Dopamine dysregulation syndrome : implications for a dopamine hypothesis of bipolar disorder

Objective: Rational therapeutic development in bipolar is hampered by a lack of pathophysiological model. However, there is a wealth of converging data on the role of dopamine in bipolar disorder. This paper therefore examines the possibility of a dopamine hypothesis for bipolar disorder.

Method: A literature search was conducted using standard search engines Embase, PyschLIT, PubMed and MEDLINE. In addition, papers and book chapters known to the authors were retrieved and examined for further relevant articles.

Results: Collectively, in excess of 100 articles were reviewed from which approximately 75% were relevant to the focus of this paper.

Conclusion: Pharmacological models suggest a role of increased dopaminergic drive in mania and the converse in depression. In Parkinson’s disease, administration of high-dose dopamine precursors can produce a ‘maniform’ picture, which switches into a depressive analogue on withdrawal. It is possible that in bipolar disorder there is a cyclical process, where increased dopaminergic transmission in mania leads to a secondary down regulation of dopaminergic receptor sensitivity over time. This may lead to a period of decreased dopaminergic transmission, corresponding with the depressive phase, and the repetition of the cycle. This model, if verified, may have implications for rational drug development.

Undoing lithium ion association in ionic liquids through the complexation by oligoethers

Tetraglyme (TG) and the recently developed trimethylsilyl capped analogue (1NM3) when used as additives in a N-methyl-N-propylpyrrolidinium bis(trifluoromethylsulfonyl) amide [C₃mpyr][NTf₂]/0.65 M LiNTf₂ electrolyte have been shown to dramatically enhance the transport properties of this electrolyte. In fact, at a concentration of 20 mol % tetraglyme (leading to a ratio of ~1:1 ether molecule per lithium ion), viscosity, conductivity, and the diffusion coefficients of the C₃mpyr⁺ and NTf₂⁻ are practically reinstated to the values observed in the absence of lithium, thereby negating the structuring effects of the lithium ion. The ⁷Li T₁ relaxation times also indicate that these additives strongly interact with the lithium ions. Furthermore, although TG has twice the viscosity of 1NM3, the greatest improvement in transport properties was observed for TG.

Electrooxidation of [(η5-C5H5)Fe(CO)2]2 as a probe of the nucleophilic properties of ionic liquid anions

The oxidative electrochemistry of [CpFe(CO)2]2, 1 (Cp = [η5-C5H5]–), was examined in detail in ionic liquids (ILs) composed of ions of widely varying Lewis acid−base properties. Cyclic voltammetric responses were strongly dependent on the nucleophilic properties of the IL anion, but all observations are consistent with the initial formation of 1+ followed by attack from the IL anion. In [NTf2]–-based ILs ([NTf2]– = bis(trifluoromethylsulfonyl)amide), the process shows nearly ideal chemical reversibility as the reaction between 1+ and [NTf2]– is very slow. This is highly significant, as 1+ is known to be highly susceptible to nucleophilic attack and its stability indicates a remarkable lack of coordinating ability of these ILs. In 1-methyl-3-butylimidazolium hexafluorophosphate, [bmim][PF6], the oxidation of 1 is still largely reversible, but there is more pronounced evidence of [PF6]– coordination. In contrast, 1 exhibits an irreversible two-electron oxidation process in a dicyanamide-based IL. This overall oxidation process is thought to proceed via an ECE mechanism, details of which are presented. Rate constants were estimated by fitting the experimental data to digital simulations of the proposed mechanism. The use of [NTf2]–-based ILs as a supporting electrolyte in CH2Cl2 was examined by using this solvent/electrolyte as a medium in which to perform bulk electrolyses of 1 and 1*, the permethylated analogue [Cp*Fe(CO)2]2 (Cp* = [η5-C5(CH3)5]–). These cleanly yielded the corresponding binuclear radical-cation species, 1+ and 1*+, which were subsequently characterized by electron paramagnetic resonance (EPR) spectroscopy. In addition to the above oxidation studies, the reduction of 1 was studied in each of the ILs; differences in cathodic peak potentials are attributed, in part, to ion-pairing effects. This study illustrates the wide range of electrochemical environments available with ILs and demonstrates their utility for the investigation of the redox properties of metal carbonyls and other organometallic compounds.

