Showing papers by "Columbia University published in 2017"

GW170817: observation of gravitational waves from a binary neutron star inspiral

Abstract: On August 17, 2017 at 12∶41:04 UTC the Advanced LIGO and Advanced Virgo gravitational-wave detectors made their first observation of a binary neutron star inspiral. The signal, GW170817, was detected with a combined signal-to-noise ratio of 32.4 and a false-alarm-rate estimate of less than one per 8.0×10^{4} years. We infer the component masses of the binary to be between 0.86 and 2.26 M_{⊙}, in agreement with masses of known neutron stars. Restricting the component spins to the range inferred in binary neutron stars, we find the component masses to be in the range 1.17-1.60 M_{⊙}, with the total mass of the system 2.74_{-0.01}^{+0.04}M_{⊙}. The source was localized within a sky region of 28 deg^{2} (90% probability) and had a luminosity distance of 40_{-14}^{+8} Mpc, the closest and most precisely localized gravitational-wave signal yet. The association with the γ-ray burst GRB 170817A, detected by Fermi-GBM 1.7 s after the coalescence, corroborates the hypothesis of a neutron star merger and provides the first direct evidence of a link between these mergers and short γ-ray bursts. Subsequent identification of transient counterparts across the electromagnetic spectrum in the same location further supports the interpretation of this event as a neutron star merger. This unprecedented joint gravitational and electromagnetic observation provides insight into astrophysics, dense matter, gravitation, and cosmology.

Neural Collaborative Filtering

Abstract: In recent years, deep neural networks have yielded immense success on speech recognition, computer vision and natural language processing. However, the exploration of deep neural networks on recommender systems has received relatively less scrutiny. In this work, we strive to develop techniques based on neural networks to tackle the key problem in recommendation --- collaborative filtering --- on the basis of implicit feedback. Although some recent work has employed deep learning for recommendation, they primarily used it to model auxiliary information, such as textual descriptions of items and acoustic features of musics. When it comes to model the key factor in collaborative filtering --- the interaction between user and item features, they still resorted to matrix factorization and applied an inner product on the latent features of users and items. By replacing the inner product with a neural architecture that can learn an arbitrary function from data, we present a general framework named NCF, short for Neural network-based Collaborative Filtering. NCF is generic and can express and generalize matrix factorization under its framework. To supercharge NCF modelling with non-linearities, we propose to leverage a multi-layer perceptron to learn the user-item interaction function. Extensive experiments on two real-world datasets show significant improvements of our proposed NCF framework over the state-of-the-art methods. Empirical evidence shows that using deeper layers of neural networks offers better recommendation performance.

Bag of Tricks for Efficient Text Classification

Abstract: This paper explores a simple and efficient baseline for text classification. Our experiments show that our fast text classifier fastText is often on par with deep learning classifiers in terms of accuracy, and many orders of magnitude faster for training and evaluation. We can train fastText on more than one billion words in less than ten minutes using a standard multicore CPU, and classify half a million sentences among 312K classes in less than a minute.

Variational Inference: A Review for Statisticians

Abstract: One of the core problems of modern statistics is to approximate difficult-to-compute probability densities. This problem is especially important in Bayesian statistics, which frames all inference about unknown quantities as a calculation involving the posterior density. In this article, we review variational inference (VI), a method from machine learning that approximates probability densities through optimization. VI has been used in many applications and tends to be faster than classical methods, such as Markov chain Monte Carlo sampling. The idea behind VI is to first posit a family of densities and then to find a member of that family which is close to the target density. Closeness is measured by Kullback–Leibler divergence. We review the ideas behind mean-field variational inference, discuss the special case of VI applied to exponential family models, present a full example with a Bayesian mixture of Gaussians, and derive a variant that uses stochastic optimization to scale up to massive data...

