Does the p38 MAP kinase inhibitor pamapimod have potential for the treatment of rheumatoid arthritis?

Background: Methotrexate alone or in combination with other agents is the standard treatment for moderate-to-severe rheumatoid arthritis. As the biological agents are expensive, they are not usually used until methotrexate has failed to give a good response. Thus, there is scope for the development of cheaper drugs that can be used instead of methotrexate or in addition to methotrexate. Objectives/methods: Pamapimod is a p38α inhibitor being developed for use in the treatment of rheumatoid arthritis. The objective was to evaluate the recent clinical trials of pamapimod in subjects with rheumatoid arthritis. Results: There is no clear cut evidence that pamapimod alone or in the presence of methotrexate is efficacious in subjects with rheumatoid arthritis, but it does cause adverse effects. Conclusion: It is unlikely that pamapimod will be useful in the treatment of rheumatoid arthritis.

Who's afraid of the dark? Transpower New Zealand Ltd

On 12 June 2006, the lights went out in New Zealand’s largest city and major commercial centre, Auckland. Business was disrupted and many thousands of people inconvenienced. The unscheduled power cut was the latest in a series of electric power problems in New Zealand over the past decade. Attention turned to state-owned enterprise [SOE] Transpower, which was in charge of maintaining and developing New Zealand’s national electricity grid. The problem of 12 June was traced to two shackles in poor condition, small but essential parts of the electricity grid infrastructure. Closer examination of New Zealand’s electricity sector indicated these shackles were merely the tip of a power supply iceberg. Transpower’s Chief Executive, Ralph Craven, was now answerable to the Prime Minister for the issues creating the problems, and a workable solution to fix them. Transpower Chief Executive Ralph Craven needed to produce answers that went well beyond the problem of the two faulty shackles. The power crisis had brought to the fore wider issues of roles, responsibilities, and expectations in relation to the supply of electric power in New Zealand. Transpower was contending with these issues on a daily basis; however, the incident on 12 June publicly highlighted the urgent need for solutions that served the stakeholders in this critical industry.

Concomitant or sequential administration of live attenuated Japanese encephalitis chimeric virus vaccine and yellow fever 17D vaccine : randomized double-blind phase II evaluation of safety and immunogenicity

A randomized, double-blind, study was conducted to evaluate the safety, tolerability and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) co-administered with live attenuated yellow fever (YF) vaccine (YF-17D strain; Stamaril(®), Sanofi Pasteur) or administered successively. Participants (n = 108) were randomized to receive: YF followed by JE-CV 30 days later, JE followed by YF 30 days later, or the co-administration of JE and YF followed or preceded by placebo 30 days later or earlier. Placebo was used in a double-dummy fashion to ensure masking. Neutralizing antibody titers against JE-CV, YF-17D and selected wild-type JE virus strains was determined using a 50% serum-dilution plaque reduction neutralization test. Seroconversion was defined as the appearance of a neutralizing antibody titer above the assay cut-off post-immunization when not present pre-injection at day 0, or a least a four-fold rise in neutralizing antibody titer measured before the pre-injection day 0 and later post vaccination samples. There were no serious adverse events. Most adverse events (AEs) after JE vaccination were mild to moderate in intensity, and similar to those reported following YF vaccination. Seroconversion to JE-CV was 100% and 91% in the JE/YF and YF/JE sequential vaccination groups, respectively, compared with 96% in the co-administration group. All participants seroconverted to YF vaccine and retained neutralizing titers above the assay cut-off at month six. Neutralizing antibodies against JE vaccine were detected in 82-100% of participants at month six. These results suggest that both vaccines may be successfully co-administered simultaneously or 30 days apart.

