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Journal ArticleDOI
TL;DR: Primary immunization with two doses of ChAdOx1 nCoV-19 or BNT162b2 vaccine provided limited protection against symptomatic disease caused by the omicron variant, but that protection waned over time.
Abstract: Abstract Background A rapid increase in coronavirus disease 2019 (Covid-19) cases due to the omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 in highly vaccinated populations has aroused concerns about the effectiveness of current vaccines. Methods We used a test-negative case–control design to estimate vaccine effectiveness against symptomatic disease caused by the omicron and delta (B.1.617.2) variants in England. Vaccine effectiveness was calculated after primary immunization with two doses of BNT162b2 (Pfizer–BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), or mRNA-1273 (Moderna) vaccine and after a booster dose of BNT162b2, ChAdOx1 nCoV-19, or mRNA-1273. Results Between November 27, 2021, and January 12, 2022, a total of 886,774 eligible persons infected with the omicron variant, 204,154 eligible persons infected with the delta variant, and 1,572,621 eligible test-negative controls were identified. At all time points investigated and for all combinations of primary course and booster vaccines, vaccine effectiveness against symptomatic disease was higher for the delta variant than for the omicron variant. No effect against the omicron variant was noted from 20 weeks after two ChAdOx1 nCoV-19 doses, whereas vaccine effectiveness after two BNT162b2 doses was 65.5% (95% confidence interval [CI], 63.9 to 67.0) at 2 to 4 weeks, dropping to 8.8% (95% CI, 7.0 to 10.5) at 25 or more weeks. Among ChAdOx1 nCoV-19 primary course recipients, vaccine effectiveness increased to 62.4% (95% CI, 61.8 to 63.0) at 2 to 4 weeks after a BNT162b2 booster before decreasing to 39.6% (95% CI, 38.0 to 41.1) at 10 or more weeks. Among BNT162b2 primary course recipients, vaccine effectiveness increased to 67.2% (95% CI, 66.5 to 67.8) at 2 to 4 weeks after a BNT162b2 booster before declining to 45.7% (95% CI, 44.7 to 46.7) at 10 or more weeks. Vaccine effectiveness after a ChAdOx1 nCoV-19 primary course increased to 70.1% (95% CI, 69.5 to 70.7) at 2 to 4 weeks after an mRNA-1273 booster and decreased to 60.9% (95% CI, 59.7 to 62.1) at 5 to 9 weeks. After a BNT162b2 primary course, the mRNA-1273 booster increased vaccine effectiveness to 73.9% (95% CI, 73.1 to 74.6) at 2 to 4 weeks; vaccine effectiveness fell to 64.4% (95% CI, 62.6 to 66.1) at 5 to 9 weeks. Conclusions Primary immunization with two doses of ChAdOx1 nCoV-19 or BNT162b2 vaccine provided limited protection against symptomatic disease caused by the omicron variant. A BNT162b2 or mRNA-1273 booster after either the ChAdOx1 nCoV-19 or BNT162b2 primary course substantially increased protection, but that protection waned over time. (Funded by the U.K. Health Security Agency.)

1,068 citations


Posted Content
TL;DR: The authors found that cooperative policies show much higher levels of emissions reductions than do non-cooperative strategies, and that there are substantial differences in the levels of controls in both the cooperative and the noncooperative policies among different countries.
Abstract: outcomes, and noncooperative equilibria. This study finds that cooperative policies show much higher levels of emissions reductions than do noncooperative strategies; that there are substantial differences in the levels of controls in both the cooperative and the noncooperative policies among different countries; and that high-income countries may be the major losers from cooperation. (JEL H41, Q4, Q2, Q20)