Structure–activity relationships of adenosines with heterocyclic N6-substituents

Two series of N⁶-substituted adenosines with monocyclic and bicyclic N⁶ substituents containing a heteroatom were synthesized in good yields. These derivatives were assessed for their affinity ([³H]CPX), potency, and intrinsic activity (cAMP accumulation) at the A₁ adenosine receptor in DDT₁ MF-2 cells. In the monocyclic series, the N⁶-tetrahydrofuran-3-yl and thiolan-3-yl adenosines (1 and 26, respectively) were found to possess similar activities, whereas the corresponding selenium analogue 27 was found to be more potent. A series of nitrogen containing analogues showed varying properties, N⁶-((3R)-1-benzyloxycarbonylpyrrolidin-3-yl)adenosine (30) was the most potent at the A₁AR; IC₅₀ = 3.2 nM. In the bicyclic series, the effect of a 7-azabicyclo[2.2.1]heptan-2-yl substituent in the N⁶-position was explored. N⁶-(7-Azabicyclo[2.2.1]heptan-2-yl)adenosine (38) proved to be a reasonably potent A₁ agonist (K_i = 51 nM, IC₅₀ = 35 nM) while further substitution on the 7″-nitrogen with tert-butoxycarbonyl (31, IC₅₀ = 2.5 nM) and 2-bromobenzyloxycarbonyl (34, IC₅₀ = 9.0 nM) gave highly potent A₁AR agonists.

Double horizons : shifting figure and ground in some Australian photography

Autonomy 2 synth stinger

An uplifting electronica synth stinger created on both analogue and software synths.

Autonomy full length ambient electronic

A full length composition that is ambient electronic in style and features analogue and software synths with electronic drums. A gentle sound-bed that would suit contemplative design projects.

Autonomy synth stinger

An uplifting electronica synth stinger created on both analogue and software synths.

Performing the technical image

The recent public multi-screen performance of formalist experimental animation by film artists such as Guy Sherwin, Bruce McLure and Greg Pope respond to the immediacy and speed of new digital technologies, the rise of Vilem Flusser’s ‘technical image’ and the consequent disappearance of reflective space identified by Prensky, Kroker, Virilio and Postman. Flusser’s ‘technical images’, benefiting from the digital’s painterly hyper-malleability structure and content, signifier and signified, so much the subject of Peter Gidal’s arguments in support of his concept of ‘materialist film’ in the 1970’s.  In the digital those formal editing strategies used to create the ‘technical image’ within analogue image construction that traditionally took place in the artist’s studio within the camers and optical printer are now executed inside the computer, having migrated into the post-production process.  Within the work of these artist’s recent multi-screen presentations these manipulations are now-elusively experienced in live ephemeral performance, re-forming and laying bare those processes that have been rendered invisible in digital technology.  The significance of this work partly lies in its ability to communicate historical information a-historically. Guy Sherwin and Lynn Loo’s method in their play with 16mm film flashes and after-images and Sherwin’s mirror performance further reproduces Goethe’s method from his Theory of Colours (1840). Greg Pope’s scratch performances re-enact the operation of Konrad Zuse’s 1930’s computing machine. Affinities are drawn between Bruce McLure’s immersive overpowering sonic and flicker performances with Edwin Land’s 1960’s experiments on colour constancy on which Land’s Retinex Theory of colour is based.

Flusser's death rattle

A live film performance using magnificent 16mm featuring Dirk De Bruyn in person. Can an image be sonic and ephemeral in the digital age? Live 3-screen film projection, shadow-play and sound poetry plumbing 35 years of experimental film practice, laying bare those processes of graffiti production splattered across the alleyways and railway lines of the planet’s inner cities but whose performance threatens to become completely hidden inside the computer. Images scratched, dyed, bleached and redrawn by hand are brought together to immerse the audience in an aural-visual rant. Does the analogue answer back to the digital media explosion or merely succumb in an angry death rattle of lost causes? Rev presents a rare opportunity to see one of Australia’s most important experimental filmmakers presenting a unique expanded cinema event.

Objective radiological disease control with Sandostatin monotherapy in metastatic neuroendocrine tumours

Conventional cytotoxic chemotherapy is not usually effective in neuroendocrine tumours (NET). Somatostatin analogues (SSA) such as octreotide (Sandostatin; octreotide LAR and lanreotide) are typically used to treat symptoms caused by NET, but not as the primary treatment aiming for an objective response. Recently, results from the PROMID (Placebo-controlled prospective Randomized study on the antiproliferative efficacy of Octreotide LAR in patients with metastatic neuroendocrine MIDgut tumours) trial were published showing that octreotide LAR significantly lengthens the time to tumour progression compared with a placebo in patients with functionally active and inactive metastatic midgut NET. We report a retrospective descriptive analysis of six patients, treated at two Australian institutions, who obtained an objective radiological tumour response on long acting SSA. In this retrospective series of NET, radiological responses were observed using single agent SSA, which was administered mainly for symptom management. This could be due to an antiproliferative and/or antiangiogenic activity of this agent in NET. A response can occur beyond 12 months, which might explain why the response rate is under reported in NET trials. Further investigation in prospective trials is warranted and the possibility for late responses might have implications for trial design.

