Showing papers by "Boston University published in 2018"
Clotilde Théry1, Kenneth W. Witwer2, Elena Aikawa3, María José Alcaraz4 +414 more•Institutions (209)
TL;DR: The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities, and a checklist is provided with summaries of key points.
Abstract: The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
5,988 citations
Gregory A. Roth1, Gregory A. Roth2, Degu Abate3, Kalkidan Hassen Abate4 +1025 more•Institutions (333)
TL;DR: Non-communicable diseases comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5–74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional causes accounted for 18·6% (17·9–19·6), and injuries 8·0% (7·7–8·2).
5,211 citations
Proceedings Article•
15 Feb 2018TL;DR: This article studied the adversarial robustness of neural networks through the lens of robust optimization and identified methods for both training and attacking neural networks that are reliable and, in a certain sense, universal.
Abstract: Recent work has demonstrated that deep neural networks are vulnerable to adversarial examples—inputs that are almost indistinguishable from natural data and yet classified incorrectly by the network. In fact, some of the latest findings suggest that the existence of adversarial attacks may be an inherent weakness of deep learning models. To address this problem, we study the adversarial robustness of neural networks through the lens of robust optimization. This approach provides us with a broad and unifying view on much of the prior work on this topic. Its principled nature also enables us to identify methods for both training and attacking neural networks that are reliable and, in a certain sense, universal. In particular, they specify a concrete security guarantee that would protect against any adversary. These methods let us train networks with significantly improved resistance to a wide range of adversarial attacks. They also suggest the notion of security against a first-order adversary as a natural and broad security guarantee. We believe that robustness against such well-defined classes of adversaries is an important stepping stone towards fully resistant deep learning models. Code and pre-trained models are available at this https URL and this https URL.
3,581 citations
Jeffrey D. Stanaway1, Ashkan Afshin1, Emmanuela Gakidou1, Stephen S Lim1 +1050 more•Institutions (346)
TL;DR: This study estimated levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs) by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017 and explored the relationship between development and risk exposure.
2,910 citations
Proceedings Article•
03 Jul 2018TL;DR: A novel discriminatively-trained Cycle-Consistent Adversarial Domain Adaptation model that adapts representations at both the pixel-level and feature-level, enforces cycle-consistency while leveraging a task loss, and does not require aligned pairs is proposed.
Abstract: Domain adaptation is critical for success in new, unseen environments. Adversarial adaptation models have shown tremendous progress towards adapting to new environments by focusing either on discovering domain invariant representations or by mapping between unpaired image domains. While feature space methods are difficult to interpret and sometimes fail to capture pixel-level and low-level domain shifts, image space methods sometimes fail to incorporate high level semantic knowledge relevant for the end task. We propose a model which adapts between domains using both generative image space alignment and latent representation space alignment. Our approach, Cycle-Consistent Adversarial Domain Adaptation (CyCADA), guides transfer between domains according to a specific discriminatively trained task and avoids divergence by enforcing consistency of the relevant semantics before and after adaptation. We evaluate our method on a variety of visual recognition and prediction settings, including digit classification and semantic segmentation of road scenes, advancing state-of-the-art performance for unsupervised adaptation from synthetic to real world driving domains.
2,459 citations
National Taiwan University1, Kumamoto University2, Heidelberg University3, University of Münster4, Boston University5, University of Messina6, University of British Columbia7, University of Barcelona8, Columbia University9, Sungkyunkwan University10, Konkuk University11, Istanbul University12, Shinshu University13, University College London14, Harvard University15, Johns Hopkins University16, Mayo Clinic17, Alnylam Pharmaceuticals18, Umeå University19
TL;DR: Patisiran improved multiple clinical manifestations of hereditary transthyretin amyloidosis with polyneuropathy and showed an effect on gait speed and modified BMI.
Abstract: BACKGROUND: Patisiran, an investigational RNA interference therapeutic agent, specifically inhibits hepatic synthesis of transthyretin.METHODS: In this phase 3 trial, we randomly assigned patients ...
1,671 citations
Verneri Anttila1, Verneri Anttila2, Brendan Bulik-Sullivan2, Brendan Bulik-Sullivan1 +717 more•Institutions (270)
TL;DR: It is demonstrated that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine, and it is shown that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures.
