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Journal ArticleDOI
11 Jun 2015-Nature
TL;DR: This work built a lightweight elastic device that acts in parallel with the user's calf muscles, off-loading muscle force and thereby reducing the metabolic energy consumed in contractions, and shows that the metabolic rate of human walking can be reduced by an unpowered ankle exoskeleton.
Abstract: With efficiencies derived from evolution, growth and learning, humans are very well-tuned for locomotion. Metabolic energy used during walking can be partly replaced by power input from an exoskeleton, but is it possible to reduce metabolic rate without providing an additional energy source? This would require an improvement in the efficiency of the human-machine system as a whole, and would be remarkable given the apparent optimality of human gait. Here we show that the metabolic rate of human walking can be reduced by an unpowered ankle exoskeleton. We built a lightweight elastic device that acts in parallel with the user's calf muscles, off-loading muscle force and thereby reducing the metabolic energy consumed in contractions. The device uses a mechanical clutch to hold a spring as it is stretched and relaxed by ankle movements when the foot is on the ground, helping to fulfil one function of the calf muscles and Achilles tendon. Unlike muscles, however, the clutch sustains force passively. The exoskeleton consumes no chemical or electrical energy and delivers no net positive mechanical work, yet reduces the metabolic cost of walking by 7.2 ± 2.6% for healthy human users under natural conditions, comparable to savings with powered devices. Improving upon walking economy in this way is analogous to altering the structure of the body such that it is more energy-effective at walking. While strong natural pressures have already shaped human locomotion, improvements in efficiency are still possible. Much remains to be learned about this seemingly simple behaviour.

682 citations


Proceedings ArticleDOI
01 Jun 2019
TL;DR: The paper describes the organization of the SemEval 2019 Task 5 about the detection of hate speech against immigrants and women in Spanish and English messages extracted from Twitter, and provides an analysis and discussion about the participant systems and the results they achieved in both subtasks.
Abstract: The paper describes the organization of the SemEval 2019 Task 5 about the detection of hate speech against immigrants and women in Spanish and English messages extracted from Twitter. The task is organized in two related classification subtasks: a main binary subtask for detecting the presence of hate speech, and a finer-grained one devoted to identifying further features in hateful contents such as the aggressive attitude and the target harassed, to distinguish if the incitement is against an individual rather than a group. HatEval has been one of the most popular tasks in SemEval-2019 with a total of 108 submitted runs for Subtask A and 70 runs for Subtask B, from a total of 74 different teams. Data provided for the task are described by showing how they have been collected and annotated. Moreover, the paper provides an analysis and discussion about the participant systems and the results they achieved in both subtasks.

682 citations


Journal ArticleDOI
27 Sep 2019-Science
TL;DR: The functional consequences of many MS susceptibility variants are characterized by identifying those that influence the expression of nearby genes in immune cells or brain by applying an ensemble of methods to prioritize 551 putative MS susceptibility genes that meet a threshold of genome-wide significance.
Abstract: We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 variants within the extended MHC. We used an ensemble of methods to prioritize 551 putative susceptibility genes that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we observed enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggered by perturbation of peripheral immune responses.

682 citations



Proceedings ArticleDOI
01 Jun 2016
TL;DR: This work introduces a linear approximation of the min operator to compute the dark channel and achieves state-of-the-art results on deblurring natural images and compares favorably methods that are well-engineered for specific scenarios.
Abstract: We present a simple and effective blind image deblurring method based on the dark channel prior. Our work is inspired by the interesting observation that the dark channel of blurred images is less sparse. While most image patches in the clean image contain some dark pixels, these pixels are not dark when averaged with neighboring highintensity pixels during the blur process. This change in the sparsity of the dark channel is an inherent property of the blur process, which we both prove mathematically and validate using training data. Therefore, enforcing the sparsity of the dark channel helps blind deblurring on various scenarios, including natural, face, text, and low-illumination images. However, sparsity of the dark channel introduces a non-convex non-linear optimization problem. We introduce a linear approximation of the min operator to compute the dark channel. Our look-up-table-based method converges fast in practice and can be directly extended to non-uniform deblurring. Extensive experiments show that our method achieves state-of-the-art results on deblurring natural images and compares favorably methods that are well-engineered for specific scenarios.

