Showing papers by "University of Gothenburg published in 2020"
TL;DR: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates, and there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries.
5,802 citations
Christopher J L Murray1, Christopher J L Murray2, Christopher J L Murray3, Aleksandr Y. Aravkin1 +2269 more•Institutions (286)
TL;DR: The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure.
3,059 citations
TL;DR: The extent of the trait data compiled in TRY is evaluated and emerging patterns of data coverage and representativeness are analyzed to conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements.
Abstract: Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
882 citations
TL;DR: Plasma P-tau18 level increased with progression of Alzheimer’s disease (AD) and differentiated AD dementia from other neurodegenerative diseases, supporting its further development as a blood-based biomarker for AD.
Abstract: Plasma phosphorylated tau181 (P-tau181) might be increased in Alzheimer’s disease (AD), but its usefulness for differential diagnosis and prognosis is unclear. We studied plasma P-tau181 in three cohorts, with a total of 589 individuals, including cognitively unimpaired participants and patients with mild cognitive impairment (MCI), AD dementia and non-AD neurodegenerative diseases. Plasma P-tau181 was increased in preclinical AD and further increased at the MCI and dementia stages. It correlated with CSF P-tau181 and predicted positive Tau positron emission tomography (PET) scans (area under the curve (AUC) = 0.87–0.91 for different brain regions). Plasma P-tau181 differentiated AD dementia from non-AD neurodegenerative diseases with an accuracy similar to that of Tau PET and CSF P-tau181 (AUC = 0.94–0.98), and detected AD neuropathology in an autopsy-confirmed cohort. High plasma P-tau181 was associated with subsequent development of AD dementia in cognitively unimpaired and MCI subjects. In conclusion, plasma P-tau181 is a noninvasive diagnostic and prognostic biomarker of AD, which may be useful in clinical practice and trials. Plasma P-tau18 level increased with progression of Alzheimer’s disease (AD) and differentiated AD dementia from other neurodegenerative diseases, supporting its further development as a blood-based biomarker for AD.
565 citations
TL;DR: Blood p-tau181 can predict tau and amyloid β pathologies, differentiate Alzheimer's disease from other neurodegenerative disorders, and identify Alzheimer's Disease across the clinical continuum.
Abstract: Summary Background CSF and PET biomarkers of amyloid β and tau accurately detect Alzheimer's disease pathology, but the invasiveness, high cost, and poor availability of these detection methods restrict their widespread use as clinical diagnostic tools. CSF tau phosphorylated at threonine 181 (p-tau181) is a highly specific biomarker for Alzheimer's disease pathology. We aimed to assess whether blood p-tau181 could be used as a biomarker for Alzheimer's disease and for prediction of cognitive decline and hippocampal atrophy. Methods We developed and validated an ultrasensitive blood immunoassay for p-tau181. Assay performance was evaluated in four clinic-based prospective cohorts. The discovery cohort comprised patients with Alzheimer's disease and age-matched controls. Two validation cohorts (TRIAD and BioFINDER-2) included cognitively unimpaired older adults (mean age 63–69 years), participants with mild cognitive impairment (MCI), Alzheimer's disease, and frontotemporal dementia. In addition, TRIAD included healthy young adults (mean age 23 years) and BioFINDER-2 included patients with other neurodegenerative disorders. The primary care cohort, which recruited participants in Montreal, Canada, comprised control participants from the community without a diagnosis of a neurological condition and patients referred from primary care physicians of the Canadian National Health Service for specialist care. Concentrations of plasma p-tau181 were compared with established CSF and PET biomarkers and longitudinal measurements using Spearman correlation, area under the curve (AUC), and linear regression analyses. Findings We studied 37 individuals in the discovery cohort, 226 in the first validation cohort (TRIAD), 763 in the second validation cohort (BioFINDER-2), and 105 in the primary care cohort (n=1131 individuals). In all cohorts, plasma p-tau181 showed gradual increases along the Alzheimer's disease continuum, from the lowest concentrations in amyloid β-negative young adults and cognitively unimpaired older adults, through higher concentrations in the amyloid β-positive cognitively unimpaired older adults and MCI groups, to the highest concentrations in the amyloid β-positive MCI and Alzheimer's disease groups (p Interpretation Blood p-tau181 can predict tau and amyloid β pathologies, differentiate Alzheimer's disease from other neurodegenerative disorders, and identify Alzheimer's disease across the clinical continuum. Blood p-tau181 could be used as a simple, accessible, and scalable test for screening and diagnosis of Alzheimer's disease. Funding Alzheimer Drug Discovery Foundation, European Research Council, Swedish Research Council, Swedish Alzheimer Foundation, Swedish Dementia Foundation, Alzheimer Society Research Program.
563 citations
TL;DR: Plasma P-tau217 levels were significantly greater among PSEN1 mutation carriers, compared with noncarriers, from approximately 25 years and older, which is 20 years prior to estimated onset of MCI among mutation carriers.
