Long-term safety and efficacy of daclizumab beta in relapsing-remitting multiple sclerosis : 6-year results from the SELECTED open-label extension study

Objective: SELECTED, an open-label extension study, evaluated daclizumab beta treatment for up to 6 years in participants with relapsing multiple sclerosis who completed the randomized SELECT/SELECTION studies. We report final results of SELECTED. Methods: Eligible participants who completed 1-2 years of daclizumab beta treatment in SELECT/SELECTION received daclizumab beta 150 mg subcutaneously every 4 weeks for up to 6 years in SELECTED. Safety assessments were evaluated for the SELECTED treatment period; efficacy data were evaluated from first dose of daclizumab beta in SELECT/SELECTION. Results: Ninety percent (410/455) of participants who completed treatment in SELECTION enrolled in SELECTED. Within SELECTED, 69% of participants received daclizumab beta for > 3 years, 39% for > 4 years, and 9% for > 5 years; 87% of participants experienced an adverse event and 26% a serious adverse event (excluding multiple sclerosis relapse). No deaths occurred. Overall, hepatic events were reported in 25% of participants; serious hepatic events in 2%. There were no confirmed cases of immune-mediated encephalitis. Based on weeks from the first daclizumab beta dose in SELECT/SELECTION, adjusted annualized relapse rate (95% confidence interval) for weeks 0-24 was 0.21 (0.16-0.29) and remained low on continued treatment. Overall incidence of 24-week confirmed disability progression was 17.4%. Mean numbers of new/newly enlarging T2 hyperintense lesions remained low; percentage change in whole brain volume decreased over time. Conclusions: The effects of daclizumab beta on clinical and radiologic outcomes were sustained for up to ~ 8 years of treatment. No new safety concerns were identified in SELECTED. Trial registration: Clinicaltrials.gov NCT01051349; first registered on January 15, 2010

Applications and Benefits of Groundwater Recirculation for Electron Donor Delivery and pH-Adjustment During Enhanced Anaerobic Dechlorination

The enhanced anaerobic dechlorination (EAD) process is used for in-situ degradation of various chlorinated organic compounds. Electron donors must be delivered to the targeted treatment area and anaerobic subsurface conditions must be maintained for a period of time to degrade both the soluble and adsorbed contaminants. The most common EAD approaches use batch addition of either small volumes of high strength electron donors such as emulsified oil or solid phase hydrogen release compounds, or large volumes of diluted dissolved donors such as molasses or other carbohydrates. Both approaches typically rely on groundwater transport to carry the additives across the entire EAD targeted area. However, groundwater flow is generally laminar, predominantly horizontal, and soluble electron donors added in batch mode can only be adequately distributed in the subsurface with either high-density point installation or large volume addition, or some balanced combination of both. In addition, both batch approaches often require relatively high groundwater flow velocity to distribute the additives down gradient in reasonable time frames and before the electron donor is fully degraded. These difficult requirements for proper batch donor addition often cause dechlorination to stall midway through the process or have a limited treatment area due to a lack of donor distribution. Proper maintenance of neutral pH is a second important requirement for EAD, and is often not controlled adequately during batch addition approaches. Dehalococcoides, the organisms responsible for breakdown of cis-dichloroethene to vinyl chloride and ethene, are not active at a pH below 6.0-6.3. Batch addition methods provide little recourse to adjust pH without excessively raising pH in the area immediately surrounding the injection location. Continuous groundwater extraction and recirculation approaches to electron donor and pH buffer addition, however, address these issues and can provide faster and more thorough remediation than the batch processes. Groundwater recirculation provides greater donor distribution through increased injection volumes and hydraulic gradients. Alkalinity can be added as needed to counter decreases in pH and conducted in the form of a large scale titration. Bioaugmentation cultures, when needed, can also be added and quickly dispersed throughout the area. Groundwater recirculation systems for EAD typically divide the treatment area into sections and recirculate and amend groundwater as needed within each section depending on the size of the target area and the aquifer conditions. The proper design and implementation of groundwater recirculation for EAD will be presented and concepts reviewed

Confinement Model for Axially Loaded Concrete Confined by Circular Fiber-Reinforced Polymer Tubes

