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Rationale Mismatch negativity (MMN) is a candidate endophenotype for schizophrenia subserved by N-methyl-D-aspartate receptor (NMDAR) function and there is increasing evidence that prolonged cannabis use adversely affects MMN generation. Few human studies have investigated the acute effects of cannabinoids on brain-based biomarkers of NMDAR function and synaptic plasticity. Objectives The current study investigated the acute effects of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) alone and in combination on the mismatch negativity (MMN). Methods In a randomised, double-blind, crossover placebo-controlled study, 18 frequent and 18 less-frequent cannabis users underwent 5 randomised drug sessions administered via vaporiser: (1) placebo; (2) THC 8 mg; (3) CBD 400 mg; (4) THC 8 mg + CBD 4 mg [THC + CBDlow]; (5) THC 12 mg + CBD 400 mg [THC + CBDhigh]. Participants completed a multifeature MMN auditory oddball paradigm with duration, frequency and intensity deviants (6% each). Results Relative to placebo, both THC and CBD were observed to increase duration and intensity MMN amplitude in less-frequent users, and THC also increased frequency MMN in this group. The addition of low-dose CBD added to THC attenuated the effect of THC on duration and intensity MMN amplitude in less-frequent users. The same pattern of effects was observed following high-dose CBD added to THC on duration and frequency MMN in frequent users. Conclusions The pattern of effects following CBD combined with THC on MMN may be subserved by different underlying neurobiological interactions within the endocannabinoid system that vary as a function of prior cannabis exposure. These results highlight the complex interplay between the acute effects of exogenous cannabinoids and NMDAR function. Further research is needed to determine how this process normalises after the acute effects dissipate and following repeated acute exposure.

What is the future of Philosophy of education? Or as many of scholars and thinkers in this final ‘future-focused’ collective piece from the Philosophy of Education in a New Key Series put it, what ...

How did Eruera Pare Hongi—who had an impact on New Zealand’s pre-Treaty constitutional and literacy history—come to get his name? Eruera Pare is a transliteration of Edward Parry, a famous Arctic explorer, also known as Admiral Sir William Edward Parry. Why would a young Ngāi Tawake man from Waimate, in the north of New Zealand, take the name of an Arctic explorer?

Te Kawehau Hoskins (Ngati Hau) is an associate professor in Te Puna Wānanga—School of Māori and Indigenous Education, and Associate Dean Māori for the Faculty of Education and Social Work at the University of Auckland. Alison Jones (Pākehā) is a professor in Te Puna Wānanga. In this talk, Te Kawehau and Alison Jones discuss their entangled trajectories as writers and thinkers. Te Kawehau and Alison each bring a critical view to their relationship and the possibilities for productive engagements between indigenous and settler subjects here in Aotearoa New Zealand.

Ambient air pollution is a leading risk factor for the global burden of disease. One possible pathway of particulate matter (PM)-induced toxicity is through iron (Fe), the most abundant metal in the atmosphere. The aim of the review was to consider the complexity of Fe-mediated toxicity following inhalation exposure focusing on the chemical and surface reactivity of Fe as a transition metal and possible pathways of toxicity via reactive oxygen species (ROS) generation as well as considerations of size, morphology, and source of PM. A broad term search of 4 databases identified 2189 journal articles and reports examining exposure to Fe via inhalation in the past 10 years. These were sequentially analyzed by title, abstract and full-text to identify 87 articles publishing results on the toxicity of Fe-containing PM by inhalation or instillation to the respiratory system. The remaining 87 papers were examined to summarize research dealing with

Supplementation of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) may enhance self-regulation (SR) and executive functioning (EF) in children of preschool age. The aim of the Omega Kid Study was to investigate the effect of n-3 LCPUFA supplementation on SR and EF in typically developing preschool-aged children. A double-blind placebo-controlled pilot trial was undertaken, the intervention was 12 weeks and consisted of 1.6 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day compared to placebo. The HS-Omega-3 Index® was assessed by capillary blood samples at baseline and post-intervention. Seventy-eight children were enrolled and randomised to either the n-3 LCPUFA treatment (n = 39) or placebo (n = 39) group. Post intervention, there was a significant three-fold increase in the HS-Omega-3 Index® in the n-3 LCPUFA group (p &lt, 0.001). There were no improvements in SR or EF outcome variables for the n-3 LCPUFA group post intervention compared to the placebo group determined by linear mixed models. At baseline, there were significant modest positive Spearman correlations found between the HS-Omega-3 index® and both behavioural self-regulation and cognitive self-regulation (r = 0.287, p = 0.015 and r = 0.242, p = 0.015 respectively). Although no treatment effects were found in typically developing children, further research is required to target children with sub-optimal self-regulation who may benefit most from n-3 LCPUFA supplementation.