Gravitational Waves and Gamma-Rays from a Binary Neutron Star Merger: GW170817 and GRB 170817A

Abstract: On 2017 August 17, the gravitational-wave event GW170817 was observed by the Advanced LIGO and Virgo detectors, and the gamma-ray burst (GRB) GRB 170817A was observed independently by the Fermi Gamma-ray Burst Monitor, and the Anti-Coincidence Shield for the Spectrometer for the International Gamma-Ray Astrophysics Laboratory. The probability of the near-simultaneous temporal and spatial observation of GRB 170817A and GW170817 occurring by chance is $5.0\times {10}^{-8}$. We therefore confirm binary neutron star mergers as a progenitor of short GRBs. The association of GW170817 and GRB 170817A provides new insight into fundamental physics and the origin of short GRBs. We use the observed time delay of $(+1.74\pm 0.05)\,{\rm{s}}$ between GRB 170817A and GW170817 to: (i) constrain the difference between the speed of gravity and the speed of light to be between $-3\times {10}^{-15}$ and $+7\times {10}^{-16}$ times the speed of light, (ii) place new bounds on the violation of Lorentz invariance, (iii) present a new test of the equivalence principle by constraining the Shapiro delay between gravitational and electromagnetic radiation. We also use the time delay to constrain the size and bulk Lorentz factor of the region emitting the gamma-rays. GRB 170817A is the closest short GRB with a known distance, but is between 2 and 6 orders of magnitude less energetic than other bursts with measured redshift. A new generation of gamma-ray detectors, and subthreshold searches in existing detectors, will be essential to detect similar short bursts at greater distances. Finally, we predict a joint detection rate for the Fermi Gamma-ray Burst Monitor and the Advanced LIGO and Virgo detectors of 0.1–1.4 per year during the 2018–2019 observing run and 0.3–1.7 per year at design sensitivity.

GW170104: Observation of a 50-Solar-Mass Binary Black Hole Coalescence at Redshift 0.2

Abstract: We describe the observation of GW170104, a gravitational-wave signal produced by the coalescence of a pair of stellar-mass black holes. The signal was measured on January 4, 2017 at 10∶11:58.6 UTC by the twin advanced detectors of the Laser Interferometer Gravitational-Wave Observatory during their second observing run, with a network signal-to-noise ratio of 13 and a false alarm rate less than 1 in 70 000 years. The inferred component black hole masses are 31.2^(8.4) _(−6.0)M_⊙ and 19.4^(5.3)_( −5.9)M_⊙ (at the 90% credible level). The black hole spins are best constrained through measurement of the effective inspiral spin parameter, a mass-weighted combination of the spin components perpendicular to the orbital plane, χ_(eff) = −0.12^(0.21)_( −0.30). This result implies that spin configurations with both component spins positively aligned with the orbital angular momentum are disfavored. The source luminosity distance is 880^(450)_(−390) Mpc corresponding to a redshift of z = 0.18^(0.08)_( −0.07) . We constrain the magnitude of modifications to the gravitational-wave dispersion relation and perform null tests of general relativity. Assuming that gravitons are dispersed in vacuum like massive particles, we bound the graviton mass to m_g ≤ 7.7 × 10^(−23) eV/c^2. In all cases, we find that GW170104 is consistent with general relativity.

Diagnosis and management of dementia with Lewy bodies Fourth consensus report of the DLB Consortium

Abstract: The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and 123iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. The diagnostic role of other neuroimaging, electrophysiologic, and laboratory investigations is also described. Minor modifications to pathologic methods and criteria are recommended to take account of Alzheimer disease neuropathologic change, to add previously omitted Lewy-related pathology categories, and to include assessments for substantia nigra neuronal loss. Recommendations about clinical management are largely based upon expert opinion since randomized controlled trials in DLB are few. Substantial progress has been made since the previous report in the detection and recognition of DLB as a common and important clinical disorder. During that period it has been incorporated into DSM-5, as major neurocognitive disorder with Lewy bodies. There remains a pressing need to understand the underlying neurobiology and pathophysiology of DLB, to develop and deliver clinical trials with both symptomatic and disease-modifying agents, and to help patients and carers worldwide to inform themselves about the disease, its prognosis, best available treatments, ongoing research, and how to get adequate support.

Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel

Abstract: Aims To appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD).