Abstract: Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
1,357 citations
Stanford University1, Katholieke Universiteit Leuven2, Max Planck Society3, Brown University4, St. Jude Children's Research Hospital5, University of Zurich6, Switch7, University of Pennsylvania8, Boston University9, Vrije Universiteit Brussel10, Hungarian Academy of Sciences11, University of Debrecen12
TL;DR: A combination of techniques from cell biology, biophysics, physical chemistry, structural biology, and bioinformatics are starting to help establish the molecular principles of an emerging field, thus paving the way for exciting discoveries, including novel therapeutic approaches for the treatment of age-related disorders.
1,317 citations
Columbia University1, Complutense University of Madrid2, Ege University3, University of Birmingham4, Rutgers University5, University of Hong Kong6, Boston University7, University of Michigan8, University of Pisa9, University of Louisville10, University of Bonn11, University of Pennsylvania12, University at Buffalo13, University of Greifswald14, Ohio State University15, VU University Amsterdam16, Technion – Israel Institute of Technology17, Peking University18, University of Geneva19, University College London20, University of North Carolina at Chapel Hill21, University of Queensland22
TL;DR: A new periodontitis classification scheme has been adopted, in which forms of the disease previously recognized as "chronic" or "aggressive" are now grouped under a single category ("periodontitis") and are further characterized based on a multi-dimensional staging and grading system as mentioned in this paper.
Abstract: A new periodontitis classification scheme has been adopted, in which forms of the disease previously recognized as "chronic" or "aggressive" are now grouped under a single category ("periodontitis") and are further characterized based on a multi-dimensional staging and grading system. Staging is largely dependent upon the severity of disease at presentation as well as on the complexity of disease management, while grading provides supplemental information about biological features of the disease including a history-based analysis of the rate of periodontitis progression; assessment of the risk for further progression; analysis of possible poor outcomes of treatment; and assessment of the risk that the disease or its treatment may negatively affect the general health of the patient. Necrotizing periodontal diseases, whose characteristic clinical phenotype includes typical features (papilla necrosis, bleeding, and pain) and are associated with host immune response impairments, remain a distinct periodontitis category. Endodontic-periodontal lesions, defined by a pathological communication between the pulpal and periodontal tissues at a given tooth, occur in either an acute or a chronic form, and are classified according to signs and symptoms that have direct impact on their prognosis and treatment. Periodontal abscesses are defined as acute lesions characterized by localized accumulation of pus within the gingival wall of the periodontal pocket/sulcus, rapid tissue destruction and are associated with risk for systemic dissemination.
1,301 citations
TL;DR: A deep learning algorithm similar in spirit to Galerkin methods, using a deep neural network instead of linear combinations of basis functions is proposed, and is implemented for American options in up to 100 dimensions.
1,290 citations
TL;DR: In insights into the role of alcohol consumption in the genetic architecture of hypertension, a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions is conducted.
Abstract: Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
University of Oxford1, University of Michigan2, Wellcome Trust Sanger Institute3, Amgen4, University of Cambridge5, University of Copenhagen6, University of Liverpool7, University of Freiburg8, Boston University9, University of Tartu10, Erasmus University Medical Center11, Leiden University Medical Center12, Pasteur Institute13, Icahn School of Medicine at Mount Sinai14, UCLA Medical Center15, Vanderbilt University Medical Center16, Wake Forest University17, National University of Singapore18, London North West Healthcare NHS Trust19, Imperial College London20, Charité21, Innsbruck Medical University22, Washington University in St. Louis23, Queen Mary University of London24, University of Southern Denmark25, National and Kapodistrian University of Athens26, Robertson Centre for Biostatistics27, University of Exeter28, Uppsala University29, University of Düsseldorf30, Steno Diabetes Center31, Aalborg University32, University of Eastern Finland33, Broad Institute34, Frederiksberg Hospital35, Lund University36, University of Bergen37, Technische Universität München38, University of North Carolina at Chapel Hill39, Ninewells Hospital40, University of Edinburgh41, University of Minnesota42, University of Glasgow43, Ludwig Maximilian University of Munich44, University of Iceland45, Aarhus University46, Science for Life Laboratory47, Stanford University48, University of Helsinki49, National Institutes of Health50, University of Dundee51, Harvard University52
TL;DR: Combining 32 genome-wide association studies with high-density imputation provides a comprehensive view of the genetic contribution to type 2 diabetes in individuals of European ancestry with respect to locus discovery, causal-variant resolution, and mechanistic insight.
