The PG500 series : novel heparan sulfate mimetics as potent angiogenesis and heparanase inhibitors for cancer therapy

Heparan sulfate mimetics, which we have called the PG500 series, have been developed to target the inhibition of both angiogenesis and heparanase activity. This series extends the technology underpinning PI-88, a mixture of highly sulfated oligosaccharides which reached Phase III clinical development for hepatocellular carcinoma. Advances in the chemistry of the PG500 series provide numerous advantages over PI-88. These new compounds are fully sulfated, single entity oligosaccharides attached to a lipophilic moiety, which have been optimized for drug development. The rational design of these compounds has led to vast improvements in potency compared to PI-88, based on in vitro angiogenesis assays and in vivo tumor models. Based on these and other data, PG545 has been selected as the lead clinical candidate for oncology and is currently undergoing formal preclinical development as a novel treatment for advanced cancer.

Current evidence on integrated treatment for serious mental disorder and substance misuse

Substance misuse in people with serious mental disorders is common and has a wideranging negative impact. The multiplicity of problems suggests that this comorbidity is better conceptualized as a type of complex disorder than by ‘dual diagnosis’. Problems with sequential and parallel treatments have led to the development of integrated approaches, with one practitioner or team addressing both the substance use and mental disorder. These treatments are typically characterized by motivation enhancement, minimizing treatment-related stress, emphasizing harm reduction as well as abstinence, and assertive outreach. A review of published randomized trials demonstrates that superior effects to controls are rarely consistent across treatment foci and over time. While motivational interventions assist engagement, more intervention is usually required for integrated treatment programs to improve long-term outcomes more than control conditions. More intensive case management does not consistently improve impact, but extended cognitive-behavioral therapies have promise. Suggestions for maximizing treatment effects and improving research evidence are provided.

A brief motivational intervention for substance misuse in recent-onset psychosis

Substance misuse is common in early psychosis, and impacts negatively on outcomes. Little is known about effective interventions for this population. We report a pilot study of brief intervention for substance misuse in early psychosis (Start Over and Survive: SOS), comparing it with Standard Care (SC). Twenty-five in-patients aged 18-35 years with early psychosis and current misuse of non-opioid drugs were allocated randomly to conditions. Substance use and related problems were assessed at baseline, 6 weeks and 3, 6 and 12 months. Final assessments were blind to condition. All 13 SOS participants who proceeded to motivational interviewing reported less substance use at 6 months, compared with 58% (7/12) in SC alone. Effects were well maintained to 12 months. However, more SOS participants lived with a relative or partner, and this also was associated with better outcomes. Engagement remained challenging: 39% (16/41) declined participation and 38% (5/13) in SOS only received rapport building. Further research will increase sample size, and address both engagement and potential confounds.

Prediction of outcome with group cognitive therapy for depression

Tested a social–cognitive model of depressive episodes and their treatment within a predictive study of treatment response. 42 clinically depressed volunteers (aged 22–60 yrs) were given self-efficacy (SE) questionnaires and other measures before and after treatment with cognitive therapy. Results support the idea that SE and skills regarding control of negative cognition mediates a sustained response to cognitive treatment for depression. Not only did mood-control variables correlate highly with concurrent changes in depression scores during treatment, but the posttreatment SE measure discriminated Ss who relapsed over the next 12 mo.

Intensive cognitive-behaviour therapy for depression : preliminary findings with four country residents

Describes a brief intensive program of cognitive therapy for depression that was designed for 4 adult residents of country towns in Australia, who resided some distance from treatment centers. Ss were assessed prior to treatment, at posttreatment, and at 4-wk, 8-wk, and 20-mo follow-ups. Treatments took place over 3 consecutive days for a total period of 15 hrs. Effects were highly consistent with the impact of group treatments delivered on a more traditional schedule. If confirmed in a controlled group study, these results suggest that cognitive therapy may be applied more economically and more widely than was previously realized.

The role of extreme sports in lifestyle enhancement and wellness

Alternative sports are fast becoming the physical activity of choice. Participation rates are even outstripping more traditional activities such as golf. At their most extreme there is no second chance, the most likely outcome of a mismanaged error or accident is death. At this level participants enjoy activities such as B.A.S.E. (Buildings, Antennae, Space, Earth) jumping, big wave surfing, waterfall kayaking, extreme skiing, rope-free climbing and extreme mountaineering. Probably the most common explanation for participation in extreme sports is the notion that participation is just a matter of some people‟s need to take unnecessary risks. This study reports on findings that indicate a more positive experience. A phenomenological method was used via unstructured interviews with 15 extreme sports participants (ages 30 – 72 years) and other firsthand accounts. Extreme sport participants directly related their experience to personal transformations that spill over to life in general. Athletes report feelings of deep psychological wellbeing and meaningfulness. The extreme sport experience enables a participant to break through personal barriers and develop an understanding of their own resourcefulness and emotional, cognitive, physical and spiritual capabilities. Furthermore such a breakthrough also seems to trigger a change in personal philosophy or view on life. The extreme sport experience transforms a participant though not in terms of working towards an external (social or cultural) perception of identity or towards some constructed perception of an ideal self, but by touching something within.