GW170814: A three-detector observation of gravitational waves from a binary black hole coalescence

Abstract: On August 14, 2017 at 10∶30:43 UTC, the Advanced Virgo detector and the two Advanced LIGO detectors coherently observed a transient gravitational-wave signal produced by the coalescence of two stellar mass black holes, with a false-alarm rate of ≲1 in 27 000 years. The signal was observed with a three-detector network matched-filter signal-to-noise ratio of 18. The inferred masses of the initial black holes are 30.5-3.0+5.7M⊙ and 25.3-4.2+2.8M⊙ (at the 90% credible level). The luminosity distance of the source is 540-210+130 Mpc, corresponding to a redshift of z=0.11-0.04+0.03. A network of three detectors improves the sky localization of the source, reducing the area of the 90% credible region from 1160 deg2 using only the two LIGO detectors to 60 deg2 using all three detectors. For the first time, we can test the nature of gravitational-wave polarizations from the antenna response of the LIGO-Virgo network, thus enabling a new class of phenomenological tests of gravity.

Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers

Abstract: Importance: The clinical management of BRCA1 and BRCA2 mutation carriers requires accurate, prospective cancer risk estimates. Objectives: To estimate age-specific risks of breast, ovarian, and contralateral breast cancer for mutation carriers and to evaluate risk modification by family cancer history and mutation location. Design, Setting, and Participants: Prospective cohort study of 6036 BRCA1 and 3820 BRCA2 female carriers (5046 unaffected and 4810 with breast or ovarian cancer or both at baseline) recruited in 1997-2011 through the International BRCA1/2 Carrier Cohort Study, the Breast Cancer Family Registry and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, with ascertainment through family clinics (94%) and population-based studies (6%). The majority were from large national studies in the United Kingdom (EMBRACE), the Netherlands (HEBON), and France (GENEPSO). Follow-up ended December 2013; median follow-up was 5 years. Exposures: BRCA1/2 mutations, family cancer history, and mutation location. Main Outcomes and Measures: Annual incidences, standardized incidence ratios, and cumulative risks of breast, ovarian, and contralateral breast cancer. Results: Among 3886 women (median age, 38 years; interquartile range [IQR], 30-46 years) eligible for the breast cancer analysis, 5066 women (median age, 38 years; IQR, 31-47 years) eligible for the ovarian cancer analysis, and 2213 women (median age, 47 years; IQR, 40-55 years) eligible for the contralateral breast cancer analysis, 426 were diagnosed with breast cancer, 109 with ovarian cancer, and 245 with contralateral breast cancer during follow-up. The cumulative breast cancer risk to age 80 years was 72% (95% CI, 65%-79%) for BRCA1 and 69% (95% CI, 61%-77%) for BRCA2 carriers. Breast cancer incidences increased rapidly in early adulthood until ages 30 to 40 years for BRCA1 and until ages 40 to 50 years for BRCA2 carriers, then remained at a similar, constant incidence (20-30 per 1000 person-years) until age 80 years. The cumulative ovarian cancer risk to age 80 years was 44% (95% CI, 36%-53%) for BRCA1 and 17% (95% CI, 11%-25%) for BRCA2 carriers. For contralateral breast cancer, the cumulative risk 20 years after breast cancer diagnosis was 40% (95% CI, 35%-45%) for BRCA1 and 26% (95% CI, 20%-33%) for BRCA2 carriers (hazard ratio [HR] for comparing BRCA2 vs BRCA1, 0.62; 95% CI, 0.47-0.82; P=.001 for difference). Breast cancer risk increased with increasing number of first- and second-degree relatives diagnosed as having breast cancer for both BRCA1 (HR for ≥2 vs 0 affected relatives, 1.99; 95% CI, 1.41-2.82; P<.001 for trend) and BRCA2 carriers (HR, 1.91; 95% CI, 1.08-3.37; P=.02 for trend). Breast cancer risk was higher if mutations were located outside vs within the regions bounded by positions c.2282-c.4071 in BRCA1 (HR, 1.46; 95% CI, 1.11-1.93; P=.007) and c.2831-c.6401 in BRCA2 (HR, 1.93; 95% CI, 1.36-2.74; P<.001). Conclusions and Relevance: These findings provide estimates of cancer risk based on BRCA1 and BRCA2 mutation carrier status using prospective data collection and demonstrate the potential importance of family history and mutation location in risk assessment.