Abstract: Importance There are limitations in current diagnostic testing approaches for Alzheimer disease (AD). Objective To examine plasma tau phosphorylated at threonine 217 (P-tau217) as a diagnostic biomarker for AD. Design, Setting, and Participants Three cross-sectional cohorts: an Arizona-based neuropathology cohort (cohort 1), including 34 participants with AD and 47 without AD (dates of enrollment, May 2007-January 2019); the Swedish BioFINDER-2 cohort (cohort 2), including cognitively unimpaired participants (n = 301) and clinically diagnosed patients with mild cognitive impairment (MCI) (n = 178), AD dementia (n = 121), and other neurodegenerative diseases (n = 99) (April 2017-September 2019); and a Colombian autosomal-dominant AD kindred (cohort 3), including 365PSEN1E280A mutation carriers and 257 mutation noncarriers (December 2013-February 2017). Exposures Plasma P-tau217. Main Outcomes and Measures Primary outcome was the discriminative accuracy of plasma P-tau217 for AD (clinical or neuropathological diagnosis). Secondary outcome was the association with tau pathology (determined using neuropathology or positron emission tomography [PET]). Results Mean age was 83.5 (SD, 8.5) years in cohort 1, 69.1 (SD, 10.3) years in cohort 2, and 35.8 (SD, 10.7) years in cohort 3; 38% were women in cohort 1, 51% in cohort 2, and 57% in cohort 3. In cohort 1, antemortem plasma P-tau217 differentiated neuropathologically defined AD from non-AD (area under the curve [AUC], 0.89 [95% CI, 0.81-0.97]) with significantly higher accuracy than plasma P-tau181 and neurofilament light chain (NfL) (AUC range, 0.50-0.72;P .15). In cohort 3, plasma P-tau217 levels were significantly greater amongPSEN1mutation carriers, compared with noncarriers, from approximately 25 years and older, which is 20 years prior to estimated onset of MCI among mutation carriers. Plasma P-tau217 levels correlated with tau tangles in participants with (Spearman ρ = 0.64;P Conclusions and Relevance Among 1402 participants from 3 selected cohorts, plasma P-tau217 discriminated AD from other neurodegenerative diseases, with significantly higher accuracy than established plasma- and MRI-based biomarkers, and its performance was not significantly different from key CSF- or PET-based measures. Further research is needed to optimize the assay, validate the findings in unselected and diverse populations, and determine its potential role in clinical care.
548 citations
TL;DR: This S3 guideline informs clinical practice, health systems, policymakers and, indirectly, the public on the available and most effective modalities to treat periodontitis and to maintain a healthy dentition for a lifetime, according to the available evidence at the time of publication.
Abstract: BACKGROUND
The recently introduced 2017 World Workshop on the classification of periodontitis, incorporating stages and grades of disease, aims to link disease classification with approaches to prevention and treatment, as it describes not only disease severity and extent but also the degree of complexity and an individual's risk. There is, therefore, a need for evidence-based clinical guidelines providing recommendations to treat periodontitis.
AIM
The objective of the current project was to develop a S3 Level Clinical Practice Guideline (CPG) for the treatment of Stage I-III periodontitis.
MATERIAL AND METHODS
This S3 CPG was developed under the auspices of the European Federation of Periodontology (EFP), following the methodological guidance of the Association of Scientific Medical Societies in Germany and the Grading of Recommendations Assessment, Development and Evaluation (GRADE). The rigorous and transparent process included synthesis of relevant research in 15 specifically commissioned systematic reviews, evaluation of the quality and strength of evidence, the formulation of specific recommendations and consensus, on those recommendations, by leading experts and a broad base of stakeholders.
RESULTS
The S3 CPG approaches the treatment of periodontitis (stages I, II and III) using a pre-established stepwise approach to therapy that, depending on the disease stage, should be incremental, each including different interventions. Consensus was achieved on recommendations covering different interventions, aimed at (a) behavioural changes, supragingival biofilm, gingival inflammation and risk factor control; (b) supra- and sub-gingival instrumentation, with and without adjunctive therapies; (c) different types of periodontal surgical interventions; and (d) the necessary supportive periodontal care to extend benefits over time.
CONCLUSION
This S3 guideline informs clinical practice, health systems, policymakers and, indirectly, the public on the available and most effective modalities to treat periodontitis and to maintain a healthy dentition for a lifetime, according to the available evidence at the time of publication.
454 citations
TL;DR: Management of gout continues to be poor, with fewer than one half of patients receiving definitive ‘curative’ urate-lowering therapy, and rates of non-persistence are high.
Abstract: Gout is the most common inflammatory arthritis and occurs when hyperuricaemia, sustained elevation of serum urate levels resulting in supersaturation of body tissues with urate, leads to the formation and deposition of monosodium urate crystals in and around the joints. Recent reports of the prevalence and incidence of gout vary widely according to the population studied and methods employed but range from a prevalence of <1% to 6.8% and an incidence of 0.58–2.89 per 1,000 person-years. Gout is more prevalent in men than in women, with increasing age, and in some ethnic groups. Despite rising prevalence and incidence, suboptimal management of gout continues in many countries. Typically, only a third to half of patients with gout receive urate-lowering therapy, which is a definitive, curative treatment, and fewer than a half of patients adhere to treatment. Many gout risk factors exist, including obesity, dietary factors and comorbid conditions. As well as a firmly established increased risk of cardiovascular disease and chronic kidney disease in those with gout, novel associations of gout with other comorbidities have been reported, including erectile dysfunction, atrial fibrillation, obstructive sleep apnoea, osteoporosis and venous thromboembolism. Discrete patterns of comorbidity clustering in individuals with gout have been described. Increasing prevalence and incidence of obesity and comorbidities are likely to contribute substantially to the rising burden of gout. Gout is a chronic crystal deposition disorder in which sustained hyperuricaemia leads to formation and deposition of monosodium urate crystals in the joints. The prevalence and incidence of gout are increasing globally, which may be related to changes in the prevalence of gout risk factors (such as obesity) and comorbidities.
427 citations
TL;DR: Plasma pTau181 concentrations are elevated specifically in patients diagnosed with Alzheimer’s disease compared to those diagnosed with frontotemporal lobar degeneration or elderly controls, supporting its further development as a blood-based biomarker for AD.