A comparison of international occupational therapy competencies : implications for Australian standards in the new millennium

Background/aim: A timely evaluation of the Australian Competency Standards for Entry-Level Occupational Therapists© (1994) was conducted. This thorough investigation comprised a literature review exploring the concept of competence and the applications of competency standards; systematic benchmarking of the Australian Occupational Therapy Competency Standards (OT AUSTRALIA, 1994) against other national and international competency standards and other affiliated documents, from occupational therapy and other cognate disciplines; and extensive nationwide consultation with the professional community. This paper explores and examines the similarities and disparities between occupational therapy competency standards documents available in English from Australia and other countries.----- Methods: An online search for national occupational therapy competency standards located 10 documents, including the Australian competencies.----- Results: Four 'frameworks' were created to categorise the documents according to their conceptual underpinnings: Technical-Prescriptive, Enabling, Educational and Meta-Cognitive. Other characteristics that appeared to impact the design, content and implementation of competency standards, including definitions of key concepts, authorship, national and cultural priorities, scope of services, intended use and review mechanisms, were revealed.----- Conclusion: The proposed 'frameworks' and identification of influential characteristics provided a 'lens' through which to understand and evaluate competency standards. While consistent application of and attention to some of these characteristics appear to consolidate and affirm the authority of competency standards, it is suggested that the national context should be a critical determinant of the design and content of the final document. The Australian Occupational Therapy Competency Standards (OT AUSTRALIA, 1994) are critiqued accordingly, and preliminary recommendations for revision are proposed.

Enhancement of DNA repair using topical T4 endonuclease V does not inhibit melanoma formation in Cdk4R24C/R24C/Tyr-NrasQ61K mice following neonatal UVR

To further investigate the use of DNA repair-enhancing agents for skin cancer prevention, we treated Cdk4R24C/R24C/NrasQ61K mice topically with the T4 endonuclease V DNA repair enzyme (known as Dimericine) immediately prior to neonatal ultraviolet radiation (UVR) exposure, which has a powerful effect in exacerbating melanoma development in the mouse model. Dimericine has been shown to reduce the incidence of basal-cell and squamous cell carcinoma. Unexpectedly, we saw no difference in penetrance or age of onset of melanoma after neonatal UVR between Dimericine-treated and control animals, although the drug reduced DNA damage and cellular proliferation in the skin. Interestingly, epidermal melanocytes removed cyclobutane pyrimidine dimers (CPDs) more efficiently than surrounding keratinocytes. Our study indicates that neonatal UVR-initiated melanomas may be driven by mechanisms other than solely that of a large CPD load and/or their inefficient repair. This is further suggestive of different mechanisms by which UVR may enhance the transformation of keratinocytes and melanocytes.

Power sharing and stability enhancement of an autonomous microgrid with inertial and non-inertial DGs with DSTATCOM

This paper proposes a method of enhancing system stability with a distribution static compensator (DSTATCOM) in an autonomous microgrid with multiple distributed generators (DG). It is assumed that there are both inertial and non-inertial DGs connected to the microgrid. The inertial DG can be a synchronous machine of smaller rating while inertia less DGs (solar) are assumed as DC sources. The inertia less DGs are connected through Voltage Source Converter (VSC) to the microgrid. The VSCs are controlled by either state feedback or current feedback mode to achieve desired voltage-current or power outputs respectively. The power sharing among the DGs is achieved by drooping voltage angle. Once the reference for the output voltage magnitude and angle is calculated from the droop, state feedback controllers are used to track the reference. The angle reference for the synchronous machine is compared with the output voltage angle of the machine and the error is fed to a PI controller. The controller output is used to set the power reference of the synchronous machine. The rate of change in the angle in a synchronous machine is restricted by the machine inertia and to mimic this nature, the rate of change in the VSCs angles are restricted by a derivative feedback in the droop control. The connected distribution static compensator (DSTATCOM) provides ride through capability during power imbalance in the microgrid, especially when the stored energy of the inertial DG is not sufficient to maintain stability. The inclusion of the DSATCOM in such cases ensures the system stability. The efficacies of the controllers are established through extensive simulation studies using PSCAD.