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Showing papers by "Indiana University published in 2017"


Journal ArticleDOI
TL;DR: These pediatric hypertension guidelines are an update to the 2004 report and include revised recommendations on when to perform echocardiography in the evaluation of newly diagnosed hypertensive pediatric patients (generally only before medication initiation), along with a revised definition of left ventricular hypertrophy.
Abstract: These pediatric hypertension guidelines are an update to the 2004 “Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents.” Significant changes in these guidelines include (1) the replacement of the term “prehypertension” with the term “elevated blood pressure,” (2) new normative pediatric blood pressure (BP) tables based on normal-weight children, (3) a simplified screening table for identifying BPs needing further evaluation, (4) a simplified BP classification in adolescents ≥13 years of age that aligns with the forthcoming American Heart Association and American College of Cardiology adult BP guidelines, (5) a more limited recommendation to perform screening BP measurements only at preventive care visits, (6) streamlined recommendations on the initial evaluation and management of abnormal BPs, (7) an expanded role for ambulatory BP monitoring in the diagnosis and management of pediatric hypertension, and (8) revised recommendations on when to perform echocardiography in the evaluation of newly diagnosed hypertensive pediatric patients (generally only before medication initiation), along with a revised definition of left ventricular hypertrophy. These guidelines include 30 Key Action Statements and 27 additional recommendations derived from a comprehensive review of almost 15 000 published articles between January 2004 and July 2016. Each Key Action Statement includes level of evidence, benefit-harm relationship, and strength of recommendation. This clinical practice guideline, endorsed by the American Heart Association, is intended to foster a patient- and family-centered approach to care, reduce unnecessary and costly medical interventions, improve patient diagnoses and outcomes, support implementation, and provide direction for future research.

2,082 citations


Journal ArticleDOI
01 Nov 2017-Nature
TL;DR: A meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project is presented, creating both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity.
Abstract: Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity.

1,676 citations


Journal ArticleDOI
TL;DR: This 2017 Consensus Statement is to provide a state-of-the-art review of the field of catheter and surgical ablation of AF and to report the findings of a writing group, convened by these five international societies.

1,626 citations


Journal ArticleDOI
TL;DR: This ESO-ESMO ABC 5 Clinical Practice Guideline provides key recommendations for managing advanced breast cancer patients, and provides updates on managing patients with all breast cancer subtypes, LABC, follow-up, palliative and supportive care.

1,514 citations


Journal ArticleDOI
05 Jul 2017-Nature
TL;DR: Scheres et al. as mentioned in this paper presented a 3.4-3.5-resolution image of the brain of an individual with Alzheimer's disease and showed that the protein cores are made of two identical protofilaments comprising residues 306-378 of tau protein.
Abstract: Alzheimer’s disease is the most common neurodegenerative disease, and there are no mechanism-based therapies. The disease is defined by the presence of abundant neurofibrillary lesions and neuritic plaques in the cerebral cortex. Neurofibrillary lesions comprise paired helical and straight tau filaments, whereas tau filaments with different morphologies characterize other neurodegenerative diseases. No high-resolution structures of tau filaments are available. Here we present cryo-electron microscopy (cryo-EM) maps at 3.4–3.5 A resolution and corresponding atomic models of paired helical and straight filaments from the brain of an individual with Alzheimer’s disease. Filament cores are made of two identical protofilaments comprising residues 306–378 of tau protein, which adopt a combined cross-β/β-helix structure and define the seed for tau aggregation. Paired helical and straight filaments differ in their inter-protofilament packing, showing that they are ultrastructural polymorphs. These findings demonstrate that cryo-EM allows atomic characterization of amyloid filaments from patient-derived material, and pave the way for investigation of a range of neurodegenerative diseases. High-resolution structures of tau filaments shed light on the ultrastructure of neurofibrillary lesions in Alzheimer’s disease. Alzheimer's disease is defined by the presence of abundant neurofibrillary lesions and neuritic plaques in the cerebral cortex. The lesions are made of paired helical and straight tau filaments (PHFs and SFs, respectively). Different tau filaments characterize other neurodegenerative diseases, suggesting that molecular conformers of aggregated tau underlie human tauopathies. No high-resolution structures of tau filaments are currently available. Here, Sjors Scheres and colleagues present cryo-electron microscopy (cryo-EM) maps at 3.5 A resolution and corresponding atomic models of PHFs and SFs from the brain of an individual with Alzheimer's disease. Their results show that cryo-EM enables atomic characterization of amyloid filaments from patient-derived material and could be used to study a range of neurodegenerative diseases.

