Predictors of fatigue severity in early systemic sclerosis: a prospective longitudinal study of the GENISOS cohort.

ObjectivesLongitudinal studies examining the baseline predictors of fatigue in SSc have not been reported. Our objectives were to examine the course of fatigue severity over time and to identify baseline clinical, demographic, and psychosocial predictors of sequentially obtained fatigue scores in early SSc. We also examined baseline predictors of change in fatigue severity over time.MethodsWe analyzed 1090 longitudinal Fatigue Severity Scale (FSS) scores belonging to 256 patients who were enrolled in the Genetics versus Environment in Scleroderma Outcomes Study (GENISOS). Predictive significance of baseline variables for sequentially obtained FSS scores was examined with generalized linear mixed models. Predictors of change in FSS over time were examined by adding an interaction term between the baseline variable and time-in-study to the model.ResultsThe patients' mean age was 48.6 years, 47% were Caucasians, and 59% had diffuse cutaneous involvement. The mean disease duration at enrollment was 2.5 years. The FSS was obtained at enrollment and follow-up visits (mean follow-up time = 3.8 years). Average baseline FSS score was 4.7(±0.96). The FSS was relatively stable and did not show a consistent trend for change over time (p = 0.221). In a multivariable model of objective clinical variables, higher Medsger Gastrointestinal (p = 0.006) and Joint (p = 0.024) Severity Indices, and anti-U1-RNP antibodies (p = 0.024) were independent predictors of higher FSS. In the final model, ineffective coping skills captured by higher Illness Behavior Questionnaire scores (p<0.001), higher self-reported pain (p = 0.006), and higher Medsger Gastrointestinal Severity Index (p = 0.009) at enrollment were independent predictors of higher longitudinal FSS scores. Baseline DLco % predicted was the only independent variable that significantly predicted a change in FSS scores over time (p = 0.013), with lower DLco levels predicting an increase in FSS over time.ConclusionsThis study identified potentially modifiable clinical and psychological factors that predict longitudinal fatigue severity in early SSc

Mechanism of Vanadium Leaching during Surface Weathering of Basic Oxygen Furnace Steel Slag Blocks: A Microfocus X-ray Absorption Spectroscopy and Electron Microscopy Study

© 2017 American Chemical Society. Basic oxygen furnace (BOF) steelmaking slag is enriched in potentially toxic V which may become mobilized in high pH leachate during weathering. BOF slag was weathered under aerated and air-excluded conditions for 6 months prior to SEM/EDS and μXANES analysis to determine V host phases and speciation in both primary and secondary phases. Leached blocks show development of an altered region in which free lime and dicalcium silicate phases were absent and Ca-Si-H was precipitated (CaCO 3 was also present under aerated conditions). μXANES analyses show that V was released to solution as V(V) during dicalcium silicate dissolution and some V was incorporated into neo-formed Ca-Si-H. Higher V concentrations were observed in leachate under aerated conditions than in the air-excluded leaching experiment. Aqueous V concentrations were controlled by Ca 3 (VO 4 ) 2 solubility, which demonstrate an inverse relationship between Ca and V concentrations. Under air-excluded conditions Ca concentrations were controlled by dicalcium silicate dissolution and Ca-Si-H precipitation, leading to relatively high Ca and correspondingly low V concentrations. Formation of CaCO 3 under aerated conditions provided a sink for aqueous Ca, allowing higher V concentrations limited by kinetic dissolution rates of dicalcium silicate. Thus, V release may be slowed by the precipitation of secondary phases in the altered region, improving the prospects for slag reuse

Prolonged treatment of genetically obese mice with conjugated linoleic acid improves glucose tolerance and lowers plasma insulin concentration: possible involvement of PPAR activation

BACKGROUND: Studies in rodents and some studies in humans have shown that conjugated linoleic acid (CLA), especially its trans-10, cis-12 isomer, reduces body fat content. However, some but not all studies in mice and humans (though none in rats) have found that CLA promotes insulin resistance. The molecular mechanisms responsible for these effects are unclear, and there are conflicting reports on the effects of CLA on peroxisomal proliferator-activated receptor-γ (PPARγ) activation and expression. We have conducted three experiments with CLA in obese mice over three weeks, and one over eleven weeks. We have also investigated the effects of CLA isomers in PPARγ and PPARα reporter gene assays. RESULTS: Inclusion of CLA or CLA enriched with its trans-10, cis-12 isomer in the diet of female genetically obese (lep(ob)/lep(ob)) mice for up to eleven weeks reduced body weight gain and white fat pad weight. After two weeks, in contrast to beneficial effects obtained with the PPARγ agonist rosiglitazone, CLA or CLA enriched with its trans-10, cis-12 isomer raised fasting blood glucose and plasma insulin concentrations, and exacerbated glucose tolerance. After 10 weeks, however, CLA had beneficial effects on glucose and insulin concentrations. At this time, CLA had no effect on the plasma TNFα concentration, but it markedly reduced the plasma adiponectin concentration. CLA and CLA enriched with either isomer raised the plasma triglyceride concentration during the first three weeks, but not subsequently. CLA enriched with its trans-10, cis-12 isomer, but not with its cis-9, trans-11 isomer, stimulated PPARγ-mediated reporter gene activity; both isomers stimulated PPARα-mediated reporter gene activity. CONCLUSIONS: CLA initially decreased but subsequently increased insulin sensitivity in lep(ob)/lep(ob )mice. Activation of both PPARγ and PPARα may contribute to the improvement in insulin sensitivity. In the short term, however, another mechanism, activated primarily by trans-10, cis-12-CLA, which probably leads to reduced adipocyte number and consequently reduced plasma adiponectin concentration, may decrease insulin sensitivity

