Load bearing improves the limits of agreement for repeated in vivo measures of the speed of sound in human Achilles tendon

Axial acoustic wave propagation has been widely used in evaluating the mechanical properties of human bone in vivo. However, application of this technique to monitor soft tissues, such as tendon, has received comparatively little scientific attention. Laboratory-based research has established that axial acoustic wave transmission is not only related to the physical properties of equine tendon but is also proportional to tensile load to which it is exposed (Miles et al., 1996; Pourcelot et al., 2005). The reproducibility of the technique for in vivo measurements in human tendon, however, has not been established. The aim of this study was to evaluate the limits of agreement for repeated measures of the speed of sound (SoS) in human Achilles tendon in vivo. Methods: A custom built ultrasound device, consisting of an A-mode 1MHz emitter and two regularly spaced receivers, was used to measure the SoS in the mid-portion of the Achilles tendon in ten healthy males and ten females (mean age: 33.8 years, range 23-56 yrs; height: 1.73±0.08 m; weight: 68.4±15.3 kg). The emitter and receivers were held at fixed positions by a polyethylene frame and maintained in close contact with the skin overlying the tendon by means of elasticated straps. Repeated SoS measurements were taken with the subject prone (non-weightbearing and relaxed Achilles tendon) and during quiet bipedal and unipedal stance. In each instance, the device was detached and repositioned prior to measurement. Results: Limits of agreement for repeated SoS measures during non-weightbearing and bipedal and unipedal stance were ±53, ±28 and ±21 m/s, respectively. The average SoS in the non-weightbearing Achilles tendon was 1804±198 m/s. There was a significant increase in the average SoS during bilateral (2122±135 m/s) (P < 0.05) and unilateral (2221±79 m/s) stance (P < 0.05). Conclusions: Repeated SoS measures in human Achilles tendon were more reliable during stance than under non-weightbearing conditions. These findings are consistent with previous research in equine tendon in which lower variability in SoS was observed with increasing tensile load (Crevier-Denoix et al, 2009). Since the limits of agreement for Achilles tendon SoS are nearly 5% of the changes previously observed during walking and therapeutic heel raise exercises, acoustic wave transmission provides a promising new non-invasive method for determining tendon properties during sports and rehabilitation related activities.

Experimental study of load bearing cold-formed steel wall systems under fire conditions

Light Gauge Steel Framing (LSF) walls made of cold-formed and thin-walled steel lipped channel studs with plasterboard linings on both sides are commonly used in commercial, industrial and residential buildings. However, there is limited data about their structural and thermal performance under fire conditions while past research showed contradicting results about the benefits of using cavity insulation. A new composite wall panel was recently proposed to improve the fire resistance rating of LSF walls, where an insulation layer was used externally between the plasterboards on both sides of the wall frame instead of using it in the cavity. In this research 11 full scale tests were conducted on conventional load bearing steel stud walls with and without cavity insulation, and the new composite panel system to study their thermal and structural performance under standard fire conditions. These tests showed that the use of cavity insulation led to inferior fire performance of walls, and provided supporting research data. They demonstrated that the use of insulation externally in a composite panel enhanced the thermal and structural performance of LSF walls and increased their fire resistance rating. This paper presents the details of the LSF wall tests and the thermal and structural performance data and fire resistance rating of load-bearing wall assemblies lined with varying plasterboard-insulation configurations under two different load ratios. Fire test results including the time–temperature and deflection profiles are presented along with the failure times and modes.

