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Showing papers by "University of Louisville published in 2019"


Journal ArticleDOI
TL;DR: Gingipains from Porphyromonas gingivalis drive Alzheimer’s pathology and can be blocked with small-molecule inhibitors, suggesting that gingipain inhibitors could be valuable for treating P. gedivalis brain colonization and neurodegeneration in Alzheimer's disease.
Abstract: Porphyromonas gingivalis, the keystone pathogen in chronic periodontitis, was identified in the brain of Alzheimer's disease patients. Toxic proteases from the bacterium called gingipains were also identified in the brain of Alzheimer's patients, and levels correlated with tau and ubiquitin pathology. Oral P. gingivalis infection in mice resulted in brain colonization and increased production of Aβ1-42, a component of amyloid plaques. Further, gingipains were neurotoxic in vivo and in vitro, exerting detrimental effects on tau, a protein needed for normal neuronal function. To block this neurotoxicity, we designed and synthesized small-molecule inhibitors targeting gingipains. Gingipain inhibition reduced the bacterial load of an established P. gingivalis brain infection, blocked Aβ1-42 production, reduced neuroinflammation, and rescued neurons in the hippocampus. These data suggest that gingipain inhibitors could be valuable for treating P. gingivalis brain colonization and neurodegeneration in Alzheimer's disease.

988 citations


Journal ArticleDOI
TL;DR: After median follow-up duration of 4·5 years, radiotherapy plus cetuximab did not meet the non-inferiority criteria for overall survival, and patients were stratified by T category (T1-T2 vs T3-T4), N category (N0-N2a vs N2b-N3), Zubrod performance status (0 vs 1), and tobacco smoking history (≤10 pack-years).

822 citations


Journal ArticleDOI
TL;DR: TMB of 10 or more mut/Mb was associated with improved response and prolonged progression-free survival in both tumor PD-L1 expression 1% or greater and less than 1% subgroups and was thus identified as a potentially relevant cutoff in the assessment of TMB as a biomarker for first-line nivolumab plus ipilimumab.
Abstract: PURPOSECheckMate 568 is an open-label phase II trial that evaluated the efficacy and safety of nivolumab plus low-dose ipilimumab as first-line treatment of advanced/metastatic non–small-cell lung cancer (NSCLC). We assessed the association of efficacy with programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB).PATIENTS AND METHODSTwo hundred eighty-eight patients with previously untreated, recurrent stage IIIB/IV NSCLC received nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks. The primary end point was objective response rate (ORR) in patients with 1% or more and less than 1% tumor PD-L1 expression. Efficacy on the basis of TMB (FoundationOne CDx assay) was a secondary end point.RESULTSOf treated patients with tumor available for testing, 252 patients (88%) of 288 were evaluable for PD-L1 expression and 98 patients (82%) of 120 for TMB. ORR was 30% overall and 41% and 15% in patients with 1% or greater and less than 1% tumor PD-L1 expression, respectively. ORR...

398 citations


Journal ArticleDOI
TL;DR: It is shown that urolithin A and a synthetic analogue enhance gut barrier function via Nrf2-dependent pathways and mitigate inflammation and colitis in mice, highlighting a potential application for inflammatory bowel diseases.
Abstract: The importance of gut microbiota in human health and pathophysiology is undisputable. Despite the abundance of metagenomics data, the functional dynamics of gut microbiota in human health and disease remain elusive. Urolithin A (UroA), a major microbial metabolite derived from polyphenolics of berries and pomegranate fruits displays anti-inflammatory, anti-oxidative, and anti-ageing activities. Here, we show that UroA and its potent synthetic analogue (UAS03) significantly enhance gut barrier function and inhibit unwarranted inflammation. We demonstrate that UroA and UAS03 exert their barrier functions through activation of aryl hydrocarbon receptor (AhR)- nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent pathways to upregulate epithelial tight junction proteins. Importantly, treatment with these compounds attenuated colitis in pre-clinical models by remedying barrier dysfunction in addition to anti-inflammatory activities. Cumulatively, the results highlight how microbial metabolites provide two-pronged beneficial activities at gut epithelium by enhancing barrier functions and reducing inflammation to protect from colonic diseases.

