Once-Daily Tacrolimus Extended-Release Formulation: 1 Year after Conversion in Stable Pediatric Kidney Transplant Recipients

It is speculated that a once-daily dosage of immunosuppression can increase adherence and thereby graft survival. Until now, there have been no studies on once-daily use of Tacrolimus extended-release formulation (TAC-ER) in children following pediatric kidney transplantation. In 11 stable pediatric kidney recipients >10 years, efficacy, safety, and tolerability of a switch to TAC-ER were observed over one year. Adherence was determined by use of the BAASIS-Scale Interview and comparison of individual variability of Tacrolimus trough levels. Over the observation period, two acute rejections were observed in one girl with nonadherence and repeated Tacrolimus trough levels of 0 ng/m. Beside this, there were no acute rejections in this trial. TAC dose was increased in 3/11 patients and decreased in 2/11 patients within the course of the study. Six patients did not require a dose adjustment. All but one patient had a maximum of 1 dose change during therapy. Mean Tacrolimus dose, trough levels, and Glomerular filtration rates were also stable. Adherence, as measured by BAASIS-Scale Interview and coefficient of variation of Tacrolimus trough levels, was good at all times. It is concluded that conversion to Tac-ER is safe in low-risk children following pediatric kidney transplantation

Tribological Effects of Metalworking Fluids in Cutting Processes

An understanding of the proper application of metalworking fluids (MWFs) is necessary for their implementation in efficient production processes. In addition, the knowledge of the process-related aspect of chip transport and the macroscopic cooling effect, the characteristics and properties of lubricant film formation, and the cooling conditions in the secondary shear zone on the chip surface, i.e., in the direct vicinity of the material separation, represent a combined fundamental scientific issue within production engineering. The aim is to transfer methods from the field of tribology of machine elements, which have already led to a considerable gain in knowledge in this discipline, to machining and to couple them with already established approaches to machining. In the case of roller bearings, the contact pressure is in the range as the pressure in the contact zone between the cutting insert and chip. Due to this, established methods might be transferred to the cutting process. In addition to classical pin-on-plate and pin-on-ring friction investigations, film thickness measurements were carried out and compared to machining tests. The coefficient of friction determined in the planing test rig is 0.48 for dry cutting, while it is 0.47 for wet cutting. These two values are much larger than the CoF with MWFs measured on the two tribometers. It is shown that the boundary friction of MWF especially influences the machining process. Thus, additives in MWF might have a high significance in machining

Allocation of body reserves during winter in eider Somateria mollissima as preparation for spring migration and reproduction

Capital breeders, such as the eider duck Somateria mollissima, accumulate resources before the start of breeding. Eiders preferentially feed on blue mussels Mytilus edulis to build up body condition during winter. We explored how body condition and gizzard mass of wintering eiders relate to mussel quality and quantity, winter climate and body condition of females at the breeding grounds. Body condition during winter (defined as scaled body mass index) of eiders increased during winter and the magnitude of the effect depended on age and mussel quality. Gizzard mass of eiders increased during winter with effects of mussel quality, mussel stocks and sex. Body condition in winter of adult females increased from the first half of January to the second half of February on average by 1.5%, equal to c. 96 g. During the same period gizzard mass of adult females increased by 12.2%, i.e., a nearly ten-fold increase compared to that observed in body condition in winter. Body condition of females at the breeding grounds in Finland (defined as body condition at hatching) was significantly positively correlated with gizzard mass in winter, but not significantly correlated with body condition in winter. Thus, eiders allocate body reserves to increase gizzard mass but less so to increase body condition in winter. This can be considered an adaptive migratory strategy of these eiders, whereby large winter (pre-migratory) gizzards increase food processing capacity, making it possible for eiders to arrive at the breeding grounds with superior body condition and a high reproductive potential.Peer reviewe

Ветроэнергетика

A new aluminum alloy (AlSi5Mg0.5Cu0.3Ag) for semisolid die-casting applications was designed, starting from computational thermodynamics calculations by Computherm Database. The goal was to obtain a combination of good castability and proper concentration of hardening elements for strengthening precipitation treatment. The predicted thixotropic properties were verified by measuring the microstructural conventional parameters, such as globule size and shape factor, and the solidification range, by means of differential scanning calorimetry. To complete the characterization of this new alloy and to evaluate its applicability in industrial production, the shear rate and time-dependent flow behavior of the alloy in the semisolid state was studied in a Searle-type rheometer. A future aim of the present research is to try to use theology testing as the tool to optimize the chemical composition, in order to design an alloy characterized by good mechanical performances and easy processability. Considering the strong influence of the solid fraction content on semisolid alloy viscosity, the theology tests were interrupted after a certain time and the alloy was deeply freezed using vaporized liquid nitrogen, in order to fix the microstructure and verify the correctness of the thermodynamic simulation

