332 research outputs found

    Where do all the spoons go? : perceptions of parents of adult heroin users

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    [From the introduction]:Research aims and objectivesThis thesis aims to discover what sorts of tensions (if any) were created for parents when their problematic drug using adult offspring were mandated into drug treatment programmes in the community, and when their offspring engaged with treatment in the prison setting. In addition, this research aims to develop an understanding about whether or not these types of intervention were welcomed by parents as a positive development towards addressing the problematic drug use of their offspring. Alternatively, did the involvement of the criminal justice system in drug treatment lead to additional or different difficulties for the parents? The objectives of the research are to analyse and interpret how the research participants (the parents of problematic drug users) experience the involvement of the criminal justice system in treating the problematic drug use of their offspring.This research does not consider whether or not the involvement of families in the treatment process of problematic drug users is effective, but rather this research investigates the application of policies that seek to involve parents in the treatment journey of problematic drug users. Moreover, this study does not attempt to offer an explanation for problematic drug use, or offer suggestions about how to encourage the parents of problematic drug users to become involved in the treatment process, or what alternatives exist for those without parents

    A new mitochondrial gene order in the banded cusk-eel Raneya brasiliensis (Actinopterygii, Ophidiiformes)

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    The complete mitochondrial genome of the banded cusk-eel, Raneya brasilensis (Kaup, 1856), was obtained using next-generation sequencing approaches. The genome sequence was 16,881 bp and exhibited a novel gene order for a vertebrate. Specifically, the WANCY and the nd6–D-loop regions were re-ordered, supporting the hypothesis that these two regions are hotspots for gene rearrangements in Actinopterygii. Phylogenetic reconstructions confirmed that R. brasiliensis is nested within Ophidiiformes. Mitochondrial genomes are required from additional ophidiins to determine whether the gene rearrangements that we observed are specific to the genus Raneya or to the subfamily Ophidiinae.Fil: Fromm, Amir. Tel Aviv University George S. Wise Faculty Of Life Sciences; IsraelFil: Atkinson, Stephen D.. State University of Oregon; Estados UnidosFil: Alama Bermejo, Gema. Universidad Nacional del Comahue. Centro de Investigación Aplicada y Transferencia Tecnológica en Recursos Marinos "Almirante Storni". - Provincia de Río Negro. Ministerio de Agricultura, Ganadería y Pesca. Centro de Investigación Aplicada y Transferencia Tecnológica en Recursos Marinos "Almirante Storni". Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Centro Nacional Patagónico. Centro de Investigación Aplicada y Transferencia Tecnológica en Recursos Marinos "Almirante Storni"; ArgentinaFil: Cartwright, Paulyn. University of Kansas; Estados UnidosFil: Bartholomew, Jerri. State University of Oregon; Estados UnidosFil: Huchon, Dorothée. Tel Aviv University George S. Wise Faculty Of Life Sciences; Israe

    Globalisation, Entrepreneurship and the South Pacific: Reframing Australian Colonial Architecture, 1800-1850

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    In 1957, Clinton Hartley Grattan, one of Australia’s most important foreign observers, wrote of the shadow of the “urban” in legends of the Australian “bush”.1 He argued that the early frontiers of Australian settlement were frontiers of men with private capital, or entrepreneurs, and those frontiers thus carried more elements of the urban than is commonly realised. Such early colonial enterprises around Australia’s south and southeastern coasts, and across the Tasman included sealing, whaling, milling and pastoralism, as well as missionary, trading and finance ventures. In advance of official settlements in the late-eighteenth and early-nineteenth centuries, entrepreneurs mapped coastlines, pioneered trade routes and colonised lands. Backed by private capital they established colonial infrastructural architecture effecting urban expansion in the Australian colonies, New Zealand and beyond. Yet this architecture is rarely a subject of architectural histories

    Inhibition of cyclin-dependent kinase 9 downregulates cytokine production without detrimentally affecting human monocyte-derived macrophage viability