Abstract: With the potential development of new disease-modifying Alzheimer's disease (AD) therapies, simple, widely available screening tests are needed to identify which individuals, who are experiencing symptoms of cognitive or behavioral decline, should be further evaluated for initiation of treatment. A blood-based test for AD would be a less invasive and less expensive screening tool than the currently approved cerebrospinal fluid or amyloid β positron emission tomography (PET) diagnostic tests. We examined whether plasma tau phosphorylated at residue 181 (pTau181) could differentiate between clinically diagnosed or autopsy-confirmed AD and frontotemporal lobar degeneration. Plasma pTau181 concentrations were increased by 3.5-fold in AD compared to controls and differentiated AD from both clinically diagnosed (receiver operating characteristic area under the curve of 0.894) and autopsy-confirmed frontotemporal lobar degeneration (area under the curve of 0.878). Plasma pTau181 identified individuals who were amyloid β-PET-positive regardless of clinical diagnosis and correlated with cortical tau protein deposition measured by 18F-flortaucipir PET. Plasma pTau181 may be useful to screen for tau pathology associated with AD.
425 citations
Massachusetts Institute of Technology1, University of Alaska Fairbanks2, Woods Hole Oceanographic Institution3, University of Bremen4, Alfred Wegener Institute for Polar and Marine Research5, California Institute of Technology6, National Oceanic and Atmospheric Administration7, Texas State University8, Lund University9, Pennsylvania State University10, Potsdam Institute for Climate Impact Research11, VU University Amsterdam12, Utah State University13, United States Naval Academy14, Environment Canada15, University of Gothenburg16, University of Cambridge17, Naval Postgraduate School18, University of California, Irvine19, University of Washington20, University College London21, Langley Research Center22, University of Wisconsin-Madison23, Finnish Meteorological Institute24, Leipzig University25, Columbia University26, Gwangju Institute of Science and Technology27
TL;DR: The Arctic has warmed more than twice as fast as the global average since the late twentieth century, a phenomenon known as Arctic amplification (AA), and progress has been made in understanding the mechanisms that link it to midlatitude weather variability as discussed by the authors.
Abstract: The Arctic has warmed more than twice as fast as the global average since the late twentieth century, a phenomenon known as Arctic amplification (AA). Recently, there have been considerable advances in understanding the physical contributions to AA, and progress has been made in understanding the mechanisms that link it to midlatitude weather variability. Observational studies overwhelmingly support that AA is contributing to winter continental cooling. Although some model experiments support the observational evidence, most modelling results show little connection between AA and severe midlatitude weather or suggest the export of excess heating from the Arctic to lower latitudes. Divergent conclusions between model and observational studies, and even intramodel studies, continue to obfuscate a clear understanding of how AA is influencing midlatitude weather.
423 citations
University of Grenoble1, Katholieke Universiteit Leuven2, ETH Zurich3, Infineon Technologies4, University of Münster5, Royal Institute of Technology6, University of Gothenburg7, Helmholtz-Zentrum Dresden-Rossendorf8, Kaiserslautern University of Technology9, Université Paris-Saclay10, University of Vienna11, University of York12, University of Lorraine13, Catalan Institution for Research and Advanced Studies14, Spanish National Research Council15, Koç University16, University of Naples Federico II17, University of Messina18, University of Salamanca19
TL;DR: In this article, the potential of spintronics in four key areas of application (memory, sensors, microwave devices, and logic devices) is examined and the challenges that need to be addressed in order to integrate spintronic materials and functionalities into mainstream microelectronic platforms.
Abstract: Spintronic devices exploit the spin, as well as the charge, of electrons and could bring new capabilities to the microelectronics industry However, in order for spintronic devices to meet the ever-increasing demands of the industry, innovation in terms of materials, processes and circuits are required Here, we review recent developments in spintronics that could soon have an impact on the microelectronics and information technology industry We highlight and explore four key areas: magnetic memories, magnetic sensors, radio-frequency and microwave devices, and logic and non-Boolean devices We also discuss the challenges—at both the device and the system level—that need be addressed in order to integrate spintronic materials and functionalities into mainstream microelectronic platforms This Review Article examines the potential of spintronics in four key areas of application —memories, sensors, microwave devices, and logic devices — and discusses the challenges that need be addressed in order to integrate spintronic materials and functionalities into mainstream microelectronic platforms
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Federal University of Paraíba1, University of North Carolina at Chapel Hill2, University of Bonn3, Merck & Co.4, University of New Mexico5, University of Gothenburg6, University of Copenhagen7, Moscow State University8, University of Strasbourg9, University of Florida10, Duke University11, North Carolina State University12, University of California, Los Angeles13, University of Toronto14, Novartis15, University of British Columbia16
TL;DR: This Perspective summarizes recent technological advances in QSAR modeling but it also highlights the applicability of algorithms, modeling methods, and validation practices developed inQSAR to a wide range of research areas outside of traditional QSar boundaries including synthesis planning, nanotechnology, materials science, biomaterials, and clinical informatics.
Abstract: Prediction of chemical bioactivity and physical properties has been one of the most important applications of statistical and more recently, machine learning and artificial intelligence methods in chemical sciences. This field of research, broadly known as quantitative structure–activity relationships (QSAR) modeling, has developed many important algorithms and has found a broad range of applications in physical organic and medicinal chemistry in the past 55+ years. This Perspective summarizes recent technological advances in QSAR modeling but it also highlights the applicability of algorithms, modeling methods, and validation practices developed in QSAR to a wide range of research areas outside of traditional QSAR boundaries including synthesis planning, nanotechnology, materials science, biomaterials, and clinical informatics. As modern research methods generate rapidly increasing amounts of data, the knowledge of robust data-driven modelling methods professed within the QSAR field can become essential for scientists working both within and outside of chemical research. We hope that this contribution highlighting the generalizable components of QSAR modeling will serve to address this challenge.
