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Showing papers by "Tufts University published in 2019"


Journal ArticleDOI
TL;DR: Scientists working on the response of bacteria to antibiotics define antibiotic persistence and provide practical guidance on how to study bacterial persister cells, and provide a guide to measuring persistence.
Abstract: Increasing concerns about the rising rates of antibiotic therapy failure and advances in single-cell analyses have inspired a surge of research into antibiotic persistence. Bacterial persister cells represent a subpopulation of cells that can survive intensive antibiotic treatment without being resistant. Several approaches have emerged to define and measure persistence, and it is now time to agree on the basic definition of persistence and its relation to the other mechanisms by which bacteria survive exposure to bactericidal antibiotic treatments, such as antibiotic resistance, heteroresistance or tolerance. In this Consensus Statement, we provide definitions of persistence phenomena, distinguish between triggered and spontaneous persistence and provide a guide to measuring persistence. Antibiotic persistence is not only an interesting example of non-genetic single-cell heterogeneity, it may also have a role in the failure of antibiotic treatments. Therefore, it is our hope that the guidelines outlined in this article will pave the way for better characterization of antibiotic persistence and for understanding its relevance to clinical outcomes.

659 citations


Journal ArticleDOI
11 Jul 2019
TL;DR: Gestational diabetes mellitus is the most common complication in pregnancy and has short-term and long-term effects in both mother and offspring, and dietary modification and increased physical activity are the primary treatments, but pharmacotherapy, usually insulin, is used when normoglycaemia is not achieved.
Abstract: Hyperglycaemia that develops during pregnancy and resolves after birth has been recognized for over 50 years, but uniform worldwide consensus is lacking about threshold hyperglycaemic levels that merit a diagnosis of ‘gestational diabetes mellitus’ (GDM) and thus treatment during pregnancy. GDM is currently the most common medical complication of pregnancy, and prevalence of undiagnosed hyperglycaemia and even overt diabetes in young women is increasing. Maternal overweight and obesity, later age at childbearing, previous history of GDM, family history of type 2 diabetes mellitus and ethnicity are major GDM risk factors. Diagnosis is usually performed using an oral glucose tolerance test (OGTT), although a non-fasting, glucose challenge test (GCT) is used in some parts of the world to screen women for those requiring a full OGTT. Dietary modification and increased physical activity are the primary treatments for GDM, but pharmacotherapy, usually insulin, is used when normoglycaemia is not achieved. Oral hypoglycaemic agents, principally metformin and glibenclamide (glyburide), are also used in some countries. Treatment improves immediate pregnancy outcomes, reducing excess fetal growth and adiposity and pregnancy-related hypertensive disorders. GDM increases the risk of long-term complications, including obesity, impaired glucose metabolism and cardiovascular disease, in both the mother and infant. Optimal management of mother and infant during long-term follow-up remains challenging, with very limited implementation of preventive strategies in most parts of the world. Gestational diabetes mellitus (GDM) is the most common complication in pregnancy and has short-term and long-term effects in both mother and offspring. This Primer discusses the definitions of GDM, diagnosis and management of the disease and areas requiring further research.

643 citations


Journal ArticleDOI
TL;DR: The current treatment algorithm provides the most appropriate initial strategy, including monotherapy, or double or triple combination therapy, and further treatment escalation is required in case low-risk status is not achieved in planned follow-up assessments.
Abstract: Pulmonary arterial hypertension (PAH) remains a severe clinical condition despite the availability over the past 15 years of multiple drugs interfering with the endothelin, nitric oxide and prostacyclin pathways. The recent progress observed in medical therapy of PAH is not, therefore, related to the discovery of new pathways, but to the development of new strategies for combination therapy and on escalation of treatments based on systematic assessment of clinical response. The current treatment strategy is based on the severity of the newly diagnosed PAH patient as assessed by a multiparametric risk stratification approach. Clinical, exercise, right ventricular function and haemodynamic parameters are combined to define a low-, intermediate- or high-risk status according to the expected 1-year mortality. The current treatment algorithm provides the most appropriate initial strategy, including monotherapy, or double or triple combination therapy. Further treatment escalation is required in case low-risk status is not achieved in planned follow-up assessments. Lung transplantation may be required in most advanced cases on maximal medical therapy.

