−1
and adopting a mass of
M
2
= 7 ± 2
M
⊙
typical for B3 V stars, we derive an orbital mass for the stripped primary of
M
1
= 1.5 ± 0.4
M
⊙
. The orbital inclination of 39 ± 4° implies a near-critical rotation for the Be secondary (
v
eq
≈ 470 km s
−1
).
Conclusions.
LB-1 does not contain a compact object. Instead, it is a rare Be binary system consisting of a stripped star (the former mass donor) and a Be star rotating at near its critical velocity (the former mass accretor). This system is a clear example that binary interactions play a decisive role in the production of rapid stellar rotators and Be stars.
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FMFMET, NUK, UL, UM, UPUK
Summary Background Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir–emtricitabine reduces the risk of HIV infection. However, this ...benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. Methods PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov ( NCT02065986 ). Findings We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64–96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3–11·3). 13 men (90% CI 9–23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients. Interpretation In this high incidence population, daily tenofovir–emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection. Funding MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract Pulmonary arterial hypertension (PAH) is an obstructive pulmonary vasculopathy, characterized by excess proliferation, apoptosis resistance, inflammation, fibrosis, and vasoconstriction. ...Although PAH therapies target some of these vascular abnormalities (primarily vasoconstriction), most do not directly benefit the right ventricle (RV). This is suboptimal because a patient's functional state and prognosis are largely determined by the success of the adaptation of the RV to the increased afterload. The RV initially hypertrophies but might ultimately decompensate, becoming dilated, hypokinetic, and fibrotic. A number of pathophysiologic abnormalities have been identified in the PAH RV, including: ischemia and hibernation (partially reflecting RV capillary rarefaction), autonomic activation (due to G protein receptor kinase 2-mediated downregulation and desensitization of β-adrenergic receptors), mitochondrial-metabolic abnormalities (notably increased uncoupled glycolysis and glutaminolysis), and fibrosis. Many RV abnormalities are detectable using molecular imaging and might serve as biomarkers. Some molecular pathways, such as those regulating angiogenesis, metabolism, and mitochondrial dynamics, are similarly deranged in the RV and pulmonary vasculature, offering the possibility of therapies that treat the RV and pulmonary circulation. An important paradigm in PAH is that the RV and pulmonary circulation constitute a unified cardiopulmonary unit. Clinical trials of PAH pharmacotherapies should assess both components of the cardiopulmonary unit.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
This paper reviews the biogeography of the Australian monsoon tropical biome to highlight general patterns in the distribution of a range of organisms and their environmental correlates and ...evolutionary history, as well as to identify knowledge gaps. Northern Australia, Australian Monsoon Tropics (AMT). The AMT is defined by areas that receive more than 85% of rainfall between November and April. Literature is summarized, including the origin of the monsoon climate, present-day environment, biota and habitat types, and phylogenetic and geographical relationships of selected organisms. Some species are widespread throughout the AMT while others are narrow-range endemics. Such contrasting distributions correspond to present-day climates, hydrologies (particularly floodplains), geological features (such as sandstone plateaux), fire regimes, and vegetation types (ranging from rain forest to savanna). Biogeographical and phylogenetic studies of terrestrial plants (e.g. eucalypts) and animals (vertebrates and invertebrates) suggest that distinct bioregions within the AMT reflect the aggregated effects of landscape and environmental history, although more research is required to determine and refine the boundaries of biogeographical zones within the AMT. Phylogenetic analyses of aquatic organisms (fishes and prawns) suggest histories of associations with drainage systems, dispersal barriers, links to New Guinea, and the existence of Lake Carpentaria, now submerged by the Gulf of Carpentaria. Complex adaptations to the landscape and climate in the AMT are illustrated by a number of species. The Australian monsoon is a component of a single global climate system, characterized by a dominant equator-spanning Hadley cell. Evidence of hot, seasonally moist climates dates back to the Late Eocene, implying that certain endemic elements of the AMT biota have a long history. Vicariant differentiation is inferred to have separated the Kimberley and Arnhem Land bioregions from Cape York Peninsula/northern Queensland. Such older patterns are overlaid by younger events, including dispersal from Southeast Asia, and range expansions and contractions. Future palaeoecological and phylogenetic investigations will illuminate the evolution of the AMT biome. Understanding the biogeography of the AMT is essential to provide a framework for ecological studies and the sustainable development of the region.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