Abstract: We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci, 135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency 2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).
TL;DR: A comprehensive genetic analysis of 304 primary DLBCLs identified low-frequency alterations, captured recurrent mutations, somatic copy number alterations, and structural variants, and defined coordinate signatures in patients with available outcome data to provide a roadmap for an actionableDLBCL classification.
Abstract: Diffuse large B cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is a clinically and genetically heterogeneous disease that is further classified into transcriptionally defined activated B cell (ABC) and germinal center B cell (GCB) subtypes. We carried out a comprehensive genetic analysis of 304 primary DLBCLs and identified low-frequency alterations, captured recurrent mutations, somatic copy number alterations, and structural variants, and defined coordinate signatures in patients with available outcome data. We integrated these genetic drivers using consensus clustering and identified five robust DLBCL subsets, including a previously unrecognized group of low-risk ABC-DLBCLs of extrafollicular/marginal zone origin; two distinct subsets of GCB-DLBCLs with different outcomes and targetable alterations; and an ABC/GCB-independent group with biallelic inactivation of TP53, CDKN2A loss, and associated genomic instability. The genetic features of the newly characterized subsets, their mutational signatures, and the temporal ordering of identified alterations provide new insights into DLBCL pathogenesis. The coordinate genetic signatures also predict outcome independent of the clinical International Prognostic Index and suggest new combination treatment strategies. More broadly, our results provide a roadmap for an actionable DLBCL classification.
Adrian F. Hernandez1, Jennifer B. Green1, Salim Janmohamed2, Ralph B. D'Agostino3 +795 more•Institutions (7)
TL;DR: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events, and evidence-based glucagon-like peptide 1 receptor agonists should be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events.
TL;DR: Initial results from the first stage of the WHO World Mental Health International College Student project are reported, in which a series of surveys in 19 colleges were carried out with the aim of estimating prevalence and basic sociodemographic correlates of common mental disorders among first-year college students.
Abstract: Increasingly, colleges across the world are contending with rising rates of mental disorders, and in many cases, the demand for services on campus far exceeds the available resources. The present study reports initial results from the first stage of the WHO World Mental Health International College Student project, in which a series of surveys in 19 colleges across 8 countries (Australia, Belgium, Germany, Mexico, Northern Ireland, South Africa, Spain, United States) were carried out with the aim of estimating prevalence and basic sociodemographic correlates of common mental disorders among first-year college students. Web-based self-report questionnaires administered to incoming first-year students (45.5% pooled response rate) screened for six common lifetime and 12-month DSM-IV mental disorders: major depression, mania/hypomania, generalized anxiety disorder, panic disorder, alcohol use disorder, and substance use disorder. We focus on the 13,984 respondents who were full-time students: 35% of whom screened positive for at least one of the common lifetime disorders assessed and 31% screened positive for at least one 12-month disorder. Syndromes typically had onsets in early to middle adolescence and persisted into the year of the survey. Although relatively modest, the strongest correlates of screening positive were older age, female sex, unmarried-deceased parents, no religious affiliation, nonheterosexual identification and behavior, low secondary school ranking, and extrinsic motivation for college enrollment. The weakness of these associations means that the syndromes considered are widely distributed with respect to these variables in the student population. Although the extent to which cost-effective treatment would reduce these risks is unclear, the high level of need for mental health services implied by these results represents a major challenge to institutions of higher education and governments. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Kaiser Permanente1, University of Iowa2, Stanford University3, Veterans Health Administration4, University of California, San Francisco5, Oregon Health & Science University6, Columbia University7, University of Pennsylvania8, University of Georgia9, Virginia Tech10, Nationwide Children's Hospital11, Virginia Commonwealth University12, Temple University13, University of Alabama at Birmingham14, University of California, Los Angeles15, Boston University16, Northwestern University17, Icahn School of Medicine at Mount Sinai18, University of Hawaii19
TL;DR: The USPSTF concludes with moderate certainty that the net benefit of PSA-based screening for prostate cancer in men aged 55 to 69 years is small for some men.
