Binang gurri: turning a deaf ear to indigenous hearing loss

Objective: This paper asks whether Indigenous health policies might be improved if governments listened to Indigenous voices, both Australian and those who drafted the Declaration on the Rights of Indigenous Peoples, 2007. Methods: A fundamental tenet of the Declaration, which Australia endorsed in 2009, is respect for Indigenous knowledge and voice. The author analyses legal, cultural and historical sources for evidence of this respect. The metaphorical and empirical framework of the analysis is the epidemic of otitis media among Indigenous children. Results: A survey of Indigenous advice about health clearly demonstrates that access to their land and respect for the diversity of Indigenous cultures should inform health policies. Despite, however, claiming to consult Indigenous peoples, policy-makers have not been listening. In many Indigenous languages not listening, or ‘bad ears’, has connotations of disrespect. Conclusions: By turning a deaf ear to Indigenous knowledge governments are undermining any respect Indigenous peoples may have for them and their policies. A new approach is needed. Implications: The Declaration on the Rights of Indigenous Peoples can provide federal, state and territory governments with benchmarks against which health policy can be developed and implemented. Authentic consultation could restore Indigenous confidence in government policies.

Gonadotropin-induced ovarian cancer cell migration and proliferation require extracellular signal-regulated kinase 1/2 activation regulated by calcium and protein kinase Cδ

The gonadotropin hypothesis proposes that elevated serum gonadotropin levels may increase the risk of epithelial ovarian cancer (EOC). We have studied the effect of treating EOC cell lines (OV207 and OVCAR-3) with FSH or LH. Both gonadotropins activated the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and increased cell migration that was inhibited by the MAPK 1 inhibitor PD98059. Both extra- and intracellular calcium ion signalling were implicated in gonadotropin-induced ERK1/2 activation as treatment with either the calcium chelator EGTA or an inhibitor of intracellular calcium release, dantrolene, inhibited gonadotropin-induced ERK1/2 activation. Verapamil was also inhibitory, indicating that gonadotropins activate calcium influx via L-type voltage-dependent calcium channels. The cAMP/protein kinase A (PKA) pathway was not involved in the mediation of gonadotropin action in these cells as gonadotropins did not increase intracellular cAMP formation and inhibition of PKA did not affect gonadotropin-induced phosphorylation of ERK1/2. Activation of ERK1/2 was inhibited by the protein kinase C (PKC) inhibitor GF 109203X as well as by the PKCδ inhibitor rottlerin, and downregulation of PKCδ was inhibited by small interfering RNA (siRNA), highlighting the importance of PKCδ in the gonadotropin signalling cascade. Furthermore, in addition to inhibition by PD98059, gonadotropin-induced ovarian cancer cell migration was also inhibited by verapamil, GF 109203X and rottlerin. Similarly, gonadotropin-induced proliferation was inhibited by PD98059, verapamil, GF 109203X and PKCδ siRNA. Taken together, these results demonstrate that gonadotropins induce both ovarian cancer cell migration and proliferation by activation of ERK1/2 signalling in a calcium- and PKCδ-dependent manner.

Morphine-induced receptor endocytosis in a novel knockin mouse reduces tolerance and dependence

Abstract Opioid drugs, such as morphine, are among the most effective analgesics available. However, their utility for the treatment of chronic pain is limited by side effects including tolerance and dependence. Morphine acts primarily through the mu-opioid receptor (MOP-R) , which is also a target of endogenous opioids. However, unlike endogenous ligands, morphine fails to promote substantial receptor endocytosis both in vitro, and in vivo. Receptor endocytosis serves at least two important functions in signal transduction. First, desensitization and endocytosis act as an "off" switch by uncoupling receptors from G protein. Second, endocytosis functions as an "on" switch, resensitizing receptors by recycling them to the plasma membrane. Thus, both the off and on function of the MOP-R are altered in response to morphine compared to endogenous ligands. To examine whether the low degree of endocytosis induced by morphine contributes to tolerance and dependence, we generated a knockin mouse that expresses a mutant MOP-R that undergoes morphine-induced endocytosis. Morphine remains an excellent antinociceptive agent in these mice. Importantly, these mice display substantially reduced antinociceptive tolerance and physical dependence. These data suggest that opioid drugs with a pharmacological profile similar to morphine but the ability to promote endocytosis could provide analgesia while having a reduced liability for promoting tolerance and dependence

Comparison of intranasal and transcutaneous immunization for induction of protective immunity against chlamydia muridarum respiratory tract infection

