Objective
To assess the frequency of obstructive sleep apnoea among women with and without hypertensive disorders of pregnancy.
Design
Cohort study.
Setting
Obstetric clinics at an academic medical ...centre.
Population
Pregnant women with hypertensive disorders (chronic hypertension, gestational hypertension, or pre‐eclampsia) and women who were normotensive.
Methods
Women completed a questionnaire about habitual snoring and underwent overnight ambulatory polysomnography.
Main outcome measures
The presence and severity of obstructive sleep apnoea.
Results
Obstructive sleep apnoea was found among 21 of 51 women with hypertensive disorders (41%), but in only three of 16 women who were normotensive (19%, chi‐square test, P = 0.005). Author correction added on 16 June 2014, after first online publication: Results mentioned in the were amended. Non‐snoring women with hypertensive disorders typically had mild obstructive sleep apnoea, but >25% of snoring women with hypertensive disorders had moderate to severe obstructive sleep apnoea. Among women with hypertensive disorders, the mean apnoea/hypopnoea index was substantially higher in snorers than in non‐snorers (19.9 ± 34.1 versus 3.4 ± 3.1, P = 0.013), and the oxyhaemoglobin saturation nadir was significantly lower (86.4 ± 6.6 versus 90.2 ± 3.5, P = 0.021). Among women with hypertensive disorders, after stratification by obesity, the pooled relative risk for obstructive sleep apnoea in snoring women with hypertension compared with non‐snoring women with hypertension was 2.0 (95% CI 1.4–2.8).
Conclusions
Pregnant women with hypertension are at high risk for unrecognised obstructive sleep apnoea. Although longitudinal and intervention studies are urgently needed, given the known relationship between obstructive sleep apnoea and hypertension in the general population, it would seem pertinent that hypertensive pregnant women who snore should be tested for obstructive sleep apnoea, a condition believed to cause or promote hypertension.
We develop a simple toy model for polarized images of synchrotron emission from an equatorial source around a Kerr black hole by using a semianalytic solution of the null geodesic equation and ...conservation of the Penrose-Walker constant. Our model is an extension of Narayan et al., which presented results for a Schwarzschild black hole, including a fully analytic approximation. Our model includes an arbitrary observer inclination, black hole spin, local boost, and local magnetic field configuration. We study the geometric effects of black hole spin on photon parallel transport and isolate these effects from the complicated combination of relativistic, gravitational, and electromagnetic processes in the emission region. Expanding in 1 / rs, we find an analytic approximation, consistent with previous work, for the geometric effect of spin on observed face-on polarization rotation in the direct image: Δ EVPA ∼ − 2a/r2s, where a is the black hole spin and rs is the emission radius. We further show that spin introduces an order unity effect on face-on subimages: Δ EVPA ∼ ± a / √ 27 . We also use our toy model to analyze polarization "loops" observed during flares of orbiting hot spots. Our model provides insight into polarimetric simulations and observations of black holes such as those made by the EHT and GRAVITY.
Entanglement lies at the core of quantum algorithms designed to solve problems that are intractable by classical approaches. One such algorithm, quantum annealing (QA), provides a promising path to a ...practical quantum processor. We have built a series of architecturally scalable QA processors consisting of networks of manufactured interacting spins (qubits). Here, we use qubit tunneling spectroscopy to measure the energy eigenspectrum of two- and eight-qubit systems within one such processor, demonstrating quantum coherence in these systems. We present experimental evidence that, during a critical portion of QA, the qubits become entangled and entanglement persists even as these systems reach equilibrium with a thermal environment. Our results provide an encouraging sign that QA is a viable technology for large-scale quantum computing.