Abstract: Importance In the United States, the lifetime risk of being diagnosed with prostate cancer is approximately 11%, and the lifetime risk of dying of prostate cancer is 2.5%. The median age of death from prostate cancer is 80 years. Many men with prostate cancer never experience symptoms and, without screening, would never know they have the disease. African American men and men with a family history of prostate cancer have an increased risk of prostate cancer compared with other men. Objective To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on prostate-specific antigen (PSA)–based screening for prostate cancer. Evidence Review The USPSTF reviewed the evidence on the benefits and harms of PSA-based screening for prostate cancer and subsequent treatment of screen-detected prostate cancer. The USPSTF also commissioned a review of existing decision analysis models and the overdiagnosis rate of PSA-based screening. The reviews also examined the benefits and harms of PSA-based screening in patient subpopulations at higher risk of prostate cancer, including older men, African American men, and men with a family history of prostate cancer. Findings Adequate evidence from randomized clinical trials shows that PSA-based screening programs in men aged 55 to 69 years may prevent approximately 1.3 deaths from prostate cancer over approximately 13 years per 1000 men screened. Screening programs may also prevent approximately 3 cases of metastatic prostate cancer per 1000 men screened. Potential harms of screening include frequent false-positive results and psychological harms. Harms of prostate cancer treatment include erectile dysfunction, urinary incontinence, and bowel symptoms. About 1 in 5 men who undergo radical prostatectomy develop long-term urinary incontinence, and 2 in 3 men will experience long-term erectile dysfunction. Adequate evidence shows that the harms of screening in men older than 70 years are at least moderate and greater than in younger men because of increased risk of false-positive results, diagnostic harms from biopsies, and harms from treatment. The USPSTF concludes with moderate certainty that the net benefit of PSA-based screening for prostate cancer in men aged 55 to 69 years is small for some men. How each man weighs specific benefits and harms will determine whether the overall net benefit is small. The USPSTF concludes with moderate certainty that the potential benefits of PSA-based screening for prostate cancer in men 70 years and older do not outweigh the expected harms. Conclusions and Recommendation For men aged 55 to 69 years, the decision to undergo periodic PSA-based screening for prostate cancer should be an individual one and should include discussion of the potential benefits and harms of screening with their clinician. Screening offers a small potential benefit of reducing the chance of death from prostate cancer in some men. However, many men will experience potential harms of screening, including false-positive results that require additional testing and possible prostate biopsy; overdiagnosis and overtreatment; and treatment complications, such as incontinence and erectile dysfunction. In determining whether this service is appropriate in individual cases, patients and clinicians should consider the balance of benefits and harms on the basis of family history, race/ethnicity, comorbid medical conditions, patient values about the benefits and harms of screening and treatment-specific outcomes, and other health needs. Clinicians should not screen men who do not express a preference for screening. (C recommendation) The USPSTF recommends against PSA-based screening for prostate cancer in men 70 years and older. (D recommendation)
Indiana University – Purdue University Indianapolis1, Federal University of Rio de Janeiro2, Boston University3, Johns Hopkins University4, Mayo Clinic5, University of California, Irvine6, University of Pavia7, Columbia University8, University College London9, University of Pennsylvania10, Oregon Health & Science University11, University of Lisbon12, University of Münster13, University of Messina14, University of Barcelona15, Auckland City Hospital16
TL;DR: Inotersen improved the course of neurologic disease and quality of life in patients with hereditary transthyretin amyloidosis and improvements were independent of disease stage, mutation type, or the presence of cardiomyopathy.
Abstract: Background Hereditary transthyretin amyloidosis is caused by pathogenic single-nucleotide variants in the gene encoding transthyretin (TTR) that induce transthyretin misfolding and systemi...
Sandia National Laboratories1, University of California, Davis2, Massachusetts Institute of Technology3, Cornell University4, United States Army Research Laboratory5, Ohio State University6, University of California, Santa Barbara7, Boston University8, North Carolina State University9, Purdue University10, Georgia Institute of Technology11, Michigan State University12, Air Force Research Laboratory13, National Institute of Information and Communications Technology14, University of South Carolina15, United States Naval Research Laboratory16, Arizona State University17, University of Illinois at Urbana–Champaign18, Vanderbilt University19
TL;DR: The UWBG semiconductor materials, such as high Al‐content AlGaN, diamond and Ga2O3, advanced in maturity to the point where realizing some of their tantalizing advantages is a relatively near‐term possibility.
