The delta opioid receptor antagonist, SoRI-9409, decreases yohimbine stress-induced reinstatement of ethanol-seeking

A major problem in treating alcohol use disorders (AUDs) is the high rate of relapse due to stress and re-exposure to cues or an environment previously associated with alcohol use. Stressors can induce relapse to alcohol-seeking in humans or reinstatement in rodents. Delta opioid peptide receptors (DOP-Rs) play a role in cue-induced reinstatement of ethanol-seeking; however, their role in stress-induced reinstatement of ethanol-seeking is not known. The objective of this study was to determine the role of DOP-Rs in yohimbine-stress-induced reinstatement of ethanol-seeking. Male, Long-Evans rats were trained to self-administer 10% ethanol in daily 30-minute operant self-administration sessions using a FR3 schedule of reinforcement, followed by extinction training. Once extinction criteria were met, we examined the effects of the DOP-R antagonist, SoRI-9409 (0–5 mg/kg, i.p.) on yohimbine (2 mg/kg, i.p.) stress-induced reinstatement. Additionally, DOP-R-stimulated [35S]GTPS binding was measured in brain membranes and plasma levels of corticosterone (CORT) were determined. Pre-treatment with SoRI-9409 decreased yohimbine stress-induced reinstatement of ethanol-seeking but did not affect yohimbine-induced increases in plasma CORT levels. Additionally, yohimbine increased DOP-R-stimulated 35[S]GTPS binding in brain membranes of ethanol-trained rats, an effect that was inhibited by SoRI-9409. This suggests that the DOP-R plays an important role in yohimbine-stress-induced reinstatement of ethanol-seeking behavior, and DOP-R antagonists may be promising candidates for further development as a treatment for AUDs.

Current status and future prospects for cultured limbal tissue transplants in Australia and New Zealand

Cultured limbal tissue transplants have become widely used over the last decade as a treatment for limbal stem cell deficiency (LSCD). While the number of patients afflicted with LSCD in Australia and New Zealand is considered to be relatively low, the impact of this disease on quality of life is so severe that the potential efficacy of cultured transplants has necessitated investigation. We presently review the basic biology and experimental strategies associated with the use of cultured limbal tissue transplants in Australia and New Zealand. In doing so, we aim to encourage informed discussion on the issues required to advance the use of cultured limbal transplants in Australia and New Zealand. Moreover, we propose that a collaborative network could be established to maintain access to the technology in conjunction with a number of other existing and emerging treatments for eye diseases.

Impact of a government triple zero awareness campaign on emergency department patient characteristics

Objective: To evaluate the impact of a government triple zero community awareness campaign on the characteristics of patients attending an ED. Methods: A study using Emergency Department Information System data was conducted in an adult metropolitan tertiary-referral teaching hospital in Brisbane. The three outcomes measured in the 3 month post-campaign period were arrival mode, Australasian Triage Scale and departure status. These measures reflect ambulance usage, clinical urgency and illness severity, respectively. They were compared with those in the 3 month pre-campaign period. Multivariate logistic regression models were used to investigate the impacts of the campaign on each of the three outcome measures after controlling for age, sex, day and time of arrival, and daily minimum temperature. Results: There were 17 920 visits in the pre- and 17 793 visits in the post-campaign period. After the campaign, fewer patients arrived at the ED by road ambulance (odds ratio [OR] 0.90, 95% confidence interval [CI] 0.80–1.00), although the impact of the campaign on the arrival mode was only close to statistical significance (Wald χ2-test, P= 0.055); and patients were significantly less likely to have higher clinical urgency (OR 0.86, 95% CI 0.79–0.94), while more likely to be admitted (OR 1.68, 95% CI 1.38–2.05) or complete treatment in the ED (OR 1.46, 95% CI 1.23–1.73) instead of leaving without waiting to be seen. Conclusions: The campaign had no significant impact on the arrival mode of the patients. After the campaign, the illness acuity of the patients decreased, whereas the illness severity of the patients increased.

The α5 neuronal nicotinic acetylcholine receptor subunits plays an important role in the sedative effects of ethanol but does not modulate consumption in mice