357 citations


Journal ArticleDOI
TL;DR: It is concluded that, although heavy drinking is a key risk factor for AUD, it is not a sufficient cause of the disorder and a total of 18 associated loci are identified.
Abstract: Alcohol consumption level and alcohol use disorder (AUD) diagnosis are moderately heritable traits. We conduct genome-wide association studies of these traits using longitudinal Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) scores and AUD diagnoses in a multi-ancestry Million Veteran Program sample (N = 274,424). We identify 18 genome-wide significant loci: 5 associated with both traits, 8 associated with AUDIT-C only, and 5 associated with AUD diagnosis only. Polygenic Risk Scores (PRS) for both traits are associated with alcohol-related disorders in two independent samples. Although a significant genetic correlation reflects the overlap between the traits, genetic correlations for 188 non-alcohol-related traits differ significantly for the two traits, as do the phenotypes associated with the traits’ PRS. Cell type group partitioning heritability enrichment analyses also differentiate the two traits. We conclude that, although heavy drinking is a key risk factor for AUD, it is not a sufficient cause of the disorder. The genetic underpinnings of alcohol use disorder and consumption are incompletely understood. Here, the authors perform GWAS for Alcohol Use Disorder (AUD) Identification Test-Consumption scores and AUD diagnosis from electronic health records of 274,424 individuals and identify a total of 18 associated loci.

317 citations


Journal ArticleDOI
TL;DR: In this paper, a review of different types of natural fibers, their characteristics and properties enabling them to be used as reinforcing agents in different polymers is presented. And the use of different additive manufacturing technologies in processing polymer composites is also discussed.
Abstract: Throughout the world there have been alarming concerns over the use of nonrenewable resources during manufacturing of goods and associated environmental legislations. Therefore, the use of natural materials and fabrication of composites therefrom, particularly, development of natural fiber reinforced polymer composites is gaining significant attention. Although natural fiber reinforced composites (NFRCs) show strong application prospects, various materials and processing related challenges needs to be addressed to achieve long-term stability and performance. In this review, we attempted to provide an overview of different types of natural fibers, their characteristics and properties enabling them to be used as reinforcing agents in different polymers. Then the unique requirement of fiber surface modification to achieve enhanced fiber-matrix bonding is discussed. The article also discusses conventional processing routes and critical issues associated with NFRCs processing. The use of different additive manufacturing (AM) technologies in processing polymer composites is also discussed. At the end, we have critically analyzed the challenges and opportunities associated with AM of NFRCs.

285 citations


Journal ArticleDOI
16 May 2019-Cell
TL;DR: It is found that two independent methods of slow delivery immunization of rhesus monkeys resulted in more robust T follicular helper (TFH) cell responses and GC B cells with improved Env-binding, tracked by longitudinal fine needle aspirates.

258 citations


Journal ArticleDOI
Georges Aad1, Alexander Kupco2, Samuel Webb3, Timo Dreyer4  +3380 moreInstitutions (206)
TL;DR: In this article, a search for high-mass dielectron and dimuon resonances in the mass range of 250 GeV to 6 TeV was performed at the Large Hadron Collider.