Finite element modelling of load bearing cold-formed steel wall systems under fire conditions

Light Gauge Steel Framing (LSF) walls are made of cold-formed, thin-walled steel lipped channel studs with plasterboard linings on both sides. However, these thin-walled steel sections heat up quickly and lose their strength under fire conditions despite the protection provided by plasterboards. A new composite wall panel was recently proposed to improve the fire resistance rating of LSF walls, where an insulation layer was used externally between the plasterboards on both sides of the wall frame instead of using it in the cavity. A research study using both fire tests and numerical studies was undertaken to investigate the structural and thermal behaviour of load bearing LSF walls made of both conventional and the new composite panels under standard fire conditions and to determine their fire resistance rating. This paper presents the details of finite element models of LSF wall studs developed to simulate the structural performance of LSF wall panels under standard fire conditions. Finite element analyses were conducted under both steady and transient state conditions using the time-temperature profiles measured during the fire tests. The developed models were validated using the fire test results of 11 LSF wall panels with various plasterboard/insulation configurations and load ratios. They were able to predict the fire resistance rating within five minutes. The use of accurate numerical models allowed the inclusion of various complex structural and thermal effects such as local buckling, thermal bowing and neutral axis shift that occurred in thin-walled steel studs under non-uniform elevated temperature conditions. Finite element analyses also demonstrated the improvements offered by the new composite panel system over the conventional cavity insulated system.

Thermal performance of load bearing cold-formed steel walls under fire conditions using numerical studies

Cold–formed Light gauge Steel Frame (LSF) wall systems are increasingly used in low-rise and multi-storey buildings and hence their fire safety has become important in the design of buildings. A composite LSF wall panel system was developed recently, where a thin insulation was sandwiched between two plasterboards to improve the fire performance of LSF walls. Many experimental and numerical studies have been undertaken to investigate the fire performance of non-load bearing LSF wall under standard conditions. However, only limited research has been undertaken to investigate the fire performance of load bearing LSF walls under standard and realistic design fire conditions. Therefore in this research, finite element thermal models of both the conventional load bearing LSF wall panels with cavity insulation and the innovative LSF composite wall panel were developed to simulate their thermal behaviour under standard and realistic design fire conditions. Suitable thermal properties were proposed for plasterboards and insulations based on laboratory tests and available literature. The developed models were then validated by comparing their results with available fire test results of load bearing LSF wall. This paper presents the details of the developed finite element models of load bearing LSF wall panels and the thermal analysis results. It shows that finite element models can be used to simulate the thermal behaviour of load bearing LSF walls with varying configurations of insulations and plasterboards. Failure times of load bearing LSF walls were also predicted based on the results from finite element thermal analyses. Finite element analysis results show that the use of cavity insulation was detrimental to the fire rating of LSF walls while the use of external insulation offered superior thermal protection to them. Effects of realistic design fire conditions are also presented in this paper.

Incongruence between self-reported and observed senior physical education teaching styles : an analysis using Mosston and Ashworth’s spectrum

