Exploration of depressive realism in depression, depression in remission, and dysphoria

This study compared how people with different levels of depression judged their control over a task. People with more severe depression were more accurate in judging their control than were people with less severe depression whilst nondepressed individuals overestimated their control over the task.

Fluoxetine for maintenance of remission and to improve quality of life in patients with Crohn's disease: a pilot randomized placebo-controlled trial.

BACKGROUND AND AIMS: Previous studies have shown that antidepressants reduce inflammation in animal models of colitis. The present trial aimed to examine whether fluoxetine added to standard therapy for Crohn's disease [CD] maintained remission, improved quality of life [QoL] and/or mental health in people with CD as compared to placebo. METHODS: A parallel randomized double-blind placebo controlled trial was conducted. Participants with clinically established CD, with quiescent or only mild disease, were randomly assigned to receive either fluoxetine 20 mg daily or placebo, and followed for 12 months. Participants provided blood and stool samples and completed mental health and QoL questionnaires. Immune functions were assessed by stimulated cytokine secretion [CD3/CD28 stimulation] and flow cytometry for cell type. Linear mixed-effects models were used to compare groups. RESULTS: Of the 26 participants, 14 were randomized to receive fluoxetine and 12 to placebo. Overall, 14 [54%] participants were male. The mean age was 37.4 [SD=13.2] years. Fluoxetine had no effect on inflammatory bowel disease activity measured using either the Crohn's Disease Activity Index [F(3, 27.5)=0.064, p=0.978] or faecal calprotectin [F(3, 32.5)=1.08, p=0.371], but did have modest effects on immune function. There was no effect of fluoxetine on physical, psychological, social or environmental QoL, anxiety or depressive symptoms as compared to placebo [all p>0.05]. CONCLUSIONS: In this small pilot clinical trial, fluoxetine was not superior to placebo in maintaining remission or improving QoL. [ID: ACTRN12612001067864.].

Veiled threats : recurrent cultural anxieties in Australia

At the end of the nineteenth century, white Australians found themselves in a turbulent and rapidly changing world. As British settlers in a vast, often-perplexing and under-populated continent, they were increasingly aware that they lived in a crowded and predominantly Asian neighbourhood. Their supposedly empty spaces seemed to invite the unwanted attention of hostile outsiders, fertile soil for speculation about vulnerable borders, invasion and violation. It was commonplace of the period for white females to be considered at once particularly vulnerable and also innocent symbols of the new nation. They needed to be protected against Asian males allegedly bent on conquest and violation. It does not follow that these “invasion narratives”, however persistent, meant that the entire population was disabled by fear and dread, but there is convincing evidence of a deeply embedded cultural anxiety about the destructive possibilities and hostile intentions of Asian outsiders. In this article, the authors examine recent representations of Muslims as hostile outsiders in Australia, focusing in particular on the veil as a marker of female oppression under Islam and a sign of the threat attributed to the Islamic community in Australia. While it would be misleading to propose a simple line of progression from late nineteenth century apprehensions to those a century or more later, there are nonetheless intriguing parallels and recurrent expressions of survivalist anxiety across the period examined in this article.

Family caregivers of the mentally ill and adaptive coping

The issue investigated in this thesis concerned the adaptive coping strategies that caregivers of the mentally ill adopt at different stages of encounter with their family member’s illness. Specifically, family caregivers’ responses to the illness were investigated within the parameters of the Spaniol and Zipple (1994) 4-stage model of the evolution of caregivers’ responses to mental illness. The accuracy of the model’s representation of the experience of caregivers across all kinship relationships to the care-recipient was evaluated. Spaniol and Zipple proposed four stages which they termed (1) Discovery/Denial, (2) Recognition/Acceptance, (3) Coping and (4) Personal/Political Advocacy. The first stage is characterised by persistent denial of mental illness and seeking answers from multiple sources. The second stage involves caregivers’ expectations of professionals providing answers when the illness is recognised. At this stage caregivers experience guilt, embarrassment and blame. The cyclical nature of the illness impedes acceptance and caregivers experience a deep sense of loss and crisis of meaning as they gradually accept the reality of the situation. In the third stage coping replaces grieving and the issues encountered include loss of faith in professionals, disruption to family life and recurrent crises. Belief in family expertise grows and the focus of coping changes. The fourth stage proposes that caregivers become more assertive, self-blame decreases and the focus is upon changing the system. New meanings and values are integrated. This study found that the model did not accurately describe the experience of all caregivers. Caregiver did not deny mental illness and adaptive coping occurred throughout all stages. Coping evolved as the issues encountered changed and was independent of resolution of grief. The issues encountered were more extensive than the model proposed and differed according to kinship relationship to the care recipient. The ways in which adaptive coping evolved were identified, as were the issues and their accompanying responses. Caregivers coped by adaptively responding to the requirements of care provision, maintaining a sense of self worth and generating positive effect.