The Hierarchical Taxonomy of Psychopathology (HiTOP): A Dimensional Alternative to Traditional Nosologies

Abstract: The reliability and validity of traditional taxonomies are limited by arbitrary boundaries between psychopathology and normality, often unclear boundaries between disorders, frequent disorder co-occurrence, heterogeneity within disorders, and diagnostic instability. These taxonomies went beyond evidence available on the structure of psychopathology and were shaped by a variety of other considerations, which may explain the aforementioned shortcomings. The Hierarchical Taxonomy Of Psychopathology (HiTOP) model has emerged as a research effort to address these problems. It constructs psychopathological syndromes and their components/subtypes based on the observed covariation of symptoms, grouping related symptoms together and thus reducing heterogeneity. It also combines co-occurring syndromes into spectra, thereby mapping out comorbidity. Moreover, it characterizes these phenomena dimensionally, which addresses boundary problems and diagnostic instability. Here, we review the development of the HiTOP and the relevant evidence. The new classification already covers most forms of psychopathology. Dimensional measures have been developed to assess many of the identified components, syndromes, and spectra. Several domains of this model are ready for clinical and research applications. The HiTOP promises to improve research and clinical practice by addressing the aforementioned shortcomings of traditional nosologies. It also provides an effective way to summarize and convey information on risk factors, etiology, pathophysiology, phenomenology, illness course, and treatment response. This can greatly improve the utility of the diagnosis of mental disorders. The new classification remains a work in progress. However, it is developing rapidly and is poised to advance mental health research and care significantly as the relevant science matures. (PsycINFO Database Record

The roads ahead: Narratives for shared socioeconomic pathways describing world futures in the 21st century

Abstract: Long-term scenarios play an important role in research on global environmental change. The climate change research community is developing new scenarios integrating future changes in climate and society to investigate climate impacts as well as options for mitigation and adaptation. One component of these new scenarios is a set of alternative futures of societal development known as the shared socioeconomic pathways (SSPs). The conceptual framework for the design and use of the SSPs calls for the development of global pathways describing the future evolution of key aspects of society that would together imply a range of challenges for mitigating and adapting to climate change. Here we present one component of these pathways: the SSP narratives, a set of five qualitative descriptions of future changes in demographics, human development, economy and lifestyle, policies and institutions, technology, and environment and natural resources. We describe the methods used to develop the narratives as well as how these pathways are hypothesized to produce particular combinations of challenges to mitigation and adaptation. Development of the narratives drew on expert opinion to (1) identify key determinants of these challenges that were essential to incorporate in the narratives and (2) combine these elements in the narratives in a manner consistent with scholarship on their inter-relationships. The narratives are intended as a description of plausible future conditions at the level of large world regions that can serve as a basis for integrated scenarios of emissions and land use, as well as climate impact, adaptation and vulnerability analyses.

Practical Bayesian model evaluation using leave-one-out cross-validation and WAIC

Abstract: Leave-one-out cross-validation (LOO) and the widely applicable information criterion (WAIC) are methods for estimating pointwise out-of-sample prediction accuracy from a fitted Bayesian model using the log-likelihood evaluated at the posterior simulations of the parameter values. LOO and WAIC have various advantages over simpler estimates of predictive error such as AIC and DIC but are less used in practice because they involve additional computational steps. Here we lay out fast and stable computations for LOO and WAIC that can be performed using existing simulation draws. We introduce an efficient computation of LOO using Pareto-smoothed importance sampling (PSIS), a new procedure for regularizing importance weights. Although WAIC is asymptotically equal to LOO, we demonstrate that PSIS-LOO is more robust in the finite case with weak priors or influential observations. As a byproduct of our calculations, we also obtain approximate standard errors for estimated predictive errors and for comparison of predictive errors between two models. We implement the computations in an R package called loo and demonstrate using models fit with the Bayesian inference package Stan.