TL;DR: Identification in Rwanda of mutations in Plasmodium falciparum capable of conferring in vitro resistance to artemisinin, an essential medicine for the treatment of malaria, underscore the crucial need for surveillance in Africa to safeguard efficacy of life-saving therapies.
Abstract: Artemisinin resistance (delayed P. falciparum clearance following artemisinin-based combination therapy), is widespread across Southeast Asia but to date has not been reported in Africa1–4. Here we genotyped the P. falciparum K13 (Pfkelch13) propeller domain, mutations in which can mediate artemisinin resistance5,6, in pretreatment samples collected from recent dihydroarteminisin-piperaquine and artemether-lumefantrine efficacy trials in Rwanda7. While cure rates were >95% in both treatment arms, the Pfkelch13 R561H mutation was identified in 19 of 257 (7.4%) patients at Masaka. Phylogenetic analysis revealed the expansion of an indigenous R561H lineage. Gene editing confirmed that this mutation can drive artemisinin resistance in vitro. This study provides evidence for the de novo emergence of Pfkelch13-mediated artemisinin resistance in Rwanda, potentially compromising the continued success of antimalarial chemotherapy in Africa. Identification in Rwanda of mutations in Plasmodium falciparum capable of conferring in vitro resistance to artemisinin, an essential medicine for the treatment of malaria, underscore the crucial need for surveillance in Africa to safeguard efficacy of life-saving therapies.
Medical University of Vienna1, Aristotle University of Thessaloniki2, IBM3, Memorial Sloan Kettering Cancer Center4, University of Queensland5, University of Modena and Reggio Emilia6, Carlos III Health Institute7, University of Barcelona8, University of Gothenburg9, Sahlgrenska University Hospital10, University of Trieste11
TL;DR: A systematic evaluation of the value of AI-based decision support in skin tumor diagnosis demonstrates the superiority of human–computer collaboration over each individual approach and supports the potential of automated approaches in diagnostic medicine.
Abstract: The rapid increase in telemedicine coupled with recent advances in diagnostic artificial intelligence (AI) create the imperative to consider the opportunities and risks of inserting AI-based support into new paradigms of care Here we build on recent achievements in the accuracy of image-based AI for skin cancer diagnosis to address the effects of varied representations of AI-based support across different levels of clinical expertise and multiple clinical workflows We find that good quality AI-based support of clinical decision-making improves diagnostic accuracy over that of either AI or physicians alone, and that the least experienced clinicians gain the most from AI-based support We further find that AI-based multiclass probabilities outperformed content-based image retrieval (CBIR) representations of AI in the mobile technology environment, and AI-based support had utility in simulations of second opinions and of telemedicine triage In addition to demonstrating the potential benefits associated with good quality AI in the hands of non-expert clinicians, we find that faulty AI can mislead the entire spectrum of clinicians, including experts Lastly, we show that insights derived from AI class-activation maps can inform improvements in human diagnosis Together, our approach and findings offer a framework for future studies across the spectrum of image-based diagnostics to improve human-computer collaboration in clinical practice
TL;DR: Patients with MS are at a generally increased risk of infections, and this differs by treatment; among newer treatments, off-label use of rituximab was associated with the highest rate of serious infections.
Abstract: Importance: Although highly effective disease-modifying therapies for multiple sclerosis (MS) have been associated with an increased risk of infections vs injectable therapies interferon beta and g ...
King's College London1, Chalmers University of Technology2, Karolinska Institutet3, Stockholm University4, Macquarie University5, University of Newcastle6, University of Gothenburg7, Dalian Institute of Chemical Physics8, KAIST9, Institut national de la recherche agronomique10, Science for Life Laboratory11, Royal Institute of Technology12
TL;DR: This work used shotgun metagenomics of mucosal biopsies to explore the microbial communities’ compositions of terminal ileum and large intestine in 5 healthy individuals, and details which species are involved with the tryptophan/indole pathway and the antimicrobial resistance biogeography along the intestine.
Abstract: Gut mucosal microbes evolved closest to the host, developing specialized local communities. There is, however, insufficient knowledge of these communities as most studies have employed sequencing technologies to investigate faecal microbiota only. This work used shotgun metagenomics of mucosal biopsies to explore the microbial communities' compositions of terminal ileum and large intestine in 5 healthy individuals. Functional annotations and genome-scale metabolic modelling of selected species were then employed to identify local functional enrichments. While faecal metagenomics provided a good approximation of the average gut mucosal microbiome composition, mucosal biopsies allowed detecting the subtle variations of local microbial communities. Given their significant enrichment in the mucosal microbiota, we highlight the roles of Bacteroides species and describe the antimicrobial resistance biogeography along the intestine. We also detail which species, at which locations, are involved with the tryptophan/indole pathway, whose malfunctioning has been linked to pathologies including inflammatory bowel disease. Our study thus provides invaluable resources for investigating mechanisms connecting gut microbiota and host pathophysiology.
TL;DR: It is found that associations between education and aging-associated cognitive declines are negligible and that a threshold model of dementia can account for the association between educational attainment and late-life dementia risk.