1,068 citations


Journal ArticleDOI
TL;DR: In this paper, the fundamental theory, experiments, and applications of TENGs are reviewed as a foundation of the energy for the new era with four major application fields: micro/nano power sources, self-powered sensors, large-scale blue energy, and direct high-voltage power sources.
Abstract: The triboelectric effect is ubiquitous in our everyday life and results from two different materials coming into contact. It is generally regarded as a negative effect in industry given that the electrostatic charges induced from it can lead to ignition, dust explosions, dielectric breakdown, electronic damage, etc. From an energy point of view, those electrostatic charges constitute a capacitive energy device when the two triboelectric surfaces are separated, which led to the invention of early electrostatic generators such as the “friction machine” and Van de Graaff generator.[1] As the world is marching into the era of the internet of things (IoTs) and artificial intelligence, the most vital development for hardware is a multifunctional array of sensing systems, which forms the foundation of the fourth industrial revolution toward an intelligent world. Given the need for mobility of these multitudes of sensors, the success of the IoTs calls for distributed energy sources, which can be provided by solar, thermal, wind, and mechanical triggering/vibrations. The triboelectric nanogenerator (TENG) for mechanical energy harvesting developed by Z.L. Wang’s group is one of the best choices for this energy for the new era, since triboelectrification is a universal and ubiquitous effect with an abundant choice of materials. The development of self-powered active sensors enabled by TENGs is revolutionary compared to externally powered passive sensors, similar to the advance from wired to wireless communication. In this paper, the fundamental theory, experiments, and applications of TENGs are reviewed as a foundation of the energy for the new era with four major application fields: micro/nano power sources, self-powered sensors, large-scale blue energy, and direct high-voltage power sources. A roadmap is proposed for the research and commercialization of TENG in the next 10 years.

1,068 citations


Journal ArticleDOI
TL;DR: With the propensity for mental health issues to hinder the success of college students, it is vital that colleges continually evaluate the mental health of their students and tailor treatment programs to specifically target their needs.

1,068 citations


Journal ArticleDOI
TL;DR: A low proportion of COVID-19 patients have a bacterial co-infection; less than in previous influenza pandemics; and these findings do not support the routine use of antibiotics in the management of confirmed CO VID-19 infection.

1,068 citations


Journal ArticleDOI
TL;DR: T careful attention to detail in producing MSC exosomes may provide a new therapeutic paradigm for cell‐free MSC‐based therapies with decreased risk.
Abstract: Mesenchymal stem cell transplantation is undergoing extensive evaluation as a cellular therapy in human clinical trials. Because MSCs are easily isolated and amenable to culture expansion in vitro there is a natural desire to test MSCs in many diverse clinical indications. This is exemplified by the rapidly expanding literature base that includes many in vivo animal models. More recently, MSC-derived extracellular vesicles (EVs), which include exosomes and microvesicles (MV), are being examined for their role in MSC-based cellular therapy. These vesicles are involved in cell-to-cell communication, cell signaling, and altering cell or tissue metabolism at short or long distances in the body. The exosomes and MVs can influence tissue responses to injury, infection, and disease. MSC-derived exosomes have a content that includes cytokines and growth factors, signaling lipids, mRNAs, and regulatory miRNAs. To the extent that MSC exosomes can be used for cell-free regenerative medicine, much will depend on the quality, reproducibility, and potency of their production, in the same manner that these parameters dictate the development of cell-based MSC therapies. However, the MSC exosome's contents are not static, but rather a product of the MSC tissue origin, its activities and the immediate intercellular neighbors of the MSCs. As such, the exosome content produced by MSCs appears to be altered when MSCs are cultured with tumor cells or in the in vivo tumor microenvironment. Therefore, careful attention to detail in producing MSC exosomes may provide a new therapeutic paradigm for cell-free MSC-based therapies with decreased risk. Stem Cells 2017;35:851-858.

1,067 citations


Journal ArticleDOI
08 Jan 2016-Science
TL;DR: To achieve true sustainability, assessments of new projects must go beyond local impacts by accounting for synergies with existing dams, as well as land cover changes and likely climatic shifts, and call for more sophisticated and holistic hydropower planning.
Abstract: The world's most biodiverse river basins—the Amazon, Congo, and Mekong—are experiencing an unprecedented boom in construction of hydropower dams. These projects address important energy needs, but advocates often overestimate economic benefits and underestimate far-reaching effects on biodiversity and critically important fisheries. Powerful new analytical tools and high-resolution environmental data can clarify trade-offs between engineering and environmental goals and can enable governments and funding institutions to compare alternative sites for dam building. Current site-specific assessment protocols largely ignore cumulative impacts on hydrology and ecosystem services as ever more dams are constructed within a watershed ( 1 ). To achieve true sustainability, assessments of new projects must go beyond local impacts by accounting for synergies with existing dams, as well as land cover changes and likely climatic shifts ( 2 , 3 ). We call for more sophisticated and holistic hydropower planning, including validation of technologies intended to mitigate environmental impacts. Should anything less be required when tampering with the world's great river ecosystems?

