A genome wide linkage scan for dizygotic twinning in 525 families of mothers of dizygotic twins

BACKGROUND: The tendency to conceive dizygotic (DZ) twins is a complex trait influenced by genetic and environmental factors. To search for new candidate loci for twinning, we conducted a genome-wide linkage scan in 525 families using microsatellite and single nucleotide polymorphism marker panels. METHODS AND RESULTS: Non-parametric linkage analyses, including 523 families containing a total of 1115 mothers of DZ twins (MODZT) from Australia and New Zealand (ANZ) and The Netherlands (NL), produced four linkage peaks above the threshold for suggestive linkage, including a highly suggestive peak at the extreme telomeric end of chromosome 6 with an exponential logarithm of odds \[(exp)LOD] score of 2.813 (P = 0.0002). Since the DZ twinning rate increases steeply with maternal age independent of genetic effects, we also investigated linkage including only families where at least one MODZT gave birth to her first set of twins before the age of 30. These analyses produced a maximum expLOD score of 2.718 (P = 0.0002), largely due to linkage signal from the ANZ cohort, however, ordered subset analyses indicated this result is most likely a chance finding in the combined dataset. Linkage analyses were also performed for two large DZ twinning families from the USA, one of which produced a peak on chromosome 2 in the region of two potential candidate genes. Sequencing of FSHR and FIGLA, along with INHBB in MODZTs from two large NL families with family specific linkage peaks directly over this gene, revealed a potentially functional variant in the 5' untranslated region of FSHR that segregated with the DZ twinning phenotype in the Utah family. CONCLUSION: Our data provide further evidence for complex inheritance of familial DZ twinning.

A genome-wide linkage scan provides evidence for both new and previously reported loci influencing common migraine

Latent class analysis was performed on migraine symptom data collected in a Dutch population sample (N = 12,210, 59% female) in order to obtain empirical groupings of individuals suffering from symptoms of migraine headache. Based on these heritable groupings (h(2) = 0.49, 95% CI: 0.41-0.57) individuals were classified as affected (migrainous headache) or unaffected. Genome-wide linkage analysis was performed using genotype data from 105 families with at least 2 affected siblings. In addition to this primary phenotype, linkage analyses were performed for the individual migraine symptoms. Significance levels, corrected for the analysis of multiple traits, were determined empirically via a novel simulation approach. Suggestive linkage for migrainous headache was found on chromosomes 1 (LOD = 1.63; pointwise P = 0.0031), 13 (LOD = 1.63; P = 0.0031), and 20 (LOD = 1.85; P = 0.0018). Interestingly, the chromosome 1 peak was located close to the ATP1A2 gene, associated with familial hemiplegic migraine type 2 (FHM2). Individual symptom analysis produced a LOD score of 1.97 (P = 0.0013) on chromosome 5 (photo/phonophobia), a LOD score of 2.13 (P = 0.0009) on chromosome 10 (moderate/severe pain intensity) and a near significant LOD score of 3.31 (P = 0.00005) on chromosome 13 (pulsating headache). These peaks were all located near regions previously reported in migraine linkage studies. Our results provide important replication and support for the presence of migraine susceptibility genes within these regions, and further support the utility of an LCA-based phenotyping approach and analysis of individual symptoms in migraine genetic research. Additionally, our novel "2-step" analysis and simulation approach provides a powerful means to investigate linkage to individual trait components.

The anatomical and biomechanical consequences of anterior vertebral stapling for the fusionless correction of scoliosis

Fusionless scoliosis surgery is an emerging treatment for idiopathic scoliosis as it offers theoretical advantages over current forms of treatment. Anterior vertebral stapling using a nitinol staple is one such treatment. Despite increasing interest in this technique, little is known about the effects on the spine following insertion, or the mechanism of action of the staple. The aims of this study were threefold; (1) to measure changes in the bending stiffness of a single motion segment following staple insertion, (2) to describe the forces that occur within the staple during spinal movement, and (3) to describe the anatomical changes that occur following staple insertion. Results suggest that staple insertion consistently decreased stiffness in all directions of motion. An explanation for the finding may be found in the outcomes of the strain gauge testing and micro-CT scan. The strain gauge testing showed that once inserted, the staple tips applied a baseline compressive force to the surrounding trabecular bone and vertebral end-plate. This finding would be consistent with the current belief that the clinical effect of the staples is via unilateral compression of the physis. Interestingly however, as each specimen progressed through the five cycles of each test, the baseline load on the staple tips gradually decreased, implying that the force at the staple tip-bone interface was decreasing. We believe that this was likely occurring as a result of structural damage to the trabecular bone and vertebral end-plate by the staple effectively causing ‘loosening’ of the staple. This hypothesis is further supported by the findings of the micro-CT scan. The pictures depict significant trabecular bone and physeal injury around the staple blades. These results suggest that the current hypothesis that stapling modulates growth through physeal compression may be incorrect, but rather the effect occurs through mechanical disruption of the vertebral growth plate.