Protocol and rationale-the efficacy of minocycline as an adjunctive treatment for major depressive disorder: a double blind, randomised, placebo controlled trial

While current pharmacotherapies are efficacious, there remain a clear shortfall between symptom remission and functional recovery. With the explosion in our understanding of the biology of these disorders, the time is ripe for the investigation of novel therapies. Recently depression is conceptualized as an immune-inflammatory and nitro-oxidative stress related disorder. Minocycline is a tetracycline antibiotic that has anti-inflammatory, pro-oxidant, glutamatergic, neurotrophic and neuroprotective properties that make it a viable target to explore as a new therapy. This double blind, randomised, placebo controlled adjunctive trial will investigate the benefits of 200 mg/day of minocycline treatment, in addition to any usual treatment, as an adjunctive treatment for moderate-severe major depressive disorder. Sixty adults are being randomised to 12 weeks of treatment (with a 4 week follow-up post-discontinuation). The primary outcome measure for the study is mean change on the Montgomery-Asberg Depression Rating Scale (MADRS), with secondary outcomes including the Social and Occupational Functioning Assessment Scale (SOFAS), Clinical Global Impressions (CGI), Hamilton Rating Scale for Anxiety (HAM-A), Patient Global Impression (PGI), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and Range of Impaired Functioning Tool (LIFE-RIFT). Biomarker analyses will also be conducted at baseline and week 12. The study has the potential to provide new treatment targets, both by showing efficacy with a new class of 'antidepressant' but also through the analysis of biomarkers that may further inform our understanding of the pathophysiology of unipolar depression.

Design of new oxazaphosphorine anticancer drugs

The oxazaphosphorines including cyclophosphamide (CPA, Cytoxan, or Neosar), ifosfamide (IFO, Ifex) and trofosfamide (Ixoten) represent an important group of therapeutic agents due to their substantial antitumor and immunomodulating activity. However, several intrinsic limitations have been uncounted during the clinical use of these oxazaphosphorines, including substantial pharmacokinetic variability, resistance and severe host toxicity. To circumvent these problems, new oxazaphosphorines derivatives have been designed and evaluated with an attempt to improve the selectivity and response with reduced host toxicity. These include mafosfamide (NSC 345842), glufosfamide (D19575, β-Dglucosylisophosphoramide mustard), S-(-)-bromofosfamide (CBM-11), NSC 612567 (aldophosphamide perhydrothiazine) and NSC 613060 (aldophosphamide thiazolidine). Mafosfamide is an oxazaphosphorine analog that is a chemically stable 4-thioethane sulfonic acid salt of 4-hydroxy-CPA. Glufosfamide is IFO derivative in which the isophosphoramide mustard, the alkylating metabolite of IFO, is glycosidically linked to a β-D-glucose molecule. Phase II studies of glufosfamide in the treatment of pancreatic cancer, non-small cell lung cancer (NCSLC), and recurrent glioblastoma multiform (GBM) have recently completed and Phase III trials are ongoing, while Phase I studies of intrathecal mafosfamide have recently completed for the treatment of meningeal malignancy secondary to leukemia, lymphoma, or solid tumors. S-(-)- bromofosfamide is a bromine-substituted IFO analog being evaluated in a few Phase I clinical trials. The synthesis and development of novel oxazaphosphorine analogs with favourable pharmacokinetic and pharmacodynamic properties still constitutes a great challenge for medicinal chemists and cancer pharmacologists.

