Cost implications of specific and non-specific treatment for young persons at ultra high risk of developing a first episode of psychosis

Aim: Costs associated with mental health treatment for young persons at 'ultra' high risk (UHR) of developing a psychotic disorder have not previously been reported. This paper reports cost implications of providing psychological and pharmacological intervention for individuals at UHR for psychosis compared with minimal psychological treatment.

Method: Mental health service costs associated with a randomized controlled trial of two treatments (Specific Preventive Intervention: SPI and Needs-Based Intervention: NBI) for UHR young persons were estimated and compared at three time points: treatment phase, short-term follow up and medium-term follow up.

Results: Although the SPI group incurred significantly higher treatment costs than the NBI group over the treatment phase, they incurred significantly lower outpatient treatment costs over the longer term.

Conclusion: This study indicates that specific interventions designed to treat young persons who are identified as being at UHR of psychosis might be associated with some cost savings compared with non-specific interventions.

Basic symptoms in young people at ultra high-risk of psychosis

Basic Symptoms are cognitive and emotional disturbances characteristic of the early stage of psychosis. This study established the utility of an instrument to identify Basic Symptoms amongst young people at high-risk for developing psychosis, thereby facilitating the pathway to treatment for these individuals. The portfolio focuses on how having an unwell parent contributes to and influences the development of psychopathology in offspring. The four clinical case studies are presented in detail, and the intervention strategies for each individual are evaluated.

Relationship between membrane fatty acids and cognitive symptoms and information processing in individuals at ultra-high risk for psychosis

Cognitive symptoms and impairment are central to schizophrenia and often an early sign of this condition. The present study investigated biological correlates of cognitive symptoms and performance in individuals at ultra-high risk (UHR) for psychosis. The study sample comprised 80 neuroleptic-naïve UHR individuals aged 13-25 years. Associations among erythrocyte membrane fatty acid levels, measured by gas chromatography, and cognitive functioning were investigated in UHR patients. Subjects were divided into terciles based on their scores on the cognitive factor of the Positive and Negative Syndrome Scale. The Zahlen-Verbindungs Test (ZVT) (the number-combination test) was also used as a measure of information-processing speed. Exploratory analysis was conducted to investigate the relationship between membrane fatty acid levels with the size of the intracranial area (ICA), a neurodevelopmental measure relevant to schizophrenia, in half of subjects (n=40) using magnetic resonance imaging. The adjusted analysis revealed that omega-9 eicosenoic and erucic acid levels were significantly higher, but omega-3 docosahexaenoic acid levels were significantly lower, in the cognitively impaired than in the cognitively intact group. We found a significant negative association of eicosenoic, erucic, and gamma-linoleic acids with ZVT scores. A negative association between ICA and membrane levels of eicosenoic acid was also found. This is the first study to demonstrate the relationship between membrane fatty acids and cognitive function in neuroleptic-naïve subjects at UHR for psychosis. The study findings indicate that abnormalities in membrane fatty acids may be associated with the neurodevelopmental disruption associated with the cognitive impairments of individuals at UHR for psychosis.

Predictors of treatment response in young people at ultra-high risk for psychosis who received long-chain omega-3 fatty acids.