561 citations


Journal ArticleDOI
TL;DR: There is a need for continued ongoing and future basic and clinical studies to better define whether vitamin D status can be optimized to improve many aspects of human health, and what is plausible regarding the health effects of vitamin D.
Abstract: The etiology of endemic rickets was discovered a century ago. Vitamin D is the precursor of 25-hydroxyvitamin D and other metabolites, including 1,25(OH)2D, the ligand for the vitamin D receptor (VDR). The effects of the vitamin D endocrine system on bone and its growth plate are primarily indirect and mediated by its effect on intestinal calcium transport and serum calcium and phosphate homeostasis. Rickets and osteomalacia can be prevented by daily supplements of 400 IU of vitamin D. Vitamin D deficiency (serum 25-hydroxyvitamin D <50 nmol/L) accelerates bone turnover, bone loss, and osteoporotic fractures. These risks can be reduced by 800 IU of vitamin D together with an appropriate calcium intake, given to institutionalized or vitamin D-deficient elderly subjects. VDR and vitamin D metabolic enzymes are widely expressed. Numerous genetic, molecular, cellular, and animal studies strongly suggest that vitamin D signaling has many extraskeletal effects. These include regulation of cell proliferation, immune and muscle function, skin differentiation, and reproduction, as well as vascular and metabolic properties. From observational studies in human subjects, poor vitamin D status is associated with nearly all diseases predicted by these extraskeletal actions. Results of randomized controlled trials and Mendelian randomization studies are supportive of vitamin D supplementation in reducing the incidence of some diseases, but, globally, conclusions are mixed. These findings point to a need for continued ongoing and future basic and clinical studies to better define whether vitamin D status can be optimized to improve many aspects of human health. Vitamin D deficiency enhances the risk of osteoporotic fractures and is associated with many diseases. We review what is established and what is plausible regarding the health effects of vitamin D.

543 citations


Journal ArticleDOI
TL;DR: This conceptual model is intended to provide guidance to researchers and policy makers in identifying the current stage of the obesity transition in a population, anticipating subpopulations that will develop obesity in the future, and enacting proactive measures to attenuate the transition, taking into consideration local contextual factors.

533 citations


Journal ArticleDOI
Frank Koopmans1, Pim van Nierop1, Maria Andres-Alonso2, Andrea Byrnes3, Tony Cijsouw4, Marcelo P. Coba5, L. Niels Cornelisse1, Ryan J. Farrell6, Hana L. Goldschmidt7, Daniel P. Howrigan3, Natasha K. Hussain7, Natasha K. Hussain8, Cordelia Imig9, Arthur P.H. de Jong10, Hwajin Jung11, Mahdokht Kohansal-Nodehi9, Barbara Kramarz, Noa Lipstein9, Ruth C. Lovering, Harold D. MacGillavry12, Vittoria Mariano13, Vittoria Mariano14, Huaiyu Mi5, Momchil Ninov9, David Osumi-Sutherland15, Rainer Pielot2, Karl-Heinz Smalla2, Haiming Tang5, Katherine Tashman3, Ruud F. Toonen1, Chiara Verpelli16, Rita Reig-Viader17, Kyoko Watanabe1, Jan R.T. van Weering1, Tilmann Achsel13, Tilmann Achsel14, Ghazaleh Ashrafi6, Nimra Asi3, Tyler C. Brown3, Pietro De Camilli18, Marc Feuermann19, Rebecca E. Foulger, Pascale Gaudet19, Anoushka Joglekar6, Alexandros K. Kanellopoulos13, Alexandros K. Kanellopoulos14, Robert C. Malenka20, Roger A. Nicoll21, Camila Pulido6, Jaime de Juan-Sanz6, Morgan Sheng22, Thomas C. Südhof23, Hagen Tilgner6, Claudia Bagni14, Claudia Bagni13, Àlex Bayés17, Thomas Biederer4, Nils Brose9, John Jia En Chua24, Daniela C. Dieterich2, Eckart D. Gundelfinger2, Casper C. Hoogenraad12, Richard L. Huganir7, Richard L. Huganir8, Reinhard Jahn9, Pascal S. Kaeser10, Eunjoon Kim11, Michael R. Kreutz2, Peter S. McPherson25, Neale Bm3, Vincent O'Connor26, Danielle Posthuma1, Timothy A. Ryan6, Carlo Sala16, Guoping Feng3, Steven E. Hyman3, Paul Thomas5, August B. Smit1, Matthijs Verhage1 
17 Jul 2019-Neuron
TL;DR: It is shown that synaptic genes are exceptionally well conserved and less tolerant to mutations than other genes, and among de novo variants associated with neurodevelopmental disorders, including schizophrenia.

