Influence of cytochrome P-450 inhibitors on the inhalative uptake of methyl chloride and methylene chloride in male B6C3F1 mice

Dichloromethane (DCM) is thought to be metabolized in vivo by two independent pathways: a glutathione (GSH) dependent pathway that yields CO2 and a cytochrome P-450 mediated one that yields both CO and CO2 (Gargas et al 1986). With a physiologically based pharmacokinetic (PB-PK) model, Andersen et al (1987) calculate the quantitative parameters for both metabolic pathways. Using the kinetic parameters thus obtained and the results of two carcinogenicity studies with rodents (Serota et al 1986; NTP 1985), the authors then estimate the tumour risk for humans.

Can synchronous online counselling increase uptake of counselling services in secondary schools and what can promote or inhibit implementation?

This research showed that online counselling has the potential to increase the help-seeking of secondary school students - especially those who suffer from high levels of psychological distress. An investigation of why school counsellors are currently reluctant to provide an online counselling service identified a number of barriers to implementing such a potentially vital service. Response to focus groups and surveys completed by students and school counsellors indicated that more distressed students prefer to use online counselling and they would use it for sensitive topics. School counsellors remain concerned about effectiveness, ethical, legal and privacy issues as well as potential misuse of the service. Recommendations for implementation are made.

Bridging the gap: Exploring the barriers to using economic evidence in healthcare decision making and strategies for improving uptake

Evidence from economic evaluations is often not used to inform healthcare policy despite being well regarded by policy makers and physicians. This article employs the accessibility and acceptability framework to review the barriers to using evidence from economic evaluation in healthcare policy and the strategies used to overcome these barriers. Economic evaluations are often inaccessible to policymakers due to the absence of relevant economic evaluations, the time and cost required to conduct and interpret economic evaluations, and lack of expertise to evaluate quality and interpret results. Consistently reported factors that limit the translation of findings from economic evaluations into healthcare policy include poor quality of research informing economic evaluations, assumptions used in economic modelling, conflicts of interest, difficulties in transferring resources between sectors, negative attitudes to healthcare rationing, and the absence of equity considerations. Strategies to overcome these barriers have been suggested in the literature, including training, structured abstract databases, rapid evaluation, reporting checklists for journals, and considering factors other than cost effectiveness in economic evaluations, such as equity or budget impact. The factors that prevent or encourage decision makers to use evidence from economic evaluations have been identified, but the relative importance of these factors to decision makers is uncertain.

What’s driving the uptake of prefabricated housing in Australia?

Prefabrication has been promoted as a means to improve the efficiency of the Australian house building industry. Issues affecting the uptake of prefabrication were identified through interviews with small and medium sized building companies. Prefabrication’s specific impact on housing construction and smaller organisations has not been frequently investigated. Similar past research has been conducted without the use of a clear theoretical grounding guiding the identification of relevant issues. The current study is guided by a combination of the Theory of Planned Behaviour (TPB) and the Technology Acceptance Model (TAM). This allowed the identification of a broad range of issues across attitudinal, normative, behavioural control and technology adaptation domains. Results revealed improved quality was often offset against practical cost implications. While a high quality of prefabricated products was reported, key technical challenges included coordinating the transporting of modules, and balancing standardisation and product flexibility. Resistance from traditional industry stakeholders regarding build methods, financing, and openness to encouraging prefabrication was commonly reported. The key role of government decision making in facilitating greater demand and competitiveness of prefabricated businesses in the consumer marketplace was also highlighted. Further research is currently being undertaken by the authors, which builds on the exploratory results of the current study through confirmatory, quantitative surveying.

