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Showing papers by "University of Texas at Austin published in 2016"


Journal ArticleDOI
Daniel J. Klionsky1, Kotb Abdelmohsen2, Akihisa Abe3, Joynal Abedin4  +2519 moreInstitutions (695)
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

5,187 citations


Journal ArticleDOI
13 Dec 2016-JAMA
TL;DR: An algorithm based on deep machine learning had high sensitivity and specificity for detecting referable diabetic retinopathy and diabetic macular edema in retinal fundus photographs from adults with diabetes.
Abstract: Importance Deep learning is a family of computational methods that allow an algorithm to program itself by learning from a large set of examples that demonstrate the desired behavior, removing the need to specify rules explicitly. Application of these methods to medical imaging requires further assessment and validation. Objective To apply deep learning to create an algorithm for automated detection of diabetic retinopathy and diabetic macular edema in retinal fundus photographs. Design and Setting A specific type of neural network optimized for image classification called a deep convolutional neural network was trained using a retrospective development data set of 128 175 retinal images, which were graded 3 to 7 times for diabetic retinopathy, diabetic macular edema, and image gradability by a panel of 54 US licensed ophthalmologists and ophthalmology senior residents between May and December 2015. The resultant algorithm was validated in January and February 2016 using 2 separate data sets, both graded by at least 7 US board-certified ophthalmologists with high intragrader consistency. Exposure Deep learning–trained algorithm. Main Outcomes and Measures The sensitivity and specificity of the algorithm for detecting referable diabetic retinopathy (RDR), defined as moderate and worse diabetic retinopathy, referable diabetic macular edema, or both, were generated based on the reference standard of the majority decision of the ophthalmologist panel. The algorithm was evaluated at 2 operating points selected from the development set, one selected for high specificity and another for high sensitivity. Results The EyePACS-1 data set consisted of 9963 images from 4997 patients (mean age, 54.4 years; 62.2% women; prevalence of RDR, 683/8878 fully gradable images [7.8%]); the Messidor-2 data set had 1748 images from 874 patients (mean age, 57.6 years; 42.6% women; prevalence of RDR, 254/1745 fully gradable images [14.6%]). For detecting RDR, the algorithm had an area under the receiver operating curve of 0.991 (95% CI, 0.988-0.993) for EyePACS-1 and 0.990 (95% CI, 0.986-0.995) for Messidor-2. Using the first operating cut point with high specificity, for EyePACS-1, the sensitivity was 90.3% (95% CI, 87.5%-92.7%) and the specificity was 98.1% (95% CI, 97.8%-98.5%). For Messidor-2, the sensitivity was 87.0% (95% CI, 81.1%-91.0%) and the specificity was 98.5% (95% CI, 97.7%-99.1%). Using a second operating point with high sensitivity in the development set, for EyePACS-1 the sensitivity was 97.5% and specificity was 93.4% and for Messidor-2 the sensitivity was 96.1% and specificity was 93.9%. Conclusions and Relevance In this evaluation of retinal fundus photographs from adults with diabetes, an algorithm based on deep machine learning had high sensitivity and specificity for detecting referable diabetic retinopathy. Further research is necessary to determine the feasibility of applying this algorithm in the clinical setting and to determine whether use of the algorithm could lead to improved care and outcomes compared with current ophthalmologic assessment.

4,810 citations


Proceedings Article
05 Dec 2016
TL;DR: This work proposes a criterion for discrimination against a specified sensitive attribute in supervised learning, where the goal is to predict some target based on available features and shows how to optimally adjust any learned predictor so as to remove discrimination according to this definition.
Abstract: We propose a criterion for discrimination against a specified sensitive attribute in supervised learning, where the goal is to predict some target based on available features. Assuming data about the predictor, target, and membership in the protected group are available, we show how to optimally adjust any learned predictor so as to remove discrimination according to our definition. Our framework also improves incentives by shifting the cost of poor classification from disadvantaged groups to the decision maker, who can respond by improving the classification accuracy. We enourage readers to consult the more complete manuscript on the arXiv.

2,690 citations


Journal ArticleDOI
TL;DR: This article provides an overview of signal processing challenges in mmWave wireless systems, with an emphasis on those faced by using MIMO communication at higher carrier frequencies.
Abstract: Communication at millimeter wave (mmWave) frequencies is defining a new era of wireless communication. The mmWave band offers higher bandwidth communication channels versus those presently used in commercial wireless systems. The applications of mmWave are immense: wireless local and personal area networks in the unlicensed band, 5G cellular systems, not to mention vehicular area networks, ad hoc networks, and wearables. Signal processing is critical for enabling the next generation of mmWave communication. Due to the use of large antenna arrays at the transmitter and receiver, combined with radio frequency and mixed signal power constraints, new multiple-input multiple-output (MIMO) communication signal processing techniques are needed. Because of the wide bandwidths, low complexity transceiver algorithms become important. There are opportunities to exploit techniques like compressed sensing for channel estimation and beamforming. This article provides an overview of signal processing challenges in mmWave wireless systems, with an emphasis on those faced by using MIMO communication at higher carrier frequencies.

