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Journal ArticleDOI
TL;DR: In this article, the idea of a topological charge pump with topologically protected transport has been realized with ultracold bosonic atoms, where the quantized motion of charge due to the slow cyclic variation of a periodic potential has been quantized.
Abstract: Thouless introduced the idea of a topological charge pump: the quantized motion of charge due to the slow cyclic variation of a periodic potential. This topologically protected transport has now been realized with ultracold bosonic atoms.

556 citations


Journal ArticleDOI
TL;DR: It is shown that the helicity of the optical transition of a quantum emitter determines the direction of single-photon emission in a specially engineered photonic-crystal waveguide.
Abstract: Engineering photon emission and scattering is central to modern photonics applications ranging from light harvesting to quantum-information processing. To this end, nanophotonic waveguides are well suited as they confine photons to a one-dimensional geometry and thereby increase the light-matter interaction. In a regular waveguide, a quantum emitter interacts equally with photons in either of the two propagation directions. This symmetry is violated in nanophotonic structures in which non-transversal local electric-field components imply that photon emission and scattering may become directional. Here we show that the helicity of the optical transition of a quantum emitter determines the direction of single-photon emission in a specially engineered photonic-crystal waveguide. We observe single-photon emission into the waveguide with a directionality that exceeds 90% under conditions in which practically all the emitted photons are coupled to the waveguide. The chiral light-matter interaction enables deterministic and highly directional photon emission for experimentally achievable on-chip non-reciprocal photonic elements. These may serve as key building blocks for single-photon optical diodes, transistors and deterministic quantum gates. Furthermore, chiral photonic circuits allow the dissipative preparation of entangled states of multiple emitters for experimentally achievable parameters, may lead to novel topological photon states and could be applied for directional steering of light.

556 citations


Journal ArticleDOI
TL;DR: Global trends in female breast cancer rates are decreasing in most high-income countries, despite increasing or stable incidence rates, and the increasing incidence and mortality rates in a number of countries are of concern, particularly those undergoing rapid changes in human development.
Abstract: Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related death among women worldwide. Herein, we examine global trends in female breast cancer rates using the most up-to-date data available. Methods: Breast cancer incidence and mortality estimates were obtained from GLOBOCAN 2012 (globocan.iarc.fr). We analyzed trends from 1993 onward using incidence data from 39 countries from the International Agency for Research on Cancer and mortality data from 57 countries from the World Health Organization. Results: Of 32 countries with incidence and mortality data, rates in the recent period diverged—with incidence increasing and mortality decreasing—in nine countries mainly in Northern/Western Europe. Both incidence and mortality decreased in France, Israel, Italy, Norway, and Spain. In contrast, incidence and death rates both increased in Colombia, Ecuador, and Japan. Death rates also increased in Brazil, Egypt, Guatemala, Kuwait, Mauritius, Mexico, and Moldova. Conclusions: Breast cancer mortality rates are decreasing in most high-income countries, despite increasing or stable incidence rates. In contrast and of concern are the increasing incidence and mortality rates in a number of countries, particularly those undergoing rapid changes in human development. Wide variations in breast cancer rates and trends reflect differences in patterns of risk factors and access to and availability of early detection and timely treatment. Impact: Increased awareness about breast cancer and the benefits of early detection and improved access to treatment must be prioritized to successfully implement breast cancer control programs, particularly in transitioning countries. Cancer Epidemiol Biomarkers Prev; 24(10); 1495–506. ©2015 AACR .

556 citations


Journal ArticleDOI
TL;DR: ADT is often a necessary component of the treatment of aggressive prostate cancer, yet it has known harms that can impair health and quality of life.

556 citations


Journal ArticleDOI
07 May 2015-Cell
TL;DR: Lymphocyte isolation fails to recover most cells and biases against certain subsets, residents greatly outnumber recirculating cells within non-lymphoid tissues, and memory subset homing to inflammation does not conform to previously hypothesized migration patterns.

