Erratum to: Genetic alterations of m6A regulators predict poorer survival in acute myeloid leukemia

Abstract Methylation of N6 adenosine (m6A) is known to be important for diverse biological processes including gene expression control, translation of protein, and messenger RNA (mRNA) splicing. However, its role in the development of human cancers is poorly understood. By analyzing datasets from the Cancer Genome Atlas Research Network (TCGA) acute myeloid leukemia (AML) study, we discover that mutations and/or copy number variations of m6A regulatory genes are strongly associated with the presence of TP53 mutations in AML patients. Further, our analyses reveal that alterations in m6A regulatory genes confer a worse survival in AML. Our work indicates that genetic alterations of m6A regulatory genes may cooperate with TP53 and/or its regulator/downstream targets in the pathogenesis and/or maintenance of AML

Melatonin for rapid eye movement sleep behavior disorder in Parkinson's disease : a randomised controlled trial

Background Melatonin may reduce REM-sleep behavior disorder (RBD) symptoms in Parkinson's disease (PD), though robust clinical trials are lacking. Objective To assess the efficacy of prolonged-release (PR) melatonin for RBD in PD. Methods Randomized, double-blind, placebo-controlled, parallel-group trial with an 8-week intervention and 4-week observation pre- and postintervention (ACTRN12613000648729). Thirty PD patients with rapid eye movement sleep behavior disorder were randomized to 4 mg of prolonged-release melatonin (Circadin) or matched placebo, ingested orally once-daily before bedtime. Primary outcome was the aggregate of rapid eye movement sleep behavior disorder incidents averaged over weeks 5 to 8 of treatment captured by a weekly diary. Data were included in a mixed-model analysis of variance (n = 15 per group). Results No differences between groups at the primary endpoint (3.4 events/week melatonin vs. 3.6 placebo; difference, 0.2; 95% confidence interval = -3.2 to 3.6; P = 0.92). Adverse events included mild headaches, fatigue, and morning sleepiness (n = 4 melatonin; n = 5 placebo). Conclusion Prolonged-release melatonin 4 mg did not reduce rapid eye movement sleep behavior disorder in PD. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

H0LiCOW III. Quantifying the effect of mass along the line of sight to the gravitational lens HE 0435-1223 through weighted galaxy counts

Based on spectroscopy and multiband wide-field observations of the gravitationally lensed quasar HE 0435-1223, we determine the probability distribution function of the external convergence $\kappa_\mathrm{ext}$ for this system. We measure the under/overdensity of the line of sight towards the lens system and compare it to the average line of sight throughout the universe, determined by using the CFHTLenS as a control field. Aiming to constrain $\kappa_\mathrm{ext}$ as tightly as possible, we determine under/overdensities using various combinations of relevant informative weighing schemes for the galaxy counts, such as projected distance to the lens, redshift, and stellar mass. We then convert the measured under/overdensities into a $\kappa_\mathrm{ext}$ distribution, using ray-tracing through the Millennium Simulation. We explore several limiting magnitudes and apertures, and account for systematic and statistical uncertainties relevant to the quality of the observational data, which we further test through simulations. Our most robust estimate of $\kappa_\mathrm{ext}$ has a median value $\kappa^\mathrm{med}_\mathrm{ext} = 0.004$ and a standard deviation of $\sigma_\kappa = 0.025$. The measured $\sigma_\kappa$ corresponds to $2.5\%$ uncertainty on the time delay distance, and hence the Hubble constant $H_0$ inference from this system. The median $\kappa^\mathrm{med}_\mathrm{ext}$ value is robust to $\sim0.005$ (i.e. $\sim0.5\%$ on $H_0$) regardless of the adopted aperture radius, limiting magnitude and weighting scheme, as long as the latter incorporates galaxy number counts, the projected distance to the main lens, and a prior on the external shear obtained from mass modeling. The availability of a well-constrained $\kappa_\mathrm{ext}$ makes \hequad\ a valuable system for measuring cosmological parameters using strong gravitational lens time delays.Comment: 24 pages, 17 figures, 6 tables. Submitted to MNRA

The SL2S Galaxy-scale Gravitational Lens Sample. I. The alignment of mass and light in massive early-type galaxies at z=0.2-0.9

