Showing papers by "Tufts University published in 2018"
TL;DR: This AASLD 2018 Hepatitis B Guidance provides a data-supported approach to screening, prevention, diagnosis, and clinical management of patients with hepatitis B.
2,399 citations
Verneri Anttila1, Verneri Anttila2, Brendan Bulik-Sullivan1, Brendan Bulik-Sullivan2 +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
TL;DR: The integration of OCTA in multimodal imaging in the evaluation of retinal vascular occlusive diseases, diabetic retinopathy, uveitis, inherited diseases, age-related macular degeneration, and disorders of the optic nerve is presented.
988 citations
Institute for Health Metrics and Evaluation1, University of Louisville2, Kermanshah University of Medical Sciences3, Karolinska Institutet4, University of Queensland5, Centre for Mental Health6, Tehran University of Medical Sciences7, South African Medical Research Council8, University of KwaZulu-Natal9, University of Colorado Boulder10, University of California, Irvine11, Fred Hutchinson Cancer Research Center12, Montefiore Medical Center13, Northeastern University14, University of Alabama at Birmingham15, Brown University16, San Diego State University17, University of Melbourne18, Albert Einstein College of Medicine19, Cambridge Health Alliance20, University of Cape Town21, Johns Hopkins University22, University of Pittsburgh23, Case Western Reserve University24, Marshall University25, University of London26, University of Illinois at Urbana–Champaign27, National Drug and Alcohol Research Centre28, Harvard University29, University of California, San Diego30, Yale University31, Georgetown University32, Veterans Health Administration33, Jackson State University34, University of Massachusetts Boston35, State University of New York System36, Simmons College37, Charles R. Drew University of Medicine and Science38, University of California, Los Angeles39, University of Oxford40, Norwegian Institute of Public Health41, Curtin University42, Pacific Institute43, Heidelberg University44, Jimma University45, Northwestern University46, Washington University in St. Louis47, Howard University48, University of New Mexico49, University at Buffalo50, University of Washington51, University of South Florida52, Tufts University53, University of Rochester Medical Center54, Kosin University55, Central South University56, Michigan State University57, Ball State University58, Nova Southeastern University59, Dalhousie University60, Mayo Clinic61, University of British Columbia62, Ohio State University63, Baylor University64, Wrocław Medical University65, Jagiellonian University Medical College66, Dartmouth College67, University of Western Ontario68, Oregon Health & Science University69, Virginia Commonwealth University70, Columbia University71, University of Canberra72, Aga Khan University73
TL;DR: There are wide differences in the burden of disease at the state level and specific diseases and risk factors, such as drug use disorders, high BMI, poor diet, high fasting plasma glucose level, and alcohol use disorders are increasing and warrant increased attention.
Abstract: Introduction Several studies have measured health outcomes in the United States, but none have provided a comprehensive assessment of patterns of health by state. Objective To use the results of the Global Burden of Disease Study (GBD) to report trends in the burden of diseases, injuries, and risk factors at the state level from 1990 to 2016. Design and Setting A systematic analysis of published studies and available data sources estimates the burden of disease by age, sex, geography, and year. Main Outcomes and Measures Prevalence, incidence, mortality, life expectancy, healthy life expectancy (HALE), years of life lost (YLLs) due to premature mortality, years lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 333 causes and 84 risk factors with 95% uncertainty intervals (UIs) were computed. Results Between 1990 and 2016, overall death rates in the United States declined from 745.2 (95% UI, 740.6 to 749.8) per 100 000 persons to 578.0 (95% UI, 569.4 to 587.1) per 100 000 persons. The probability of death among adults aged 20 to 55 years declined in 31 states and Washington, DC from 1990 to 2016. In 2016, Hawaii had the highest life expectancy at birth (81.3 years) and Mississippi had the lowest (74.7 years), a 6.6-year difference. Minnesota had the highest HALE at birth (70.3 years), and West Virginia had the lowest (63.8 years), a 6.5-year difference. The leading causes of DALYs in the United States for 1990 and 2016 were ischemic heart disease and lung cancer, while the third leading cause in 1990 was low back pain, and the third leading cause in 2016 was chronic obstructive pulmonary disease. Opioid use disorders moved from the 11th leading cause of DALYs in 1990 to the 7th leading cause in 2016, representing a 74.5% (95% UI, 42.8% to 93.9%) change. In 2016, each of the following 6 risks individually accounted for more than 5% of risk-attributable DALYs: tobacco consumption, high body mass index (BMI), poor diet, alcohol and drug use, high fasting plasma glucose, and high blood pressure. Across all US states, the top risk factors in terms of attributable DALYs were due to 1 of the 3 following causes: tobacco consumption (32 states), high BMI (10 states), or alcohol and drug use (8 states). Conclusions and Relevance There are wide differences in the burden of disease at the state level. Specific diseases and risk factors, such as drug use disorders, high BMI, poor diet, high fasting plasma glucose level, and alcohol use disorders are increasing and warrant increased attention. These data can be used to inform national health priorities for research, clinical care, and policy.