Investigation of educator adoption of knowledge media

Human development has occurred against a timeline that has seen the creation of and diffusion of one innovation after another. These innovations range from language to complex computing and information technologies. The latter are assisting with the distribution of information, and extend to the distribution of the human species beyond the planet Earth. From early times, information has been published and mostly for a fee to the publisher. The absorption and use of information has had a high priority in most societies from early times, and has become institutionalised in universities and institutes of technical learning. For most in Western societies, education is now a matter of ‘lifelong learning’. Today, we see higher education institutions, worldwide, adapting their organisational structures and operating procedures and forming strategic alliances with communications content providers and carriers as well as with information technology companies. Modern educational institutes seek productivity and efficiency. Many also seek to differentiate themselves from competitors. Technological convergence is often seen by management to be a saviour in many educational organisations. It is hoped that lower capital and recurrent costs can be achieved, and that competitors in an increasingly globalised industry can be held at bay by strategic use of knowledge media (Eisenstadt, 1995) commonly associated with distance education in the campus setting. Knowledge media set up costs, intellectual property costs and training costs for staff and students are often so high as to make their use not viable for Australian institutes of higher education. Against this backdrop, one might expect greater educator and student use of publisher produced textbooks and digital enhancements to the textbook, particularly those involved in distance education. A major issue is whether or not the timing of instructor adoption of converging information technology and communications technologies aligns with the wishes of both higher education management and government, and with those who seek commercial gain from the diffusion and adoption of such technologies. Also at issue is whether or not it is possible to explain variance in stated intentions to recommend adoption of new learning technologies in higher education and implementation. Will there occur educator recommendation for adoption of individual knowledge media such as World Wide Web access to study materials by students? And what will be the form of this tool and others used in higher education? This thesis reports on more recent changes in the technological environment and seeks to contribute to an understanding of the factors that lead to a willingness, or unwillingness, on the part of higher education instructors, as influencers and content providers, to utilise these technologies. As such, it is a diffusion study which seeks to fill a gap in the literature. Diffusion studies typically focus on predicting adoption based on characteristics of the potential adopter. Few studies examine the relationship between characteristics of the innovation and adoption. Nearly all diffusion studies involve what is termed discontinuous innovation (Robertson, 1971). That is, the innovation involves adoptees in a major departure from previous practice. This study seeks to examine the relationship between previous experience of related technologies and adoption or rejection of dynamically continuous innovation. Continuous and dynamically continuous innovations are the most numerous in the real world, yet they are numerically the least scrutinised by way of academic research. Moreover, the three-year longitudinal study of educators in Australian and New Zealand meets important criteria laid down by researchers Tornatzky and Klein (1982) and Rogers (1995), that are often not met by similar studies. In particular the study examines diffusion as it is unfolding, rather than selectively examining a single innovation and after the fact, thus avoiding a possible pro-innovation bias. The study examines the situation for both ‘all educators’ and ‘marketing / management educators’ alone in seeking to meet the following aim: Establish if intended adopters of specific knowledge media have had more experience of other computer-based technologies than have those not intending to adopt said knowledge media. The analytical phase entails use of factor analysis and discriminant analysis to conclude that it is possible to discriminate adopters of selected knowledge media based on previous use of related technologies. The study does not find any generalised factor that enables such discrimination among educators. Thus the study supports the literature in part, but fails to find generalised factors that enable unambiguous prediction of knowledge media adoption or otherwise among each grouping of educators examined. The implications are that even in the case of related products and services (continuous or dynamically continuous innovation), there is not statistical certainty that prior usage of related products or technologies is related to intentions to use knowledge media in the future. In this regard, the present study might be said to confirm the view that Rogers and Shoemaker's (1971) conceptualisation of perceived innovation characteristics may only apply to discontinuous innovations (Stratton, Lumpkin & Vitell, 1997). The implications for stakeholders such as higher education management is that when seeking to appoint new educators or existing staff to knowledge media project teams, there is some support for the notion that those who already use World Wide Web based technologies are likely to take these technologies into teaching situations. The same claim cannot be made for computer software use in general, nor Internet use in general.

Efficacy of atypical antipsychotics in bipolar disorder

Bipolar disorder is a severe and recurrent disorder. Atypical antipsychotics have emerged as both an alternative and adjunct to conventional mood stabilisers. The manic phase of the illness is the best studied, and it appears that a class effect with regards to efficacy is present in both monotherapy and augmentation studies. Evidence for efficacy of atypical antipsychotics in depression is emerging. At this stage controlled data are available for both olanzapine and quetiapine. Maintenance data demonstrating efficacy are available for olanzapine. Atypical antipsychotics have utility in treating acute agitation and aggression in manic episodes of bipolar disorder. Subgroup analyses from trials treating manic phase bipolar disorder, and an open-label study of rapid cycling, have suggested that atypical antipsychotics may be useful for the treatment of mixed states and rapid cycling. Several studies have suggested that atypical antipsychotics may be useful in treatment-refractory episodes of bipolar disorder. The current available data suggest greater efficacy of the atypical antipsychotics in mania than in depression, although the data are fairly clear that induction of depression is not an issue with the atypical antipsychotics. A number of trials are underway that will hopefully address many of the questions still pending.