425 citations


Journal ArticleDOI
TL;DR: This review provides summaries of the key messages and food guides that are used to communicate national dietary guidance, organized by food group, and evaluates the extent to which each set of FBDG includes existing recommendations articulated by the WHO.

383 citations


Journal ArticleDOI
TL;DR: Among persons at high risk for type 2 diabetes not selected for vitamin D insufficiency, vitamin D3 supplementation at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo.
Abstract: Background Observational studies support an association between a low blood 25-hydroxyvitamin D level and the risk of type 2 diabetes. However, whether vitamin D supplementation lowers the...

378 citations


Journal ArticleDOI
TL;DR: How cells acquire plasticity and the role of plasticity in initiating cancer, cancer progression, and metastasis and in developing therapy resistance are discussed and potential therapeutic avenues are considered.

356 citations


Journal ArticleDOI
TL;DR: Surgical techniques, including tissue-engineered products, that are currently in clinical use, as well as a discussion of state-of-the-art tissue engineering strategies and technologies that are being developed for use in articular cartilage and meniscus repair and regeneration are provided.
Abstract: Injuries to articular cartilage and menisci can lead to cartilage degeneration that ultimately results in arthritis. Different forms of arthritis affect ~50 million people in the USA alone, and it is therefore crucial to identify methods that will halt or slow the progression to arthritis, starting with the initiating events of cartilage and meniscus defects. The surgical approaches in current use have a limited capacity for tissue regeneration and yield only short-term relief of symptoms. Tissue engineering approaches are emerging as alternatives to current surgical methods for cartilage and meniscus repair. Several cell-based and tissue-engineered products are currently in clinical trials for cartilage lesions and meniscal tears, opening new avenues for cartilage and meniscus regeneration. This Review provides a summary of surgical techniques, including tissue-engineered products, that are currently in clinical use, as well as a discussion of state-of-the-art tissue engineering strategies and technologies that are being developed for use in articular cartilage and meniscus repair and regeneration. The obstacles to clinical translation of these strategies are also included to inform the development of innovative tissue engineering approaches.

343 citations


Journal ArticleDOI
TL;DR: In this paper, the authors present guidelines for the diagnosis and treatment of myxomatous mitral valve disease (MMVD), also known as endocardiosis and degenerative or chronic valvular heart disease in dogs.
Abstract: This report, issued by the ACVIM Specialty of Cardiology consensus panel, revises guidelines for the diagnosis and treatment of myxomatous mitral valve disease (MMVD, also known as endocardiosis and degenerative or chronic valvular heart disease) in dogs, originally published in 2009. Updates were made to diagnostic, as well as medical, surgical, and dietary treatment recommendations. The strength of these recommendations was based on both the quantity and quality of available evidence supporting diagnostic and therapeutic decisions. Management of MMVD before the onset of clinical signs of heart failure has changed substantially compared with the 2009 guidelines, and new strategies to diagnose and treat advanced heart failure and pulmonary hypertension are reviewed.

Journal ArticleDOI
TL;DR: This review will examine the data representing the research on prominent intervention agents n-3 polyunsaturated fatty acids, micronutrients, and functional foods including probiotics and tea components for their immunological effects, working mechanisms, and clinical relevance.
Abstract: It is well-established that the nutritional deficiency or inadequacy can impair immune functions. Growing evidence suggests that for certain nutrients increased intake above currently recommended levels may help optimize immune functions including improving defense function and thus resistance to infection, while maintaining tolerance. This review will examine the data representing the research on prominent intervention agents n-3 polyunsaturated fatty acids (PUFA), micronutrients (zinc, vitamins D and E), and functional foods including probiotics and tea components for their immunological effects, working mechanisms, and clinical relevance. Many of these nutritive and non-nutritive food components are related in their functions to maintain or improve immune function including inhibition of pro-inflammatory mediators, promotion of anti-inflammatory functions, modulation of cell-mediated immunity, alteration of antigen-presenting cell functions, and communication between the innate and adaptive immune systems. Both animal and human studies present promising findings suggesting a clinical benefit of vitamin D, n-3 PUFA, and green tea catechin EGCG in autoimmune and inflammatory disorders, and vitamin D, vitamin E, zinc, and probiotics in reduction of infection. However, many studies report divergent and discrepant results/conclusions due to various factors. Chief among them, and thus call for attention, includes more standardized trial designs, better characterized populations, greater consideration for the intervention doses used, and more meaningful outcome measurements chosen.