962 citations
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)
745 citations
University of North Carolina at Chapel Hill1, University of Pennsylvania2, University of Colorado Denver3, Tel Aviv University4, Baylor University Medical Center5, Durham University6, University of California, San Diego7, Mayo Clinic8, Northwestern University9, Nestlé10, Tufts University11, Boston Children's Hospital12, Icahn School of Medicine at Mount Sinai13, University of Texas Southwestern Medical Center14, Cincinnati Children's Hospital Medical Center15, Baylor College of Medicine16, Nationwide Children's Hospital17, University of Paris18, University of Health Sciences Antigua19, University of Illinois at Urbana–Champaign20, Shimane University21, University Hospitals Coventry and Warwickshire NHS Trust22, Harvard University23, Juntendo University24, University of Ljubljana25, National and Kapodistrian University of Athens26, University of Utah27, University of Adelaide28, University of South Florida29, University of Lausanne30, University College London31, Kaiser Permanente32, University of Newcastle33, Vanderbilt University34, Vrije Universiteit Brussel35, Federal University of Paraná36, Children's Memorial Hospital37, University of Amsterdam38
TL;DR: An updated diagnostic algorithm for EoE was developed, with removal of the PPI trial requirement, and the evidence suggests that PPIs are better classified as a treatment for esophageal eosinophilia that may be due to EOE than as a diagnostic criterion.
621 citations
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.
598 citations
University of Birmingham1, University of Texas Health Science Center at San Antonio2, The Forsyth Institute3, University of Adelaide4, Charité5, Goethe University Frankfurt6, University of Alabama at Birmingham7, University at Buffalo8, University of Toronto9, Hadassah Medical Center10, Tufts University11, University of Copenhagen12, University of Iowa13, University of California, San Francisco14, University of Bern15, University of Giessen16, Osaka University17, Texas A&M University18, University of São Paulo19, Ohio State University20, Katholieke Universiteit Leuven21, University of Ferrara22, University of Basel23, University of Graz24, Niigata University25
TL;DR: While gingival health and gingivitis have many clinical features, case definitions are primarily predicated on presence or absence of bleeding on probing, which creates differences in the way in which a "case" of gedival health or gingIVitis is defined for clinical practice as opposed to epidemiologically in population prevalence surveys.
Abstract: Periodontal health is defined by absence of clinically detectable inflammation. There is a biological level of immune surveillance that is consistent with clinical gingival health and homeostasis. Clinical gingival health may be found in a periodontium that is intact, i.e. without clinical attachment loss or bone loss, and on a reduced periodontium in either a non-periodontitis patient (e.g. in patients with some form of gingival recession or following crown lengthening surgery) or in a patient with a history of periodontitis who is currently periodontally stable. Clinical gingival health can be restored following treatment of gingivitis and periodontitis. However, the treated and stable periodontitis patient with current gingival health remains at increased risk of recurrent periodontitis, and accordingly, must be closely monitored. Two broad categories of gingival diseases include non-dental plaque biofilm-induced gingival diseases and dental plaque-induced gingivitis. Non-dental plaque biofilm-induced gingival diseases include a variety of conditions that are not caused by plaque and usually do not resolve following plaque removal. Such lesions may be manifestations of a systemic condition or may be localized to the oral cavity. Dental plaque-induced gingivitis has a variety of clinical signs and symptoms, and both local predisposing factors and systemic modifying factors can affect its extent, severity, and progression. Dental plaque-induced gingivitis may arise on an intact periodontium or on a reduced periodontium in either a non-periodontitis patient or in a currently stable "periodontitis patient" i.e. successfully treated, in whom clinical inflammation has been eliminated (or substantially reduced). A periodontitis patient with gingival inflammation remains a periodontitis patient (Figure 1), and comprehensive risk assessment and management are imperative to ensure early prevention and/or treatment of recurrent/progressive periodontitis. Precision dental medicine defines a patient-centered approach to care, and therefore, creates differences in the way in which a "case" of gingival health or gingivitis is defined for clinical practice as opposed to epidemiologically in population prevalence surveys. Thus, case definitions of gingival health and gingivitis are presented for both purposes. While gingival health and gingivitis have many clinical features, case definitions are primarily predicated on presence or absence of bleeding on probing. Here we classify gingival health and gingival diseases/conditions, along with a summary table of diagnostic features for defining health and gingivitis in various clinical situations.