Abstract: Cognitive abilities are important predictors of educational and occupational performance, socioeconomic attainment, health, and longevity. Declines in cognitive abilities are linked to impairments in older adults' everyday functions, but people differ from one another in their rates of cognitive decline over the course of adulthood and old age. Hence, identifying factors that protect against compromised late-life cognition is of great societal interest. The number of years of formal education completed by individuals is positively correlated with their cognitive function throughout adulthood and predicts lower risk of dementia late in life. These observations have led to the propositions that prolonging education might (a) affect cognitive ability and (b) attenuate aging-associated declines in cognition. We evaluate these propositions by reviewing the literature on educational attainment and cognitive aging, including recent analyses of data harmonized across multiple longitudinal cohort studies and related meta-analyses. In line with the first proposition, the evidence indicates that educational attainment has positive effects on cognitive function. We also find evidence that cognitive abilities are associated with selection into longer durations of education and that there are common factors (e.g., parental socioeconomic resources) that affect both educational attainment and cognitive development. There is likely reciprocal interplay among these factors, and among cognitive abilities, during development. Education-cognitive ability associations are apparent across the entire adult life span and across the full range of education levels, including (to some degree) tertiary education. However, contrary to the second proposition, we find that associations between education and aging-associated cognitive declines are negligible and that a threshold model of dementia can account for the association between educational attainment and late-life dementia risk. We conclude that educational attainment exerts its influences on late-life cognitive function primarily by contributing to individual differences in cognitive skills that emerge in early adulthood but persist into older age. We also note that the widespread absence of educational influences on rates of cognitive decline puts constraints on theoretical notions of cognitive aging, such as the concepts of cognitive reserve and brain maintenance. Improving the conditions that shape development during the first decades of life carries great potential for improving cognitive ability in early adulthood and for reducing public-health burdens related to cognitive aging and dementia.
Brigham and Women's Hospital1, Baylor University Medical Center2, Imperial College London3, United States Department of Veterans Affairs4, Medical University of South Carolina5, University of Gothenburg6, Montreal Heart Institute7, Karolinska University Hospital8, Copenhagen University Hospital9, University of Minnesota10, University of Arizona11, Semmelweis University12, Carol Davila University of Medicine and Pharmacy13, National Yang-Ming University14, Novartis15, British Heart Foundation16
TL;DR: The therapeutic effects of sacubitril/valsartan, compared with a renin-angiotensin-aldosterone–system inhibitor alone, vary by LVEF with treatment benefits, particularly for heart failure hospitalization, that appear to extend to patients with heart failure and mildly reduced ejection fraction.
Abstract: Background: While disease-modifying therapies exist for heart failure (HF) with reduced left ventricular ejection fraction (LVEF), few options are available for patients in the higher range of LVEF...
British Heart Foundation1, University of Toronto2, Yale University3, University of Minnesota4, First Faculty of Medicine, Charles University in Prague5, Saarland University6, Taipei Veterans General Hospital7, National Yang-Ming University8, University Medical Center Groningen9, Brigham and Women's Hospital10, Medical University of Łódź11, Comenius University in Bratislava12, Fudan University13, University of Calgary14, University of Gothenburg15, Semmelweis University16, University of São Paulo17, Montreal Heart Institute18, Copenhagen University Hospital19, University of Missouri–Kansas City20, AstraZeneca21, National University of Cordoba22, Wrocław Medical University23
TL;DR: In this exploratory analysis of a randomized trial of patients with HFrEF, dapagliflozin compared with placebo, when added to recommended therapy, significantly reduced the risk of worsening heart failure or cardiovascular death independently of diabetes status.
Abstract: Importance Additional treatments are needed for heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 (SGLT2) inhibitors may be an effective treatment for patients with HFrEF, even those without diabetes. Objective To evaluate the effects of dapagliflozin in patients with HFrEF with and without diabetes. Design, Setting, and Participants Exploratory analysis of a phase 3 randomized trial conducted at 410 sites in 20 countries. Patients with New York Heart Association classification II to IV with an ejection fraction less than or equal to 40% and elevated plasma N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. Interventions Addition of once-daily 10 mg of dapagliflozin or placebo to recommended therapy. Main Outcomes and Measures The primary outcome was the composite of an episode of worsening heart failure or cardiovascular death. This outcome was analyzed by baseline diabetes status and, in patients without diabetes, by glycated hemoglobin level less than 5.7% vs greater than or equal to 5.7%. Results Among 4744 patients randomized (mean age, 66 years; 1109 [23%] women; 2605 [55%] without diabetes), 4742 completed the trial. Among participants without diabetes, the primary outcome occurred in 171 of 1298 (13.2%) in the dapagliflozin group and 231 of 1307 (17.7%) in the placebo group (hazard ratio, 0.73 [95% CI, 0.60-0.88]). In patients with diabetes, the primary outcome occurred in 215 of 1075 (20.0%) in the dapagliflozin group and 271 of 1064 (25.5%) in the placebo group (hazard ratio, 0.75 [95% CI, 0.63-0.90]) (Pvalue for interaction = .80). Among patients without diabetes and a glycated hemoglobin level less than 5.7%, the primary outcome occurred in 53 of 438 patients (12.1%) in the dapagliflozin group and 71 of 419 (16.9%) in the placebo group (hazard ratio, 0.67 [95% CI, 0.47-0.96]). In patients with a glycated hemoglobin of at least 5.7%, the primary outcome occurred in 118 of 860 patients (13.7%) in the dapagliflozin group and 160 of 888 (18.0%) in the placebo group (hazard ratio, 0.74 [95% CI, 0.59-0.94]) (Pvalue for interaction = .72). Volume depletion was reported as an adverse event in 7.3% of patients in the dapagliflozin group and 6.1% in the placebo group among patients without diabetes and in 7.8% of patients in the dapagliflozin group and 7.8% in the placebo group among patients with diabetes. A kidney adverse event was reported in 4.8% of patients in the dapagliflozin group and 6.0% in the placebo group among patients without diabetes and in 8.5% of patients in the dapagliflozin group and 8.7% in the placebo group among patients with diabetes. Conclusions and Relevance In this exploratory analysis of a randomized trial of patients with HFrEF, dapagliflozin compared with placebo, when added to recommended therapy, significantly reduced the risk of worsening heart failure or cardiovascular death independently of diabetes status. Trial Registration ClinicalTrials.gov Identifier:NCT03036124
TL;DR: In this paper, a bathymetric sill in Sherard Osborn Fjord, northwest Greenland shields Ryder Glacier from melting by warm Atlantic water found at the bottom of the fjord.
