Lifetime risk and genetic predisposition to post-traumatic OA of the knee in the UK Biobank

Objective Acute knee injury is associated with post-traumatic OA (PTOA). Very little is known about the genome-wide associations of PTOA when compared with idiopathic OA (iOA). Our objective was to describe the development of knee OA after knee injury and its genetic associations in UK Biobank (UKB). Design Clinically significant structural knee injuries in those <=50 years were identified from electronic health record and self-reported data in 502,409 UKB participants. Time-to-first knee OA code was compared in injured cases and age-/sex-matched non-injured controls using Cox Proportional Hazards models. A time-to-OA genome-wide association study (GWAS) sought evidence for PTOA risk variants 6 months-20 years following injury. Evidence for associations of two iOA polygenic risk scores (PRS) was sought. Results Of 4233 knee injury cases, 1896 (44.8%) were female (mean age at injury 34.1 years [SD10.4]). Over a median of 30.2 (IQR19.5-45.4) years, 1096 (25.9%) of injured cases developed knee OA. The overall hazards ratio (HR) for knee OA after injury was 1.81[1.70,1.93],P=8.9x10-74. Female sex and increasing age at injury were associated with knee OA following injury (HR1.15[1.02,1.30];1.07[1,07,1.07] respectively). OA risk was highest in the first 5 years after injury (HR3.26[2.67,3.98]), persisting for 40 years. In 3074 knee injury cases included in the time-to-OA GWAS, no variants reached genome-wide significance. iOA PRS was not associated with time-to-OA (HR 0.43[0.02,8.41]). Conclusions Increasing age at injury and female sex appear to be associated with future development of PTOA in UKB, the risk of which was greatest in the 5 years after injury. Further international efforts towards a better-powered meta-analysis will definitively elucidate genetic similarities and differences of PTOA and iOA

Historical (1700–2012) global multi-model estimates of the fire emissions from the Fire Modeling Intercomparison Project (FireMIP)

Fire emissions are a critical component of carbon and nutrient cycles and strongly affect climate and air quality. Dynamic global vegetation models (DGVMs) with interactive fire modeling provide important estimates for long-term and large-scale changes in fire emissions. Here we present the first multi-model estimates of global gridded historical fire emissions for 1700–2012, including carbon and 33 species of trace gases and aerosols. The dataset is based on simulations of nine DGVMs with different state-of-the-art global fire models that participated in the Fire Modeling Intercomparison Project (FireMIP), using the same and standardized protocols and forcing data, and the most up-to-date fire emission factor table based on field and laboratory studies in various land cover types. We evaluate the simulations of present-day fire emissions by comparing them with satellite-based products. The evaluation results show that most DGVMs simulate present-day global fire emission totals within the range of satellite-based products. They can capture the high emissions over the tropical savannas and low emissions over the arid and sparsely vegetated regions, and the main features of seasonality. However, most models fail to simulate the interannual variability, partly due to a lack of modeling peat fires and tropical deforestation fires. Before the 1850s, all models show only a weak trend in global fire emissions, which is consistent with the multi-source merged historical reconstructions used as input data for CMIP6. On the other hand, the trends are quite different among DGVMs for the 20th century, with some models showing an increase and others a decrease in fire emissions, mainly as a result of the discrepancy in their simulated responses to human population density change and land use and land cover change (LULCC). Our study provides an important dataset for further development of regional and global multi-source merged historical reconstructions, analyses of the historical changes in fire emissions and their uncertainties, and quantification of the role of fire emissions in the Earth system. It also highlights the importance of accurately modeling the responses of fire emissions to LULCC and population density change in reducing uncertainties in historical reconstructions of fire emissions and providing more reliable future projections

New model ensemble reveals how forcing uncertainty and model structure alter climate simulated across CMIP generations of the Community Earth System Model

Climate simulation uncertainties arise from internal variability, model structure, and external forcings. Model intercomparisons (such as the Coupled Model Intercomparison Project; CMIP) and single-model large ensembles have provided insight into uncertainty sources. Under the Community Earth System Model (CESM) project, large ensembles have been performed for CESM2 (a CMIP6-era model) and CESM1 (a CMIP5-era model). We refer to these as CESM2-LE and CESM1-LE. The external forcing used in these simulations has changed to be consistent with their CMIP generation. As a result, differences between CESM2-LE and CESM1-LE ensemble means arise from changes in both model structure and forcing. Here we present new ensemble simulations which allow us to separate the influences of these model structural and forcing differences. Our new CESM2 simulations are run with CMIP5 forcings equivalent to those used in the CESM1-LE. We find a strong influence of historical forcing uncertainty due to aerosol effects on simulated climate. For the historical period, forcing drives reduced global warming and ocean heat uptake in CESM2-LE relative to CESM1-LE that is counteracted by the influence of model structure. The influence of the model structure and forcing vary across the globe, and the Arctic exhibits a distinct signal that contrasts with the global mean. For the 21st century, the importance of scenario forcing differences (SSP3–7.0 for CESM2-LE and RCP8.5 for CESM1-LE) is evident. The new simulations presented here allow us to diagnose the influence of model structure on 21st century change, despite large scenario forcing differences, revealing that differences in the meridional distribution of warming are caused by model structure. Feedback analysis reveals that clouds and their impact on shortwave radiation explain many of these structural differences between CESM2 and CESM1. In the Arctic, albedo changes control transient climate evolution differences due to structural differences between CESM2 and CESM1.</p

A new process-based and scale-aware desert dust emission scheme for global climate models – Part II: Evaluation in the Community Earth System Model version 2 (CESM2)

Desert dust is an important atmospheric aerosol that affects the Earth's climate, biogeochemistry, and air quality. However, current Earth system models (ESMs) struggle to accurately capture the impact of dust on the Earth's climate and ecosystems, in part because these models lack several essential aeolian processes that couple dust with climate and land surface processes. In this study, we address this issue by implementing several new parameterizations of aeolian processes detailed in our companion paper in the Community Earth System Model version 2 (CESM2). These processes include (1) incorporating a simplified soil particle size representation to calculate the dust emission threshold friction velocity, (2) accounting for the drag partition effect of rocks and vegetation in reducing wind stress on erodible soils, (3) accounting for the intermittency of dust emissions due to unresolved turbulent wind fluctuations, and (4) correcting the spatial variability of simulated dust emissions from native to higher spatial resolutions on spatiotemporal dust variability. Our results show that the modified dust emission scheme significantly reduces the model bias against observations compared with the default scheme and improves the correlation against observations of multiple key dust variables such as dust aerosol optical depth (DAOD), surface particulate matter (PM) concentration, and deposition flux. Our scheme's dust also correlates strongly with various meteorological and land surface variables, implying higher sensitivity of dust to future climate change than other schemes' dust. These findings highlight the importance of including additional aeolian processes for improving the performance of ESM aerosol simulations and potentially enhancing model assessments of how dust impacts climate and ecosystem changes.</p

Overview of the 2010 Carbonaceous Aerosols and Radiative Effects Study (CARES)

Substantial uncertainties still exist in the scientific understanding of the possible interactions between urban and natural (biogenic) emissions in the production and transformation of atmospheric aerosol and the resulting impact on climate change. The US Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) program's Carbonaceous Aerosol and Radiative Effects Study (CARES) carried out in June 2010 in Central Valley, California, was a comprehensive effort designed to improve this understanding. The primary objective of the field study was to investigate the evolution of secondary organic and black carbon aerosols and their climate-related properties in the Sacramento urban plume as it was routinely transported into the forested Sierra Nevada foothills area. Urban aerosols and trace gases experienced significant physical and chemical transformations as they mixed with the reactive biogenic hydrocarbons emitted from the forest. Two heavily-instrumented ground sites – one within the Sacramento urban area and another about 40 km to the northeast in the foothills area – were set up to characterize the evolution of meteorological variables, trace gases, aerosol precursors, aerosol size, composition, and climate-related properties in freshly polluted and "aged" urban air. On selected days, the DOE G-1 aircraft was deployed to make similar measurements upwind and across the evolving Sacramento plume in the morning and again in the afternoon. The NASA B-200 aircraft, carrying remote sensing instruments, was also deployed to characterize the vertical and horizontal distribution of aerosols and aerosol optical properties within and around the plume. This overview provides: (a) the scientific background and motivation for the study, (b) the operational and logistical information pertinent to the execution of the study, (c) an overview of key observations and initial findings from the aircraft and ground-based sampling platforms, and (d) a roadmap of planned data analyses and focused modeling efforts that will facilitate the integration of new knowledge into improved representations of key aerosol processes and properties in climate models.United States. Dept. of Energy. Atmospheric System Research Program (Contract DE-AC06-76RLO 1830)United States. National Oceanic and Atmospheric AdministrationUnited States. National Aeronautics and Space Administration. HQ Science Mission Directorate Radiation Sciences ProgramUnited States. National Aeronautics and Space Administration. CALIPSO ProgramUnited States. Dept. of Energy. Atmospheric Radiation Measurement Program (Interagency Agreement No. DE-AI02-05ER63985

Prevalence of foot pain across an international consortium of population based cohorts.

OBJECTIVE: Despite the potential burden of foot pain, some of the most fundamental epidemiological questions surrounding the foot remain poorly explored. The prevalence of foot pain has proved difficult to compare across existing studies due to variations in case definitions. The objective of this study was to investigate the prevalence of foot pain in a number of international population-based cohorts using original data and to explore differences in the case definitions used. METHODS: Foot pain variables were examined in five cohorts (the Chingford Women Study, the Johnston County Osteoarthritis Project, the Framingham Foot Study, the Clinical Assessment Study of the Foot and the North West Adelaide Health Study). One foot pain question was chosen from each cohort based on its similarity to the American College of Rheumatology (ACR) pain question. RESULTS: The precise definition of foot pain varied between the cohorts. The prevalence of foot pain ranged from 13 to 36% and was lowest within the cohort that used a case definition specific to pain, compared to the four remaining cohorts that included components of pain, aching or stiffness. Foot pain was generally more prevalent in women, the obese and generally increased with age, being much lower in younger participants (20-44 years). CONCLUSION: Foot pain is common and is associated with female sex, older age and obesity. The prevalence of foot pain is likely affected by the case definition used, therefore consideration must be given for future population studies to use consistent measures of data collection. This article is protected by copyright. All rights reserved

Towards prevention of post-traumatic osteoarthritis: report from an international expert working group on considerations for the design and conduct of interventional studies following acute knee injury

ObjectiveThere are few guidelines for clinical trials of interventions for prevention of post-traumatic osteoarthritis (PTOA), reflecting challenges in this area. An international multi-disciplinary expert group including patients was convened to generate points to consider for the design and conduct of interventional studies following acute knee injury.DesignAn evidence review on acute knee injury interventional studies to prevent PTOA was presented to the group, alongside overviews of challenges in this area, including potential targets, biomarkers and imaging. Working groups considered pre-identified key areas: eligibility criteria and outcomes, biomarkers, injury definition and intervention timing including multi-modality interventions. Consensus agreement within the group on points to consider was generated and is reported here after iterative review by all contributors.ResultsThe evidence review identified 37 studies. Study duration and outcomes varied widely and 70% examined surgical interventions. Considerations were grouped into three areas: justification of inclusion criteria including the classification of injury and participant age (as people over 35 may have pre-existing OA); careful consideration in the selection and timing of outcomes or biomarkers; definition of the intervention(s)/comparator(s) and the appropriate time-window for intervention (considerations may be particular to intervention type). Areas for further research included demonstrating the utility of patient-reported outcomes, biomarkers and imaging outcomes from ancillary/cohort studies in this area, and development of surrogate clinical trial endpoints that shorten the duration of clinical trials and are acceptable to regulatory agencies.ConclusionsThese considerations represent the first international consensus on the conduct of interventional studies following acute knee joint trauma

Analysis of the impact of sex and age on the variation in the prevalence of antinuclear autoantibodies in Polish population: a nationwide observational, cross-sectional study

The detection of antinuclear autoantibody (ANA) is dependent on many factors and varies between the populations. The aim of the study was first to assess the prevalence of ANA in the Polish adult population depending on age, sex and the cutoff threshold used for the results obtained. Second, we estimated the occurrence of individual types of ANA-staining patterns. We tested 1731 patient samples using commercially available IIFA using two cutoff thresholds of 1:100 and 1:160. We found ANA in 260 participants (15.0%), but the percentage of positive results strongly depended on the cutoff level. For a cutoff threshold 1:100, the positive population was 19.5% and for the 1:160 cutoff threshold, it was 11.7%. The most prevalent ANA-staining pattern was AC-2 Dense Fine speckled (50%), followed by AC-21 Reticular/AMA (14.38%) ANA more common in women (72%); 64% of ANA-positive patients were over 50 years of age. ANA prevalence in the Polish population is at a level observed in other highly developed countries and is more prevalent in women and elderly individuals. To reduce the number of positive results released, we suggest that Polish laboratories should set 1:160 as the cutoff threshold

Hand osteoarthritis: clinical phenotypes, molecular mechanisms and disease management

Osteoarthritis (OA) is a highly prevalent condition and the hand is the most commonly affected site. Patients with hand OA frequently report symptoms of pain, functional limitations, and frustration in undertaking everyday activities. The condition presents clinically with changes to the bone, ligaments, cartilage and synovial tissue, which can be observed using radiography, ultrasonography or MRI. Hand OA is a heterogeneous disorder and is considered to be multifactorial in aetiology. This review provides an overview of the epidemiology, presentation and burden of hand OA, including an update on hand OA imaging (including the development of novel techniques), disease mechanisms and management. In particular, areas for which new evidence has substantially changed the way we understand, consider and treat hand OA are highlighted. For example, genetic studies, clinical trials and careful prospective imaging studies from the past 5 years are beginning to provide insights into the pathogenesis of hand OA that might uncover new therapeutic targets in disease