Orexin/hypocretin role in reward: implications for opioid and other addictions

Addiction is a devastating disorder that affects 15.3 million people worldwide. While prevalent, few effective treatments exist. Orexin receptors have been proposed as a potential target for anti-craving medications. Orexins, also known as hypocretins, are neuropeptides produced in neurons of the lateral and dorsomedial hypothalamus and perifornical area, which project widely throughout the brain. The absence of orexins in rodents and humans leads to narcolepsy. However, orexins also have an established role in reward seeking. This review will discuss some of the original studies describing the roles of the orexins in reward seeking as well as specific works that were presented at the 2013 International Narcotics Research Conference. Orexin signalling can promote drug-induced plasticity of glutamatergic synapses onto dopamine neurons of the ventral tegmental area (VTA), a brain region implicated in motivated behaviour. Additional evidence suggests that orexin signalling can also promote drug seeking by initiating an endocannabinoid-mediated synaptic depression of GABAergic inputs to the VTA, and thereby disinhibiting dopaminergic neurons. Orexin neurons co-express the inhibitory opioid peptide dynorphin. It has been proposed that orexin in the VTA may not mediate reward per se, but rather occludes the ‘anti-reward’ effects of dynorphin. Finally, orexin signalling in the prefrontal cortex and the central amygdala is implicated in reinstatement of reward seeking. This review will highlight recent work describing the role of orexin signalling in cellular processes underlying addiction-related behaviours and propose novel hypotheses for the mechanisms by which orexin signalling may impart drug seeking.

Improved Kalman filter initialisation using neurofuzzy estimation

It is traditional to initialise Kalman filters and extended Kalman filters with estimates of the states calculated directly from the observed (raw) noisy inputs, but unfortunately their performance is extremely sensitive to state initialisation accuracy: good initial state estimates ensure fast convergence whereas poor estimates may give rise to slow convergence or even filter divergence. Divergence is generally due to excessive observation noise and leads to error magnitudes that quickly become unbounded (R.J. Fitzgerald, 1971). When a filter diverges, it must be re initialised but because the observations are extremely poor, re initialised states will have poor estimates. The paper proposes that if neurofuzzy estimators produce more accurate state estimates than those calculated from the observed noisy inputs (using the known state model), then neurofuzzy estimates can be used to initialise the states of Kalman and extended Kalman filters. Filters whose states have been initialised with neurofuzzy estimates should give improved performance by way of faster convergence when the filter is initialised, and when a filter is re started after divergence

Sectionalizing strategies for minimizing outage durations of critical loads in parallel power system restoration with bi-level programming

Fast restoration of critical loads and non-black-start generators can significantly reduce the economic losses caused by power system blackouts. In a parallel power system restoration scenario, the sectionalization of restoration subsystems plays a very important role in determining the pickup of critical loads before synchronization. Most existing research mainly focuses on the startup of non-black-start generators. The restoration of critical loads, especially the loads with cold load characteristics, has not yet been addressed in optimizing the subsystem divisions. As a result, sectionalized restoration subsystems cannot achieve the best coordination between the pickup of loads and the ramping of generators. In order to generate sectionalizing strategies considering the pickup of critical loads in parallel power system restoration scenarios, an optimization model considering power system constraints, the characteristics of the cold load pickup and the features of generator startup is proposed in this paper. A bi-level programming approach is employed to solve the proposed sectionalizing model. In the upper level the optimal sectionalizing problem for the restoration subsystems is addressed, while in the lower level the objective is to minimize the outage durations of critical loads. The proposed sectionalizing model has been validated by the New-England 39-bus system and the IEEE 118-bus system. Further comparisons with some existing methods are carried out as well.

Ocular refractive and biometric characteristics in patients with tilted disc syndrome

Purpose: To evaluate the ocular refractive and biometric characteristics in patients with tilted disc syndrome (TDS). Methods: This case-control study comprised 41 eyes of 25 patients with established TDS and forty eyes of 20 age- and sex-matched healthy control subjects. All had a complete ocular examination including refraction and analysis using Fourier transformation, slit lamp biomicroscopy, pachymetry keratometry, and ocular biometry. Corneal topography examinations were performed in the syndrome group only. Results: There were no significant differences in spherical equivalent (p = 0.334) and total astigmatism (p= 0.246) between groups. However, mean best spectacular corrected visual acuity was significantly worse in TDS patients (P < 0.001). The lenticular astigmatism was significantly greater in the syndrome group, while the corneal component was greater in the controls (p = 0.004 and p = 0.002, respectively). The measured biometric features were the same in both groups, except for the lens thickness, relative lens position, and lens-axial length factor which were greater in the TDS group (p = 0.002, p = 0.015, and p = 0.025, respectively). Conclusions: Clinically significant lenticular astigmatism, more oblique corneal astigmatism, and thicker lens were characteristic findings in patients with TDS.