Attachment in relation to affect regulation and interpersonal functioning among substance use disorder inpatients

Attachment theory has been conceptualised as an affect regulation theory, proposing that attachment is associated with the expression and recognition of emotions as well as interpersonal functioning. Previous research has reported affect regulation difficulties in substance use disorders and addiction has been considered an attachment disorder. However, scarce empirical research exists on the relationship of attachment in relation to affect regulation and interpersonal functioning in those with substance use problems. Thus, the objective of the present study was to investigate potential associations between attachment, negative mood regulation (NMR) expectancies, fear of intimacy and self-differentiation in substance abusers. The revised adult attachment scale (RAAS), the NMR expectancies scale, the fear of intimacy scale and the differentiation of self inventory were administered to a sample of 100 substance use disorder inpatients. Attachment accounted for significant variance in NMR expectancies and was also a strong predictor of fear of intimacy. The predictive utility of attachment also extended to self-differentiation, suggesting that attachment was strongly related to overall self-differentiation score, Emotional reactivity, Emotional cut-off and I position. These findings support attachment theory suggesting that attachment is associated with and predicts affect regulation abilities and difficulties in interpersonal functioning in a sample of substance use disorder inpatients. The inclusion and assessment of attachment appears to be important in the development of treatment programmes for substance abusing individuals.

Substrate recognition and catalysis by the Holliday junction resolving enzyme Hje

Two archaeal Holliday junction resolving enzymes, Holliday junction cleavage (Hjc) and Holliday junction endonuclease (Hje), have been characterized. Both are members of a nuclease superfamily that includes the type II restriction enzymes, although their DNA cleaving activity is highly specific for four-way junction structure and not nucleic acid sequence. Despite 28% sequence identity, Hje and Hjc cleave junctions with distinct cutting patterns—they cut different strands of a four-way junction, at different distances from the junction centre. We report the high-resolution crystal structure of Hje from Sulfolobus solfataricus. The structure provides a basis to explain the differences in substrate specificity of Hje and Hjc, which result from changes in dimer organization, and suggests a viral origin for the Hje gene. Structural and biochemical data support the modelling of an Hje:DNA junction complex, highlighting a flexible loop that interacts intimately with the junction centre. A highly conserved serine residue on this loop is shown to be essential for the enzyme's activity, suggesting a novel variation of the nuclease active site. The loop may act as a conformational switch, ensuring that the active site is completed only on binding a four-way junction, thus explaining the exquisite specificity of these enzymes.

Full circle : the future of sustainable fashion manufacturing in New Zealand

Many fashion businesses in New Zealand have followed a global trend towards inexpensive off shore manufacturing. The transfer of the production of garments to overseas workers has had consequences for the wellbeing of local businesses, fashion designers and garment makers. The gradual decline of fashion manufacturing also appears to have resulted in a local fashion scene where many garments look the same in style, colour, fabric, cut and fit. The excitement of the past, where the majority of fashion designers established their own individuality through the cut and shape of the garments that they produced, may have been inadvertently lost in an effort to take advantage of cost savings achieved through mass production and manufacturing methods which are now largely unavailable in New Zealand. Consequently, a sustainable local fashion and manufacturing industry, with design integrity, seems further out of reach. This paper is focussed upon the thesis that the design and manufacture of a fashion garment, bearing in mind certain economic and practical restrictions at its inception, can contribute to a more sustainable fashion manufacturing industry in New Zealand.

Graphcut-based interactive segmentation using colour and depth cues

Segmentation of novel or dynamic objects in a scene, often referred to as background sub- traction or foreground segmentation, is critical for robust high level computer vision applica- tions such as object tracking, object classifca- tion and recognition. However, automatic real- time segmentation for robotics still poses chal- lenges including global illumination changes, shadows, inter-re ections, colour similarity of foreground to background, and cluttered back- grounds. This paper introduces depth cues provided by structure from motion (SFM) for interactive segmentation to alleviate some of these challenges. In this paper, two prevailing interactive segmentation algorithms are com- pared; Lazysnapping [Li et al., 2004] and Grab- cut [Rother et al., 2004], both based on graph- cut optimisation [Boykov and Jolly, 2001]. The algorithms are extended to include depth cues rather than colour only as in the original pa- pers. Results show interactive segmentation based on colour and depth cues enhances the performance of segmentation with a lower er- ror with respect to ground truth.