556 citations


Journal ArticleDOI
TL;DR: Evidence presented here suggests that the systemic insecticides, neonicotinoids and fipronil, are capable of exerting direct and indirect effects on terrestrial and aquatic vertebrate wildlife, thus warranting further review of their environmental safety.
Abstract: Concerns over the role of pesticides affecting vertebrate wildlife populations have recently focussed on systemic products which exert broad-spectrum toxicity. Given that the neonicotinoids have become the fastest-growing class of insecticides globally, we review here 150 studies of their direct (toxic) and indirect (e.g. food chain) effects on vertebrate wildlife—mammals, birds, fish, amphibians and reptiles. We focus on two neonicotinoids, imidacloprid and clothianidin, and a third insecticide, fipronil, which also acts in the same systemic manner. Imidacloprid and fipronil were found to be toxic to many birds and most fish, respectively. All three insecticides exert sub-lethal effects, ranging from genotoxic and cytotoxic effects, and impaired immune function, to reduced growth and reproductive success, often at concentrations well below those associated with mortality. Use of imidacloprid and clothianidin as seed treatments on some crops poses risks to small birds, and ingestion of even a few treated seeds could cause mortality or reproductive impairment to sensitive bird species. In contrast, environmental concentrations of imidacloprid and clothianidin appear to be at levels below those which will cause mortality to freshwater vertebrates, although sub-lethal effects may occur. Some recorded environmental concentrations of fipronil, however, may be sufficiently high to harm fish. Indirect effects are rarely considered in risk assessment processes and there is a paucity of data, despite the potential to exert population-level effects. Our research revealed two field case studies of indirect effects. In one, reductions in invertebrate prey from both imidacloprid and fipronil uses led to impaired growth in a fish species, and in another, reductions in populations in two lizard species were linked to effects of fipronil on termite prey. Evidence presented here suggests that the systemic insecticides, neonicotinoids and fipronil, are capable of exerting direct and indirect effects on terrestrial and aquatic vertebrate wildlife, thus warranting further review of their environmental safety.

556 citations


Journal ArticleDOI
TL;DR: This work shows that inflammasomes are activated in response to SARS-CoV-2 infection in vitro and in COVID-19 patients, contributing to the exacerbated inflammatory response, impacting disease progression and clinical outcome.
Abstract: Severe cases of COVID-19 are characterized by a strong inflammatory process that may ultimately lead to organ failure and patient death. The NLRP3 inflammasome is a molecular platform that promotes inflammation via cleavage and activation of key inflammatory molecules including active caspase-1 (Casp1p20), IL-1β, and IL-18. Although participation of the inflammasome in COVID-19 has been highly speculated, the inflammasome activation and participation in the outcome of the disease are unknown. Here we demonstrate that the NLRP3 inflammasome is activated in response to SARS-CoV-2 infection and is active in COVID-19 patients. Studying moderate and severe COVID-19 patients, we found active NLRP3 inflammasome in PBMCs and tissues of postmortem patients upon autopsy. Inflammasome-derived products such as Casp1p20 and IL-18 in the sera correlated with the markers of COVID-19 severity, including IL-6 and LDH. Moreover, higher levels of IL-18 and Casp1p20 are associated with disease severity and poor clinical outcome. Our results suggest that inflammasomes participate in the pathophysiology of the disease, indicating that these platforms might be a marker of disease severity and a potential therapeutic target for COVID-19.

556 citations


Proceedings ArticleDOI
01 Jul 2017
TL;DR: Wang et al. as mentioned in this paper proposed to use deep convolutional neural networks to learn long-term temporal information of the skeleton sequence from the frames of the generated clips, and then use a Multi-Task Learning Network (MTLN) to jointly process all frames in parallel to incorporate spatial structural information for action recognition.
Abstract: This paper presents a new method for 3D action recognition with skeleton sequences (i.e., 3D trajectories of human skeleton joints). The proposed method first transforms each skeleton sequence into three clips each consisting of several frames for spatial temporal feature learning using deep neural networks. Each clip is generated from one channel of the cylindrical coordinates of the skeleton sequence. Each frame of the generated clips represents the temporal information of the entire skeleton sequence, and incorporates one particular spatial relationship between the joints. The entire clips include multiple frames with different spatial relationships, which provide useful spatial structural information of the human skeleton. We propose to use deep convolutional neural networks to learn long-term temporal information of the skeleton sequence from the frames of the generated clips, and then use a Multi-Task Learning Network (MTLN) to jointly process all frames of the clips in parallel to incorporate spatial structural information for action recognition. Experimental results clearly show the effectiveness of the proposed new representation and feature learning method for 3D action recognition.

556 citations


Journal ArticleDOI
TL;DR: Patients with type 2 diabetes who had been randomly assigned to intensive glucose control for 5.6 years had 8.6 fewer major cardiovascular events per 1000 person-years than those assigned to standard therapy, but no improvement was seen in the rate of overall survival.
Abstract: BackgroundThe Veterans Affairs Diabetes Trial previously showed that intensive glucose lowering, as compared with standard therapy, did not significantly reduce the rate of major cardiovascular events among 1791 military veterans (median follow-up, 5.6 years). We report the extended follow-up of the study participants. MethodsAfter the conclusion of the clinical trial, we followed participants, using central databases to identify procedures, hospitalizations, and deaths (complete cohort, with follow-up data for 92.4% of participants). Most participants agreed to additional data collection by means of annual surveys and periodic chart reviews (survey cohort, with 77.7% follow-up). The primary outcome was the time to the first major cardiovascular event (heart attack, stroke, new or worsening congestive heart failure, amputation for ischemic gangrene, or cardiovascular-related death). Secondary outcomes were cardiovascular mortality and all-cause mortality. ResultsThe difference in glycated hemoglobin level...

