Icelandic Transport Authority

Adenine phosphoribosyltransferase (APRT) deficiency is a rare, autosomal recessive disorder characterized by urinary excretion of the poorly soluble 2,8-dihydroxyadenine (DHA), leading to kidney stones and chronic kidney disease. Treatment with the xanthine oxidoreductase (XOR) inhibitors allopurinol and febuxostat reduces DHA production. DHA and adenine were measured in 122 paired plasma and urine samples from 26 individuals with confirmed APRT deficiency, using ultra-performance liquid chromatography-tandem mass spectrometry assays. The relationship between plasma DHA and adenine concentrations, urine DHA-to-creatinine (DHA/Cr) and adenine-to-creatinine (adenine/Cr) ratios, and age and estimated glomerular filtration rate (eGFR) was evaluatedin a subset of 87 paired plasma and urine samples from 23 individuals using Spearman's rank correlation. Allopurinol and febuxostat treatment reduced plasma DHA, with the median (range) concentration decreasing from 249 (123-1315) ng/mL in untreated individuals to below the limit of detection in those receiving higher doses. Plasma adenine increased during XOR inhibitor treatment. In untreated individuals, a strong negative correlation was observed between plasma DHA and eGFR (rs = -0.74, p < 0.0001). Plasma DHA correlated with urine DHA/Cr ratio in individuals treated with allopurinol or febuxostat (rs = 0.65, p < 0.0001), while no significant correlation was observed in untreated individuals (rs = -0.26, p = 0.14). Treatment with XOR inhibitors effectively reduces the plasma concentration and urinary excretion of DHA. The strong correlation between plasma DHA and eGFR, combined with the lack of correlation between plasma DHA and urine DHA/Cr ratio in untreated individuals, suggests that plasma DHA may be a more reliable marker of systemic DHA burden.

Abstract Background and Aims Adenine phosphoribosyltransferase (APRT) deficiency is a rare disorder of purine metabolism, characterized by urinary excretion of the poorly soluble 2,8-dihydroxyadenine (DHA), leading to nephrolithiasis and chronic kidney disease (CKD). Treatment with xanthine oxidoreductase (XOR) inhibitor, allopurinol or febuxostat, reduces DHA excretion and slows or halts CKD progression. The aim of the study was to optimize and validate an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS)-based assay for simultaneous quantification of DHA, adenine, allopurinol, oxypurinol and febuxostat in human plasma, for monitoring of pharmacotherapy in patients with APRT deficiency. Method The UPLC-MS/MS-based assay was optimized employing the chemometric approach design of experiments, using the software Modde Pro 13 (Sartorius, Umeå, Sweden). The assay was validated and used for absolute quantification of DHA, adenine, allopurinol, oxypurinol and febuxostat in plasma samples from both untreated and treated APRTd patients and healthy controls. Results Accuracy and precision were within ±15% for all analytes, and the analytes were stable in plasma for 12 months at −80°C. The median (range) concentration of DHA in plasma samples from six APRT deficiency patients was 204.0 (187.2–315.8) ng/mL when they were untreated and 69.2 (below the limit of quantification [BLQ]–131.6) ng/mL when treated with allopurinol (400 mg/day), and BLQ when febuxostat (80 mg/day) was the therapeutic agent. The median (range) plasma adenine concentration was 238.1 (218–502) ng/mL in the untreated patients, and 561.1 (418–2104) and 856.0 (726–1711) ng/mL in those on treatment with allopurinol and febuxostat, respectively. DHA was not detected in plasma samples from healthy controls. The median (range) plasma concentration of allopurinol, oxypurinol and febuxostat in patients receiving XOR inhibitor therapy was 1657 (BLQ-3266) ng/mL, 8102 (4778–34906) ng/mL and 109 (BLQ-1657) ng/mL, respectively. Conclusion The UPLC-MS/MS-based assay provides accurate and precise quantification of DHA, adenine, allopurinol, oxypurinol and febuxostat in human plasma. Measurement of plasma DHA is being implemented as a diagnostic test for APRT deficiency and the full assay for monitoring of XOR inhibitor treatment in patients with the disorder.

To eliminate climate gas emissions from aluminum electrolysis, modifying a cryolite-based electrolyte partly replacing Na with K reduces liquidus, allowing a process temperature of 800°C. This enables the use of various metallic alloys for oxygen-evolving inert anode technology. This alternative process requires a higher energy efficiency to compensate for an increased reaction voltage, which highlights the importance of evaluating the kinetics and overpotential on oxygen-evolving anodes. This study evaluates anodic overpotentials using steady-state polarization on platinum and three Ni-Fe-Cu-based alloy compositions in a KF-NaF-AlF3-Al2O3(sat.) electrolyte at 800°C. The polarization curve on the platinum anode reveals two linear Tafel regions, while Ni-Fe-Cu anodes exhibit a single Tafel region. Notably, Ni-Fe-Cu anodes treated with high-temperature air oxidation to develop a pre-formed oxide layer exhibit better electrocatalytic activity than untreated anodes of corresponding composition. The kinetic equations, based on a theoretical model for the proposed mechanism of the oxygen evolution reaction, are derived and utilized to simulate overpotential and current, taking into account surface coverage. This model accurately predicts the two experimentally observed Tafel regions on the platinum anode, indicating a two-step charge transfer-controlled mechanism. We illustrate that multiple Tafel slopes can be attributed to the potential-dependent surface coverage of an adsorbate and can be correlated with the particular rate-determining step.