Chlamydia pneumoniae causes a range of respiratory infections including bronchitis, pharyngitis and pneumonia. Infection has also been implicated in exacerbation/initiation of asthma and chronic obstructive pulmonary disease (COPD) and may play a role in atherosclerosis and Alzheimer's disease. We have used a mouse model of Chlamydia respiratory infection to determine the effectiveness of intranasal (IN) and transcutaneous immunization (TCI) to prevent Chlamydia lung infection. Female BALB/c mice were immunized with chlamydial major outer membrane protein (MOMP) mixed with cholera toxin and CpG oligodeoxynucleotide adjuvants by either the IN or TCI routes. Serum and bronchoalveolar lavage (BAL) were collected for antibody analysis. Mononuclear cells from lung-draining lymph nodes were stimulated in vitro with MOMP and cytokine mRNA production determined by real time PCR. Animals were challenged with live Chlamydia and weighed daily following challenge. At day 10 (the peak of infection) animals were sacrificed and the numbers of recoverable Chlamydia in lungs determined by real time PCR. MOMP-specific antibody-secreting cells in lung tissues were also determined at day 10 post-infection. Both IN and TCI protected animals against weight loss compared to non-immunized controls with both immunized groups gaining weight by day 10-post challenge while controls had lost 6% of body weight. Both immunization protocols induced MOMP-specific IgG in serum and BAL while only IN immunization induced MOMP-specific IgA in BAL. Both immunization routes resulted in high numbers of MOMP-specific antibody-secreting cells in lung tissues (IN > TCI). Following in vitro re-stimulation of lung-draining lymph node cells with MOMP; IFNγ mRNA increased 20-fold in cells from IN immunized animals (compared to non-immunized controls) while IFNγ levels increased 6- to 7-fold in TCI animals. Ten days post challenge non-immunized animals had >7000 IFU in their lungs, IN immunized animals <50 IFU and TCI immunized animals <1500 IFU. Thus, both intranasal and transcutaneous immunization protected mice against respiratory challenge with Chlamydia. The best protection was obtained following IN immunization and correlated with IFNγ production by mononuclear cells in lung-draining LN and MOMP-specific IgA in BAL.

Inhibition of orexin-1/hypocretin-1 receptors inhibits yohimbine-induced reinstatement of ethanol and sucrose seeking in Long-Evans rats

Abstract RATIONALE: Previous studies have shown that orexin-1/hypocretin-1 receptors play a role in self-administration and cue-induced reinstatement of food, drug, and ethanol seeking. In the current study, we examined the role of orexin-1/hypocretin-1 receptors in operant self-administration of ethanol and sucrose and in yohimbine-induced reinstatement of ethanol and sucrose seeking. MATERIALS AND METHODS: Rats were trained to self-administer either 10% ethanol or 5% sucrose (30 min/day). The orexin-1 receptor antagonist SB334867 (0, 5, 10, 15, 20 mg/kg, i.p.) was administered 30 min before the operant self-administration sessions. After these experiments, the operant self-administration behaviors were extinguished in both the ethanol and sucrose-trained rats. Upon reaching extinction criteria, SB334867 (0, 5, 10 mg/kg, i.p.) was administered 30 min before yohimbine (0 or 2 mg/kg, i.p.). In a separate experiment, the effect of SB334867 (0, 15, or 20 mg/kg, i.p.) on general locomotor activity was determined using the open-field test. RESULTS: The orexin-1 receptor antagonist, SB334867 (10, 15 and 20 mg/kg) decreased operant self-administration of 10% ethanol but not 5% sucrose self-administration. Furthermore, SB334867 (5 and 10 mg/kg) significantly decreased yohimbine-induced reinstatement of both ethanol and sucrose seeking. SB334867 did not significantly affect locomotor activity measured using the open-field test. CONCLUSIONS: The results suggest that inhibition of OX-1/Hcrt-1 receptors modulates operant ethanol self-administration and also plays a significant role in yohimbine-induced reinstatement of both ethanol and sucrose seeking in rats.

Coherent superposition of exciton states in quantum dots induced by surface plasmons

We present an experimental demonstration of strong optical coupling between CdSequantum dots of different sizes which is induced by a surface plasmon propagating on a planar silver thin film. Attenuated total reflection measurements demonstrate the hybridization of exciton states, characterized by the observation of two avoided crossings in the energy dispersion measured for the interacting system.

Evaluating multivariate volatility forecasts : how effective are statistical and economic loss functions?