Abstract: The processes controlling advance and retreat of outlet glaciers in fjords draining the Greenland Ice Sheet remain poorly known, undermining assessments of their dynamics and associated sea-level rise in a warming climate. Mass loss of the Greenland Ice Sheet has increased six-fold over the last four decades, with discharge and melt from outlet glaciers comprising key components of this loss. Here we acquired oceanographic data and multibeam bathymetry in the previously uncharted Sherard Osborn Fjord in northwest Greenland where Ryder Glacier drains into the Arctic Ocean. Our data show that warmer subsurface water of Atlantic origin enters the fjord, but Ryder Glacier’s floating tongue at its present location is partly protected from the inflow by a bathymetric sill located in the innermost fjord. This reduces under-ice melting of the glacier, providing insight into Ryder Glacier’s dynamics and its vulnerability to inflow of Atlantic warmer water. A bathymetric sill in Sherard Osborn Fjord, northwest Greenland shields Ryder Glacier from melting by warm Atlantic water found at the bottom of the fjord, according to high-resolution bathymetric mapping and oceanographic data.
TL;DR: Neurochemical evidence of neuronal injury and glial activation in patients with moderate and severe COVID-19 is shown, perhaps reflecting a sequence of early astrocytic response and more delayed axonal injury.
Abstract: OBJECTIVE: To test the hypothesis that coronavirus disease 2019 (COVID-19) has an impact on the CNS by measuring plasma biomarkers of CNS injury. METHODS: We recruited 47 patients with mild (n = 20), moderate (n = 9), or severe (n = 18) COVID-19 and measured 2 plasma biomarkers of CNS injury by single molecule array, neurofilament light chain protein (NfL; a marker of intra-axonal neuronal injury) and glial fibrillary acidic protein (GFAp; a marker of astrocytic activation/injury), in samples collected at presentation and again in a subset after a mean of 11.4 days. Cross-sectional results were compared with results from 33 age-matched controls derived from an independent cohort. RESULTS: The patients with severe COVID-19 had higher plasma concentrations of GFAp (p = 0.001) and NfL (p < 0.001) than controls, while GFAp was also increased in patients with moderate disease (p = 0.03). In patients with severe disease, an early peak in plasma GFAp decreased on follow-up (p < 0.01), while NfL showed a sustained increase from first to last follow-up (p < 0.01), perhaps reflecting a sequence of early astrocytic response and more delayed axonal injury. CONCLUSION: We show neurochemical evidence of neuronal injury and glial activation in patients with moderate and severe COVID-19. Further studies are needed to clarify the frequency and nature of COVID-19-related CNS damage and its relation to both clinically defined CNS events such as hypoxic and ischemic events and mechanisms more closely linked to systemic severe acute respiratory syndrome coronavirus 2 infection and consequent immune activation, as well as to evaluate the clinical utility of monitoring plasma NfL and GFAp in the management of this group of patients.
Massachusetts Institute of Technology1, University of Glasgow2, Boston University3, Max Planck Society4, University of Hamburg5, Technische Universität München6, Jacobs University Bremen7, University of Groningen8, Charles University in Prague9, University of Toronto10, University of Michigan11, Johannes Kepler University of Linz12, Nanyang Technological University13, Columbia University14, University of Gothenburg15, Lund University16
TL;DR: It is demonstrated that interexciton coherences are too short lived to have any functional significance in photosynthetic energy transfer and this work revise the interpretation of coherence signals in photosynthesis systems and leads to a more detailed understanding of the quantum aspects of dissipation.
Abstract: Photosynthesis is a highly optimized process from which valuable lessons can be learned about the operating principles in nature. Its primary steps involve energy transport operating near theoretical quantum limits in efficiency. Recently, extensive research was motivated by the hypothesis that nature used quantum coherences to direct energy transfer. This body of work, a cornerstone for the field of quantum biology, rests on the interpretation of small-amplitude oscillations in two-dimensional electronic spectra of photosynthetic complexes. This Review discusses recent work reexamining these claims and demonstrates that interexciton coherences are too short lived to have any functional significance in photosynthetic energy transfer. Instead, the observed long-lived coherences originate from impulsively excited vibrations, generally observed in femtosecond spectroscopy. These efforts, collectively, lead to a more detailed understanding of the quantum aspects of dissipation. Nature, rather than trying to avoid dissipation, exploits it via engineering of exciton-bath interaction to create efficient energy flow.
01 Jul 2020
TL;DR: Lactate and pyruvate together serve as a circulating redox buffer that equilibrates the NADH/NAD ratio across cells and tissues in mammals as discussed by the authors.
Abstract: Lactate, perhaps the best-known metabolic waste product, was first isolated from sour milk, in which it is produced by lactobacilli. Whereas microbes also generate other fermentation products, such as ethanol or acetone, lactate dominates in mammals. Lactate production increases when the demand for ATP and oxygen exceeds supply, as occurs during intense exercise and ischaemia. The build-up of lactate in stressed muscle and ischaemic tissues has established lactate's reputation as a deleterious waste product. In this Perspective, we summarize emerging evidence that, in mammals, lactate also serves as a major circulating carbohydrate fuel. By providing mammalian cells with both a convenient source and sink for three-carbon compounds, circulating lactate enables the uncoupling of carbohydrate-driven mitochondrial energy generation from glycolysis. Lactate and pyruvate together serve as a circulating redox buffer that equilibrates the NADH/NAD ratio across cells and tissues. This reconceptualization of lactate as a fuel-analogous to how Hans Christian Andersen's ugly duckling is actually a beautiful swan-has the potential to reshape the field of energy metabolism.