Comparing cystatin C and creatinine in the diagnosis of pediatric acute renal allograft dysfunction

Allograft function following renal transplantation is commonly monitored using serum creatinine. Multiple cross-sectional studies have shown that serum cystatin C is superior to creatinine for detection of mild to moderate chronic kidney dysfunction. Recent data in adults indicate that cystatin C might also be a more sensitive marker of acute renal dysfunction. This study aims to compare cystatin C and creatinine for detection of acute allograft dysfunction in children using pediatric RIFLE (risk of renal dysfunction, injury to the kidney, failure or loss of kidney function, end stage renal disease) criteria for acute kidney injury. Retrospective chart review of post-transplant period in 24 patients in whom creatinine and cystatin C were measured every day. Allograft dysfunction was defined as a sustained rise in marker concentration above the mean of the three preceding measurements. In total, there were 13 episodes of allograft dysfunction. Maximum RIFLE stages with creatinine were 'R' in 7, 'I' in 4, and 'F' in 2, with cystatin C 'R' in 6, 'I' in 4 and 'F' in 3, respectively. In 9/13 cases, both markers rose simultaneously, in three, the rise in creatinine preceded cystatin C by 1-5 days (median 4). In one case, the rise in cystatin C preceded creatinine by 1 day. The time lag was not statistically different. The maximum relative rise of creatinine was significantly higher than cystatin C. By multiple linear regression analysis, the maximum rise of cystatin C was related to the maximum rise of creatinine, but independent of patient age, gender, steroid dose, and anthropometric data. In this pediatric population, cystatin C was not superior to creatinine for the detection of acute allograft dysfunctio

Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome

Atypical hemolytic uremic syndrome (aHUS) is caused by alternative complement pathway dysregulation, leading to systemic thrombotic microangiopathy (TMA) and severe end-organ damage. Based on 2 prospective studies in mostly adults and retrospective data in children, eculizumab, a terminal complement inhibitor, is approved for aHUS treatment. Here we prospectively evaluated efficacy and safety of weight-based dosing of eculizumab in eligible pediatric patients with aHUS in an open-label phase II study. The primary end point was complete TMA response by 26 weeks. Twenty-two patients (aged 5 months-17 years) were treated; 16 were newly diagnosed, 12 had no prior plasma exchange/infusion during current TMA symptomatology, 11 received baseline dialysis, and 2 had prior renal transplants. By week 26, 14 achieved a complete TMA response, 18 achieved hematologic normalization, and 16 had 25% or better improvement in serum creatinine. Plasma exchange/infusion was discontinued in all, and 9 of the 11 patients who required dialysis at baseline discontinued, whereas none initiated new dialysis. Eculizumab was well tolerated; no deaths or meningococcal infections occurred. Bone marrow failure, wrist fracture, and acute respiratory failure were reported as unrelated severe adverse events. Thus, our findings establish the efficacy and safety of eculizumab for pediatric patients with aHUS and are consistent with proposed immediate eculizumab initiation following diagnosis in children

Urinary proteome pattern in children with renal Fanconi syndrome

Background. The renal Fanconi syndrome (FS) is characterized by renal glucosuria, loss of electrolytes, bicarbonate and lactate, generalized hyperaminoaciduria and low-molecular-weight proteinuria. We studied the urinary low-molecular-weight proteome to identify excreted peptides indicative of a pathogenetic mechanism leading to tubular dysfunction. Methods. We established a urinary proteome pattern using capillary electrophoresis mass spectrometry (CE-MS) of 7 paediatric patients with cystinosis and 6 patients with ifosfamide-induced FS as the study group, and 54 healthy volunteers and 45 patients suffering from other renal diseases such as lupus nephritis (n = 8), focal segmental glomerulosclerosis (n = 27), minimal change disease (n = 7) and membranous glomerulonephritis (n = 3) as controls. Consequently, we conducted a blinded study consisting of 11 FS patients and 9 patients with renal disease other than FS. Additionally, we applied this pattern to 294 previously measured samples of patients with different renal diseases. Amino acid sequences of some marker proteins were obtained. Results. Specificity for detecting FS was 89% and sensitivity was 82%. The marker peptides constituting the proteome pattern are fragments derived from osteopontin, uromodulin and collagen alpha-1. Conclusions. CE-MS can be used to diagnose FS in paediatric patients and might be a future tool for the non-invasive diagnosis of FS. The reduced amount of the marker proteins osteopontin and uromodulin indicates loss of function of tubular excretion in all patients suffering from FS regardless of the underlying cause. In addition, the six different fragments of the collagen alpha-1 (I) chain were either elevated or reduced in the urine. This indicates a change of proteases in collagen degradation as observed in interstitial fibrosis. These changes were prominent irrespectively of the stages of FS. This indicates fibrosis as an early starting pathogenetic reason for the development of renal insufficiency in FS patient