1,067 citations


Journal ArticleDOI
26 Mar 2020-JAMA
TL;DR: This JAMA Insights Clinical Update discusses the need to better understand the dynamics of respiratory disease transmission by better characterizing transmission routes, the role of patient physiology in shaping them, and best approaches for source control in the context of the COVID-19 outbreak.
Abstract: This JAMA Insights Clinical Update discusses the need to better understand the dynamics of respiratory disease transmission by better characterizing transmission routes, the role of patient physiology in shaping them, and best approaches for source control in the context of the COVID-19 outbreak

1,067 citations


Journal ArticleDOI
TL;DR: It is demonstrated that autophagy contributes to ferroptosis by degradation of ferritin in fibroblasts and cancer cells by knocking out or knockdown of Atg5 and Atg7, which provides novel insight into the interplay between Autophagy and regulated cell death.
Abstract: Macroautophagy/autophagy is an evolutionarily conserved degradation pathway that maintains homeostasis. Ferroptosis, a novel form of regulated cell death, is characterized by a production of reactive oxygen species from accumulated iron and lipid peroxidation. However, the relationship between autophagy and ferroptosis at the genetic level remains unclear. Here, we demonstrated that autophagy contributes to ferroptosis by degradation of ferritin in fibroblasts and cancer cells. Knockout or knockdown of Atg5 (autophagy-related 5) and Atg7 limited erastin-induced ferroptosis with decreased intracellular ferrous iron levels, and lipid peroxidation. Remarkably, NCOA4 (nuclear receptor coactivator 4) was a selective cargo receptor for the selective autophagic turnover of ferritin (namely ferritinophagy) in ferroptosis. Consistently, genetic inhibition of NCOA4 inhibited ferritin degradation and suppressed ferroptosis. In contrast, overexpression of NCOA4 increased ferritin degradation and promoted ferr...

1,067 citations


Journal ArticleDOI
31 Mar 2017-Science
TL;DR: It is shown that the co-receptor CD28 is strongly preferred over the TCR as a target for dephosphorylation by PD-1–recruited Shp2 phosphatase, suggesting that costimulatory pathways play key roles in regulating effector T cell function and responses to anti-PD-L1/PD-1 therapy.
Abstract: Programmed cell death–1 (PD-1) is a coinhibitory receptor that suppresses T cell activation and is an important cancer immunotherapy target. Upon activation by its ligand PD-L1, PD-1 is thought to suppress signaling through the T cell receptor (TCR). By titrating PD-1 signaling in a biochemical reconstitution system, we demonstrate that the co-receptor CD28 is strongly preferred over the TCR as a target for dephosphorylation by PD-1–recruited Shp2 phosphatase. We also show that CD28, but not the TCR, is preferentially dephosphorylated in response to PD-1 activation by PD-L1 in an intact cell system. These results reveal that PD-1 suppresses T cell function primarily by inactivating CD28 signaling, suggesting that costimulatory pathways play key roles in regulating effector T cell function and responses to anti–PD-L1/PD-1 therapy.

1,067 citations


Journal ArticleDOI
Lan Lan1, Dan Xu1, Guangming Ye1, Chen Xia, Shaokang Wang, Yirong Li1, Haibo Xu1 
21 Apr 2020-JAMA
TL;DR: This case series describes reverse transcriptase–polymerase chain reaction (RT-PCR) test results in 4 health professionals discharged from hospitalization or quarantine after 2 negative RT- PCR test results and resolution of clinical COVID-19 infection.
Abstract: This case series describes reverse transcriptase–polymerase chain reaction (RT-PCR) test results in 4 health professionals discharged from hospitalization or quarantine after 2 negative RT-PCR test results and resolution of clinical COVID-19 infection.

Book ChapterDOI
TL;DR: In this paper, the authors outline the development of the idea of "stakeholder management" as it has come to be applied in strategic management and suggest several related characteristics that serve as distinguishing features.
Abstract: The purpose of this chapter is to outline the development of the idea of "stakeholder management" as it has come to be applied in strategic management. We begin by developing a brief history of the concept. We then suggest that traditionally the stakeholder approach to strategic management has several related characteristics that serve as distinguishing features. We review recent work on stakeholder theory and suggest how stakeholder management has affected the practice of management. We end by suggesting further research questions.