Previous efforts in the prospective evaluation of individuals who experience attenuated psychotic symptoms have attempted to isolate mechanisms underlying the onset of full-threshold psychotic illness. In contrast, there has been little research investigating specific predictors of positive outcomes. In this study, we sought to determine biological and clinical factors associated with treatment response, here indexed by functional improvement in a pre-post examination of a 12-week randomized controlled intervention in individuals at ultra-high risk (UHR) for psychosis. Participants received either long-chain omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) or placebo. To allow the determination of factors specifically relevant to each intervention, and to be able to contrast them, both treatment groups were investigated in parallel. Univariate linear regression analysis indicated that higher levels of erythrocyte membrane α-linolenic acid (ALA; the parent fatty acid of the ω-3 family) and more severe negative symptoms at baseline predicted subsequent functional improvement in the treatment group, whereas less severe positive symptoms and lower functioning at baseline were predictive in the placebo group. A multivariate machine learning analysis, known as Gaussian Process Classification (GPC), confirmed that baseline fatty acids predicted response to treatment in the ω-3 PUFA group with high levels of sensitivity, specificity and accuracy. In addition, GPC revealed that baseline fatty acids were predictive in the placebo group. In conclusion, our investigation indicates that UHR patients with higher levels of ALA may specifically benefit from ω-3 PUFA supplementation. In addition, multivariate machine learning analysis suggests that fatty acids could potentially be used to inform prognostic evaluations and treatment decisions at the level of the individual. Notably, multiple statistical analyses were conducted in a relatively small sample, limiting the conclusions that can be drawn from what we believe to be a first-of-its-kind study. Additional studies with larger samples are therefore needed to evaluate the generalizability of these findings.

Effects of omega-3 PUFA on the vitamin E and glutathione antioxidant defense system in individuals at ultra-high risk of psychosis

BACKGROUND: Oxidative stress and impaired antioxidant defenses are reported in schizophrenia and are associated with disturbed neurodevelopment, brain structural alterations, glutamatergic imbalance, increased negative symptoms, and cognitive impairment. There is evidence that oxidative stress predates the onset of acute psychotic illness. Here, we investigate the effects of omega-3 PUFA on the vitamin E and glutathione antioxidant defense system (AODS). METHOD: In 64 help-seeking UHR-individuals (13-25 years of age), vitamin E levels and glutathione were investigated before and after 12 weeks of treatment with either 1.2g/d omega-3 (PUFA-E) or saturated fatty acids (SFA-E), with each condition also containing 30.4mg/d alpha-tocopherol to ensure absorption without additional oxidative risk. RESULTS: In multivariate tests, the effects on the AODS (alpha-tocopherol, total glutathione) were not significantly different (p=0.13, p=0.11, respectively) between treatment conditions. According to univariate findings, only PUFA-E caused a significant alpha-tocopherol increase, while PUFA-E and SFA-E caused a significant gamma- and delta-tocopherol decrease. Total glutathione (GSHt) was decreased by PUFA-E supplementation. CONCLUSION: Effects of the PUFA-E condition on the vitamin E and glutathione AODS could be mechanisms underlying its clinical effectiveness. In terms of the vitamin E protection system, PUFA-E seems to directly support the antioxidative defense at membrane level. The effect of PUFA-E on GSHt is not yet fully understood, but could reflect antioxidative effects, resulting in decreased demand for glutathione. It is still necessary to further clarify which type of PUFA/antioxidant combination, and in which dose, is effective at each stage of psychotic illness.

Niacin skin sensitivity is increased in adolescents at ultra-high risk for psychosis

BACKGROUND: Most studies provide evidence that the skin flush response to nicotinic acid (niacin) stimulation is impaired in schizophrenia. However, only little is known about niacin sensitivity in the ultra-high risk (UHR) phase of psychotic disorders.

METHODS: We compared visual ratings of niacin sensitivity between adolescents at UHR for psychosis according to the one year transition outcome (UHR-T n = 11; UHR-NT n = 55) with healthy controls (HC n = 25) and first episode schizophrenia patients (FEP n = 25) treated with atypical antipsychotics.

RESULTS: Contrary to our hypothesis niacin sensitivity of the entire UHR group was not attenuated, but significantly increased compared to the HC group, whereas no difference could be found between the UHR-T and UHR-NT groups. As expected, niacin sensitivity of FEP was attenuated compared to HC group. In UHR individuals niacin sensitivity was inversely correlated with omega-6 and -9 fatty acids (FA), but positively correlated with phospholipase A2 (inPLA2) activity, a marker of membrane lipid repair/remodelling.