248 citations


Journal ArticleDOI
Abulikemu Abudurexiti1, Scott Adkins2, Daniela Alioto3, S. V. Alkhovsky, Tatjana Avšič-Županc4, Matthew J. Ballinger5, Dennis A. Bente6, Martin Beer7, Eric Bergeron1, Carol D. Blair8, Thomas Briese9, Michael J. Buchmeier10, Felicity J. Burt11, Charles H. Calisher8, Chénchén Cháng12, Rémi N. Charrel13, Il-Ryong Choi14, J. Christopher S. Clegg, Juan Carlos de la Torre15, Xavier de Lamballerie13, Fēi Dèng, Francesco Di Serio, Michele Digiaro, Michael A. Drebot16, Xiǎoméi Duàn12, Hideki Ebihara17, Toufic Elbeaino, Koray Ergünay18, Charles F. Fulhorst6, Aura R. Garrison19, George Fú Gāo20, Jean-Paul Gonzalez21, Martin H. Groschup7, Stephan Günther22, Anne Lise Haenni23, Roy A. Hall24, Jussi Hepojoki25, Jussi Hepojoki26, Roger Hewson27, Zhìhóng Hú, Holly R. Hughes1, Miranda Gilda Jonson28, Sandra Junglen29, Boris Klempa30, Jonas Klingström31, Chūn Kòu12, Lies Laenen32, Amy J. Lambert1, Stanley A. Langevin33, Dan Liu34, Igor S. Lukashevich35, Tāo Luò1, Chuánwèi Lǚ, Piet Maes32, William Marciel de Souza36, Marco Marklewitz29, Giovanni P. Martelli37, Keita Matsuno38, Nicole Mielke-Ehret39, Maria Minutolo3, Ali Mirazimi40, Abulimiti Moming12, Hans Peter Mühlbach39, Rayapati A. Naidu41, Beatriz Navarro, Márcio Roberto Teixeira Nunes, Gustavo Palacios19, Anna Papa42, Alex Pauvolid-Corrêa43, Janusz T. Paweska, Jié Qiáo, Sheli R. Radoshitzky19, R. O. Resende44, Víctor Romanowski45, Amadou A. Sall46, Maria S. Salvato47, Takahide Sasaya48, Shū Shěn, Xiǎohóng Shí49, Yukio Shirako50, Peter Simmonds51, Manuela Sironi, Jin Won Song52, Jessica R. Spengler1, Mark D. Stenglein8, Zhèngyuán Sū, Sùróng Sūn12, Shuāng Táng, Massimo Turina53, Bó Wáng, Chéng Wáng1, Huálín Wáng, Jūn Wáng, Taiyun Wei54, Anna E. Whitfield55, F. Murilo Zerbini56, Jìngyuàn Zhāng12, Lěi Zhāng, Yànfāng Zhāng, Yong-Zhen Zhang20, Yong-Zhen Zhang57, Yújiāng Zhāng1, Xueping Zhou, Lìyǐng Zhū, Jens H. Kuhn58 
Centers for Disease Control and Prevention1, United States Department of Agriculture2, University of Naples Federico II3, University of Ljubljana4, Mississippi State University5, University of Texas Medical Branch6, Friedrich Loeffler Institute7, Colorado State University8, Columbia University9, University of California, Irvine10, University of the Free State11, Xinjiang University12, Aix-Marseille University13, International Rice Research Institute14, Scripps Research Institute15, Public Health Agency of Canada16, Mayo Clinic17, Hacettepe University18, United States Army Medical Research Institute of Infectious Diseases19, Chinese Center for Disease Control and Prevention20, Kansas State University21, Bernhard Nocht Institute for Tropical Medicine22, Paris Diderot University23, University of Queensland24, University of Zurich25, University of Helsinki26, Public Health England27, Seoul National University28, Charité29, Slovak Academy of Sciences30, Karolinska Institutet31, Katholieke Universiteit Leuven32, University of Washington33, Wuhan University of Science and Technology34, University of Louisville35, University of São Paulo36, University of Bari37, Hokkaido University38, University of Hamburg39, Public Health Agency of Sweden40, Washington State University41, Aristotle University of Thessaloniki42, Oswaldo Cruz Foundation43, University of Brasília44, National University of La Plata45, Pasteur Institute46, University of Maryland, Baltimore47, National Agriculture and Food Research Organization48, University of Glasgow49, University of Tokyo50, University of Oxford51, Korea University52, National Research Council53, Fujian Agriculture and Forestry University54, North Carolina State University55, Universidade Federal de Viçosa56, Fudan University57, National Institutes of Health58
TL;DR: The updated taxonomy of the order Bunyavirales now accepted by the International Committee on Taxonomy of Viruses (ICTV) is presented.
Abstract: In February 2019, following the annual taxon ratification vote, the order Bunyavirales was amended by creation of two new families, four new subfamilies, 11 new genera and 77 new species, merging of two species, and deletion of one species. This article presents the updated taxonomy of the order Bunyavirales now accepted by the International Committee on Taxonomy of Viruses (ICTV).

