Defect model for the mixed mobile ion effect revisited: an importance of deformation rates

The progress in understanding the behavior of glassy mixed ionic conductors within the concept of the defect model for the mixed mobile ion effect (V. Belostotsky, J. Non-Cryst. Solids 353 (2007) 1078) is reported. It is shown that in a mixed ionic conductor (e.g., mixed alkali glass) containing two or more types of dissimilar mobile ions of unequal size sufficient local strain arising from the size mismatch of a mobile ion entering a foreign site can not be, in principle, absorbed by the surrounding network-forming matrix without its damage. Primary site rearrangement occurs immediately, on the time scale close to that of the ion migration process, through the formation of intrinsic defects in the nearest glass network. Neither anelastic relaxation below glass transition temperature, Tg, nor viscoelastic or viscous behavior at or above Tg can be expected being observed in this case because the character of the stress relaxation in a wide temperature range is dictated above all by the deformation rates employed locally to the adjacent network-forming matrix. Since the ion migration occurs on the picosecond time scale, the primary rearrangement of the glass network adjacent to an ionic site occurs at rates orders of magnitude higher than those of the critical minimum values, so the matrix demonstrates brittle-elastic response to the arising strain even at temperatures well above Tg, which explains, among other things, why mixed alkali effect is observable in glass melts.Comment: 6 pages, 1 figure, 1 tabl

Deviations from the Expected Relationship Between Serum FGF23 and Other Markers in Children with CKD: a cross-sectional study.

BACKGROUND: High levels of fibroblast growth factor-23 (FGF23) are associated with mortality. In chronic kidney disease (CKD), FGF23 levels rise as renal function declines. We analyzed the contribution of laboratory values to the variance of FGF23 levels in relationship to a curve of expected FGF23 levels for a given GFR. METHODS: Following approval by the research ethics boards, we measured FGF23, CysC eGFR, creatinine, urea, albumin, calcium, phosphate, vitamin D metabolites, PTH, alkaline phosphatase, CRP, and venous gases in 141 pediatric CKD patients (45, 37, 32, 13 and 14 CKD stages I, II, III, IV, and V, respectively). Data were expressed as median (25th, 75th percentile). RESULTS: FGF23 correlated significantly with CysC, CysC eGFR, PTH, 1.25 (OH) CONCLUSIONS: Our data emphasize the importance of phosphate and 1.25 (OH

A cross-sectional study measuring vanadium and chromium levels in paediatric patients with CKD

Objectives Although many secondary effects of high levels of vanadium (V) and chromium (Cr) overlap with symptoms seen in paediatric patients with chronic kidney disease (CKD), their plasma V and Cr levels are understudied. Design Ancillary cross-sectional study to a prospective, longitudinal, randomised controlled trial. Setting Children\u27s Hospital of Western Ontario, London Health Sciences Centre, London, Ontario, Canada. Participants 36 children and adolescents 4-18 years of age with CKD. Interventions 1-6 trace element measurements per patient. Cystatin C (CysC) estimated glomerular filtration rate (eGFR) was calculated using the Filler formula. Plasma V and Cr levels were measured using high-resolution sector field inductively coupled mass spectrometry. Anthropomorphic data and blood parameters were collected from our electronic chart programme. Water Cr and V data were obtained from the Ontario Water (Stream) Quality Monitoring Network. Primary and secondary outcome measures Primary outcomes: Plasma Cr and V. Secondary outcomes: Age, season, CysC, CysC eGFR, and Cr and V levels in environmental water. Results The median (IQR) eGFR was 51 mL/min/1.73 m 2 (35, 75). The median V level was 0.12 μg/L (0.09, 0.18), which was significantly greater than the 97.5th percentile of the reference interval of 0.088 μg/L; 32 patients had at least one set of V levels above the published reference interval. The median Cr level was 0.43 μg/L (0.36, 0.54), which was also significantly greater than the established reference interval; 34 had at least one set of Cr levels above the published reference interval. V and Cr levels were moderately correlated. Only some patients had high environmental exposure. Conclusions Our study suggests that paediatric patients with CKD have elevated plasma levels of V and Cr. This may be the result of both environmental exposure and a low eGFR. It may be necessary to monitor V and Cr levels in patients with an eGFR \u3c30 mL/min/1.73 m2