2,380 citations


Journal ArticleDOI
TL;DR: In this paper, the authors used the Wide Field Camera 3 (WFC3) on the Hubble Space Telescope (HST) to reduce the uncertainty in the local value of the Hubble constant from 3.3% to 2.4%.
Abstract: We use the Wide Field Camera 3 (WFC3) on the Hubble Space Telescope (HST) to reduce the uncertainty in the local value of the Hubble constant from 3.3% to 2.4%. The bulk of this improvement comes from new near-infrared (NIR) observations of Cepheid variables in 11 host galaxies of recent type Ia supernovae (SNe Ia), more than doubling the sample of reliable SNe Ia having a Cepheid-calibrated distance to a total of 19, these in turn leverage the magnitude-redshift relation based on ∼300 SNe Ia at z < 0.15. All 19 hosts as well as the megamaser system NGC 4258 have been observed with WFC3 in the optical and NIR, thus nullifying cross-instrument zeropoint errors in the relative distance estimates from Cepheids. Other noteworthy improvements include a 33% reduction in the systematic uncertainty in the maser distance to NGC 4258, a larger sample of Cepheids in the Large Magellanic Cloud (LMC), a more robust distance to the LMC based on late-type detached eclipsing binaries (DEBs), HST observations of Cepheids in M31, and new HST-based trigonometric parallaxes for Milky Way (MW) Cepheids. We consider four geometric distance calibrations of Cepheids: (i) megamasers in NGC 4258, (ii) 8 DEBs in the LMC, (iii) 15 MW Cepheids with parallaxes measured with HST/FGS, HST/WFC3 spatial scanning and/or Hipparcos, and (iv) 2 DEBs in M31. The Hubble constant from each is 72.25 ± 2.51, 72.04 ± 2.67, 76.18 ± 2.37, and 74.50 ± 3.27 km s(−)(1) Mpc(−)(1), respectively. Our best estimate of H (0) = 73.24 ± 1.74 km s(−)(1) Mpc(−)(1) combines the anchors NGC 4258, MW, and LMC, yielding a 2.4% determination (all quoted uncertainties include fully propagated statistical and systematic components). This value is 3.4σ higher than 66.93 ± 0.62 km s(−)(1) Mpc(−)(1) predicted by ΛCDM with 3 neutrino flavors having a mass of 0.06 eV and the new Planck data, but the discrepancy reduces to 2.1σ relative to the prediction of 69.3 ± 0.7 km s(−)(1) Mpc(−)(1) based on the comparably precise combination of WMAP+ACT+SPT+BAO observations, suggesting that systematic uncertainties in CMB radiation measurements may play a role in the tension. If we take the conflict between Planck high-redshift measurements and our local determination of H (0) at face value, one plausible explanation could involve an additional source of dark radiation in the early universe in the range of ΔN (eff) ≈ 0.4–1. We anticipate further significant improvements in H (0) from upcoming parallax measurements of long-period MW Cepheids.

2,228 citations


Journal ArticleDOI
TL;DR: The American Pain Society, with input from the American Society of Anesthesiologists, developed a clinical practice guideline to promote evidence-based, effective, and safer postoperative pain management in children and adults.

1,806 citations


Journal ArticleDOI
TL;DR: New genomic data from over 1,000 uncultivated and little known organisms, together with published sequences, are used to infer a dramatically expanded version of the tree of life, with Bacteria, Archaea and Eukarya included.
Abstract: The tree of life is one of the most important organizing principles in biology1. Gene surveys suggest the existence of an enormous number of branches2, but even an approximation of the full scale of the tree has remained elusive. Recent depictions of the tree of life have focused either on the nature of deep evolutionary relationships3–5 or on the known, well-classified diversity of life with an emphasis on eukaryotes6. These approaches overlook the dramatic change in our understanding of life's diversity resulting from genomic sampling of previously unexamined environments. New methods to generate genome sequences illuminate the identity of organisms and their metabolic capacities, placing them in community and ecosystem contexts7,8. Here, we use new genomic data from over 1,000 uncultivated and little known organisms, together with published sequences, to infer a dramatically expanded version of the tree of life, with Bacteria, Archaea and Eukarya included. The depiction is both a global overview and a snapshot of the diversity within each major lineage. The results reveal the dominance of bacterial diversification and underline the importance of organisms lacking isolated representatives, with substantial evolution concentrated in a major radiation of such organisms. This tree highlights major lineages currently underrepresented in biogeochemical models and identifies radiations that are probably important for future evolutionary analyses. An update to the ‘tree of life’ has revealed a dominance of bacterial diversity in many ecosystems and extensive evolution in some branches of the tree. It also highlights how few organisms we have been able to cultivate for further investigation.