Pedagogical styles, methods, models, practices or strategies are valued for what they claim they can achieve. In recent times curriculum documents and governments have called for a range of teaching approaches to meet the variety of learner differences and allow students to make more independent decision making in physical education (Hardy and Mawer, 1999). One well known system of categorizing teaching styles is the Mosston and Ashworth’s Spectrum of Teaching Styles (2002). In Queensland, prior to 2005, no research had been conducted on the teaching styles used by teachers of Physical Education. However, many teachers self-reported that they employed a variety of teaching styles depending on the aims and content of the material to be taught (Cothran, et al., 2005). This research, for the first time, collected teacher’s self-reported use of teaching styles and through observations verify the styles that were being used to teach Senior Physical Education in Queensland. More specifically the aims of the research were to determine: a) What teaching styles teachers of Senior Physical Education in Queensland believe they use? i) Were they using a range of teaching styles? ii) Were teachers of Senior Physical Education in Queensland using teaching styles that the Queensland Senior Physical Education Syllabus (2004) required? b) If Mosston and Ashworth’s (2002) Spectrum of Teaching Styles were used to categorise styles observed during the teaching of Senior Physical Education did the styles being used provide opportunities for evaluating as described by the Queensland Senior Physical Education Syllabus (2004)? The research was conducted in two phases. Part A involved use of a questionnaire to determine the teaching styles Queensland teachers of Senior Physical Education reported using and how often they reported using them. The questionnaire was administered to 110 teachers throughout Queensland. The sample was determined from 346 schools teaching Senior Physical Education (in 2006) across the state of Queensland, Australia. 286 questionnaires were sent to 77 non-randomised schools. There were 66 male and 44 female respondents in the sample. A wide range of teaching styles were reportedly used by teachers of Senior Physical Education with Practice Style-Style B, Command Style-Style A and Divergent Discovery Style-Style H, the most reportedly used. The Self-Teaching Style-Style K was reportedly used the least by teachers involved in this study. From the respondents a group of teachers were identified to form the participants for Part B. Part B of the study involved observation of a group of volunteer participants (from those who had completed the questionnaire) who displayed many of the ‘typical’ characteristics, and a cross-section of backgrounds, of teachers of Senior Physical Education in Queensland. In the case of this study, the criteria used to select the group of teachers to be observed teaching were, teaching experience (number of years: 0-4, 5-10 and 11 years and over), gender, geographical location of schools (focused on Brisbane and near area for travel/access purposes), profile of the students at schools (girls, boys or co-educational), nature of school (Government or Private) and the physical activities being taught in a school (activities to reflect all the areas of physical activity outlined within the syllabus). A total of 27 questionnaire respondents from Part A indicated that they were willing to be observed teaching practical lessons. The respondents who volunteered to be involved in Part B of the study came from different regions across the state of Queensland and was not confined to the Brisbane metropolitan area or large cities. From the group of people who volunteered for Part B four came from outside Brisbane and 23 from the Brisbane area. The final observation group of nine participants included eight teachers from the Brisbane area and one from a rural area. The characteristics of the final group included three females and six males from private and public schools with a range of teaching experience in years and a range of physical activities. Four year 12 and five year 11 teachers and their classes were videoed on three occasions as they progressed through an eight – nine week unit of work. This resulted in 24 hours 48 minutes and 20 seconds (or 4465 observations) of video teaching data which was subsequently coded by several researchers (99% interobserver reliability) to determine the teaching styles employed by the participants. This research indicated that, based on Mosston and Ashworth’s (2002) Spectrum of Teaching Styles, teachers of Senior Physical Education in Queensland used predominantly one style to teach 27 observed lessons. This is in sharp contrast to the variety of styles 110 teachers self- reportedly used and in spite of the Queensland Senior Physical Education Syllabus (2004) suggesting a range of specific styles be used. These results are discussed in the context of the Queensland Senior Physical Education Syllabus (2004), teacher knowledge of teaching styles and high-stakes curriculum and external pressures such as national testing and the publication of data from schools in tabloid newspapers. The data and findings in this research provide a rationale for improving teacher knowledge regarding teaching styles and the need for a clear definition of terminology in syllabus documents. Careful examination of the effects that the publishing of school data may have on teaching styles is advised. This research not only collected teacher’s perceptions of the teaching styles they believed they used it also verified these claims through direct observations of the teachers while teaching. These findings are relevant to syllabus writers, teacher educators, policy makers within education and teachers.

Effects of air pollution exposure on adult bicycle commuters : an investigation of respiratory health, motorised traffic proximity and the utility of commute re-routing

