Combination pharmacotherapy in unipolar depression

It is estimated that between 60 and 80% of those with major depressive disorder do not achieve full symptomatic remission from first-line antidepressant monotherapy. Residual depressive symptoms substantially impair quality of life and add to the risk of recurrence. It is now clear that depression would benefit from more vigorous treatment, in order to ameliorate its disease burden. While there are established algorithms in situations of treatment resistance, the use of combination pharmacotherapy in unipolar depression is a relatively under-investigated area of treatment and may be an effective and tolerable strategy that maximizes the available resources. This paper reviews the current evidence for combination pharmacotherapy in unipolar depression and discusses its clinical applications.

Ecological notes on the East Gippsland burrowing crayfish Engaeus orientalis, including burrow structure and associated fauna

Despite Australia having a high diversity of freshwater crayfish species, the ecology of many of these species remains poorly known, particularly burrowing crayfish of the genus Engaeus. Biological information on colour, behaviour, burrow structure, associated burrow fauna and habitat of the East Gippsland Burrowing Crayfish Engaeus orientalis obtained during incidental observations in 2007 and 2008 is provided. The burrow structure took the form of radiating runways under a rock slab, while the burrow location was in a semi-disturbed site away from water. Both are atypical for this species.

Aiming for change by degrees

Our federal Education Minister believes too many Australians are falling through the cracks, writes Joanna Mather.

Addressing a group of doctoral graduates in Melbourne recently, federal Education Minister Julia Gillard used Barack Obama's election victory in the US to drive home the social and economic imperatives for getting more poor and disadvantaged Australians into universities.

Manipulating Islam and democracy in Iraq’s ‘Pluralised Authoritarianism’

With the realisation that the initial motives for the 2003 invasion of Iraq – Saddam’s alleged stockpile of Weapons of Mass Destruction (WMD) and his links to Al-Qaeda – were grievous intelligence errors the Bush administration, with varying degrees of success, were able to spin the war’s rasion d’etre and redefine the parameters of victory. A central tenet of this approach was to begin speaking about democracy as if it had always been one of the aims of the war itself. For the first few years, the effort to democratise Iraq appeared to gain some credible momentum: a complex array of political, religious and ethno-sectarian factions formed political parties and civil society movements; uncensored news was enthusiastically consumed across the nation; Iraqi citizens took to the streets to protest key government decisions; and millions of Iraqis voted in relatively free and fair national elections (Davis, 2004, 2007, Isakhan, 2008, 2011b). Central to each of these developments were various Iraqi religious establishments – but especially those of the Shia Arab population of Iraq – who saw no distinction between their Islamic faith and the notion of democracy. Not surprisingly, a body of literature has emerged which has been very optimistic about Iraq’s engagement with both ‘Islam’ and ‘democracy’ in the post-Baathist period, while acknowledging the challenges it faces in creating a stable, egalitarian and democratic society (Al-Musawi, 2006, Cole, 2006, Davis, 2005, Dawisha, 2009, Isakhan, 2011a, Stansfield, 2007).

However, there have been virtually no studies which have sought to question this optimism in the light of more recent events. Addressing this lacuna, this paper documents the last few years (2006- 2011) which have seen many elements within the Iraqi political elite – most notably the Maliki government and his State of Law Coalition (SLC) – demonstrate what has been referred to in literature on other Arab states alternatively as ‘liberalised autocracy’ (Brumberg, 2002), ‘semi-authoritarianism’ (Ottaway, 2003) or ‘pluralised authoritarianism’ (Posusney and Angrist, 2005). That is to say, that these states consolidate their incumbency while putting in place measures that can be considered more or less liberal. To do this, the regime actually utilises (and controls) nominally democratic mechanisms such as elections, media freedoms, political opposition and civil society as part of their strategy to retain power. Of particular interest here are the ways in which the Maliki government – and Shia Arab Iraqi political factions more broadly – have manipulated both ‘Islam’ and ‘democracy’ towards such ‘pluralised authoritarianism’.

The Liam Jurrah story : from Yuendumu to the MCG

Known as the 'Warlpiri Warrior,' the 'Jurrahcane' and 'Cougar,' Liam Jurrah is a rising star of the AFL, known for his startling displays of skill, artistry and the 'deadly' impact of his football ability. But despite Liam's prodigious talent, he is a relative newcomer to the AFL. This book tells the incredible journey travelled by Liam, a fully initiated Warlpiri man, from the remote Aboriginal desert community of Yuendumu to the MCG, as the first of his kind to play football at an elite level. Along the way the book describes how the author and his family came to understand and treasure the richness of Liam's Warlpiri culture.