University of Tartu1, American Museum of Natural History2, University of Gothenburg3, Swedish University of Agricultural Sciences4, University of Oslo5, University of Hawaii at Manoa6, University of Copenhagen7, Purdue University8, Academy of Sciences of the Czech Republic9, University of Turin10, Harvard University11, Synlab Group12, Universidad Mayor13, Universidad Santo Tomás14, University of Electronic Science and Technology of China15, University of Warsaw16, Swedish Museum of Natural History17, Mae Fah Luang University18, University of Florida19, Laos Ministry of Agriculture and Forestry20, São Paulo Federal Institute of Education, Science and Technology21, Estonian University of Life Sciences22, Federal University of Pernambuco23, United States Department of Energy24, Del Rosario University25, National Autonomous University of Mexico26, Ghent University27, West Bengal State University28, Beijing Forestry University29, Pontifical Catholic University of Chile30, Chinese Academy of Sciences31, Field Museum of Natural History32, Leibniz Association33, University of Potsdam34, University of Gilan35, University of Alaska Fairbanks36, University of Tokyo37, University of Costa Rica38, Forest Research Institute39, University of Sydney40, Westmead Hospital41, Uppsala University42, Landcare Research43, University of Chittagong44, University of Memphis45, United Arab Emirates University46, Ministry of Land and Resources of the People's Republic of China47, University of Pretoria48, Royal Botanic Gardens49, Ocean University of China50, Guizhou University51, Mie University52, Hokkaido University53
TL;DR: Fungal traits and character database FungalTraits operating at genus and species hypothesis levels is presented in this article, which includes 17 lifestyle related traits of fungal and Stramenopila genera.
Abstract: The cryptic lifestyle of most fungi necessitates molecular identification of the guild in environmental studies. Over the past decades, rapid development and affordability of molecular tools have tremendously improved insights of the fungal diversity in all ecosystems and habitats. Yet, in spite of the progress of molecular methods, knowledge about functional properties of the fungal taxa is vague and interpretation of environmental studies in an ecologically meaningful manner remains challenging. In order to facilitate functional assignments and ecological interpretation of environmental studies we introduce a user friendly traits and character database FungalTraits operating at genus and species hypothesis levels. Combining the information from previous efforts such as FUNGuild and Fun(Fun) together with involvement of expert knowledge, we reannotated 10,210 and 151 fungal and Stramenopila genera, respectively. This resulted in a stand-alone spreadsheet dataset covering 17 lifestyle related traits of fungal and Stramenopila genera, designed for rapid functional assignments of environmental studies. In order to assign the trait states to fungal species hypotheses, the scientific community of experts manually categorised and assigned available trait information to 697,413 fungal ITS sequences. On the basis of those sequences we were able to summarise trait and host information into 92,623 fungal species hypotheses at 1% dissimilarity threshold.
TL;DR: In this paper, a stochastic-robust optimization method was developed to consider both low impact variations and extreme events, and applied to 30 cities in Sweden, by considering 13 climate change scenarios, reveal that uncertainties in renewable energy potential and demand can lead to a significant performance gap brought by future climate variations and a drop in power supply reliability due to extreme weather events.
Abstract: Climate induced extreme weather events and weather variations will affect both the demand of energy and the resilience of energy supply systems. The specific potential impact of extreme events on energy systems has been difficult to quantify due to the unpredictability of future weather events. Here we develop a stochastic-robust optimization method to consider both low impact variations and extreme events. Applications of the method to 30 cities in Sweden, by considering 13 climate change scenarios, reveal that uncertainties in renewable energy potential and demand can lead to a significant performance gap (up to 34% for grid integration) brought by future climate variations and a drop in power supply reliability (up to 16%) due to extreme weather events. Appropriate quantification of the climate change impacts will ensure robust operation of the energy systems and enable renewable energy penetration above 30% for a majority of the cities.
University of Paris1, Ghent University Hospital2, Medical University of Vienna3, University of Lisbon4, Autonomous University of Barcelona5, Technische Universität München6, Guy's and St Thomas' NHS Foundation Trust7, King's College London8, University of Gothenburg9, Utrecht University10, Humanitas University11
TL;DR: The COVID-19 pandemic has had an overwhelming psychological impact on intensivists and follow-up, and management are warranted to assess long-term psychological outcomes and alleviate the psychological burden of the pandemic on frontline personnel.