556 citations


Journal Article
TL;DR: This work investigates how to leverage abundant monolingual corpora for neural machine translation to improve results for En-Fr and En-De translation and extends to high resource languages such as Cs-En and De-En.
Abstract: Recent work on end-to-end neural network-based architectures for machine translation has shown promising results for En-Fr and En-De translation. Arguably, one of the major factors behind this success has been the availability of high quality parallel corpora. In this work, we investigate how to leverage abundant monolingual corpora for neural machine translation. Compared to a phrase-based and hierarchical baseline, we obtain up to $1.96$ BLEU improvement on the low-resource language pair Turkish-English, and $1.59$ BLEU on the focused domain task of Chinese-English chat messages. While our method was initially targeted toward such tasks with less parallel data, we show that it also extends to high resource languages such as Cs-En and De-En where we obtain an improvement of $0.39$ and $0.47$ BLEU scores over the neural machine translation baselines, respectively.

556 citations


Journal ArticleDOI
TL;DR: Wang et al. as mentioned in this paper investigated the relationship between the transmissibility of COVID-19 and the temperature/humidity, by controlling for various demographic, socioeconomic, geographic, healthcare and policy factors and correcting for cross-sectional correlation.
Abstract: With the ongoing global pandemic of COVID-19, a question is whether the coming summer in the northern hemisphere will reduce the transmission intensity of COVID-19 with increased humidity and temperature. In this paper, we investigate this problem using the data from the cases with symptom-onset dates from January 19 to February 10, 2020 for 100 Chinese cities, and cases with confirmed dates from March 15 to April 25 for 1,005 U.S. counties. Statistical analysis is performed to assess the relationship between the transmissibility of COVID-19 and the temperature/humidity, by controlling for various demographic, socio-economic, geographic, healthcare and policy factors and correcting for cross-sectional correlation. We find a similar influence of the temperature and relative humidity on effective reproductive number (R values) of COVID-19 for both China and the U.S. before lockdown in both countries: one-degree Celsius increase in temperature reduces R value by about 0.023 (0.026 (95% CI [-0.0395,-0.0125]) in China and 0.020 (95% CI [-0.0311, -0.0096]) in the U.S.), and one percent relative humidity rise reduces R value by 0.0078 (0.0076 (95% CI [-0.0108,-0.0045]) in China and 0.0080 (95% CI [-0.0150,-0.0010]) in the U.S.). If assuming a 30 degree and 25 percent increase in temperature and relative humidity from winter to summer in the northern hemisphere, we expect the R values to decline about 0.89 (0.69 by temperature and 0.20 by humidity). Moreover, after the lockdowns in China and the U.S., temperature and relative humidity still play an important role in reducing the R values but to a less extent. Given the notion that the non-intervened R values are around 2.5 to 3, only weather factors cannot make the R values below their critical condition of R<1, under which the epidemic diminishes gradually. Therefore, public health intervention such as social distancing is crucial to block the transmission of COVID-19 even in summer.

Journal ArticleDOI
TL;DR: Object-based time-weighted dynamic time warping (TWDTW) method achieved comparable classification results to RF in Romania and Italy, but RF achieved better results in the USA, where the classified crops present high intra-class spectral variability.

Proceedings Article
11 Nov 2016
TL;DR: This work considers jointly learning the goal-driven reinforcement learning problem with auxiliary depth prediction and loop closure classification tasks and shows that data efficiency and task performance can be dramatically improved by relying on additional auxiliary tasks leveraging multimodal sensory inputs.
Abstract: Learning to navigate in complex environments with dynamic elements is an important milestone in developing AI agents. In this work we formulate the navigation question as a reinforcement learning problem and show that data efficiency and task performance can be dramatically improved by relying on additional auxiliary tasks leveraging multimodal sensory inputs. In particular we consider jointly learning the goal-driven reinforcement learning problem with auxiliary depth prediction and loop closure classification tasks. This approach can learn to navigate from raw sensory input in complicated 3D mazes, approaching human-level performance even under conditions where the goal location changes frequently. We provide detailed analysis of the agent behaviour, its ability to localise, and its network activity dynamics, showing that the agent implicitly learns key navigation abilities.