Reconceptualizing green infrastructure for climate change adaptation: Barriers to adoption and drivers for uptake by spatial planners

Urban green infrastructure can help cities adapt to climate change. Spatial planning can play an important role in utilizing green infrastructure for adaptation. Yet climate change risks represent a different sort of challenge for planning institutions. This paper aims to address two issues arising from this challenge. First, it defines the concept of green infrastructure within the context of climate adaptation. Second, it identifies and puts into perspective institutional barriers to adopting green infrastructure for climate adaptation, including path dependence. We begin by arguing that there is growing confusion among planners and policy makers about what constitutes green infrastructure. Definitional ambiguity may contribute to inaction on climate change adaptation, because it muddies existing programs and initiatives that are to do with green-space more broadly, which in turn feeds path dependency. We then report empirical findings about how planners perceive the institutional challenge arising from climate change and the adoption of green infrastructure as an adaptive response. The paper concludes that spatial planners generally recognize multiple rationales associated with green infrastructure. However they are not particularly keen on institutional innovation and there is a tendency for path dependence. We propose a conceptual model that explicitly recognizes such institutional factors. This paper contributes to the literature by showing that agency and institutional dimensions are a limiting factor in advancing the concept of green infrastructure within the context of climate change adaptation.

Impact of technology uptake on an Australian electricity distribution network

This paper presents simulation results for future electricity grids using an agent-based model developed with MODAM (MODular Agent-based Model). MODAM is introduced and its use demonstrated through four simulations based on a scenario that expects a rise of on-site renewable generators and electric vehicles (EV) usage. The simulations were run over many years, for two areas in Townsville, Australia, capturing variability in space of the technology uptake, and for two charging methods for EV, capturing people's behaviours and their impact on the time of the peak load. Impact analyses of these technologies were performed over the areas, down to the distribution transformer level, where greater variability of their contribution to the assets peak load was observed. The MODAM models can be used for different purposes such as impact of renewables on grid sizing, or on greenhouse gas emissions. The insights gained from using MODAM for technology assessment are discussed.

Uptake of influenza vaccination in pregnancy amongst Australian Aboriginal and Torres Strait Islander women: A mixed-methods pilot study

Background Influenza infection during pregnancy is associated with significant morbidity and mortality. Immunisation against influenza is recommended during pregnancy in several countries but uptake of vaccine is poor. There are limited data on vaccine uptake, and the determinants of vaccination, in Australian Aboriginal and/or Torres Islander women during pregnancy. This study aimed to establish an appropriate methodology and collect pilot data on vaccine uptake and attitudes towards, and perceptions of, maternal influenza vaccination in that population in order to inform the development of larger studies. Methods A mixed-methods study comprised of a cross-sectional survey and yarning circles (focus groups) amongst Aboriginal and Torres Strait Islander women attending two primary health care services. The women were between 28 weeks gestation and less than 16 weeks post-birth. These data were supplemented by data collected in an ongoing national Australian study of maternal influenza vaccination. Aboriginal research officers collected community data and data from the yarning circles which were based on a narrative enquiry framework. Descriptive statistics were used to analyse quantitative data and thematic analyses were applied to qualitative data. Results Quantitative data were available for 53 women and seven of these women participated in the yarning circles. The proportion of women who reported receipt of an influenza vaccine during their pregnancy was 9/53. Less than half of the participants (21/53) reported they had been offered the vaccine in pregnancy. Forty-three percent reported they would get a vaccine if they became pregnant again. Qualitative data suggested perceived benefits to themselves and their infants were important factors in the decision to be vaccinated but there was insufficient information available to women to make that choice. Conclusions The rates of influenza immunisation may continue to remain low for Aboriginal and/or Torres Strait Islander women during pregnancy. Access to services and recommendations by a health care worker may be factors in the lower rates. Our findings support the need for larger studies directed at monitoring and understanding the determinants of maternal influenza vaccine uptake during pregnancy in Australian Aboriginal and Torres Strait Islander women. This research will best be achieved using methods that account for the social and cultural contexts of Aboriginal and Torres Strait Islander communities in Australia.