573 citations
Richard A. Klein1, Michelangelo Vianello2, Fred Hasselman3, Byron G. Adams4 +187 more•Institutions (118)
TL;DR: This paper conducted preregistered replications of 28 classic and contemporary published findings, with protocols that were peer reviewed in advance, to examine variation in effect magnitudes across samples and settings, and found that very little heterogeneity was attributable to the order in which the tasks were performed or whether the task were administered in lab versus online.
Abstract: We conducted preregistered replications of 28 classic and contemporary published findings, with protocols that were peer reviewed in advance, to examine variation in effect magnitudes across samples and settings. Each protocol was administered to approximately half of 125 samples that comprised 15,305 participants from 36 countries and territories. Using the conventional criterion of statistical significance (p < .05), we found that 15 (54%) of the replications provided evidence of a statistically significant effect in the same direction as the original finding. With a strict significance criterion (p < .0001), 14 (50%) of the replications still provided such evidence, a reflection of the extremely high-powered design. Seven (25%) of the replications yielded effect sizes larger than the original ones, and 21 (75%) yielded effect sizes smaller than the original ones. The median comparable Cohen’s ds were 0.60 for the original findings and 0.15 for the replications. The effect sizes were small (< 0.20) in 16 of the replications (57%), and 9 effects (32%) were in the direction opposite the direction of the original effect. Across settings, the Q statistic indicated significant heterogeneity in 11 (39%) of the replication effects, and most of those were among the findings with the largest overall effect sizes; only 1 effect that was near zero in the aggregate showed significant heterogeneity according to this measure. Only 1 effect had a tau value greater than .20, an indication of moderate heterogeneity. Eight others had tau values near or slightly above .10, an indication of slight heterogeneity. Moderation tests indicated that very little heterogeneity was attributable to the order in which the tasks were performed or whether the tasks were administered in lab versus online. Exploratory comparisons revealed little heterogeneity between Western, educated, industrialized, rich, and democratic (WEIRD) cultures and less WEIRD cultures (i.e., cultures with relatively high and low WEIRDness scores, respectively). Cumulatively, variability in the observed effect sizes was attributable more to the effect being studied than to the sample or setting in which it was studied.
495 citations
TL;DR: The results uncover a form of caspase-8–mediated pyroptosis and suggest a hypothesis for the increased sensitivity of humans to Yersinia infection compared with the rodent reservoir.
Abstract: Cell death and inflammation are intimately linked during Yersinia infection. Pathogenic Yersinia inhibits the MAP kinase TGFβ-activated kinase 1 (TAK1) via the effector YopJ, thereby silencing cytokine expression while activating caspase-8–mediated cell death. Here, using Yersinia pseudotuberculosis in corroboration with costimulation of lipopolysaccharide and (5Z)-7-Oxozeaenol, a small-molecule inhibitor of TAK1, we show that caspase-8 activation during TAK1 inhibition results in cleavage of both gasdermin D (GSDMD) and gasdermin E (GSDME) in murine macrophages, resulting in pyroptosis. Loss of GsdmD delays membrane rupture, reverting the cell-death morphology to apoptosis. We found that the Yersinia-driven IL-1 response arises from asynchrony of macrophage death during bulk infections in which two cellular populations are required to provide signal 1 and signal 2 for IL-1α/β release. Furthermore, we found that human macrophages are resistant to YopJ-mediated pyroptosis, with dampened IL-1β production. Our results uncover a form of caspase-8–mediated pyroptosis and suggest a hypothesis for the increased sensitivity of humans to Yersinia infection compared with the rodent reservoir.
480 citations
TL;DR: Clinical evidence of the heterogeneity of resistance in advanced NSCLC is provided and a need for clinical trial strategies that can overcome multiple concomitant resistance mechanisms or strategies for preventing such resistance is provided.