Abstract: J. Y. Tsao,* S. Chowdhury, M. A. Hollis,* D. Jena, N. M. Johnson, K. A. Jones, R. J. Kaplar,* S. Rajan, C. G. Van de Walle, E. Bellotti, C. L. Chua, R. Collazo, M. E. Coltrin, J. A. Cooper, K. R. Evans, S. Graham, T. A. Grotjohn, E. R. Heller, M. Higashiwaki, M. S. Islam, P. W. Juodawlkis, M. A. Khan, A. D. Koehler, J. H. Leach, U. K. Mishra, R. J. Nemanich, R. C. N. Pilawa-Podgurski, J. B. Shealy, Z. Sitar, M. J. Tadjer, A. F. Witulski, M. Wraback, and J. A. Simmons
University of Iowa1, Virginia Commonwealth University2, Stanford University3, Veterans Health Administration4, Harvard University5, Oregon Health & Science University6, Columbia University7, University of Pennsylvania8, Virginia Tech9, Nationwide Children's Hospital10, Temple University11, University of Alabama at Birmingham12, University of California, Los Angeles13, Brown University14, Boston University15, Northwestern University16, University of Hawaii17, Tufts University18
TL;DR: The USPSTF concludes with high certainty that the benefits of screening every 3 years with cytology alone in women aged 21 to 29 years substantially outweigh the harms and screening women younger than 21 years does not provide significant benefit.
Abstract: Importance The number of deaths from cervical cancer in the United States has decreased substantially since the implementation of widespread cervical cancer screening and has declined from 2.8 to 2.3 deaths per 100 000 women from 2000 to 2015. Objective To update the US Preventive Services Task Force (USPSTF) 2012 recommendation on screening for cervical cancer. Evidence Review The USPSTF reviewed the evidence on screening for cervical cancer, with a focus on clinical trials and cohort studies that evaluated screening with high-risk human papillomavirus (hrHPV) testing alone or hrHPV and cytology together (cotesting) compared with cervical cytology alone. The USPSTF also commissioned a decision analysis model to evaluate the age at which to begin and end screening, the optimal interval for screening, the effectiveness of different screening strategies, and related benefits and harms of different screening strategies. Findings Screening with cervical cytology alone, primary hrHPV testing alone, or cotesting can detect high-grade precancerous cervical lesions and cervical cancer. Screening women aged 21 to 65 years substantially reduces cervical cancer incidence and mortality. The harms of screening for cervical cancer in women aged 30 to 65 years are moderate. The USPSTF concludes with high certainty that the benefits of screening every 3 years with cytology alone in women aged 21 to 29 years substantially outweigh the harms. The USPSTF concludes with high certainty that the benefits of screening every 3 years with cytology alone, every 5 years with hrHPV testing alone, or every 5 years with both tests (cotesting) in women aged 30 to 65 years outweigh the harms. Screening women older than 65 years who have had adequate prior screening and women younger than 21 years does not provide significant benefit. Screening women who have had a hysterectomy with removal of the cervix for indications other than a high-grade precancerous lesion or cervical cancer provides no benefit. The USPSTF concludes with moderate to high certainty that screening women older than 65 years who have had adequate prior screening and are not otherwise at high risk for cervical cancer, screening women younger than 21 years, and screening women who have had a hysterectomy with removal of the cervix for indications other than a high-grade precancerous lesion or cervical cancer does not result in a positive net benefit. Conclusions and Recommendation The USPSTF recommends screening for cervical cancer every 3 years with cervical cytology alone in women aged 21 to 29 years. (A recommendation) The USPSTF recommends screening every 3 years with cervical cytology alone, every 5 years with hrHPV testing alone, or every 5 years with hrHPV testing in combination with cytology (cotesting) in women aged 30 to 65 years. (A recommendation) The USPSTF recommends against screening for cervical cancer in women younger than 21 years. (D recommendation) The USPSTF recommends against screening for cervical cancer in women older than 65 years who have had adequate prior screening and are not otherwise at high risk for cervical cancer. (D recommendation) The USPSTF recommends against screening for cervical cancer in women who have had a hysterectomy with removal of the cervix and do not have a history of a high-grade precancerous lesion or cervical cancer. (D recommendation)
Columbia University1, Complutense University of Madrid2, Ege University3, University of Birmingham4, Rutgers University5, University of Hong Kong6, Boston University7, University of Michigan8, University of Pisa9, University of Louisville10, University of Bonn11, University of Pennsylvania12, University at Buffalo13, University of Greifswald14, Ohio State University15, VU University Amsterdam16, Technion – Israel Institute of Technology17, Peking University18, University of Geneva19, University College London20, University of North Carolina at Chapel Hill21, University of Queensland22
TL;DR: A new periodontitis classification scheme has been adopted, in which forms of the disease previously recognized as "chronic" or "aggressive" are now grouped under a single category ("periodontitis") and are further characterized based on a multi-dimensional staging and grading system.