Posted ContentDOI
15 Jun 2015-bioRxiv
TL;DR: A new methodology to analyze single-cell transcriptomic data is presented that models this bimodality within a coherent generalized linear modeling framework, and the cellular detection rate, the fraction of genes turned on in a cell, is introduced.
Abstract: Single-cell transcriptomic profiling enables the unprecedented interrogation of gene expression heterogeneity in rare cell populations that would otherwise be obscured in bulk RNA sequencing experiments. The stochastic nature of transcription is revealed in the bimodality of single-cell transcriptomic data, a feature shared across single-cell expression platforms. There is, however, a paucity of computational tools that take advantage of this unique characteristic. We present a new methodology to analyze single-cell transcriptomic data that models this bimodality within a coherent generalized linear modeling framework. We propose a two-part, generalized linear model that allows one to characterize biological changes in the proportions of cells that are expressing each gene, and in the positive mean expression level of that gene. We introduce the cellular detection rate, the fraction of genes turned on in a cell, and show how it can be used to simultaneously adjust for technical variation and so-called “extrinsic noise” at the single-cell level without the use of control genes. Our model permits direct inference on statistics formed by collections of genes, facilitating gene set enrichment analysis. The residuals defined by such models can be manipulated to interrogate cellular heterogeneity and gene-gene correlation across cells and conditions, providing insights into the temporal evolution of networks of co-expressed genes at the single-cell level. Using two single-cell RNA-seq datasets, including newly generated data from Mucosal Associated Invariant T (MAIT) cells, we show how model residuals can be used to identify significant changes across biologically relevant gene sets that are missed by other methods and characterize cellular heterogeneity in response to stimulation.

Proceedings ArticleDOI
16 May 2015
TL;DR: IccTA, a static taint analyzer to detect privacy leaks among components in Android applications goes beyond state-of-the-art approaches by supporting inter- component detection and propagating context information among components, which improves the precision of the analysis.
Abstract: Shake Them All is a popular "Wallpaper" application exceeding millions of downloads on Google Play. At installation, this application is given permission to (1) access the Internet (for updating wallpapers) and (2) use the device microphone (to change background following noise changes). With these permissions, the application could silently record user conversations and upload them remotely. To give more confidence about how Shake Them All actually processes what it records, it is necessary to build a precise analysis tool that tracks the flow of any sensitive data from its source point to any sink, especially if those are in different components. Since Android applications may leak private data carelessly or maliciously, we propose IccTA, a static taint analyzer to detect privacy leaks among components in Android applications. IccTA goes beyond state-of-the-art approaches by supporting inter- component detection. By propagating context information among components, IccTA improves the precision of the analysis. IccTA outperforms existing tools on two benchmarks for ICC-leak detectors: DroidBench and ICC-Bench. Moreover, our approach detects 534 ICC leaks in 108 apps from MalGenome and 2,395 ICC leaks in 337 apps in a set of 15,000 Google Play apps.

Journal ArticleDOI
TL;DR: In this paper, the authors explain how the first chapter of the massive MIMO research saga has come to an end, while the story has just begun, and outline five new massive antenna array related research directions.

01 Jan 2016
TL;DR: In this article, the parB+ locus mediates plasmid stability by killing cells that have lost the par-B+ during the preceding cell division, thereby ensuring that a growing bacterial culture predominantly con- sists of Plasmid-containing cells.
Abstract: The stability locus parB+ of plasmid Rl has been found to specify a unique type of plasmid maintenance function. Two genes, hok (host killing) and sok (suppressor of killing), are required for the stabilizing activity. The hok gene encodes a highly toxic gene product, whose overexpression causes a rapid killing and a concomitant dramatic change in morphology of the host cell. The other gene, sok, was found to encode a product that counteracts the hok gene-mediated killing. The parB+ region was inserted in a plasmid with a temperature-sensitive replication system. At nonpermissive temperature, the parB+ plasmid was maintained in the popu- lation for a significantly longer period than the corresponding parB- plasmid. Coupled to this extended maintenance, a large fraction of the population was shown to be nonviable plasmid- free cells with the characteristic hok-induced change in mor- phology. Based on these findings, we propose that the parB+ locus mediates plasmid stability by killing cells that have lost the parB+ plasmid during the preceding cell division, thereby ensuring that a growing bacterial culture predominantly con- sists of plasmid-containing cells.