Background: Australia’s closest neighbours in the Western Pacific face many procurement, distribution and regulatory challenges providing patients with quality pharmaceuticals on limited budgets. This study tested the hypothesis that some antibiotics being used within the healthcare systems of Papua New Guinea, Vanuatu and the Solomon Islands were substandard, and through this pilot project explored challenges and constraints around collaborative regional pharmaceutical quality testing opportunities. Methods: A list of 11 commonly used and ‘essential’ acute care intravenous and oral antibiotic products was compiled. A purposive sample of 20 units of each listed medicine was collected at the earliest possible point of the supply chain within the three participating nations. These samples were transported to Australia for analysis. Results: All oral and intravenous product samples complied with uniformity of mass standards, except for oral amoxicillin from Country 3. Most antibiotics showed uniformity of content except for cloxacillin. Conclusion: Most samples met quality standards, except for cloxacillin, which failed dramatically and this may indicate increased susceptibility to degradation in tropical settings. Although the results are reassuring compared with recent studies of pharmaceutical quality in this region, products of substandard quality were identified. The issues encountered in the timely testing of samples demonstrate the need for innovative solutions to promote pharmaceutical quality assurance, particularly in resource-limited settings. Strategic regional cooperation could greatly increase testing capability for Small Island Nations, benefiting the most vulnerable populations and strengthening antibiotic stewardship across the region.

Remifentanil is a short acting opioid currently used in anesthesia and as an analgesic. This paper describes a simple, fast HPLC-MS/MS methodology that allows detection of remifentanil in l...

Background Hospital-treated deliberate self-harm (DSH) is common, costly and has high repetition rates. Since brief contact interventions (BCIs) may reduce the risk of DSH repetition, we aim to evaluate whether a SMS (Short Message Service) text message Intervention plus Treatment As Usual (TAU) compared to TAU alone will reduce hospital DSH re-presentation rates in Western Sydney public hospitals in Australia. Methods/design Our study is a 24-month randomized controlled trial (RCT). Adult patients who present with DSH to hospital emergency, psychiatric, and mental health triage and assessment departments will be randomly assigned to an Intervention condition plus TAU receiving nine SMS text messages at 1, 2, 3, 4, 5, 6, 8, 10 and 12-months post-discharge. Each message will contain telephone numbers for two mental health crises support tele-services. Primary outcomes will be the difference in the number of DSH re-presentations, and the time to first re-presentation, within 12-months of discharge. Discussion This study protocol describes the design and implementation of an RCT using SMS text messages, which aim to reduce hospital re-presentation rates for DSH. Positive study findings would support the translation of an SMS-aftercare protocol into mental health services at minimal expense. Trial registration and ethics approval This trial has been registered with the Australian and New Zealand Clinical Trials Registry (Trial registration: ACTRN12617000607370. Registered 28 April 2017) and has been approved by two Local Health Districts (LHDs). Western Sydney LHD Human Research Ethics Committee approved the study for Westmead Hospital and Blacktown Hospital (Protocol: HREC/16/WMEAD/336). Nepean Blue Mountains LHD Research Governance Office approved the study for Nepean Hospital (SSA/16/Nepean/170).

There were increased reports of fevers and febrile reactions in young children (particularly children aged5 years) receiving the Seqirus/CSL Southern Hemisphere 2010 trivalent inactivated influenza vaccine (IIV3). Modifying the vaccine manufacturing process by increasing the minimum concentration of splitting agent (sodium taurodeoxycholate [TDOC]) from 0.5% w/v to 1.5% w/v for all strains resolved this issue. The current analysis compared fever rates in three pediatric studies of Seqirus IIV3 (S-IIV3) or quadrivalent inactivated influenza vaccine (S-IIV4), prepared using the modified manufacturing process, with fever rates in three pediatric studies of historical (pre-2010) IIV3 formulations. The historical IIV3 formulations, S-IIV3, and S-IIV4 had 0/3, 2/3, and 4/4 vaccine strains split at 1.5% TDOC, respectively.For each study, fever rates (any grade and severe) were determined for the following age subgroups (as applicable), using the fever intensity grading system used in the S-IIV3/S-IIV4 studies: 6 months to3 years; 3 to5 years; 5 to9 years; and 9 to18 years.For each age subgroup, the any grade and severe fever rates were lower in the S-IIV3/S-IIV4 studies than in the historical IIV3 formulation studies, with the greatest differences in fever rates observed in the youngest age groups. In the 6 months to3 years group, the any grade fever rate was 7.0% (severe fever: 2.5%) in one S-IIV4 study compared with 38.7% to 40.0% (severe fever: 9.6% to 17.8%) in the historical IIV3 formulation studies. In the 3 to5 years subgroup, the any grade fever rate was 4.9% (severe fever: 1.2%) in one S-IIV4 study compared with 34.1% to 36.0% (severe fever: 6.3% to 16.5%) in the historical IIV3 formulation studies.This analysis provides clinical evidence that the modified manufacturing process improved the fever profile across all pediatric age groups, in particular, in children aged5 years.