Alcohol use disorders (AUDs) are a major public health problem, and the few treatment options available to those seeking treatment offer only modest success rates. There remains a need to identify novel targets for the treatment of AUDs. The neuronal nicotinic acetylcholine receptors (nAChRs) represent a potential therapeutic target in the brain, as recent human genetic studies have implicated gene variants in the α5 nAChR subunit as high risk factors for developing alcohol dependence. Here, we evaluate the role of 5* nAChR for ethanol-mediated behaviors using α5+/+ and α5-/- mice. We characterized the effect of hypnotic doses of ethanol and investigated drinking behavior using an adapted Drinking-in-the Dark (DID) paradigm that has been shown to induce high ethanol consumption in mice. We found the α5 subunit to be critical in mediating the sedative effects of ethanol. The α5-/- mice showed slower recovery from ethanol-induced sleep, as measured by loss of righting reflex. Additionally the α5-/- mice showed enhanced impairment to ethanol-induced ataxia. We found the initial sensitivity to ethanol and ethanol metabolism to be similar in both α5+/+ and α5-/- mice. Hence the enhanced sedation is likely due to a difference in the acute tolerance of ethanol in mice deficient of the α5 subunit. However the α5 subunit did not play a role in ethanol consumption for ethanol concentrations ranging from 5% to 30% in the DID paradigm. Additionally, varenicline (Chantix®) was effective in reducing ethanol intake in α5-/- mice. Together, our data suggest that the α5 nAChR subunit is important for the sedative hypnotic doses of ethanol but does not play a role in ethanol consumption. Varenicline can be a treatment option even when there is loss of function of the α5 nAChR subunit.

What do emergency physicians think of law?

What do emergency physicians think of law? Do they know the law? What role does it have in the practice of emergency medicine? Emergency physicians in New South Wales, Victoria and Queensland are being asked about these issues in a study by the Queensland University of Technology, Brisbane, Australia, titled ‘Withholding and withdrawing life-sustaining treatment from adults who lack capacity: The role of law in medical practice’. The study aims to examine the role that law plays in decisions to withhold or withdraw life-sustaining treatment from adults who lack capacity.

Should law have a role in end-of-life care?

What do physicians think of law? Do they know the law? What role does it have in the provision of end-of-life care? Physicians in New South Wales, Victoria and Queensland are being asked about these issues in a study by the Queensland University of Technology entitled ‘Withholding and withdrawing life-sustaining treatment from adults who lack capacity: The role of law in medical practice’. This research aims to examine the role that law plays in decisions to withhold or withdraw life-sustaining treatment from adults who lack capacity.

Factors influencing health behaviours of younger women after menopause-inducing cancer treatment

Objective To investigate the health promotion and risk reduction behaviors of younger women previously treated for cancer. Design and Sample Guided by the Precede-Proceed framework, a mixed-method descriptive investigation of the health behaviors of younger women with cancer treatment-induced menopause in one health jurisdiction in Australia was undertaken. Measures This article reports the results of the qualitative interview component of the study. Results Of the 85 women who responded to surveys that quantified their health behaviors, 22 consented to interviews that explored how and why these behaviors might occur. Conclusions Several predisposing, enabling and reinforcing factors that influenced participants will or ability to engage with health-promoting behaviors after cancer treatment were identified in the interviews. These include entrenched precancer diagnosis health behaviors, the disabilities resulting from cancer treatments, perceptions of risk, focused intervention by health professionals and the nature of participants social support. The results indicate a need for flexibility when planning public health initiatives to prepare this cohort for a healthy life after cancer, which accounts for their developmental, knowledge and posttreatment needs.

Preparation, characterization, and in vitro bioactivity of nagelschmidtite bioceramics

The aim of this study is to prepare Ca, P and Si-containing ternary oxide nagelschmidtite (NAGEL, Ca7Si2P2O16) bioceramics and explore their in vitro bioactivity for potential bone tissue regeneration. We prepared dense NAGEL ceramics through high-temperature sintering of NAGEL ceramic powders. The apatite-mineralization ability, dissolution rate, and human osteoblast response (including cytotoxicity analysis, attachment, morphology, proliferation, and bone-related gene expression) to NAGEL ceramics have been systematically studied by comparing with conventional β-tricalcium phosphate (β-TCP) ceramics. The results showed that NAGEL ceramics possessed more obvious apatite mineralization and dissolution (degradation) and stimulated bone-related gene expression (OCN and OPN) of osteoblasts than β-TCP ceramics. NAGEL ceramics also showed no significant cytotoxicity. NAGEL ceramics supported osteoblast attachment, proliferation, and osteogenic gene expression, with a comparable cell proliferation activity with β-TCP ceramics. These results indicate that novel NAGEL bioceramics with the specific composition of Ca7Si2P2O16, are a promising biomaterial for bone tissue regeneration application.

Occupational Access and Wage Discrimination

This article presents a study on the quantification of the level of occupational access and wage discrimination in Great Britain. The traditional approach to quantifying the level of sex discrimination is to distinguish gender differences in productive characteristics from the unequal treatment of characteristics according to gender. The role of inter- versus intra-occupational effects in determining the magnitude of wage differences between men and women was examined. The econometric results provided estimates of the wage differential in six broad occupational classifications together with an aggregate picture of how important the occupational distribution of females is in explaining their lower average wage. In summary, the results of the study suggest that the vast majority of the male and female wage differential arises from intra-occupation effects. The results provide evidence to suggest that occupational segregation is not a major contributor to the observed male/female wage differential.