Postural balance under normal and altered sensory conditions in normal-weight and overweight children

Background Little or no research has been done in the overweight child on the relative contribution of multisensory information to maintain postural stability. Therefore, the purpose of this study was to investigate postural balance control under normal and experimentally altered sensory conditions in normal-weight versus overweight children. Methods Sixty children were stratified into a younger (7–9 yr) and an older age group (10–12 yr). Participants were also classified as normal-weight (n = 22) or overweight (n = 38), according to the international BMI cut-off points for children. Postural stability was assessed during quiet bilateral stance in four sensory conditions (eyes open or closed, normal or reduced plantar sensation), using a Kistler force plate to quantify COP dynamics. Coefficients of variation were calculated as well to describe intra-individual variability. Findings Removal of vision resulted in systematically higher amounts of postural sway, but no significant BMI group differences were demonstrated across sensory conditions. However, under normal conditions lower plantar cutaneous sensation was associated with higher COP velocities and maximal excursion of the COP in the medial-lateral direction for the overweight group. Regardless of condition, higher variability was shown in the overweight children within the 7–9 yr old subgroup for postural sway velocity, and more specifically medial–lateral velocity. Interpretation In spite of these subtle differences, results did not establish any clear underlying sensory organization impairments that may affect standing balance performance in overweight children compared to normal-weight peers. Consequently, it is believed that other factors account for overweight children's functional balance deficiencies.

Obesity screening for young Japanese males and females using skin fold measurements : the classification revisited

Anthropometric assessment is a simple, safe, and cost-efficient method to examine the health status of individu-als. The Japanese obesity classification based on the sum of two skin folds (Σ2SF) was proposed nearly 40 years ago therefore its applicability to Japanese living today is unknown. The current study aimed to determine Σ2SF cut-off values that correspond to percent body fat (%BF) and BMI values using two datasets from young Japa-nese adults (233 males and 139 females). Using regression analysis, Σ2SF and height-corrected Σ2SF (HtΣ2SF) values that correspond to %BF of 20, 25, and 30% for males and 30, 35, and 40% for females were determined. In addition, cut-off values of both Σ2SF and HtΣ2SF that correspond to BMI values of 23 kg/m2, 25 kg/m2 and 30 kg/m2 were determined. In comparison with the original Σ2SF values, the proposed values are smaller by about 10 mm at maximum. The proposed values show an improvement in sensitivity from about 25% to above 90% to identify individuals with ≥20% body fat in males and ≥30% body fat in females with high specificity of about 95% in both genders. The results indicate that the original Σ2SF cut-off values to screen obese individuals cannot be applied to young Japanese adults living today and modification is required. Application of the pro-posed values may assist screening in the clinical setting.

Theoretical comparison of innovative window daylighting devices for a sub-tropical climate using radiance

Daylighting in tropical and sub-tropical climates presents a unique challenge that is generally not well understood by designers. In a sub-tropical region such as Brisbane, Australia the majority of the year comprises of sunny clear skies with few overcast days and as a consequence windows can easily become sources of overheating and glare. The main strategy in dealing with this issue is extensive shading on windows. However, this in turn prevents daylight penetration into buildings often causing an interior to appear gloomy and dark even though there is more than sufficient daylight available. As a result electric lighting is the main source of light, even during the day. Innovative daylight devices which redirect light from windows offer a potential solution to this issue. These devices can potentially improve daylighting in buildings by increasing the illumination within the environment decreasing the high contrast between the window and work regions and deflecting potentially glare causing sunlight away from the observer. However, the performance of such innovative daylighting devices are generally quantified under overcast skies (i.e. daylight factors) or skies without sun, which are typical of European climates and are misleading when considering these devices for tropical or sub-tropical climates. This study sought to compare four innovative window daylighting devices in RADIANCE; light shelves, laser cut panels, micro-light guides and light redirecting blinds. These devices were simulated in RADIANCE under sub-tropical skies (for Brisbane) within the test case of a typical CBD office space. For each device the quantity of light redirected and its distribution within the space was used as the basis for comparison. In addition, glare analysis on each device was conducted using Weinold and Christoffersons evalglare. The analysis was conducted for selected hours for a day in each season. The majority of buildings that humans will occupy in their lifetime are already constructed, and extensive remodelling of most of these buildings is unlikely. Therefore the most effective way to improve daylighting in the near future will be through the alteration existing window spaces. Thus it will be important to understand the performance of daylighting systems with respect to the climate it is to be used in. This type of analysis is important to determine the applicability of a daylighting strategy so that designers can achieve energy efficiency as well the health benefits of natural daylight.