Ethnic differences in the BMI-%BF relationships between young Japanese and Australian-Caucasian males living in Australia using dual-energy X-ray absorptiometry

The Body Mass Index (BMI) has been used worldwide as an indicator of fatness. However, the universal cut-off points by the World Health Organisation (WHO) classification may not be appropriate for every ethnic group when consider the relationship with their actual total body fatness(%BF). The application of population-specific classifications to assess BMI may be more relevant to public health. Ethnic differences in the BMI%BF relationship between 45 Japanese and 42 Australian-Caucasian males were assessed using whole body dual-energy X-ray absorptiometry (DXA) scan and anthropometry using a standard protocol. Japanese males had significantly (p<0.05) greater %BF at given BMI values than Australian males. When this is taken into account the newly proposed Asia-Pacific BMI classification of BMI 23 as overweight and 25 as obese may better assess the level of obesity that is associated increased health risks for this population. To clarify the current findings, further studies that compare the relationships across other Japanese populations are recommended.

Addressing Challenges for Internationalisation and Mobility in Engineering Through CDIO Standards

There is a growing need for international transparency of engineering qualifications, and mechanisms to support and facilitate student mobility. In response, there are a number of global initiatives attempting to address these needs, particularly in Europe, North America and Australia. The Conceive-Design-Implement-Operate (CDIO) Initiative has a set of standards, competencies, and proficiency levels developed through a global community of practice. It is a well-structured framework in which best-practice internationalisation and student mobility can be embedded. However, the current 12 CDIO Standards do not address international qualifications or student mobility. Based on an environmental scan of global activities, the underpinning principles of best practice are identified and form the basis of the proposed 13th CDIO Standard — “Internationalization and Mobility”.

Queensland government agency libraries review : literature review

Dr Gillian Hallam is project leader for the Queensland Government Agency Libraries Review. As an initial step in the project, a literature review was commissioned to guide the research activities and inform the development of options for potential future service delivery models for the Government agency libraries. The review presents an environmental scan and review of the professional and academic literature to consider a range of current perspectives on library and information services. Significant in this review is the focus on the specific issues and challenges impacting on contemporary government libraries and their staff. The review incorporates four key areas: current directions in government administration; trends in government library services; issues in contemporary special libraries; and the skills and competencies of special librarians. Rather than representing an exhaustive review, the research has primarily centred on recent journal articles, conference papers, reports and web resources. Commentary prepared by national and international library associations has also played a role informing this review, as does the relevant State and Federal government documentation and reporting.

Blackcloud

The work was derived from terrestrial laser scan data of a bio-diverse landscape on the SE coast of Western Australia. The digital three dimensional scan data has been converged and then a portion of that computer aided design (CAD) file has been captured via ‘screen capture’ to produce Blackcloud.---------- The primary intention behind the production of the work was to expand understanding on the means of representing and then designing for sites in ‘kwongan’ landscapes which are constituted by highly biodiverse, bushfire prone heath vegetation.

Before and after the fire

The work was derived from terrestrial laser scan data of a bio-diverse landscape on the SE coast of Western Australia. The scanning was conducted both before and after a significant bushfire event. The digital three dimensional scan data has been converged and then abstracted into a two dimensional vertical sections or slice which reveals the vegetal surface of heath vegetation and the surface of the landform.---------- This abstraction converts the complex data into spatial information so that it is meaningful in the context the architectural and landscape architectural design process. The primary intention behind the production of the work was to expand understanding on the means of representing and then designing for sites in ‘kwongan’ landscapes which are constituted by highly biodiverse, bushfire prone heath vegetation.