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    Cyclin-dependent kinase (CDK) inhibitor drugs (CDKi), such as R-roscovitine and AT7519, induce neutrophil apoptosis in vitro and enhance the resolution of inflammation in a number of in vivo models. This class of compounds are potential novel therapeutic agents that could promote the resolution of acute and chronic inflammatory conditions where neutrophil activation contributes to tissue damage and aberrant tissue repair. In this study we investigated CDKi effects on macrophage pro-inflammatory mediator production and viability. Treatment of human monocyte-derived macrophages (MDMs) with the CDKi AT7519 and R-roscovitine at concentrations that induce neutrophil apoptosis had no significant effect on control or LPS-activated MDM apoptosis and viability, and did not detrimentally affect MDM efferocytosis of apoptotic cells. In addition, enhanced efferocytosis, induced by the glucocorticoid dexamethasone, was also unaffected after a short time treatment with R-roscovitine. Macrophage cytokine responses to inflammatory stimuli are also of importance during inflammation and resolution. As a key target of CDKi, CDK9, is involved in protein transcription via the RNA polymerase II complex, we investigated the effect of CDKi drugs on cytokine production. Our data show that treatment with AT7519 significantly downregulated expression and release of key MDM cytokines IL-6, TNF, IL-10 and IL-1β, as well as markers of pro-inflammatory macrophage polarisation. R-Roscovitine was also able to downregulate inflammatory cytokine protein secretion from MDMs. Using siRNA transfection, we demonstrate that genetic knock-down of CDK9 replicates these findings, reducing expression and release of pro-inflammatory cytokines. Furthermore, overexpression of CDK9 in THP-1 cells can promote a pro-inflammatory phenotype in these cells, suggesting that CDK9 plays an important role in the inflammatory phenotype of macrophages. Overall, this study demonstrates that pharmacological and genetic targeting of CDK9 inhibits an inflammatory phenotype in human MDMs. As such these data indicate that CDK9 may be key to therapeutically targeting pro-inflammatory macrophage functions during chronic inflammation

    Physiological concentrations of bile acids down-regulate agonist induced secretion in colonic epithelial cells

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    In patients with bile acid malabsorption, high concentrations of bile acids enter the colon and stimulate Cl− and fluid secretion, thereby causing diarrhoea. However, deoxycholic acid (DCA), the predominant colonic bile acid, is normally present at lower concentrations where its role in regulating transport is unclear. Thus, the current study set out to investigate the effects of physiologically relevant DCA concentrations on colonic epithelial secretory function. Cl− secretion was measured as changes in short-circuit current across voltage-clamped T84 cell monolayers. At high concentrations (0.5–1 mM), DCA acutely stimulated Cl− secretion but this effect was associated with cell injury, as evidenced by decreased transepithelial resistance (TER) and increased lactate dehydrogenase (LDH) release. In contrast, chronic (24 hrs) exposure to lower DCA concentrations (10–200 μM) inhibited responses to Ca2+ and cAMP-dependent secretagogues without altering TER, LDH release, or secretagogue-induced increases in intracellular second messengers. Other bile acids – taurodeoxycholic acid, chenodeoxycholic acid and cholic acid – had similar antisecretory effects. DCA (50 μM) rapidly stimulated phosphorylation of the epidermal growth factor receptor (EGFr) and both ERK and p38 MAPKs (mitogen-activated protein kinases). The EGFr inhibitor, AG1478, and the protein synthesis inhibitor, cycloheximide, reversed the antisecretory effects of DCA, while the MAPK inhibitors, PD98059 and SB203580, did not. In summary, our studies suggest that, in contrast to its acute prosecretory effects at pathophysiological concentrations, lower, physiologically relevant, levels of DCA chronically down-regulate colonic epithelial secretory function. On the basis of these data, we propose a novel role for bile acids as physiological regulators of colonic secretory capacity

    High thermal stress responses of Echinolittorina snails at their range edge predict population vulnerability to future warming