1,265 citations


Book
20 Jan 2017
TL;DR: In this article, the authors present a state-of-the-art account of probability on networks, including percolation, isoperimetric inequalities, eigenvalues, transition probabilities, and random walks.
Abstract: Starting around the late 1950s, several research communities began relating the geometry of graphs to stochastic processes on these graphs. This book, twenty years in the making, ties together research in the field, encompassing work on percolation, isoperimetric inequalities, eigenvalues, transition probabilities, and random walks. Written by two leading researchers, the text emphasizes intuition, while giving complete proofs and more than 850 exercises. Many recent developments, in which the authors have played a leading role, are discussed, including percolation on trees and Cayley graphs, uniform spanning forests, the mass-transport technique, and connections on random walks on graphs to embedding in Hilbert space. This state-of-the-art account of probability on networks will be indispensable for graduate students and researchers alike.

803 citations


Journal ArticleDOI
Philip S. Cowperthwaite1, Edo Berger1, V. A. Villar1, Brian D. Metzger2  +158 moreInstitutions (47)
TL;DR: In this article, the Gordon and Betty Moore Foundation (GBMF5076) and the Heising-Simons Foundation (HSPF) have contributed to the creation of the DES-Brazil Consortium.
Abstract: NSF [AST-1411763, AST-1714498, DGE 1144152, PHY-1707954, AST-1518052]; NASA [NNX15AE50G, NNX16AC22G]; National Science Foundation; Kavli Foundation; Danish National Research Foundation; Niels Bohr International Academy; DARK Cosmology Centre; Gordon & Betty Moore Foundation; Heising-Simons Foundation; UCSC; Alfred P. Sloan Foundation; David and Lucile Packard Foundation; European Research Council [ERC-StG-335936]; Gordon and Betty Moore Foundation [GBMF5076]; DOE (USA); NSF (USA); MISE (Spain); STFC (UK); HEFCE (UK); NCSA (UIUC); KICP (U. Chicago); CCAPP (Ohio State); MIFPA (Texas AM); MINECO (Spain); DFG (Germany); CNPQ (Brazil); FAPERJ (Brazil); FINEP (Brazil); Argonne Lab; UC Santa Cruz; University of Cambridge; CIEMAT-Madrid; University of Chicago; University College London; DES-Brazil Consortium; University of Edinburgh; ETH Zurich; Fermilab; University of Illinois; ICE (IEEC-CSIC); IFAE Barcelona; Lawrence Berkeley Lab; LMU Munchen; Excellence Cluster Universe; University of Michigan; NOAO; University of Nottingham; Ohio State University; University of Pennsylvania; University of Portsmouth; SLAC National Lab; Stanford University; University of Sussex; Texas AM University; Gemini Observatory [GS-2017B-Q-8, GS-2017B-DD-4]

788 citations


Journal ArticleDOI
TL;DR: In this article, the authors present a framework for research in digital marketing that highlights the touchpoints in the marketing process as well as in marketing strategy process where digital technologies are having and will have a significant impact.