Optimising the life cycle energy performance of residential buildings

A holistic approach to low-energy building design is essential to ensure that any efficiency improvement strategies provide a net energy benefit over the life of the building. Previous work by the authors has established a model for informing low-energy building design based on a comparison of the life cycle energy demand associated with a broad range of building assemblies. This model ranks assemblies based on their combined initial and recurrent embodied energy and operational energy demand. The current study applies this model to an actual residential building in order to demonstrate the application of the model for optimising a building’s life cycle energy performance. The aim of this study was to demonstrate how the availability of comparable energy performance information at the building design stage can be used to better optimise a building’s energy performance. The life cycle energy demand of the case study building, located in the temperate climate of Melbourne, Australia, was quantified using a comprehensive embodied energy assessment technique and TRNSYS thermal energy simulation software. The building was then modelled with variations to its external assemblies in an attempt to optimise its life cycle energy performance. The alternative assemblies chosen were those shown through the author’s previous modelling to result in the lowest life cycle energy demand for each building element. The best performing assemblies for each of the main external building elements were then combined into a best-case scenario to quantify the potential life cycle energy savings possible compared to the original building. The study showed that significant life cycle energy savings are possible through the modelling of individual building elements for the case study building. While these findings relate to a very specific case, this study demonstrates the application of a model for optimising building life cycle energy performance that may be applied more broadly during early-stage building design to optimise life cycle energy performance.

Bevacizumab for the treatment of high-grade glioma

Introduction: Gliomas are highly vascular and rich in vascular endothelial growth factor (VEGF) that promotes angiogenesis. Bevacizumab is a monoclonal antibody against VEGF inhibiting angiogenesis by preventing receptor activation. Phase II clinical trials using bevacizumab in both newly diagnosed and recurrent high-grade glioma (HGG) showed promising results.

Areas covered: This is a review of clinical trials investigating bevacizumab in newly diagnosed and recurrent HGGs with a focus on outcome results. A future perspective about the expected role of bevacizumab is given. Bevacizumab efficacy, safety and tolerability, the combination of radiation and bevacizumab as well as the use of bevacizumab to treat pseudoprogression are discussed. Further criteria of response evaluation needed to be adjusted in the age of anti-angiogenic therapy and this will be discussed.

Expert opinion: Bevacizumab has been shown to be safe and tolerable in HGG. In the recurrent disease setting, bevacizumab alone might be sufficient for a clinical benefit and is currently approved as a single agent for this indication. While clinical trials demonstrate a prolonged progression-free survival in bevacizumab-treated HGG, a benefit on OS has not been demonstrated yet. Bevacizumab has also been introduced into other settings in neuro-oncology including concurrent administration with re-irradiation for recurrent HGG.

Bevacizumab for the treatment of high-grade glioma: an update after phase III trials.

Gliomas are highly vascular and rich in VEGF, which promotes angiogenesis. Bevacizumab is a monoclonal antibody against VEGF, inhibiting angiogenesis by preventing receptor activation. Early Phase II clinical trials using bevacizumab in both newly diagnosed and recurrent high-grade gliomas (HGG) showed promising results, but these have not been confirmed in recent Phase III trials. This review is an update including recently reported Phase II and III study results.

Physical health comorbidities in women with personality disorder: data from the Geelong osteoporosis study

BACKGROUND: Associations between common psychiatric disorders, psychotic disorders and physical health comorbidities are frequently investigated. The complex relationship between personality disorders (PDs) and physical health is less understood, and findings to date are varied. This study aims to investigate associations between PDs with a number of prevalent physical health conditions. METHODS: This study examined data collected from women (n=765;≥25years) participating in a population-based study located in south-eastern Australia. Lifetime history of psychiatric disorders was assessed using the semi-structured clinical interviews (SCID-I/NP and SCID-II). The presence of physical health conditions (lifetime) were identified via a combination of self-report, medical records, medication use and clinical data. Socioeconomic status, and information regarding medication use, lifestyle behaviors, and sociodemographic information was collected via questionnaires. Logistic regression models were used to investigate associations. RESULTS: After adjustment for sociodemographic variables (age, socioeconomic status) and health-related factors (body mass index, physical activity, smoking, psychotropic medication use), PDs were consistently associated with a range of physical health conditions. Novel associations were observed between Cluster A PDs and gastro-oesophageal reflux disease (GORD); Cluster B PDs with syncope and seizures, as well as arthritis; and Cluster C PDs with GORD and recurrent headaches. CONCLUSIONS: PDs were associated with physical comorbidity. The current data contribute to a growing evidence base demonstrating associations between PDs and a number of physical health conditions independent of psychiatric comorbidity, sociodemographic and lifestyle factors. Longitudinal studies are now required to investigate causal pathways, as are studies determining pathological mechanisms.