Access to cannabis and cannabinoid products is increasing worldwide for recreational and medicinal use. Two primary compounds within cannabis plant matter, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are both psychoactive, but only THC is considered intoxicating. There is significant interest in potential therapeutic properties of these cannabinoids and of CBD in particular. Some research has suggested that CBD may ameliorate adverse effects of THC, but this may be dose dependent as other evidence suggests possible potentiating effects of THC by low doses of CBD. We conducted a randomised placebo controlled trial to examine the acute effects of these compounds alone and in combination when administered by vaporisation to frequent and infrequent cannabis users. Participants (n = 36; 31 male) completed 5 drug conditions spaced one week apart, with the following planned contrasts: placebo vs CBD alone (400 mg); THC alone (8 mg) vs THC combined with low (4 mg) or high (400 mg) doses of CBD. Objective (blind observer ratings) and subjective (self-rated) measures of intoxication were the primary outcomes, with additional indices of intoxication examined. CBD showed some intoxicating properties relative to placebo. Low doses of CBD when combined with THC enhanced, while high doses of CBD reduced the intoxicating effects of THC. The enhancement of intoxication by low-dose CBD was particularly prominent in infrequent cannabis users and was consistent across objective and subjective measures. Most effects were significant at p

Background In the Southern Hemisphere 2010 influenza season, Seqirus’ split-virion, trivalent inactivated influenza vaccine was associated with increased reports of fevers and febrile reactions in young children. A staged clinical development program of a quadrivalent vaccine (Seqirus IIV4 [S-IIV4]; Afluria® Quadrivalent/Afluria Quad™/Afluria Tetra™), wherein each vaccine strain is split using a higher detergent concentration to reduce lipid content (considered the cause of the increased fevers and febrile reactions), is now complete. Methods Children aged 6–59 months were randomized 3:1 and stratified by age (6–35 months/36–59 months) to receive S-IIV4 (n = 1684) or a United States (US)-licensed comparator IIV4 (C-IIV4; Fluzone® Quadrivalent; n = 563) during the Northern Hemisphere 2016–2017 influenza season. The primary objective was to demonstrate noninferior immunogenicity of S-IIV4 versus C-IIV4. Immunogenicity was assessed by hemagglutination inhibition (baseline, 28 days postvaccination). Solicited, unsolicited, and serious adverse events were assessed for 7, 28, and 180 days postvaccination, respectively. Results S-IIV4 met the immunogenicity criteria for noninferiority. Adjusted geometric mean titer ratios (C-IIV4/S-IIV4) for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria strains were 0.79 (95% CI: 0.72, 0.88), 1.27 (1.15, 1.42), 1.12 (1.01, 1.24), and 0.97 (0.86, 1.09), respectively. Corresponding values for differences in seroconversion rates (C-IIV4 minus S-IIV4) were −10.3 (−15.4, −5.1), 2.6 (−2.5, 7.8), 3.1 (−2.1, 8.2), and 0.9 (−4.2, 6.1). Solicited, unsolicited, and serious adverse events were similar between vaccines in both age cohorts, apart from fever. Fever rates were lower with S-IIV4 (5.8%) than C-IIV4 (8.4%), with no febrile convulsions reported with either vaccine during the 7 days postvaccination. Conclusion S-IIV4, manufactured with a higher detergent concentration, demonstrated noninferior immunogenicity to the US-licensed C-IIV4, with similar postvaccination safety and tolerability, in children aged 6–59 months. This completes the program demonstrating the immunogenicity and safety of S-IIV4 in participants aged 6 months and older. Funding Seqirus Pty Ltd; ClinicalTrials.gov identifier: NCT02914275 .

E-cigarettes are increasingly common around the world, particularly among youth. Ingestion of nicotine-containing e-liquid, while relatively rare, is the major toxicological risk associated with their use. Current Australian regulation has nicotine for use in e-cigarettes listed as a dangerous poison in Schedule 7, with its supply or sale illegal in all states and territories, while regulation on the sale of e-cigarettes and accessories varies by state. However, with increasing evidence that e-cigarettes produce far fewer toxic by-products than their combustible counterparts perhaps it is time to review this regulation.

This work was supported by the United Kingdom Department of Health under the Pharmacogenetics Research programme (grant number PHGX23A). Background and aims: Anthracyclines are highly effective chemotherapeutic agents which may cause long-term cardiac damage (chronic anthracycline cardiotoxicity) and heart failure. The pathogenesis of anthracycline cardiotoxicity remains incompletely understood and individual susceptibility difficult to predict. We sought clinical features which might contribute to improved risk assessment. Methods: Subjects were women with early breast cancer, free of pre-existing cardiac disease. Left ventricular ejection fraction was measured using cardiovascular magnetic resonance before and >12 months after anthracycline-based chemotherapy (>3 months post-Trastuzumab). Variables associated with subclinical cardiotoxicity (defined as a fall in left ventricular ejection fraction of ≥5%) were identified by logistic regression. Results: One hundred and sixty-five women (mean age 48.3 years at enrollment) completed the study 21.7 months [IQR 18.0-26.8] after starting chemotherapy. All received anthracyclines (98.8% epirubicin, cumulative dose 400 [300-450] mg/m2); 18% Trastuzumab. Baseline blood pressure was elevated (≥140/90mmHg, mean 147.3/86.1mmHg) in 18 subjects. Thirty-four subjects (20.7%) were identified with subclinical cardiotoxicity, independent predictors of which were the number of anthracycline cycles (odds ratio, OR 1.64 [1.17-2.30] per cycle), blood pressure ≥140/90mmHg (OR 5.36 [1.73-17.61]), body surface area (OR 2.08 [1.36-3.20] per standard deviation (0.16m2) increase), and Trastuzumab therapy (OR 3.35 [1.18-9.51]). The resultant predictive-model had an area under the receiver operating characteristics curve of 0.78 [0.70-0.86]. Conclusions: We found subclinical cardiotoxicity to be common even within this low risk cohort. Risk of cardiotoxicity was associated with modestly elevated baseline blood pressure-indicating that close attention should be paid to blood pressure in patients considered for anthracycline based chemotherapy. The association with higher body surface area suggests that indexing of anthracycline doses to surface area may not be appropriate for all, and points to the need for additional research in this area.