Journal ArticleDOI
28 Jul 2015-JAMA
TL;DR: The ACA's first 2 open enrollment periods were associated with significantly improved trends in self-reported coverage, access to primary care and medications, affordability, and health.
Abstract: Importance The Affordable Care Act (ACA) completed its second open enrollment period in February 2015. Assessing the law’s effects has major policy implications. Objectives To estimate national changes in self-reported coverage, access to care, and health during the ACA’s first 2 open enrollment periods and to assess differences between low-income adults in states that expanded Medicaid and in states that did not expand Medicaid. Design, Setting, and Participants Analysis of the 2012-2015 Gallup-Healthways Well-Being Index, a daily national telephone survey. Using multivariable regression to adjust for pre-ACA trends and sociodemographics, we examined changes in outcomes for the nonelderly US adult population aged 18 through 64 years (n = 507 055) since the first open enrollment period began in October 2013. Linear regressions were used to model each outcome as a function of a linear monthly time trend and quarterly indicators. Then, pre-ACA (January 2012-September 2013) and post-ACA (January 2014-March 2015) changes for adults with incomes below 138% of the poverty level in Medicaid expansion states (n = 48 905 among 28 states and Washington, DC) vs nonexpansion states (n = 37 283 among 22 states) were compared using a differences-in-differences approach. Exposures Beginning of the ACA’s first open enrollment period (October 2013). Main Outcomes and Measures Self-reported rates of being uninsured, lacking a personal physician, lacking easy access to medicine, inability to afford needed care, overall health status, and health-related activity limitations. Results Among the 507 055 adults in this survey, pre-ACA trends were significantly worsening for all outcomes. Compared with the pre-ACA trends, by the first quarter of 2015, the adjusted proportions who were uninsured decreased by 7.9 percentage points (95% CI, −9.1 to −6.7); who lacked a personal physician, −3.5 percentage points (95% CI, −4.8 to −2.2); who lacked easy access to medicine, −2.4 percentage points (95% CI, −3.3 to −1.5); who were unable to afford care, −5.5 percentage points (95% CI, −6.7 to −4.2); who reported fair/poor health, −3.4 percentage points (95% CI, −4.6 to −2.2); and the percentage of days with activities limited by health, −1.7 percentage points (95% CI, −2.4 to −0.9). Coverage changes were largest among minorities; for example, the decrease in the uninsured rate was larger among Latino adults (−11.9 percentage points [95% CI, −15.3 to −8.5]) than white adults (−6.1 percentage points [95% CI, −7.3 to −4.8]). Medicaid expansion was associated with significant reductions among low-income adults in the uninsured rate (differences-in-differences estimate, −5.2 percentage points [95% CI, −7.9 to −2.6]), lacking a personal physician (−1.8 percentage points [95% CI, −3.4 to −0.3]), and difficulty accessing medicine (−2.2 percentage points [95% CI, −3.8 to −0.7]). Conclusions and Relevance The ACA’s first 2 open enrollment periods were associated with significantly improved trends in self-reported coverage, access to primary care and medications, affordability, and health. Low-income adults in states that expanded Medicaid reported significant gains in insurance coverage and access compared with adults in states that did not expand Medicaid.

Journal ArticleDOI
TL;DR: This review, contributed by scientists of complementary disciplines related to carotenoid research, covers recent advances and provides a perspective on future directions on the subjects of carotENoid metabolism, biotechnology, and nutritional and health benefits.

Book
15 Jun 2015
TL;DR: The authors analyzes the extent of income inequality from a global perspective, its drivers, and what to do about it and finds that increasing the income share of the poor and the middle class actually increases growth.
Abstract: This paper analyzes the extent of income inequality from a global perspective, its drivers, and what to do about it. The drivers of inequality vary widely amongst countries, with some common drivers being the skill premium associated with technical change and globalization, weakening protection for labor, and lack of financial inclusion in developing countries. We find that increasing the income share of the poor and the middle class actually increases growth while a rising income share of the top 20 percent results in lower growth—that is, when the rich get richer, benefits do not trickle down. This suggests that policies need to be country specific but should focus on raising the income share of the poor, and ensuring there is no hollowing out of the middle class. To tackle inequality, financial inclusion is imperative in emerging and developing countries while in advanced economies, policies should focus on raising human capital and skills and making tax systems more progressive.


Journal ArticleDOI
01 Jan 2017-Thorax
TL;DR: A new classification of core processes involved in chest EIT examinations and data analysis is provided, and a structured framework to categorise and understand the relationships among analysis approaches and their clinical roles is provided.
Abstract: Electrical impedance tomography (EIT) has undergone 30 years of development. Functional chest examinations with this technology are considered clinically relevant, especially for monitoring regional lung ventilation in mechanically ventilated patients and for regional pulmonary function testing in patients with chronic lung diseases. As EIT becomes an established medical technology, it requires consensus examination, nomenclature, data analysis and interpretation schemes. Such consensus is needed to compare, understand and reproduce study findings from and among different research groups, to enable large clinical trials and, ultimately, routine clinical use. Recommendations of how EIT findings can be applied to generate diagnoses and impact clinical decision-making and therapy planning are required. This consensus paper was prepared by an international working group, collaborating on the clinical promotion of EIT called TRanslational EIT developmeNt stuDy group. It addresses the stated needs by providing (1) a new classification of core processes involved in chest EIT examinations and data analysis, (2) focus on clinical applications with structured reviews and outlooks (separately for adult and neonatal/paediatric patients), (3) a structured framework to categorise and understand the relationships among analysis approaches and their clinical roles, (4) consensus, unified terminology with clinical user-friendly definitions and explanations, (5) a review of all major work in thoracic EIT and (6) recommendations for future development (193 pages of online supplements systematically linked with the chief sections of the main document). We expect this information to be useful for clinicians and researchers working with EIT, as well as for industry producers of this technology.