1,614 citations


Journal ArticleDOI
TL;DR: Aasld Guidelines for Treatment of Chronic Hepatitis B Norah Terrault;Natalie Bzowej;Kyong-Mi Chang;Jessica Hwang;Maureen Jonas;Hassan Murad; Hepatology

1,596 citations


Journal ArticleDOI
TL;DR: This chapter will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice, providing specific examples in relevant bacterial pathogens.
Abstract: The discovery, commercialization, and routine administration of antimicrobial compounds to treat infections revolutionized modern medicine and changed the therapeutic paradigm. Indeed, antibiotics have become one of the most important medical interventions needed for the development of complex medical approaches such as cutting-edge surgical procedures, solid organ transplantation, and management of patients with cancer, among others. Unfortunately, the marked increase in antimicrobial resistance among common bacterial pathogens is now threatening this therapeutic accomplishment, jeopardizing the successful outcomes of critically ill patients. In fact, the World Health Organization has named antibiotic resistance as one of the three most important public health threats of the 21st century ( 1 ).

1,429 citations


Journal ArticleDOI
TL;DR: G graphene doped with gold and combined with a gold mesh has improved electrochemical activity over bare graphene, sufficient to form a wearable patch for sweat-based diabetes monitoring and feedback therapy and can be thermally actuated to deliver Metformin and reduce blood glucose levels in diabetic mice.
Abstract: Owing to its high carrier mobility, conductivity, flexibility and optical transparency, graphene is a versatile material in micro- and macroelectronics. However, the low density of electrochemically active defects in graphene synthesized by chemical vapour deposition limits its application in biosensing. Here, we show that graphene doped with gold and combined with a gold mesh has improved electrochemical activity over bare graphene, sufficient to form a wearable patch for sweat-based diabetes monitoring and feedback therapy. The stretchable device features a serpentine bilayer of gold mesh and gold-doped graphene that forms an efficient electrochemical interface for the stable transfer of electrical signals. The patch consists of a heater, temperature, humidity, glucose and pH sensors and polymeric microneedles that can be thermally activated to deliver drugs transcutaneously. We show that the patch can be thermally actuated to deliver Metformin and reduce blood glucose levels in diabetic mice.

1,301 citations


Journal ArticleDOI
TL;DR: In this article, a review of the design and properties of active acoustic metamaterials can be found, as well as an overview of future directions in the field of sound manipulation.
Abstract: Acoustic metamaterials can manipulate and control sound waves in ways that are not possible in conventional materials. Metamaterials with zero, or even negative, refractive index for sound offer new possibilities for acoustic imaging and for the control of sound at subwavelength scales. The combination of transformation acoustics theory and highly anisotropic acoustic metamaterials enables precise control over the deformation of sound fields, which can be used, for example, to hide or cloak objects from incident acoustic energy. Active acoustic metamaterials use external control to create effective material properties that are not possible with passive structures and have led to the development of dynamically reconfigurable, loss-compensating and parity–time-symmetric materials for sound manipulation. Challenges remain, including the development of efficient techniques for fabricating large-scale metamaterial structures and converting laboratory experiments into useful devices. In this Review, we outline the designs and properties of materials with unusual acoustic parameters (for example, negative refractive index), discuss examples of extreme manipulation of sound and, finally, provide an overview of future directions in the field. Acoustic metamaterials can be used manipulate sound waves with a high degree of control. Their applications include acoustic imaging and cloaking. This Review outlines the designs and properties of these materials, discussing transformation acoustics theory, anisotropic materials and active acoustic metamaterials.

Journal ArticleDOI
TL;DR: This paper presents a method of using deep neural networks to learn a model for the Reynolds stress anisotropy tensor from high-fidelity simulation data and proposes a novel neural network architecture which uses a multiplicative layer with an invariant tensor basis to embed Galilean invariance into the predicted anisotropic tensor.
Abstract: There exists significant demand for improved Reynolds-averaged Navier–Stokes (RANS) turbulence models that are informed by and can represent a richer set of turbulence physics. This paper presents a method of using deep neural networks to learn a model for the Reynolds stress anisotropy tensor from high-fidelity simulation data. A novel neural network architecture is proposed which uses a multiplicative layer with an invariant tensor basis to embed Galilean invariance into the predicted anisotropy tensor. It is demonstrated that this neural network architecture provides improved prediction accuracy compared with a generic neural network architecture that does not embed this invariance property. The Reynolds stress anisotropy predictions of this invariant neural network are propagated through to the velocity field for two test cases. For both test cases, significant improvement versus baseline RANS linear eddy viscosity and nonlinear eddy viscosity models is demonstrated.