Journal ArticleDOI
TL;DR: After standard neoadjuvant chemotherapy containing anthracycline, taxane, or both, the addition of adjuvant capecitabine therapy was safe and effective in prolonging disease‐free survival and overall survival among patients with HER2‐negative breast cancer who had residual invasive disease on pathological testing.
Abstract: BackgroundPatients who have residual invasive carcinoma after the receipt of neoadjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2)–negative breast cancer have poor prognoses. The benefit of adjuvant chemotherapy in these patients remains unclear. MethodsWe randomly assigned 910 patients with HER2-negative residual invasive breast cancer after neoadjuvant chemotherapy (containing anthracycline, taxane, or both) to receive standard postsurgical treatment either with capecitabine or without (control). The primary end point was disease-free survival. Secondary end points included overall survival. ResultsThe result of the prespecified interim analysis met the primary end point, so this trial was terminated early. The final analysis showed that disease-free survival was longer in the capecitabine group than in the control group (74.1% vs. 67.6% of the patients were alive and free from recurrence or second cancer at 5 years; hazard ratio for recurrence, second cancer, or death, 0.70; 95% ...

Journal ArticleDOI
TL;DR: In this article, a catalog of modified theories of gravity for which strong-field predictions have been computed and contrasted to Einstein's theory is presented, and the current understanding of the structure and dynamics of compact objects in these theories is summarized.
Abstract: One century after its formulation, Einstein's general relativity (GR) has made remarkable predictions and turned out to be compatible with all experimental tests. Most of these tests probe the theory in the weak-field regime, and there are theoretical and experimental reasons to believe that GR should be modified when gravitational fields are strong and spacetime curvature is large. The best astrophysical laboratories to probe strong-field gravity are black holes and neutron stars, whether isolated or in binary systems. We review the motivations to consider extensions of GR. We present a (necessarily incomplete) catalog of modified theories of gravity for which strong-field predictions have been computed and contrasted to Einstein's theory, and we summarize our current understanding of the structure and dynamics of compact objects in these theories. We discuss current bounds on modified gravity from binary pulsar and cosmological observations, and we highlight the potential of future gravitational wave measurements to inform us on the behavior of gravity in the strong-field regime.

Journal ArticleDOI
TL;DR: It is reported that nuclear factor erythroid 2‐related factor 2 (NRF2) plays a central role in protecting hepatocellular carcinoma (HCC) cells against ferroptosis, and the status of NRF2 is a key factor that determines the therapeutic response to ferroPTosis‐targeted therapies in HCC cells.

Journal ArticleDOI
TL;DR: There are several reasons why causal estimates from the MR-Egger method may be biased and have inflated Type 1 error rates in practice, including violations of the InSIDE assumption and the influence of outlying variants.
Abstract: Stephen Burgess is supported by Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 204623/Z/16/Z). Simon G. Thompson is supported by the British Heart Foundation (Grant Number CH/12/2/ 29428).

Journal ArticleDOI
29 Jun 2017
TL;DR: Vitamin B12 deficiency causes reversible megaloblastic anemia, demyelinating disease, or both; current assays have insufficient sensitivity and specificity; methylmalonic acid levels are useful to confirm diagnosis.
Abstract: Vitamin B12 deficiency causes reversible megaloblastic anemia, demyelinating disease, or both. Current assays have insufficient sensitivity and specificity; methylmalonic acid levels are useful to confirm diagnosis. Parenteral or high-dose oral vitamin B12 is effective therapy.