682 citations


Journal ArticleDOI
TL;DR: Rapidly emerging data with selective inhibitors of CDK4/6 have validated these cell-cycle kinases as anticancer drug targets, corroborating longstanding preclinical predictions.
Abstract: Biochemical and genetic characterization of D-type cyclins, their cyclin D–dependent kinases (CDK4 and CDK6), and the polypeptide CDK4/6 inhibitor p16INK4 over two decades ago revealed how mammalian cells regulate entry into the DNA synthetic (S) phase of the cell-division cycle in a retinoblastoma protein–dependent manner. These investigations provided proof-of-principle that CDK4/6 inhibitors, particularly when combined with coinhibition of allied mitogen-dependent signal transduction pathways, might prove valuable in cancer therapy. FDA approval of the CDK4/6 inhibitor palbociclib used with the aromatase inhibitor letrozole for breast cancer treatment highlights long-sought success. The newest findings herald clinical trials targeting other cancers. Significance: Rapidly emerging data with selective inhibitors of CDK4/6 have validated these cell-cycle kinases as anticancer drug targets, corroborating longstanding preclinical predictions. This review addresses the discovery of these CDKs and their regulators, as well as translation of CDK4/6 biology to positive clinical outcomes and development of rational combinatorial therapies. Cancer Discov; 6(4); 353–67. ©2015 AACR .

682 citations


Journal ArticleDOI
TL;DR: This work uses Cre recombination–based AAV targeted evolution (CREATE) to generate AAV variants that efficiently and widely transduce the adult mouse central nervous system (CNS) after intravenous injection and demonstrates the potential of CREATE to produce customized AAV vectors for biomedical applications.
Abstract: Recombinant adeno-associated viruses (rAAVs) are commonly used vehicles for in vivo gene transfer. However, the tropism repertoire of naturally occurring AAVs is limited, prompting a search for novel AAV capsids with desired characteristics. Here we describe a capsid selection method, called Cre recombination-based AAV targeted evolution (CREATE), that enables the development of AAV capsids that more efficiently transduce defined Cre-expressing cell populations in vivo. We use CREATE to generate AAV variants that efficiently and widely transduce the adult mouse central nervous system (CNS) after intravenous injection. One variant, AAV-PHP.B, transfers genes throughout the CNS with an efficiency that is at least 40-fold greater than that of the current standard, AAV9 (refs. 14,15,16,17), and transduces the majority of astrocytes and neurons across multiple CNS regions. In vitro, it transduces human neurons and astrocytes more efficiently than does AAV9, demonstrating the potential of CREATE to produce customized AAV vectors for biomedical applications.

682 citations


Journal ArticleDOI
TL;DR: A vital extension to partial least squares path modeling is introduced: consistency, which provides two key improvements: path coefficients, parameters of simultaneous equations, construct correlations, and indicator loadings are estimated consistently.

682 citations


Journal ArticleDOI
TL;DR: The review reveals that several opportunities are available for utilizing big data in smart cities; however, there are still many issues and challenges to be addressed to achieve better utilization of this technology.
Abstract: Many governments are considering adopting the smart city concept in their cities and implementing big data applications that support smart city components to reach the required level of sustainability and improve the living standards. Smart cities utilize multiple technologies to improve the performance of health, transportation, energy, education, and water services leading to higher levels of comfort of their citizens. This involves reducing costs and resource consumption in addition to more effectively and actively engaging with their citizens. One of the recent technologies that has a huge potential to enhance smart city services is big data analytics. As digitization has become an integral part of everyday life, data collection has resulted in the accumulation of huge amounts of data that can be used in various beneficial application domains. Effective analysis and utilization of big data is a key factor for success in many business and service domains, including the smart city domain. This paper reviews the applications of big data to support smart cities. It discusses and compares different definitions of the smart city and big data and explores the opportunities, challenges and benefits of incorporating big data applications for smart cities. In addition it attempts to identify the requirements that support the implementation of big data applications for smart city services. The review reveals that several opportunities are available for utilizing big data in smart cities; however, there are still many issues and challenges to be addressed to achieve better utilization of this technology.

682 citations


01 Jan 2015
TL;DR: Nutrition policies to tackle child obesity need to promote healthy growth and household nutrition security and protect children from inducements to be inactive or to overconsume foods of poor nutritional quality.
Abstract: The prevalence of childhood overweight and obesity has risen substantially worldwide in less than one generation. In the USA, the average weight of a child has risen by more than 5 kg within three decades, to a point where a third of the country’s children are overweight or obese. Some low-income and middle-income countries have reported similar or more rapid rises in child obesity, despite continuing high levels of undernutrition. Nutrition policies to tackle child obesity need to promote healthy growth and household nutrition security and protect children from inducements to be inactive or to overconsume foods of poor nutritional quality. The promotion of energy-rich and nutrient-poor products will encourage rapid weight gain in early childhood and exacerbate risk factors for chronic disease in all children, especially those showing poor linear growth. Whereas much public health eff ort has been expended to restrict the adverse marketing of breastmilk substitutes, similar eff ort now needs to be expanded and strengthened to protect older children from increasingly sophisticated marketing of sedentary activities and energy-dense, nutrient-poor foods and beverages. To meet this challenge, the governance of food supply and food markets should be improved and commercial activities subordinated to protect and promote children’s health.