Journal ArticleDOI
TL;DR: The addition of daratumumab to lenalidomide and dexamethasone significantly lengthened progression-free survival among patients with relapsed or refractory multiple myeloma.
Abstract: BackgroundDaratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1–2 study involving patients with relapsed or refractory multiple myeloma. MethodsIn this phase 3 trial, we randomly assigned 569 patients with multiple myeloma who had received one or more previous lines of therapy to receive lenalidomide and dexamethasone either alone (control group) or in combination with daratumumab (daratumumab group). The primary end point was progression-free survival. ResultsAt a median follow-up of 13.5 months in a protocol-specified interim analysis, 169 events of disease progression or death were observed (in 53 of 286 patients [18.5%] in the daratumumab group vs. 116 of 283 [41.0%] in the control group; hazard ratio, 0.37; 95% confidence interval [CI], 0.27 to 0.52; P<0.001 by stratified log-rank test). The Kaplan–Meier rate of progression-free survival at 12 months was 83.2% (95% CI, 78.3 to 87.2) in the daratumumab group, as compared with 60.1% (95% CI, 54.0 to 65.7) in t...

Journal ArticleDOI
TL;DR: The results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.
Abstract: Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.

Journal ArticleDOI
25 Aug 2016-Nature
TL;DR: Observations reveal the presence of a small planet with a minimum mass of about 1.3 Earth masses orbiting Proxima with a period of approximately 11.2 days at a semi-major-axis distance of around 0.05 astronomical units.
Abstract: At a distance of 1.295 parsecs, the red dwarf Proxima Centauri (α Centauri C, GL 551, HIP 70890 or simply Proxima) is the Sun's closest stellar neighbour and one of the best-studied low-mass stars. It has an effective temperature of only around 3,050 kelvin, a luminosity of 0.15 per cent of that of the Sun, a measured radius of 14 per cent of the radius of the Sun and a mass of about 12 per cent of the mass of the Sun. Although Proxima is considered a moderately active star, its rotation period is about 83 days (ref. 3) and its quiescent activity levels and X-ray luminosity are comparable to those of the Sun. Here we report observations that reveal the presence of a small planet with a minimum mass of about 1.3 Earth masses orbiting Proxima with a period of approximately 11.2 days at a semi-major-axis distance of around 0.05 astronomical units. Its equilibrium temperature is within the range where water could be liquid on its surface.

Journal ArticleDOI
TL;DR: The authors survey institutional investors to understand their role in the corporate governance of firms and find that most investors use proxy advisors and believe that the information provided by such advisors improves their own voting decisions.
Abstract: We survey institutional investors to better understand their role in the corporate governance of firms. Consistent with a number of theories, we document widespread behind-the-scenes intervention as well as governance-motivated exit. These governance mechanisms are viewed as complementary devices, with intervention typically occurring prior to a potential exit. We further find that long-term investors and investors that are less concerned about stock liquidity intervene more intensively. Finally, we find that most investors use proxy advisors and believe that the information provided by such advisors improves their own voting decisions.

Journal ArticleDOI
11 Nov 2016
TL;DR: This work proposes a novel active learning method capable of enriching massive geometric datasets with accurate semantic region annotations, and demonstrates that incorporating verification of all produced labelings within this unified objective improves both accuracy and efficiency of the active learning procedure.
Abstract: Large repositories of 3D shapes provide valuable input for data-driven analysis and modeling tools. They are especially powerful once annotated with semantic information such as salient regions and functional parts. We propose a novel active learning method capable of enriching massive geometric datasets with accurate semantic region annotations. Given a shape collection and a user-specified region label our goal is to correctly demarcate the corresponding regions with minimal manual work. Our active framework achieves this goal by cycling between manually annotating the regions, automatically propagating these annotations across the rest of the shapes, manually verifying both human and automatic annotations, and learning from the verification results to improve the automatic propagation algorithm. We use a unified utility function that explicitly models the time cost of human input across all steps of our method. This allows us to jointly optimize for the set of models to annotate and for the set of models to verify based on the predicted impact of these actions on the human efficiency. We demonstrate that incorporating verification of all produced labelings within this unified objective improves both accuracy and efficiency of the active learning procedure. We automatically propagate human labels across a dynamic shape network using a conditional random field (CRF) framework, taking advantage of global shape-to-shape similarities, local feature similarities, and point-to-point correspondences. By combining these diverse cues we achieve higher accuracy than existing alternatives. We validate our framework on existing benchmarks demonstrating it to be significantly more efficient at using human input compared to previous techniques. We further validate its efficiency and robustness by annotating a massive shape dataset, labeling over 93,000 shape parts, across multiple model classes, and providing a labeled part collection more than one order of magnitude larger than existing ones.