Journal ArticleDOI
TL;DR: An overview for the new classification of periodontal and peri-implant diseases and conditions is presented, along with a condensed scheme for each of four workgroup sections, but readers are directed to the pertinent consensus reports and review papers for a thorough discussion of the rationale, criteria, and interpretation of the proposed classification.
Abstract: A classification scheme for periodontal and peri-implant diseases and conditions is necessary for clinicians to properly diagnose and treat patients as well as for scientists to investigate etiology, pathogenesis, natural history, and treatment of the diseases and conditions. This paper summarizes the proceedings of the World Workshop on the Classification of Periodontal and Peri-implant Diseases and Conditions. The workshop was co-sponsored by the American Academy of Periodontology (AAP) and the European Federation of Periodontology (EFP) and included expert participants from all over the world. Planning for the conference, which was held in Chicago on November 9 to 11, 2017, began in early 2015. An organizing committee from the AAP and EFP commissioned 19 review papers and four consensus reports covering relevant areas in periodontology and implant dentistry. The authors were charged with updating the 1999 classification of periodontal diseases and conditions and developing a similar scheme for peri-implant diseases and conditions. Reviewers and workgroups were also asked to establish pertinent case definitions and to provide diagnostic criteria to aid clinicians in the use of the new classification. All findings and recommendations of the workshop were agreed to by consensus. This introductory paper presents an overview for the new classification of periodontal and peri-implant diseases and conditions, along with a condensed scheme for each of four workgroup sections, but readers are directed to the pertinent consensus reports and review papers for a thorough discussion of the rationale, criteria, and interpretation of the proposed classification. Changes to the 1999 classification are highlighted and discussed. Although the intent of the workshop was to base classification on the strongest available scientific evidence, lower level evidence and expert opinion were inevitably used whenever sufficient research data were unavailable. The scope of this workshop was to align and update the classification scheme to the current understanding of periodontal and peri-implant diseases and conditions. This introductory overview presents the schematic tables for the new classification of periodontal and peri-implant diseases and conditions and briefly highlights changes made to the 1999 classification. It cannot present the wealth of information included in the reviews, case definition papers, and consensus reports that has guided the development of the new classification, and reference to the consensus and case definition papers is necessary to provide a thorough understanding of its use for either case management or scientific investigation. Therefore, it is strongly recommended that the reader use this overview as an introduction to these subjects. Accessing this publication online will allow the reader to use the links in this overview and the tables to view the source papers (Table 1).

Journal ArticleDOI
TL;DR: Oral edoxaban was noninferior to subcutaneous dalteparin with respect to the composite outcome of recurrent venous thromboembolism or major bleeding during the 12 months after randomization, regardless of treatment duration.
Abstract: Background Low-molecular-weight heparin is the standard treatment for cancer-associated venous thromboembolism. The role of treatment with direct oral anticoagulant agents is unclear. Methods In this open-label, noninferiority trial, we randomly assigned patients with cancer who had acute symptomatic or incidental venous thromboembolism to receive either low-molecular-weight heparin for at least 5 days followed by oral edoxaban at a dose of 60 mg once daily (edoxaban group) or subcutaneous dalteparin at a dose of 200 IU per kilogram of body weight once daily for 1 month followed by dalteparin at a dose of 150 IU per kilogram once daily (dalteparin group). Treatment was given for at least 6 months and up to 12 months. The primary outcome was a composite of recurrent venous thromboembolism or major bleeding during the 12 months after randomization, regardless of treatment duration. Results Of the 1050 patients who underwent randomization, 1046 were included in the modified intention-to-treat analys...

Journal ArticleDOI
TL;DR: In patients with MCI, exercise training (6 months) is likely to improve cognitive measures and cognitive training may improve cognitive Measures, and no high-quality evidence exists to support pharmacologic treatments for MCI.
Abstract: Objective To update the 2001 American Academy of Neurology (AAN) guideline on mild cognitive impairment (MCI). Methods The guideline panel systematically reviewed MCI prevalence, prognosis, and treatment articles according to AAN evidence classification criteria, and based recommendations on evidence and modified Delphi consensus. Results MCI prevalence was 6.7% for ages 60–64, 8.4% for 65–69, 10.1% for 70–74, 14.8% for 75–79, and 25.2% for 80–84. Cumulative dementia incidence was 14.9% in individuals with MCI older than age 65 years followed for 2 years. No high-quality evidence exists to support pharmacologic treatments for MCI. In patients with MCI, exercise training (6 months) is likely to improve cognitive measures and cognitive training may improve cognitive measures. Major recommendations Clinicians should assess for MCI with validated tools in appropriate scenarios (Level B). Clinicians should evaluate patients with MCI for modifiable risk factors, assess for functional impairment, and assess for and treat behavioral/neuropsychiatric symptoms (Level B). Clinicians should monitor cognitive status of patients with MCI over time (Level B). Cognitively impairing medications should be discontinued where possible and behavioral symptoms treated (Level B). Clinicians may choose not to offer cholinesterase inhibitors (Level B); if offering, they must first discuss lack of evidence (Level A). Clinicians should recommend regular exercise (Level B). Clinicians may recommend cognitive training (Level C). Clinicians should discuss diagnosis, prognosis, long-term planning, and the lack of effective medicine options (Level B), and may discuss biomarker research with patients with MCI and families (Level C).