The Kepler space mission provided near-continuous and high-precision photometry of about 207 000 stars, which can be used for asteroseismology. However, for successful seismic modeling it is equally ...important to have accurate stellar physical parameters. Therefore, supplementary ground-based data are needed. We report the results of the analysis of high-resolution spectroscopic data of A- and F-type stars from the Kepler field, which were obtained with the HERMES spectrograph on the Mercator telescope. We determined spectral types, atmospheric parameters and chemical abundances for a sample of 117 stars. Hydrogen Balmer, Fe i, and Fe ii lines were used to derive effective temperatures, surface gravities, and microturbulent velocities. We determined chemical abundances and projected rotational velocities using a spectrum synthesis technique. The atmospheric parameters obtained were compared with those from the Kepler Input Catalogue (KIC), confirming that the KIC effective temperatures are underestimated for A stars. Effective temperatures calculated by spectral energy distribution fitting are in good agreement with those determined from the spectral line analysis. The analysed sample comprises stars with approximately solar chemical abundances, as well as chemically peculiar stars of the Am, Ap, and λ Boo types. The distribution of the projected rotational velocity, vsin i, is typical for A and F stars and ranges from 8 to about 280 km s−1, with a mean of 134 km s−1.
ABSTRACT
V453 Cyg is an eclipsing binary containing 14 and 11 $\, {\rm M}_\odot$ stars in an eccentric short-period orbit. We have discovered β Cep-type pulsations in this system using Transiting ...Exoplanet Survey Satellite data. We identify seven significant pulsation frequencies, between 2.37 and 10.51 d−1, in the primary star. These include six frequencies that are separated by yet significantly offset from harmonics of the orbital frequency, indicating they are tidally perturbed modes. We have determined the physical properties of the system to high precision: V453 Cyg A is the first β Cep pulsator with a precise mass measurement. The system is a vital tracer of the physical processes that govern the evolution of massive single and binary stars.
Tree species exceeding 70 m in height are rare globally. Giant gymnosperms are concentrated near the Pacific coast of the USA, while the tallest angiosperms are eucalypts (Eucalyptus spp.) in ...southern and eastern Australia. Giant eucalypts co-occur with rain-forest trees in eastern Australia, creating unique vegetation communities comprising fire-dependent trees above fire-intolerant rain-forest. However, giant eucalypts can also tower over shrubby understoreys (e.g. in Western Australia). The local abundance of giant eucalypts is controlled by interactions between fire activity and landscape setting. Giant eucalypts have features that increase flammability (e.g. oil-rich foliage and open crowns) relative to other rain-forest trees but it is debatable if these features are adaptations. Probable drivers of eucalypt gigantism are intense intra-specific competition following severe fires, and inter-specific competition among adult trees. However, we suggest that this was made possible by a general capacity of eucalypts for ‘hyper-emergence’. We argue that, because giant eucalypts occur in rain-forest climates and share traits with rain-forest pioneers, they should be regarded as long-lived rain-forest pioneers, albeit with a particular dependence on fire for regeneration. These unique ecosystems are of high conservation value, following substantial clearing and logging over 150 yr.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
In temperate and boreal ecosystems, seasonal cycles of growth and dormancy allow perennial plants to adapt to winter conditions. We show, in hybrid aspen trees, that photoperiodic regulation of ...dormancy is mechanistically distinct from autumnal growth cessation. Dormancy sets in when symplastic intercellular communication through plasmodesmata is blocked by a process dependent on the phytohormone abscisic acid. The communication blockage prevents growth-promoting signals from accessing the meristem. Thus, precocious growth is disallowed during dormancy. The dormant period, which supports robust survival of the aspen tree in winter, is due to loss of access to growth-promoting signals.
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