Journal ArticleDOI
12 Feb 2019-JAMA
TL;DR: It is concluded with moderate certainty that providing or referring pregnant or postpartum women at increased risk to counseling interventions has a moderate net benefit in preventing perinatal depression.
Abstract: Importance Perinatal depression, which is the occurrence of a depressive disorder during pregnancy or following childbirth, affects as many as 1 in 7 women and is one of the most common complications of pregnancy and the postpartum period. It is well established that perinatal depression can result in adverse short- and long-term effects on both the woman and child. Objective To issue a new US Preventive Services Task Force (USPSTF) recommendation on interventions to prevent perinatal depression. Evidence Review The USPSTF reviewed the evidence on the benefits and harms of preventive interventions for perinatal depression in pregnant or postpartum women or their children. The USPSTF reviewed contextual information on the accuracy of tools used to identify women at increased risk of perinatal depression and the most effective timing for preventive interventions. Interventions reviewed included counseling, health system interventions, physical activity, education, supportive interventions, and other behavioral interventions, such as infant sleep training and expressive writing. Pharmacological approaches included the use of nortriptyline, sertraline, and omega-3 fatty acids. Findings The USPSTF found convincing evidence that counseling interventions, such as cognitive behavioral therapy and interpersonal therapy, are effective in preventing perinatal depression. Women with a history of depression, current depressive symptoms, or certain socioeconomic risk factors (eg, low income or young or single parenthood) would benefit from counseling interventions and could be considered at increased risk. The USPSTF found adequate evidence to bound the potential harms of counseling interventions as no greater than small, based on the nature of the intervention and the low likelihood of serious harms. The USPSTF found inadequate evidence to assess the benefits and harms of other noncounseling interventions. The USPSTF concludes with moderate certainty that providing or referring pregnant or postpartum women at increased risk to counseling interventions has a moderate net benefit in preventing perinatal depression. Conclusions and Recommendation The USPSTF recommends that clinicians provide or refer pregnant and postpartum persons who are at increased risk of perinatal depression to counseling interventions. (B recommendation)

Journal ArticleDOI
24 Sep 2019-JAMA
TL;DR: Serial cross-sectional analysis of the US nationally representative 24-hour dietary recall data from 9 National Health and Nutrition Examination Survey cycles (1999-2016) among adults aged 20 years or older found that from 1999 to 2016, US adults experienced a significant decrease in percentage of energy intake from low-quality carbohydrates and significant increases in percentage from high- quality carbohydrates, plant protein, and polyunsaturated fat.
Abstract: Importance Changes in the economy, nutrition policies, and food processing methods can affect dietary macronutrient intake and diet quality. It is essential to evaluate trends in dietary intake, food sources, and diet quality to inform policy makers. Objective To investigate trends in dietary macronutrient intake, food sources, and diet quality among US adults. Design, Setting, and Participants Serial cross-sectional analysis of the US nationally representative 24-hour dietary recall data from 9 National Health and Nutrition Examination Survey cycles (1999-2016) among adults aged 20 years or older. Exposure Survey cycle. Main Outcomes and Measures Dietary intake of macronutrients and their subtypes, food sources, and the Healthy Eating Index 2015 (range, 0-100; higher scores indicate better diet quality; a minimal clinically important difference has not been defined). Results There were 43 996 respondents (weighted mean age, 46.9 years; 51.9% women). From 1999 to 2016, the estimated energy from total carbohydrates declined from 52.5% to 50.5% (difference, −2.02%; 95% CI, −2.41% to −1.63%), whereas that of total protein and total fat increased from 15.5% to 16.4% (difference, 0.82%; 95% CI, 0.67%-0.97%) and from 32.0% to 33.2% (difference, 1.20%; 95% CI, 0.84%-1.55%), respectively (allP Conclusions and Relevance From 1999 to 2016, US adults experienced a significant decrease in percentage of energy intake from low-quality carbohydrates and significant increases in percentage of energy intake from high-quality carbohydrates, plant protein, and polyunsaturated fat. Despite improvements in macronutrient composition and diet quality, continued high intake of low-quality carbohydrates and saturated fat remained.

