Sustained low-efficiency dialysis with filtration (SLEDD-f) in the management of acute sodium valproate intoxication

Hemodialysis is only infrequently used in drug overdosage situations. The efficacy of hemodialysis to remove the drug depends upon the pharmacokinetics and pharmacodynamics of the drug. At normal therapeutic concentrations, valproic acid is predominantly protein bound and therefore removal by hemodialysis is limited. In an overdose situation, protein binding is rapidly saturated and therefore the substantially larger quantities of the free drug can rapidly cause toxicity. Slow low-efficient daily diafiltration (SLEDD) has not previously been utilized in a drug overdose situation. We report the effective use of SLEDD to remove high toxic concentrations of valproic acid in an overdose situation. Slow low-efficient daily diafiltration also prevented the rebound phenomenon that can occur as the excess drug is released from its protein-bound stores. Hybrid dialysis therapies deserve further evaluation in the management of other poisonings where extra-corporeal therapy is indicated.

Glass transition and free volume behaviour of poly(acrylonitrile)/LiCF3SO3 polymer-in-salt electrolytes compared to poly(ether urethane)/LiClO4 solid polymer electrolytes

Measurements of the glass transition temperature (T_g) and free volume behaviour of poly(acrylonitrile) (PAN) and PAN/lithium triflate (LiTf), with varying salt composition from 10 to 66 wt% LiTf, were made by positron annihilation lifetime spectroscopy (PALS). Addition of salt from 10 to 45 wt% LiTf resulted in an increase in the mean free volume cavity size at room temperature (r.t.) as measured by the orthoPositronium (oPs) pickoff lifetime, τ₃, with little change in relative concentration of free volume sites as measured by oPs pickoff intensity, I₃. The region from 45 to 66 wt% salt displayed no variation in relative free volume cavity size and concentration. This salt concentration range (45 wt%<[LiTf]<66 wt%) corresponds to a region of high ionic conductivity of order 10⁻⁵ to 10⁻⁶ S cm⁻¹ at T_g as measured by PALS. A percolation phenomenon is postulated to describe conduction in this composition region. Salt addition was shown to lower the T_g as measured by PALS; T_g was 115°C for PAN and 85°C for PAN/66 wt% LiTf. The T_g and free volume behaviour of this polymer-in-salt electrolyte (PISE) was compared to a poly(ether urethane)/LiClO₄ where the polymer is the major component, i.e. traditional solid polymer electrolyte (SPE). In contrast to the PISE, the T_g of the SPE was shown to increase with increasing salt concentration from 5.3 to 15.9 wt%. The relative free volume cavity size and concentration at r.t. were shown to decrease with increasing salt concentration. Ionic conductivity in this SPE was of order 10⁻⁵ S cm⁻¹ at r.t., which is over 60°C above T_g, 10⁻⁸ S cm⁻¹ at 25°C above T_g, and conductivity was not measurable at T_g.

Exercise performance and V0₂ kinetics during upright and recumbent high-intensity cycling exercise

This study investigated cycling performance and oxygen uptake (VO₂) kinetics between upright and two commonly used recumbent (R) postures, 65ºR and 30ºR. On three occasions, ten young active males performed three bouts of high-intensity constant-load (85% peak workload achieved during a graded test) cycling in one of the three randomly assigned postures (upright, 65ºR or 30ºR). The first bout was performed to fatigue and second and third bouts were limited to 7 min. A subset of seven subjects performed a final constant-load test to failure in the supine posture. Exercise time to failure was not altered when the body inclination was lowered from the upright (13.1 ± 4.5 min) to 65ºR (10.5 ± 2.7 min) and 30ºR (11.5 ± 4.6 min) postures; but it was significantly shorter in the supine posture (5.8 ± 2.1 min) when compared with the three inclined postures. Resulting kinetic parameters from a tri-exponential analysis of breath-by-breath VO₂ data during the first 7 min of exercise were also not different between the three inclined postures. However, inert gas rebreathing analysis of cardiac output revealed a greater cardiac output and stroke volume in both recumbent postures compared with the upright posture at 30 s into the exercise. These data suggest that increased cardiac function may counteract the reduction of hydrostatic pressure from upright ~25 mmHg; to 65ºR ~22 mmHg; and 30ºR ~18 mmHg such that perfusion of active muscle presumably remains largely unchanged, and also therefore, VO₂ kinetics and performance during high-intensity cycling.