Effects of exercise on the isoelectric patterns of erythropoietin

Objectives: Recombinant erythropoietin has a strong impact on aerobic power and is therefore one of the most potent doping agents in endurance sports. The anti-doping control of this synthetic hormone relies on the detection, in the urine, of its isoelectric pattern, which differs from that of the corresponding natural hormone, the latter being typically more acidic than the former. However, a small number of natural urinary patterns, referred to as atypical patterns, are less acidic than the dominant form. Based on anecdotal evidence, the occurrence of such patterns seems to be related to particular strenuous exercises. This study aimed to demonstrate this relation using a strenuous exercise protocol.

Design: Seven athletes took part in a training protocol including a series of supramaximal short-duration exercises. Urine and blood samples were collected throughout the protocols.

Settings: World Cycling Center, Aigle, Switzerland, and research laboratories.

Participants: Seven top-level athletes (cyclists) were involved in this study.

Main Outcome Measures: Erythropoietin (EPO) isoelectric patterns were obtained by submitting blood and urine samples to isoelectric focusing. Additional protein dosages were performed.

Results: Supramaximal short-duration exercises induced the transformation of typical urinary natural EPO patterns into atypical ones. None of the obtained atypical patterns fulfilled the 3 criteria mandatory for reporting an adverse analytical finding. Serum EPO patterns were not affected by the exercises that caused the transformation of urinary patterns.

Conclusion: An exercise-induced transient renal dysfunction is proposed as a hypothetic explanation for these observations that rely on parallel investigations of proteinuria in the same samples.

Brief report : maltreatment in childhood and body concerns in adulthood

Objective: We examined the relationship between maltreatment in childhood and body concerns in adulthood.

Method: A community sample of 156 women and 143 men completed measures of maltreatment – frequency of sexual abuse, physical abuse, physical neglect, emotional abuse and emotional neglect – in childhood. They also reported current dissatisfaction with body weight and shape and drive for thinness and drive for muscle.

Results and conclusions: Childhood maltreatment was associated with drive for muscle in women and body dissatisfaction and drive for thinness in men. The results provide some evidence that adverse conditions in childhood can be associated with gender-atypical body concerns in adulthood.

Nef binds p6* in gagpol during replication of human immunodeficiency virus type 1

The atypical Nef protein (NefF12) from human immunodeficiency virus type 1 strain F12 (HIV-1F12) interferes with virion production and infectivity via a mysterious mechanism. The correlation of these effects with the unusual perinuclear subcellular localization of NefF12 suggested that the wild-type Nef protein could bind to assembly intermediates in late stages of viral replication. To test this hypothesis, Nef from HIV-1NL4-3 was fused to an endoplasmic reticulum (ER) retention signal (NefKKXX). This mutant NefKKXX protein recapitulated fully the effects of NefF12 on Gag processing and virion production, either alone or as a CD8 fusion protein. Importantly, the mutant NefKKXX protein also localized to the intermediate compartment, between the ER and the trans-Golgi network. Furthermore, Nef bound the GagPol polyprotein in vitro and in vivo. This binding mapped to the C-terminal flexible loop in Nef and the transframe p6* protein in GagPol. The significance of this interaction was demonstrated by a genetic assay in which the release of a mutant HIV-1 provirus lacking the PTAP motif in the late domain that no longer binds Tsg101 was rescued by a Nef.Tsg101 chimera. Importantly, this rescue as well as incorporation of Nef into HIV-1 virions correlated with the ability of Nef to interact with GagPol. Our data demonstrate that the retention of Nef in the intermediate compartment interferes with viral replication and suggest a new role for Nef in the production of HIV-1.

Description of systenobythere gen. nov. (Ostracoda, Crustacea) from the late miocene of southeastern Australia with comments on its problematical taxonomic and palaeoecological affinities

A new ostracod genus and species, Systenobythere archboldi, is described from late Miocene open neritic strata of southeastern Australia. Specimens occur in argillaceous glauconitic sands deposited in offshore continental shelf settings that were periodically influenced by coastal upwelling. Systenobythere archboldi possesses an adductor muscle scar pattern typical of the Bythocytheridae, but has a pentodont hinge and sieve-type normal pore canals atypical of this family.

Contests with the probability of a draw : a stochastic foundation

This article proposes a stochastic foundation for the contest success function (CSF for short) with a richer structure on the set of possible outcomes of the contest. Specifically, the analysis allows for the possibility of a draw, so that no contestant can claim a victory over all other players. Under plausible conditions, this article not only discovers new functional forms of CSFs, but also shows the newly derived CSFs have very different properties in equilibrium to those of conventional CSFs. For example, in contrast to the CSFs discussed in the contest literature, which always generate a unique pure strategy Nash equilibrium, the newly discovered CSFs admit the possibility of multiple equilibria.

Winners and losers : the ALP leadership spill and the triumph of the insiders

Julia Gillard won an impressive victory today, one that Kevin Rudd will find it very difficult to come back from. The scale of her victory contrasted with support for Rudd among the broader public or even among Labor voters.