Abstract: A new periodontitis classification scheme has been adopted, in which forms of the disease previously recognized as \"chronic\" or \"aggressive\" are now grouped under a single category (\"periodontitis\") and are further characterized based on a multi-dimensional staging and grading system. Staging is largely dependent upon the severity of disease at presentation as well as on the complexity of disease management, while grading provides supplemental information about biological features of the disease including a history-based analysis of the rate of periodontitis progression; assessment of the risk for further progression; analysis of possible poor outcomes of treatment; and assessment of the risk that the disease or its treatment may negatively affect the general health of the patient. Necrotizing periodontal diseases, whose characteristic clinical phenotype includes typical features (papilla necrosis, bleeding, and pain) and are associated with host immune response impairments, remain a distinct periodontitis category. Endodontic-periodontal lesions, defined by a pathological communication between the pulpal and periodontal tissues at a given tooth, occur in either an acute or a chronic form, and are classified according to signs and symptoms that have direct impact on their prognosis and treatment. Periodontal abscesses are defined as acute lesions characterized by localized accumulation of pus within the gingival wall of the periodontal pocket/sulcus, rapid tissue destruction and are associated with risk for systemic dissemination.
TL;DR: In this paper, the authors examine the concerns that new technologies will render labor redundant in a framework in which tasks previously performed by labor can be automated and new versions of existing tasks, in which labor has a comparative advantage, can be created.
Abstract: We examine the concerns that new technologies will render labor redundant in a framework in which tasks previously performed by labor can be automated and new versions of existing tasks, in which labor has a comparative advantage, can be created. In a static version where capital is fixed and technology is exogenous, automation reduces employment and the labor share, and may even reduce wages, while the creation of new tasks has the opposite effects. Our full model endogenizes capital accumulation and the direction of research towards automation and the creation of new tasks. If the long-run rental rate of capital relative to the wage is sufficiently low, the long-run equilibrium involves automation of all tasks. Otherwise, there exists a stable balanced growth path in which the two types of innovations go hand-in-hand. Stability is a consequence of the fact that automation reduces the cost of producing using labor, and thus discourages further automation and encourages the creation of new tasks. In an extension with heterogeneous skills, we show that inequality increases during transitions driven both by faster automation and introduction of new tasks, and characterize the conditions under which inequality is increasing or stable in the long run.
TL;DR: A way of integrating photonics with silicon nanoelectronics is described, using polycrystalline silicon on glass islands alongside transistors on bulk silicon complementary metal–oxide–semiconductor chips to address the demand for high-bandwidth optical interconnects in data centres and high-performance computing.
Abstract: Electronic and photonic technologies have transformed our lives-from computing and mobile devices, to information technology and the internet. Our future demands in these fields require innovation in each technology separately, but also depend on our ability to harness their complementary physics through integrated solutions1,2. This goal is hindered by the fact that most silicon nanotechnologies-which enable our processors, computer memory, communications chips and image sensors-rely on bulk silicon substrates, a cost-effective solution with an abundant supply chain, but with substantial limitations for the integration of photonic functions. Here we introduce photonics into bulk silicon complementary metal-oxide-semiconductor (CMOS) chips using a layer of polycrystalline silicon deposited on silicon oxide (glass) islands fabricated alongside transistors. We use this single deposited layer to realize optical waveguides and resonators, high-speed optical modulators and sensitive avalanche photodetectors. We integrated this photonic platform with a 65-nanometre-transistor bulk CMOS process technology inside a 300-millimetre-diameter-wafer microelectronics foundry. We then implemented integrated high-speed optical transceivers in this platform that operate at ten gigabits per second, composed of millions of transistors, and arrayed on a single optical bus for wavelength division multiplexing, to address the demand for high-bandwidth optical interconnects in data centres and high-performance computing3,4. By decoupling the formation of photonic devices from that of transistors, this integration approach can achieve many of the goals of multi-chip solutions 5 , but with the performance, complexity and scalability of 'systems on a chip'1,6-8. As transistors smaller than ten nanometres across become commercially available 9 , and as new nanotechnologies emerge10,11, this approach could provide a way to integrate photonics with state-of-the-art nanoelectronics.