Multivariate volatility forecasts are an important input in many financial applications, in particular portfolio optimisation problems. Given the number of models available and the range of loss functions to discriminate between them, it is obvious that selecting the optimal forecasting model is challenging. The aim of this thesis is to thoroughly investigate how effective many commonly used statistical (MSE and QLIKE) and economic (portfolio variance and portfolio utility) loss functions are at discriminating between competing multivariate volatility forecasts. An analytical investigation of the loss functions is performed to determine whether they identify the correct forecast as the best forecast. This is followed by an extensive simulation study examines the ability of the loss functions to consistently rank forecasts, and their statistical power within tests of predictive ability. For the tests of predictive ability, the model confidence set (MCS) approach of Hansen, Lunde and Nason (2003, 2011) is employed. As well, an empirical study investigates whether simulation findings hold in a realistic setting. In light of these earlier studies, a major empirical study seeks to identify the set of superior multivariate volatility forecasting models from 43 models that use either daily squared returns or realised volatility to generate forecasts. This study also assesses how the choice of volatility proxy affects the ability of the statistical loss functions to discriminate between forecasts. Analysis of the loss functions shows that QLIKE, MSE and portfolio variance can discriminate between multivariate volatility forecasts, while portfolio utility cannot. An examination of the effective loss functions shows that they all can identify the correct forecast at a point in time, however, their ability to discriminate between competing forecasts does vary. That is, QLIKE is identified as the most effective loss function, followed by portfolio variance which is then followed by MSE. The major empirical analysis reports that the optimal set of multivariate volatility forecasting models includes forecasts generated from daily squared returns and realised volatility. Furthermore, it finds that the volatility proxy affects the statistical loss functions’ ability to discriminate between forecasts in tests of predictive ability. These findings deepen our understanding of how to choose between competing multivariate volatility forecasts.

Experimentally induced diesel engine injector faults and some preliminary acoustic emission signal observations

Diesel engine fuel injector faults can lead to reduced power, increased fuel consumption and greater exhaust emission levels and if left unchecked, can eventually lead to premature engine failure. This paper provides an overview of the Diesel, or compression ignition combustion process, and of the two basic fuel injector nozzle designs used in Diesel engines, namely, the pintle-type and hole-type nozzles. Also described are some common faults associated with these two types of fuel injector nozzles and the techniques previously used to experimentally simulate these faults. This paper also presents a recent experimental campaign undertaken using two different diesel engines whereby various fuel injector nozzle faults were induced into the engines. The first series of tests was undertaken using a turbo-charged 5.9 litre; Cummins Diesel engine whist the second series of tests was undertaken using a naturally aspirated 4 cylinder, 2.216 litre, Perkins Diesel engine. Data corresponding to different injector fault conditions was captured using in-cylinder pressure, and acoustic emission transducers along with both crank-angle encoder and top-dead centre reference signals. Using averaged in-cylinder pressure signals, it was possible to qualify the severity of the faults whilst averaged acoustic emission signals were in turn, used as the basis for wavelets decomposition. Initial observations from this signal decomposition are also presented and discussed.

Substance-induced psychosis : a diagnostic conundrum

Objective: To critically examine the DSM-IV-TR criteria for Substance-Induced Psychotic Disorder (SIPD). Data sources: Leading electronic databases (such as Medline, Pubmed) were searched for the years 1992 through 2007, using combinations of the following key search terms: substance abuse/dependence, alcohol, marijuana, cannabis, methamphetamine, crack, cocaine, amphetamine, ecstasy, ketamine, phencyclidine, LSD, mental health, drug-induced psychosis, substance-induced psychosis, psychosis, schizophrenia. References identified from bibliographies of pertinent articles and books in the field were also collected and reviewed. Data extraction: Only research studies or case reports series that presented data on populations diagnosed with SIPD using clinical or structured diagnostic interviews published in English were used to assess the validity of the current SIPD criteria. Data synthesis: We identified 49 articles that presented clinical data on SIPD. The majority of these publications were case reports, with only 18 articles specifically focusing on delineating the clinical characteristics or outcomes of individuals diagnosed with SIPD. While several large studies have recently been conducted to assess the stability of SIPD, there is a dearth of research rigorously examining the validity of DSM-IV diagnostic criteria across substances. Conclusions: There remains a striking paucity of information on the outcome, treatment and best practice for substance-associated psychotic episodes. Further work is clearly required before the advent of DSM-V. We propose an alternative, broader classification that better reflects the current evidence base, inferring association rather than causation.