CONCLUSIONS: Increased niacin sensitivity in UHR states likely indicates an impaired balance of eicosanoids and omega-6/-9 FA at a membrane level. Our findings suggest that the emergence of psychosis is associated with an increased mobilisation of eicosanoids prior to the transition to psychosis possibly reflecting a "pro-inflammatory state", whereas thereafter eicosanoid mobilisation seems to be attenuated. Potential treatment implications for the UHR state should be further investigated.

Extending light-weighting and mass-production of ultra high strength steels via condition-based maintenance

The use of ultra high strength steels (UHSS) in the automotive industry presents a significant opportunity for continued vehicle light-weighting, due to possible strength-to-weight improvements of three to four times that of conventional sheet steel grades. This performance benefit is achievable whist maintaining most of the advantages of low-cost mass-production associated with the cold stamping of sheet steel for automotive body components. However, the introduction of UHSS can result in significantly increased wear of the stamping tools, which is difficult to predict at the design stage and can lead to unexpected process failure during mass-production. Therefore, there is a need to be able to monitor and predict the onset of severe wear, such that the best course of condition-based maintenance can be scheduled and unscheduled stoppages due to tool wear eradicated. This paper describes a novel active monitoring system that is being developed by researchers at Deakin University, The Australian National University and Ford Motor Company, Asia Pacific and Africa. The aim of the active monitoring system is to detect the initial onset of a change of state, such as wear, through the measurement of variables such as punch force and audio signals. A semi-industrial stamping process, using a progressive die setup and high strength steel sheet with hardened tool steel tooling, is the experimental basis for the initial model and system development.

Directional water transport fabrics with durable ultra-high one-way transport capacity

Fabrics with automatic one-way water transport ability are highly desirable for applications in daily life, industry, health, and defense. However, most of the studies on one-way water transport fabrics only report the qualitative water transport results. The lack of quantitative measure makes it hard to assess the directional transport quality. Here, it is proved that a hydrophilic fabric after being electrosprayed with a thin layer of hydrophobic coating on one side shows one-way water transport ability. By using moisture management tester, the water transport property is qualitatively characterized and the effect of hydrophobic fabric layer thickness on one-way water transport feature is examined. The hydrophobic fabric layer thickness is found to play a key role in deciding the one-way transport ability. When a plain woven fabric with an overall thickness of 420 μm and average pore size of 33 μm is used as fabric substrate, a hydrophobic fabric layer thickness between 22 and 62 μm allows the treated fabric to show a one-way droplet transport feature. A one-way transport index as high as 861 can be attained. The one-way water transport is durable enough to withstand repeated washing. This novel fabric may be useful for development of “smart” textiles for various applications.

Vanadium microalloying for ultra-high strength steel sheet treated by hot-dip metallising

Ultra-high strength steel sheets have been subjected to heat treatments that simulate the thermal cycles in hot-dip galvanising and galvannealing processes and evaluated with respect to their resulting mechanical properties and microstructures. The steels contained suitable contents of carbon (∼0.2%), manganese (1.2%) and chromium (0.4%) to ensure that they could be fully transformed to martensite after austenitisation followed by rapid cooling in a continuous annealing line, prior to galvanising. Different contents of vanadium (0–0.1%) and nitrogen (0.002–0.012%) were used to investigate the possible role of these microalloying elements on the strength of the tempered martensite. Vanadium, especially when in combination with a raised nitrogen content, helps to resist the effect of tempering so that a larger proportion of the initial strengthening is preserved after the galvanising cycle, giving tensile strength levels exceeding 1000 MPa. Different deoxidation practices using aluminium or silicon have also been included. These showed similar strength levels at corresponding carbon contents but the bendability of the Si-killed steel sheet was considerably superior. Microstructural examinations have been made on the annealed steels but the reason for the beneficial effect of vanadium is still not fully explained. It is concluded that microalloying with vanadium is a very promising approach in the development of corrosion-resistant ultra-high strength steel sheet products.