Heathsections

The work was derived from terrestrial laser scan data of a bio-diverse landscape on the SE coast of Western Australia. The three dimensional scan data has been abstracted into two dimensional side sections or slices – in a manner which converts the complex data into spatial information which is meaningful in the context of the act of architectural and landscape architectural design. The primary intention behind the production of the work was to expand understanding on the means of representation of ‘kwongan’ landscapes which are constituted by highly biodiverse - and thus difficult to measure - heath vegetation.

Horizonal

Horizonal was derived from terrestrial laser scan data of a bio-diverse landscape on the SE coast of Western Australia. The digital three dimensional scan data has been converged with geospatial survey of the landform captured through RTKGPS survey technology. Also incorporated into the image is a series of photographs taken using a photogrammetric technique wherein the position and view angle of each photograph is measured relative to a geographic datum point. The primary intention behind the production of the work was to expand understandings on the relationship between scenic photography and geospatial maps of remote, bio-diverse landscapes which are experiencing urban development for the first time.

Heathprint

The work was derived from terrestrial laser scan data of a bio-diverse landscape on the SE coast of Western Australia. The digital three dimensional scan data has been abstracted into two dimensional horizontal sections or slices. This abstraction converts the complex data into spatial information which is meaningful in the context of the act of architectural and landscape architectural design. The primary intention behind the production of the work was to expand understanding on the means of representing and then designing for sites in 'kwongan' landscapes which are constituted by highly biodiverse - and thus difficult to measure - heath vegetation. From Heathprint the author generated contour intervals of the landform upon which an associate (Daniela Simon architect) designed a work of architecture, which subsequently was awarded a commendation for residential architecture in the WA Chapter Australia Institute of Architects awards 2007.

3D lung and rib cage reconstruction using low dose CT scans of adolescent idiopathic scoliosis pre and post anterior thoracoscopic correction

Adolescent Idiopathic Scoliosis (AIS) has been associated with reduced pulmonary function believed to be due to a restriction of lung volume by the deformed thoracic cavity. A recent study by our group examined the changes in lung volume pre and post anterior thoracoscopic scoliosis correction using pulmonary function testing (1), however the anatomical changes in ribcage shape and left/right lung volume after thoracoscopic surgery which govern overall respiratory capacity are unknown. The aim of this study was to use 3D rendering from CT scan data to compare lung and ribcage anatomical changes from pre to two years post thoracoscopic anterior scoliosis correction. The study concluded that 3D volumetric reconstruction from CT scans is a powerful means of evaluating changes in pulmonary and thoracic anatomy following surgical AIS correction. Most likely, lung volume changes following thoracoscopic scoliosis correction are multifactorial and affected by changes in height (due to residual growth), ribcage shape, diaphragm positioning, Cobb angle correction in the thoracic spine. Further analysis of the 3D reconstructions will be performed to assess how each of these factors affect lung volume in this patient cohort.

Comprehensive evaluation of driver gaze pattern using fuzzy rules for driver training

The over representation of novice drivers in crashes is alarming. Research indicates that one in five drivers’ crashes within their first year of driving. Driver training is one of the interventions aimed at decreasing the number of crashes that involve young drivers. Currently, there is a need to develop comprehensive driver evaluation system that benefits from the advances in Driver Assistance Systems. Since driving is dependent on fuzzy inputs from the driver (i.e. approximate distance calculation from the other vehicles, approximate assumption of the other vehicle speed), it is necessary that the evaluation system is based on criteria and rules that handles uncertain and fuzzy characteristics of the drive. This paper presents a system that evaluates the data stream acquired from multiple in-vehicle sensors (acquired from Driver Vehicle Environment-DVE) using fuzzy rules and classifies the driving manoeuvres (i.e. overtake, lane change and turn) as low risk or high risk. The fuzzy rules use parameters such as following distance, frequency of mirror checks, gaze depth and scan area, distance with respect to lanes and excessive acceleration or braking during the manoeuvre to assess risk. The fuzzy rules to estimate risk are designed after analysing the selected driving manoeuvres performed by driver trainers. This paper focuses mainly on the difference in gaze pattern for experienced and novice drivers during the selected manoeuvres. Using this system, trainers of novice drivers would be able to empirically evaluate and give feedback to the novice drivers regarding their driving behaviour.