682 citations


Posted ContentDOI
27 Feb 2020-medRxiv
TL;DR: Comorbidities are present in around one fourth of patients with COVID-19 in China, and predispose to poorer clinical outcomes, and have significantly escalated risks of reaching to the composite endpoint compared with those who had a single comorbidity.
Abstract: Objective To evaluate the spectrum of comorbidities and its impact on the clinical outcome in patients with coronavirus disease 2019 (COVID-19). Design Retrospective case studies Setting 575 hospitals in 31 province/autonomous regions/provincial municipalities across China Participants 1,590 laboratory-confirmed hospitalized patients. Data were collected from November 21st, 2019 to January 31st, 2020. Main outcomes and measures Epidemiological and clinical variables (in particular, comorbidities) were extracted from medical charts. The disease severity was categorized based on the American Thoracic Society guidelines for community-acquired pneumonia. The primary endpoint was the composite endpoints, which consisted of the admission to intensive care unit (ICU), or invasive ventilation, or death. The risk of reaching to the composite endpoints was compared among patients with COVID-19 according to the presence and number of comorbidities. Results Of the 1,590 cases, the mean age was 48.9 years. 686 patients (42.7%) were females. 647 (40.7%) patients were managed inside Hubei province, and 1,334 (83.9%) patients had a contact history of Wuhan city. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached to the composite endpoints. 399 (25.1%) reported having at least one comorbidity. 269 (16.9%), 59 (3.7%), 30 (1.9%), 130 (8.2%), 28 (1.8%), 24 (1.5%), 21 (1.3%), 18 (1.1%) and 3 (0.2%) patients reported having hypertension, cardiovascular diseases, cerebrovascular diseases, diabetes, hepatitis B infections, chronic obstructive pulmonary disease, chronic kidney diseases, malignancy and immunodeficiency, respectively. 130 (8.2%) patients reported having two or more comorbidities. Patients with two or more comorbidities had significantly escalated risks of reaching to the composite endpoint compared with those who had a single comorbidity, and even more so as compared with those without (all P Conclusion Comorbidities are present in around one fourth of patients with COVID-19 in China, and predispose to poorer clinical outcomes. Highlights What is already known on this topic -Since November 2019, the rapid outbreak of coronavirus disease 2019 (COVID-19) has recently become a public health emergency of international concern. There have been 79,331 laboratory-confirmed cases and 2,595 deaths globally as of February 25th, 2020 -Previous studies have demonstrated the association between comorbidities and other severe acute respiratory diseases including SARS and MERS. -No study with a nationwide representative cohort has demonstrated the spectrum of comorbidities and the impact of comorbidities on the clinical outcomes in patients with COVID-19. What this study adds -In this nationwide study with 1,590 patients with COVID-19, comorbidities were identified in 399 patients. Comorbidities of COVID-19 mainly included hypertension, cardiovascular diseases, cerebrovascular diseases, diabetes, hepatitis B infections, chronic obstructive pulmonary disease, chronic kidney diseases, malignancy and immunodeficiency. -The presence of as well as the number of comorbidities predicted the poor clinical outcomes (admission to intensive care unit, invasive ventilation, or death) of COVID-19. -Comorbidities should be taken into account when estimating the clinical outcomes of patients with COVID-19 on hospital admission.

Journal ArticleDOI
17 Dec 2016
TL;DR: This work proposes a different approach to perceive forest trials based on a deep neural network used as a supervised image classifier that outperforms alternatives, and yields an accuracy comparable to the accuracy of humans that are tested on the same image classification task.
Abstract: We study the problem of perceiving forest or mountain trails from a single monocular image acquired from the viewpoint of a robot traveling on the trail itself. Previous literature focused on trail segmentation, and used low-level features such as image saliency or appearance contrast; we propose a different approach based on a deep neural network used as a supervised image classifier. By operating on the whole image at once, our system outputs the main direction of the trail compared to the viewing direction. Qualitative and quantitative results computed on a large real-world dataset (which we provide for download) show that our approach outperforms alternatives, and yields an accuracy comparable to the accuracy of humans that are tested on the same image classification task. Preliminary results on using this information for quadrotor control in unseen trails are reported. To the best of our knowledge, this is the first letter that describes an approach to perceive forest trials, which is demonstrated on a quadrotor micro aerial vehicle.