The Failure of Northern Rock: A multi-dimensional Case Study

In August 2007 the United Kingdom experienced its first bank run in over 140 years. Although Northern Rock was not a particularly large bank (it was at the time ranked 7th in terms of assets) it was nevertheless a significant retail bank and a substantial mortgage lender. In fact, ten years earlier it had converted from a mutual building society whose activities were limited by regulation largely to retail deposits and mortgages. Graphic television news pictures showed very long queues outside the bank as depositors rushed to withdraw their deposits. There was always a fear that this could spark a systemic run on bank deposits. After failed attempts to secure a buyer in the private sector, the government nationalised the bank and, for the first time, in effect socialised the credit risk of the bank. It is now a fully state-owned bank..

Blood Neutrophil Count and Neutrophil-to-Lymphocyte Ratio for Prediction of Disease Progression and Mortality in Two Independent Systemic Sclerosis Cohorts

OBJECTIVE: To assess the predictive significance of blood neutrophil count and the ratio between neutrophil and lymphocyte count (neutrophil-to-lymphocyte ratio [NLR]) for disease severity and mortality in systemic sclerosis (SSc). METHODS: Neutrophil and lymphocyte counts were prospectively measured in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) and the Scleroderma Lung Study II (SLS II). Forced vital capacity percent predicted (FVC%) and modified Rodnan skin thickness score (MRSS) were used as surrogate measures for disease severity. Longitudinal analyses were performed using generalized linear mixed models. Cox proportional hazards models evaluated the predictive significance of these cell counts for mortality. RESULTS: Of the 447 SSc patients in the GENISOS cohort at the time of analysis, 377 (84.3%) had available baseline blood neutrophil and lymphocyte counts. Higher baseline neutrophil count and NLR predicted lower serially obtained FVC% (b = -4.74, P = 0.009 and b = -2.68, P = 0.028, respectively) and higher serially obtained MRSS (b = 4.07, P \u3c 0.001 and b = 2.32, P \u3c 0.001, respectively). Longitudinal neutrophil and NLR measurements also significantly correlated with lower concurrently obtained FVC% measurements and higher concurrently obtained MRSS. Baseline neutrophil count and NLR predicted increased risk of long-term mortality, even after adjustment for baseline demographic and clinical factors (hazard ratio [HR] 1.42, P = 0.02 and HR 1.48, P \u3c 0.001, respectively). The predictive significance of higher baseline neutrophil count and NLR for declining FVC% and increased long-term mortality was confirmed in the SLS II. CONCLUSION: Higher blood neutrophil count and NLR are predictive of more severe disease course and increased mortality, indicating that these easily obtainable laboratory studies might be a reflection of pathologic immune processes in SSc

Blood Neutrophil Count and Neutrophil-to-Lymphocyte Ratio for Prediction of Disease Progression and Mortality in Two Independent Systemic Sclerosis Cohorts