Journal ArticleDOI
TL;DR: Li-rich layered oxides have attracted much research interest as cathodes for Li-ion batteries due to their low cost and higher discharge capacities compared to those of LiCoO2 and LiMn2O4 as mentioned in this paper.
Abstract: Ni-rich layered oxides and Li-rich layered oxides are topics of much research interest as cathodes for Li-ion batteries due to their low cost and higher discharge capacities compared to those of LiCoO2 and LiMn2O4. However, Ni-rich layered oxides have several pitfalls, including difficulty in synthesizing a well-ordered material with all Ni3+ ions, poor cyclability, moisture sensitivity, a thermal runaway reaction, and formation of a harmful surface layer caused by side reactions with the electrolyte. Recent efforts towards Ni-rich layered oxides have centered on optimizing the composition and processing conditions to obtain controlled bulk and surface compositions to overcome the capacity fade. Li-rich layered oxides also have negative aspects, including oxygen loss from the lattice during first charge, a large first cycle irreversible capacity loss, poor rate capability, side reactions with the electrolyte, low tap density, and voltage decay during extended cycling. Recent work on Li-rich layered oxides has focused on understanding the surface and bulk structures and eliminating the undesirable properties. Followed by a brief introduction, an account of recent developments on the understanding and performance gains of Ni-rich and Li-rich layered oxide cathodes is provided, along with future research directions.

Journal ArticleDOI
TL;DR: In this paper, the authors combined satellite-based estimates, chemical transport model simulations, and ground measurements from 79 different countries to produce global estimates of annual average fine particle (PM2.5) and ozone concentrations at 0.1° × 0. 1° spatial resolution for five-year intervals from 1990 to 2010 and the year 2013.
Abstract: Exposure to ambient air pollution is a major risk factor for global disease. Assessment of the impacts of air pollution on population health and evaluation of trends relative to other major risk factors requires regularly updated, accurate, spatially resolved exposure estimates. We combined satellite-based estimates, chemical transport model simulations, and ground measurements from 79 different countries to produce global estimates of annual average fine particle (PM2.5) and ozone concentrations at 0.1° × 0.1° spatial resolution for five-year intervals from 1990 to 2010 and the year 2013. These estimates were applied to assess population-weighted mean concentrations for 1990-2013 for each of 188 countries. In 2013, 87% of the world's population lived in areas exceeding the World Health Organization Air Quality Guideline of 10 μg/m(3) PM2.5 (annual average). Between 1990 and 2013, global population-weighted PM2.5 increased by 20.4% driven by trends in South Asia, Southeast Asia, and China. Decreases in population-weighted mean concentrations of PM2.5 were evident in most high income countries. Population-weighted mean concentrations of ozone increased globally by 8.9% from 1990-2013 with increases in most countries-except for modest decreases in North America, parts of Europe, and several countries in Southeast Asia.

Journal ArticleDOI
TL;DR: In this article, a detailed discussion of the unobserved heterogeneity in highway accident data and analysis is presented along with their strengths and weaknesses, as well as a summary of the fundamental issues and directions for future methodological work that address this problem.

Journal ArticleDOI
TL;DR: TAVR with SAPIEN 3 in intermediate-risk patients with severe aortic stenosis is associated with low mortality, strokes, and regurgitation at 1 year after implantation, and a significant superiority for the composite outcome with TAVR compared with surgery is indicated.

Journal ArticleDOI
TL;DR: The authors deployed the reconfigurable fabric in a bed of 1,632 servers and FPGAs in a production datacenter and successfully used it to accelerate the ranking portion of the Bing Web search engine by nearly a factor of two.
Abstract: Datacenter workloads demand high computational capabilities, flexibility, power efficiency, and low cost It is challenging to improve all of these factors simultaneously To advance datacenter capabilities beyond what commodity server designs can provide, we designed and built a composable, reconfigurable hardware fabric based on field programmable gate arrays (FPGA) Each server in the fabric contains one FPGA, and all FPGAs within a 48-server rack are interconnected over a low-latency, high-bandwidth networkWe describe a medium-scale deployment of this fabric on a bed of 1632 servers, and measure its effectiveness in accelerating the ranking component of the Bing web search engine We describe the requirements and architecture of the system, detail the critical engineering challenges and solutions needed to make the system robust in the presence of failures, and measure the performance, power, and resilience of the system Under high load, the large-scale reconfigurable fabric improves the ranking throughput of each server by 95% at a desirable latency distribution or reduces tail latency by 29% at a fixed throughput In other words, the reconfigurable fabric enables the same throughput using only half the number of servers