Formulation optimization for high drug loading colonic drug delivery carrier

High drug loading (DL) carrier is an effective way to cure the cancerous cells. High drug loading is also one of the key issues in the drug delivery research, especially the colonic drug delivery system by oral administration. The times of drug intake could be remarkably reduced if high drug loading carriers are administered. At the same time, the related formulation materials could be effectively utilized. One major obstacle with the preparation of this system is the difficulty to encapsulate the hydrophilic drug into hydrophobic encapsulation polymer. A design of high drug loading delivery system with biodegradable, biocompatible materials and optimization of the fabrication process is a potential solution to solve the problem. So in this research, 5-Fluorouracil (5-FU) loaded Poly (lactide-co-glycolide) (PLGA) nanoparticles were prepared by double emulsion and solvent evaporation method. Several fabrication parameters including theoretical drug loading, volume ratio of outer water phase to the first emulsion, pH value of outer aqueous phase and emulsifier PVA concentration were optimized to get a high drug loading nanoparticles. The result shows that with the increase of theoretical drug loading, the actual drug loading increased gradually. When adjusted the pH value of outer aqueous phase to the isoelectric point (8.02) of 5-Fluorouracil, the drug loading exhibited a higher one compared to other pH value solution. Relative higher volume ratio of outer water phase to the first emulsion was also beneficial for the enhancement of drug loading. But the nanoparticles size increased simultaneously due to the lower shearing force. When increased the PVA concentration, the drug loading showed an increase first and following a drop.

The Australian and New Zealand dialysis workforce

Aim: To capture a "snapshot" of the current Australian and New Zealand dialysis workforce in order to contribute to the future renal workforce challenges.

Methods: A web-based survey of dialysis managers (n=221) were asked fifteen questions relating to demographics, age, full-time equivalent information, workforce designation, post-registration qualifications, subjective perceptions of staffing levels, staffing strategies and future dialysis research recommendations

Results: In Australia in 2008 there were 2433 registered nurses, 188 enrolled nurses and 295 dialysis professionals (technicians) and 327 registered nurses (RNs), 8 enrolled nurses (ENs) and 64 dialysis professionals in New Zealand. There were significant variations in staff/patient ratios, workforce profiles and post-registration qualifications. There is a significant association between staff/ patient and home dialysis ratios. A high proportion of renal staff worked part-time, particularly in Australia. The dialysis workforce reflects the aging nature of the general nursing population in Australia and New Zealand. The majority of dialysis nurse managers perceived they had sufficient staff.

Conclusion: Workforce variations found in this study may be useful to identify future workforce challenges and strategies.

Dialysis residential care : a future dialysis service model

People with chronic kidney disease are ageing and have increasing co-morbidities. The current delivery of renal replacement therapy, dialysis and transplantation, needs to adjust to changing patient needs. This paper proposes a potential future service delivery model featuring a dialysis residential care facility and a care coordination focus. The residential care facility would be composed of four levels of care; high, hostel, independent and outpatient. The paper argues that this model may result in decreased morbidity, improved patient quality of life and may prove cost effective. Patients' nutritional status, medication adherence and transport efficiency may be improved. We propose this model to stimulate further debate in order to meet the needs of current and future chronic kidney disease patients.

Performance of suspended and attached growth MBR systems in treating high strength synthetic wastewater

The performance of laboratory-scale attached growth (AG) and suspended growth (SG) membrane bioreactors (MBRs) was evaluated in treating synthetic wastewater simulating high strength domestic wastewater. This study investigated the influence of sponge suspended carriers in AG-MBR system, occupying 15% reactor volume, on the removal of chemical oxygen demand (COD), total nitrogen (TN) and total phosphorus (TP), and compared it to that of SG-MBR. Results showed that the removal efficiencies of COD, TN and TP in AG-MBR were 98%, 89% and 58%, respectively as compared to 98%, 74% and 38%, respectively in SG-MBR. Improved TN removal in AG-MBR systems was primarily based on simultaneous nitrification and denitrification (SND) process. These results infer that the presence of small bio-particles having higher microbial activity and the growth of complex biomass captured within the suspended sponge carriers resulted in improved TN and TP removal in AG-MBR.

Comparative study on performance of yeast and bacterial membrane bioreactors for high salinity wastewater treatment

Two laboratory-scale membrane bioreactor systems were investigated to treat high saline wastewater containing 1,000 mg/L COD and 32 g/L NaCl, namely: the yeast membrane bioreactor (YMBR) and the bacterial membrane bioreactor (BMBR). COD removal of both processes was above 90% at a hydraulic retention time (HRT) of 5 hours (volumetric loading of 5 kg COD/m³.d), sludge retention time (SRT) of 50 days (the MLSS of above 14 g/L and the F/M of 0.4 d-1). Under these operating conditions, the YMBR could run at a ten-fold lower transmembrane pressure with significantly reduced membrane fouling rate compared to BMBR. This may be because of low production of adhesive extracellular polymers (ECP) and the secondary filtration layer formed from large yeast cells. ECP production of bacterial sludge was increased considerably at high salt concentrations (32 g/L and 45 g/L) and long SRTs. For the bacterial sludge, the increased salinity led to increase in ECP, whereas the ECP content of the yeast sludge was relatively small.

Molecular alignment in nematic liquid crystals : a comparison between the results of experiments at high pressure and predictions based on mean field theories

The effects of high pressure on molecular arrangment in liquid crystals were observed by optical measurements on two nematogens. It was possible to deduce how volume varies as a factor of temperature and pressure and how nematic order parameter changes under the influence of high pressure.

Association between the oxytocin receptor gene and amygdalar volume in healthy adults

Background: Recent studies have suggested that oxytocin affects social cognition and behavior mediated by the oxytocin receptor (OXTR) in amygdala in humans as well as in experimental animals. Genetic studies have revealed a link between the OXTR gene and the susceptibility to autism spectrum disorders (ASD), especially in the social dysfunctional feature of ASD.

