Bayesian latent trait modeling of migraine symptom data

Definition of disease phenotype is a necessary preliminary to research into genetic causes of a complex disease. Clinical diagnosis of migraine is currently based on diagnostic criteria developed by the International Headache Society. Previously, we examined the natural clustering of these diagnostic symptoms using latent class analysis (LCA) and found that a four-class model was preferred. However, the classes can be ordered such that all symptoms progressively intensify, suggesting that a single continuous variable representing disease severity may provide a better model. Here, we compare two models: item response theory and LCA, each constructed within a Bayesian context. A deviance information criterion is used to assess model fit. We phenotyped our population sample using these models, estimated heritability and conducted genome-wide linkage analysis using Merlin-qtl. LCA with four classes was again preferred. After transformation, phenotypic trait values derived from both models are highly correlated (correlation = 0.99) and consequently results from subsequent genetic analyses were similar. Heritability was estimated at 0.37, while multipoint linkage analysis produced genome-wide significant linkage to chromosome 7q31-q33 and suggestive linkage to chromosomes 1 and 2. We argue that such continuous measures are a powerful tool for identifying genes contributing to migraine susceptibility.

Linkage and heritability analysis of migraine symptom groupings: A comparison of three different clustering methods on twin data

Migraine is a painful disorder for which the etiology remains obscure. Diagnosis is largely based on International Headache Society criteria. However, no feature occurs in all patients who meet these criteria, and no single symptom is required for diagnosis. Consequently, this definition may not accurately reflect the phenotypic heterogeneity or genetic basis of the disorder. Such phenotypic uncertainty is typical for complex genetic disorders and has encouraged interest in multivariate statistical methods for classifying disease phenotypes. We applied three popular statistical phenotyping methods—latent class analysis, grade of membership and grade of membership “fuzzy” clustering (Fanny)—to migraine symptom data, and compared heritability and genome-wide linkage results obtained using each approach. Our results demonstrate that different methodologies produce different clustering structures and non-negligible differences in subsequent analyses. We therefore urge caution in the use of any single approach and suggest that multiple phenotyping methods be used.

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.

Simulation and enhancement of a cardiovascular device test rig

Cardiovascular assist devices are tested in mock circulation loops (MCLs) prior to animal and clinical testing. These MCLs rely on characteristics such as pneumatic parameters to create pressure and flow, and pipe dimensions to replicate the resistance, compliance and fluid inertia of the natural cardiovascular system. A mathematical simulation was developed in SIMULINK to simulate an existing MCL. Model validation was achieved by applying the physical MCL characteristics to the simulation and comparing the resulting pressure traces. These characteristics were subsequently altered to improve and thus predict the performance of a more accurate physical system. The simulation was successful in simulating the physical mock circulation loop, and proved to be a useful tool in the development of improved cardiovascular device test rigs.

The rate-limiting mechanism for the heterogeneous burning of cylindrical iron rods

This paper presents the findings of an investigation into the rate-limiting mechanism for the heterogeneous burning in oxygen under normal gravity and microgravity of cylindrical iron rods. The original objective of the work was to determine why the observed melting rate for burning 3.2-mm diameter iron rods is significantly higher in microgravity than in normal gravity. This work, however, also provided fundamental insight into the rate-limiting mechanism for heterogeneous burning. The paper includes a summary of normal-gravity and microgravity experimental results, heat transfer analysis and post-test microanalysis of quenched samples. These results are then used to show that heat transfer across the solid/liquid interface is the rate-limiting mechanism for melting and burning, limited by the interfacial surface area between the molten drop and solid rod. In normal gravity, the work improves the understanding of trends reported during standard flammability testing for metallic materials, such as variations in melting rates between test specimens with the same cross-sectional area but different crosssectional shape. The work also provides insight into the effects of configuration and orientation, leading to an improved application of standard test results in the design of oxygen system components. For microgravity applications, the work enables the development of improved methods for lower cost metallic material flammability testing programs. In these ways, the work provides fundamental insight into the heterogeneous burning process and contributes to improved fire safety for oxygen systems in applications involving both normal-gravity and microgravity environments.