Targeting ASCT2-mediated glutamine uptake blocks prostate cancer growth and tumour development

Glutamine is conditionally essential in cancer cells, being utilized as a carbon and nitrogen source for macromolecule production, as well as for anaplerotic reactions fuelling the tricarboxylic acid (TCA) cycle. In this study, we demonstrated that the glutamine transporter ASCT2 (SLC1A5) is highly expressed in prostate cancer patient samples. Using LNCaP and PC-3 prostate cancer cell lines, we showed that chemical or shRNA-mediated inhibition of ASCT2 function in vitro decreases glutamine uptake, cell cycle progression through E2F transcription factors, mTORC1 pathway activation and cell growth. Chemical inhibition also reduces basal oxygen consumption and fatty acid synthesis, showing that downstream metabolic function is reliant on ASCT2-mediated glutamine uptake. Furthermore, shRNA knockdown of ASCT2 in PC-3 cell xenografts significantly inhibits tumour growth and metastasis in vivo, associated with the down-regulation of E2F cell cycle pathway proteins. In conclusion, ASCT2-mediated glutamine uptake is essential for multiple pathways regulating the cell cycle and cell growth, and is therefore a putative therapeutic target in prostate cancer.

Biophysical response of living cells to boron nitride nanoparticles: Uptake mechanism and bio-mechanical characterization

Boron nitride nanomaterials have attracted significant interest due to their superior chemical and physical properties. Despite these novel properties, investigation on the interaction between boron nitride nanoparticle (BN NP) and living systems has been limited. In this study, BN NP (100–250 nm) is assessed as a promising biomaterial for medical applications. The toxicity of BN NP is evaluated by assessing the cells behaviours both biologically (MTT assay, ROS detection etc.) and physically (atomic force microscopy). The uptake mechanism of BN NP is studied by analysing the alternations in cellular morphology based on cell imaging techniques. The results demonstrate in vitro cytocompatibility of BN NP with immense potential for use as an effective nanoparticle for various bio-medical applications.

Geometry Of Proline And Hydroxyproline .1. An Analysis Of X-Ray Crystal-Structure Data

We have carried out an analysis of crystal structure data on prolyl and hydroxyprolyl moieties in small molecules. The flexibility of the pyrrolidine ring due to the pyramidal character of nitrogen has been defined in terms of two projection angles δ1 and δ2. The distribution of these parameters in the crystal structures is found to be consistent with results of the energy calculations carried out on prolyl moieties in our laboratory.

Drivers for uptake of environmental management systems by pastoralists in western Queensland

Pastoralists from 37 beef cattle and sheep properties in western Queensland developed and implemented an environmental management system (EMS) over 18 months. The EMS implemented by them was customised for the pastoral industry as part of a national EMS pilot project, and staff from this project encouraged and assisted pastoralists during this trial. The 31 pastoralists surveyed at the end of the pilot project identified few benefits of EMS implementation, and these were largely associated with environmental management and sustainability. In terms of the reasons for uptake of an EMS, these pastoralists identified drivers similar to those reported in other primary industry sectors. These included improving property and environmental management, financial incentives, a range of market benefits, assistance with red tape issues, access to other training opportunities and assistance and support with the development of their EMS. However, these drivers are weak, and are not motivating pastoralists to adopt an EMS. In contrast, barriers to adoption such as the time involved in developing and implementing EMS are tangible and immediate. Given a lack of effective drivers and that pastoralists are under considerable pressure from ongoing rural adjustment processes, it is not surprising that an EMS is a low priority. It is concluded that widespread uptake and on-going use of an EMS in the pastoral industry will not occur unless pastoralists are required or rewarded for this by markets, governments, financiers, and regional natural resource management bodies.