Reliability analysis and economic equipment replacement appraisal for substation and sub-transmission systems with explicit inclusion of non-repairable failures

The modern society has come to expect the electrical energy on demand, while many of the facilities in power systems are aging beyond repair and maintenance. The risk of failure is increasing with the aging equipments and can pose serious consequences for continuity of electricity supply. As the equipments used in high voltage power networks are very expensive, economically it may not be feasible to purchase and store spares in a warehouse for extended periods of time. On the other hand, there is normally a significant time before receiving equipment once it is ordered. This situation has created a considerable interest in the evaluation and application of probability methods for aging plant and provisions of spares in bulk supply networks, and can be of particular importance for substations. Quantitative adequacy assessment of substation and sub-transmission power systems is generally done using a contingency enumeration approach which includes the evaluation of contingencies, classification of the contingencies based on selected failure criteria. The problem is very complex because of the need to include detailed modelling and operation of substation and sub-transmission equipment using network flow evaluation and to consider multiple levels of component failures. In this thesis a new model associated with aging equipment is developed to combine the standard tools of random failures, as well as specific model for aging failures. This technique is applied in this thesis to include and examine the impact of aging equipments on system reliability of bulk supply loads and consumers in distribution network for defined range of planning years. The power system risk indices depend on many factors such as the actual physical network configuration and operation, aging conditions of the equipment, and the relevant constraints. The impact and importance of equipment reliability on power system risk indices in a network with aging facilities contains valuable information for utilities to better understand network performance and the weak links in the system. In this thesis, algorithms are developed to measure the contribution of individual equipment to the power system risk indices, as part of the novel risk analysis tool. A new cost worth approach was developed in this thesis that can make an early decision in planning for replacement activities concerning non-repairable aging components, in order to maintain a system reliability performance which economically is acceptable. The concepts, techniques and procedures developed in this thesis are illustrated numerically using published test systems. It is believed that the methods and approaches presented, substantially improve the accuracy of risk predictions by explicit consideration of the effect of equipment entering a period of increased risk of a non-repairable failure.

Uncertainty and innovation in fashion design

Generally speaking, psychologists have suggested three traditional views of how people cope with uncertainty. They are the certainty maximiser, the intuitive statistician-economist and the knowledge seeker (Smithson, 2008). In times of uncertainty, such as the recent global financial crisis, these coping methods often result in innovation in industry. Richards (2003) identifies innovation as different from creativity in that innovation aims to transform and implement rather than simply explore and invent. An examination of the work of iconic fashion designers, through case study and situational analysis, reveals that coping with uncertainty manifests itself in ways that have resulted in innovations in design, marketing methods, production and consumption. In relation to contemporary fashion, where many garments look the same in style, colour, cut and fit (Finn, 2008), the concept of innovation is an important one. This paper explores the role of uncertainty as a driver of innovation in fashion design. A key aspect of seeking knowledge, as a mechanism to cope with this uncertainty, is a return to basics. This is a problem for contemporary fashion designers who are no longer necessarily makers and therefore do not engage with the basic materials and methods of garment construction. In many cases design in fashion has become digital, communicated to an unseen, unknown production team via scanned image and specification alone. The disconnection between the design and the making of garments, as a result of decades of off-shore manufacturing, has limited the opportunity for this return to basics. The authors argue that the role of the fashion designer has become about the final product and as a result there is a lack of innovation in the process of making: in the form, fit and function of fashion garments. They propose that ‘knowledge seeking’ as a result of uncertainty in the fashion industry, in particular through re-examination of the methods of making, could hold the key to a new era of innovation in fashion design.