Changes in white matter connectivity following therapy for anomia post stroke

Background. The majority of studies investigating the neural mechanisms underlying treatment-induced recovery in aphasia have focused on the cortical regions associated with language processing. However, the integrity of the white matter connecting these regions may also be crucial to understanding treatment mechanisms. Objective. This study investigated the integrity of the arcuate fasciculus (AF) and uncinate fasciculus (UF) before and after treatment for anomia in people with aphasia. Method. Eight people with aphasia received 12 treatment sessions to improve naming; alternating between phonologically-based and semantic-based tasks, with high angular resolution diffusion imaging conducted pre and post treatment. The mean generalized fractional anisotropy (GFA), a measure of fiber integrity, and number of fibers in the AF and UF were compared pre and post treatment, as well as with a group of 14 healthy older controls. Results. Pre treatment, participants with aphasia had significantly fewer fibers and lower mean GFA in the left AF compared with controls. Post treatment, mean GFA increased in the left AF to be statistically equivalent to controls. Additionally, mean GFA in the left AF pre and post treatment positively correlated with maintenance of the phonologically based treatment. No differences were found in the right AF, or the UF in either hemisphere, between participants with aphasia and controls, and no changes were observed in these tracts following treatment. Conclusions. Anomia treatments may improve the integrity of the white matter connecting cortical language regions. These preliminary results add to the understanding of the mechanisms underlying treatment outcomes in people with aphasia post stroke.

A happy compromise: Collaborative approaches to school library designing

Designing a school library is a complex, costly and demanding process with important educational and social implications for the whole school community. Drawing upon recent research, this paper presents contrasting snapshots of two school libraries to demonstrate the impacts of greater and lesser collaboration in the designing process. After a brief literature review, the paper outlines the research design (qualitative case study, involving collection and inductive thematic analysis of interview data and student drawings). The select findings highlight the varying experiences of each school’s teacher-librarian through the four designing phases of imagining, transitioning, experiencing and reimagining. Based on the study’s findings, the paper concludes that design outcomes are enhanced through collaboration between professional designers and key school stakeholders including teacher-librarians, teachers, principals and students. The findings and recommendations are of potential interest to teacher-librarians, school principals, education authorities, information professionals and library managers, to guide user-centred library planning and resourcing.

Wastewater analysis of Census day samples to investigate per capita input of organophosphorus flame retardants and plasticizers into wastewater

The use of organophosphate esters (PFRs) as flame retardants and plasticizers has increased due to the ban of some brominated flame retardants. There is however some concern regarding the toxicity, particularly carcinogenicity and neurotoxicity, of some of the PFRs. In this study we applied wastewater analysis to assess use of PFRs by the Australian population. Influent samples were collected from eleven wastewater treatment plants (STPs) in Australia on Census day and analysed for PFRs using gas chromatography coupled with mass spectrometry (GC-MS). Per capita mass loads of PFRs were calculated using the accurate Census head counts. The results indicate that tris(2-butoxyethyl) phosphate (TBOEP) has the highest per capita input into wastewater followed by tris(2-chloroisopropyl) phosphate (TCIPP), tris(isobutyl) phosphate (TIBP), tris(2-chloroethyl) phosphate (TCEP) and tris(1,3-dichloroisopropyl) phosphate (TDCIPP). Similar PFR profiles were observed across the Australian STPs and a comparison with European and U.S. STPs indicated similar PFR concentrations. We estimate that approximately 2.1 mg person−1 day−1 of PFRs are input into Australian wastewater which equates to 16 tonnes per annum.

Copper-doped mesoporous silica nanospheres, a promising immunomodulatory agent for inducing osteogenesis