The Australian Government recently walked away from changes to the importation of nicotine-containing electronic cigarette fluids, originally due to come into force on 1 January 2021. Additionally, the Therapeutic Goods Administration is in the process of rescheduling nicotine for use in e-fluids. We are concerned that the 270 000 daily vapers in Australia will purchase high concentrations of nicotine (≥100 mg/mL) for mixing with nicotine-free locally purchased e-fluids, which is a pathway of increased relative harm. We would like to see regulation of these products to limit the maximum concentration of nicotine, ensure appropriate child-resistant containers and compulsory labelling for all nicotine-containing e-fluid bottles.

Background Interventions to better manage aggressive behaviour and reduce recidivism are a primary concern for corrective services. Nutritional interventions to correct prisoner behaviour have been largely overlooked in the literature. Emerging evidence suggests that dietary intake influences aggressive behaviours and that nutritional supplementation with omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) could attenuate both the severity and frequency of aggressive behaviour. Methods Adult male prisoners who have a history of aggressive behaviour (n = 600) will be recruited from at least 6 Correctional Centres and randomised to receive either n-3 LCPUFA or placebo supplementation for a 16-week duration. Treatment will be with either 1 g/day of n-3 LCPUFA (694 mg DHA and 397 mg EPA) or placebo capsules, which are a corn/soy oil blend and are identical in size and colour. The primary outcome measure is the Inmate Behavioural Observation Scale (IBOS): an objective measure of aggressive behaviour. Secondary outcome measures include questionnaires (including aggression, attention deficit disorder, impulsivity, depression/anxiety/stress scales), engagement in programmes, recidivism and quality of life. Baseline and post-intervention assessments include the IBOS, questionnaires and blood to measure the levels of n-3 LCPUFA. Discussion To conclusively test the potential that increasing n-3 LCPUFA intakes can improve rates of prisoner aggression and associated mental health and violence-related social system management costs, we propose an adequately powered multi-centre, double-blind, randomised controlled trial, examining the effects of n-3 LCPUFA supplementation on aggressive behaviour in adult male prisoners. If successful, this study will inform prisoner policy with respect to nutrition and by inference contribute to a broader community approach to preventative mental health practices. Trial registration Australian New Zealand Clinical Trial Registry (ANZCTR) ACTRN12618001665224. Registered on 10 October 2018.

Overdose due to opioid abuse is an ever increasing problem, especially in the United States, with the last few years seeing a dramatic rise in the number of synthetic opioid-related deaths. The pur...

Tuai of Ngare Raumati was probably the most written-about Māori in the first quarter of the 19th century. He was a man who lived in unstable times, who moved flexibly within European and Māori society, and who engaged with almost everyone he met, according to a French observer, with “the tact and shrewdness which enabled [him] to realise with whom he had to deal and by what means he could commend himself to all” (Dumont D’Urville in Sharp 1971: 38). His name—or a version of it—appears in most indexes of books about the pre-1830s Bay of Islands. But almost all modern references to him are in passing. Our article seeks to bring into focus this shadowy figure who played a significant role in New Zealand history, and in particular the relationships between Māori and the first Pākehā settlers in the north of New Zealand.

This book is a history of story-making about the experiences of three Indigenous Australian travellers: Bundle (a Dharawal man), Boongaree (a Kurringgai man), and Migeo (a man of Whadjuk Nyungar). ...

Background: Evidence indicates that the serum concentration of uric acid (UA) in patients may relate both to the pathophysiology and therapeutics of bipolar disorder (BPD). The purpose of this study was to examine the changes and clinical significance of serum UA concentrations in first-episode manic patients suffering from BPD. Methods: Seventy-six drug-naive patients with first-episode bipolar mania and 76 age- and gender-matched healthy subjects were recruited. Young Mania Rating Scale and Hamilton Depression Rating Scale were used to assess clinical symptoms. We tested serum UA concentrations by sandwich enzyme-linked immunosorbent assay at baseline and at the end of 8-week treatment in BPD patients and in the control group. Results: After 8-week quetiapine and sodium valproate treatment, this study revealed that the serum UA concentrations in remitted patients were significantly lower than nonremitted patients; however, those remitted patients still had higher serum UA than healthy controls. We discovered that the baseline UA concentration was higher in nonremitted than remitted patients after 8 weeks of treatment. Finally, a positive association was found between serum UA and symptom relief in the first episode of manic disorder patients. Conclusion: Patients with first-episode BPD had high levels of serum UA, which responds to treatment mainly in remitted patients. Our results suggest that serum UA concentrations might present potentially a trait marker in bipolar patients.