Journal ArticleDOI
TL;DR: A new class of Single-Atom Alloys (SAAs) that comprise catalytically active elements like Pt, Pd, and Ni alloyed in more inert host metals at the single-atom limit are described, which showed high selectivity, stability and resistance to poisoning in industrially relevant hydrogenation reactions.
Abstract: ConspectusHeterogeneous catalysts are workhorses in the industrial production of most commodity and specialty chemicals, and have widespread energy and environmental applications, with the annual market value of the catalysts themselves reaching almost $20 billion in 2018. These catalysts are complex, comprising multicomponent materials and multiple structures, making their rational design challenging, if not impossible. Furthermore, typical active metals like Pt, Pd, and Rh are expensive and can be susceptible to poisoning by CO, coking, and they are not always 100% selective. Efforts to use these elements sparingly and improve their selectivity has led to recent identification of single-atom heterogeneous catalysts in which individual transition metal atoms anchored on oxide or carbon-based supports are excellent catalysts for reactions like the CO oxidation, water–gas shift, alcohol dehydrogenation, and steam reforming.In this Account, we describe a new class of single-atom heterogeneous catalysts, nam...

Journal ArticleDOI
20 Aug 2019-JAMA
TL;DR: It is recommended that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have an ancestry associated with BRCA1/2 gene mutations with an appropriate brief familial risk assessment tool.
Abstract: Importance Potentially harmful mutations of the breast cancer susceptibility 1 and 2 genes (BRCA1/2) are associated with increased risk for breast, ovarian, fallopian tube, and peritoneal cancer. For women in the United States, breast cancer is the most common cancer after nonmelanoma skin cancer and the second leading cause of cancer death. In the general population,BRCA1/2mutations occur in an estimated 1 in 300 to 500 women and account for 5% to 10% of breast cancer cases and 15% of ovarian cancer cases. Objective To update the 2013 US Preventive Services Task Force (USPSTF) recommendation on risk assessment, genetic counseling, and genetic testing forBRCA-related cancer. Evidence Review The USPSTF reviewed the evidence on risk assessment, genetic counseling, and genetic testing for potentially harmfulBRCA1/2mutations in asymptomatic women who have never been diagnosed withBRCA-related cancer, as well as those with a previous diagnosis of breast, ovarian, tubal, or peritoneal cancer who have completed treatment and are considered cancer free. In addition, the USPSTF reviewed interventions to reduce the risk for breast, ovarian, tubal, or peritoneal cancer in women with potentially harmfulBRCA1/2mutations, including intensive cancer screening, medications, and risk-reducing surgery. Findings For women whose family or personal history is associated with an increased risk for harmful mutations in theBRCA1/2genes, or who have an ancestry associated withBRCA1/2gene mutations, there is adequate evidence that the benefits of risk assessment, genetic counseling, genetic testing, and interventions are moderate. For women whose personal or family history or ancestry is not associated with an increased risk for harmful mutations in theBRCA1/2genes, there is adequate evidence that the benefits of risk assessment, genetic counseling, genetic testing, and interventions are small to none. Regardless of family or personal history, the USPSTF found adequate evidence that the overall harms of risk assessment, genetic counseling, genetic testing, and interventions are small to moderate. Conclusions and Recommendation The USPSTF recommends that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have an ancestry associated withBRCA1/2gene mutations with an appropriate brief familial risk assessment tool. Women with a positive result on the risk assessment tool should receive genetic counseling and, if indicated after counseling, genetic testing. (B recommendation) The USPSTF recommends against routine risk assessment, genetic counseling, or genetic testing for women whose personal or family history or ancestry is not associated with potentially harmfulBRCA1/2gene mutations. (D recommendation)

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.