Abstract: Importance Osimertinib mesylate is used globally to treatEGFR-mutant non–small cell lung cancer (NSCLC) with tyrosine kinase inhibitor resistance mediated by theEGFRT790M mutation. Acquired resistance to osimertinib is a growing clinical challenge that is poorly understood. Objective To understand the molecular mechanisms of acquired resistance to osimertinib and their clinical behavior. Design, Setting, and Participants Patients with advanced NSCLC who received osimertinib for T790M-positive acquired resistance to prior EGFR tyrosine kinase inhibitor were identified from a multi-institutional cohort (n = 143) and a confirmatory trial cohort (NCT01802632) (n = 110). Next-generation sequencing of tumor biopsies after osimertinib resistance was performed. Genotyping of plasma cell-free DNA was studied as an orthogonal approach, including serial plasma samples when available. The study and analysis were finalized on November 9, 2017. Main Outcomes and Measures Mechanisms of resistance and their association with time to treatment discontinuation on osimertinib. Results Of the 143 patients evaluated, 41 (28 [68%] women) had tumor next-generation sequencing after acquired resistance to osimertinib. Among 13 patients (32%) with maintained T790M at the time of resistance,EGFRC797S was seen in 9 patients (22%). Among 28 individuals (68%) with loss of T790M, a range of competing resistance mechanisms was detected, including novel mechanisms such as acquiredKRASmutations and targetable gene fusions. Time to treatment discontinuation was shorter in patients with T790M loss (6.1 vs 15.2 months), suggesting emergence of pre-existing resistant clones; this finding was confirmed in a validation cohort of 110 patients with plasma cell-free DNA genotyping performed after osimertinib resistance. In studies of serial plasma levels of mutantEGFR, loss of T790M at resistance was associated with a smaller decrease in levels of theEGFRdriver mutation after 1 to 3 weeks of therapy (100% vs 83% decrease;P = .01). Conclusions and Relevance Acquired resistance to osimertinib mediated by loss of the T790M mutation is associated with early resistance and a range of competing resistance mechanisms. These data provide clinical evidence of the heterogeneity of resistance in advanced NSCLC and a need for clinical trial strategies that can overcome multiple concomitant resistance mechanisms or strategies for preventing such resistance.
The Heart Research Institute1, Saint Louis University2, Wake Forest University3, University of Maryland, Baltimore4, Heidelberg University5, University of Florida6, University of Milan7, University of Miami8, University of Erlangen-Nuremberg9, Université du Québec à Montréal10, University of Otago11, University of Adelaide12, Agostino Gemelli University Polyclinic13, United States Department of Veterans Affairs14, Tufts University15, Kyung Hee University16, Dalhousie University17, King's College London18, Sichuan University19, The Chinese University of Hong Kong20, University of Western Australia21, National Institutes of Health22, National University of Singapore23, Uppsala University24, University of São Paulo25, Memorial Hospital of South Bend26, Vrije Universiteit Brussel27, Maastricht University28, Universidad Pública de Navarra29, Centre Hospitalier Universitaire de Toulouse30
TL;DR: Evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR) are presented.
Abstract: Sarcopenia, defined as an age-associated loss of skeletal muscle function and muscle mass, occurs in approximately 6 - 22 % of older adults. This paper presents evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR). To develop the guidelines, we drew upon the best available evidence from two systematic reviews paired with consensus statements by international working groups on sarcopenia. Eight topics were selected for the recommendations: (i) defining sarcopenia; (ii) screening and diagnosis; (iii) physical activity prescription; (iv) protein supplementation; (v) vitamin D supplementation; (vi) anabolic hormone prescription; (vii) medications under development; and (viii) research. The ICSFR task force evaluated the evidence behind each topic including the quality of evidence, the benefitharm balance of treatment, patient preferences/values, and cost-effectiveness. Recommendations were graded as either strong or conditional (weak) as per the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Consensus was achieved via one face-to-face workshop and a modified Delphi process. We make a conditional recommendation for the use of an internationally accepted measurement tool for the diagnosis of sarcopenia including the EWGSOP and FNIH definitions, and advocate for rapid screening using gait speed or the SARC-F. To treat sarcopenia, we strongly recommend the prescription of resistance-based physical activity, and conditionally recommend protein supplementation/a protein-rich diet. No recommendation is given for Vitamin D supplementation or for anabolic hormone prescription. There is a lack of robust evidence to assess the strength of other treatment options.
TL;DR: In this article, a trapped-ion implementation of one such hybrid algorithm is used to solve a quantum chemistry problem, which is a promising approach for near-term practical applications of quantum computers.
Abstract: Quantum-classical hybrid algorithms are a promising approach for near-term practical applications of quantum computers. A new experiment demonstrates how a trapped-ion implementation of one such algorithm solves a quantum chemistry problem.
19 Oct 2018
TL;DR: The application of VQE to the simulation of molecular energies using the unitary coupled cluster (UCC) ansatz is studied and an analytical method to compute the energy gradient is proposed that reduces the sampling cost for gradient estimation by several orders of magnitude compared to numerical gradients.