DiGeorge syndrome (DGS) is a primary immunodeficiency characterized by various degrees of T-cell deficiency. In partial DGS (pDGS), other risk factors could predispose to recurrent infections, autoimmunity, and allergy. The aim of this study was to assess the effect of different factors in the development of infections, autoimmunity, and/or allergy in patients with pDGS. We studied 467 pDGS patients in follow-up at Great Ormond Street Hospital. Using a multivariate approach, we observed that palatal anomalies represent a risk factor for the development of recurrent otitis media with effusion. Gastroesophageal reflux/dysphagia and asthma/rhinitis represent a risk factor for the development of recurrent upper respiratory tract infections. Allergy and autoimmunity were associated with persistently low immunoglobulin M levels and lymphopenia, respectively. Patients with autoimmunity showed lower levels of CD3+, CD3+CD4+, and naïve CD4+CD45RA+CD27+ T lymphocytes compared with pDGS patients without autoimmunity. We also observed that the physiological age-related decline of the T-cell number was slower in pDGS patients compared with age-matched controls. The age-related recovery of the T-cell number depended on a homeostatic peripheral proliferation of T cells, as suggested by an accelerated decline of the naïve T lymphocytes in pDGS as well as a more skewed T-cell repertoire in older pDGS patients. These evidences suggest that premature CD4+ T-cell aging and lymphopenia induced spontaneous peripheral T-cell proliferation might contribute to the pathogenesis of autoimmunity in patients with pDGS. Infections in these patients represent, in most of the cases, a complication of anatomical or gastroenterological anomalies rather than a feature of the underlying immunodeficiency.

Pasifika social science researchers in Pacific contexts are encouraged to use research methods that reflect the lived realities of their participants, rather than reproduce what are seen as Western methods of research. As a Pasifika process, talanoa has become a popular research method, often likened to narrative interviews. It has been defined as an open, informal conversation between people in which they share their stories, thoughts and feelings (Vaioleti, 2006). This paper is a critique of how talanoa as a research method is represented in the literature, based on an account of the difficulties I have encountered as a beginning researcher grappling with the idea and practice of talanoa in my own research practice. I argue that improving the practice and understanding of talanoa requires open discussion about the practical dilemmas sometimes experienced by researchers attempting to use this approach.

Hospital-treated deliberate self-poisoning (DSP) by central nervous system depressant drugs (CNS-D) has been associated with impairments in cognitive and psychomotor functions at the time of discharge. We aimed to replicate this finding and to compare recovery in the first month after discharge for CNS-D and CNS nondepressant drug ingestions. We also examined a series of multivariate explanatory models of recovery of neurocognitive outcomes over time. The CNS-D group was impaired at discharge compared with the CNS-nondepressant group in cognitive flexibility, cognitive efficiency, and working memory. There were no significant differences at discharge in visual attention, processing speed, visuomotor speed, or inhibition speed. Both groups improved in the latter measures over 1 month of follow-up. However, the CNS-D group's recovery was significantly slower for key neurocognitive domains underlying driving in complex traffic situations, namely, cognitive flexibility, cognitive efficiency, and working memory. Patients discharged after DSP with CNS-D drugs have impairments of some critical cognitive functions that may require up to 1 month to recover. Although more pre- than post-DSP variables were retained as explanatory models of neurocognitive performance overall, recovery over time could not be explained by any one of the measured covariates. Tests of cognitive flexibility could be used in clinical settings as a proxy measure for recovery of driving ability. Regulatory authorities should also consider the implications of these results for the period of nondriving advised after ingestion of CNS-D in overdose. Future research, with adequate sample size, should examine contributions of other variables to the pattern of recovery over time. Language: en

In order to enhance and/or control critical current density (Jc) in superconducting YBa2Cu3O$_{7-\delta}$ (YBCO) thin films, different arrays of 3 µm large ferromagnetic (iron) dots with differing configurations and shapes have been deposited on top of high-quality YBCO thin films post-buffered with a layer of CeO2. Some tremendous Jc enhancement of up to nearly 100% have been obtained at high temperatures and low fields. However, the Jc performance is strongly dependent on the array configurations, shape and amount of ferromagnetic iron involved. We show that it is possible to enhance Jc at high or low magnetic field ranges. The results are clearly different to similar non magnetic array structures used to previously manipulate Jc in YBCO films, which proves the magnetic origin of the changes in Jc we observed. The enhancement is likely due to the flux localization and magnetic pinning effects, rather than magnetic shielding alone, which is effective at relatively low fields only. The results also suggest that the observed Jc changes depend on rather minor variations in initial pinning and corresponding Jc levels of the films. At the same time a common trend for all of the various investigated magnetic arrays could not be established due to explained factors.

