[1] This study investigated the sensitivity of streamflow to changes in climate and glacier cover for the Bridge River basin, British Columbia, using a semi-distributed conceptual hydrological model coupled with a glacier response model. Mass balance data were used to constrain model parameters. Climate scenarios included a continuation of the current climate and two transient GCM scenarios with greenhouse gas forcing. Modelled glacier mass balance was used to re-scale the glacier every decade using a volume-area scaling relation. Glacier area and summer streamflow declined strongly even under the steadyclimate scenario, with the glacier retreating to a new equilibrium within 100 years. For the warming scenarios, glacier retreat continued with no evidence of reaching a new equilibrium. Uncertainty in parameters governing glacier melt produced uncertainty in future glacier retreat and streamflow response. Where mass balance information is not available to assist with calibration, model-generated future scenarios will be subject to significant uncertainty.

Objectives-To investigate the potential relation between cumulative exposure to cigarette smoking in patients with or without rheumatoid arthritis (RA) and a positive family history of the disease. Methods-239 outpatient based patients with RA were compared with 239 controls matched for age, sex, and social class. A detailed smoking history was recorded and expressed as pack years smoked. Conditional logistic regression was used to calculate the association between RA and pack years smoked. The patients with RA were also interviewed about a family history of disease and recorded as positive if a first or second degree relative had RA. The smoking history at the time of the study of the patients with RA with or without a family history of the disease was compared directly with that of their respective controls. Patients with RA with or without a family history of the disease were also compared retrospectively for current smoking at the time of disease onset. Results-An increasing association between increased pack years smoked and RA was found. There was a striking association between heavy cigarette smoking and RA. A history for 41-50 pack years smoked was associated with RA (odds ratio (OR) 13.54, 95% confidence interval (95% CI) 2.89 to 63.

ObjectiveTo investigate whether antidrug antibodies and/or drug non‐trough levels predict the long‐term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.MethodsA total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme‐linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non‐trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.ResultsAmong patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.ConclusionPharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months.

This study examined the spatial and temporal variability of throughflow in a shallow forest oil in terms of the controls exerted by topography, soil properties and the shape of the water table. Hillslope outflow was measured at nine troughs installed at a road cut, and hydraulic head was measured at 37 piezometers installed to the confining till surface at the base of the soil. At the lowest flows, the distribution of throughflow across the hillslope conformed reasonably to the distribution of upslope contributing area computed from the topography of the confining basal till layer. At higher flows, however, the distribution of throughflow shifted, partly as a result of changes in the orientation in flow tubes as the piezometric surface changed. At high flows, surface topography appeared to provide a reasonable proxy for the shape of the water table. Shunting of water through discrete macropores, however, can apparently overwhelm topographic controls on throughflow, at least for slope widths less than about 10 m. Effective hydraulic conductivities computed at the scale of the troughs varied over two orders of magnitude and displayed no consistent relationship with the thickness of the saturated layer. Estimates at the plot scale (c. 10 m hillslope width) were far less variable, and for higher flows displayed an approximately linear relationship with saturated zone thickness. Copyright © 2000 John Wiley & Sons, Ltd.

Objective. To determine whether the relationship between smoking and disease severity in women with rheumatoid arthritis (RA) is associated with polymorphism at the glutathione S-transferase (GST) M1 locus.Methods. Genotyping for GSTM1 was carried out using polymerase chain reaction methodology on 164 women with established RA. Smoking history was obtained on each patient. Radiographic damage was measured by the Larsen score, and functional outcome was assessed by the Health Assessment Questionnaire (HAQ). Data were analyzed by multiple regression analyses, with correction for age and disease duration.Results. Ever having smoked was associated with a worse radiographic and functional outcome than was never having smoked. Both past and current smoking were associated with increased disease severity. Stratification by GSTM1 status revealed that polymorphism at this locus affected the relationship between smoking and disease outcome measures. Patients who lacked the GSTM1 gene and had ever smoked had significantly higher Larsen and HAQ scores than did those who lacked the gene and had never smoked. Radiographic outcome in these patients was worse than that in patients who had the GSTM1 gene and who had smoked. The associations were not affected by correction for socioeconomic status. Rheumatoid factor (RF) production was found to be associated with smoking in only the GSTM1-null patients.Conclusion. Our data suggest that disease outcome in female RA patients with a history of smoking is significantly worse than in those who have never smoked. Smoking was associated with the most severe disease in patients who carried the GSTM1-null polymorphism. This association may be due in part to a relationship between the GSTM1 polymorphism and RF production in smokers.