749 citations


Journal ArticleDOI
TL;DR: Three new measures: the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of intervention Measure (FIM) are developed and psychometrically assessed and demonstrate promising psychometric properties.
Abstract: Implementation outcome measures are essential for monitoring and evaluating the success of implementation efforts. Yet, currently available measures lack conceptual clarity and have largely unknown reliability and validity. This study developed and psychometrically assessed three new measures: the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM). Thirty-six implementation scientists and 27 mental health professionals assigned 31 items to the constructs and rated their confidence in their assignments. The Wilcoxon one-sample signed rank test was used to assess substantive and discriminant content validity. Exploratory and confirmatory factor analysis (EFA and CFA) and Cronbach alphas were used to assess the validity of the conceptual model. Three hundred twenty-six mental health counselors read one of six randomly assigned vignettes depicting a therapist contemplating adopting an evidence-based practice (EBP). Participants used 15 items to rate the therapist’s perceptions of the acceptability, appropriateness, and feasibility of adopting the EBP. CFA and Cronbach alphas were used to refine the scales, assess structural validity, and assess reliability. Analysis of variance (ANOVA) was used to assess known-groups validity. Finally, half of the counselors were randomly assigned to receive the same vignette and the other half the opposite vignette; and all were asked to re-rate acceptability, appropriateness, and feasibility. Pearson correlation coefficients were used to assess test-retest reliability and linear regression to assess sensitivity to change. All but five items exhibited substantive and discriminant content validity. A trimmed CFA with five items per construct exhibited acceptable model fit (CFI = 0.98, RMSEA = 0.08) and high factor loadings (0.79 to 0.94). The alphas for 5-item scales were between 0.87 and 0.89. Scale refinement based on measure-specific CFAs and Cronbach alphas using vignette data produced 4-item scales (α’s from 0.85 to 0.91). A three-factor CFA exhibited acceptable fit (CFI = 0.96, RMSEA = 0.08) and high factor loadings (0.75 to 0.89), indicating structural validity. ANOVA showed significant main effects, indicating known-groups validity. Test-retest reliability coefficients ranged from 0.73 to 0.88. Regression analysis indicated each measure was sensitive to change in both directions. The AIM, IAM, and FIM demonstrate promising psychometric properties. Predictive validity assessment is planned.

736 citations


Journal ArticleDOI
Rebecca Sims1, Sven J. van der Lee2, Adam C. Naj3, Céline Bellenguez4  +484 moreInstitutions (120)
TL;DR: Three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease are observed, providing additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's Disease.
Abstract: We identified rare coding variants associated with Alzheimer's disease in a three-stage case–control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10−4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10−8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10−10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10−10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10−14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein–protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

730 citations


Journal ArticleDOI
TL;DR: Research on crisis management and resilience has sought to explain how individuals and organizations anticipate and respond to adversity, yet there has been little integration across different disciplines as discussed by the authors. But, surprisingly, there have been few integration across disciplines.
Abstract: Research on crisis management and resilience has sought to explain how individuals and organizations anticipate and respond to adversity, yet—surprisingly—there has been little integration across t...

Journal ArticleDOI
TL;DR: The determination of the light-quark masses, the form factor, and the decay constant ratio arising in the semileptonic $$K \rightarrow \pi $$K→π transition at zero momentum transfer are reported on.
Abstract: We review lattice results related to pion, kaon, D- and B-meson physics with the aim of making them easily accessible to the particle-physics community. More specifically, we report on the determination of the light-quark masses, the form factor [Formula: see text], arising in the semileptonic [Formula: see text] transition at zero momentum transfer, as well as the decay constant ratio [Formula: see text] and its consequences for the CKM matrix elements [Formula: see text] and [Formula: see text]. Furthermore, we describe the results obtained on the lattice for some of the low-energy constants of [Formula: see text] and [Formula: see text] Chiral Perturbation Theory. We review the determination of the [Formula: see text] parameter of neutral kaon mixing as well as the additional four B parameters that arise in theories of physics beyond the Standard Model. The latter quantities are an addition compared to the previous review. For the heavy-quark sector, we provide results for [Formula: see text] and [Formula: see text] (also new compared to the previous review), as well as those for D- and B-meson-decay constants, form factors, and mixing parameters. These are the heavy-quark quantities most relevant for the determination of CKM matrix elements and the global CKM unitarity-triangle fit. Finally, we review the status of lattice determinations of the strong coupling constant [Formula: see text].

Journal ArticleDOI
TL;DR: The 2017 plasmas roadmap as mentioned in this paper is the first update of a planned series of periodic updates of the Plasma Roadmap, which was published by the Journal of Physics D: Applied Physics in 2012.
Abstract: Journal of Physics D: Applied Physics published the first Plasma Roadmap in 2012 consisting of the individual perspectives of 16 leading experts in the various sub-fields of low temperature plasma science and technology. The 2017 Plasma Roadmap is the first update of a planned series of periodic updates of the Plasma Roadmap. The continuously growing interdisciplinary nature of the low temperature plasma field and its equally broad range of applications are making it increasingly difficult to identify major challenges that encompass all of the many sub-fields and applications. This intellectual diversity is ultimately a strength of the field. The current state of the art for the 19 sub-fields addressed in this roadmap demonstrates the enviable track record of the low temperature plasma field in the development of plasmas as an enabling technology for a vast range of technologies that underpin our modern society. At the same time, the many important scientific and technological challenges shared in this roadmap show that the path forward is not only scientifically rich but has the potential to make wide and far reaching contributions to many societal challenges.