RGB Wattle Park chalet

New technologies have arguably displaced the hegemony of painting within the hierarchies of contemporary art. Projectors and other digital imaging technologies in particular continue to expand the contemporary artist’s aesthetic and conceptual possibilities beyond canvas, paper, and stone. Yet painting - the practice of smearing coloured mud about - far from being superseded, simply continues to cannibalise these powerful technologies extruding them into its own analogue processes. Whether intentionally or as an by-product of this cannibalisation, painting tends to create a critical distance in which the tacit aspects of these technologies – their representational language and ‘special effects’ - are made fully visible. Of course 'easel' painting practices persist not only to critique new technologies. Rather new technologies inevitably fold back into the now souped-up vocabularies of contemporary painting, expanding the medium’s physical boundaries, formal strategies, and modes of display.

YGR Fontainebleau

New technologies have arguably displaced the hegemony of painting in the hierarchies of contemporary art. Projectors and other digital imaging tools in particular continue to expand the artist’s aesthetic and conceptual possibilities beyond canvas, paper, and stone. Yet painting, (the practice of smearing coloured mud about) far from being marginalised, simply continues to cannibalise these new technologies extruding them into its own analogue processes. Whether intentionally or as a by-product of this cannibalisation, painting creates a critical distance in which the tacit aspects of these technologies – their representational language and ‘special effects’ - are made fully visible. Of course ‘traditional’ easel painting practices persist not just to critique new technologies. Digital imaging technologies inevitably feed back into the souped-up vocabularies of contemporary painting, expanding the medium’s physical boundaries, formal strategies, and modes of display. The work for this project explores the ways in which projection and virtual geographical mapping invite new configurations for the practice of landscape painting.

YGR Warrandyte

New technologies have arguably displaced the hegemony of painting in the hierarchies of contemporary art. Projectors and other digital imaging tools in particular continue to expand the artist’s aesthetic and conceptual possibilities beyond canvas, paper, and stone. Yet painting, (the practice of smearing coloured mud about) far from being marginalised, simply continues to cannibalise these new technologies extruding them into its own analogue processes. Whether intentionally or as an by-product of this cannibalisation, painting creates a critical distance in which the tacit aspects of these technologies – their representational language and ‘special effects’ - are made visible. Of course ‘traditional’ easel painting practices persist not just to critique new technologies. Digital imaging technologies inevitably feed back into the souped-up vocabularies of contemporary painting, expanding the medium’s physical boundaries, formal strategies, and modes of display. The work for this project explores the ways in which projection and virtual geographical mapping invite new configurations for the practice of landscape painting.

Scientific foundations for an IUCN red list of ecosystems

 An understanding of risks to biodiversity is needed for planning action to slow current rates of decline and secure ecosystem services for future human use. Although the IUCN Red List criteria provide an effective assessment protocol for species, a standard global assessment of risks to higher levels of biodiversity is currently limited. In 2008, IUCN initiated development of risk assessment criteria to support a global Red List of ecosystems. We present a new conceptual model for ecosystem risk assessment founded on a synthesis of relevant ecological theories. To support the model, we review key elements of ecosystem definition and introduce the concept of ecosystem collapse, an analogue of species extinction. The model identifies four distributional and functional symptoms of ecosystem risk as a basis for assessment criteria: a) rates of decline in ecosystem distribution; b) restricted distributions with continuing declines or threats; c) rates of environmental (abiotic) degradation; and d) rates of disruption to biotic processes. A fifth criterion, e) quantitative estimates of the risk of ecosystem collapse, enables integrated assessment of multiple processes and provides a conceptual anchor for the other criteria. We present the theoretical rationale for the construction and interpretation of each criterion. The assessment protocol and threat categories mirror those of the IUCN Red List of species. A trial of the protocol on terrestrial, subterranean, freshwater and marine ecosystems from around the world shows that its concepts are workable and its outcomes are robust, that required data are available, and that results are consistent with assessments carried out by local experts and authorities. The new protocol provides a consistent, practical and theoretically grounded framework for establishing a systematic Red List of the world’s ecosystems. This will complement the Red List of species and strengthen global capacity to report on and monitor the status of biodiversity.