237 citations


Journal ArticleDOI
TL;DR: Trastuzumab deruxtecan had a manageable safety profile and showed preliminary activity in trastuzuumab emtansine-pretreated patients with HER2-positive breast cancer, which suggest that further development in phase 2 and 3 clinical trials for Her2- positive breast cancer is warranted.
Abstract: Summary Background Trastuzumab deruxtecan (DS-8201a) is a novel HER2-targeted antibody–drug conjugate with a humanised anti-HER2 antibody, cleavable peptide-based linker, and potent topoisomerase I inhibitor payload. A phase 1, non-randomised, open-label, multiple-dose study was done to assess the safety, tolerability, and activity of trastuzumab deruxtecan in HER2-expressing, advanced solid tumours. The dose escalation (part 1) has previously been reported and the recommended doses for expansion of 5·4 mg/kg or 6·4 mg/kg were established. In this Article, we report the safety and preliminary activity results from this phase 1 trial in all patients with HER2-positive advanced-stage breast cancer with previous trastuzumab emtansine treatment who received trastuzumab deruxtecan at the recommended doses for expansion. Methods We did an open-label, dose-escalation and dose-expansion phase 1 trial at eight hospitals and clinics in the USA and six in Japan. Eligible patients were at least 18 years old in the USA and at least 20 years of age in Japan and had advanced solid tumours (regardless of HER2 expression in dose escalation or HER2 expression or mutation in dose expansion). The recommended doses for expansion of 5·4 mg/kg or 6·4 mg/kg trastuzumab deruxtecan were administered intravenously to patients once every 3 weeks until withdrawal of consent, unacceptable toxicity, or progressive disease. In this Article, all patients with HER2-positive advanced-stage breast cancer with previous trastuzumab emtansine treatment who received trastuzumab deruxtecan at the recommended doses for expansion were analysed together. The primary endpoints of the study were safety and preliminary activity (proportion of patients who achieved an objective response as assessed by the investigators). The activity evaluable set included all patients who received at least one dose of trastuzumab deruxtecan at the recommended doses for expansion, and for whom both baseline and post-treatment activity data were available. The safety analysis set included all patients who received at least one dose of trastuzumab deruxtecan at the recommended doses for expansion. Enrolment for patients with HER2-positive breast cancer has been completed. This trial is registered at ClinicalTrials.gov, number NCT02564900, and ClinicalTrials.jp, number JapicCTI-152978. Findings Between Aug 28, 2015, and Aug 10, 2018, 115 of 118 patients with HER2-positive breast cancer were treated with at least one dose of trastuzumab deruxtecan at the recommended doses for expansion. All patients had at least one treatment-emergent adverse event. Frequent grade 3 or worse treatment-emergent adverse events included anaemia (19 [17%] of 115) and decreased neutrophil (16 [14%]), white blood cell (ten [9%]), and platelet (nine [8%]) counts. At least one serious treatment-emergent adverse event occurred for 22 (19%) patients. Investigators reported 20 cases of interstitial lung disease, pneumonitis, or organising pneumonia, including one grade 3 event and two treatment-related deaths due to pneumonitis. One death unrelated to study treatment was due to progressive disease. 66 (59·5%; 95% CI 49·7–68·7) of 111 patients had a confirmed objective response. Interpretation Trastuzumab deruxtecan had a manageable safety profile and showed preliminary activity in trastuzumab emtansine-pretreated patients with HER2-positive breast cancer. These results suggest that further development in phase 2 and 3 clinical trials for HER2-positive breast cancer is warranted. Funding Daiichi Sankyo Co, Ltd.

208 citations


Journal ArticleDOI
01 Feb 2019
TL;DR: T tobacco-naive youths who initiate e-cigarettes may be at greater risk of subsequently initiating cigarette smoking, according to this cohort study using data from the Population Assessment of Tobacco and Health Study (2013-2016).
Abstract: Importance The use of electronic cigarettes (e-cigarettes) and other noncigarette tobacco products may increase the odds of cigarette initiation, even among low-risk youths. Objective To evaluate the associations of prior e-cigarette use and other tobacco product use with subsequent cigarette initiation within 2 years of follow-up. Design, Setting, and Participants In this prospective cohort study, data from waves 1 through 3 of the Population Assessment of Tobacco and Health Study (2013-2016) were used to assess youths aged 12 to 15 years who had never used cigarettes, e-cigarettes, or other tobacco products at wave 1. This was a nationally representative study of the US population. Data analysis was conducted in 2018. Exposures First noncigarette tobacco product used (none, e-cigarette, or other tobacco product) between wave 1 and wave 3. Main Outcomes and Measures Ever cigarette use and current cigarette use at wave 3. Results In the sample (N = 6123), respondents were 49.5% female; 54.1% non-Hispanic, white; and the mean (SD) age was 13.4 (1.2) years. Of these, 8.6% reported e-cigarettes as their first tobacco product, while 5.0% reported using another noncigarette product first; 3.3% reported using cigarettes first. Cigarette use at wave 3 was higher among prior e-cigarette users (20.5%) compared with youths with no prior tobacco use (3.8%). Prior e-cigarette use was associated with more than 4 times the odds of ever cigarette use (odds ratio, 4.09; 95% CI, 2.97-5.63) and nearly 3 times the odds of current cigarette use (odds ratio, 2.75; 95% CI, 1.60-4.73) compared with no prior tobacco use. Prior use of other tobacco products was similarly associated with subsequent ever cigarette use (OR, 3.84; 95% CI, 2.63-5.63) and current cigarette use (OR, 3.43; 95% CI, 1.88-6.26) compared with no prior tobacco use. The association of prior e-cigarette use with cigarette initiation was stronger among low-risk youths (OR, 8.57; 95% CI, 3.87-18.97), a pattern not seen for prior other product use. Over the 2 years between 2013 and 2014 and 2015 and 2016, 21.8% of new cigarette ever use (178 850 youths) and 15.3% of current cigarette use (43 446 youths) among US youths aged 12 to 15 years may be attributable to prior e-cigarette use. Conclusions and Relevance This study’s findings support the notion that e-cigarette use is associated with increased risk for cigarette initiation and use, particularly among low-risk youths. At the population level, the use of e-cigarettes may be a contributor to the initiation of cigarette smoking among youths.