13 Jul 2017
TL;DR: It is demonstrated that cryo-EM allows atomic characterization of amyloid filaments from patient-derived material, and pave the way for investigation of a range of neurodegenerative diseases.
Abstract: Alzheimer’s disease is the most common neurodegenerative disease, and there are no mechanism-based therapies. The disease is defined by the presence of abundant neurofibrillary lesions and neuritic plaques in the cerebral cortex. Neurofibrillary lesions comprise paired helical and straight tau filaments, whereas tau filaments with different morphologies characterize other neurodegenerative diseases. No high-resolution structures of tau filaments are available. Here we present cryo-electron microscopy (cryo-EM) maps at 3.4–3.5 A resolution and corresponding atomic models of paired helical and straight filaments from the brain of an individual with Alzheimer’s disease. Filament cores are made of two identical protofilaments comprising residues 306–378 of tau protein, which adopt a combined cross-β/β-helix structure and define the seed for tau aggregation. Paired helical and straight filaments differ in their inter-protofilament packing, showing that they are ultrastructural polymorphs. These findings demonstrate that cryo-EM allows atomic characterization of amyloid filaments from patient-derived material, and pave the way for investigation of a range of neurodegenerative diseases. High-resolution structures of tau filaments shed light on the ultrastructure of neurofibrillary lesions in Alzheimer’s disease. Alzheimer's disease is defined by the presence of abundant neurofibrillary lesions and neuritic plaques in the cerebral cortex. The lesions are made of paired helical and straight tau filaments (PHFs and SFs, respectively). Different tau filaments characterize other neurodegenerative diseases, suggesting that molecular conformers of aggregated tau underlie human tauopathies. No high-resolution structures of tau filaments are currently available. Here, Sjors Scheres and colleagues present cryo-electron microscopy (cryo-EM) maps at 3.5 A resolution and corresponding atomic models of PHFs and SFs from the brain of an individual with Alzheimer's disease. Their results show that cryo-EM enables atomic characterization of amyloid filaments from patient-derived material and could be used to study a range of neurodegenerative diseases.

Journal ArticleDOI
20 Jun 2017-JAMA
TL;DR: Among patients with KRAS wt untreated advanced or metastatic colorectal cancer, there was no significant difference in overall survival between the addition of cetuximab vs bevacizumab to chemotherapy as initial biologic treatment.
Abstract: Importance Combining biologic monoclonal antibodies with chemotherapeutic cytotoxic drugs provides clinical benefit to patients with advanced or metastatic colorectal cancer, but the optimal choice of the initial biologic therapy in previously untreated patients is unknown. Objective To determine if the addition of cetuximab vs bevacizumab to the combination of leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6) regimen or the combination of leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen is superior as first-line therapy in advanced or metastatic KRAS wild-type (wt) colorectal cancer. Design, Setting, and Participants Patients (≥18 years) enrolled at community and academic centers throughout the National Clinical Trials Network in the United States and Canada (November 2005-March 2012) with previously untreated advanced or metastatic colorectal cancer whose tumors were KRAS wt chose to take either the mFOLFOX6 regimen or the FOLFIRI regimen as chemotherapy and were randomized to receive either cetuximab (n = 578) or bevacizumab (n = 559). The last date of follow-up was December 15, 2015. Interventions Cetuximab vs bevacizumab combined with either mFOLFOX6 or FOLFIRI chemotherapy regimen chosen by the treating physician and patient. Main Outcomes and Measures The primary end point was overall survival. Secondary objectives included progression-free survival and overall response rate, site-reported confirmed or unconfirmed complete or partial response. Results Among 1137 patients (median age, 59 years; 440 [39%] women), 1074 (94%) of patients met eligibility criteria. As of December 15, 2015, median follow-up for 263 surviving patients was 47.4 months (range, 0-110.7 months), and 82% of patients (938 of 1137) experienced disease progression. The median overall survival was 30.0 months in the cetuximab-chemotherapy group and 29.0 months in the bevacizumab-chemotherapy group with a stratified hazard ratio (HR) of 0.88 (95% CI, 0.77-1.01; P = .08). The median progression-free survival was 10.5 months in the cetuximab-chemotherapy group and 10.6 months in the bevacizumab-chemotherapy group with a stratified HR of 0.95 (95% CI, 0.84-1.08; P = .45). Response rates were not significantly different, 59.6% vs 55.2% for cetuximab and bevacizumab, respectively (difference, 4.4%, 95% CI, 1.0%-9.0%, P = .13). Conclusions and Relevance Among patients with KRAS wt untreated advanced or metastatic colorectal cancer, there was no significant difference in overall survival between the addition of cetuximab vs bevacizumab to chemotherapy as initial biologic treatment. Trial Registration clinicaltrials.gov identifier:NCT00265850