Abstract: The variational quantum eigensolver (VQE) algorithm combines the ability of quantum computers to efficiently compute expectation values with a classical optimization routine in order to approximate ground state energies of quantum systems. In this paper, we study the application of VQE to the simulation of molecular energies using the unitary coupled cluster (UCC) ansatz. We introduce new strategies to reduce the circuit depth for the implementation of UCC and improve the optimization of the wavefunction based on efficient classical approximations of the cluster amplitudes. Additionally, we propose an analytical method to compute the energy gradient that reduces the sampling cost for gradient estimation by several orders of magnitude compared to numerical gradients. We illustrate our methodology with numerical simulations for a system of four hydrogen atoms that exhibit strong correlation and show that the circuit depth of VQE using a UCC ansatz can be reduced without introducing significant loss of accuracy in the final wavefunctions and energies.
TL;DR: Indocyanine green, a clinically approved near-IR dye, exhibits a remarkable amount of SWIR emission, which enables state-of-the-art SWIR imaging with direct translation potential into clinical settings, and even outperforms other commercially available SWIR emitters.
Abstract: Fluorescence imaging is a method of real-time molecular tracking in vivo that has enabled many clinical technologies. Imaging in the shortwave IR (SWIR; 1,000-2,000 nm) promises higher contrast, sensitivity, and penetration depths compared with conventional visible and near-IR (NIR) fluorescence imaging. However, adoption of SWIR imaging in clinical settings has been limited, partially due to the absence of US Food and Drug Administration (FDA)-approved fluorophores with peak emission in the SWIR. Here, we show that commercially available NIR dyes, including the FDA-approved contrast agent indocyanine green (ICG), exhibit optical properties suitable for in vivo SWIR fluorescence imaging. Even though their emission spectra peak in the NIR, these dyes outperform commercial SWIR fluorophores and can be imaged in the SWIR, even beyond 1,500 nm. We show real-time fluorescence imaging using ICG at clinically relevant doses, including intravital microscopy, noninvasive imaging in blood and lymph vessels, and imaging of hepatobiliary clearance, and show increased contrast compared with NIR fluorescence imaging. Furthermore, we show tumor-targeted SWIR imaging with IRDye 800CW-labeled trastuzumab, an NIR dye being tested in multiple clinical trials. Our findings suggest that high-contrast SWIR fluorescence imaging can be implemented alongside existing imaging modalities by switching the detection of conventional NIR fluorescence systems from silicon-based NIR cameras to emerging indium gallium arsenide-based SWIR cameras. Using ICG in particular opens the possibility of translating SWIR fluorescence imaging to human clinical applications. Indeed, our findings suggest that emerging SWIR-fluorescent in vivo contrast agents should be benchmarked against the SWIR emission of ICG in blood.
University of Liège1, Catholic University of the Sacred Heart2, University of Toulouse3, Tufts University4, VU University Amsterdam5, VU University Medical Center6, University of Erlangen-Nuremberg7, National Research Council8, University of Southampton9, King Saud University10, University of Oldenburg11, Vrije Universiteit Brussel12, University of Florence13, University of Oxford14, University of Sheffield15, Arthritis Research UK16, Ghent University Hospital17, Geneva College18, University Hospital Southampton NHS Foundation Trust19, Australian Catholic University20
TL;DR: The aim of this study was to review the methods to assess muscle mass and to reach consensus on the development of a reference standard for measuring lean body mass.
Abstract: BACKGROUND: All proposed definitions of sarcopenia include the measurement of muscle mass, but the techniques and threshold values used vary. Indeed, the literature does not establish consensus on the best technique for measuring lean body mass. Thus, the objective measurement of sarcopenia is hampered by limitations intrinsic to assessment tools. The aim of this study was to review the methods to assess muscle mass and to reach consensus on the development of a reference standard. METHODS: Literature reviews were performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis working group on frailty and sarcopenia. Face-to-face meetings were organized for the whole group to make amendments and discuss further recommendations. RESULTS: A wide range of techniques can be used to assess muscle mass. Cost, availability, and ease of use can determine whether the techniques are better suited to clinical practice or are more useful for research. No one technique subserves all requirements but dual energy X-ray absorptiometry could be considered as a reference standard (but not a gold standard) for measuring muscle lean body mass. CONCLUSIONS: Based on the feasibility, accuracy, safety, and low cost, dual energy X-ray absorptiometry can be considered as the reference standard for measuring muscle mass.
TL;DR: Pt/Cu SAAs offer a new approach to coke-resistant C-H activation chemistry, with the added economic benefit that the precious metal is diluted at the atomic limit.
Abstract: The recent availability of shale gas has led to a renewed interest in C-H bond activation as the first step towards the synthesis of fuels and fine chemicals. Heterogeneous catalysts based on Ni and Pt can perform this chemistry, but deactivate easily due to coke formation. Cu-based catalysts are not practical due to high C-H activation barriers, but their weaker binding to adsorbates offers resilience to coking. Using Pt/Cu single-atom alloys (SAAs), we examine C-H activation in a number of systems including methyl groups, methane and butane using a combination of simulations, surface science and catalysis studies. We find that Pt/Cu SAAs activate C-H bonds more efficiently than Cu, are stable for days under realistic operating conditions, and avoid the problem of coking typically encountered with Pt. Pt/Cu SAAs therefore offer a new approach to coke-resistant C-H activation chemistry, with the added economic benefit that the precious metal is diluted at the atomic limit.