Journal ArticleDOI
TL;DR: An overview of different methods available and applicable in clinical settings and the use of grip strength to measure muscle strength and theUse of 4-m gait speed or the Short Physical Performance Battery test to measure physical performance in daily practice are proposed.
Abstract: It is well recognized that poor muscle function and poor physical performance are strong predictors of clinically relevant adverse events in older people. Given the large number of approaches to measure muscle function and physical performance, clinicians often struggle to choose a tool that is appropriate and validated for the population of older people they deal with. In this paper, an overview of different methods available and applicable in clinical settings is proposed. This paper is based on literature reviews performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group on frailty and sarcopenia. Face-to-face meetings were organized afterwards where the whole group could amend and discuss the recommendations further. Several characteristics should be considered when choosing a tool: (1) purpose of the assessment (intervention, screening, diagnosis); (2) patient characteristics (population, settings, functional ability, etc.); (3) psychometric properties of the tool (test–retest reliability, inter-rater reliability, responsiveness, floor and ceiling effects, etc.); (4) applicability of the tool in clinical settings (overall cost, time required for the examination, level of training, equipment, patient acceptance, etc.); (5) prognostic reliability for relevant clinical outcomes. Based on these criteria and the available evidence, the expert group advises the use of grip strength to measure muscle strength and the use of 4-m gait speed or the Short Physical Performance Battery test to measure physical performance in daily practice. The tools proposed are relevant for the assessment of muscle weakness and physical performance. Subjects with low values should receive additional diagnostic workups to achieve a full diagnosis of the underlying condition responsible (sarcopenia, frailty or other).

Journal ArticleDOI
TL;DR: In this paper, the authors reviewed observed and projected impacts on river flows along both the Mekong mainstream and its tributaries, including the effects of diversions and inter-basin transfers.

Journal ArticleDOI
Morad Aaboud, Georges Aad1, Brad Abbott2, Dale Charles Abbott3  +2936 moreInstitutions (198)
TL;DR: An exclusion limit on the H→invisible branching ratio of 0.26(0.17_{-0.05}^{+0.07}) at 95% confidence level is observed (expected) in combination with the results at sqrt[s]=7 and 8 TeV.
Abstract: Dark matter particles, if sufficiently light, may be produced in decays of the Higgs boson. This Letter presents a statistical combination of searches for H→invisible decays where H is produced according to the standard model via vector boson fusion, Z(ll)H, and W/Z(had)H, all performed with the ATLAS detector using 36.1 fb^{-1} of pp collisions at a center-of-mass energy of sqrt[s]=13 TeV at the LHC. In combination with the results at sqrt[s]=7 and 8 TeV, an exclusion limit on the H→invisible branching ratio of 0.26(0.17_{-0.05}^{+0.07}) at 95% confidence level is observed (expected).

Journal ArticleDOI
TL;DR: It is found that China is likely to peak its emissions well in advance of 2030 and achieve its non-fossil target conditional on full and effective implementation of all current policies, successful conclusion of power-sector reform, and full implementation of a national emissions-trading system after 2020.
Abstract: China committed to peak its carbon emissions around 2030, with best efforts to peak early, and also to achieve 20% non-fossil energy as a proportion of primary energy supply by 2030. These commitments were included in China’s nationally-determined contribution to the 2015 Paris Agreement on climate change. We develop and apply a mixed-method methodology for analyzing the likelihood of current Chinese policies reducing greenhouse gas emissions in accordance with China’s Paris commitments. We find that China is likely to peak its emissions well in advance of 2030 and achieve its non-fossil target conditional on full and effective implementation of all current policies, successful conclusion of power-sector reform, and full implementation of a national emissions-trading system (ETS) for the power and additional major industrial sectors after 2020. Several policy gaps are identified and discussed. The extent to which China’s existing and forthcoming policies would lead to emission reductions domestically has not been well understood. Here the authors combined expert elicitation and a system dynamic model and showed that China is on track to peak its emissions well in advance of 2030.

Journal ArticleDOI
Georges Aad1, Alexander Kupco2, Samuel Webb3, Timo Dreyer4  +2962 moreInstitutions (195)
TL;DR: In this article, an improved energy clustering algorithm is introduced, and its implications for the measurement and identification of prompt electrons and photons are discussed in detail, including corrections and calibrations that affect performance, including energy calibration, identification and isolation efficiencies.
Abstract: This paper describes the reconstruction of electrons and photons with the ATLAS detector, employed for measurements and searches exploiting the complete LHC Run 2 dataset. An improved energy clustering algorithm is introduced, and its implications for the measurement and identification of prompt electrons and photons are discussed in detail. Corrections and calibrations that affect performance, including energy calibration, identification and isolation efficiencies, and the measurement of the charge of reconstructed electron candidates are determined using up to 81 fb−1 of proton-proton collision data collected at √s=13 TeV between 2015 and 2017.