We present constraints on extensions of the minimal cosmological models dominated by dark matter and dark energy, ΛCDM and wCDM, by using a combined analysis of galaxy clustering and weak ...gravitational lensing from the first-year data of the Dark Energy Survey (DES Y1) in combination with external data. We consider four extensions of the minimal dark energy-dominated scenarios: (1) nonzero curvature Ωk, (2) number of relativistic species Neff different from the standard value of 3.046, (3) time-varying equation-of-state of dark energy described by the parameters w0 and wa (alternatively quoted by the values at the pivot redshift, wp, and wa), and (4) modified gravity described by the parameters μ0 and Σ0 that modify the metric potentials. We also consider external information from Planck cosmic microwave background measurements; baryon acoustic oscillation measurements from SDSS, 6dF, and BOSS; redshift-space distortion measurements from BOSS; and type Ia supernova information from the Pantheon compilation of datasets. Constraints on curvature and the number of relativistic species are dominated by the external data; when these are combined with DES Y1, we find Ωk=0.0020−0.0032+0.0037 at the 68% confidence level, and the upper limit Neff<3.28(3.55) at 68% (95%) confidence, assuming a hard prior Neff>3.0. For the time-varying equation-of-state, we find the pivot value (wp,wa)=(−0.91−0.23+0.19,−0.57−1.11+0.93) at pivot redshift zp=0.27 from DES alone, and (wp,wa)=(−1.01−0.04+0.04,−0.28−0.48+0.37) at zp=0.20 from DES Y1 combined with external data; in either case we find no evidence for the temporal variation of the equation of state. For modified gravity, we find the present-day value of the relevant parameters to be Σ0=0.43−0.29+0.28 from DES Y1 alone, and (Σ0,μ0)=(0.06−0.07+0.08,−0.11−0.46+0.42) from DES Y1 combined with external data. These modified-gravity constraints are consistent with predictions from general relativity.
We manipulate a single electron in a fully tunable double quantum dot using microwave excitation. Under resonant conditions, microwaves drive transitions between the (1,0) and (0,1) charge states of ...the double dot. Local quantum point contact charge detectors enable a direct measurement of the photon-induced change in occupancy of the charge states. From charge sensing measurements, we find T1 approximately 16 ns and a lower bound estimate for T*(2) of 400 ps for the charge two-level system.
The Event Horizon Telescope (EHT) has led to the first images of a supermassive black hole, revealing the central compact objects in the elliptical galaxy M87 and the Milky Way. Proposed upgrades to ...this array through the next-generation EHT (ngEHT) program would sharply improve the angular resolution, dynamic range, and temporal coverage of the existing EHT observations. These improvements will uniquely enable a wealth of transformative new discoveries related to black hole science, extending from event-horizon-scale studies of strong gravity to studies of explosive transients to the cosmological growth and influence of supermassive black holes. Here, we present the key science goals for the ngEHT and their associated instrument requirements, both of which have been formulated through a multi-year international effort involving hundreds of scientists worldwide.
Recent clinical data support the utility/superiority of a new AKI biomarker ("NephroCheck"), the arithmetic product of urinary TIMP × IGFBP7 concentrations. However, the pathophysiologic basis for ...its utility remains ill defined.
To clarify this issue, CD-1 mice were subjected to either nephrotoxic (glycerol, maleate) or ischemic AKI. Urinary TIMP2/IGFBP7 concentrations were determined at 4 and 18 hours postinjury and compared with urinary albumin levels. Gene transcription was assessed by measuring renal cortical and/or medullary TIMP2/IGFBP7 mRNAs (4 and 18 hours after AKI induction). For comparison, the mRNAs of three renal "stress" biomarkers (NGAL, heme oxygenase 1, and p21) were assessed. Renal cortical TIMP2/IGFBP7 protein was gauged by ELISA. Proximal tubule-specific TIMP2/IGFBP7 was assessed by immunohistochemistry.
Each AKI model induced prompt (4 hours) and marked urinary TIMP2/IGFBP7 increases without an increase in renal cortical concentrations. Furthermore, TIMP2/IGFBP7 mRNAs remained at normal levels. Endotoxemia also failed to increase TIMP2/IGFBP7 mRNAs. In contrast, each AKI model provoked massive NGAL, HO-1, and p21 mRNA increases, confirming that a renal "stress response" had occurred. Urinary albumin rose up to 100-fold and strongly correlated (
=0.87-0.91) with urinary TIMP2/IGFBP7 concentrations. Immunohistochemistry showed progressive TIMP2/IGFBP7 losses from injured proximal tubule cells. Competitive inhibition of endocytic protein reabsorption in normal mice tripled urinary TIMP2/IGFBP7 levels, confirming this pathway's role in determining urinary excretion.
AKI-induced urinary TIMP2/IGFBP7 elevations are not due to stress-induced gene transcription. Rather, increased filtration, decreased tubule reabsorption, and proximal tubule cell TIMP2/IGFBP7 urinary leakage seem to be the most likely mechanisms.