Journal ArticleDOI
TL;DR: The nasopharynx is a reservoir for microbes associated with acute respiratory infections (ARIs) and targeting pathogenic bacteria within the NP microbiome could represent a prophylactic approach to asthma.

Proceedings Article
30 Apr 2020
TL;DR: By sampling text from the dynamic nucleus of the probability distribution, which allows for diversity while effectively truncating the less reliable tail of the distribution, the resulting text better demonstrates the quality of human text, yielding enhanced diversity without sacrificing fluency and coherence.
Abstract: Despite considerable advances in neural language modeling, it remains an open question what the best decoding strategy is for text generation from a language model (e.g. to generate a story). The counter-intuitive empirical observation is that even though the use of likelihood as training objective leads to high quality models for a broad range of language understanding tasks, maximization-based decoding methods such as beam search lead to degeneration — output text that is bland, incoherent, or gets stuck in repetitive loops. To address this we propose Nucleus Sampling, a simple but effective method to draw considerably higher quality text out of neural language models. Our approach avoids text degeneration by truncating the unreliable tail of the probability distribution, sampling from the dynamic nucleus of tokens containing the vast majority of the probability mass. To properly examine current maximization-based and stochastic decoding methods, we compare generations from each of these methods to the distribution of human text along several axes such as likelihood, diversity, and repetition. Our results show that (1) maximization is an inappropriate decoding objective for open-ended text generation, (2) the probability distributions of the best current language models have an unreliable tail which needs to be truncated during generation and (3) Nucleus Sampling is the best decoding strategy for generating long-form text that is both high-quality — as measured by human evaluation — and as diverse as human-written text.

Journal ArticleDOI
06 Jan 2017-Science
TL;DR: Studying mouse models, it is demonstrated that Rb1 loss facilitates lineage plasticity and metastasis of prostate adenocarcinoma initiated by Pten mutation and Clinically relevant Ezh2 inhibitors restore androgen receptor expression and sensitivity to antiandrogen therapy.
Abstract: Prostate cancer relapsing from antiandrogen therapies can exhibit variant histology with altered lineage marker expression, suggesting that lineage plasticity facilitates therapeutic resistance. The mechanisms underlying prostate cancer lineage plasticity are incompletely understood. Studying mouse models, we demonstrate that Rb1 loss facilitates lineage plasticity and metastasis of prostate adenocarcinoma initiated by Pten mutation. Additional loss of Trp53 causes resistance to antiandrogen therapy. Gene expression profiling indicates that mouse tumors resemble human prostate cancer neuroendocrine variants; both mouse and human tumors exhibit increased expression of epigenetic reprogramming factors such as Ezh2 and Sox2. Clinically relevant Ezh2 inhibitors restore androgen receptor expression and sensitivity to antiandrogen therapy. These findings uncover genetic mutations that enable prostate cancer progression; identify mouse models for studying prostate cancer lineage plasticity; and suggest an epigenetic approach for extending clinical responses to antiandrogen therapy.

Book ChapterDOI
01 Jan 2017
TL;DR: A system for visual odometry and mapping using an RGB-D camera, and its application to autonomous flight, which enables 3D flight in cluttered environments using only onboard sensor data.
Abstract: RGB-D cameras provide both a color image and per-pixel depth estimates. The richness of their data and the recent development of low-cost sensors have combined to present an attractive opportunity for mobile robotics research. In this paper, we describe a system for visual odometry and mapping using an RGB-D camera, and its application to autonomous flight. By leveraging results from recent state-of-the-art algorithms and hardware, our system enables 3D flight in cluttered environments using only onboard sensor data. All computation and sensing required for local position control are performed onboard the vehicle, reducing the dependence on unreliable wireless links. We evaluate the effectiveness of our system for stabilizing and controlling a quadrotor micro air vehicle, demonstrate its use for constructing detailed 3D maps of an indoor environment, and discuss its limitations.