Porosity-related characteristics of biomedical three-dimensional (3D) scaffolds govern mass transport properties which, in turn, dictate the success of implants in vivo. The accurate determination of permeability and microstructural properties in highly-porous materials – like implantable bone scaffolds – still represents a challenge due to the complex architecture of struts and voids in 3D. In the present study, the complete set of mass transport properties of bioactive glass scaffolds produced by vat photopolymerization was reliably determined by combining experimental assessment, advanced imaging and mathematical modelling based on the Ergun-Wu approach. Specifically, the intrinsic permeability of the scaffolds was experimentally estimated by acoustic measurements, and the pore diameter was calculated through implementing an innovative fractal model. An accurate statistical analysis of the results provided evidence of the robustness of the overall strategy, which can be potentially extended and adapted to the analysis of other types of sintered porous (bio)materials.

This study focuses on the finite element simulation and micromechanical characterization of bioactive glass-ceramic scaffolds using Computed micro Tomography (μ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\upmu$$\\end{document}CT) imaging. The main purpose of this work is to quantify the effect of sintering temperature on the morphometry and mechanical performance of the scaffolds. In particular, the scaffolds were produced using a novel bioactive glass material (47.5B) through foam replication, applying six different sintering temperatures. Through μ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\upmu$$\\end{document}CT imaging, detailed three-dimensional images of the scaffold’s internal structure are obtained, enabling the extraction of important geometric features and how these features change with sintering temperature. A finite element model is then developed based on the μ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\upmu$$\\end{document}CT images to simulate the fracture process under uniaxial compression loading. The model incorporates scaffold heterogeneity and material properties—also depending on sintering temperature—to capture the mechanical response, including crack initiation, propagation, and failure. Scaffolds sintered at temperatures equal to or higher than 700 ∘\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{\\circ }$$\\end{document}C exhibit two-scale porosity, with micro and macro pores. Finite element analyses revealed that the dual porosity significantly affects fracture mechanisms, as micro-pores attract cracks and weaken strength. Interestingly, scaffolds sintered at high temperatures, the overall strength of which is higher due to greater intrinsic strength, showed lower normalized strength compared to low-temperature scaffolds. By using a combined strategy of finite element simulation and μ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\upmu$$\\end{document}CT-based characterization, bioactive glass-ceramic scaffolds can be optimized for bone tissue engineering applications by learning more about their micromechanical characteristics and fracture response.

(Appeared originally in Journal of Affective Disorders 2019; 259:266-270).

Armourstone are the most important construction material for berm breakwaters as well as for other rubble mound structures. The paper discusses several issues regarding the preparation for and design of armourstone projects. Firstly, what sizes of armourstone are available for the design? It is important to know what sizes can be quarried from nearby quarry or quarries and in what yield. Secondly, the choice of grading for an armourstone class, standard grading or non-standard, and the choice of median mass within the chosen grading. These factors can influence the cost of the structure greatly. Thirdly, quarrying for large armourstone is a discipline that not many quarry operators master. It is easy to blast the rock into small fragments but more difficult just to loosen up the rock to maximise the sizes of armourstone. Fourthly, placement of primary armour is important to achieve stable interlocked armour layer. The last issue addressed in this paper is the definition of rock surface and survey methods. Contracts based on volume need a definition of the rock surface.

Professionals who embrace evidence-based practice (EBP) continually search for research evidence, appraise, and apply it, while interacting with each client in his/her situation. This dynamic learning process takes a substantial commitment from professionals and requires a positive attitude toward EBP. The main objective of this research was to explore the following: 1) distinct dimensions of attitudes toward adoption of EBP among physical therapists and social workers and 2) the relationship between these dimensions of attitudes and selected background characteristics of the compared professions. Cross-sectional web-based surveys were conducted in 2012 and 2013 on a population-based sample from the Icelandic Physical Therapy Association and the Icelandic Association of Social Workers. The participants were 214 physical therapists (76.3% women) and 163 social workers (92.2% women). The Evidence-Based Practice Attitude Scale (EBPAS) and its four subscales were used to survey dimensions of attitudes toward EBP. Scores on the total EBPAS range from zero to five, with a higher score indicating a more positive attitude toward EBPs. Linear regression was used to explore the relationship between the EBPAS scales and selected background variables. The overall response rate was 39%. Both professions generally held positive attitudes toward adoption of EBP, with an average EBPAS total score of 3.06 (SD = 0.46). The professionals' background characteristics were independently related to at least one dimension of attitudes toward EBP. More positive attitudes were associated with being a physical therapist, a woman, in a younger age group, having a graduate degree, working with individual clients, and having at least five same-profession coworkers. The results may be useful to design continuing education focusing on EBP. Such inventions should be targeted to professional attitudes, background, and other contextual factors.