Johns Hopkins University1, University of Pennsylvania2, Centre national de la recherche scientifique3, Tufts University4, Arizona State University5, Dresden University of Technology6, Clarkson University7, National Institutes of Health8, University of Illinois at Urbana–Champaign9, Saarland University10
TL;DR: This Analysis compares and contrasts methods for measuring the mechanical properties of cells by applying the different approaches to the same breast cancer cell line, highlighting how elastic and viscous moduli of MCF-7 breast cancer cells can vary 1,000-fold and 100-fold.
Abstract: The mechanical properties of cells influence their cellular and subcellular functions, including cell adhesion, migration, polarization, and differentiation, as well as organelle organization and trafficking inside the cytoplasm. Yet reported values of cell stiffness and viscosity vary substantially, which suggests differences in how the results of different methods are obtained or analyzed by different groups. To address this issue and illustrate the complementarity of certain approaches, here we present, analyze, and critically compare measurements obtained by means of some of the most widely used methods for cell mechanics: atomic force microscopy, magnetic twisting cytometry, particle-tracking microrheology, parallel-plate rheometry, cell monolayer rheology, and optical stretching. These measurements highlight how elastic and viscous moduli of MCF-7 breast cancer cells can vary 1,000-fold and 100-fold, respectively. We discuss the sources of these variations, including the level of applied mechanical stress, the rate of deformation, the geometry of the probe, the location probed in the cell, and the extracellular microenvironment.
TL;DR: This Review summarizes hierarchical design strategies of cellulose, silk and chitin, focusing on nanoconfinement, fibrillar orientation and alignment in 2D and 3D structures, and highlights the contribution of rational material design strategies to the development of mechanically anisotropic and responsive materials.
Abstract: Nanofibrillar materials, such as cellulose, chitin and silk, are highly ordered architectures, formed through the self-assembly of repetitive building blocks into higher-order structures, which are stabilized by non-covalent interactions. This hierarchical building principle endows many biological materials with remarkable mechanical strength, anisotropy, flexibility and optical properties, such as structural colour. These features make nanofibrillar biopolymers interesting candidates for the development of strong, sustainable and biocompatible materials for environmental, energy, optical and biomedical applications. However, recreating their architecture is challenging from an engineering perspective. Rational design approaches, applying a combination of theoretical and experimental protocols, have enabled the design of biopolymer-based materials through mimicking nature's multiscale assembly approach. In this Review, we summarize hierarchical design strategies of cellulose, silk and chitin, focusing on nanoconfinement, fibrillar orientation and alignment in 2D and 3D structures. These multiscale architectures are discussed in the context of mechanical and optical properties, and different fabrication strategies for the manufacturing of biopolymer nanofibril-based materials are investigated. We highlight the contribution of rational material design strategies to the development of mechanically anisotropic and responsive materials and examine the future of the material-by-design paradigm. Nanofibrils are abundant and critical structural components in nature that can be exploited for novel and sustainable materials. In this Review, hierarchical design strategies for cellulose, silk and chitin nanofibrils in nature and in materials engineering are discussed.
TL;DR: The scope of this review is to summarize the extensive researches addressing agarose-based biomaterials in order to provide an in-depth understanding of its tissue engineering-related applications.
TL;DR: In this study, single-cell transcriptional profiles of the murine non-myocyte cardiac cellular landscape are characterized using single- cell RNA sequencing (scRNA-seq) and revealed the diversity of the cardiac cellulome and facilitated the development of techniques to isolate understudied cardiac cell populations.
TL;DR: It is shown that cationic lipid-mediated in vivo delivery of Cas9–guide RNA–lipid complexes can ameliorate hearing loss in a mouse model of human genetic deafness, suggesting that protein–RNA complex delivery of target gene-disrupting agents in vivo is a potential strategy for the treatment of some types of autosomal-dominant hearing loss.