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    Populations at the edge of their species' distribution ranges are typically living at the physiological extreme of the environmental conditions they can tolerate. As a species' response to global change is likely to be largely determined by its physiological performance, subsequent changes in environmental conditions can profoundly influence populations at range edges, resulting in range extensions or retractions. To understand the differential physiological performance among populations at their distribution range edge and center, we measured levels of mRNA for heat shock protein 70 (hsp70) as an indicator of temperature sensitivity in two high-shore littorinid snails, Echinolittorina malaccana and E. radiata, between 1°N to 36°N along the NW Pacific coast. These Echinolittorina snails are extremely heat-tolerant and frequently experience environmental temperatures in excess of 55°C when emersed. It was assumed that animals exhibiting high temperature sensitivity will synthesize higher levels of mRNA, which will thus lead to higher energetic costs for thermal defense. Populations showed significant geographic variation in temperature sensitivity along their range. Snails at the northern range edge of E. malaccana and southern range edge of E. radiata exhibited higher levels of hsp70 expression than individuals collected from populations at the center of their respective ranges. The high levels of hsp70 mRNA in populations at the edge of a species' distribution range may serve as an adaptive response to locally stressful thermal environments, suggesting populations at the edge of their distribution range are potentially more sensitive to future global warming

    A face for all seasons:searching for context-specific leadership traits and discovering a general preference for perceived health

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    Previous research indicates that followers tend to contingently match particular leader qualities to evolutionarily consistent situations requiring collective action (i.e., context-specific cognitive leadership prototypes) and information processing undergoes categorization which ranks certain qualities as first-order context-general and others as second-order context-specific. To further investigate this contingent categorization phenomenon we examined the “attractiveness halo”—a first-order facial cue which significantly biases leadership preferences. While controlling for facial attractiveness, we independently manipulated the underlying facial cues of health and intelligence and then primed participants with four distinct organizational dynamics requiring leadership (i.e., competition vs. cooperation between groups and exploratory change vs. stable exploitation). It was expected that the differing requirements of the four dynamics would contingently select for relatively healthier- or intelligent-looking leaders. We found perceived facial intelligence to be a second-order context-specific trait—for instance, in times requiring a leader to address between-group cooperation—whereas perceived health is significantly preferred across all contexts (i.e., a first-order trait). The results also indicate that facial health positively affects perceived masculinity while facial intelligence negatively affects perceived masculinity, which may partially explain leader choice in some of the environmental contexts. The limitations and a number of implications regarding leadership biases are discussed

    A machine learning-driven approach to predicting thermo-elasto-hydrodynamic lubrication in journal bearings

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    Traditional methods of evaluating the performance of journal bearings, for example thermal-elastic-hydrodynamic- lubrication theory, are limited to simplified conditions that often fail to accurately model real-world components. Numerical models that include additional phenomena such as cavitation and fully coupled effects like deformation, temperature, pressure and viscosity can be more accurate but require a large amount of computational overhead, making analysis slower and more costly. To address this limitation, a novel machine learning-driven approach is developed to predict the 2D distribution of surface deformation, film thickness, temperature, and pressure across the bearing surface as a function of design variables such as load and speed. The training dataset, generated using a fully coupled Reynolds’ Equation solver implemented in OpenFOAM, contains a significantly extended range of conditions than in previous studies with approximately 39 000 000 points encompassing 4925 different test cases. Modelled bearing speeds range from 2000 to 10 000 rpm, while load values are varied between 1 and 30 kN. Predicting surface deformation, film thickness, temperature and pressure across the bearing surface results in a mean absolute percentage error below 0.4 % or better. The work also demonstrates that the trained models have a strong ability to generalise the prediction beyond the original training data range with only a 1 % error at up to 200 % of the highest trained speed. This work also demonstrates that machine learning-based processes are a practical alternative to physics-based numerical modelling, especially in cases where rapid performance evaluation is desired as real-time calculation is possible with significantly reduced computational cost. This has the potential to enable development of rapid design optimisation tools and real-time performance monitoring at high resolution and with low latency. Using consumer hardware, it is found that the neural network-based approach is faster than the existing numerical modelling technique by a factor of over 10 000, enabling real-time predictions of lubrication systems
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