We study the relative alignment of mass and light in a sample of 16 massive early-type galaxies at z=0.2-0.9 that act as strong gravitational lenses. The sample was identified from deep multi-band images obtained as part of the Canada France Hawaii Telescope Legacy Survey as part of the Strong Lensing Legacy Survey (SL2S). Higher resolution follow-up imaging is available for a subset of 10 systems. We construct gravitational lens models and infer total enclosed mass, elongation, and position angle of the mass distribution. By comparison with the observed distribution of light we infer that there is a substantial amount of external shear with mean value $= 0.12 \pm 0.05$, arising most likely from the environment of the SL2S lenses. In a companion paper, we combine these measurements with follow-up Keck spectroscopy to study the evolution of the stellar and dark matter content of early-type galaxies as a function of cosmic time

A realtime observatory for laboratory simulation of planetary flows

Motivated by the large-scale circulation of the atmosphere and ocean, we develop a system that uses observations from a laboratory analog to constrain, in real time, a numerical simulation of the laboratory flow. This system provides a tool to rapidly prototype new methods for state and parameter estimation, and facilitates the study of prediction, predictability, and transport of geophysical fluids where observations or numerical simulations would not independently suffice. A computer vision system is used to extract measurements of the physical simulation. Observations are used to constrain the model-state of the MIT General Circulation Model in a probabilistic, ensemble based assimilation approach. Using a combination of parallelism, domain decomposition and an efficient scheme to select ensembles of model-states, we show that estimates that effectively track the fluid state can be produced. To the best of our knowledge this is the first such observatory for laboratory analogs of planetary circulation that functions in real time.National Science Foundation (U.S.) (CNS-0540259)National Science Foundation (U.S.) (grant CNS-0540248

A Bayesian Approach to Strong Lens Finding in the Era of Wide-area Surveys

The arrival of the Vera C. Rubin Observatory's Legacy Survey of Space and Time (LSST), Euclid-Wide and Roman wide area sensitive surveys will herald a new era in strong lens science in which the number of strong lenses known is expected to rise from $\mathcal{O}(10^3)$ to $\mathcal{O}(10^5)$. However, current lens-finding methods still require time-consuming follow-up visual inspection by strong-lens experts to remove false positives which is only set to increase with these surveys. In this work we demonstrate a range of methods to produce calibrated probabilities to help determine the veracity of any given lens candidate. To do this we use the classifications from citizen science and multiple neural networks for galaxies selected from the Hyper Suprime-Cam (HSC) survey. Our methodology is not restricted to particular classifier types and could be applied to any strong lens classifier which produces quantitative scores. Using these calibrated probabilities, we generate an ensemble classifier, combining citizen science and neural network lens finders. We find such an ensemble can provide improved classification over the individual classifiers. We find a false positive rate of $10^{-3}$ can be achieved with a completeness of $46\%$, compared to $34\%$ for the best individual classifier. Given the large number of galaxy-galaxy strong lenses anticipated in LSST, such improvement would still produce significant numbers of false positives, in which case using calibrated probabilities will be essential for population analysis of large populations of lenses.Comment: Submitted to MNRAS, 14 pages, 9 figures. Comments welcom

H0LiCOW XII. Lens mass model of WFI2033-4723 and blind measurement of its time-delay distance and H0H_0

We present the lens mass model of the quadruply-imaged gravitationally lensed quasar WFI2033-4723, and perform a blind cosmographical analysis based on this system. Our analysis combines (1) time-delay measurements from 14 years of data obtained by the COSmological MOnitoring of GRAvItational Lenses (COSMOGRAIL) collaboration, (2) high-resolution $\textit{Hubble Space Telescope}$ imaging, (3) a measurement of the velocity dispersion of the lens galaxy based on ESO-MUSE data, and (4) multi-band, wide-field imaging and spectroscopy characterizing the lens environment. We account for all known sources of systematics, including the influence of nearby perturbers and complex line-of-sight structure, as well as the parametrization of the light and mass profiles of the lensing galaxy. After unblinding, we determine the effective time-delay distance to be $4784_{-248}^{+399}~\mathrm{Mpc}$, an average precision of $6.6\%$. This translates to a Hubble constant $H_{0} = 71.6_{-4.9}^{+3.8}~\mathrm{km~s^{-1}~Mpc^{-1}}$, assuming a flat $\Lambda$CDM cosmology with a uniform prior on $\Omega_\mathrm{m}$ in the range [0.05, 0.5]. This work is part of the $H_0$ Lenses in COSMOGRAIL's Wellspring (H0LiCOW) collaboration, and the full time-delay cosmography results from a total of six strongly lensed systems are presented in a companion paper (H0LiCOW XIII).Comment: Version accepted by MNRAS. 29 pages including appendix, 17 figures, 6 tables. arXiv admin note: text overlap with arXiv:1607.0140

