► Ordinary Portland cement (OPC) has high embodied energy arising from manufacturing. ► Carbon footprint of geopolymers, an alternative binder to OPC, was estimated. ► CO2-e of geopolymer concrete is ...9% less than OPC: unlike past studies (26–80%). ► Key factors for high CO2-e of geopolymers: energy expended on alkali activators. ► Geopolymers need high temperature curing for strength: a further source of CO2-e
Concrete for construction has traditionally been based on an Ordinary Portland Cement (OPC) binder. Geopolymers, an alternative binder based on fly ash (a fine waste collected from the emissions liberated by coal burning power stations) that is activated by an alkaline activator, have potential to lower the significant carbon footprint of OPC concrete. This paper presents the results of comprehensive carbon footprint estimates for both geopolymer and OPC concrete, including energy expending activities associated with mining and transport of raw materials, manufacturing and concrete construction. Previous studies have shown a wide variation of reported emission estimates: the results of this study are benchmarked with data from those studies.
Cementitious composites incorporating well-dispersed carbon nanotubes (CNTs) have demonstrated significant mechanical performance enhancements, however, there has only been limited investigation into ...the nanocomposite microstructure and pore structure. In this study, the effects of (i) CNT dispersion with and without the assistance of a dispersant, (ii) CNT dose at 0.05–0.25 wt% of cement, and (iii) CNT dispersion quality upon the composite microstructure after 7- and 28-days' hydration were investigated using quantitative image analysis of backscattered electron microscopy and X-ray computed microtomographic datasets. Results show that dispersed CNTs promoted the formation of low- and higher-density hydration products within 7 days of hydration and reduced the pore size distribution by 28 days, although 3D X-ray results showed some large CNT agglomerations formed in the nanocomposite. Further, poorly-dispersed CNTs increased the 28-day pore size distribution, but had a beneficial effect, similar to well-dispersed CNTs, upon the microstructural composition of the hydrated phases.
•The geopolymeric recycled concrete (GRC) is a new constructional material.•The structural properties of GRCFST columns were firstly tested and analysed.•The influence of RCA replacement ratio to ...GRCFST and RACFST columns were discussed.•A theoretical simulation model of GRCFST columns under axial loading was proposed.
Geopolymeric recycled concrete (GRC) is a new construction material which takes environmental sustainability into account. In this paper, an experimental study was carried on 12 concrete filled steel tubular columns under axial loading, in order to fill a knowledge gap on the engineering and structural properties of GRC filled steel tube (GRCFST). Two section sizes of square hollow sections filled with GRC and recycled aggregate concrete (RAC) respectively, with different recycled aggregate (RA) replacement ratios of 0%, 50% and 100%, were used in the experiments. The test results indicated that the ultimate strength was reduced when adding more RAs in the columns, while the peak strain increased. The ductility of the columns was improved by increasing the RA replacement ratio. Overall, the influence of RA on the strength and ductility of GRCFST columns is greater than that of RAC filled steel tubular (RACFST) columns. The assumed theoretical model for predicting load versus deformation relation of GRCFST columns under axial loading was examined, and a revised theoretical model proposed. The results of the new model show good correlation with the experimental results.
In 2007, the International Knockout Mouse Consortium (IKMC) made the ambitious promise to generate mutations in virtually every protein-coding gene of the mouse genome in a concerted worldwide ...action. Now, 5 years later, the IKMC members have developed high-throughput gene trapping and, in particular, gene-targeting pipelines and generated more than 17,400 mutant murine embryonic stem (ES) cell clones and more than 1,700 mutant mouse strains, most of them conditional. A common IKMC web portal (www.knockoutmouse.org) has been established, allowing easy access to this unparalleled biological resource. The IKMC materials considerably enhance functional gene annotation of the mammalian genome and will have a major impact on future biomedical research.
The addition of carbon nanotubes (CNTs) to cementitious nanocomposites have demonstrated significant mechanical performance enhancements, however, there has been only limited research of the effects ...of CNTs upon hydration kinetics. Isothermal calorimetry was used to study in detail (i) CNT dispersion with and without a polycarboxylate-based superplasticiser, (ii) CNT dose at 0.05–0.25 wt% of cement, and (iii) CNT dispersion quality upon cement hydration. Results show a 45-min acceleration and 17% increase in principal hydration peak at a CNT dose of 0.1 wt% without superplasticiser, indicating enhanced nucleation with CNTs. Varying CNT dose, delaying effects of the superplasticiser dominated, although there was an increase in hydration peak of 17% with 0.25 wt% CNTs. Finally, it was found that CNT content, not ‘good’ or ‘poor’ dispersion quality, had a greater effect upon the overall nanocomposite hydration and microstructural development, facilitating further optimisation of CNT dispersion and microstructural development for CNT-cement nanocomposites.
Aims
Recombinant factor IX Fc fusion protein (rFIX‐Fc) is an extended half‐life factor concentrate administered to haemophilia B patients. So far, a population pharmacokinetic (PK) model has only ...been published for patients aged ≥12 years. The aim was to externally evaluate the predictive performance of the published rFIX‐Fc population PK model for patients of all ages and develop a model that describes rFIX‐Fc PK using real‐world data.