Journal ArticleDOI
15 Nov 2016-JAMA
TL;DR: A restrictive RBC transfusion threshold is safe in most clinical settings and the current blood banking practices of using standard-issue blood should be continued.
Abstract: Importance More than 100 million units of blood are collected worldwide each year, yet the indication for red blood cell (RBC) transfusion and the optimal length of RBC storage prior to transfusion are uncertain. Objective To provide recommendations for the target hemoglobin level for RBC transfusion among hospitalized adult patients who are hemodynamically stable and the length of time RBCs should be stored prior to transfusion. Evidence Review Reference librarians conducted a literature search for randomized clinical trials (RCTs) evaluating hemoglobin thresholds for RBC transfusion (1950-May 2016) and RBC storage duration (1948-May 2016) without language restrictions. The results were summarized using the Grading of Recommendations Assessment, Development and Evaluation method. For RBC transfusion thresholds, 31 RCTs included 12 587 participants and compared restrictive thresholds (transfusion not indicated until the hemoglobin level is 7-8 g/dL) with liberal thresholds (transfusion not indicated until the hemoglobin level is 9-10 g/dL). The summary estimates across trials demonstrated that restrictive RBC transfusion thresholds were not associated with higher rates of adverse clinical outcomes, including 30-day mortality, myocardial infarction, cerebrovascular accident, rebleeding, pneumonia, or thromboembolism. For RBC storage duration, 13 RCTs included 5515 participants randomly allocated to receive fresher blood or standard-issue blood. These RCTs demonstrated that fresher blood did not improve clinical outcomes. Findings It is good practice to consider the hemoglobin level, the overall clinical context, patient preferences, and alternative therapies when making transfusion decisions regarding an individual patient. Recommendation 1: a restrictive RBC transfusion threshold in which the transfusion is not indicated until the hemoglobin level is 7 g/dL is recommended for hospitalized adult patients who are hemodynamically stable, including critically ill patients, rather than when the hemoglobin level is 10 g/dL (strong recommendation, moderate quality evidence). A restrictive RBC transfusion threshold of 8 g/dL is recommended for patients undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease (strong recommendation, moderate quality evidence). The restrictive transfusion threshold of 7 g/dL is likely comparable with 8 g/dL, but RCT evidence is not available for all patient categories. These recommendations do not apply to patients with acute coronary syndrome, severe thrombocytopenia (patients treated for hematological or oncological reasons who are at risk of bleeding), and chronic transfusion–dependent anemia (not recommended due to insufficient evidence). Recommendation 2: patients, including neonates, should receive RBC units selected at any point within their licensed dating period (standard issue) rather than limiting patients to transfusion of only fresh (storage length: Conclusions and Relevance Research in RBC transfusion medicine has significantly advanced the science in recent years and provides high-quality evidence to inform guidelines. A restrictive transfusion threshold is safe in most clinical settings and the current blood banking practices of using standard-issue blood should be continued.

Journal ArticleDOI
TL;DR: A cross-linked polymer containing pendant molecules attached to the polymer framework is shown to form flexible and low-cost membranes, and all-solid-state Li/LiFePO4 cells showed a notably high Coulombic efficiency of 99.8-100% over 640 cycles.
Abstract: A cross-linked polymer containing pendant molecules attached to the polymer framework is shown to form flexible and low-cost membranes, to be a solid Li+ electrolyte up to 270 °C, much higher than those based on poly(ethylene oxide), to be wetted by a metallic lithium anode, and to be not decomposed by the metallic anode if the anions of the salt are blocked by a ceramic electrolyte in a polymer/ceramic membrane/polymer sandwich electrolyte (PCPSE). In this sandwich architecture, the double-layer electric field at the Li/polymer interface is reduced due to the blocked salt anion transfer. The polymer layer adheres/wets the lithium metal surface and makes the Li-ion flux at the interface more homogeneous. This structure integrates the advantages of the ceramic and polymer. With the PCPSE, all-solid-state Li/LiFePO4 cells showed a notably high Coulombic efficiency of 99.8–100% over 640 cycles.