Journal ArticleDOI
TL;DR: The authors argue that sampling is better understood in methodological terms of range restriction and omitted variables bias, which has far-reaching implications because in industrial-organizational (I-O) psychology, as in most social sciences, virtually all of the samples are convenience samples.
Abstract: Sampling strategy has critical implications for the validity of a researcher’s conclusions. Despite this, sampling is frequently neglected in research methods textbooks, during the research design process, and in the reporting of our journals. The lack of guidance on this issue often leads reviewers and journal editors to rely on simple rules of thumb, myth, and tradition for judgments about sampling, which promotes the unnecessary and counterproductive characterization of sampling strategies as universally “good” or “bad.” Such oversimpli fiation, especially by journal editors and reviewers, slows the progress of the social sciences by considering legitimate data sources to be categorically unacceptable. Instead, we argue that sampling is better understood in methodological terms of range restriction and omitted variables bias. This considered approach has far-reaching implications because in industrial– organizational (I-O) psychology, as in most social sciences, virtually all of the samples are convenience samples. Organizational samples are not gold standard research sources; instead, they are merely a specific type of convenience sample with their own positive and negative implications for validity. This fact does not condemn the science of I-O psychology but does highlight the need for more careful consideration of how and when a finding may generalize based on the particular mix of validityrelated affordances provided by each sample source that might be used to investigate a particular research question. We call for researchers to explore such considerations cautiously and explicitly both in the publication and in the review of research.

Journal ArticleDOI
07 Apr 2015-JAMA
TL;DR: Among adults with hypertension in China without a history of stroke or MI, the combined use of enalapril and folic acid, compared with en alapril alone, significantly reduced the risk of first stroke.
Abstract: Importance Uncertainty remains about the efficacy of folic acid therapy for the primary prevention of stroke because of limited and inconsistent data. Objective To test the primary hypothesis that therapy with enalapril and folic acid is more effective in reducing first stroke than enalapril alone among Chinese adults with hypertension. Design, Setting, and Participants The China Stroke Primary Prevention Trial, a randomized, double-blind clinical trial conducted from May 19, 2008, to August 24, 2013, in 32 communities in Jiangsu and Anhui provinces in China. A total of 20 702 adults with hypertension without history of stroke or myocardial infarction (MI) participated in the study. Interventions Eligible participants, stratified by MTHFR C677T genotypes (CC, CT, and TT), were randomly assigned to receive double-blind daily treatment with a single-pill combination containing enalapril, 10 mg, and folic acid, 0.8 mg (n = 10 348) or a tablet containing enalapril, 10 mg, alone (n = 10 354). Main Outcomes and Measures The primary outcome was first stroke. Secondary outcomes included first ischemic stroke; first hemorrhagic stroke; MI; a composite of cardiovascular events consisting of cardiovascular death, MI, and stroke; and all-cause death. Results During a median treatment duration of 4.5 years, compared with the enalapril alone group, the enalapril–folic acid group had a significant risk reduction in first stroke (2.7% of participants in the enalapril–folic acid group vs 3.4% in the enalapril alone group; hazard ratio [HR], 0.79; 95% CI, 0.68-0.93), first ischemic stroke (2.2% with enalapril–folic acid vs 2.8% with enalapril alone; HR, 0.76; 95% CI, 0.64-0.91), and composite cardiovascular events consisting of cardiovascular death, MI, and stroke (3.1% with enalapril–folic acid vs 3.9% with enalapril alone; HR, 0.80; 95% CI, 0.69-0.92). The risks of hemorrhagic stroke (HR, 0.93; 95% CI, 0.65-1.34), MI (HR, 1.04; 95% CI, 0.60-1.82), and all-cause deaths (HR, 0.94; 95% CI, 0.81-1.10) did not differ significantly between the 2 treatment groups. There were no significant differences between the 2 treatment groups in the frequencies of adverse events. Conclusions and Relevance Among adults with hypertension in China without a history of stroke or MI, the combined use of enalapril and folic acid, compared with enalapril alone, significantly reduced the risk of first stroke. These findings are consistent with benefits from folate use among adults with hypertension and low baseline folate levels. Trial Registration clinicaltrials.gov Identifier:NCT00794885