Abstract: Although genetic factors contribute to almost half of all cases of deafness, treatment options for genetic deafness are limited. We developed a genome-editing approach to target a dominantly inherited form of genetic deafness. Here we show that cationic lipid-mediated in vivo delivery of Cas9-guide RNA complexes can ameliorate hearing loss in a mouse model of human genetic deafness. We designed and validated, both in vitro and in primary fibroblasts, genome editing agents that preferentially disrupt the dominant deafness-associated allele in the Tmc1 (transmembrane channel-like gene family 1) Beethoven (Bth) mouse model, even though the mutant Tmc1Bth allele differs from the wild-type allele at only a single base pair. Injection of Cas9-guide RNA-lipid complexes targeting the Tmc1Bth allele into the cochlea of neonatal Tmc1Bth/+ mice substantially reduced progressive hearing loss. We observed higher hair cell survival rates and lower auditory brainstem response thresholds in injected ears than in uninjected ears or ears injected with control complexes that targeted an unrelated gene. Enhanced acoustic startle responses were observed among injected compared to uninjected Tmc1Bth/+ mice. These findings suggest that protein-RNA complex delivery of target gene-disrupting agents in vivo is a potential strategy for the treatment of some types of autosomal-dominant hearing loss.
TL;DR: In this paper, a search for new phenomena in final states with an energetic jet and large missing transverse momentum is reported, and the results are translated into exclusion limits in models with pair-produced weakly interacting dark-matter candidates, large extra spatial dimensions, and supersymmetric particles in several compressed scenarios.
Abstract: Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses proton-proton collision data corresponding to an integrated luminosity of 36.1 fb−1 at a centre-of-mass energy of 13 TeV collected in 2015 and 2016 with the ATLAS detector at the Large Hadron Collider. Events are required to have at least one jet with a transverse momentum above 250 GeV and no leptons (e or μ). Several signal regions are considered with increasing requirements on the missing transverse momentum above 250 GeV. Good agreement is observed between the number of events in data and Standard Model predictions. The results are translated into exclusion limits in models with pair-produced weakly interacting dark-matter candidates, large extra spatial dimensions, and supersymmetric particles in several compressed scenarios.
University of California, Los Angeles1, King's College London2, University of Florida3, Washington University in St. Louis4, Abbott Northwestern Hospital5, University of Michigan6, University of Kansas7, Columbia University Medical Center8, Indiana University9, Overlook Medical Center10, University of Rochester Medical Center11, Rush University Medical Center12, Rutgers University13, University of Cincinnati14, Hackensack University Medical Center15, University of California, Irvine16, Winthrop-University Hospital17, Rhode Island Hospital18, University of Colorado Hospital19, Henry Ford Health System20, University of Texas Health Science Center at San Antonio21, University of Pennsylvania22, University of North Carolina at Chapel Hill23, City of Hope National Medical Center24, Thomas Jefferson University25, St. Joseph Hospital26, Vanderbilt University27, Beth Israel Deaconess Medical Center28, Baylor University Medical Center29, Medical University of South Carolina30, Mount Sinai Hospital31, Dresden University of Technology32, Tufts University33, Stony Brook University34, Université de Sherbrooke35, University of California, San Diego36, Houston Methodist Hospital37, Geisinger Health System38, Kaiser Permanente39, University of Kentucky40, Montreal Neurological Institute and Hospital41, Hofstra University42, University of Washington43, Northwest Biotherapeutics44
TL;DR: Addition of DCVax-L to standard therapy is feasible and safe in glioblastoma patients, and may extend survival, and overall adverse events withDCVax were comparable to standard Therapy alone.
Abstract: Following publication of the original article [1], the authors reported an error in the spelling of one of the author names. In this Correction the incorrect and correct author names are indicated and the author name has been updated in the original publication. The authors also reported an error in the Methods section of the original article. In this Correction the incorrect and correct versions of the affected sentence are indicated. The original article has not been updated with regards to the error in the Methods section.
TL;DR: The results suggest that gut microbiota could influence inflammatory responses in the liver through metabolites engaging host receptors, and these effects are AhR dependent.
TL;DR: Current knowledge on the associations between dietary patterns and cancer, coronary heart disease, stroke, and type 2 diabetes is discussed, focusing on areas of uncertainty and future research directions.
Abstract: Matthias B Schulze and colleagues discuss current knowledge on the associations between dietary patterns and cancer, coronary heart disease, stroke, and type 2 diabetes, focusing on areas of uncertainty and future research directions
Mayo Clinic1, Yale University2, Johns Hopkins University3, Rhode Island Hospital4, University of North Carolina at Chapel Hill5, Medical College of Wisconsin6, Cleveland Clinic7, Beaumont Health8, Dartmouth College9, University of Louisville10, Tufts University11, NorthShore University HealthSystem12, Rutgers University13
TL;DR: This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions.