Methods
We collected prospective and retrospective data from patients with haemophilia B treated with rFIX‐Fc and included in the OPTI‐CLOT TARGET study (NTR7523) or United Kindom (UK)‐EHL Outcomes Registry (NCT02938156). Predictive performance was assessed by comparing predicted with observed FIX activity levels. A new population PK model was constructed using nonlinear mixed‐effects modelling.
Results
Real‐world data were obtained from 37 patients (median age: 16 years, range 2–71) of whom 14 were aged <12 years. Observed FIX activity levels were significantly higher than levels predicted using the published model, with a median prediction error of −48.8%. The new model showed a lower median prediction error (3.4%) and better described rFIX‐Fc PK, especially for children aged <12 years. In the new model, an increase in age was correlated with a decrease in clearance (P < .01).
Conclusions
The published population PK model significantly underpredicted FIX activity levels. The new model better describes rFIX‐Fc PK, especially for children aged <12 years. This study underlines the necessity to strive for representative population PK models, thereby avoiding extrapolation outside the studied population.
Cementitious binders consisting of ground granulated iron slag and an alkaline activator (alkali activated slag) have considerable environmental benefits when used as an alternative to conventional ...100% ordinary portland cement binders. The objective of this paper is to demonstrate the effect of pore cross section shape on unsaturated flow and to contrast the laboratory and numerical predictions of alkali activated slag binders and 100% portland cement binders. Convection-based uptake of water within capillary pores is modeled using pore size distribution data; however, most existing predictive models are based on the assumption of a circular cross section. This model allows for changeable capillary cross-sectional shape by employing ellipses ranging in shape from circular to slit. By applying a shape factor that accounts for departure from circularity of the pore cross section, the prediction model shows reasonable agreement with water sorptivity test data. As well as different binder types, the predictive model is assessed over a range of concrete ages and curing conditions.
Turoctocog alfa pegol (N8-GP) is a novel glycoPEGylated extended half-life recombinant factor VIII (FVIII) product developed for prophylaxis and treatment of bleeds in patients with haemophilia A, to ...enable higher activity levels with less frequent injections compared with standard FVIII products. This phase III (NCT01480180), multinational, open-label, non-randomised trial evaluated the safety and clinical efficacy of N8-GP when administered for treatment of bleeds and for prophylaxis, in previously treated patients aged ≥12 years with severe haemophilia A. Patients were allocated to receive N8-GP for prophylaxis or on-demand treatment for up to 1.8 years. Patients on prophylaxis were administered one dose of 50 IU/kg of N8-GP every fourth day. Bleeds were treated with doses of 20-75 IU/kg. Total exposure to N8-GP in the trial was 14,114 exposure days (159 patient-years). For the prophylaxis arm (n=175), the median annualised bleeding rate (ABR) was 1.33 (interquartile range, 0.00-4.61), the mean ABR was 3.70 (95 % confidence interval 2.94-4.66) and 70 (40 %) patients had no bleeds during the trial. Across treatment arms, 83.6 % of bleeds resolved with one injection and 95.5 % with up to two injections. N8-GP had a favourable safety profile and was well tolerated. The frequency and types of adverse events reported were as expected in this population. One patient developed inhibitory antibodies against FVIII (≥0.6 Bethesda units BU) after 93 N8-GP exposure days. No clinically significant safety concerns were identified and N8-GP was effective for prophylaxis and treatment of bleeds in previously treated patients.
The mechanisms underlying the anti-tumorigenic properties of cyclooxygenase inhibitors are not well understood. One novel hypothesis is alterations in gene expression. To test this hypothesis ...sulindac sulfide, which is used to treat familial adenomatous polyposis, was selected to detect gene modulation in human colorectal cells at physiological concentrations with microarray analysis. At micromolar concentrations, sulindac sulfide stimulated apoptosis and inhibited the growth of colorectal cancer cells on soft agar. Sulindac sulfide (10 microm) altered the expression of 65 genes in SW-480 colorectal cancer cells, which express cyclooxygenase-1 but little cyclooxygenase-2. A more detailed study of 11 genes revealed that their expression was altered in a time- and dose-dependent manner as measured by real-time RT-PCR. Northern analysis confirmed the expression of 9 of these genes, and Western analysis supported the conclusion that sulindac sulfide altered the expression of these proteins. Cyclooxygenase-deficient HCT-116 cells were more responsive to sulindac sulfide-induced gene expression than SW-480 cells. However, this response was diminished in HCT-116 cells overexpressing cyclooxygenase-1 compared with normal HCT-116 cells suggesting the presence of cyclooxygenase attenuates this response. However, prostaglandin E2, the main product of cyclooxygenase, only suppressed the sulindac sulfide-induced expression of two genes, with little known biological function while it modulated the expression of two more. The most likely explanation for this finding is the metabolism of sulindac sulfide to inactive metabolites by the peroxidase activity of cyclooxygenase. In conclusion, this is the first report showing sulindac sulfide, independent of cyclooxygenase, altered the expression of several genes possibly linked to its anti-tumorigenic and pro-apoptotic activity.
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