163 research outputs found
Pharmacokinetic aspects of meloxicam in koalas: including its hepatic microsomal metabolism compared with other selected species
Get PDFPrior to this research, no disposition studies of meloxicam (nor any other non steroidal anti-inflammatory drugs) had been conducted in koalas (a specialist Eucalyptus spp. foliage feeder) despite being readily administered to this species, in the field. Thus, aspects of the in-vivo pharmacokinetic profile of meloxicam in the koala and the in-vitro metabolism of meloxicam in the koala and selected species were investigated. In the first stage of the research, a simple, sensitive and improved method using high performance liquid chromatography equipped with photo diode array detection was developed and validated to determine meloxicam concentrations in koala plasma, applicable for in-vivo pharmacokinetic study. Following intravenous injection, meloxicam exhibited a rapid plasma clearance of 0.44 ± 0.20 L/h/kg in koalas (n = 5). Median plasma terminal elimination t1/2 was 1.19 h (range 0.71 to 1.62 h). In koalas, bioavailability after the subcutaneous injection was approximately 56 to 70 % where oral bioavailability was negligible. Plasma protein binding of meloxicam was about 98%. Three hydroxylated metabolites of meloxicam (M1, M2 and M3) were detected in the koala plasma with one (M1) identified as the 5-hydroxy methyl metabolite. According to the in-vitro hepatic microsomal metabolism of meloxicam, it was demonstrated that biotransformation of meloxicam, likely mediated via cytochrome P450 enzymes, were much faster in koalas (and also in other Eucalyptus spp. foliage feeders: ringtail possums and brushtail possums) compared to rats or dogs. The rank order of apparent in-vitro intrinsic clearance was brushtail possums (n = 3) (mean: 394 μL/min/mg protein) > koalas (n = 6) (50 μL/min/mg protein) > ringtail possums (n = 2) (36 μL/min/mg protein) (with no significant difference between koalas and ringtail possums) > pooled rats (3.2 μL/min/mg protein) > pooled dogs (not determined as the rate of metabolism was too slow). According to the in-vitro study, single hydroxylated metabolite (M1) was determined as the major product of meloxicam in brushtail possums and the rat whereas multiple hydroxylated metabolites were observed in the koala (M1, M2, and M3) and the ringtail possum (M1 and M3). Using a well-stirred model, this research showed applicability of predicting in-vivo clearance of meloxicam in koalas and the rat from the apparent in-vitro intrinsic clearance data (average fold error for prediction was less than 2). While cytochrome P4502C9 is the major responsible enzymes for metabolism of meloxicam, the research also found that the stability of other cytochrome P4502C9 substrates, particularly non steroidal anti-inflammatory drugs were also generally not stable in hepatic microsomes of koala and other Eucalyptus.spp foliage feeders than the rat. Particularly, there was some similarity on the pattern of CYP2C9 substrates stabilities between koala and ringtail possum (Eucalyptus spp. foliage specialist feeders). This research demonstrated that koalas exhibited rapid plasma clearance and extremely poor oral bioavailability of meloxicam compared with other eutherian species. Due to differences in the rate of hepatic metabolism on meloxicam, other eutherians such as rats or dogs are inadequate model for dosage extrapolation of this drug in koalas. Furthermore, as catalytic activity of cytochrome P4502C-like enzymes appeared to be different in these Eucalyptus spp. foliage feeders, it is highly recommended to consider when extrapolating dosage of therapeutic drugs (cytochrome P4502C9 substrates), particularly non steroidal anti-inflammatory drugs, from other eutherians. On the other hand, as in-vivo clearance is one of the pharmacokinetic indexes for determining the dosage of drug, this study demonstrates the utility of in-vitro to in-vivo scaling as an alternative prediction method of drug clearance in koalas
'We always come here': investigating the social in social learning
Get PDFThis paper investigates student choices around the 'Third Space' for learning; that which is not either a teaching space or a private space. In mapping the use of such spaces around the University of Northampton's campuses and through the use of semi-structured interviews with students as they use the spaces it constructs a model to help understand why students choose a particular space to work in and influence decisions in the deliberate creation of such spaces in future.
The research shows four, often overlapping, influences on student choice of space; resources, environment, social and emotional. That resource rich spaces that allow social interaction and learning to take place in attractive environments are popular should not be surprising but it is the emotional response to space that is of particular interest. Space attachment theory has usually centred on home or places with religious or national symbolism. This paper identifies an element of emotional resonance to areas of the university campus, especially the library, that will warrant further research
Silver Ion Biocide Delivery System for Water Disinfection
Get PDFUnited StatesReactive Innovations, LLCNASA Johnson Space Center303ICES303: Physio-Chemical Life Support- Water Recovery & Management Systems- Technology and Process DevelopmentVienna, AustriaBenjamin M. Slote, Reactive Innovations, LLC, USAEdward Salley, Reactive Innovations, LLC, USAMichael C. Kimble, Reactive Innovations, LLC, USADaniel Carr, Reactive Innovations, LLC, USANiklas Adam, NASA Johnson Space Center, USAThe 46th International Conference on Environmental Systems was held in Vienna, Austria, USA on 10 July 2016 through 14 July 2016.U.S. space exploration missions have long considered returning to the Moon and exploration of Mars that challenge life support systems. For these long duration missions, there is interest in replacing the iodine water treatment system with ionic silver, a proven biocide. Although iodine treated water has been used successfully with the International Space Station, its use requires that the iodine be removed before being consumed by astronauts due to its adverse effects on the thyroid. For long duration exploration missions, it is imperative that an effective biocide be used that prevents microbial growth, biofilm formation, and microbially induced corrosion in the water storage and distribution systems while minimizing logistical supply requirements associated with the biocide delivery system.