Journal ArticleDOI
TL;DR: New features, datasets, reagent collections, and data presentations are described that address the needs of the Drosophila research community, including enhanced orthology data, Human Disease Model Reports, protein domain search and visualization, concise gene summaries, and a portal for external resources.
Abstract: Since 1992, FlyBase (flybaseorg) has been an essential online resource for the Drosophila research community Concentrating on the most extensively studied species, Drosophila melanogaster, FlyBase includes information on genes (molecular and genetic), transgenic constructs, phenotypes, genetic and physical interactions, and reagents such as stocks and cDNAs Access to data is provided through a number of tools, reports, and bulk-data downloads Looking to the future, FlyBase is expanding its focus to serve a broader scientific community In this update, we describe new features, datasets, reagent collections, and data presentations that address this goal, including enhanced orthology data, Human Disease Model Reports, protein domain search and visualization, concise gene summaries, a portal for external resources, video tutorials and the FlyBase Community Advisory Group

Journal ArticleDOI
TL;DR: In this paper, the authors outline contributions to the entrepreneurial ecosystem approach and conclude with a promising new line of research to our understanding of the emergence, growth, and context of start-ups that have achieved great impact by developing new platforms.
Abstract: In its most abstract sense, an ecosystem is a biotic community, encompassing its physical environment, and all the interactions possible in the complex of living and nonliving components. Economics has always been about systems that explain differential output and outcomes. However, economics has generally ignored the role of entrepreneurship in economic systems, just as entrepreneurship studies have largely overlooked the role of systems in explaining the prevalence and performance of entrepreneurship. The entrepreneurial ecosystem approach has the promise to correct these shortcomings. Its two dominant lineages are the regional development literature and the strategy literature. Both lineages share common roots in ecological systems thinking, providing fresh insights into the interdependence of actors in a particular community to create new value. But studies of both regional development and strategic management have largely ignored the role of entrepreneurs in new value creation. In this paper, we will outline contributions to the entrepreneurial ecosystem approach and conclude with a promising new line of research to our understanding of the emergence, growth, and context of start-ups that have achieved great impact by developing new platforms.

Journal ArticleDOI
TL;DR: In this article, the authors report world averages of measurements of b-hadron, c-, c-, and tau-lepton properties obtained by the Heavy Flavor Averaging Group (HFAG) using results available through the end of 2011.
Abstract: This article reports world averages of measurements of b-hadron, c-hadron, and tau-lepton properties obtained by the Heavy Flavor Averaging Group (HFAG) using results available through the end of 2011. In some cases results available in the early part of 2012 are included. For the averaging, common input parameters used in the various analyses are adjusted (rescaled) to common values, and known correlations are taken into account. The averages include branching fractions, lifetimes, neutral meson mixing parameters, CP violation parameters, parameters of semileptonic decays and CKM matrix elements.

Journal ArticleDOI
TL;DR: Although CTTA CT texture analysis seems to be a promising imaging biomarker, there is marked variability in methods, parameters reported, and strength of associations with biologic correlates.
Abstract: CT texture analysis of tumor heterogeneity has shown promise in lesion characterization, pretreatment tumor assessment, and response evaluation for some tumor types and may also have a spectrum of potential nononcologic applications, including assessment of hepatic and pulmonary fibrosis; however, a variety of challenges, including standardization of segmentation/measurement, postprocessing, and reporting, as well as ongoing delineation of pathologic correlates, need to be resolved before widespread implementation.