Typical accuracy and quality control of a process for creating CT-Based virtual bone models

A pragmatic method for assessing the accuracy and precision of a given processing pipeline required for converting computed tomography (CT) image data of bones into representative three dimensional (3D) models of bone shapes is proposed. The method is based on coprocessing a control object with known geometry which enables the assessment of the quality of resulting 3D models. At three stages of the conversion process, distance measurements were obtained and statistically evaluated. For this study, 31 CT datasets were processed. The final 3D model of the control object contained an average deviation from reference values of −1.07±0.52 mm standard deviation (SD) for edge distances and −0.647±0.43 mm SD for parallel side distances of the control object. Coprocessing a reference object enables the assessment of the accuracy and precision of a given processing pipeline for creating CTbased 3D bone models and is suitable for detecting most systematic or human errors when processing a CT-scan. Typical errors have about the same size as the scan resolution.

Image acquisition and manipulation protocols for CT-PET fusion to improve the accuracy of gross tumour volume localisation for 3D conformal radiotherapy for lung cancer

Aims: To develop clinical protocols for acquiring PET images, performing CT-PET registration and tumour volume definition based on the PET image data, for radiotherapy for lung cancer patients and then to test these protocols with respect to levels of accuracy and reproducibility. Method: A phantom-based quality assurance study of the processes associated with using registered CT and PET scans for tumour volume definition was conducted to: (1) investigate image acquisition and manipulation techniques for registering and contouring CT and PET images in a radiotherapy treatment planning system, and (2) determine technology-based errors in the registration and contouring processes. The outcomes of the phantom image based quality assurance study were used to determine clinical protocols. Protocols were developed for (1) acquiring patient PET image data for incorporation into the 3DCRT process, particularly for ensuring that the patient is positioned in their treatment position; (2) CT-PET image registration techniques and (3) GTV definition using the PET image data. The developed clinical protocols were tested using retrospective clinical trials to assess levels of inter-user variability which may be attributed to the use of these protocols. A Siemens Somatom Open Sensation 20 slice CT scanner and a Philips Allegro stand-alone PET scanner were used to acquire the images for this research. The Philips Pinnacle3 treatment planning system was used to perform the image registration and contouring of the CT and PET images. Results: Both the attenuation-corrected and transmission images obtained from standard whole-body PET staging clinical scanning protocols were acquired and imported into the treatment planning system for the phantom-based quality assurance study. Protocols for manipulating the PET images in the treatment planning system, particularly for quantifying uptake in volumes of interest and window levels for accurate geometric visualisation were determined. The automatic registration algorithms were found to have sub-voxel levels of accuracy, with transmission scan-based CT-PET registration more accurate than emission scan-based registration of the phantom images. Respiration induced image artifacts were not found to influence registration accuracy while inadequate pre-registration over-lap of the CT and PET images was found to result in large registration errors. A threshold value based on a percentage of the maximum uptake within a volume of interest was found to accurately contour the different features of the phantom despite the lower spatial resolution of the PET images. Appropriate selection of the threshold value is dependant on target-to-background ratios and the presence of respiratory motion. The results from the phantom-based study were used to design, implement and test clinical CT-PET fusion protocols. The patient PET image acquisition protocols enabled patients to be successfully identified and positioned in their radiotherapy treatment position during the acquisition of their whole-body PET staging scan. While automatic registration techniques were found to reduce inter-user variation compared to manual techniques, there was no significant difference in the registration outcomes for transmission or emission scan-based registration of the patient images, using the protocol. Tumour volumes contoured on registered patient CT-PET images using the tested threshold values and viewing windows determined from the phantom study, demonstrated less inter-user variation for the primary tumour volume contours than those contoured using only the patient’s planning CT scans. Conclusions: The developed clinical protocols allow a patient’s whole-body PET staging scan to be incorporated, manipulated and quantified in the treatment planning process to improve the accuracy of gross tumour volume localisation in 3D conformal radiotherapy for lung cancer. Image registration protocols which factor in potential software-based errors combined with adequate user training are recommended to increase the accuracy and reproducibility of registration outcomes. A semi-automated adaptive threshold contouring technique incorporating a PET windowing protocol, accurately defines the geometric edge of a tumour volume using PET image data from a stand alone PET scanner, including 4D target volumes.