A proposed qualitative framework for heterogeneous burning of metallic materials : the 'melting rate triangle'

This paper presents a proposed qualitative framework to discuss the heterogeneous burning of metallic materials, through parameters and factors that influence the melting rate of the solid metallic fuel (either in a standard test or in service). During burning, the melting rate is related to the burning rate and is therefore an important parameter for describing and understanding the burning process, especially since the melting rate is commonly recorded during standard flammability testing for metallic materials and is incorporated into many relative flammability ranking schemes. However, whilst the factors that influence melting rate (such as oxygen pressure or specimen diameter) have been well characterized, there is a need for an improved understanding of how these parameters interact as part of the overall melting and burning of the system. Proposed here is the ‘Melting Rate Triangle’, which aims to provide this focus through a conceptual framework for understanding how the melting rate (of solid fuel) is determined and regulated during heterogeneous burning. In the paper, the proposed conceptual model is shown to be both (a) consistent with known trends and previously observed results, and (b)capable of being expanded to incorporate new data. Also shown are examples of how the Melting Rate Triangle can improve the interpretation of flammability test results. Slusser and Miller previously published an ‘Extended Fire Triangle’ as a useful conceptual model of ignition and the factors affecting ignition, providing industry with a framework for discussion. In this paper it is shown that a ‘Melting Rate Triangle’ provides a similar qualitative framework for burning, leading to an improved understanding of the factors affecting fire propagation and extinguishment.

Validation of the impact of Health Information Technology (I-HIT) scale : an international collaborative

In 2005, the Healthcare Information Management Systems Society (HIMSS) Nursing Informatics Community developed a survey to measure the impact of health information technology (HIT), the IHIT Scale, on the role of nurses and interdisciplinary communication in hospital settings. In 2007, nursing informatics colleagues from Australia, England, Finland, Ireland, New Zealand, Scotland and the United States formed a research collaborative to validate the IHIT across countries. All teams have completed construct and face validation in their countries. Five out of six teams have initiated reliability testing by practicing nurses. This paper reports the international collaborative’s validation of the IHIT Scale completed to date.

Optimal allocation and sizing of DGs in a distribution system using PSO

In this paper, the optimal allocation and sizing of distributed generators (DGs) in a distribution system is studied. To achieve this goal, an optimization problem should be solved in which the main objective is to minimize the DGs cost and to maximise the reliability simultaneously. The active power balance between loads and DGs during the isolation time is used as a constraint. Another point considered in this process is the load shedding. It means that if the summation of DGs active power in a zone, isolated by the sectionalizers because of a fault, is less than the total active power of loads located in that zone, the program start shedding the loads in one-by-one using the priority rule still the active power balance is satisfied. This assumption decreases the reliability index, SAIDI, compared with the case loads in a zone are shed when total DGs power is less than the total load power. To validate the proposed method, a 17-bus distribution system is employed and the results are analysed.

Effect of section geometry on the lateral distortional buckling of LiteSteel beams

The LiteSteel Beam (LSB) is a new hollow flange section developed by OneSteel Australian Tube Mills using their patented dual electric resistance welding and automated continuous roll-forming technologies. It has a unique geometry consisting of torsionally rigid rectangular hollow flanges and a relatively slender web. It has found increasing popularity in residential, industrial and commercial buildings as flexural members. The LSB is considerably lighter than traditional hot-rolled steel beams and provides both structural and construction efficiencies. However, the LSB flexural members are subjected to a relatively new lateral distortional buckling mode, which reduces their member moment capacities. Unlike the commonly observed lateral torsional buckling of steel beams, the lateral distortional buckling of LSBs is characterised by simultaneous lateral defection, twist and cross sectional change due to web distortion. The current design rules in AS/NZS 4600 (SA, 2005) for flexural members subject to lateral distortional buckling were found to be conservative by about 8% in the inelastic buckling region. Therefore, a new design rule was developed for LSBs subject to lateral distortional buckling based on finite element analyses of LSBs. The effect of section geometry was then considered and several geometrical parameters were used to develop an advanced set of design rules. This paper presents the details of the finite element analyses and the design curve development for hollow flange sections subject to lateral distortional buckling.

Ultimate shear strength of LiteSteel beams

This paper presents the details of an investigation on the shear behaviour of a recently developed, cold-formed steel beam known as LiteSteel Beam (LSB).The LSB section has a unique shape of a channel beam with two rectangular hollow flanges and is produced by a patented manufacturing process involving simultaneous cold-forming and dual electric resistance welding. In the present investigation, a series of numerical analyses based on three-dimensional finite element modeling and an experimental study were carried out to investigate the shear behaviour of 10 different LSB sections. It was found that the current design rules in cold-formed steel structures design codes are very conservative for the shear design of LiteSteel beams. Significant improvements to web shear buckling occurred due to the presence of rectangular hollow flanges while considerable post-buckling strength was also observed. Therefore the design rules were further modified to include the available post-buckling strength. Suitable design rules were also developed under the direct strength method format. This paper presents the details of this investigation and the results including the final design rules for the shear capacity of LSBs. It also presents new shear strength formulae for lipped channel beams based on the current design equations for shear strength given in AISI (2007) using the same approach used for LSBs.