Methods: We examined the relationship between amygdala volume measured with manual tracing methodology and seven single nucleotide polymorphisms and one haplotype-block in OXTR, which were previously reported to be associated with ASD, in 208 socially intact Japanese adults with no neuropsychiatric history or current diagnosis.

Results: The rs2254298A allele of OXTR was significantly associated with larger bilateral amygdala volume. The rs2254298A allele effect on amygdala volume varied in proportion to the dose of this allele. The larger the number of rs2254298A alleles an individual had, the larger their amygdala volume. Such an association was not observed with hippocampal volume or with global brain volumes, including whole gray, white matter, and cerebrospinal-fluid space. Furthermore, two three–single nucleotide polymorphism haplotypes, including rs2254298G allele, showed significant associations with the smaller bilateral amygdala volume.

Conclusions: The present results suggest that OXTR might be associated with the susceptibility to ASD, especially in its aspects of social interaction and communication mediated by a modulation of amygdala development, one of the most distributed brain regions with high density of OXTR. Furthermore, amygdala volume measured with magnetic resonance imaging could be a useful intermediate phenotype to uncover the complex link between OXTR and social dysfunction in ASD.

Spectroscopic study of the effects of pressure media on high-pressure phase transitions in natrolite

Structural phase transitions in natrolite have been investigated as a function of pressure and different hydrostatic media using micro-Raman scattering and synchrotron infrared (IR) spectroscopy. Natrolite undergoes two reversible phase transitions at 0.86 and 1.53 GPa under pure water pressure medium. These phase transitions are characterized by the changes in the vibrational frequencies of four- and eight-membered rings related to the variations in the bridging T−O−T angles and the geometry of the elliptical eight-ring channels under pressure. Concomitant to the changes in the framework vibrational modes, the number of the O−H stretching vibrational modes of natrolite changes as a result of the rearrangements of the hydrogen bonds in the channels caused by a successive increase in the hydration level under hydrostatic pressure. Similar phase transitions were also observed at relatively higher pressures (1.13 and 1.59 GPa) under alcohol−water pressure medium. Furthermore, no phase transition was found up to 2.52 GPa if a lower volume ratio of the alcohol−water to natrolite was employed. This indicates that the water content in the pressure media plays a crucial role in triggering the pressure-induced phase transitions in natrolite. In addition, the average of the mode Grüneisen parameters is calculated to be about 0.6, while the thermodynamic Grüneisen parameter is found to be 1.33. This might be attributed to the contrast in the rigidity between the TO4 tetrahedral primary building units and other flexible secondary building units in the natrolite framework upon compression and subsequent water insertion.

Microstructures and properties of ferrite/bainite dual-phase steels with high hole-expanding ratio

The effects of Si and Mn contents on microstructure, mechanical properties and formability of low carbon Si-Mn steels were studied, and the crack propagation of ferrite/bainite dual-phase steel was also investigated. The results showed that the increase in Si content increases the volume fraction of equiaxed ferrite. However, the increase in Mn content increases both strength and ductility, but decreases elongation and hole-expanding ratio. The crack of ferrite/bainite dual-phase steel is formed by the mode of microvoid coalescence. When a microcrack meets the bainite, it mostly propagates along the phase interface between ferrite and bainite and by cutting off ferrite grains. The hot-rolled ferrite/bainite dual-phase steel, which has a hole-expanding ratio of 95% and good property combination, could be produced by designing proper contents of Si and Mn as well as parameters of TMCP.

Multiscale modelling of stress and strain partitioning in high strength dual phase steels

Multiscale modelling of stress and strain partitioning in DP steel was carried out using both realistic microstructure-based RVE models as well as stochastic microstructures generated by Monte Carlo method. The stochastic microstructure models were shown to resemble that of realistic microstructures, enabling research on the specific aspects of the microstructure that could be difficult to control and study during experimental work. One such feature of the realistic microstructures studied in this work was the grain size and microstructure morphology. The microstructures were generated with varying average grain sizes while all other parameters, such as boundary conditions, material properties and volume fractions of martensite and ferrite were kept constant. It is found that the effect of grain size is much more pronounced during the initial localisation of the plastic deformation at and around the interface of the phases. In addition, the decrease in ductility and increase in strength of the DP steels are directly related to the refinement of grain sizes of each phase and the stress-strain partitioning in between them.

Addressing retained austenite stability in advanced high strength steels

Advances in the development of new high strength steels have resulted in microstructures containing significant volume fractions of retained austenite. The transformation of retained austenite to martensite upon straining contributes towards improving the ductility. However, in order to gain from the above beneficial effect, the volume fraction, size, morphology and distribution of the retained austenite need to be controlled. In this regard, it is well known that carbon concentration in the retained austenite is responsible for its chemical stability, whereas its size and morphology determines its mechanical stability. Thus, to achieve the required mechanical properties, control of the processing parameters affecting the microstructure development is essential.