Bicycle commuting has the potential to be an effective contributing solution to address some of modern society’s biggest issues, including cardiovascular disease, anthropogenic climate change and urban traffic congestion. However, individuals shifting from a passive to an active commute mode may be increasing their potential for air pollution exposure and the associated health risk. This project, consisting of three studies, was designed to investigate the health effects of bicycle commuters in relation to air pollution exposure, in a major city in Australia (Brisbane). The aims of the three studies were to: 1) examine the relationship of in-commute air pollution exposure perception, symptoms and risk management; 2) assess the efficacy of commute re-routing as a risk management strategy by determining the exposure potential profile of ultrafine particles along commute route alternatives of low and high proximity to motorised traffic; and, 3) evaluate the feasibility of implementing commute re-routing as a risk management strategy by monitoring ultrafine particle exposure and consequential physiological response from using commute route alternatives based on real-world circumstances; 3) investigate the potential of reducing exposure to ultrafine particles (UFP; < 0.1 µm) during bicycle commuting by lowering proximity to motorised traffic with real-time air pollution and acute inflammatory measurements in healthy individuals using their typical, and an alternative to their typical, bicycle commute route. The methods of the three studies included: 1) a questionnaire-based investigation with regular bicycle commuters in Brisbane, Australia. Participants (n = 153; age = 41 ± 11 yr; 28% female) reported the characteristics of their typical bicycle commute, along with exposure perception and acute respiratory symptoms, and amenability for using a respirator or re-routing their commute as risk management strategies; 2) inhaled particle counts measured along popular pre-identified bicycle commute route alterations of low (LOW) and high (HIGH) motorised traffic to the same inner-city destination at peak commute traffic times. During commute, real-time particle number concentration (PNC; mostly in the UFP range) and particle diameter (PD), heart and respiratory rate, geographical location, and meteorological variables were measured. To determine inhaled particle counts, ventilation rate was calculated from heart-rate-ventilation associations, produced from periodic exercise testing; 3) thirty-five healthy adults (mean ± SD: age = 39 ± 11 yr; 29% female) completed two return trips of their typical route (HIGH) and a pre-determined altered route of lower proximity to motorised traffic (LOW; determined by the proportion of on-road cycle paths). Particle number concentration (PNC) and diameter (PD) were monitored in real-time in-commute. Acute inflammatory indices of respiratory symptom incidence, lung function and spontaneous sputum (for inflammatory cell analyses) were collected immediately pre-commute, and one and three hours post-commute. The main results of the three studies are that: 1) healthy individuals reported a higher incidence of specific acute respiratory symptoms in- and post- (compared to pre-) commute (p < 0.05). The incidence of specific acute respiratory symptoms was significantly higher for participants with respiratory disorder history compared to healthy participants (p < 0.05). The incidence of in-commute offensive odour detection, and the perception of in-commute air pollution exposure, was significantly lower for participants with smoking history compared to healthy participants (p < 0.05). Females reported significantly higher incidence of in-commute air pollution exposure perception and other specific acute respiratory symptoms, and were more amenable to commute re-routing, compared to males (p < 0.05). Healthy individuals have indicated a higher incidence of acute respiratory symptoms in- and post- (compared to pre-) bicycle commuting, with female gender and respiratory disorder history indicating a comparably-higher susceptibility; 2) total mean PNC of LOW (compared to HIGH) was reduced (1.56 x e4 ± 0.38 x e4 versus 3.06 x e4 ± 0.53 x e4 ppcc; p = 0.012). Total estimated ventilation rate did not vary significantly between LOW and HIGH (43 ± 5 versus 46 ± 9 L•min; p = 0.136); however, due to total mean PNC, accumulated inhaled particle counts were 48% lower in LOW, compared to HIGH (7.6 x e8 ± 1.5 x e8 versus 14.6 x e8 ± 1.8 x e8; p = 0.003); 3) LOW resulted in a significant reduction in mean PNC (1.91 x e4 ± 0.93 x e4 ppcc vs. 2.95 x e4 ± 1.50 x e4 ppcc; p ≤ 0.001). Commute distance and duration were not significantly different between LOW and HIGH (12.8 ± 7.1 vs. 12.0 ± 6.9 km and 44 ± 17 vs. 42 ± 17 mins, respectively). Besides incidence of in-commute offensive odour detection (42 vs. 56 %; p = 0.019), incidence of dust and soot observation (33 vs. 47 %; p = 0.038) and nasopharyngeal irritation (31 vs. 41 %; p = 0.007), acute inflammatory indices were not significantly associated to in-commute PNC, nor were these indices reduced with LOW compared to HIGH. The main conclusions of the three studies are that: 1) the perception of air pollution exposure levels and the amenability to adopt exposure risk management strategies where applicable will aid the general population in shifting from passive, motorised transport modes to bicycle commuting; 2) for bicycle commuting at peak morning commute times, inhaled particle counts and therefore cardiopulmonary health risk may be substantially reduced by decreasing exposure to motorised traffic, which should be considered by both bicycle commuters and urban planners; 3) exposure to PNC, and the incidence of offensive odour and nasopharyngeal irritation, can be significantly reduced when utilising a strategy of lowering proximity to motorised traffic whilst bicycle commuting, without significantly increasing commute distance or duration, which may bring important benefits for both healthy and susceptible individuals. In summary, the findings from this project suggests that bicycle commuters can significantly lower their exposure to ultrafine particle emissions by varying their commute route to reduce proximity to motorised traffic and associated combustion emissions without necessarily affecting their time of commute. While the health endpoints assessed with healthy individuals were not indicative of acute health detriment, individuals with pre-disposing physiological-susceptibility may benefit considerably from this risk management strategy – a necessary research focus with the contemporary increased popularity of both promotion and participation in bicycle commuting.