SCA-CNN: Spatial and Channel-Wise Attention in Convolutional Networks for Image Captioning

Abstract: Visual attention has been successfully applied in structural prediction tasks such as visual captioning and question answering. Existing visual attention models are generally spatial, i.e., the attention is modeled as spatial probabilities that re-weight the last conv-layer feature map of a CNN encoding an input image. However, we argue that such spatial attention does not necessarily conform to the attention mechanism — a dynamic feature extractor that combines contextual fixations over time, as CNN features are naturally spatial, channel-wise and multi-layer. In this paper, we introduce a novel convolutional neural network dubbed SCA-CNN that incorporates Spatial and Channel-wise Attentions in a CNN. In the task of image captioning, SCA-CNN dynamically modulates the sentence generation context in multi-layer feature maps, encoding where (i.e., attentive spatial locations at multiple layers) and what (i.e., attentive channels) the visual attention is. We evaluate the proposed SCA-CNN architecture on three benchmark image captioning datasets: Flickr8K, Flickr30K, and MSCOCO. It is consistently observed that SCA-CNN significantly outperforms state-of-the-art visual attention-based image captioning methods.

Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015

Abstract: Importance Elevated systolic blood (SBP) pressure is a leading global health risk. Quantifying the levels of SBP is important to guide prevention policies and interventions. Objective To estimate the association between SBP of at least 110 to 115 mm Hg and SBP of 140 mm Hg or higher and the burden of different causes of death and disability by age and sex for 195 countries and territories, 1990-2015. Design A comparative risk assessment of health loss related to SBP. Estimated distribution of SBP was based on 844 studies from 154 countries (published 1980-2015) of 8.69 million participants. Spatiotemporal Gaussian process regression was used to generate estimates of mean SBP and adjusted variance for each age, sex, country, and year. Diseases with sufficient evidence for a causal relationship with high SBP (eg, ischemic heart disease, ischemic stroke, and hemorrhagic stroke) were included in the primary analysis. Main Outcomes and Measures Mean SBP level, cause-specific deaths, and health burden related to SBP (≥110-115 mm Hg and also ≥140 mm Hg) by age, sex, country, and year. Results Between 1990-2015, the rate of SBP of at least 110 to 115 mm Hg increased from 73 119 (95% uncertainty interval [UI], 67 949-78 241) to 81 373 (95% UI, 76 814-85 770) per 100 000, and SBP of 140 mm Hg or higher increased from 17 307 (95% UI, 17 117-17 492) to 20 526 (95% UI, 20 283-20 746) per 100 000. The estimated annual death rate per 100 000 associated with SBP of at least 110 to 115 mm Hg increased from 135.6 (95% UI, 122.4-148.1) to 145.2 (95% UI 130.3-159.9) and the rate for SBP of 140 mm Hg or higher increased from 97.9 (95% UI, 87.5-108.1) to 106.3 (95% UI, 94.6-118.1). Loss of disability-adjusted life-years (DALYs) associated with SBP of at least 110 to 115 mm Hg increased from 148 million (95% UI, 134-162 million) to 211 million (95% UI, 193-231 million), and for SBP of 140 mm Hg or higher, the loss increased from 95.9 million (95% UI, 87.0-104.9 million) to 143.0 million (95% UI, 130.2-157.0 million). The largest numbers of SBP-related deaths were caused by ischemic heart disease (4.9 million [95% UI, 4.0-5.7 million]; 54.5%), hemorrhagic stroke (2.0 million [95% UI, 1.6-2.3 million]; 58.3%), and ischemic stroke (1.5 million [95% UI, 1.2-1.8 million]; 50.0%). In 2015, China, India, Russia, Indonesia, and the United States accounted for more than half of the global DALYs related to SBP of at least 110 to 115 mm Hg. Conclusions and Relevance In international surveys, although there is uncertainty in some estimates, the rate of elevated SBP (≥110-115 and ≥140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased. Projections based on this sample suggest that in 2015, an estimated 3.5 billion adults had SBP of at least 110 to 115 mm Hg and 874 million adults had SBP of 140 mm Hg or higher.