Proceedings ArticleDOI
23 Aug 2021
TL;DR: Wang et al. as discussed by the authors proposed a strong baseline model SwinIR for image restoration based on the Swin Transformer, which consists of three parts: shallow feature extraction, deep feature extraction and high-quality image reconstruction.
Abstract: Image restoration is a long-standing low-level vision problem that aims to restore high-quality images from low-quality images (e.g., downscaled, noisy and compressed images). While state-of-the-art image restoration methods are based on convolutional neural networks, few attempts have been made with Transformers which show impressive performance on high-level vision tasks. In this paper, we propose a strong baseline model SwinIR for image restoration based on the Swin Transformer. SwinIR consists of three parts: shallow feature extraction, deep feature extraction and high-quality image reconstruction. In particular, the deep feature extraction module is composed of several residual Swin Transformer blocks (RSTB), each of which has several Swin Transformer layers together with a residual connection. We conduct experiments on three representative tasks: image super-resolution (including classical, lightweight and real-world image super-resolution), image denoising (including grayscale and color image denoising) and JPEG compression artifact reduction. Experimental results demonstrate that SwinIR outperforms state-of-the-art methods on different tasks by $\textbf{up to 0.14$\sim$0.45dB}$, while the total number of parameters can be reduced by $\textbf{up to 67%}$.


Journal ArticleDOI
TL;DR: This Review will focus the discussion on three basic principles that define this unique therapeutic approach and highlight how anti-PD therapy is distinct from other immunotherapeutic approaches, namely tumor site immune modulation, targeting tumor-induced immune defects, and repairing ongoing (rather than generating de novo) tumor immunity.
Abstract: Major progress has been made toward our understanding of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway (referred to as the PD pathway). mAbs are already being used to block the PD pathway to treat human cancers (anti-PD therapy), especially advanced solid tumors. This therapy is based on principles that were discovered through basic research more than a decade ago, but the great potential of this pathway to treat a broad spectrum of advanced human cancers is just now becoming apparent. In this Review, we will briefly review the history and development of anti-PD therapy, from the original benchwork to the most up-to-date clinical results. We will then focus the discussion on three basic principles that define this unique therapeutic approach and highlight how anti-PD therapy is distinct from other immunotherapeutic approaches, namely tumor site immune modulation, targeting tumor-induced immune defects, and repairing ongoing (rather than generating de novo) tumor immunity. We believe that these fundamental principles set the standard for future immunotherapies and will guide our efforts to develop more efficacious and less toxic immune therapeutics to treat human cancers.