Journal ArticleDOI
TL;DR: In this paper, the authors focused on acute myocardial infarction (AMI) complicated by cardiogenic shock (AMICS) in cardiac intensive care units (CICUs).
Abstract: Background Clinical investigations of shock in cardiac intensive care units (CICUs) have primarily focused on acute myocardial infarction (AMI) complicated by cardiogenic shock (AMICS). Few studies...

Journal ArticleDOI
TL;DR: This research presents a novel probabilistic approach that allows us to assess the importance of knowing the carrier and removal status of canine coronavirus as a source of infection for other animals.
Abstract: Although coronary thrombus overlying a disrupted atherosclerotic plaque has long been considered the hallmark and the primary therapeutic target for acute myocardial infarction (MI), multiple other mechanisms are now known to cause or contribute to MI. It is further recognized that an MI is just one of many types of acute myocardial injury. The Fourth Universal Definition of Myocardial Infarction provides a taxonomy for acute myocardial injury, including 5 subtypes of MI and nonischemic myocardial injury. The diagnosis of MI is reserved for patients with myocardial ischemia as the cause of myocardial injury, whether attributable to acute atherothrombosis (type 1 MI) or supply/demand mismatch without acute atherothrombosis (type 2 MI). Myocardial injury in the absence of ischemia is categorized as acute or chronic nonischemic myocardial injury. However, optimal evaluation and treatment strategies for these etiologically distinct diagnoses have yet to be defined. Herein, we review the epidemiology, risk factor associations, and diagnostic tools that may assist in differentiating between nonischemic myocardial injury, type 1 MI, and type 2 MI. We identify limitations, review new research, and propose a framework for the diagnostic and therapeutic approach for patients who have suspected MI or other causes of myocardial injury.

Journal ArticleDOI
TL;DR: A set of large-scale gridded datasets representing population counts or densities is presented, compares and discusses and focuses on data properties, methodological approaches and relative quality aspects that are important to fully understand the characteristics of the data with regard to the intended uses.
Abstract: . Population data represent an essential component in studies focusing on human–nature interrelationships, disaster risk assessment and environmental health. Several recent efforts have produced global- and continental-extent gridded population data which are becoming increasingly popular among various research communities. However, these data products, which are of very different characteristics and based on different modeling assumptions, have never been systematically reviewed and compared, which may impede their appropriate use. This article fills this gap and presents, compares and discusses a set of large-scale (global and continental) gridded datasets representing population counts or densities. It focuses on data properties, methodological approaches and relative quality aspects that are important to fully understand the characteristics of the data with regard to the intended uses. Written by the data producers and members of the user community, through the lens of the “fitness for use” concept, the aim of this paper is to provide potential data users with the knowledge base needed to make informed decisions about the appropriateness of the data products available in relation to the target application and for critical analysis.

Journal ArticleDOI
Morad Aaboud, Georges Aad1, Brad Abbott2, Dale Charles Abbott3  +3001 moreInstitutions (220)
TL;DR: In this paper, the decays of B0 s! + and B0! + have been studied using 26 : 3 fb of 13TeV LHC proton-proton collision data collected with the ATLAS detector in 2015 and 2016.
Abstract: A study of the decays B0 s ! + and B0 ! + has been performed using 26 : 3 fb of 13TeV LHC proton-proton collision data collected with the ATLAS detector in 2015 and 2016. Since the detector resolut ...