Journal ArticleDOI
TL;DR: To estimate procedure‐related risks of miscarriage following amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and a meta‐analysis.
Abstract: Objectives To estimate procedure-related risks of miscarriage following amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and a meta-analysis. Methods A search of MEDLINE, EMBASE, CINHAL and The Cochrane Library (2000-2014) was performed to review relevant citations reporting procedure-related complications of amniocentesis and CVS. Only studies reporting data on more than 1000 procedures were included in this review to minimize the effect of bias from smaller studies. Heterogeneity between studies was estimated using Cochran's Q, the I(2) statistic and Egger bias. Meta-analysis of proportions was used to derive weighted pooled estimates for the risk of miscarriage before 24 weeks' gestation. Incidence-rate difference meta-analysis was used to estimate pooled procedure-related risks. Results The weighted pooled risks of miscarriage following invasive procedures were estimated from analysis of controlled studies including 324 losses in 42 716 women who underwent amniocentesis and 207 losses in 8899 women who underwent CVS. The risk of miscarriage prior to 24 weeks in women who underwent amniocentesis and CVS was 0.81% (95% CI, 0.58-1.08%) and 2.18% (95% CI, 1.61-2.82%), respectively. The background rates of miscarriage in women from the control group that did not undergo any procedures were 0.67% (95% CI, 0.46-0.91%) for amniocentesis and 1.79% (95% CI, 0.61-3.58%) for CVS. The weighted pooled procedure-related risks of miscarriage for amniocentesis and CVS were 0.11% (95% CI, -0.04 to 0.26%) and 0.22% (95% CI, -0.71 to 1.16%), respectively. Conclusion The procedure-related risks of miscarriage following amniocentesis and CVS are much lower than are currently quoted.

Journal ArticleDOI
TL;DR: The detection of daily-life behavioral markers using mobile phone global positioning systems and usage sensors and their use in identifying depressive symptom severity suggest that phone sensors offer numerous clinical opportunities, including continuous monitoring of at-risk populations with little patient burden and interventions that can provide just-in-time outreach.
Abstract: Background: Depression is a common, burdensome, often recurring mental health disorder that frequently goes undetected and untreated. Mobile phones are ubiquitous and have an increasingly large complement of sensors that can potentially be useful in monitoring behavioral patterns that might be indicative of depressive symptoms. Objective: The objective of this study was to explore the detection of daily-life behavioral markers using mobile phone global positioning systems (GPS) and usage sensors, and their use in identifying depressive symptom severity. Methods: A total of 40 adult participants were recruited from the general community to carry a mobile phone with a sensor data acquisition app (Purple Robot) for 2 weeks. Of these participants, 28 had sufficient sensor data received to conduct analysis. At the beginning of the 2-week period, participants completed a self-reported depression survey (PHQ-9). Behavioral features were developed and extracted from GPS location and phone usage data. Results: A number of features from GPS data were related to depressive symptom severity, including circadian movement (regularity in 24-hour rhythm; r =-.63, P =.005), normalized entropy (mobility between favorite locations; r =-.58, P =.012), and location variance (GPS mobility independent of location; r =-.58, P =.012). Phone usage features, usage duration, and usage frequency were also correlated ( r =.54, P =.011, and r =.52, P =.015, respectively). Using the normalized entropy feature and a classifier that distinguished participants with depressive symptoms (PHQ-9 score ≥5) from those without (PHQ-9 score <5), we achieved an accuracy of 86.5%. Furthermore, a regression model that used the same feature to estimate the participants’ PHQ-9 scores obtained an average error of 23.5%. Conclusions: Features extracted from mobile phone sensor data, including GPS and phone usage, provided behavioral markers that were strongly related to depressive symptom severity. While these findings must be replicated in a larger study among participants with confirmed clinical symptoms, they suggest that phone sensors offer numerous clinical opportunities, including continuous monitoring of at-risk populations with little patient burden and interventions that can provide just-in-time outreach. [J Med Internet Res 2015;17(7):e175]

Journal ArticleDOI
TL;DR: It is shown that interspecies metabolic exchanges are widespread in natural communities, and that such exchanges can provide group advantage under nutrient-poor conditions, and highlight metabolic dependencies as a major driver of species co-occurrence.
Abstract: Microbial communities populate most environments on earth and play a critical role in ecology and human health. Their composition is thought to be largely shaped by interspecies competition for the available resources, but cooperative interactions, such as metabolite exchanges, have also been implicated in community assembly. The prevalence of metabolic interactions in microbial communities, however, has remained largely unknown. Here, we systematically survey, by using a genome-scale metabolic modeling approach, the extent of resource competition and metabolic exchanges in over 800 communities. We find that, despite marked resource competition at the level of whole assemblies, microbial communities harbor metabolically interdependent groups that recur across diverse habitats. By enumerating flux-balanced metabolic exchanges in these co-occurring subcommunities we also predict the likely exchanged metabolites, such as amino acids and sugars, that can promote group survival under nutritionally challenging conditions. Our results highlight metabolic dependencies as a major driver of species co-occurrence and hint at cooperative groups as recurring modules of microbial community architecture.