Journal ArticleDOI
30 Mar 2017-Oncogene
TL;DR: It is shown that CAFs exposed to chemotherapy have an active role in regulating the survival and proliferation of cancer cells and the potential for exosome inhibitors as treatment options alongside chemotherapy for overcoming PDAC chemoresistance is shown.
Abstract: Cancer-associated fibroblasts (CAFs) comprise the majority of the tumor bulk of pancreatic ductal adenocarcinomas (PDACs). Current efforts to eradicate these tumors focus predominantly on targeting the proliferation of rapidly growing cancer epithelial cells. We know that this is largely ineffective with resistance arising in most tumors following exposure to chemotherapy. Despite the long-standing recognition of the prominence of CAFs in PDAC, the effect of chemotherapy on CAFs and how they may contribute to drug resistance in neighboring cancer cells is not well characterized. Here, we show that CAFs exposed to chemotherapy have an active role in regulating the survival and proliferation of cancer cells. We found that CAFs are intrinsically resistant to gemcitabine, the chemotherapeutic standard of care for PDAC. Further, CAFs exposed to gemcitabine significantly increase the release of extracellular vesicles called exosomes. These exosomes increased chemoresistance-inducing factor, Snail, in recipient epithelial cells and promote proliferation and drug resistance. Finally, treatment of gemcitabine-exposed CAFs with an inhibitor of exosome release, GW4869, significantly reduces survival in co-cultured epithelial cells, signifying an important role of CAF exosomes in chemotherapeutic drug resistance. Collectively, these findings show the potential for exosome inhibitors as treatment options alongside chemotherapy for overcoming PDAC chemoresistance.