The application of mesoporous silica nanospheres (MSNs) loaded with drugs/growth factors to induce osteogenic differentiation of stem cells has been trialed by a number of researchers recently. However, limitations such as high cost, complex fabrication and unintended side effects from supraphysiological concentrations of the drugs/growth factors represent major obstacles to any potential clinical application in the near term. In this study we reported an in situ one-pot synthesis strategy of MSNs doped with hypoxia-inducing copper ions and systematically evaluated the nanospheres by in vitro biological assessments. The Cu-containing mesoporous silica nanospheres (Cu-MSNs) had uniform spherical morphology (∼100 nm), ordered mesoporous channels (∼2 nm) and homogeneous Cu distribution. Cu-MSNs demonstrated sustained release of both silicon (Si) and Cu ions and controlled degradability. The Cu-MSNs were phagocytized by immune cells and appeared to modulate a favorable immune environment by initiating proper pro-inflammatory cytokines, inducing osteogenic/angiogenic factors and suppressing osteoclastogenic factors by the immune cells. The immune microenvironment induced by the Cu-MSNs led to robust osteogenic differentiation of bone mesenchymal stem cells (BMSCs) via the activation of Oncostation M (OSM) pathway. These results suggest that the novel Cu-MSNs could be used as an immunomodulatory agent with osteostimulatory capacity for bone regeneration/therapy application. Statement of significance In order to stimulate both osteogenesis and angiogenesis of stem cells for further bone regeneration, a new kind of hypoxia-inducing copper doped mesoporous silica nanospheres (Cu-MSNs) were prepared via one-pot synthesis. Biological assessments under immune environment which better reflect the in vivo response revealed that the nanospheres possessed osteostimulatory capacity and had potential as immunomodulatory agent for bone regeneration/therapy application. The strategy of introducing controllable amount of therapeutic ions instead of loading expensive drugs/growth factors in mesoporous silica nanosphere provides new options for bioactive nanomaterial functionalization.

A lifespan perspective on psychological contracts and their relations with organizational commitment

The current study investigated the influence of age-related constructs on the psychological contract and its relationships with continuance and normative commitment. It was proposed that as people age, their future time perspective (FTP) decreases. Consequently, it was expected that contract fulfilment would be positively related to continuance commitment for workers with short FTP, while it would be positively related to normative commitment for workers with long FTP. Conversely, it was argued that, with age, workers’ perceived work-related expertise increases, resulting in stronger reactions to obligation fulfilment on normative commitment. A study among 334 employees showed that FTP and work-related expertise indeed moderated the relationships between contract fulfilment and organizational commitment. The results showed that the influence of age on the relations between contract fulfilment with outcomes is dependent upon FTP and occupational expertise. The study shows the value of a lifespan perspective on psychological contracts and their relations with organizational commitment.

An insight into the adoption of accountable-eHealth systems: n empirical research model based on the Australian context

This paper provides a first look at the acceptance of Accountable-eHealth (AeH) systems–a new genre of eHealth systems designed to manage information privacy concerns that hinder the proliferation of eHealth. The underlying concept of AeH systems is appropriate use of information through after-the-fact accountability for intentional misuse of information by healthcare professionals. An online questionnaire survey was utilised for data collection from three educational institutions in Queensland, Australia. A total of 23 hypotheses relating to 9 constructs were tested using a structural equation modelling technique. The moderation effects on the hypotheses were also tested based on six moderation factors to understand their role on the designed research model. A total of 334 valid responses were received. The cohort consisted of medical, nursing and other health related students studying at various levels in both undergraduate and postgraduate courses. Hypothesis testing provided sufficient data to accept 7 hypotheses. The empirical research model developed was capable of predicting 47.3% of healthcare professionals’ perceived intention to use AeH systems. All six moderation factors showed significant influence on the research model. A validation of this model with a wider survey cohort is recommended as a future study.

The radical in arts education research

Arts education research, as an interdisciplinary field, has developed in the shadows of a number of research traditions. However amid all the methodological innovation, I believe there is one particular, distinctive and radical research strategy which arts educators have created to research the practice of arts education: namely arts-based research. For many, and Elliot Eisner from Stanford University was among the first, arts education needed a research approach which could deal with the complex dynamics of arts education in the classroom. What was needed was ‘an approach to the conduct of educational research that was rooted in the arts and that used aesthetically crafted forms to reveal aspects of practice that mattered educationally’ (Eisner 2006: 11). While arts education researchers were crafting the principles and practices of arts-based research, fellow artist/researchers in the creative arts were addressing similar needs and fashioning their own exacting research strategies. This chapter aligns arts-based research with the complementary research practices established in creative arts studios and identifies the shared and truly radical nature of these moves. Finally, and in a contemporary turn many will find surprising, I will discuss how the radical aspects of these methodologies are now being held up as core elements of what is being called the fourth paradigm of scientific research, known as eScience. Could it be that the radical dynamics of arts-based research pre-figured the needs of eScience researchers who are currently struggling to manage the ‘deluge of Big Data’ which is disrupting their well-established scientific methods?

Comparison of partial extraction reagents for assessing potential bioavailability of heavy metals in sediments

Assessment of heavy metal bioavailability in sediments is complex because of the number of partial extraction methods available for the assessment and the general lack of certified reference materials. This study evaluates five different extraction methodologies to ascertain the relative strengths and weaknesses of each method. The results are then compared to previously published work to ascertain the most effective partial extraction technique, which was established to be dilute (0.75 – 1 M) nitric acid solutions. These results imply that single reagent; weak acid extractions provide a better assessment of potentially bioavailable metals than the chelating agents used in sequential extraction methods.