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TL;DR: In this article, the authors proposed a new deep learning approach, Moment Matching for Multi-source Domain Adaptation M3SDA, which aims to transfer knowledge learned from multiple labeled source domains to an unlabeled target domain by dynamically aligning moments of their feature distributions.
Abstract: Conventional unsupervised domain adaptation (UDA) assumes that training data are sampled from a single domain. This neglects the more practical scenario where training data are collected from multiple sources, requiring multi-source domain adaptation. We make three major contributions towards addressing this problem. First, we collect and annotate by far the largest UDA dataset, called DomainNet, which contains six domains and about 0.6 million images distributed among 345 categories, addressing the gap in data availability for multi-source UDA research. Second, we propose a new deep learning approach, Moment Matching for Multi-Source Domain Adaptation M3SDA, which aims to transfer knowledge learned from multiple labeled source domains to an unlabeled target domain by dynamically aligning moments of their feature distributions. Third, we provide new theoretical insights specifically for moment matching approaches in both single and multiple source domain adaptation. Extensive experiments are conducted to demonstrate the power of our new dataset in benchmarking state-of-the-art multi-source domain adaptation methods, as well as the advantage of our proposed model. Dataset and Code are available at \url{this http URL}.
TL;DR: It is reported that cooperative cation-π interactions between tyrosines in the LC domain and arginines in structured C-terminal domains also contribute to phase separation, and transportin acts as a physiological molecular chaperone of FUS in neuron terminals, reducing phase separation and gelation of methylated and hypomethylated FUS and rescuing protein synthesis.
TL;DR: Monitoring the assembly of hundreds of soil- and plant-derived microbiomes in well-controlled minimal synthetic media shows that the community-level function and the coarse-grained taxonomy of the resulting communities are highly predictable and governed by nutrient availability, despite substantial species variability.
Abstract: A major unresolved question in microbiome research is whether the complex taxonomic architectures observed in surveys of natural communities can be explained and predicted by fundamental, quantitative principles. Bridging theory and experiment is hampered by the multiplicity of ecological processes that simultaneously affect community assembly in natural ecosystems. We addressed this challenge by monitoring the assembly of hundreds of soil- and plant-derived microbiomes in well-controlled minimal synthetic media. Both the community-level function and the coarse-grained taxonomy of the resulting communities are highly predictable and governed by nutrient availability, despite substantial species variability. By generalizing classical ecological models to include widespread nonspecific cross-feeding, we show that these features are all emergent properties of the assembly of large microbial communities, explaining their ubiquity in natural microbiomes.
TL;DR: This work develops split-pool recognition of interactions by tag extension (SPRITE), a method that enables genome-wide detection of higher-order interactions within the nucleus and generates a global model whereby nuclear bodies act as inter-chromosomal hubs that shape the overall packaging of DNA in the nucleus.
TL;DR: In this paper, a multivariable Cox proportional hazards model was used to examine MOUD as a monthly time-varying exposure variable to predict time to all-cause and opioid-related mortality.