Journal ArticleDOI
10 Feb 2020-Viruses
TL;DR: To assess the potential of the Wuhan 2019-nCoV to cause maternal, fetal and neonatal morbidity and other poor obstetrical outcomes, this communication reviews the published data addressing the epidemiological and clinical effects of SARS, MERS, and other coronavirus infections on pregnant women and their infants.
Abstract: In early December 2019 a cluster of cases of pneumonia of unknown cause was identified in Wuhan, a city of 11 million persons in the People’s Republic of China. Further investigation revealed these cases to result from infection with a newly identified coronavirus, initially termed 2019-nCoV and subsequently SARS-CoV-2. The infection moved rapidly through China, spread to Thailand and Japan, extended into adjacent countries through infected persons travelling by air, eventually reaching multiple countries and continents. Similar to such other coronaviruses as those causing the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS), the new coronavirus was reported to spread via natural aerosols from human-to-human. In the early stages of this epidemic the case fatality rate is estimated to be approximately 2%, with the majority of deaths occurring in special populations. Unfortunately, there is limited experience with coronavirus infections during pregnancy, and it now appears certain that pregnant women have become infected during the present 2019-nCoV epidemic. In order to assess the potential of the Wuhan 2019-nCoV to cause maternal, fetal and neonatal morbidity and other poor obstetrical outcomes, this communication reviews the published data addressing the epidemiological and clinical effects of SARS, MERS, and other coronavirus infections on pregnant women and their infants. Recommendations are also made for the consideration of pregnant women in the design, clinical trials, and implementation of future 2019-nCoV vaccines.

Journal ArticleDOI
TL;DR: Research since 2010 confirms the importance of alcohol use as a risk factor for disease and injuries; for some health outcomes, more than one dimension of use needs to be considered.
Abstract: Background and aims Alcohol use is a major contributor to injuries, mortality and the burden of disease. This review updates knowledge on risk relations between dimensions of alcohol use and health ...

Journal ArticleDOI
02 Apr 2020-Gut
TL;DR: GI tract may be a potential transmission route and target organ of SARS-CoV-2, potentially aggravated by various drugs including antibiotics.
Abstract: Objective To study the GI symptoms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. Design We analysed epidemiological, demographic, clinical and laboratory data of 95 cases with SARS-CoV-2 caused coronavirus disease 2019. Real-time reverse transcriptase PCR was used to detect the presence of SARS-CoV-2 in faeces and GI tissues. Results Among the 95 patients, 58 cases exhibited GI symptoms of which 11 (11.6%) occurred on admission and 47 (49.5%) developed during hospitalisation. Diarrhoea (24.2%), anorexia (17.9%) and nausea (17.9%) were the main symptoms with five (5.3%), five (5.3%) and three (3.2%) cases occurred on the illness onset, respectively. A substantial proportion of patients developed diarrhoea during hospitalisation, potentially aggravated by various drugs including antibiotics. Faecal samples of 65 hospitalised patients were tested for the presence of SARS-CoV-2, including 42 with and 23 without GI symptoms, of which 22 (52.4%) and 9 (39.1%) were positive, respectively. Six patients with GI symptoms were subjected to endoscopy, revealing oesophageal bleeding with erosions and ulcers in one severe patient. SARS-CoV-2 RNA was detected in oesophagus, stomach, duodenum and rectum specimens for both two severe patients. In contrast, only duodenum was positive in one of the four non-severe patients. Conclusions GI tract may be a potential transmission route and target organ of SARS-CoV-2.

Journal ArticleDOI
TL;DR: The results demonstrated the presence of Sars‐CoV‐2 RNA in the feces of COVID‐19 patients and suggested the possibility of SARS‐Cov‐2 transmission via the fecal‐oral route.
Abstract: In December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, and has spread globally. However, the transmission route of SARS-CoV-2 has not been fully understood. In this study, we aimed to investigate SARS-CoV-2 shedding in the excreta of COVID-19 patients. Electronical medical records, including demographics, clinical characteristics, laboratory and radiological findings of enrolled patients were extracted and analyzed. Pharyngeal swab, stool, and urine specimens were collected and tested for SARS-CoV-2 RNA by real-time reverse transcription polymerase chain reaction. Viral shedding at multiple time points in specimens was recorded, and its correlation analyzed with clinical manifestations and the severity of illness. A total of 42 laboratory-confirmed patients were enrolled, 8 (19.05%) of whom had gastrointestinal symptoms. A total of 28 (66.67%) patients tested positive for SARS-CoV-2 RNA in stool specimens, and this was not associated with the presence of gastrointestinal symptoms and the severity of illness. Among them, 18 (64.29%) patients remained positive for viral RNA in the feces after the pharyngeal swabs turned negative. The duration of viral shedding from the feces after negative conversion in pharyngeal swabs was 7 (6-10) days, regardless of COVID-19 severity. The demographics, clinical characteristics, laboratory and radiologic findings did not differ between patients who tested positive and negative for SARS-CoV-2 RNA in the feces. Viral RNA was not detectable in urine specimens from 10 patients. Our results demonstrated the presence of SARS-CoV-2 RNA in the feces of COVID-19 patients and suggested the possibility of SARS-CoV-2 transmission via the fecal-oral route.