Second generation antipsychotics, particularly olanzapine, induce severe obesity, which is associated with their antagonistic effect on the histamine H1 receptor (H1R). We have previously demonstrated that oral administration of olanzapine increases the concentration of neuropeptide Y (NPY) in the hypothalamus of rats, accompanied by hyperphagia and weight gain. However, it is unclear if the increased NPY after olanzapine administration is due to its direct effect on hypothalamic neurons and its H1R antagonistic property. In the present study, we showed that with an inverted U-shape dose-response curve, olanzapine increased NPY expression in the NPY-GFP hypothalamic neurons; however, this was not the case in the hypothalamic neurons of H1R knockout mice. Olanzapine inhibited the interaction of H1R and GHSR1a (ghrelin receptor) in the primary mouse hypothalamic neurons and NPY-GFP neurons examined by confocal fluorescence resonance energy transfer (FRET) technology. Furthermore, an H1R agonist, FMPH inhibited olanzapine activation of GHSR1a downstream signaling pAMPK and transcription factors of NPY (pFOXO1 and pCREB) in the hypothalamic NPY-GFP cell. However, an olanzapine analogue (E-Olan) with lower affinity to H1R presented negligible enhancement of pCREB within the nucleus of NPY neurons. These findings suggest that the H1R antagonist property of olanzapine inhibits the interaction of H1R and GHSR1a, activates GHSR1a downstream signaling pAMPK-FOXO1/pCREB and increases hypothalamic NPY: this could be one of the important molecular mechanisms of H1R antagonism of olanzapine-induced obesity in antipsychotic management of psychiatric disorders.

Partially (blind) or fully perforated antidots (BADs or ADs, respectively) fabricated by laser lithography and ion beam etching in superconducting YBa2Cu3O7 (YBCO) films possess a cumulative circumference wall surface, which is found to be responsible for pinning vortices and/or magnetic flux, whereby increasing the critical current density (J c) relative to corresponding plain (unpatterned) films. Using a variety of contrastingly shaped, relatively large 2 μm to 5 μm BADs and ADs, the J c of YBCO thin films has been effectively increased within the relatively narrow band of wall surfaces of antidots, independent whether patterns are AD or BAD type. Independence of antidot types indicates that enhancement is insensitive whether magnetic flux is inside the ADs, or vortices are inside the BADs. Within this AD wall surface band region a clear shape dependence also emerges. This finding may also provide a guide for superconducting devices requiring maximal J c and reduced associated vortex movement noise.

E-cigarettes are increasingly common around the world, particularly among youth. Ingestion of nicotine-containing e-liquid, while relatively rare, is the major toxicological risk associated with their use. Current Australian regulation has nicotine for use in e-cigarettes listed as a dangerous poison in Schedule 7, with its supply or sale illegal in all states and territories, while regulation on the sale of e-cigarettes and accessories varies by state. However, with increasing evidence that e-cigarettes produce far fewer toxic by-products than their combustible counterparts perhaps it is time to review this regulation.

Paediatric patients, particularly preterm neonates, present many pharmacological challenges. Due to the difficulty in conducting clinical trials in these populations dosing information is often extrapolated from adult populations. As the processes of absorption, distribution, metabolism and excretion of drugs change throughout growth and development extrapolation presents risk of over or underestimating the doses required. Information about the development these processes, particularly drug metabolism pathways, is still limited with weight based dose adjustment presenting the best method of estimating pharmacokinetic changes due to growth and development. New innovations in pharmacokinetic research, such as population pharmacokinetic modelling, present unique opportunities to conduct clinical trials in these populations improving the safety and effectiveness of the drugs used. More research is required into this area to ensure the best outcomes for our most vulnerable patients.

Maori leaders visiting Australia invited a Pakeha (in this case, English) teacher to come to New Zealand to teach the children to read and write. On 12th August 1816, 200 years ago this year, the first school in New Zealand opened. Twenty-four Maori children came on that day, and each had his or her name written down. The teacher Thomas Kendall noted on the roll that the students were to learn their ‘alphabet’ or ‘monosyllables’. Te Pahi’s son, seventeen-year-old ‘Towha’ [Tōwai], who knew the alphabet, was the teacher’s assistant. To commemorate the school’s opening, our article describes the first school and some of what went on there, and comments on its short 2-year life.