Maternal uptake of pertussis cocooning strategy and other pregnancy related recommended immunzations

Accepted author version posted online: 25 Feb 2015Maternal immunization is an important strategy to prevent severe morbidity and mortality in mothers and their offspring. This study aimed to identify whether new parents were following immunization recommendations prior to pregnancy, during pregnancy, and postnatally. A cross-sectional survey was conducted by a questionnaire administered antenatally to pregnant women attending a maternity hospital with a follow-up telephone interview at 8-10 weeks post-delivery. Factors associated with uptake of pertussis vaccination within the previous five years or postnatally and influenza vaccination during pregnancy were explored using log binomial regression models. A total of 297 pregnant women completed the questionnaire. For influenza vaccine, 20.3% were immunized during pregnancy and 3.0% postnatally. For pertussis vaccine, 13.1% were vaccinated within five years prior to pregnancy and 31 women received the vaccine postnatally, 16 (51.6%) received the vaccine > 4 weeks after delivery. Receiving a recommendation from a healthcare practitioner (HCP) was an independent predictor for receipt of both pertussis (RR 2.07, p<0.001) and influenza vaccine (RR 2.26, p=0.001). Non-English speaking mothers were significantly less likely to have received pertussis vaccination prior to pregnancy or postnatally (RR 0.24, p=0.011). Multiparous pregnant women were less likely to have received an influenza vaccine during their current pregnancy (p=0.015). Uptake of pregnancy related immunization is low and likely due to poor knowledge of availability, language barriers and lack of recommendations from HCPs. Strategies to improve maternal vaccine uptake should include education about recommended vaccines for both HCPs and parents and written information in a variety of languages.C Y Wong, N J Thomas, M Clarke, C Boros, J Tuckerman & H S Marshal

COSMOGRAIL XVIII: time delays of the quadruply lensed quasar WFI2033-4723

We present new measurements of the time delays of WFI2033-4723. The data sets used in this work include 14 years of data taken at the 1.2m Leonhard Euler Swiss telescope, 13 years of data from the SMARTS 1.3m telescope at Las Campanas Observatory and a single year of high-cadence and high-precision monitoring at the MPIA 2.2m telescope. The time delays measured from these different data sets, all taken in the R-band, are in good agreement with each other and with previous measurements from the literature. Combining all the time-delay estimates from our data sets results in Dt_AB = 36.2-0.8+0.7 days (2.1% precision), Dt_AC = -23.3-1.4+1.2 days (5.6%) and Dt_BC = -59.4-1.3+1.3 days (2.2%). In addition, the close image pair A1-A2 of the lensed quasars can be resolved in the MPIA 2.2m data. We measure a time delay consistent with zero in this pair of images. We also explore the prior distributions of microlensing time-delay potentially affecting the cosmological time-delay measurements of WFI2033-4723. There is however no strong indication in our measurements that microlensing time delay is neither present nor absent. This work is part of a H0LiCOW series focusing on measuring the Hubble constant from WFI2033-4723.Comment: Submitted to Astronomy and Astrophysic

A Screen for Morphological Complexity Identifies Regulators of Switch-like Transitions between Discrete Cell Shapes

The way in which cells adopt different morphologies is not fully understood. Cell shape could be a continuous variable or restricted to a set of discrete forms. We developed quantitative methods to describe cell shape and show that Drosophila hemocytes in culture are a heterogeneous mixture of five discrete morphologies. In an RNAi screen of genes affecting the morphological complexity of heterogeneous populations, we found that most genes regulate the transition between discrete shapes rather than generating new morphologies. In particular, we identified a subset of genes, including the tumour suppressor PTEN, that decrease the heterogeneity of the population leading to populations enriched in rounded or elongated forms. We show that these genes have a highly conserved function as regulators of cell shape in both mouse and human metastatic melanoma cells