Nutrient uptake in tropical turfgrasses growing in winter in southern Queensland

The effects of fertilisers on 8 tropical turfgrasses growing in 100-L bags of sand were studied over winter in Murrumba Downs, just north of Brisbane in southern Queensland (latitude 27.4°S, longitude 153.1°E). The species used were: Axonopus compressus (broad-leaf carpetgrass), Cynodon dactylon (bermudagrass 'Winter Green') and C. dactylon x C. transvaalensis hybrid ('Tifgreen'), Digitaria didactyla (Queensland blue couch), Paspalum notatum (bahiagrass '38824'), Stenotaphrum secundatum (buffalograss 'Palmetto'), Eremochloa ophiuroides (centipedegrass 'Centec') and Zoysia japonica (zoysiagrass 'ZT-11'). Control plots were fertilised with complete fertilisers every month from May to September (72 kg N/ha, 31 kg P/ha, 84 kg K/ha, 48 kg S/ha, 30 kg Ca/ha and 7.2 kg Mg/ha), and unfertilised plots received no fertiliser. Carpetgrass and standard bermudagrass were the most sensitive species to nutrient supply, with lower shoot dry weights in the unfertilised plots (shoots mowed to thatch level) compared with the fertilised plots in June. There were lower shoot dry weights in the unfertilised plots in July for all species, except for buffalograss, centipedegrass and zoysiagrass, and lower shoot dry weights in the unfertilised plots in August for all species, except for centipedegrass. At the end of the experiment in September, unfertilised plots were 11% of the shoot dry weights of fertilised plots, with all species affected. Mean shoot nitrogen concentrations fell from 3.2 to 1.7% in the unfertilised plots from May to August, below the sufficiency range for turfgrasses (2.8-3.5%). There were also declines in P (0.45-0.36%), K (2.4-1.5%), S (0.35-0.25%), Mg (0.24-0.18%) and B (9-6 mg/kg), which were all in the sufficiency range. The shoots in the control plots took up the following levels (kg/ha.month) of nutrients: N, 10.0-27.0; P, 1.6-4.0; K, 8.2-19.8; S, 1.0-4.2; Ca, 1.1-3.3; and Mg, 0.8-2.2, compared with applications (kg/ha.month) of: N, 72; P, 31; K, 84; S, 48; Ca, 30; and Mg, 7.2, indicating a recovery of 14-38% for N, 5-13% for P, 10-24% for K, 2-9% for S, 4-11% for Ca and 11-30% for Mg. These results suggest that buffalograss, centipedegrass and zoysiagrass are less sensitive to low nutrient supply than carpetgrass, bermudagrass, blue couch and bahiagrass. Data on nutrient uptake showed that the less sensitive species required only half or less of the nitrogen required to maintain the growth of the other grasses, indicating potential savings for turf managers in fertiliser costs and the environment in terms of nutrients entering waterways.

Proline ring conformations corresponding to a bistable jump model from 13C spin-lattice relaxation times

A formalism for extracting the conformations of a proline ring based on the bistable jump model of R. E. London [(1978) J. Am. Chem. Soc. 100, 2678-2685] from 13C spin-lattice relaxation times (T1) is given. The method is such that the relaxation data are only partially used to generate the conformations; these conformations are constrained to satisfy the rest of the relaxation data and to yield acceptable ring geometry. An alternate equation for T1 of 13C nuclei to that of London is given. The formalism is illustrated through an example.

A linear root water uptake model

A model of root water extraction is proposed, in which a linear variation of extraction rate with depth is assumed. Five crops are chosen for simulation studies of the model, and soil moisture depletion under optimal conditions from different layers for each crop is calculated. Similar calculations are also made using the constant extraction rate model. Rooting depth is assumed to vary linearly with potential evapotranspiration for each crop during the vegetative phase. The calculated depletion patterns are compared with measured mean depletion patterns for each crop. It is shown that the constant extraction rate model results in large errors in the prediction of soil moisture depletion, while the proposed linear extraction rate model gives satisfactory results. Hypothetical depletion patterns predicted by the model in combination with a moisture tension-dependent sink term developed elsewhere are indicated.

Proline-containing β-turns in peptides and proteins: Analysis of structural data on globular proteins

Tetrapeptide sequences of the type Z-Pro-Y-X were obtained from the crystal structure data on 34 globular proteins, and used in an analysis of the positional preferences of the individual amino acid residues in the β-turn conformation. The effect of fixing proline as the second position residue in the tetrapeptide sequence was studied by comparing the data obtained on the positional preferences with the corresponding data obtained by Chou and Fasman using the Z-R-Y-X sequence, where no particular residue was fixed in any of the four positions. While, in general, several amino acid residues having relatively very high or very low preferences for specific positions were found to be common to both the Z-Pro-Y-X and Z-R-Y-X sequences, many significant differences were found between the two sets of data, which are to be attributed to specific interactions arising from the presence of the proline residue.