Journal ArticleDOI
TL;DR: It is concluded that neuroscience continues to support the brain disease model of addiction, which has led to the development of more effective methods of prevention and treatment and to more informed public health policies.
Abstract: This article reviews scientific advances in the prevention and treatment of substance-use disorder and related developments in public policy. In the past two decades, research has increasingly supported the view that addiction is a disease of the brain. Although the brain disease model of addiction has yielded effective preventive measures, treatment interventions, and public health policies to address substance-use disorders, the underlying concept of substance abuse as a brain disease continues to be questioned, perhaps because the aberrant, impulsive, and compulsive behaviors that are characteristic of addiction have not been clearly tied to neurobiology. Here we review recent advances in the neurobiology of addiction to clarify the link between addiction and brain function and to broaden the understanding of addiction as a brain disease. We review findings on the desensitization of reward circuits, which dampens the ability to feel pleasure and the motivation to pursue everyday activities; the increasing strength of conditioned responses and stress reactivity, which results in increased cravings for alcohol and other drugs and negative emotions when these cravings are not sated; and the weakening of the brain regions involved in executive functions such as decision making, inhibitory control, and self-regulation that leads to repeated relapse. We also review the ways in which social environments, developmental stages, and genetics are intimately linked to and influence vulnerability and recovery. We conclude that neuroscience continues to support the brain disease model of addiction. Neuroscience research in this area not only offers new opportunities for the prevention and treatment of substance addictions and related behavioral addictions (e.g., to food, sex, and gambling) but may also improve our understanding of the fundamental biologic processes involved in voluntary behavioral control. In the United States, 8 to 10% of people 12 years of age or older, or 20 to 22 million people, are addicted to alcohol or other drugs. 1 The abuse of tobacco, alcohol, and illicit drugs in the United States exacts more than $700 billion annually in costs related to crime, lost work productivity, and health care. 2-4 After centuries of efforts to reduce addiction and its related costs by punishing addictive behaviors failed to produce adequate results, recent basic and clinical research has provided clear evidence that addiction might be better considered and treated as an acquired disease of the brain (see Box 1 for definitions of substance-use disorder and addiction). Research guided by the brain disease model of addiction has led to the development of more effective methods of prevention and treatment and to more informed public health policies. Notable examples include the Mental Health Parity and Addiction Equity Act of 2008, which requires medical insurance plans to provide the same coverage for substance-use disorders and other mental illnesses that is provided for other illnesses, 5 and the proposed bipartisan Senate legislation that From the National Institute on Drug Abuse (N.D.V.) and the National Institute of Alcohol Abuse and Alcoholism (G.F.K.) — both in Bethesda, MD; and the Treatment Research Institute, Philadelphia (A.T.M.). Address reprint requests to Dr. Volkow at the National Institute on Drug Abuse, 6001 Executive Bld., Rm. 5274, Bethesda, MD 20892, or at nvolkow@ nida . nih . gov.

Book ChapterDOI
01 Dec 2018
TL;DR: Preliminary performance data on a subset of TPC-H is presented and it is shown that the system the team is building, C-Store, is substantially faster than popular commercial products.
Abstract: This paper presents the design of a read-optimized relational DBMS that contrasts sharply with most current systems, which are write-optimized. Among the many differences in its design are: storage of data by column rather than by row, careful coding and packing of objects into storage including main memory during query processing, storing an overlapping collection of column-oriented projections, rather than the current fare of tables and indexes, a non-traditional implementation of transactions which includes high availability and snapshot isolation for read-only transactions, and the extensive use of bitmap indexes to complement B-tree structures.We present preliminary performance data on a subset of TPC-H and show that the system we are building, C-Store, is substantially faster than popular commercial products. Hence, the architecture looks very encouraging.

Journal ArticleDOI
TL;DR: It is concluded that the ever-increasing production and consumption of ultra-processed products is a world crisis, to be confronted, checked and reversed as part of the work of the UN Sustainable Development Goals and its Decade of Nutrition.
Abstract: Given evident multiple threats to food systems and supplies, food security, human health and welfare, the living and physical world and the biosphere, the years 2016-2025 are now designated by the UN as the Decade of Nutrition, in support of the UN Sustainable Development Goals. For these initiatives to succeed, it is necessary to know which foods contribute to health and well-being, and which are unhealthy. The present commentary outlines the NOVA system of food classification based on the nature, extent and purpose of food processing. Evidence that NOVA effectively addresses the quality of diets and their impact on all forms of malnutrition, and also the sustainability of food systems, has now accumulated in a number of countries, as shown here. A singular feature of NOVA is its identification of ultra-processed food and drink products. These are not modified foods, but formulations mostly of cheap industrial sources of dietary energy and nutrients plus additives, using a series of processes (hence 'ultra-processed'). All together, they are energy-dense, high in unhealthy types of fat, refined starches, free sugars and salt, and poor sources of protein, dietary fibre and micronutrients. Ultra-processed products are made to be hyper-palatable and attractive, with long shelf-life, and able to be consumed anywhere, any time. Their formulation, presentation and marketing often promote overconsumption. Studies based on NOVA show that ultra-processed products now dominate the food supplies of various high-income countries and are increasingly pervasive in lower-middle- and upper-middle-income countries. The evidence so far shows that displacement of minimally processed foods and freshly prepared dishes and meals by ultra-processed products is associated with unhealthy dietary nutrient profiles and several diet-related non-communicable diseases. Ultra-processed products are also troublesome from social, cultural, economic, political and environmental points of view. We conclude that the ever-increasing production and consumption of these products is a world crisis, to be confronted, checked and reversed as part of the work of the UN Sustainable Development Goals and its Decade of Nutrition.