Journal ArticleDOI
Adam M. Session1, Adam M. Session2, Yoshinobu Uno3, Taejoon Kwon4, Taejoon Kwon5, Jarrod Chapman2, Atsushi Toyoda6, Shuji Takahashi7, Akimasa Fukui8, Akira Hikosaka7, Atsushi Suzuki7, Mariko Kondo9, Simon J. van Heeringen10, Ian K. Quigley11, Sven Heinz11, Hajime Ogino12, Haruki Ochi13, Uffe Hellsten2, Jessica B. Lyons1, Oleg Simakov14, Nicholas H. Putnam, Jonathan C. Stites, Yoko Kuroki, Toshiaki Tanaka15, Tatsuo Michiue9, Minoru Watanabe16, Ozren Bogdanovic17, Ryan Lister17, Georgios Georgiou10, Sarita S. Paranjpe10, Ila van Kruijsbergen10, Shengquiang Shu2, Joseph W. Carlson2, Tsutomu Kinoshita18, Yuko Ohta19, Shuuji Mawaribuchi20, Jerry Jenkins2, Jane Grimwood2, Jeremy Schmutz2, Therese Mitros1, Sahar V. Mozaffari21, Yutaka Suzuki9, Yoshikazu Haramoto22, Takamasa S. Yamamoto23, Chiyo Takagi23, Rebecca Heald1, Kelly E. Miller1, Christian D. Haudenschild24, Jacob O. Kitzman25, Takuya Nakayama26, Yumi Izutsu27, Jacques Robert28, Joshua D. Fortriede29, Kevin A. Burns, Vaneet Lotay30, Kamran Karimi30, Yuuri Yasuoka14, Darwin S. Dichmann1, Martin F. Flajnik19, Douglas W. Houston31, Jay Shendure25, Louis DuPasquier32, Peter D. Vize30, Aaron M. Zorn29, Michihiko Ito20, Edward M. Marcotte5, John B. Wallingford5, Yuzuru Ito22, Makoto Asashima22, Naoto Ueno23, Naoto Ueno33, Yoichi Matsuda3, Gert Jan C. Veenstra10, Asao Fujiyama33, Asao Fujiyama34, Asao Fujiyama6, Richard M. Harland1, Masanori Taira9, Daniel S. Rokhsar2, Daniel S. Rokhsar14, Daniel S. Rokhsar1 
20 Oct 2016-Nature
TL;DR: The Xenopus laevis genome is sequenced and it is estimated that the two diploid progenitor species diverged around 34 million years ago and combined to form an allotetraploid around 17–18 Ma, where more than 56% of all genes were retained in two homoeologous copies.
Abstract: To explore the origins and consequences of tetraploidy in the African clawed frog, we sequenced the Xenopus laevis genome and compared it to the related diploid X. tropicalis genome. We characterize the allotetraploid origin of X. laevis by partitioning its genome into two homoeologous subgenomes, marked by distinct families of 'fossil' transposable elements. On the basis of the activity of these elements and the age of hundreds of unitary pseudogenes, we estimate that the two diploid progenitor species diverged around 34 million years ago (Ma) and combined to form an allotetraploid around 17-18 Ma. More than 56% of all genes were retained in two homoeologous copies. Protein function, gene expression, and the amount of conserved flanking sequence all correlate with retention rates. The subgenomes have evolved asymmetrically, with one chromosome set more often preserving the ancestral state and the other experiencing more gene loss, deletion, rearrangement, and reduced gene expression.

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TL;DR: In this paper, the authors consolidate and review the progress of the research field towards methods and tools of forecasting natural disaster related power system disturbances, hardening and pre-storm operations, and restoration models.
Abstract: Natural disasters can cause large blackouts. Research into natural disaster impacts on electric power systems is emerging to understand the causes of the blackouts, explore ways to prepare and harden the grid, and increase the resilience of the power grid under such events. At the same time, new technologies such as smart grid, micro grid, and wide area monitoring applications could increase situational awareness as well as enable faster restoration of the system. This paper aims to consolidate and review the progress of the research field towards methods and tools of forecasting natural disaster related power system disturbances, hardening and pre-storm operations, and restoration models. Challenges and future research opportunities are also presented in the paper.