Mania : diagnosis and treatment recommendations

This article provides recommendations for the diagnosis and treatment of mania, which characterizes bipolar I disorder (BD I). Failure to detect mania leads to misdiagnosis and suboptimal treatment. To diagnose mania, clinicians should include a detailed mood history within their assessment of patients presenting with depression, agitation, psychosis or insomnia. With regards to treatment, by synthesizing the findings from recent treatment guidelines, and reviewing relevant literature, this paper has distilled recommendations for both acute and long-term management. Antimanic agents including atypical antipsychotics and traditional mood stabilizers are employed to reduce acute manic symptoms, augmented by benzodiazepines if needed, and in refractory or severe cases with behavioural and/or psychotic disturbance, electroconvulsive therapy may occasionally be necessary. Maintenance/prophylaxis therapy aims to reduce recurrences/relapse, for which the combination of psychological interventions with pharmacotherapy is beneficial as it ensures adherence and monitoring of tolerability.

An investigation of porphyrinuria in Australian children with autism

Two recent studies, from France (Nataf et al., 200614. Nataf, R., Skorupka, C., Amet, L., Lam, A., Springbett, A. and Lathe, R. 2006. Porphyrinuria in childhood autistic disorder: Implications for environmental toxicity. Toxicol. Appl. Pharmacol., 214: 99–108. [CrossRef], [PubMed], [Web of Science ®] View all references) and the United States (Geier & Geier, 20079. Geier, D. A. and Geier, M. R. 2007. A prospective study of mercury toxicity biomarkers in autistic spectrum disorders. J. Toxicol. Environ. Health, A, 70: 1723–1730. [Taylor & Francis Online], [PubMed], [Web of Science ®] View all references), identified atypical urinary porphyrin profiles in children with an autism spectrum disorder (ASD). These profiles serve as an indirect measure of environmental toxicity generally, and mercury (Hg) toxicity specifically, with the latter being a variable proposed as a causal mechanism of ASD (Bernard et al., 20012. Bernard, S., Enayati, A., Redwood, L., Roger, H. and Binstock, T. 2001. Autism: A novel form of mercury poisoning. Med. Hypoth., 56: 462–471. [CrossRef], [PubMed], [Web of Science ®] View all references; Mutter et al., 200515. Mutter, J., Naumann, J., Schneider, R., Walach, H. and Haley, B. 2005. Mercury and autism: Accelerating evidence?. Neuroendocrinol. Lett., 26: 439–446. [PubMed], [Web of Science ®] View all references). To examine whether this phenomenon occurred in a sample of Australian children with ASD, an analysis of urinary porphyrin profiles was conducted. A consistent trend in abnormal porphyrin levels was evidenced when data was compared with those previously reported in the literature. The results are suggestive of environmental toxic exposure impairing heme synthesis. Three independent studies from three continents have now demonstrated that porphyrinuria is concomitant with ASD, and that Hg may be a likely xenobiotic to produce porphyrin profiles of this nature.

Understanding macrographia in children with autism spectrum disorders

It has been consistently reported that children with autism spectrum disorders (ASD) show considerable handwriting difficulties, specifically relating to accurate and consistent letter formation, and maintaining appropriate letter size. The aim of this study was to investigate the underlying factors that contribute to these difficulties, specifically relating to motor control.

We examined the integrity of fundamental handwriting movements and contributions of neuromotor noise in 26 children with ASD aged 8-13 years (IQ. >. 75), and 17 typically developing controls. Children wrote a series of four cursive letter l's using a graphics tablet and stylus.

Children with ASD had significantly larger stroke height and width, more variable movement trajectory, and higher movement velocities. The absolute level of neuromotor noise in the velocity profiles, as measured by power spectral density analysis, was significantly higher in children with ASD; relatively higher neuromotor noise was found in bands >3. Hz.

Our findings suggest that significant instability of fundamental handwriting movements, in combination with atypical biomechanical strategies, contribute to larger and less consistent handwriting in children with ASD.

Establishing Competitive Domination Cycles for Peer-to-peer Game Combat

Games require balance to be fair and enjoyable. In two player combat settings balance can be achieved by ensuring that both units are equally capable. The possibility of alliances changes the nature of balance when additional players are introduced. One approach to achieving balance is to use a domination loop between agents in a rock, scissors, paper style approach. This paper investigates whether such loops exist within the existing rules of game combat. Search processes within the attribute space of the game units are used to identify loops within an existing game architecture. A dominance metric is used to identify cycles where the victory is achieved by a clear threshold. Cycles with up to 5 players are demonstrated, although larger cycles require more effort to find. Use of models of game play and attribute space search are recommended as a mechanism for balancing games of this format.