Ultralight scalars as cosmological dark matter

Abstract: Many aspects of the large-scale structure of the Universe can be described successfully using cosmological models in which $27\ifmmode\pm\else\textpm\fi{}1%$ of the critical mass-energy density consists of cold dark matter (CDM). However, few---if any---of the predictions of CDM models have been successful on scales of $\ensuremath{\sim}10\text{ }\text{ }\mathrm{kpc}$ or less. This lack of success is usually explained by the difficulty of modeling baryonic physics (star formation, supernova and black-hole feedback, etc.). An intriguing alternative to CDM is that the dark matter is an extremely light ($m\ensuremath{\sim}{10}^{\ensuremath{-}22}\text{ }\text{ }\mathrm{eV}$) boson having a de Broglie wavelength $\ensuremath{\lambda}\ensuremath{\sim}1\text{ }\text{ }\mathrm{kpc}$, often called fuzzy dark matter (FDM). We describe the arguments from particle physics that motivate FDM, review previous work on its astrophysical signatures, and analyze several unexplored aspects of its behavior. In particular, (i) FDM halos or subhalos smaller than about $1{0}^{7}(m/{10}^{\ensuremath{-}22}\text{ }\text{ }\mathrm{eV}{)}^{\ensuremath{-}3/2}$ ${M}_{\ensuremath{\bigodot}}$ do not form, and the abundance of halos smaller than a few times $1{0}^{10}(m/{10}^{\ensuremath{-}22}\text{ }\text{ }\mathrm{eV}{)}^{\ensuremath{-}4/3}$ ${M}_{\ensuremath{\bigodot}}$ is substantially smaller in FDM than in CDM. (ii) FDM halos are comprised of a central core that is a stationary, minimum-energy solution of the Schr\"odinger-Poisson equation, sometimes called a ``soliton,'' surrounded by an envelope that resembles a CDM halo. The soliton can produce a distinct signature in the rotation curves of FDM-dominated systems. (iii) The transition between soliton and envelope is determined by a relaxation process analogous to two-body relaxation in gravitating N-body systems, which proceeds as if the halo were composed of particles with mass $\ensuremath{\sim}\ensuremath{\rho}{\ensuremath{\lambda}}^{3}$ where $\ensuremath{\rho}$ is the halo density. (iv) Relaxation may have substantial effects on the stellar disk and bulge in the inner parts of disk galaxies, but has negligible effect on disk thickening or globular cluster disruption near the solar radius. (v) Relaxation can produce FDM disks but a FDM disk in the solar neighborhood must have a half-thickness of at least $\ensuremath{\sim}300(m/{10}^{\ensuremath{-}22}\text{ }\text{ }\mathrm{eV}{)}^{\ensuremath{-}2/3}\text{ }\text{ }\mathrm{pc}$ and a midplane density less than $0.2(m/{10}^{\ensuremath{-}22}\text{ }\text{ }\mathrm{eV}{)}^{2/3}$ times the baryonic disk density. (vi) Solitonic FDM subhalos evaporate by tunneling through the tidal radius and this limits the minimum subhalo mass inside $\ensuremath{\sim}30\text{ }\text{ }\mathrm{kpc}$ of the Milky Way to a few times $1{0}^{8}(m/{10}^{\ensuremath{-}22}\text{ }\text{ }\mathrm{eV}{)}^{\ensuremath{-}3/2}$ ${M}_{\ensuremath{\bigodot}}$. (vii) If the dark matter in the Fornax dwarf galaxy is composed of CDM, most of the globular clusters observed in that galaxy should have long ago spiraled to its center, and this problem is resolved if the dark matter is FDM. (viii) FDM delays galaxy formation relative to CDM but its galaxy-formation history is consistent with current observations of high-redshift galaxies and the late reionization observed by Planck. If the dark matter is composed of FDM, most observations favor a particle mass $\ensuremath{\gtrsim}{10}^{\ensuremath{-}22}\text{ }\text{ }\mathrm{eV}$ and the most significant observational consequences occur if the mass is in the range $1--10\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}22}\text{ }\text{ }\mathrm{eV}$. There is tension with observations of the Lyman-$\ensuremath{\alpha}$ forest, which favor $m\ensuremath{\gtrsim}10--20\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}22}\text{ }\text{ }\mathrm{eV}$ and we discuss whether more sophisticated models of reionization may resolve this tension.

Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy

Abstract: BackgroundSpinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonu...

Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis

Abstract: Enigmatic lipid peroxidation products have been claimed as the proximate executioners of ferroptosis-a specialized death program triggered by insufficiency of glutathione peroxidase 4 (GPX4). Using quantitative redox lipidomics, reverse genetics, bioinformatics and systems biology, we discovered that ferroptosis involves a highly organized oxygenation center, wherein oxidation in endoplasmic-reticulum-associated compartments occurs on only one class of phospholipids (phosphatidylethanolamines (PEs)) and is specific toward two fatty acyls-arachidonoyl (AA) and adrenoyl (AdA). Suppression of AA or AdA esterification into PE by genetic or pharmacological inhibition of acyl-CoA synthase 4 (ACSL4) acts as a specific antiferroptotic rescue pathway. Lipoxygenase (LOX) generates doubly and triply-oxygenated (15-hydroperoxy)-diacylated PE species, which act as death signals, and tocopherols and tocotrienols (vitamin E) suppress LOX and protect against ferroptosis, suggesting a homeostatic physiological role for vitamin E. This oxidative PE death pathway may also represent a target for drug discovery.

GW170608: Observation of a 19 solar-mass binary black hole coalescence

Abstract: On 2017 June 8 at 02:01:16.49 UTC, a gravitational-wave (GW) signal from the merger of two stellar-mass black holes was observed by the two Advanced Laser Interferometer Gravitational-Wave Observatory detectors with a network signal-to-noise ratio of 13. This system is the lightest black hole binary so far observed, with component masses of ${12}_{-2}^{+7}\,{M}_{\odot }$ and ${7}_{-2}^{+2}\,{M}_{\odot }$ (90% credible intervals). These lie in the range of measured black hole masses in low-mass X-ray binaries, thus allowing us to compare black holes detected through GWs with electromagnetic observations. The source's luminosity distance is ${340}_{-140}^{+140}\,\mathrm{Mpc}$, corresponding to redshift ${0.07}_{-0.03}^{+0.03}$. We verify that the signal waveform is consistent with the predictions of general relativity.

Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline

Abstract: Objective To update the "Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline," published by the Endocrine Society in 2009. Participants The participants include an Endocrine Society-appointed task force of nine experts, a methodologist, and a medical writer. Evidence This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. Consensus process Group meetings, conference calls, and e-mail communications enabled consensus. Endocrine Society committees, members and cosponsoring organizations reviewed and commented on preliminary drafts of the guidelines. Conclusion Gender affirmation is multidisciplinary treatment in which endocrinologists play an important role. Gender-dysphoric/gender-incongruent persons seek and/or are referred to endocrinologists to develop the physical characteristics of the affirmed gender. They require a safe and effective hormone regimen that will (1) suppress endogenous sex hormone secretion determined by the person's genetic/gonadal sex and (2) maintain sex hormone levels within the normal range for the person's affirmed gender. Hormone treatment is not recommended for prepubertal gender-dysphoric/gender-incongruent persons. Those clinicians who recommend gender-affirming endocrine treatments-appropriately trained diagnosing clinicians (required), a mental health provider for adolescents (required) and mental health professional for adults (recommended)-should be knowledgeable about the diagnostic criteria and criteria for gender-affirming treatment, have sufficient training and experience in assessing psychopathology, and be willing to participate in the ongoing care throughout the endocrine transition. We recommend treating gender-dysphoric/gender-incongruent adolescents who have entered puberty at Tanner Stage G2/B2 by suppression with gonadotropin-releasing hormone agonists. Clinicians may add gender-affirming hormones after a multidisciplinary team has confirmed the persistence of gender dysphoria/gender incongruence and sufficient mental capacity to give informed consent to this partially irreversible treatment. Most adolescents have this capacity by age 16 years old. We recognize that there may be compelling reasons to initiate sex hormone treatment prior to age 16 years, although there is minimal published experience treating prior to 13.5 to 14 years of age. For the care of peripubertal youths and older adolescents, we recommend that an expert multidisciplinary team comprised of medical professionals and mental health professionals manage this treatment. The treating physician must confirm the criteria for treatment used by the referring mental health practitioner and collaborate with them in decisions about gender-affirming surgery in older adolescents. For adult gender-dysphoric/gender-incongruent persons, the treating clinicians (collectively) should have expertise in transgender-specific diagnostic criteria, mental health, primary care, hormone treatment, and surgery, as needed by the patient. We suggest maintaining physiologic levels of gender-appropriate hormones and monitoring for known risks and complications. When high doses of sex steroids are required to suppress endogenous sex steroids and/or in advanced age, clinicians may consider surgically removing natal gonads along with reducing sex steroid treatment. Clinicians should monitor both transgender males (female to male) and transgender females (male to female) for reproductive organ cancer risk when surgical removal is incomplete. Additionally, clinicians should persistently monitor adverse effects of sex steroids. For gender-affirming surgeries in adults, the treating physician must collaborate with and confirm the criteria for treatment used by the referring physician. Clinicians should avoid harming individuals (via hormone treatment) who have conditions other than gender dysphoria/gender incongruence and who may not benefit from the physical changes associated with this treatment.