Journal ArticleDOI
TL;DR: Gaussian boson sampling was performed by sending 50 indistinguishable single-mode squeezed states into a 100-mode ultralow-loss interferometer with full connectivity and random matrix and sampling the output using 100 high-efficiency single-photon detectors, and the obtained samples were validated against plausible hypotheses exploiting thermal states, distinguishable photons, and uniform distribution.
Abstract: Gaussian boson sampling exploits squeezed states to provide a highly efficient way to demonstrate quantum computational advantage. We perform experiments with 50 input single-mode squeezed states with high indistinguishability and squeezing parameters, which are fed into a 100-mode ultralow-loss interferometer with full connectivity and random transformation, and sampled using 100 high-efficiency single-photon detectors. The whole optical set-up is phase-locked to maintain a high coherence between the superposition of all photon number states. We observe up to 76 output photon-clicks, which yield an output state space dimension of $10^{30}$ and a sampling rate that is $10^{14}$ faster than using the state-of-the-art simulation strategy and supercomputers. The obtained samples are validated against various hypotheses including using thermal states, distinguishable photons, and uniform distribution.

Journal ArticleDOI
21 Aug 2019-Nature
TL;DR: In this paper, Li et al. established the analytical method of titration gas chromatography to quantify the contribution of unreacted metallic Li0 to the total amount of inactive lithium and proposed strategies for making lithium plating and stripping more efficient so that lithium metal anodes can be used for next-generation high energy batteries.
Abstract: Lithium metal anodes offer high theoretical capacities (3,860 milliampere-hours per gram)1, but rechargeable batteries built with such anodes suffer from dendrite growth and low Coulombic efficiency (the ratio of charge output to charge input), preventing their commercial adoption2,3. The formation of inactive ('dead') lithium- which consists of both (electro)chemically formed Li+ compounds in the solid electrolyte interphase and electrically isolated unreacted metallic Li0 (refs 4,5)-causes capacity loss and safety hazards. Quantitatively distinguishing between Li+ in components of the solid electrolyte interphase and unreacted metallic Li0 has not been possible, owing to the lack of effective diagnostic tools. Optical microscopy6, in situ environmental transmission electron microscopy7,8, X-ray microtomography9 and magnetic resonance imaging10 provide a morphological perspective with little chemical information. Nuclear magnetic resonance11, X-ray photoelectron spectroscopy12 and cryogenic transmission electron microscopy13,14 can distinguish between Li+ in the solid electrolyte interphase and metallic Li0, but their detection ranges are limited to surfaces or local regions. Here we establish the analytical method of titration gas chromatography to quantify the contribution of unreacted metallic Li0 to the total amount of inactive lithium. We identify the unreacted metallic Li0, not the (electro)chemically formed Li+ in the solid electrolyte interphase, as the dominant source of inactive lithium and capacity loss. By coupling the unreacted metallic Li0 content to observations of its local microstructure and nanostructure by cryogenic electron microscopy (both scanning and transmission), we also establish the formation mechanism of inactive lithium in different types of electrolytes and determine the underlying cause of low Coulombic efficiency in plating and stripping (the charge and discharge processes, respectively, in a full cell) of lithium metal anodes. We propose strategies for making lithium plating and stripping more efficient so that lithium metal anodes can be used for next-generation high-energy batteries.