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TL;DR: Milk-derived exosomes represent a viable natural nano-carrier for the delivery of siRNA for therapeutic application against cancer and demonstrate that the siRNA of loaded exosome is stable and resist degradation.

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TL;DR: Attention to childhood trauma and the need for trauma-informed care has contributed to the emerging discourse in schools related to teaching practices, school climate, and the delivery of trauma-re... as mentioned in this paper.
Abstract: Attention to childhood trauma and the need for trauma-informed care has contributed to the emerging discourse in schools related to teaching practices, school climate, and the delivery of trauma-re...

Journal ArticleDOI
TL;DR: The solid-based and liquid-based synthetic methods of LATP and LAGP solid electrolytes and the key influencing factors are described, and the crystal structure and phase purity from different synthetic approaches will be introduced.
Abstract: Inorganic solid electrolytes play a critical role in solid-state lithium batteries achieving high safety levels and high energy densities. The synthetic approaches to solid electrolytes are important for both fundamental research and practical applications. Li1+x Alx Ti2-x (PO4 )3 (LATP) and Li1+x Alx Ge2-x (PO4 )3 (LAGP) are two representative solid electrolytes with a sodium superionic conductor (NaSICON) structure. Herein, LATP and LAGP solid electrolytes are reviewed from the synthesis perspective, and correlated with their structure and conductive properties, as well as their electrochemical applications in batteries. First, the solid- and liquid-based synthetic methods to LATP and LAGP solid electrolytes and the key influencing factors are described. Second, the crystal structures and phase purities obtained from different synthetic approaches are introduced. Third, the conductive mechanisms, composition effects, and synthetic effects on the conductivities of LATP and LAGP solid electrolytes are compared. Fourth, the electrochemical applications of these two solid electrolytes in full batteries are discussed, including roles as solid electrolytes, composite components in electrodes, and surface coatings on electrodes. In the last section, a brief outlook is provided on the future development of NaSICON-type solid electrolytes for all-solid-state batteries.

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TL;DR: Reduced levels of MALAT1 augment atherosclerotic lesion formation in mice and are associated with human atherosclerosis disease, which is associated with a worse prognosis.
Abstract: Background: The majority of the human genome comprises noncoding sequences, which are in part transcribed as long noncoding RNAs (lncRNAs). lncRNAs exhibit multiple functions, including the epigene...

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TL;DR: ERAS in spine surgery may provide reductions in complications, readmissions, length of stay, and opioid use, in combination with improvements in patient-reported outcomes and functional recovery, as well as the study design and internal validation methods.

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TL;DR: In this article, the authors investigate the light-induced melting of a unidirectional charge density wave (CDW) in LaTe and find that a fast recovery of the CDW amplitude is followed by a slower re-establishment of phase coherence.
Abstract: Upon excitation with an intense laser pulse, a symmetry-broken ground state can undergo a non-equilibrium phase transition through pathways different from those in thermal equilibrium. The mechanism underlying these photoinduced phase transitions has long been researched in the study of condensed matter systems1, but many details in this ultrafast, non-adiabatic regime still remain to be clarified. To this end, we investigate the light-induced melting of a unidirectional charge density wave (CDW) in LaTe3. Using a suite of time-resolved probes, we independently track the amplitude and phase dynamics of the CDW. We find that a fast (approximately 1 picosecond) recovery of the CDW amplitude is followed by a slower re-establishment of phase coherence. This longer timescale is dictated by the presence of topological defects: long-range order is inhibited and is only restored when the defects annihilate. Our results provide a framework for understanding other photoinduced phase transitions by identifying the generation of defects as a governing mechanism. Three different ultrafast probes investigate a non-adiabatic phase transition and find substantial evidence of topological defects inhibiting the reformation of the equilibrium phase.

Journal ArticleDOI
18 Jun 2019
TL;DR: Applications of the geospatial archive are demonstrated by producing multi-temporal gridded population outputs for Africa and using these to derive health and development metrics.
Abstract: Multi-temporal, globally consistent, high-resolution human population datasets provide consistent and comparable population distributions in support of mapping sub-national heterogeneities in health, wealth, and resource access, and monitoring change in these over time. The production of more reliable and spatially detailed population datasets is increasingly necessary due to the importance of improving metrics at sub-national and multi-temporal scales. This is in support of measurement and monitoring of UN Sustainable Development Goals and related agendas. In response to these agendas, a method has been developed to assemble and harmonise a unique, open access, archive of geospatial datasets. Datasets are provided as global, annual time series, where pertinent at the timescale of population analyses and where data is available, for use in the construction of population distribution layers. The archive includes sub-national census-based population estimates, matched to a geospatial layer denoting administrative unit boundaries, and a number of co-registered gridded geospatial factors that correlate strongly with population presence and density. Here, we describe these harmonised datasets and their limitations, along with the production workflow. Further, we demonstrate applications of the archive by producing multi-temporal gridded population outputs for Africa and using these to derive health and development metrics. The geospatial archive is available at https://doi.org/10.5258/SOTON/WP00650.