Abstract: The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician/advanced practice provider and the microbiologists who provide enormous value to the healthcare team. This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. This document presents a system-based approach rather than specimen-based approach, and includes bloodstream and cardiovascular system infections, central nervous system infections, ocular infections, soft tissue infections of the head and neck, upper and lower respiratory infections, infections of the gastrointestinal tract, intra-abdominal infections, bone and joint infections, urinary tract infections, genital infections, and other skin and soft tissue infections; or into etiologic agent groups, including arthropod-borne infections, viral syndromes, and blood and tissue parasite infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also emphasized. There is intentional redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a guidance for physicians in choosing tests that will aid them to quickly and accurately diagnose infectious diseases in their patients.
TL;DR: The application and development of machine-learning methods used in experiments at the frontiers of particle physics (such as the Large Hadron Collider) are reviewed, including recent advances based on deep learning.
Abstract: Our knowledge of the fundamental particles of nature and their interactions is summarized by the standard model of particle physics Advancing our understanding in this field has required experiments that operate at ever higher energies and intensities, which produce extremely large and information-rich data samples The use of machine-learning techniques is revolutionizing how we interpret these data samples, greatly increasing the discovery potential of present and future experiments Here we summarize the challenges and opportunities that come with the use of machine learning at the frontiers of particle physics
TL;DR: It is hypothesized that different macrophage lineages respond divergently to Mtb infection, with IMs exhibiting nutritional restriction and controlling bacterial growth and AMs representing a more nutritionally permissive environment.
Abstract: To understand how infection by Mycobacterium tuberculosis (Mtb) is modulated by host cell phenotype, we characterized those host phagocytes that controlled or supported bacterial growth during early infection, focusing on the ontologically distinct alveolar macrophage (AM) and interstitial macrophage (IM) lineages. Using fluorescent Mtb reporter strains, we found that bacilli in AM exhibited lower stress and higher bacterial replication than those in IM. Interestingly, depletion of AM reduced bacterial burden, whereas depletion of IM increased bacterial burden. Transcriptomic analysis revealed that IMs were glycolytically active, whereas AMs were committed to fatty acid oxidation. Intoxication of infected mice with the glycolytic inhibitor, 2-deoxyglucose, decreased the number of IMs yet increased the bacterial burden in the lung. Furthermore, in in vitro macrophage infections, 2-deoxyglucose treatment increased bacterial growth, whereas the fatty acid oxidation inhibitor etomoxir constrained bacterial growth. We hypothesize that different macrophage lineages respond divergently to Mtb infection, with IMs exhibiting nutritional restriction and controlling bacterial growth and AMs representing a more nutritionally permissive environment.
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, University of Texas at Austin15, Boston University16, Northwestern University17, University of Hawaii18, Tufts University19
TL;DR: The USPSTF found that the evidence is inadequate to assess the effectiveness of drug therapies in reducing subsequent fracture rates in men without previous fractures, and recommends screening for osteoporosis with bone measurement testing to prevent osteooporotic fractures in women 65 years and older.
Abstract: Importance By 2020, approximately 12.3 million individuals in the United States older than 50 years are expected to have osteoporosis. Osteoporotic fractures, particularly hip fractures, are associated with limitations in ambulation, chronic pain and disability, loss of independence, and decreased quality of life, and 21% to 30% of patients who experience a hip fracture die within 1 year. The prevalence of primary osteoporosis (ie, osteoporosis without underlying disease) increases with age and differs by race/ethnicity. With the aging of the US population, the potential preventable burden is likely to increase in future years. Objective To update the 2011 US Preventive Services Task Force (USPSTF) recommendation on screening for osteoporosis. Evidence review The USPSTF reviewed the evidence on screening for and treatment of osteoporotic fractures in men and women, as well as risk assessment tools, screening intervals, and efficacy of screening and treatment in subgroups. The screening population was postmenopausal women and older men with no known previous osteoporotic fractures and no known comorbid conditions or medication use associated with secondary osteoporosis. Findings The USPSTF found convincing evidence that bone measurement tests are accurate for detecting osteoporosis and predicting osteoporotic fractures in women and men. The USPSTF found adequate evidence that clinical risk assessment tools are moderately accurate in identifying risk of osteoporosis and osteoporotic fractures. The USPSTF found convincing evidence that drug therapies reduce subsequent fracture rates in postmenopausal women. The USPSTF found that the evidence is inadequate to assess the effectiveness of drug therapies in reducing subsequent fracture rates in men without previous fractures. Conclusions and recommendation The USPSTF recommends screening for osteoporosis with bone measurement testing to prevent osteoporotic fractures in women 65 years and older. (B recommendation) The USPSTF recommends screening for osteoporosis with bone measurement testing to prevent osteoporotic fractures in postmenopausal women younger than 65 years at increased risk of osteoporosis, as determined by a formal clinical risk assessment tool. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis to prevent osteoporotic fractures in men. (I statement).