Journal ArticleDOI
01 Oct 2017-Europace
TL;DR: This 2017 Consensus Statement is to provide a state-of-the-art review of the field of catheter and surgical ablation of AF and to report the findings of a writing group, convened by these five international societies.
Abstract: During the past three decades, catheter and surgical ablation of atrial fibrillation (AF) have evolved from investigational procedures to their current role as effective treatment options for patients with AF. Surgical ablation of AF, using either standard, minimally invasive, or hybrid techniques, is available in most major hospitals throughout the world. Catheter ablation of AF is even more widely available, and is now the most commonly performed catheter ablation procedure. In 2007, an initial Consensus Statement on Catheter and Surgical AF Ablation was developed as a joint effort of the Heart Rhythm Society (HRS), the European Heart Rhythm Association (EHRA), and the European Cardiac Arrhythmia Society (ECAS).1 The 2007 document was also developed in collaboration with the Society of Thoracic Surgeons (STS) and the American College of Cardiology (ACC). This Consensus Statement on Catheter and Surgical AF Ablation was rewritten in 2012 to reflect the many advances in AF ablation that had occurred in the interim.2 The rate of advancement in the tools, techniques, and outcomes of AF ablation continue to increase as enormous research efforts are focused on the mechanisms, outcomes, and treatment of AF. For this reason, the HRS initiated an effort to rewrite and update this Consensus Statement. Reflecting both the worldwide importance of AF, as well as the worldwide performance of AF ablation, this document is the result of a joint partnership between the HRS, EHRA, ECAS, the Asia Pacific Heart Rhythm Society (APHRS), and the Latin American Society of Cardiac Stimulation and Electrophysiology (Sociedad Latinoamericana de Estimulacion Cardiaca y Electrofisiologia [SOLAECE]). The purpose of this 2017 Consensus Statement is to provide a state-of-the-art review of the field of catheter and surgical ablation of AF and to report the findings of a writing group, convened by these five international societies. The writing group is charged with defining the indications, techniques, and outcomes of AF ablation procedures. Included within this document are recommendations pertinent to the design of clinical trials in the field of AF ablation and the reporting of outcomes, including definitions relevant to this topic. The writing group is composed of 60 experts representing 11 organizations: HRS, EHRA, ECAS, APHRS, SOLAECE, STS, ACC, American Heart Association (AHA), Canadian Heart Rhythm Society (CHRS), Japanese Heart Rhythm Society (JHRS), and Brazilian Society of Cardiac Arrhythmias (Sociedade Brasileira de Arritmias Cardiacas [SOBRAC]). All the members of the writing group, as well as peer reviewers of the document, have provided disclosure statements for all relationships that might be perceived as real or potential conflicts of interest. All author and peer reviewer disclosure information is provided in Appendix A and Appendix B. In writing a consensus document, it is recognized that consensus does not mean that there was complete agreement among all the writing group members. Surveys of the entire writing group were used to identify areas of consensus concerning performance of AF ablation procedures and to develop recommendations concerning the indications for catheter and surgical AF ablation. These recommendations were systematically balloted by the 60 writing group members and were approved by a minimum of 80% of these members. The recommendations were also subject to a 1-month public comment period. Each partnering and collaborating organization then officially reviewed, commented on, edited, and endorsed the final document and recommendations. The grading system for indication of class of evidence level was adapted based on that used by the ACC and the AHA.3,4 It is important to state, however, that this document is not a guideline. The indications for catheter and surgical ablation of AF, as well as recommendations for procedure performance, are presented with a Class and Level of Evidence (LOE) to be consistent with what the reader is familiar with seeing in guideline statements. A Class I recommendation means that the benefits of the AF ablation procedure markedly exceed the risks, and that AF ablation should be performed; a Class IIa recommendation means that the benefits of an AF ablation procedure exceed the risks, and that it is reasonable to perform AF ablation; a Class IIb recommendation means that the benefit of AF ablation is greater or equal to the risks, and that AF ablation may be considered; and a Class III recommendation means that AF ablation is of no proven benefit and is not recommended. The writing group reviewed and ranked evidence supporting current recommendations with the weight of evidence ranked as Level A if the data were derived from high-quality evidence from more than one randomized clinical trial, meta-analyses of high-quality randomized clinical trials, or one or more randomized clinical trials corroborated by high-quality registry studies. The writing group ranked available evidence as Level B-R when there was moderate-quality evidence from one or more randomized clinical trials, or meta-analyses of moderate-quality randomized clinical trials. Level B-NR was used to denote moderate-quality evidence from one or more well-designed, well-executed nonrandomized studies, observational studies, or registry studies. This designation was also used to denote moderate-quality evidence from meta-analyses of such studies. Evidence was ranked as Level C-LD when the primary source of the recommendation was randomized or nonrandomized observational or registry studies with limitations of design or execution, meta-analyses of such studies, or physiological or mechanistic studies of human subjects. Level C-EO was defined as expert opinion based on the clinical experience of the writing group. Despite a large number of authors, the participation of several societies and professional organizations, and the attempts of the group to reflect the current knowledge in the field adequately, this document is not intended as a guideline. Rather, the group would like to refer to the current guidelines on AF management for the purpose of guiding overall AF management strategies.5,6 This consensus document is specifically focused on catheter and surgical ablation of AF, and summarizes the opinion of the writing group members based on an extensive literature review as well as their own experience. It is directed to all health care professionals who are involved in the care of patients with AF, particularly those who are caring for patients who are undergoing, or are being considered for, catheter or surgical ablation procedures for AF, and those involved in research in the field of AF ablation. This statement is not intended to recommend or promote catheter or surgical ablation of AF. Rather, the ultimate judgment regarding care of a particular patient must be made by the health care provider and the patient in light of all the circumstances presented by that patient. The main objective of this document is to improve patient care by providing a foundation of knowledge for those involved with catheter ablation of AF. A second major objective is to provide recommendations for designing clinical trials and reporting outcomes of clinical trials of AF ablation. It is recognized that this field continues to evolve rapidly. As this document was being prepared, further clinical trials of catheter and surgical ablation of AF were under way.

Journal ArticleDOI
TL;DR: In this article, a consensus committee of 32 experts in CF diagnosis from 9 countries to develop clear and actionable consensus guidelines on the diagnosis of CF and to clarify diagnostic criteria and terminology for other disorders associated with CFTR mutations.

Journal ArticleDOI
TL;DR: An overview of the remarkable progress in the field of heavy-quark exotic hadrons over the past 15 years can be found in this article, where the authors present a pedagogical rather than exhaustive review of the progress and specific results of experimental discoveries.