Acquired resistance (AR) to programmed cell death protein 1/programmed death-ligand 1 PD-(L)1 blockade is frequent in non-small-cell lung cancer (NSCLC), occurring in a majority of initial ...responders. Patients with AR may have unique properties of persistent antitumor immunity that could be re-harnessed by investigational immunotherapies. The absence of a consistent clinical definition of AR to PD-(L)1 blockade and lack of uniform criteria for ensuing enrollment in clinical trials remains a major barrier to progress; such clinical definitions have advanced biologic and therapeutic discovery. We examine the considerations and potential controversies in developing a patient-level definition of AR in NSCLC treated with PD-(L)1 blockade. Taking into account the specifics of NSCLC biology and corresponding treatment strategies, we propose a practical, clinical definition of AR to PD-(L)1 blockade for use in clinical reports and prospective clinical trials. Patients should meet the following criteria: received treatment that includes PD-(L)1 blockade; experienced objective response on PD-(L)1 blockade (inclusion of a subset of stable disease will require future investigation); have progressive disease occurring within 6 months of last anti-PD-(L)1 antibody treatment or rechallenge with anti-PD-(L)1 antibody in patients not exposed to anti-PD-(L)1 in 6 months.
•In NSCLC, acquired resistance to immunotherapy is common and poorly understood.•A uniform clinical definition is imperative to further characterize patients and develop a rational approach to overcoming acquired resistance.•The proposed definition seeks to unify language for future reports and clinical trials in NSCLC.•We also highlight specific areas of uncertainty in classification of acquired resistance that require urgent attention and could lead to further refinements in the future.
Abstract
We present estimates for the number of shadow-resolved supermassive black hole (SMBH) systems that can be detected using radio interferometers, as a function of angular resolution, flux ...density sensitivity, and observing frequency. Accounting for the distribution of SMBHs across mass, redshift, and accretion rate, we use a new semianalytic spectral energy distribution model to derive the number of SMBHs with detectable and optically thin horizon-scale emission. We demonstrate that (sub)millimeter interferometric observations with ∼0.1
μ
as resolution and ∼1
μ
Jy sensitivity could access >10
6
SMBH shadows. We then further decompose the shadow source counts into the number of black holes for which we could expect to observe the first- and second-order lensed photon rings. Accessing the bulk population of first-order photon rings requires ≲2
μ
as resolution and ≲0.5 mJy sensitivity, whereas doing the same for second-order photon rings requires ≲0.1
μ
as resolution and ≲5
μ
Jy sensitivity. Our model predicts that with modest improvements to sensitivity, as many as ∼5 additional horizon-resolved sources should become accessible to the current Event Horizon Telescope (EHT), whereas a next-generation EHT observing at 345 GHz should have access to ∼3 times as many sources. More generally, our results can help guide enhancements of current arrays and specifications for future interferometric experiments that aim to spatially resolve a large population of SMBH shadows or higher-order photon rings.
Creatine transporter deficiency is a monogenic cause of X-linked intellectual disability. Since its first description in 2001 several case reports have been published but an overview of phenotype, ...genotype and phenotype--genotype correlation has been lacking.
We performed a retrospective study of clinical, biochemical and molecular genetic data of 101 males with X-linked creatine transporter deficiency from 85 families with a pathogenic mutation in the creatine transporter gene (SLC6A8).
Most patients developed moderate to severe intellectual disability; mild intellectual disability was rare in adult patients. Speech language development was especially delayed but almost a third of the patients were able to speak in sentences. Besides behavioural problems and seizures, mild to moderate motor dysfunction, including extrapyramidal movement abnormalities, and gastrointestinal problems were frequent clinical features. Urinary creatine to creatinine ratio proved to be a reliable screening method besides MR spectroscopy, molecular genetic testing and creatine uptake studies, allowing definition of diagnostic guidelines. A third of patients had a de novo mutation in the SLC6A8 gene. Mothers with an affected son with a de novo mutation should be counselled about a recurrence risk in further pregnancies due to the possibility of low level somatic or germline mosaicism. Missense mutations with residual activity might be associated with a milder phenotype and large deletions extending beyond the 3' end of the SLC6A8 gene with a more severe phenotype. Evaluation of the biochemical phenotype revealed unexpected high creatine levels in cerebrospinal fluid suggesting that the brain is able to synthesise creatine and that the cerebral creatine deficiency is caused by a defect in the reuptake of creatine within the neurones.
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