SemEval-2017 Task 4: Sentiment Analysis in Twitter

Abstract: This paper describes the fifth year of the Sentiment Analysis in Twitter task. SemEval-2017 Task 4 continues with a rerun of the subtasks of SemEval-2016 Task 4, which include identifying the overall sentiment of the tweet, sentiment towards a topic with classification on a two-point and on a five-point ordinal scale, and quantification of the distribution of sentiment towards a topic across a number of tweets: again on a two-point and on a five-point ordinal scale. Compared to 2016, we made two changes: (i) we introduced a new language, Arabic, for all subtasks, and (ii) we made available information from the profiles of the Twitter users who posted the target tweets. The task continues to be very popular, with a total of 48 teams participating this year.

First Dark Matter Search Results from the XENON1T Experiment

Abstract: We report the first dark matter search results from XENON1T, a ∼2000-kg-target-mass dual-phase (liquid-gas) xenon time projection chamber in operation at the Laboratori Nazionali del Gran Sasso in Italy and the first ton-scale detector of this kind The blinded search used 342 live days of data acquired between November 2016 and January 2017 Inside the (1042±12)-kg fiducial mass and in the [5,40] keVnr energy range of interest for weakly interacting massive particle (WIMP) dark matter searches, the electronic recoil background was (193±025)×10-4 events/(kg×day×keVee), the lowest ever achieved in such a dark matter detector A profile likelihood analysis shows that the data are consistent with the background-only hypothesis We derive the most stringent exclusion limits on the spin-independent WIMP-nucleon interaction cross section for WIMP masses above 10 GeV/c2, with a minimum of 77×10-47 cm2 for 35-GeV/c2 WIMPs at 90% CL

Active sites for CO2 hydrogenation to methanol on Cu/ZnO catalysts

Abstract: The active sites over commercial copper/zinc oxide/aluminum oxide (Cu/ZnO/Al2O3) catalysts for carbon dioxide (CO2) hydrogenation to methanol, the Zn-Cu bimetallic sites or ZnO-Cu interfacial sites, have recently been the subject of intense debate. We report a direct comparison between the activity of ZnCu and ZnO/Cu model catalysts for methanol synthesis. By combining x-ray photoemission spectroscopy, density functional theory, and kinetic Monte Carlo simulations, we can identify and characterize the reactivity of each catalyst. Both experimental and theoretical results agree that ZnCu undergoes surface oxidation under the reaction conditions so that surface Zn transforms into ZnO and allows ZnCu to reach the activity of ZnO/Cu with the same Zn coverage. Our results highlight a synergy of Cu and ZnO at the interface that facilitates methanol synthesis via formate intermediates.

Association analysis identifies 65 new breast cancer risk loci

Abstract: Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.