Bayesian experimental design for models with intractable likelihoods

In this paper we present a methodology for designing experiments for efficiently estimating the parameters of models with computationally intractable likelihoods. The approach combines a commonly used methodology for robust experimental design, based on Markov chain Monte Carlo sampling, with approximate Bayesian computation (ABC) to ensure that no likelihood evaluations are required. The utility function considered for precise parameter estimation is based upon the precision of the ABC posterior distribution, which we form efficiently via the ABC rejection algorithm based on pre-computed model simulations. Our focus is on stochastic models and, in particular, we investigate the methodology for Markov process models of epidemics and macroparasite population evolution. The macroparasite example involves a multivariate process and we assess the loss of information from not observing all variables.

Gaps in organizational leadership : linking strategic and operational activities through design-led propositions

The relationship between design process and business systems has been of interest to both practitioners and researchers exploring the numerous opportunities and challenges of this unlikely relationship. Often the relationship is presented as building design thinking capability within an organization, which can be broadly described as the union of design and strategy. Brown (2008) notes that design thinking is ‘‘a discipline that uses the designer’s sensibility and methods to match people’s needs with what is technically feasible and what business strategy can convert into customer value and market opportunities’’ (p. 1). The value that design thinking brings to an organization is a different way of framing situations and possibilities, doing things, and tackling problems: essentially a cultural transformation of the way it undertakes its business. The work of Martin (2009) has clearly shown the generalized differences between design thinking and business thinking, highlighting many instances in which these differences have been overcome, but also noting the many obstacles of trying to unify both approaches within an organization. Liedtka (2010) encourages firms to try and persist in overcoming these barriers, as she has noted that ‘‘business strategy desperately needs design ... because design is all about action and business strategy too often turns out to be only about talk ... fewer than 10 percent of new strategies are ever fully executed’’ (p. 9).

A quantum probability perspective on borderline vagueness

The term “vagueness” describes a property of natural concepts, which normally have fuzzy boundaries, admit borderline cases, and are susceptible to Zeno’s sorites paradox. We will discuss the psychology of vagueness, especially experiments investigating the judgment of borderline cases and contradictions. In the theoretical part, we will propose a probabilistic model that describes the quantitative characteristics of the experimental finding and extends Alxatib’s and Pelletier’s (2011) theoretical analysis. The model is based on a Hopfield network for predicting truth values. Powerful as this classical perspective is, we show that it falls short of providing an adequate coverage of the relevant empirical results. In the final part, we will argue that a substan- tial modification of the analysis put forward by Alxatib and Pelletier and its probabilistic pendant is needed. The proposed modification replaces the standard notion of probabilities by quantum probabilities. The crucial phenomenon of borderline contradictions can be explained then as a quantum interference phenomenon.

Experimenting with affirmative action : the Coate and Loury Model

Coate and Loury (1993) suggest the impact of affirmative action on a negative stereotype is theoretically ambiguous leading to either: a benign equilibrium in which affirmative action eradicates the negative stereotype and leads to equal proportional representation of the two groups; or alternatively a patronising equilibrium in which the stereotype persists. The current paper examines this theoretical ambiguity within the context of a laboratory experiment. Although benign and patronising equilibria are equally plausible in theory, the laboratory experiments easily replicate most features of the benign equilibrium, but diverge from the theoretically predicted patronising equilibrium.

Identification of bone morphogenetic proteins 2 and 4 in commercial demineralized freeze-dried bone allograft preparations : pilot study

BACKGROUND: Demineralized freeze-dried bone allografts (DFDBAs) have been proposed as a useful adjunct in periodontal therapy to induce periodontal regeneration through the induction of new bone formation. The presence of bone morphogenetic proteins (BMPs) within the demineralized matrix has been proposed as a possible mechanism through which DFDBA may exert its biologic effect. However, in recent years, the predictability of results using DFDBA has been variable and has led to its use being questioned. One reason for the variability in tissue response may be attributed to differences in the processing of DFDBA, which may lead to loss of activity of any bioactive substances within the DFDBA matrix. Therefore, the purpose of this investigation was to determine whether there are detectable levels of bone morphogenetic proteins in commercial DFDBA preparations. METHODS: A single preparation of DFDBA was obtained from three commercial sources. Each preparation was studied in triplicate. Proteins within the DFDBA samples were first extracted with 4M guanidinium HCI for seven days at 40 degrees celsius and the residue was further extracted with 4M guanidinium HCL/EDTA for seven days at 40 degrees celsius. Two anti-human BMP-2 and -4 antibodies were used for the detection of the presence of BMP's in the extracts. RESULTS: Neither BMP-2 nor BMP-4 was detected in any of the extracts. When recombinant human BMP-2 and -4 were added throughout the extraction process of DFDBA extraction, not only were intact proteins detected but smaller molecular weight fragments were also noted in the extract. CONCLUSIONS: These results indicate that all of the DFDBA samples tested had no detectable amounts of BMP-2 and -4. In addition, an unknown substance present in the DFDBA may be responsible for degradation of whatever BMPs might be present.