Journal ArticleDOI
11 Jun 2019-JAMA
TL;DR: The USPSTF concludes with high certainty that the magnitude of benefit of PrEP with oral tenofovir disoproxil fumarate-based therapy to reduce the risk of acquisition of HIV infection in persons at high risk is substantial.
Abstract: Importance An estimated 1.1 million individuals in the United States are currently living with HIV, and more than 700 000 persons have died of AIDS since the first cases were reported in 1981. In 2017, there were 38 281 new diagnoses of HIV infection reported in the United States; 81% of these new diagnoses were among males and 19% were among females. Although treatable, HIV infection has no cure and has significant health consequences. Objective To issue a new US Preventive Services Task Force (USPSTF) recommendation on preexposure prophylaxis (PrEP) for the prevention of HIV infection. Evidence Review The USPSTF reviewed the evidence on the benefits of PrEP for the prevention of HIV infection with oral tenofovir disoproxil fumarate monotherapy or combined tenofovir disoproxil fumarate and emtricitabine and whether the benefits vary by risk group, population subgroup, or regimen or dosing strategy; the diagnostic accuracy of risk assessment tools to identify persons at high risk of HIV acquisition; the rates of adherence to PrEP in primary care settings; the association between adherence and effectiveness of PrEP; and the harms of PrEP when used for HIV prevention. Findings The USPSTF found convincing evidence that PrEP is of substantial benefit in decreasing the risk of HIV infection in persons at high risk of HIV acquisition. The USPSTF also found convincing evidence that adherence to PrEP is highly associated with its efficacy in preventing the acquisition of HIV infection; thus, adherence to PrEP is central to realizing its benefit. The USPSTF found adequate evidence that PrEP is associated with small harms, including kidney and gastrointestinal adverse effects. The USPSTF concludes with high certainty that the magnitude of benefit of PrEP with oral tenofovir disoproxil fumarate–based therapy to reduce the risk of acquisition of HIV infection in persons at high risk is substantial. Conclusions and Recommendation The USPSTF recommends offering PrEP with effective antiretroviral therapy to persons at high risk of HIV acquisition. (A recommendation)


Journal ArticleDOI
TL;DR: Why RIPK1 inhibitors present an opportunity for developing oral drugs for a range of human degenerative and inflammatory diseases, especially CNS pathologies, including ALS, Alzheimer's disease, Parkinson’s disease, traumatic brain injury, stroke, and lysosomal storage diseases is discussed.
Abstract: RIPK1 kinase has emerged as a promising therapeutic target for the treatment of a wide range of human neurodegenerative, autoimmune, and inflammatory diseases. This was supported by extensive studies which demonstrated that RIPK1 is a key mediator of apoptotic and necrotic cell death as well as inflammatory pathways. Furthermore, human genetic evidence has linked the dysregulation of RIPK1 to the pathogenesis of ALS as well as other inflammatory and neurodegenerative diseases. Importantly, unique allosteric small-molecule inhibitors of RIPK1 that offer high selectivity have been developed. These molecules can penetrate the blood–brain barrier, thus offering the possibility to target neuroinflammation and cell death which drive various neurologic conditions including Alzheimer’s disease, ALS, and multiple sclerosis as well as acute neurological diseases such as stroke and traumatic brain injuries. We discuss the current understanding of RIPK1 regulatory mechanisms and emerging evidence for the pathological roles of RIPK1 in human diseases, especially in the context of the central nervous systems.

Journal ArticleDOI
Georges Aad1, Alexander Kupco2, Samuel Webb3, Timo Dreyer4  +2961 moreInstitutions (196)
TL;DR: In this article, the ATLAS Collaboration during Run 2 of the Large Hadron Collider (LHC) was used to identify jets containing b-hadrons, and the performance of the algorithms was evaluated in the s...
Abstract: The algorithms used by the ATLAS Collaboration during Run 2 of the Large Hadron Collider to identify jets containing b-hadrons are presented. The performance of the algorithms is evaluated in the s ...