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TL;DR: In this article, a hot Earth was detected around LHS 3844, an M-dwarf located 15 pc away from Earth, with a radius of 1.303 ± 0.022 R⊕ and orbits the star every 11 hr.
Abstract: Data from the newly commissioned Transiting Exoplanet Survey Satellite has revealed a "hot Earth" around LHS 3844, an M dwarf located 15 pc away. The planet has a radius of 1.303 ± 0.022 R⊕ and orbits the star every 11 hr. Although the existence of an atmosphere around such a strongly irradiated planet is questionable, the star is bright enough (I = 11.9, K = 9.1) for this possibility to be investigated with transit and occultation spectroscopy. The star's brightness and the planet's short period will also facilitate the measurement of the planet's mass through Doppler spectroscopy.

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TL;DR: The results suggest significantly higher odds of cardiovascular disease among dual users of e-cigarettes + combustible cigarettes compared with smoking alone, and support the critical need to conduct longitudinal studies exploring cardiovascular disease risk associated with e-cigarette use, particularly amongDual users.

Journal ArticleDOI
TL;DR: In a contemporary network of tertiary care CICUs, respiratory failure and shock predominated indications for admission and carried a poor prognosis, while patterns of practice varied considerably between centers, a substantial, low-risk population was identified.
Abstract: Importance Single-center and claims-based studies have described substantial changes in the landscape of care in the cardiac intensive care unit (CICU). Professional societies have recommended research to guide evidence-based CICU redesigns. Objective To characterize patients admitted to contemporary, advanced CICUs. Design, Setting, and Participants This study established the Critical Care Cardiology Trials Network (CCCTN), an investigator-initiated multicenter network of 16 advanced, tertiary CICUs in the United States and Canada. For 2 months in each CICU, data for consecutive admissions were submitted to the central data coordinating center (TIMI Study Group). The data were collected and analyzed between September 2017 and 2018. Main Outcomes and Measures Demographics, diagnoses, management, and outcomes. Results Of 3049 participants, 1132 (37.1%) were women, 797 (31.4%) were individuals of color, and the median age was 65 years (25th and 75th percentiles, 55-75 years). Between September 2017 and September 2018, 3310 admissions were included, among which 2557 (77.3%) were for primary cardiac problems, 337 (10.2%) for postprocedural care, 253 (7.7%) for mixed general and cardiac problems, and 163 (4.9%) for overflow from general medical ICUs. When restricted to the initial 2 months of medical CICU admissions for each site, the primary analysis population included 3049 admissions with a high burden of noncardiovascular comorbidities. The top 2 CICU admission diagnoses were acute coronary syndrome (969 [31.8%]) and heart failure (567 [18.6%]); however, the proportion of acute coronary syndrome was highly variable across centers (15%-57%). The primary indications for CICU care included respiratory insufficiency (814 [26.7%]), shock (643 [21.1%]), unstable arrhythmia (521 [17.1%]), and cardiac arrest (265 [8.7%]). Advanced CICU therapies or monitoring were required for 1776 patients (58.2%), including intravenous vasoactive medications (1105 [36.2%]), invasive hemodynamic monitoring (938 [30.8%]), and mechanical ventilation (652 [21.4%]). The overall CICU mortality rate was 8.3% (95% CI, 7.3%-9.3%). The CICU indications that were associated with the highest mortality rates were cardiac arrest (101 [38.1%]), cardiogenic shock (140 [30.6%]), and the need for renal replacement therapy (51 [34.5%]). Notably, patients admitted solely for postprocedural observation or frequent monitoring had a mortality rate of 0.2% to 0.4%. Conclusions and Relevance In a contemporary network of tertiary care CICUs, respiratory failure and shock predominated indications for admission and carried a poor prognosis. While patterns of practice varied considerably between centers, a substantial, low-risk population was identified. Multicenter collaborative networks, such as the CCCTN, could be used to help redesign cardiac critical care and to test new therapeutic strategies.