Journal ArticleDOI
TL;DR: Cultural trends contributing to an increase in mood disorders and suicidal thoughts and behaviors since the mid-2000s, including the rise of electronic communication and digital media and declines in sleep duration, may have had a larger impact on younger people, creating a cohort effect.
Abstract: Drawing from the National Survey on Drug Use and Health (NSDUH; N = 611,880), a nationally representative survey of U.S. adolescents and adults, we assess age, period, and cohort trends in mood disorders and suicide-related outcomes since the mid-2000s. Rates of major depressive episode in the last year increased 52% 2005-2017 (from 8.7% to 13.2%) among adolescents aged 12 to 17 and 63% 2009-2017 (from 8.1% to 13.2%) among young adults 18-25. Serious psychological distress in the last month and suicide-related outcomes (suicidal ideation, plans, attempts, and deaths by suicide) in the last year also increased among young adults 18-25 from 2008-2017 (with a 71% increase in serious psychological distress), with less consistent and weaker increases among adults ages 26 and over. Hierarchical linear modeling analyses separating the effects of age, period, and birth cohort suggest the trends among adults are primarily due to cohort, with a steady rise in mood disorder and suicide-related outcomes between cohorts born from the early 1980s (Millennials) to the late 1990s (iGen). Cultural trends contributing to an increase in mood disorders and suicidal thoughts and behaviors since the mid-2000s, including the rise of electronic communication and digital media and declines in sleep duration, may have had a larger impact on younger people, creating a cohort effect. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Journal ArticleDOI
07 Jun 2016-JAMA
TL;DR: Among healthy children with a single anesthesia exposure before age 36 months, compared with healthy siblings with no anesthesia exposure, there were no statistically significant differences in IQ scores in later childhood.
Abstract: Importance Exposure of young animals to commonly used anesthetics causes neurotoxicity including impaired neurocognitive function and abnormal behavior. The potential neurocognitive and behavioral effects of anesthesia exposure in young children are thus important to understand. Objective To examine if a single anesthesia exposure in otherwise healthy young children was associated with impaired neurocognitive development and abnormal behavior in later childhood. Design, Setting, and Participants Sibling-matched cohort study conducted between May 2009 and April 2015 at 4 university-based US pediatric tertiary care hospitals. The study cohort included sibling pairs within 36 months in age and currently 8 to 15 years old. The exposed siblings were healthy at surgery/anesthesia. Neurocognitive and behavior outcomes were prospectively assessed with retrospectively documented anesthesia exposure data. Exposures A single exposure to general anesthesia during inguinal hernia surgery in the exposed sibling and no anesthesia exposure in the unexposed sibling, before age 36 months. Main Outcomes and Measures The primary outcome was global cognitive function (IQ). Secondary outcomes included domain-specific neurocognitive functions and behavior. A detailed neuropsychological battery assessed IQ and domain-specific neurocognitive functions. Parents completed validated, standardized reports of behavior. Results Among the 105 sibling pairs, the exposed siblings (mean age, 17.3 months at surgery/anesthesia; 9.5% female) and the unexposed siblings (44% female) had IQ testing at mean ages of 10.6 and 10.9 years, respectively. All exposed children received inhaled anesthetic agents, and anesthesia duration ranged from 20 to 240 minutes, with a median duration of 80 minutes. Mean IQ scores between exposed siblings (scores: full scale = 111; performance = 108; verbal = 111) and unexposed siblings (scores: full scale = 111; performance = 107; verbal = 111) were not statistically significantly different. Differences in mean IQ scores between sibling pairs were: full scale = −0.2 (95% CI, −2.6 to 2.9); performance = 0.5 (95% CI, −2.7 to 3.7); and verbal = −0.5 (95% CI, −3.2 to 2.2). No statistically significant differences in mean scores were found between sibling pairs in memory/learning, motor/processing speed, visuospatial function, attention, executive function, language, or behavior. Conclusions and Relevance Among healthy children with a single anesthesia exposure before age 36 months, compared with healthy siblings with no anesthesia exposure, there were no statistically significant differences in IQ scores in later childhood. Further study of repeated exposure, prolonged exposure, and vulnerable subgroups is needed.

Journal ArticleDOI
TL;DR: High rates of recurrent SCAD; its association with female sex, pregnancy, and physical and emotional stress triggers; and concurrent systemic arteriopathies, particularly fibromuscular dysplasia highlight the differences in clinical characteristics of SCAD compared with atherosclerotic disease.
Abstract: Spontaneous coronary artery dissection (SCAD) has emerged as an important cause of acute coronary syndrome, myocardial infarction, and sudden death, particularly among young women and individuals with few conventional atherosclerotic risk factors. Patient-initiated research has spurred increased awareness of SCAD, and improved diagnostic capabilities and findings from large case series have led to changes in approaches to initial and long-term management and increasing evidence that SCAD not only is more common than previously believed but also must be evaluated and treated differently from atherosclerotic myocardial infarction. High rates of recurrent SCAD; its association with female sex, pregnancy, and physical and emotional stress triggers; and concurrent systemic arteriopathies, particularly fibromuscular dysplasia, highlight the differences in clinical characteristics of SCAD compared with atherosclerotic disease. Recent insights into the causes of, clinical course of, treatment options for, outcomes of, and associated conditions of SCAD and the many persistent knowledge gaps are presented.

Journal ArticleDOI
Gilberto Pastorello1, Carlo Trotta2, E. Canfora2, Housen Chu1  +300 moreInstitutions (119)
TL;DR: The FLUXNET2015 dataset provides ecosystem-scale data on CO 2 , water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe, and is detailed in this paper.
Abstract: The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.