Journal ArticleDOI
06 Aug 2019-JAMA
TL;DR: The USPSTF reaffirms its previous conclusion that the potential benefits of screening for pancreatic cancer in asymptomatic adults do not outweigh the potential harms.
Abstract: Importance Pancreatic cancer is an uncommon cancer with an age-adjusted annual incidence of 12.9 cases per 100 000 person-years. However, the death rate is 11.0 deaths per 100 000 person-years because the prognosis of pancreatic cancer is poor. Although its incidence is low, pancreatic cancer is the third most common cause of cancer death in the United States. Because of the increasing incidence of pancreatic cancer, along with improvements in early detection and treatment of other types of cancer, it is estimated that pancreatic cancer may soon become the second-leading cause of cancer death in the United States. Objective To update the 2004 US Preventive Services Task Force (USPSTF) recommendation on screening for pancreatic cancer. Evidence Review The USPSTF reviewed the evidence on the benefits and harms of screening for pancreatic cancer, the diagnostic accuracy of screening tests for pancreatic cancer, and the benefits and harms of treatment of screen-detected or asymptomatic pancreatic cancer. Findings The USPSTF found no evidence that screening for pancreatic cancer or treatment of screen-detected pancreatic cancer improves disease-specific morbidity or mortality, or all-cause mortality. The USPSTF found adequate evidence that the magnitude of the benefits of screening for pancreatic cancer in asymptomatic adults can be bounded as no greater than small. The USPSTF found adequate evidence that the magnitude of the harms of screening for pancreatic cancer and treatment of screen-detected pancreatic cancer can be bounded as at least moderate. The USPSTF reaffirms its previous conclusion that the potential benefits of screening for pancreatic cancer in asymptomatic adults do not outweigh the potential harms. Conclusions and Recommendation The USPSTF recommends against screening for pancreatic cancer in asymptomatic adults. (D recommendation)

Journal ArticleDOI
TL;DR: In this article, the influence of FEC on LiPF6/ethylene carbonate (EC) electrolytes for Si anodes is investigated through classical molecular dynamics, Fourier transform infrared spectroscopy, and quantum chemical calculations.

Journal ArticleDOI
21 Feb 2019
TL;DR: In this article, a review of existing early clinical manifestations of Alzheimer's disease and a path to the respective sensor and mobile/wearable device usage to acquire domain-centric data towards objective, high frequency and passive digital phenotyping is presented.
Abstract: Alzheimer’s Disease (AD) represents a major and rapidly growing burden to the healthcare ecosystem. A growing body of evidence indicates that cognitive, behavioral, sensory, and motor changes may precede clinical manifestations of AD by several years. Existing tests designed to diagnose neurodegenerative diseases, while well-validated, are often less effective in detecting deviations from normal cognitive decline trajectory in the earliest stages of the disease. In the quest for gold standards for AD assessment, there is a growing interest in the identification of readily accessible digital biomarkers, which harness advances in consumer grade mobile and wearable technologies. Topics examined include a review of existing early clinical manifestations of AD and a path to the respective sensor and mobile/wearable device usage to acquire domain-centric data towards objective, high frequency and passive digital phenotyping.

Journal ArticleDOI
TL;DR: The authors demonstrate that the solution for CO oxidation is to tackle the issue of lacking neighboring Pt atoms in the single-atom Pt1/CeO2 system, which is well-represented by a Pt8O14 model cluster that retains 100% metal dispersion.
Abstract: Despite the maximized metal dispersion offered by single-atom catalysts, further improvement of intrinsic activity can be hindered by the lack of neighboring metal atoms in these systems. Here we report the use of isolated Pt1 atoms on ceria as "seeds" to develop a Pt-O-Pt ensemble, which is well-represented by a Pt8O14 model cluster that retains 100% metal dispersion. The Pt atom in the ensemble is 100-1000 times more active than their single-atom Pt1/CeO2 parent in catalyzing the low-temperature CO oxidation under oxygen-rich conditions. Rather than the Pt-O-Ce interfacial catalysis, the stable catalytic unit is the Pt-O-Pt site itself without participation of oxygen from the 10-30 nm-size ceria support. Similar Pt-O-Pt sites can be built on various ceria and even alumina, distinguishable by facile activation of oxygen through the paired Pt-O-Pt atoms. Extending this design to other reaction systems is a likely outcome of the findings reported here.