OBJECTIVE: To assess the predictive significance of blood neutrophil count and the ratio between neutrophil and lymphocyte count (neutrophil-to-lymphocyte ratio [NLR]) for disease severity and mortality in systemic sclerosis (SSc). METHODS: Neutrophil and lymphocyte counts were prospectively measured in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) and the Scleroderma Lung Study II (SLS II). Forced vital capacity percent predicted (FVC%) and modified Rodnan skin thickness score (MRSS) were used as surrogate measures for disease severity. Longitudinal analyses were performed using generalized linear mixed models. Cox proportional hazards models evaluated the predictive significance of these cell counts for mortality. RESULTS: Of the 447 SSc patients in the GENISOS cohort at the time of analysis, 377 (84.3%) had available baseline blood neutrophil and lymphocyte counts. Higher baseline neutrophil count and NLR predicted lower serially obtained FVC% (b = -4.74, P = 0.009 and b = -2.68, P = 0.028, respectively) and higher serially obtained MRSS (b = 4.07, P \u3c 0.001 and b = 2.32, P \u3c 0.001, respectively). Longitudinal neutrophil and NLR measurements also significantly correlated with lower concurrently obtained FVC% measurements and higher concurrently obtained MRSS. Baseline neutrophil count and NLR predicted increased risk of long-term mortality, even after adjustment for baseline demographic and clinical factors (hazard ratio [HR] 1.42, P = 0.02 and HR 1.48, P \u3c 0.001, respectively). The predictive significance of higher baseline neutrophil count and NLR for declining FVC% and increased long-term mortality was confirmed in the SLS II. CONCLUSION: Higher blood neutrophil count and NLR are predictive of more severe disease course and increased mortality, indicating that these easily obtainable laboratory studies might be a reflection of pathologic immune processes in SSc

Simulating the influences of groundwater on regional geomorphology using a distributed, dynamic, landscape evolution modelling platform

A dynamic landscape evolution modelling platform (CLiDE) is presented that allows a variety of Earth system interactions to be explored under differing environmental forcing factors. Representation of distributed surface and subsurface hydrology within CLiDE is suited to simulation at sub-annual to centennial time-scales. In this study the hydrological components of CLiDE are evaluated against analytical solutions and recorded datasets. The impact of differing groundwater regimes on sediment discharge is examined for a simple, idealised catchment, Sediment discharge is found to be a function of the evolving catchment morphology. Application of CLiDE to the upper Eden Valley catchment, UK, suggests the addition of baseflow-return from groundwater into the fluvial system modifies the total catchment sediment discharge and the spatio-temporal distribution of sediment fluxes during storm events. The occurrence of a storm following a period of appreciable antecedent rainfall is found to increase simulated sediment fluxes

Regulating Systemic Risk

The failure to spot emerging systemic risk and prevent the current global financial crisis warrants a reexamination of the approach taken so far to crisis prevention. The paper argues that financial crises can be prevented, as they build up over time due to policy mistakes and eventually erupt in slow motion. While one cannot predict the precise timing of crises, one can avert them by identifying and dealing with sources of instability. For this purpose, policymakers need to strengthen top-down macroprudential supervision, complemented by bottom-up microprudential supervision. The paper explores such a strategy and the institutional setting required to implement it at the national level. Given that the recent regulatory reforms that have been undertaken to address systemic risks are inadequate to prevent and combat future crises, the paper argues that national measures to promote financial stability are crucial and that the Westphalian principles governing international financial oversight should be rejected. The paper proposes that while an effective national systemic regulator should be established, strong international cooperation is indispensable for financial stability

System size and centrality dependence of the balance function in A+A collisions at sqrt[sNN]=17.2 GeV

Electric charge correlations were studied for p+p, C+C, Si+Si, and centrality selected Pb+Pb collisions at sqrt[sNN]=17.2 GeV with the NA49 large acceptance detector at the CERN SPS. In particular, long-range pseudorapidity correlations of oppositely charged particles were measured using the balance function method. The width of the balance function decreases with increasing system size and centrality of the reactions. This decrease could be related to an increasing delay of hadronization in central Pb+Pb collisions

Environmental and Lifestyle Factors Associated with Perceived Facial Age in Chinese Women

Perceived facial age has been proposed as a biomarker of ageing with ‘looking young for one’s age' linked to physical and cognitive functioning and to increased survival for Caucasians. We have investigated the environmental and lifestyle factors associated with perceived facial ageing in Chinese women. Facial photographs were collected from 250 Chinese women, aged 25–70 years in Shanghai, China. Perceived facial age was determined and related to chronological age for each participant. Lifestyle and health information was collected by questionnaire. Bivariate analyses (controlling for chronological age) identified and quantified lifestyle variables associated with perceived facial age. Independent predictors of perceived age were identified by multivariate modelling. Factors which significantly associated with looking younger for one's chronological age included greater years of education (p<0.001), fewer household members (p = 0.027), menopausal status (p = 0.020), frequency of visiting one's doctor (p = 0.013), working indoors (p<0.001), spending less time in the sun (p = 0.015), moderate levels of physical activity (p = 0.004), higher frequency of teeth cleaning (p<0.001) and more frequent use of facial care products: cleanser (p<0.001); moisturiser (p = 0.016) or night cream (p = 0.016). Overall, 36.5% of the variation in the difference between perceived and chronological age could be explained by a combination of chronological age and 6 independent lifestyle variables. We have thus identified and quantified a number of factors associated with younger appearance in Chinese women. Presentation of these factors in the context of facial appearance could provide significant motivation for the adoption of a range of healthy behaviours at the level of both individuals and populations