An examination of the knowledge barriers in participatory design and the prospects for embedded research

Participatory design has the moral and pragmatic tenet of including those who will be most affected by a design into the design process. However, good participation is hard to achieve and results linking project success and degree of participation are inconsistent. Through three case studies examining some of the challenges that different properties of knowledge - novelty, difference, dependence - can impose on the participatory endeavour we examine some of the consequences to the participatory process of failing to bridge across knowledge boundaries - syntactic, semantic, and pragmatic. One pragmatic consequence, disrupting the user's feeling of involvement to the project, has been suggested as a possible explanation for the inconsistent results linking participation and project success. To aid in addressing these issues a new form of participatory research, called embedded research, is proposed and examined within the framework of the case studies and knowledge framework with a call for future research into its possibilities.

Lateral-torsional buckling of cold-formed steel beams at ambient temperature

Cold-formed steel beams are increasingly used as floor joists and bearers in residential, industrial and commercial buildings. Their structural behaviour and moment capacities are influenced by lateral-torsional buckling and hence a research study was undertaken to investigate the lateral-torsional buckling behaviour of cold-formed steel lipped channel beams at ambient and elevated temperatures. For this purpose a finite element model of a simply supported cold-formed steel lipped channel beam under uniform bending was developed first and validated using available numberical and experimental results. It was then used in a detailed parametric study to simulate the lateral-torsional behaviour of cold-formed steel beams under varying conditions. The moment capacity results were then compared with the predictions from the current ambient temperature design rules in Australia, New Zealand, American and European codes for cold-formed steel structures. Some very interesting results have been obtained. European design rules are found to be conservative while Australian and American design rules are unsafe. This paper presents the results of finite element analyses for ambient temperature conditions, and the comparison with the current design rules.

Selective growth of carbon nanotubes on bare silicon : MWNT sinthesys on patterned substrates without predeposition of metal catalyst

Carbon nanotubes (CNTs) are expected to become the ideal constituent of many technologes, in particular for future generation electronics. This considerable interest is due to their unique electrical and mechanical properties. They show indeed super-high current-carrying capacity, ballistic electron transport and good field-emission properties. Then, these superior features make CNTs the most promising building blocks for electronic devices, as organic solar cells and organic light emitting devices (OLED). By using Focused Ion Beam (FIB) patterning it is possible to a obtain a high control on position, relative distances and diameter of CNTs. The present work shows how to grow three-dimensional architecture made of vertical-aligned CNTs directly on silicon. Thanks to the higher activity of a pre-patterned surface the synthesis process results very quick, cheap and simple. Such large area growths of CNTs could be used in preliminary test for application as electrodes for organic solar cells.

Validation of the WHOQOL-BREF among women following childbirth

Background: There is an increasing interest in measuring quality of life (QOL) in clinical settings and in clinical trials. None of the commonly used QOL instrument have been validated for use postnatally. Aim: To assess the psychometric properties of the 26-item WHOQOL-BREF among women following childbirth. Methods: Using a prospective cohort design we recruited 320 women within the first few days of childbirth. At six weeks postpartum, participants were asked to complete the WHOQOL-BREF, the Edinburgh Postnatal Depression Index and the Australian Unity Wellbeing Index. Validation of the WHOQOL-BREF included an analysis of internal consistency, discriminate validity, convergent validity and an examination of the domain structure. Results: 221 (69.1%) women returned their six-week questionnaire. All domains of the WHOQOL-BREF met reliability standards (alpha coefficient exceeding 0.70). The questionnaire discriminated well between known groups (depressed and non-depressed women. P = <0.000) and demonstrated satisfactory correlations with the Australian Unity Wellbeing index (r = >0.45). The domain structure of the WHOQOL-BREF was also valid in this population of new mothers, with moderate to high correlation between individual items and the domain structure to which the items were originally assigned. Conclusion: The WHOQOL-BRF is well-accepted and valid instrument in this population and may be used in postnatal clinical settings or for assessing intervention effects in research studies.