Background There is a strong interest in the concept of developmental origins of health and disease and their influence on various factors “from cradle to grave”. Despite the increasing appreciation of this lifelong legacy across the human life course, many gaps remain in the scientific understanding of mechanisms influencing these formative phases. Cross-generational susceptibility to health problems is emerging as a focus of research in the context of birth cohort studies. The primary aim of the Illawarra Born study is to make scientific discoveries associated with improving health and wellbeing across the lifespan, with a particular focus on preventable chronic diseases, especially mental health. This birth cohort study will follow and collect data from three cohorts representing different stages across the lifespan: infants, adults (parents) and older adults (grandparents). The multi-generational, cross-sectional and longitudinal design of this birth cohort study supports a focus on the contributions of genetics, environment and lifestyle on health and wellbeing. The feasibility of conducting a multi-generational longitudinal birth cohort project was conducted through a small pilot study. Methods/design The purpose of this paper is to report on the feasibility and acceptability of the research protocol for a collaborative cross-generation health study in the community and test recruitment and outcome measures for the main study. This feasibility study included pregnant women who were intending to give birth in the Illawarra-Shoalhaven region in Eastern Australia. The area includes a large, regional referral hospital, with capacity to treat specialist and complex cases. Pregnant women were asked to participate in five data collection waves beginning at 22 weeks gestation and ending with a 6-month post-partum appointment. Recruitment was then extended, via the pregnant women, to also include fathers and maternal grandmothers. Discussion This feasibility study focused on the perinatal period and collected data across three multi-disciplinary domains including mental health, diet, exposures to toxins and the role of these in maternal and infant outcomes. Forty-one families participated in extensive data collection from 22 weeks gestation to 6-months post-partum. Factors impacting on viability and feasibility including recruitment solutions provide the basis for a large-scale study.

Context: In the United States, regional poison centers frequently receive calls about toxic workplace exposures. Most poison centers do not share call details routinely with governmental regulatory agencies. Worker health and safety could be enhanced if regulators such as the Occupational Safety and Health Administration (OSHA) had the ability to investigate these events and prevent similar incidents. With this goal in mind, the Georgia Poison Center (GPC) began referring occupational exposures to OSHA in July 2014. Methods: GPC began collecting additional employer details when handling occupational exposure calls. When workers granted permission, GPC forwarded call details to the OSHA Regional Office in Atlanta. These referrals enabled OSHA to initiate several investigations. We also analyzed all occupational exposures reported to GPC during the study period to characterize the events, detect violations of OSHA reporting requirements, and identify hazardous scenarios that could form the basis for future OSHA rulemaking or guidance. Results: GPC was informed about 953 occupational exposures between 1 July, 2014 and 7 January, 2016. Workers were exposed to 217 unique substances, and 70.3% of victims received treatment in a healthcare facility. Hydrogen sulfide was responsible for the largest number of severe clinical effects. GPC obtained permission to refer 89 (9.3%) calls to OSHA. As a result of these referrals, OSHA conducted 39 investigations and cited 15 employers for “serious” violations. OSHA forwarded several other referrals to other regulatory agencies when OSHA did not have jurisdiction. At least one employer failed to comply with OSHA’s new rule that mandates reporting of all work-related hospitalizations. This collaboration increased OSHA’s awareness of dangerous job tasks including hydrofluoric acid exposure among auto detailers and carbon monoxide poisoning with indoor use of gasoline-powered tools. Conclusions: Collaboration with the GPC generated a useful source of referrals to OSHA. OSHA investigations led to abatement of existing hazards, and OSHA acquired new knowledge of occupational exposure scenarios.

Background Seqirus 2010 Southern Hemisphere split-virion trivalent inactivated influenza vaccine (IIV3) was associated with increased febrile reactions in children. Studies in vitro concluded that increasing concentrations of splitting agent decreased residual lipids and attenuated proinflammatory cytokine signals associated with fever. We assessed immunogenicity and safety of a quadrivalent inactivated influenza vaccine (IIV4; produced using higher concentration of splitting agent) versus a United States-licensed comparator IIV4 in healthy children aged 5–17 years. Methods Participants (N = 2278) were randomized 3:1 and stratified by age (5–8 years; 9–17 years) to receive IIV4 (n = 1709) or comparator IIV4 (n = 569). Primary objective was to demonstrate noninferiority of IIV4 versus comparator IIV4 as assessed by hemagglutination inhibition (HI) geometric mean titer (GMT) ratio (upper bound of two-sided 95% confidence interval [CI] ≤ 1.5) and difference in seroconversion rate (upper bound of two-sided 95% CI ≤ 10%) for all four vaccine strains. HI antibody titers were assessed at baseline and 28 days postvaccination. Solicited and unsolicited adverse events were assessed during each 7- and 28-day postvaccination period, respectively. Results IIV4 met immunogenicity criteria for noninferiority. Adjusted GMT ratios (comparator IIV4/IIV4) for A/H1N1, A/H3N2, B/Yamagata, and B/Victoria strains were 1.01 (95% CI; 0.93, 1.09), 1.05 (0.96, 1.15), 0.89 (0.81, 0.98), and 0.92 (0.83, 1.02), respectively. Corresponding values for differences (95% CI) in seroconversion rates (comparator IIV4 minus IIV4) were −3.1 (−8.0, 1.8), 0.4 (−4.5, 5.3), −3.4 (−8.3, 1.5), and −2.0 (−6.9, 2.9). Fever rates were numerically higher, but not statistically different, with IIV4 versus comparator IIV4. No new safety signals were reported. Conclusion IIV4 demonstrated immunological noninferiority to the comparator IIV4 with a clinically acceptable safety profile in children aged 5–17 years. Increased levels of virus splitting agent seem to have reduced fever rates observed in children with Seqirus IIV3, particularly those aged 5–8 years. Funding: Seqirus Pty Ltd; Clinicaltrials.gov identifier: NCT02545543 .