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TL;DR: The results confirm that the addition of concomitant chemotherapy to radiotherapy significantly improves survival in patients with locoregionally advanced nasopharyngeal carcinoma.
Abstract: Summary Background A previous individual patient data meta-analysis by the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma (MAC-NPC) collaborative group to assess the addition of chemotherapy to radiotherapy showed that it improves overall survival in nasopharyngeal carcinoma. This benefit was restricted to patients receiving concomitant chemotherapy and radiotherapy. The aim of this study was to update the meta-analysis, include recent trials, and to analyse separately the benefit of concomitant plus adjuvant chemotherapy. Methods We searched PubMed, Web of Science, Cochrane Controlled Trials meta-register, ClinicalTrials.gov, and meeting proceedings to identify published or unpublished randomised trials assessing radiotherapy with or without chemotherapy in patients with non-metastatic nasopharyngeal carcinoma and obtained updated data for previously analysed studies. The primary endpoint of interest was overall survival. All trial results were combined and analysed using a fixed-effects model. The statistical analysis plan was pre-specified in a protocol. All data were analysed on an intention-to-treat basis. Findings We analysed data from 19 trials and 4806 patients. Median follow-up was 7·7 years (IQR 6·2–11·9). We found that the addition of chemotherapy to radiotherapy significantly improved overall survival (hazard ratio [HR] 0·79, 95% CI 0·73–0·86, p Interpretation Our results confirm that the addition of concomitant chemotherapy to radiotherapy significantly improves survival in patients with locoregionally advanced nasopharyngeal carcinoma. To our knowledge, this is the first analysis that examines the effect of concomitant chemotherapy with and without adjuvant chemotherapy as distinct groups. Further studies on the specific benefits of adjuvant chemotherapy after concomitant chemoradiotherapy are needed. Funding French Ministry of Health (Programme d'actions integrees de recherche VADS), Ligue Nationale Contre le Cancer, and Sanofi-Aventis.

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TL;DR: In this article, the authors proposed a novel method for phase recognition that uses a convolutional neural network (CNN) to automatically learn features from cholecystectomy videos and that relies uniquely on visual information.
Abstract: Surgical workflow recognition has numerous potential medical applications, such as the automatic indexing of surgical video databases and the optimization of real-time operating room scheduling, among others. As a result, surgical phase recognition has been studied in the context of several kinds of surgeries, such as cataract, neurological, and laparoscopic surgeries. In the literature, two types of features are typically used to perform this task: visual features and tool usage signals. However, the used visual features are mostly handcrafted. Furthermore, the tool usage signals are usually collected via a manual annotation process or by using additional equipment. In this paper, we propose a novel method for phase recognition that uses a convolutional neural network (CNN) to automatically learn features from cholecystectomy videos and that relies uniquely on visual information. In previous studies, it has been shown that the tool usage signals can provide valuable information in performing the phase recognition task. Thus, we present a novel CNN architecture, called EndoNet, that is designed to carry out the phase recognition and tool presence detection tasks in a multi-task manner. To the best of our knowledge, this is the first work proposing to use a CNN for multiple recognition tasks on laparoscopic videos. Experimental comparisons to other methods show that EndoNet yields state-of-the-art results for both tasks.

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TL;DR: The proposed PdM methodology allows dynamical decision rules to be adopted for maintenance management, and can be used with high-dimensional and censored data problems, and the effectiveness of the methodology is demonstrated.
Abstract: In this paper, a multiple classifier machine learning (ML) methodology for predictive maintenance (PdM) is presented. PdM is a prominent strategy for dealing with maintenance issues given the increasing need to minimize downtime and associated costs. One of the challenges with PdM is generating the so-called “health factors,” or quantitative indicators, of the status of a system associated with a given maintenance issue, and determining their relationship to operating costs and failure risk. The proposed PdM methodology allows dynamical decision rules to be adopted for maintenance management, and can be used with high-dimensional and censored data problems. This is achieved by training multiple classification modules with different prediction horizons to provide different performance tradeoffs in terms of frequency of unexpected breaks and unexploited lifetime, and then employing this information in an operating cost-based maintenance decision system to minimize expected costs. The effectiveness of the methodology is demonstrated using a simulated example and a benchmark semiconductor manufacturing maintenance problem.