Journal ArticleDOI
TL;DR: Recommendations include discussions not present in previous ISHLT guidelines, including lung allocation scores, bridging to transplant with mechanical circulatory and ventilator support, and expanded indications for lung transplantation.
Abstract: The appropriate selection of lung transplant recipients is an important determinant of outcomes. This consensus document is an update of the recipient selection guidelines published in 2006. The Pulmonary Council of the International Society for Heart and Lung Transplantation (ISHLT) organized a Writing Committee of international experts to provide consensus opinion regarding the appropriate timing of referral and listing of candidates for lung transplantation. A comprehensive search of the medical literature was conducted with the assistance of a medical librarian. Writing Committee members were assigned specific topics to research and discuss. The Chairs of the Writing Committee were responsible for evaluating the completeness of the literature search, providing editorial support for the manuscript, and organizing group discussions regarding its content. The consensus document makes specific recommendations regarding the timing of referral and of listing for lung transplantation. These recommendations include discussions not present in previous ISHLT guidelines, including lung allocation scores, bridging to transplant with mechanical circulatory and ventilator support, and expanded indications for lung transplantation. In the absence of high-grade evidence to support decision making, these consensus guidelines remain part of a continuum of expert opinion based on available studies and personal experience. Some positions are immutable. Although transplant is rightly a treatment of last resort for end-stage lung disease, early referral allows proper evaluation and thorough patient education. Subsequent waiting list activation implies a tacit agreement that transplant offers a significant individual survival advantage. It is both the challenge and the responsibility of the transplant community globally to ensure organ allocation maximizes the potential benefits of a scarce resource, thereby achieving that advantage.

Journal ArticleDOI
TL;DR: A heterogeneous lamella structure in Ti produced by asymmetric rolling and partial recrystallization that can produce an unprecedented property combination: as strong as ultrafine-grained metal and at the same time as ductile as conventional coarse- grained metal.
Abstract: Grain refinement can make conventional metals several times stronger, but this comes at dramatic loss of ductility. Here we report a heterogeneous lamella structure in Ti produced by asymmetric rolling and partial recrystallization that can produce an unprecedented property combination: as strong as ultrafine-grained metal and at the same time as ductile as conventional coarse-grained metal. It also has higher strain hardening than coarse-grained Ti, which was hitherto believed impossible. The heterogeneous lamella structure is characterized with soft micrograined lamellae embedded in hard ultrafine-grained lamella matrix. The unusual high strength is obtained with the assistance of high back stress developed from heterogeneous yielding, whereas the high ductility is attributed to back-stress hardening and dislocation hardening. The process discovered here is amenable to large-scale industrial production at low cost, and might be applicable to other metal systems.

Journal ArticleDOI
TL;DR: Looking at outcomes for prostate cancer treated with radical prostatectomy or radiation therapy and validated a new grading system with more accurate grade stratification than current systems, including a simplified grading system of five grades and the lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa.

Proceedings ArticleDOI
13 Jun 2017
TL;DR: This work describes the ongoing collection of the “something-something” database of video prediction tasks whose solutions require a common sense understanding of the depicted situation, and describes the challenges in crowd-sourcing this data at scale.
Abstract: Neural networks trained on datasets such as ImageNet have led to major advances in visual object classification. One obstacle that prevents networks from reasoning more deeply about complex scenes and situations, and from integrating visual knowledge with natural language, like humans do, is their lack of common sense knowledge about the physical world. Videos, unlike still images, contain a wealth of detailed information about the physical world. However, most labelled video datasets represent high-level concepts rather than detailed physical aspects about actions and scenes. In this work, we describe our ongoing collection of the “something-something” database of video prediction tasks whose solutions require a common sense understanding of the depicted situation. The database currently contains more than 100,000 videos across 174 classes, which are defined as caption-templates. We also describe the challenges in crowd-sourcing this data at scale.