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TL;DR: In recent years, policing scholars have increasingly used survey methods to gain insight into officers’ attitudes and behaviours as mentioned in this paper. Yet, surprisingly, methodological research analysing surveys of pol...
Abstract: In recent years, policing scholars have increasingly used survey methods to gain insight into officers’ attitudes and behaviours. Yet, surprisingly, methodological research analysing surveys of pol...

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TL;DR: The IL-1β-IL-1R signaling pathway may contribute to skin inflammation and psoriasis pathogenesis via the direct regulation of dermal IL-17-producing cells and stimulation of keratinocytes for amplifying inflammatory cascade.

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TL;DR: CCBT with a modest amount of support from a clinician or other helping person was found to be efficacious with relatively large mean effect sizes on measures of depressive symptoms and self-guided CCBT for depression was considerably less effective.
Abstract: Objective To evaluate the efficacy of computer-assisted forms of cognitive-behavior therapy for major depressive disorder (MDD) and examine the role of clinician support and other factors that might affect outcomes. Data sources Ovid MEDLINE, PsycINFO, PubMed, and Scopus from their beginnings to July 18, 2016. Keywords were "randomized, controlled trials of computer-assisted cognitive-behavior therapy for depression" and "randomized, controlled trials of mobile apps for cognitive-behavior therapy of depression." Study selection Of 223 studies identified in the search, 183 were excluded yielding a sample of 40 randomized, controlled investigations of computer-assisted cognitive-behavior therapy (CCBT) for depression. Data extraction Data were abstracted independently by two authors, and consensus was reached by discussion with a third author. Results The overall mean effect size for CCBT compared to control conditions was g = 0.502, a moderately large effect. Studies that provided support from a clinician or other person yielded significantly larger effects (g = 0.673) than studies in which no support was provided (g = 0.239). Completion rate and study setting also influenced outcomes. Lower mean effect sizes were observed in studies with lower completion rates and in studies conducted in primary care practices. Conclusions CCBT with a modest amount of support from a clinician or other helping person was found to be efficacious with relatively large mean effect sizes on measures of depressive symptoms. Self-guided CCBT for depression was considerably less effective. Future research should focus on enhancing the implementation of CCBT, including evaluating the amount and type of support needed for effective delivery, methods to improve engagement with computer-assisted therapies, and ways to improve treatment outcome in primary care settings.

Journal ArticleDOI
TL;DR: A novel image‐based methodology for normalizing surgical therapies across a large multicenter cohort is leveraged to quantify the effects of surgical targeting on seizure outcomes in LITT for mTLE.
Abstract: Objective Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) has reported seizure freedom rates between 36% and 78% with at least 1 year of follow-up. Unfortunately, the lack of robust methods capable of incorporating the inherent variability of patient anatomy, the variability of the ablated volumes, and clinical outcomes have limited three-dimensional quantitative analysis of surgical targeting and its impact on seizure outcomes. We therefore aimed to leverage a novel image-based methodology for normalizing surgical therapies across a large multicenter cohort to quantify the effects of surgical targeting on seizure outcomes in LITT for mTLE. Methods This multicenter, retrospective cohort study included 234 patients from 11 centers who underwent LITT for mTLE. To investigate therapy location, all ablation cavities were manually traced on postoperative magnetic resonance imaging (MRI), which were subsequently nonlinearly normalized to a common atlas space. The association of clinical variables and ablation location to seizure outcome was calculated using multivariate regression and Bayesian models, respectively. Results Ablations including more anterior, medial, and inferior temporal lobe structures, which involved greater amygdalar volume, were more likely to be associated with Engel class I outcomes. At both 1 and 2 years after LITT, 58.0% achieved Engel I outcomes. A history of bilateral tonic-clonic seizures decreased chances of Engel I outcome. Radiographic hippocampal sclerosis was not associated with seizure outcome. Significance LITT is a viable treatment for mTLE in patients who have been properly evaluated at a comprehensive epilepsy center. Consideration of surgical factors is imperative to the complete assessment of LITT. Based on our model, ablations must prioritize the amygdala and also include the hippocampal head, parahippocampal gyrus, and rhinal cortices to maximize chances of seizure freedom. Extending the ablation posteriorly has diminishing returns. Further work is necessary to refine this analysis and define the minimal zone of ablation necessary for seizure control.