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TL;DR: This paper proposes a successive interference cancelation (SIC)-based hybrid precoding with near-optimal performance and low complexity, and proposes a low-complexity algorithm to realize SIC-based Hybrid precoding, which can avoid the need for the singular value decomposition and matrix inversion.
Abstract: Millimeter wave (mmWave) MIMO will likely use hybrid analog and digital precoding, which uses a small number of RF chains to reduce the energy consumption associated with mixed signal components like analog-to-digital components not to mention baseband processing complexity. However, most hybrid precoding techniques consider a fully connected architecture requiring a large number of phase shifters, which is also energy-intensive. In this paper, we focus on the more energy-efficient hybrid precoding with subconnected architecture, and propose a successive interference cancelation (SIC)-based hybrid precoding with near-optimal performance and low complexity. Inspired by the idea of SIC for multiuser signal detection, we first propose to decompose the total achievable rate optimization problem with nonconvex constraints into a series of simple subrate optimization problems, each of which only considers one subantenna array. Then, we prove that maximizing the achievable subrate of each subantenna array is equivalent to simply seeking a precoding vector sufficiently close (in terms of Euclidean distance) to the unconstrained optimal solution. Finally, we propose a low-complexity algorithm to realize SIC-based hybrid precoding, which can avoid the need for the singular value decomposition (SVD) and matrix inversion. Complexity evaluation shows that the complexity of SIC-based hybrid precoding is only about 10% as complex as that of the recently proposed spatially sparse precoding in typical mmWave MIMO systems. Simulation results verify that SIC-based hybrid precoding is near-optimal and enjoys higher energy efficiency than the spatially sparse precoding and the fully digital precoding.

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TL;DR: This work attempts to rationalize the high activities of La1−xSrxCoO3−δ through the electronic structure and participation of lattice oxygen in the mechanism of water electrolysis as revealed through ab initio modelling.
Abstract: Perovskite oxides are attractive candidates as catalysts for the electrolysis of water in alkaline energy storage and conversion systems. However, the rational design of active catalysts has been hampered by the lack of understanding of the mechanism of water electrolysis on perovskite surfaces. Key parameters that have been overlooked include the role of oxygen vacancies, B-O bond covalency, and redox activity of lattice oxygen species. Here we present a series of cobaltite perovskites where the covalency of the Co-O bond and the concentration of oxygen vacancies are controlled through Sr(2+) substitution into La(1-x)Sr(x)CoO(3-δ) . We attempt to rationalize the high activities of La(1-x)Sr(x)CoO(3-δ) through the electronic structure and participation of lattice oxygen in the mechanism of water electrolysis as revealed through ab initio modelling. Using this approach, we report a material, SrCoO2.7, with a high, room temperature-specific activity and mass activity towards alkaline water electrolysis.

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TL;DR: An overview of the contemporary context for LGBT youth is provided, followed by a review of current science on LGBT youth mental health, which point to promising directions for prevention, intervention, and treatment.
Abstract: Today's lesbian, gay, bisexual, and transgender (LGBT) youth come out at younger ages, and public support for LGBT issues has dramatically increased, so why do LGBT youth continue to be at high risk for compromised mental health? We provide an overview of the contemporary context for LGBT youth, followed by a review of current science on LGBT youth mental health. Research in the past decade has identified risk and protective factors for mental health, which point to promising directions for prevention, intervention, and treatment. Legal and policy successes have set the stage for advances in programs and practices that may foster LGBT youth mental health. Implications for clinical care are discussed, and important areas for new research and practice are identified.

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University of Utah1, University of Colorado Boulder2, Stanford University3, Oregon Health & Science University4, University of Chicago5, Rush University Medical Center6, University of Barcelona7, Harvard University8, Vanderbilt University9, University of Arizona10, University of Texas Health Science Center at Houston11, University of Pennsylvania12, Emory University13, Université de Montréal14, Samsung Medical Center15, University of Auckland16, University of Pittsburgh17, University of Amsterdam18, University of Ioannina19, University of California, San Francisco20, Eastern Virginia Medical School21, University of New South Wales22, Katholieke Universiteit Leuven23, Guy's and St Thomas' NHS Foundation Trust24, University of Lorraine25, University of British Columbia26, Northwestern University27, Georgia Regents University28, Johns Hopkins University29, New York University30, Korea University31, University of Texas at Austin32, Uniformed Services University of the Health Sciences33, Jikei University School of Medicine34, University of Washington35, University of Siena36, Medical College of Wisconsin37, University of Adelaide38, West Virginia University39, Innsbruck Medical University40, Pusan National University41, University of Calgary42, Medical University of South Carolina43, University of North Carolina at Chapel Hill44, Cleveland Clinic45, Loyola University Chicago46, Cornell University47, Temple University48, University of São Paulo49, National University of Singapore50, San Antonio Military Medical Center51, University of Alabama at Birmingham52, University of Alberta53, Capital Medical University54
TL;DR: This dissertation aims to provide a history of Chinese medical practice in the United States from 1989 to 2002, a period chosen in order to explore its roots as well as specific cases up to and including the year in which descriptions of “modern China” began to circulate.
Abstract: Background The body of knowledge regarding rhinosinusitis(RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS). Methods Evidence-based reviews with recommendations(EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR)was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus. Results The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS)with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AECRS), and pediatric RS. Conclusion As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too often the foundation upon which these recommendations are based is comprised of lower level evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed.