We present a community data set of daily forcing and hydrologic response data for 671 small- to medium-sized basins across the contiguous United States (median basin size of 336 km2) that spans a ...very wide range of hydroclimatic conditions. Area-averaged forcing data for the period 1980-2010 was generated for three basin spatial configurations - basin mean, hydrologic response units (HRUs) and elevation bands - by mapping daily, gridded meteorological data sets to the subbasin (Daymet) and basin polygons (Daymet, Maurer and NLDAS). Daily streamflow data was compiled from the United States Geological Survey National Water Information System. The focus of this paper is to (1) present the data set for community use and (2) provide a model performance benchmark using the coupled Snow-17 snow model and the Sacramento Soil Moisture Accounting Model, calibrated using the shuffled complex evolution global optimization routine. After optimization minimizing daily root mean squared error, 90% of the basins have Nash-Sutcliffe efficiency scores greater than or equal to 0.55 for the calibration period and 34% greater than or equal to 0.8. This benchmark provides a reference level of hydrologic model performance for a commonly used model and calibration system, and highlights some regional variations in model performance. For example, basins with a more pronounced seasonal cycle generally have a negative low flow bias, while basins with a smaller seasonal cycle have a positive low flow bias. Finally, we find that data points with extreme error (defined as individual days with a high fraction of total error) are more common in arid basins with limited snow and, for a given aridity, fewer extreme error days are present as the basin snow water equivalent increases.
The systemic immune response induced by non-infectious agents is called systemic inflammatory response syndrome (SIRS) and infection-induced systemic immune response is called sepsis. The host ...inflammatory response in SIRS and sepsis is similar and may lead to multiple organ dysfunction syndrome (MODS) and ultimately death. The mortality and morbidity in SIRS and sepsis (i.e. critical illness) remain high despite advances in diagnostic and organ supporting possibilities in intensive care units. In critical illness, the acute immune response is organized and executed by innate immunity influenced by the neuroendocrine system. This response starts with sensing of danger by pattern-recognition receptors on the immune competent cells and endothelium. The sensed danger signals, through specific signalling pathways, activate nuclear transcription factor κB and other transcription factors and gene regulatory systems which up-regulate the expression of pro-inflammatory mediators. The plasma cascades are also activated which together with the produced pro-inflammatory mediators stimulate further the production of inflammatory biomarkers. The acute inflammatory response underlies the pathophysiological mechanisms involved in the development of MODS. The inflammatory mediators directly affect organ function and cause a decline in remote organ function by mediating the production of nitric oxide leading to mitochondrial anergy and cytopathic hypoxia, a condition of cellular inability to use oxygen. Understanding the mechanisms of acute immune responses in critical illness is necessary for the development of urgently needed therapeutics. The aim of this review is to provide a description of the key components and mechanisms involved in the immune response in SIRS and sepsis.
Giant cell arteritis (GCA) is the most common systemic vasculitis in persons older than 50 years. The highest incidence rates of the disease have been reported in Scandinavian countries. Our ...objective was to determine the epidemiology of GCA in an expected high-incidence region during a 41-year period.
This is a hospital-based, retrospective, cohort study. Patients diagnosed with GCA in Bergen health area during 1972-2012 were identified through computerized hospital records (n = 1341). Clinical information was extracted from patients' medical journals, which were reviewed by a standardized method. We excluded patients if data were unavailable (n = 253), if the reviewing rheumatologist found GCA to be an implausible diagnosis (n = 207) or if the American College of Rheumatology (ACR) 1990 classification criteria for GCA were not fulfilled (n = 89). Descriptive methods were used to characterize the sample. Incidence was analyzed by graphical methods and Poisson regression.
A total of 792 patients were included. The average annual cumulative incidence of GCA was 16.7 (95% CI 15.5-18.0) per 100,000 of the population ≥ 50 years old. The corresponding incidence for biopsy-verified GCA was 11.2 (95% CI 10.2-12.3). The annual cumulative incidence increased with time in the period 1972-1992 (relative risk (RR) 1.1, p < 0.001) but not in 1993-2012 (RR 1.0, p = 0.543). The incidence was higher in women compared to men (average annual incidence 37.7 (95% CI 35.8-39.6) vs. 14.3 (95% CI 13.2-15.5), p < 0.001) with women having a twofold to threefold higher incidence rate throughout the study period. Average annual incidence increased with age until the 7th decade of life in both sexes throughout the study period (2.8 (95% CI 2.3-3.3) for age <60, 15.5 (95% CI 14.4-16.8) for age 60-69, 34.5 (95% CI 32.8-36.4) for age 70-79 and 26.8 (95% CI 25.3-28.4) for age ≥80 years, p < 0.001 for all age adjustments).
Our study confirms an incidence of GCA comparable to previous reports on Scandinavian populations. Our results show increasing incidence from 1972 through 1992, after which the incidence has levelled out.
Summary
There is a close cross‐talk between complement, Toll‐like receptors (TLRs) and coagulation. The role of the central complement component 5 (C5) in physiological and pathophysiological ...hemostasis has not, however, been fully elucidated. This study examined the effects of C5 in normal hemostasis and in Escherichia coli‐induced coagulation and tissue factor (TF) up‐regulation. Fresh whole blood obtained from six healthy donors and one C5‐deficient individual (C5D) was anti‐coagulated with the thrombin inhibitor lepirudin. Blood was incubated with or without E. coli in the presence of the C5 inhibitor eculizumab, a blocking anti‐CD14 monoclonal antibody (anti‐CD14) or the TLR‐4 inhibitor eritoran. C5D blood was reconstituted with purified human C5. TF mRNA was measured by quantitative polymerase chain reaction (qPCR) and monocyte TF and CD11b surface expression by flow cytometry. Prothrombin fragment 1+2 (PTF1·2) in plasma and microparticles exposing TF (TF‐MP) was measured by enzyme‐linked immunosorbent assay (ELISA). Coagulation kinetics were analyzed by rotational thromboelastometry and platelet function by PFA‐200. Normal blood with eculizumab as well as C5D blood with or without reconstitution with C5 displayed completely normal biochemical hemostatic patterns. In contrast, E. coli‐induced TF mRNA and TF‐MP were significantly reduced by C5 inhibition. C5 inhibition combined with anti‐CD14 or eritoran completely inhibited the E. coli‐induced monocyte TF, TF‐MP and plasma PTF1·2. Addition of C5a alone did not induce TF expression on monocytes. In conclusion, C5 showed no impact on physiological hemostasis, but substantially contributed to E. coli‐induced procoagulant events, which were abolished by the combined inhibition of C5 and CD14 or TLR‐4.
Effect of eculizumab, anti‐CD14 or the TLR‐4 inhibitor eritoran on Escherichia coli (E. coli)‐induced monocyte tissue factor (TF) surface expression (a), tissue factor function in plasma microparticles (TF‐MP) (b) and prothrombin fragment 1+2 (PTF1·2) levels in plasma (c). Inhibition of C5 using eculizumab reduced the E. coli‐induced TF‐MP level. C5 inhibition combined with anti‐CD14 or eritoran completely inhibited the E. coli‐induced monocyte TF, TF‐MP and plasma PTF1·2.
Our objective was to determine the survival and causes of death in a large and well-characterized cohort of patients with giant cell arteritis (GCA).
This is a hospital-based, retrospective, ...observational cohort study including patients diagnosed with GCA in Western Norway during 1972-2012. Patients were identified through computerized hospital records using the International Classification of Diseases (ICD)-coding system. Medical records were reviewed. Patients were randomly assigned population controls matched on age, sex, and geography from the Central Population Registry of Norway (CPRN). Date and cause of death were obtained from the Norwegian Cause of Death Registry (NCoDR). The survival was analyzed using Kaplan-Meier methods with the Gehan-Breslow test and the causes of death using cumulative incidence and Cox models for competing risks.
We identified 881 cases with a clinical diagnosis of GCA of which 792 fulfilled the American College of Rheumatology (ACR) 1990 classification criteria. Among those fulfilling the ACR criteria, 528 were also biopsy-verified. Cases were matched with 2577 population controls. A total of 490 (56%) GCA patients and 1517 (59%) controls died during the study period. We found no difference in the overall survival of GCA patients compared to controls, p = 0.413. The most frequent underlying causes of death in both groups were diseases of the circulatory system followed by cancer. GCA patients had increased risk of dying of circulatory disease (HR 1.31, 95% CI 1.13-1.51, p < 0.001) but lower risk of dying of cancer (HR 0.56, 95% CI 0.42-0.73, p < 0.001) compared to population controls.
We found no difference in the overall survival of GCA patients compared to matched controls, but there were differences in the distribution of underlying death causes.
Lifestyle factors, including a low intake of carbohydrates, dieting, alcohol consumption, cigarette smoking and stress are some of the possible triggers of attacks in acute intermittent porphyria ...(AIP). The influence of lifestyle factors, including energy intake, diet and alcohol consumption on the biochemical disease activity in AIP and biochemical nutritional markers were examined.
A case-control study with 50 AIP cases and 50 controls matched for age, sex and place of residence was performed. Dietary intake was registered using a food diary in 46 matched pairs. Symptoms, alcohol intake, stress and other triggering factors of the last AIP attack were recorded on questionnaires. Porphyrin precursors, liver and kidney function markers, vitamins, diabetogenic hormones and other nutritional biomarkers were analyzed by routine methods. The Wilcoxon matched-pairs signed rank test was used to compare the cases vs. controls. The Spearman's rank correlation coefficient was used on the cases.
Increasing total energy intake was negatively correlated with the biochemical disease activity. The intake of carbohydrates was lower than recommended, i.e., 40 and 39% of total energy intake in the AIP cases and controls, respectively. The plasma resistin level was significantly higher (p = .03) in the symptomatic than asymptomatic cases. Plasma insulin was lower in those with high porphobilinogen levels. The intake of sugar and candies were higher in the AIP cases with low U-delta aminolevulinic acid (ALA) levels (p = .04). Attacks were triggered by psychological stress (62%), physical strain (38%), food items (24%) and alcohol (32%) in the 34 symptomatic cases. Alcohol was used regularly by 88% of the cases (3.2 g ethanol/day) and 90% of the controls (6.3 g/day), but the intake was significantly lower in symptomatic than in asymptomatic cases (p = .045).
A high intake of energy, sugar and candies and a higher insulin level were associated with a lower biochemical disease activity. The resistin level was higher in the symptomatic than the asymptomatic cases. AIP patients drink alcohol regularly, but the intake was significantly lower in the symptomatic cases.
ClinicalTrials.gov Identifier: NCT01617642.
•Diet, alcohol and diabetogenic hormones was studied in 50 acute intermittent porphyria (AIP) cases and matched controls•AIP patients had lower carbohydrate and fiber intake, and higher saturated fat and added sugar intake than recommended•Alcohol was regularly used by most AIP patients, but the intake was lower in the symptomatic than asymptomatic cases•Plasma Resistin was higher in symptomatic than asymptomatic cases suggesting higher inflammation in the symptomatic cases
Summary
This study aimed to examine whether acute intermittent porphyria (AIP) is associated with systemic inflammation and whether the inflammation correlates with disease activity. A case–control ...study with 50 AIP cases and age‐, sex‐ and place of residence‐matched controls was performed. Plasma cytokines, insulin and C‐peptide were analysed after an overnight fast using multiplex assay. Long pentraxin‐3 (PTX3) and complement activation products (C3bc and TCC) were analysed using enzyme‐linked immunosorbent assay (ELISA). Urine porphobilinogen ratio (U‐PBG, µmol/mmol creatinine), haematological and biochemical tests were performed using routine methods. Questionnaires were used to register AIP symptoms, medication and other diseases. All 27 cytokines, chemokines and growth factors investigated were increased significantly in symptomatic AIP cases compared with controls (P < 0·0004). Hierarchical cluster analyses revealed a cluster with high visfatin levels and several highly expressed cytokines including interleukin (IL)‐17, suggesting a T helper type 17 (Th17) inflammatory response in a group of AIP cases. C3bc (P = 0·002) and serum immunoglobulin (Ig)G levels (P = 0·03) were increased significantly in cases with AIP. The U‐PBG ratio correlated positively with PTX3 (r = 0·38, P = 0·006), and with terminal complement complex (TCC) levels (r = 0·33, P = 0·02). PTX3 was a significant predictor of the biochemical disease activity marker U‐PBG in AIP cases after adjustment for potential confounders in multiple linear regression analyses (P = 0·032). Prealbumin, C‐peptide, insulin and kidney function were all decreased in the symptomatic AIP cases, but not in the asymptomatic cases. These results indicate that AIP is associated with systemic inflammation. Decreased C‐peptide levels in symptomatic AIP cases indicate that reduced insulin release is associated with enhanced disease activity and reduced kidney function.
This case‐control study examined systemic inflammation in patients with acute intermittent porphyria (AIP), and whether the inflammation correlated with the disease activity markers delta‐aminolevulinic acid (ALA), porphobilinogen (PBG) and porphyrins. Reduced prealbumin indicate inflammation in the liver, and decreased C‐peptide levels in symptomatic AIP cases indicated that reduced insulin release was associated with enhanced disease activity and reduced kidney function. Organ damage may activate complement measured as increased levels of the terminal complement complex (TCC) and C5a which activates cells to release cytokines, interleukins and growth factors.
Agricultural practices have been linked to soil carbon (C) and nitrogen (N) stores through exchanges with the atmosphere in the form of greenhouse gases (GHGs) of carbon dioxide (CO2), nitrous oxide ...(N2O), and methane (CH4). However, regional and management‐specific research is needed to ultimately understand the drivers of these atmosphere warming molecules. We established research on four grassland sites: a native, mixed‐species warm‐season site and a non‐native, warm‐season, grass‐species site at the Grazinglands Research Laboratory at El Reno, OK; a native, mixed‐species warm‐season site at Noble Research Institute's Oswalt Ranch in Ardmore, OK; and a native, mixed‐species, warm‐season site at Oklahoma State University's Range Research Station at Marena, OK. Greenhouse gases, along with soil properties were measured biweekly and summed by season in 2015 and 2016. A comparison of GHGs with soil variables indicated that mineralization of soil nutrients mediated GHG fluxes. The sites were sources of CO2 and N2O emissions, but sinks for CH4, particularly in diverse native grassland sites. In spring, CO2 emissions were driven by soil water content, soil temperature, and soil N. The N2O emissions were highest in the fertilized monoculture pasture. Overall, fluxes of the GHGs were driven by primarily by water content, soil nitrate, soil temperature, and ammonia content. By better understanding GHG fluxes and the abiotic and biotic drivers, we can identify management options to foster C sequestration and mitigate the GHG footprint for these forage‐based systems.
Core Ideas
Grassland pasture is a major global land use, including in the U.S. Great Plains.
C and N fluxes within the grassland ecosystems include greenhouse gas forms CO2, CH4, and N2O
Mean fluxes of CO2 and N2O were positive from three grassland sites in Oklahoma.
All study sites were a soil sink for CH4 across seasons.
Understanding factors impacting these fluxes is important to mitigate emissions.
There is an increasing awareness of the spectrum of phenotypes in giant cell arteritis (GCA). However, there is sparse evidence concerning the phenotypic distribution which may be influenced by both ...genetic background and the environment. We established a cohort of all GCA-patients in the Bergen Health Area (Western Norway), to describe the phenotypic distribution and whether phenotypes differ with regards to incidence and clinical features.
This is a retrospective cohort study including all GCA-patients in the Bergen Health Area from 2013-2020. Data were collected by reviewing patient records, and patients considered clinically likely GCA were included if they fulfilled at least one set of classification criteria. Temporal artery biopsy (TAB) and imaging results were used to classify the patients according to phenotype. The phenotype "cranial GCA" was used for patients with a positive TAB or halo sign on temporal artery ultrasound. "Non-cranial GCA" was used for patients with positive findings on FDG-PET/CT, MRI-, or CT angiography, or wall thickening indicative of vasculitis on ultrasound of axillary arteries. Patients with features of both these phenotypes were labeled "mixed." Patients that could not be classified due to negative or absent examination results were labeled "unclassifiable".
257 patients were included. The overall incidence of GCA was 20.7 per 100,000 persons aged 50 years or older. Overall, the cranial phenotype was dominant, although more than half of the patients under 60 years of age had the non-cranial phenotype. The diagnostic delay was twice as long for patients of non-cranial and mixed phenotype compared to those of cranial phenotype. Headache was the most common clinical feature (78% of patients). Characteristic clinic features occurred less frequently in patients of non-cranial phenotype compared to cranial phenotype.
The overall incidence for GCA was comparable to earlier reports from this region. The cranial phenotype dominated although the non-cranial phenotype was more common in patients under 60 years of age. The diagnostic delay was longer in patients with the non-cranial versus cranial phenotype, indicating a need for examination of non-cranial arteries when suspecting GCA.
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