A biocide delivery system has been developed that electrochemically produces silver ions for disinfecting water throughout the water storage and distribution system. This system produces an abundance of silver ions at the 1000 ppb level upstream in the water distribution system to prevent biofilm growth that is followed by a downstream collection module that electrochemically removes these silver ions before the water is discharged. Although low levels of silver ions are compatible for human ingestion, maintaining a sufficiently high level of silver throughout the water storage and distribution system prevents biofilm formation. This overcomes present concerns where spurious silver deposition occurs on the container and flow line surfaces thus lowering the silver ion concentration to unsatisfactory disinfection levels.
The design of the silver ion biocide delivery system is discussed including the development of a new hybrid micro-filtration and ion-exchange membrane that minimizes ohmic losses in the electrochemical cell, performance data for the introduction and removal of silver ions in flowing water streams, mechanisms for minimizing and controlling deleterious silver oxide growth, and design options for a long duration silver ion biocide delivery system
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Get PDFAuthor response to: Comment on: “Randomized clinical trial of negative pressure wound therapy as an adjunctive treatment for small-area thermal burns in children” by Frear et al
No full textDear Editor We thank Agarwal and Sharma for their interest in our paper1. We wish to submit the following points for their consideration: In partial-thickness burn management, the risk of progressive injury and protracted re-epithelialisation cannot be dismissed, particularly for deep dermal partial-thickness burns, which constituted one-third of our sample. The well-known relationship between time to re-epithelialisation and hypertrophic scarring highlights the critical importance of facilitating prompt epithelial closure in the treatment of all burns. We concur that collagen dressings hold promise. However, randomised trials demonstrating their efficacy are lacking, and there is evidence they might be inferior to silver-impregnated dressings. The potential value of NPWT has been shown in several acute, chronic, and post-operative settings, including burn care. Aware of its possible practical challenges, we assessed the intervention’s effects on ease of management and movement. Given the substantial treatment burden observed among younger children, we encourage clinicians to explore less cumbersome, ultraportable NPWT systems. As noted in the published protocol, collection of data to inform an economic evaluation was integrated into the trial. This evaluation is currently undergoing peer review and suggests the costs of NPWT are reasonable in relation to the identified benefits. Our study showed statistically significant reductions in time to re-epithelialisation, dressing change requirements, and referrals to scar management. Scar assessments were conducted at both 3- and 6-months post-injury. These measures revealed a significant difference in relative scar thickness at 3 months. The 6-month assessments were constrained by high rates of attrition. This trial provides the first high-quality evidence of the intervention’s efficacy as an adjunct to silver-impregnated dressings when applied within one week of injury and set to a continuous subatmospheric pressure of 80 mmHg. We agree that further research is necessary to define the optimal NPWT regimenFull Tex
Book Review: The Handbook for Storytellers
No full textThis is an updated and expanded edition of a popular, professional classic with a new co-author. A great storyteller, former school librarian, and now library school adjunct professor, Judy Freeman is a worthy successor to the groundbreaking Caroline Feller Bauer, who died in 2013. Described as a companion volume to The Handbook for Storytime Programs (forthcoming from ALA in 2015), this is a true handbook covering the entire process, from story selection to program promotion to taking care of one’s voice
Letter to the Editor and Author Response for "A systematic review and meta-analysis of randomized trials evaluating the efficacy of autologous skin cell suspensions for re-epithelialization of acute partial thickness burn injuries and split-thickness skin graft donor sites" by Bairagi, et al
No full textDear Editor,
We thank Holmes et al. for their interest in our systematic review and meta-analysis [1] and would like to submit the following response for their consideration:
1. Randomized trials eligible for evaluation in this study were limited to partial thickness burn injuries managed with an autologous skin cell suspension which was a pre-specified inclusion criteria for our systematic review, published on the PROSPERO International Prospective Register of Systematic Reviews prior to commencing screening of database results (PROSPERO Record ID = CRD42019133171) [2]. As such, findings from a study conducted in full-thickness burn wounds although significant [3], were excluded from evaluation as they were beyond the scope of our systematic review and meta-analysis. The role of autologous skin cell suspensions (ASCS) in the management of full thickness burn wounds, could be better understood in a future review examining full thickness wounds. The findings from the study conducted in full thickness burn wounds that was referred to by the authors of the letter to the editor could be included in such a review [3].No Full Tex
Overcoming phonon-induced dephasing for indistinguishable photon sources
Get PDFReliable single photon sources constitute the basis of schemes for quantum communication and measurement based quantum computing. Solid state single photon sources based on quantum dots are convenient and versatile but the electronic transitions that generate the photons are subject to interactions with lattice vibrations. Using a microscopic model of electron-phonon interactions and a quantum master equation, we here examine phonon-induced decoherence and assess its impact on the rate of production, and indistinguishability, of single photons emitted from an optically driven quantum dot system. We find that, above a certain threshold of desired indistinguishability, it is possible to mitigate the deleterious effects of phonons by exploiting a three-level Raman process for photon production.Peer reviewe
Optical interferometers with reduced sensitivity to thermal noise
Get PDFA fundamental limit to the sensitivity of optical interferometry is thermal noise that drives fluctuations in the positions of the surfaces of the interferometer's mirrors, and thereby in the phase of the intracavity field. Schemes for reducing this thermally driven phase noise are presented that rely upon the coherent character of the underlying displacements and strains. Although the position of the physical surface fluctuates, the optical phase upon reflection can have reduced sensitivity to this motion. While practical implementation of such schemes for coherent compensation face certain challenges, we hope to stimulate further work on this important thermal noise problem
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