Abstract: The COVID-19 pandemic has resulted in an unprecedented healthcare crisis with a high prevalence of psychological distress in healthcare providers. We sought to document the prevalence of burnout syndrome amongst intensivists facing the COVID-19 outbreak. Cross-sectional survey among intensivists part of the European Society of Intensive Care Medicine. Symptoms of severe burnout, anxiety and depression were collected. Factors independently associated with severe burnout were assessed using Cox model. Response rate was 20% (1001 completed questionnaires were returned, 45 years [39–53], 34% women, from 85 countries, 12 regions, 50% university-affiliated hospitals). The prevalence of symptoms of anxiety and depression or severe burnout was 46.5%, 30.2%, and 51%, respectively, and varied significantly across regions. Rating of the relationship between intensivists and other ICU stakeholders differed significantly according to the presence of anxiety, depression, or burnout. Similar figures were reported for their rating of the ethical climate or the quality of the decision-making. Factors independently associated with anxiety were female gender (HR 1.85 [1.33–2.55]), working in a university-affiliated hospital (HR 0.58 [0.42–0.80]), living in a city of > 1 million inhabitants (HR 1.40 [1.01–1.94]), and clinician’s rating of the ethical climate (HR 0.83 [0.77–0.90]). Independent determinants of depression included female gender (HR 1.63 [1.15–2.31]) and clinician’s rating of the ethical climate (HR 0.84 [0.78–0.92]). Factors independently associated with symptoms of severe burnout included age (HR 0.98/year [0.97–0.99]) and clinician’s rating of the ethical climate (HR 0.76 [0.69–0.82]). The COVID-19 pandemic has had an overwhelming psychological impact on intensivists. Follow-up, and management are warranted to assess long-term psychological outcomes and alleviate the psychological burden of the pandemic on frontline personnel.
TL;DR: Influence of the gut microbiome on the human immune system is revealed by systems analysis of vast clinical data from decades of electronic health records paired with massive longitudinal microbiome sequencing, with implications for microbiota-driven modulation of immunity.
Abstract: The gut microbiota influences development1–3 and homeostasis4–7 of the mammalian immune system, and is associated with human inflammatory8 and immune diseases9,10 as well as responses to immunotherapy11–14. Nevertheless, our understanding of how gut bacteria modulate the immune system remains limited, particularly in humans, where the difficulty of direct experimentation makes inference challenging. Here we study hundreds of hospitalized—and closely monitored—patients with cancer receiving haematopoietic cell transplantation as they recover from chemotherapy and stem-cell engraftment. This aggressive treatment causes large shifts in both circulatory immune cell and microbiota populations, enabling the relationships between the two to be studied simultaneously. Analysis of observed daily changes in circulating neutrophil, lymphocyte and monocyte counts and more than 10,000 longitudinal microbiota samples revealed consistent associations between gut bacteria and immune cell dynamics. High-resolution clinical metadata and Bayesian inference allowed us to compare the effects of bacterial genera in relation to those of immunomodulatory medications, revealing a considerable influence of the gut microbiota—together and over time—on systemic immune cell dynamics. Our analysis establishes and quantifies the link between the gut microbiota and the human immune system, with implications for microbiota-driven modulation of immunity. Influence of the gut microbiome on the human immune system is revealed by systems analysis of vast clinical data from decades of electronic health records paired with massive longitudinal microbiome sequencing.
Karolinska Institutet1, Science for Life Laboratory2, University of Oulu3, Baker IDI Heart and Diabetes Institute4, Karolinska University Hospital5, Pfizer6, Mental Health Services7, Translational Genomics Research Institute8, University Medical Center Groningen9, University of Queensland10, Sun Yat-sen University11, Western General Hospital12, University of Tartu13, Broad Institute14, University of Bristol15, Lund University16, Uppsala University17, University of Edinburgh18, Uppsala University Hospital19, Harvard University20, Lancaster University21, University of Split22, University of Cambridge23, University of Gothenburg24, The George Institute for Global Health25, Clinical Trial Service Unit26, Sunnybrook Health Sciences Centre27, Stanford University28
TL;DR: The utility of large-scale mapping of the genetics of the proteome is demonstrated and pQTLs are provided as a resource for future precision studies of circulating proteins in human health.
Abstract: Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
TL;DR: In this article, the authors compared six bioinformatic pipelines for the analysis of amplicon sequence data: three OTU-level flows (QIIME-uclust, MOTHUR, and USEARCH-UPARSE) and three ASV-level (DADA2, Qiime2-Deblur, and Uplabel-UNOISE3).
Abstract: Microbial amplicon sequencing studies are an important tool in biological and biomedical research. Widespread 16S rRNA gene microbial surveys have shed light on the structure of many ecosystems inhabited by bacteria, including the human body. However, specialized software and algorithms are needed to convert raw sequencing data into biologically meaningful information (i.e. tables of bacterial counts). While different bioinformatic pipelines are available in a rapidly changing and improving field, users are often unaware of limitations and biases associated with individual pipelines and there is a lack of agreement regarding best practices. Here, we compared six bioinformatic pipelines for the analysis of amplicon sequence data: three OTU-level flows (QIIME-uclust, MOTHUR, and USEARCH-UPARSE) and three ASV-level (DADA2, Qiime2-Deblur, and USEARCH-UNOISE3). We tested workflows with different quality control options, clustering algorithms, and cutoff parameters on a mock community as well as on a large (N = 2170) recently published fecal sample dataset from the multi-ethnic HELIUS study. We assessed the sensitivity, specificity, and degree of consensus of the different outputs. DADA2 offered the best sensitivity, at the expense of decreased specificity compared to USEARCH-UNOISE3 and Qiime2-Deblur. USEARCH-UNOISE3 showed the best balance between resolution and specificity. OTU-level USEARCH-UPARSE and MOTHUR performed well, but with lower specificity than ASV-level pipelines. QIIME-uclust produced large number of spurious OTUs as well as inflated alpha-diversity measures and should be avoided in future studies. This study provides guidance for researchers using amplicon sequencing to gain biological insights.
TL;DR: One-third of asthma patients in Sweden were SABA overusers (three or more canisters per year), of whom 28% had no collection of anti-inflammatory drugs, and monitoring of SABA usage should be key in improving asthma management.
Abstract: Background: Overuse of short-acting beta(2)-agonists (SABA) may indicate poor asthma control and adverse health outcomes. Contemporary population-based data on use, risk factors and impact of SABA ...