Journal ArticleDOI
22 May 2017-Nature
TL;DR: It is found that the genomic architecture of flowering time has been shaped by the most recent whole-genome duplication, which suggests that ancient paralogues can remain in the same regulatory networks for dozens of millions of years.
Abstract: The domesticated sunflower, Helianthus annuus L, is a global oil crop that has promise for climate change adaptation, because it can maintain stable yields across a wide variety of environmental conditions, including drought Even greater resilience is achievable through the mining of resistance alleles from compatible wild sunflower relatives, including numerous extremophile species Here we report a high-quality reference for the sunflower genome (36 gigabases), together with extensive transcriptomic data from vegetative and floral organs The genome mostly consists of highly similar, related sequences and required single-molecule real-time sequencing technologies for successful assembly Genome analyses enabled the reconstruction of the evolutionary history of the Asterids, further establishing the existence of a whole-genome triplication at the base of the Asterids II clade and a sunflower-specific whole-genome duplication around 29 million years ago An integrative approach combining quantitative genetics, expression and diversity data permitted development of comprehensive gene networks for two major breeding traits, flowering time and oil metabolism, and revealed new candidate genes in these networks We found that the genomic architecture of flowering time has been shaped by the most recent whole-genome duplication, which suggests that ancient paralogues can remain in the same regulatory networks for dozens of millions of years This genome represents a cornerstone for future research programs aiming to exploit genetic diversity to improve biotic and abiotic stress resistance and oil production, while also considering agricultural constraints and human nutritional needs

Posted Content
TL;DR: This work presents a framework to detect social bots on Twitter, and describes several subclasses of accounts, including spammers, self promoters, and accounts that post content from connected applications.
Abstract: Increasing evidence suggests that a growing amount of social media content is generated by autonomous entities known as social bots. In this work we present a framework to detect such entities on Twitter. We leverage more than a thousand features extracted from public data and meta-data about users: friends, tweet content and sentiment, network patterns, and activity time series. We benchmark the classification framework by using a publicly available dataset of Twitter bots. This training data is enriched by a manually annotated collection of active Twitter users that include both humans and bots of varying sophistication. Our models yield high accuracy and agreement with each other and can detect bots of different nature. Our estimates suggest that between 9% and 15% of active Twitter accounts are bots. Characterizing ties among accounts, we observe that simple bots tend to interact with bots that exhibit more human-like behaviors. Analysis of content flows reveals retweet and mention strategies adopted by bots to interact with different target groups. Using clustering analysis, we characterize several subclasses of accounts, including spammers, self promoters, and accounts that post content from connected applications.

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Morad Aaboud, Georges Aad1, Brad Abbott2, Jalal Abdallah3  +2845 moreInstitutions (197)
TL;DR: This paper presents a short overview of the changes to the trigger and data acquisition systems during the first long shutdown of the LHC and shows the performance of the trigger system and its components based on the 2015 proton–proton collision data.
Abstract: During 2015 the ATLAS experiment recorded 3.8 fb(-1) of proton-proton collision data at a centre-of-mass energy of 13 TeV. The ATLAS trigger system is a crucial component of the experiment, respons ...

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TL;DR: In this paper, a meta-aggregative approach was used to analyze the results of 14 selected studies to further understand the link between teachers' pedagogical beliefs and their educational uses of technology.
Abstract: This review was designed to further our understanding of the link between teachers’ pedagogical beliefs and their educational uses of technology. The synthesis of qualitative findings integrates the available evidence about this relationship with the ultimate goal being to facilitate the integration of technology in education. A meta-aggregative approach was utilized to analyze the results of the 14 selected studies. The findings are reported in terms of five synthesis statements, describing (1) the bi-directional relationship between pedagogical beliefs and technology use, (2) teachers’ beliefs as perceived barriers, (3) the association between specific beliefs with types of technology use, (4) the role of beliefs in professional development, and (5) the importance of the school context. By interpreting the results of the review, recommendations are provided for practitioners, policy makers, and researchers focusing on pre- and in-service teacher technology training.

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TL;DR: In this article, the authors focus on regional entrepreneurial ecosystems and offer a complex model of start-ups, Regional Entrepreneurship and Development Index (REDI) and six domains of the entrepreneurial ecosystem (culture, formal institutions, infrastructure and amenities, IT, Melting Pot and demand).
Abstract: This study focuses on regional entrepreneurial ecosystems and offers a complex model of start-ups, Regional Entrepreneurship and Development Index (REDI) and six domains of the entrepreneurial ecosystem (culture, formal institutions, infrastructure and amenities, IT, Melting Pot and demand). Altogether they capture the contextual features of socioeconomic, institutional and information environment in cities. To explain variations in entrepreneurship in a cross-section of 70 European cities, we utilize exploratory factor analysis and structural equation modelling for regional systems of entrepreneurship using individual perception surveys by Eurostat and the REDI. This study supports policymakers and scholars in development of new policies conducive to regional systems of innovation and entrepreneurship and serves as a basis for future research on urban entrepreneurial ecosystems.