AimLearning from Excellence (LfE), a positive reporting initiative, has two main objectives: to capture and learn from episodes of excellent practice and boost morale through positive feedback. The PRAISe project,2 tests the hypothesis that positive reporting and appreciative inquiry (AI) can be used as interventions to facilitate behavioural change and improvement in antimicrobial stewardship.MethodsLfE was applied as a quality improvement (QI) intervention for antimicrobial use on PICU over a 12 month period: baseline (3 months), intervention (6 months) and post intervention (3 months) phases. 31 PICU charts were screened weekly by PICU research nurses, this included any documentation added by a pharmacist to improve antimicrobial stewardship. Positive reports (IR2) were generated for gold standard prescriptions and excellence in antimicrobial stewardship, followed up by AI. QI suggestions derived from AIs were applied to the antimicrobial stewardship programme of the unit e.g. RAG rating antibiotics to the prescription charts. PICU pharmacists recorded interventions relating to antimicrobials during the data collection period. Pharmacist interventions were split into proactive or reactive: proactive involving advance confirmation that prescriptions were individualised to best therapy for patients and reactive if a prescription was incorrectly written or no clarification was sought from the pharmacist during ward round. Mini-AI interviews were conducted with the pharmacists at the end of the QI project to assess their opinions on changes to the antimicrobial stewardship programme.ResultsThe chart reviews by nursing staff highlighted 98 pharmacist interventions at baseline, 275 during the intervention phase and 80 post intervention. The pharmacists recorded an extra 138, 340 and 135 baseline, during and post intervention. Proactive intervening increased during each phase 68 (49.2%), 183 (53.8%) and 84 (62.2%), respectively. Thirty eight out of the 613 (6.2%) extra interventions were not accepted, with 25 (65.7%) of these being reactive.Gold standard prescribing improved during the intervention stage and was sustained in the post intervention phase. QI interventions brought out from the AIs involving pharmacists included RAG rating antibiotics according to priority to de- escalate to a narrower spectrum and presence at the daily microbiology round to document and communicate decisions to the wider team. AIs held with the pharmacists post project included the following themes: improved antimicrobial knowledge and understanding for directed therapy, greater communication ‘as now part of the PICU microbiology team’, ‘increased confidence to challenge antimicrobial decisions’. The pharmacists perceive there continues to be an increase in antimicrobial discussions on the daily PICU ward round.ConclusionPositive re-enforcement can improve a prescriber’s antimicrobial prescribing and documentation and encourage them to proactively seek pharmacy input to ensure best directed therapy for antimicrobials. This contributes to the overall quality of antimicrobial stewardship and patient care on the unit.ReferencesKelly N et al Learning from excellence in healthcare: a new approach to incident reporting. http://adc.bmj.com/content/101/9/7882Plunkett A, et al. Positive Reporting and Appreciative Inquiry in Sepsis (PRAISe). https://www.health.org.uk/improvement-projects/positive-reporting-and-appreciative-inquiry-in-sepsis-praise (Accessed 13 May 2019)

Objective To examine the physical and mental health status of individuals directly affected by the 2002 Bali bombing, 8 years after the incident. Design, setting and participants Cross-sectional study of people directly exposed to and/or bereaved by the 2002 Bali bombing who had participated in a New South Wales Health therapeutic support program. Telephone interviews were conducted during July - November 2010. The sample was weighted to reflect the population of interest, registered participants in the program (n = 115). Main outcome measures Self-rated physical health, personal resilience (Connor-Davidson Resilience Scale), past-03 psychological distress and daily functioning (Kessler Psychological Distress Scale), and traumatic stress-related symptoms (Primary Care PTSD Screen). Results Of 81 individuals contacted, 55 responded (68%). Mean age of respondents was 50 years (range, 20-73 years), 32 were female, and seven were physically injured in the bombing. Most (45/55) reported good physical health, but 12 were experiencing high or very high levels of psychological distress. Being injured in the attack was associated with current functional impairment (P = 0.04) and very high levels of distress (P = 0.005). Lower distress was associated with perceived family support (P> = 0.03) and being in a marital or de facto relationship (P = 0.02). Complicated grief factors were consistently associated with high psychological distress, traumatic stress-related symptoms and lower personal resilience. Conclusions Eight years after the bombing, directly affected individuals had good physical health but relatively high rates of psychological distress. Marital or de facto relationships and perceived family support appear to be protective factors against long-term distress. Bereavement factors were the strongest correlates of trauma symptoms and distress. Outreach and screening programs incorporating complicated grief items may be useful in the longer-term support of such individuals.