Journal ArticleDOI
14 Jun 2016-BMJ
TL;DR: Evidence is provided that whole grain intake is associated with a reduced risk of coronary heart disease, cardiovascular disease, and total cancer, and mortality from all causes, respiratory diseases, infectious diseases, diabetes, and all non-cardiovascular, non-cancer causes.
Abstract: Objective To quantify the dose-response relation between consumption of whole grain and specific types of grains and the risk of cardiovascular disease, total cancer, and all cause and cause specific mortality. Data sources PubMed and Embase searched up to 3 April 2016. Study selection Prospective studies reporting adjusted relative risk estimates for the association between intake of whole grains or specific types of grains and cardiovascular disease, total cancer, all cause or cause specific mortality. Data synthesis Summary relative risks and 95% confidence intervals calculated with a random effects model. Results 45 studies (64 publications) were included. The summary relative risks per 90 g/day increase in whole grain intake (90 g is equivalent to three servings—for example, two slices of bread and one bowl of cereal or one and a half pieces of pita bread made from whole grains) was 0.81 (95% confidence interval 0.75 to 0.87; I 2 =9%, n=7 studies) for coronary heart disease, 0.88 (0.75 to 1.03; I 2 =56%, n=6) for stroke, and 0.78 (0.73 to 0.85; I 2 =40%, n=10) for cardiovascular disease, with similar results when studies were stratified by whether the outcome was incidence or mortality. The relative risks for morality were 0.85 (0.80 to 0.91; I 2 =37%, n=6) for total cancer, 0.83 (0.77 to 0.90; I 2 =83%, n=11) for all causes, 0.78 (0.70 to 0.87; I 2 =0%, n=4) for respiratory disease, 0.49 (0.23 to 1.05; I 2 =85%, n=4) for diabetes, 0.74 (0.56 to 0.96; I 2 =0%, n=3) for infectious diseases, 1.15 (0.66 to 2.02; I 2 =79%, n=2) for diseases of the nervous system disease, and 0.78 (0.75 to 0.82; I 2 =0%, n=5) for all non-cardiovascular, non-cancer causes. Reductions in risk were observed up to an intake of 210-225 g/day (seven to seven and a half servings per day) for most of the outcomes. Intakes of specific types of whole grains including whole grain bread, whole grain breakfast cereals, and added bran, as well as total bread and total breakfast cereals were also associated with reduced risks of cardiovascular disease and/or all cause mortality, but there was little evidence of an association with refined grains, white rice, total rice, or total grains. Conclusions This meta-analysis provides further evidence that whole grain intake is associated with a reduced risk of coronary heart disease, cardiovascular disease, and total cancer, and mortality from all causes, respiratory diseases, infectious diseases, diabetes, and all non-cardiovascular, non-cancer causes. These findings support dietary guidelines that recommend increased intake of whole grain to reduce the risk of chronic diseases and premature mortality.

Proceedings ArticleDOI
12 May 2019
TL;DR: This paper proposes a new method to expose AI-generated fake face images or videos based on the observations that Deep Fakes are created by splicing synthesized face region into the original image, and in doing so, introducing errors that can be revealed when 3D head poses are estimated from the face images.
Abstract: In this paper, we propose a new method to expose AI-generated fake face images or videos (commonly known as the Deep Fakes). Our method is based on the observations that Deep Fakes are created by splicing synthesized face region into the original image, and in doing so, introducing errors that can be revealed when 3D head poses are estimated from the face images. We perform experiments to demonstrate this phenomenon and further develop a classification method based on this cue. Using features based on this cue, an SVM classifier is evaluated using a set of real face images and Deep Fakes.

Journal ArticleDOI
TL;DR: Circlator, the first tool to automate assembly circularization and produce accurate linear representations of circular sequences, correctly circularized 26 of 27 circularizable sequences.
Abstract: The assembly of DNA sequence data is undergoing a renaissance thanks to emerging technologies capable of producing reads tens of kilobases long. Assembling complete bacterial and small eukaryotic genomes is now possible, but the final step of circularizing sequences remains unsolved. Here we present Circlator, the first tool to automate assembly circularization and produce accurate linear representations of circular sequences. Using Pacific Biosciences and Oxford Nanopore data, Circlator correctly circularized 26 of 27 circularizable sequences, comprising 11 chromosomes and 12 plasmids from bacteria, the apicoplast and mitochondrion of Plasmodium falciparum and a human mitochondrion. Circlator is available at http://sanger-pathogens.github.io/circlator/.

Journal ArticleDOI
TL;DR: A deterministic transmission model was used to simulate potential HIV infections averted through structural changes in regions with concentrated and generalised epidemics, and high HIV prevalence among FSWs, and suggested that elimination of sexual violence alone could avert 17% of HIV infections in Kenya and 20% in Canada in the next decade.