An analytical model is introduced in this paper to predict the behavior of axially loaded circular concrete columns confined by fiber-reinforced polymer (FRP) tubes. The model is an extension to the confinement model introduced by Mander et al. for concrete confined by steel reinforcement. The model is based on equilibrium, compatibility conditions, and the biaxial strength failure criteria of FRP tubes. It can be used to predict the behavior of prefabricated FRP tubes totally filled or partially filled with concrete, as well as concrete wrapped with FRP sheets. The model can account for the case of axially loaded concrete core only as well as the composite section of the concrete core and FRP tube. The model is verified by experimental results reported by the authors and other researchers. A parametric study is presented to examine the effect of stiffness of the FRP tube, the effect of loading the FRP tube axially, and the effect of presence of inner hole inside the concrete core. The study showed that increasing the central hole size reduces the confinement effect, increasing the stiffness of the tube improves the confinement, and axial loading of the FRP tube significantly reduces the confinement

Rectangular Filament-Wound Glass Fiber Reinforced Polymer Tubes Filled with Concrete under Flexural and Axial Loading: Experimental Investigation

This paper presents results of an experimental investigation on three beams and five short columns, consisting of glass fiber reinforced polymer concrete-filled rectangular filament-wound tubes (CFRFTs). The tubes included fibers oriented at ±45° and 90° with respect to the longitudinal axis. Additional longitudinal fibers [0°] were provided in flanges for flexural rigidity. Beams included totally filled tubes and a tube partially filled with concrete, which had a central hole for reducing deadweight. The effect of reinforcement ratio was examined by using tubes of two different sizes. Flexural behavior of CFRFT was compared to concrete-filled rectangular steel tubes (CFRSTs) of similar reinforcement ratios. Short columns were tested under eccentricity ratios (e∕h) of 0, 0.09, 0.18, and 0.24, where h is the section depth. Transverse strains were measured around the perimeter of concentrically loaded column to evaluate confinement effect. The study showed that CFRFT is a feasible system that could offer similar flexural strength to CFRST. The tube laminate structure and its progressive failure contribute to the slightly nonlinear behavior of beams. The CFRFT beam with inner hole had an overall strength-to-weight ratio, 77% higher than the totally filled beam, but failed in compression. Bulging of CFRFT columns has limited their confinement effectiveness

Experimental and Analytical Modeling of Concrete-Filled Fiber-Reinforced Polymer Tubes Subjected to Combined Bending and Axial Loads

This paper presents test results of an experimental program, and proposes an analytical model to describe the behavior of concrete-filled, fiber-reinforced polymer (FRP) tubes subjected to combined axial compression loads and bending moments. The experimental program included 10 specimens subjected to eccentric axial loads, 2 specimens tested under concentric axial loads, and 2 specimens tested in bending. Glass FRP tubes with 2 different laminate structures were considered, and axial load/bending moment interaction curves are given. An analytical model is presented that accounts for variable confinement of concrete as a result of the gradual change of the biaxial state of stresses developed in the tube as the eccentricity changes. A parametric study was conducted to evaluate effects of diameter-to-thickness ratio and laminate structure of the tube, including different fiber proportions in the axial and hoop directions. The study evaluated the confinement as affected by the eccentricity of the applied axial load as well as the influence of the FRP laminate structure. Findings indicate that the interaction curves are significantly affected by both the laminate structure and diameter-to-thickness ratios of the tubes

Concrete-Filled Steel Tubes Subjected to Axial Compression and Lateral Cyclic Loads

This paper presents an experimental work and analytical modeling for concrete-filled steel tubes (CFSTs) subjected to concentric axial compression and combined axial compression and lateral cyclic loading. The objective of the study is to evaluate the strength and ductility of CFST short columns and beam-column members under different bond and end loading conditions. Both bonded and unbonded specimens were tested, including application of the axial load to the composite steel-concrete section and to the concrete core only. Research findings indicate that the bond and end loading conditions did not affect the flexural strength of beam-column members significantly. On the other hand, the axial strengths of the unbonded short columns were slightly increased, compared to those of the bonded ones, while the stiffness of the unbonded specimens was slightly reduced. Test results were compared with the available design specifications, which were found to be conservative. The paper also presents an analytical model capable of predicting the flexural and axial load strength of CFST members. Experimental results were found to be in good agreement with the predicted values