Abstract: Background Opioid overdose survivors have an increased risk for death. Whether use of medications for opioid use disorder (MOUD) after overdose is associated with mortality is not known. Objective To identify MOUD use after opioid overdose and its association with all-cause and opioid-related mortality. Design Retrospective cohort study. Setting 7 individually linked data sets from Massachusetts government agencies. Participants 17 568 Massachusetts adults without cancer who survived an opioid overdose between 2012 and 2014. Measurements Three types of MOUD were examined: methadone maintenance treatment (MMT), buprenorphine, and naltrexone. Exposure to MOUD was identified at monthly intervals, and persons were considered exposed through the month after last receipt. A multivariable Cox proportional hazards model was used to examine MOUD as a monthly time-varying exposure variable to predict time to all-cause and opioid-related mortality. Results In the 12 months after a nonfatal overdose, 2040 persons (11%) enrolled in MMT for a median of 5 months (interquartile range, 2 to 9 months), 3022 persons (17%) received buprenorphine for a median of 4 months (interquartile range, 2 to 8 months), and 1099 persons (6%) received naltrexone for a median of 1 month (interquartile range, 1 to 2 months). Among the entire cohort, all-cause mortality was 4.7 deaths (95% CI, 4.4 to 5.0 deaths) per 100 person-years and opioid-related mortality was 2.1 deaths (CI, 1.9 to 2.4 deaths) per 100 person-years. Compared with no MOUD, MMT was associated with decreased all-cause mortality (adjusted hazard ratio [AHR], 0.47 [CI, 0.32 to 0.71]) and opioid-related mortality (AHR, 0.41 [CI, 0.24 to 0.70]). Buprenorphine was associated with decreased all-cause mortality (AHR, 0.63 [CI, 0.46 to 0.87]) and opioid-related mortality (AHR, 0.62 [CI, 0.41 to 0.92]). No associations between naltrexone and all-cause mortality (AHR, 1.44 [CI, 0.84 to 2.46]) or opioid-related mortality (AHR, 1.42 [CI, 0.73 to 2.79]) were identified. Limitation Few events among naltrexone recipients preclude confident conclusions. Conclusion A minority of opioid overdose survivors received MOUD. Buprenorphine and MMT were associated with reduced all-cause and opioid-related mortality. Primary funding source National Center for Advancing Translational Sciences of the National Institutes of Health.
TL;DR: A new backpropagation scheme, called Excitation Backprop, is proposed to pass along top-down signals downwards in the network hierarchy via a probabilistic Winner-Take-All process, and the concept of contrastive attention is introduced to make the top- down attention maps more discriminative.
Abstract: We aim to model the top-down attention of a convolutional neural network (CNN) classifier for generating task-specific attention maps. Inspired by a top-down human visual attention model, we propose a new backpropagation scheme, called Excitation Backprop, to pass along top-down signals downwards in the network hierarchy via a probabilistic Winner-Take-All process. Furthermore, we introduce the concept of contrastive attention to make the top-down attention maps more discriminative. We show a theoretic connection between the proposed contrastive attention formulation and the Class Activation Map computation. Efficient implementation of Excitation Backprop for common neural network layers is also presented. In experiments, we visualize the evidence of a model’s classification decision by computing the proposed top-down attention maps. For quantitative evaluation, we report the accuracy of our method in weakly supervised localization tasks on the MS COCO, PASCAL VOC07 and ImageNet datasets. The usefulness of our method is further validated in the text-to-region association task. On the Flickr30k Entities dataset, we achieve promising performance in phrase localization by leveraging the top-down attention of a CNN model that has been trained on weakly labeled web images. Finally, we demonstrate applications of our method in model interpretation and data annotation assistance for facial expression analysis and medical imaging tasks.
TL;DR: An iterative cluster Primal Dual Splitting algorithm for solving the large-scale sSVM problem in a decentralized fashion, which extracts important features discovered by the algorithm that are predictive of future hospitalizations, thus providing a way to interpret the classification results and inform prevention efforts.
TL;DR: Recent advances in the understanding of the clinical evaluation and treatment of Alzheimer’s disease are discussed, with updates regarding clinical trials still in progress.
Abstract: Alzheimer’s disease is the most common cause of dementia worldwide, with the prevalence continuing to grow in part because of the aging world population. This neurodegenerative disease process is characterized classically by two hallmark pathologies: β-amyloid plaque deposition and neurofibrillary tangles of hyperphosphorylated tau. Diagnosis is based upon clinical presentation fulfilling several criteria as well as fluid and imaging biomarkers. Treatment is currently targeted toward symptomatic therapy, although trials are underway that aim to reduce the production and overall burden of pathology within the brain. Here, we discuss recent advances in our understanding of the clinical evaluation and treatment of Alzheimer’s disease, with updates regarding clinical trials still in progress.