Punitiveness and the criminalisation of the other : State wards, unlawful non-citizens and Indigenous youth

This paper explores the genealogies of bio-power that cut across punitive state interventions aimed at regulating or normalising several distinctive ‘problem’ or ‘suspect’ deviant populations, such as state wards, non-lawful citizens and Indigenous youth. It begins by making some general comments about the theoretical approach to bio-power taken in this paper. It then outlines the distinctive features of bio-power in Australia and how these intersected with the emergence of penal welfarism to govern the unruly, unchaste, unlawful, and the primitive. The paper draws on three examples to illustrate the argument – the gargantuan criminalisation rates of Aboriginal youth, the history of incarcerating state wards in state institutions, and the mandatory detention of unlawful non-citizens and their children. The construction of Indigenous people as a dangerous presence, alongside the construction of the unruly neglected children of the colony — the larrikin descendants of convicts as necessitating special regimes of internal controls and institutions, found a counterpart in the racial and other exclusionary criteria operating through immigration controls for much of the twentieth century. In each case the problem child or population was expelled from the social body through forms of bio-power, rationalised as strengthening, protecting or purifying the Australian population.

Development of new evaluation methods for qualitative alternatives, using fuzzy calculations

Evaluation, selection and finally decision making are all among important issues, which engineers face in long run of projects. Engineers implement mathematical and nonmathematical methods to make accurate and correct decisions, whenever needed. As extensive as these methods are, effects of any selected method on outputs achieved and decisions made are still suspicious. This is more controversial and challengeable, where evaluation is made among non-quantitative alternatives. In civil engineering and construction management problems, criteria include both quantitative and qualitative ones, such as aesthetic, construction duration, building and operation costs, and environmental considerations. As the result, decision making frequently takes place among non-quantitative alternatives. It should be noted that traditional comparison methods, including clear-cut and inflexible mathematics, have always been criticized. This paper demonstrates a brief review of traditional methods of evaluating alternatives. It also offers a new decision making method using, fuzzy calculations. The main focus of this research is some engineering issues, which have flexible nature and vague borders. Suggested method provides analyzability of evaluation for decision makers. It is also capable to overcome multi criteria and multi-referees problems. In order to ease calculations, a program named DeMA is introduced.

Show

Script for non-verbal performance. ----- ----- ----- Research Component: Silent Treatment: Creating Non-verbal Performance Works for Children ----- ----- ----- The research field of theatre for young people draws on theories of child development and popular culture. SHOW explored personal and social development, friendship and creative play through the lens of the experience of girls aged 8-12. This project consolidated and refined innovative approaches to creating non-verbal theatre performance, and addressed challenges inherent in the creation of a performance by adults for young audiences. A significant finding of the project was the unanticipated convergence of creative practice and research into child behaviour and development: the congruence of content (Female bullying) and theatrical form (non-verbal performance: “Within the hidden culture of aggression, girls fight with body language and relationships instead of fists and knives. In this world, friendship is a weapon, and the sting of a shout pales in comparison to a day of someone’s silence. There is no gesture more devastating than the back turning away Simmons, Rachel (2002:3) Odd Girl Out: The Hidden Culture Of Aggression In Girls Schwartz Books The creative development and drafting process focussed on negotiating the conceptual design and practical constraints of incorporating diegetic music and video sources into the narrative. The authorial (and production) challenges of creating a script that could facilitate the re-mount a non-verbal work for a company specialising in text-based theatre . ----- ----- ----- Show was commissioned by the Queensland Theatre Company in 2003, toured into Queensland Schools by the Queensland Arts Council and in 2004 was performed at the Sydney Opera House.