PHYOX2: a pivotal randomized study of nedosiran in primary hyperoxaluria type 1 or 2

Nedosiran is an investigational RNA interference agent designed to inhibit expression of hepatic lactate dehydrogenase, the enzyme thought responsible for the terminal step of oxalate synthesis. Oxalate overproduction is the hallmark of all genetic subtypes of primary hyperoxaluria (PH). In this double-blind, placebo-controlled study, we randomly assigned (2:1) 35 participants with PH1 (n = 29) or PH2 (n = 6) with eGFR ≥30 mL/min/1.73 m2 to subcutaneous nedosiran or placebo once monthly for 6 months. The area under the curve (AUC) of percent reduction from baseline in 24-hour urinary oxalate (Uox) excretion (primary endpoint), between day 90-180, was significantly greater with nedosiran vs placebo (least squares mean [SE], +3507 [788] vs -1664 [1190], respectively; difference, 5172; 95% CI 2929-7414; P < 0.001). A greater proportion of participants receiving nedosiran vs placebo achieved normal or near-normal (<0.60 mmol/24 hours; <1.3 × ULN) Uox excretion on ≥2 consecutive visits starting at day 90 (50% vs 0; P = 0.002); this effect was mirrored in the nedosiran-treated PH1 subgroup (64.7% vs 0; P < 0.001). The PH1 subgroup maintained a sustained Uox reduction while on nedosiran, whereas no consistent effect was seen in the PH2 subgroup. Nedosiran-treated participants with PH1 also showed a significant reduction in plasma oxalate versus placebo (P = 0.017). Nedosiran was generally safe and well tolerated. In the nedosiran arm, the incidence of injection-site reactions was 9% (all mild and self-limiting). In conclusion, participants with PH1 receiving nedosiran had clinically meaningful reductions in Uox, the mediator of kidney damage in PH

Defect model for the mixed mobile ion effect

This paper presents a new defect model for the mixed mobile ion effect. The essential physical concept involved is that simultaneous migration of two unlike mobile ions in mixed ionic glass is accompanied by expansion or contraction of the guest-occupied sites with distortion of surrounding glass matrix; in many cases, an intensity of the local stresses in glass matrix surrounding ionic sites occupied by foreign ions is much greater than, or at least comparable to the glass network binding energy. Hence, when the stress exceeds the breaking threshold, relaxation occurs almost immediately via the rupture of the bonds in the nearest glass matrix with generation of pairs of intrinsic structural defects. The specificity of the mechanism of defect generation leads to the clustering of negatively charged defects, so that rearranged sites act as high energy anion traps in glass matrix. This results in the immobilization of almost all minority mobile species and part of majority mobile species, so mixed mobile ion glass behaves as single mobile ion glass of much lower concentration of charge carriers. Generation of defects leads also to the depolymerization of glass network, which in turn results in the reduction of the glass viscosity and Tg as well as in the compaction of glass structure (thermometer effect). The magnitude of the mixed mobile ion effect is defined by the size mismatch of unlike mobile ions, their total and relative concentrations, the binding energy of the glass-forming network, and temperature. Although the proposed model is based upon the exploration of alkali silicate glass-forming system, the approach developed here can be easily adopted to other mixed ionic systems such as crystalline and even liquid ionic conductors.Comment: 33 pages, 2 figure

Suture line reinforcement using suction-assisted bioglue application during surgery for acute aortic dissection

Bioglue has been widely and variously applied in treating acute aortic dissection according to the pathological process and surgeon’s preference. This publication outlines a new hemostatic technique using suction-assisted bioglue application for aortic suture line reinforcement during surgery on acute aortic dissection. Twenty consecutive patients were treated in our center for acute aortic dissection using this technique. There were no bleeding complications during surgery and there were no re-explorations or early deaths as a result of bleeding. Average daily chest tube drainage was 582"150 mlyday, with the duration of drainage of 2"0.9 days. In conclusion, this new hemostatic technique is simple to use and demonstrates excellent, immediate and early postoperative results

Direct circular repair for left ventricle aneurysm

Most patients with large left ventricular aneurysm undergo either linear resection of the dyskinetic area or endoventricular patch repair. Both techniques have numerous beneficial effects, but also several adverse ones. In order to avoid these imperfections, direct circular repair (OCR) was created