Development of optimal designs of insulated rail joints

Proper functioning of Insulated Rail Joints (IRJs) is essential for the safe operation of the railway signalling systems and broken rail identification circuitries. The Conventional IRJ (CIRJ) resembles structural butt joints consisting of two pieces of rails connected together through two joint bars on either side of their web and the assembly is held together through pre-tensioned bolts. As the IRJs should maintain electrical insulation between the two rails, a gap between the rail ends must be retained at all times and all metal contacting surfaces should be electrically isolated from each other using non-conductive material. At the gap, the rail ends lose longitudinal continuity and hence the vertical sections of the rail ends are often severely damaged, especially at the railhead, due to the passage of wheels compared to other continuously welded rail sections. Fundamentally, the reason for the severe damage can be related to the singularities of the wheel-rail contact pressure and the railhead stress. No new generation designs that have emerged in the market to date have focussed on this fundamental; they only have provided attention to either the higher strength materials or the thickness of the sections of various components of the IRJs. In this thesis a novel method of shape optimisation of the railhead is developed to eliminate the pressure and stress singularities through changes to the original sharp corner shaped railhead into an arc profile in the longitudinal direction. The optimal shape of the longitudinal railhead profile has been determined using three nongradient methods in search of accuracy and efficiency: (1) Grid Search Method; (2) Genetic Algorithm Method and (3) Hybrid Genetic Algorithm Method. All these methods have been coupled with a parametric finite element formulation for the evaluation of the objective function for each iteration or generation depending on the search algorithm employed. The optimal shape derived from these optimisation methods is termed as Stress Minimised Railhead (SMRH) in this thesis. This optimal SMRH design has exhibited significantly reduced stress concentration that remains well below the yield strength of the head hardened rail steels and has shifted the stress concentration location away from the critical zone of the railhead end. The reduction in the magnitude and the relocation of the stress concentration in the SMRH design has been validated through a full scale wheel – railhead interaction test rig; Railhead strains under the loaded wheels have been recorded using a non-contact digital image correlation method. Experimental study has confirmed the accuracy of the numerical predications. Although the SMRH shaped IRJs eliminate stress singularities, they can still fail due to joint bar or bolt hole cracking; therefore, another conceptual design, termed as Embedded IRJ (EIRJ) in this thesis, with no joint bars and pre-tensioned bolts has been developed using a multi-objective optimisation formulation based on the coupled genetic algorithm – parametric finite element method. To achieve the required structural stiffness for the safe passage of the loaded wheels, the rails were embedded into the concrete of the post tensioned sleepers; the optimal solutions for the design of the EIRJ is shown to simplify the design through the elimination of the complex interactions and failure modes of the various structural components of the CIRJ. The practical applicability of the optimal shapes SMRH and EIRJ is demonstrated through two illustrative examples, termed as improved designs (IMD1 & IMD2) in this thesis; IMD1 is a combination of the CIRJ and the SMRH designs, whilst IMD2 is a combination of the EIRJ and SMRH designs. These two improved designs have been simulated for two key operating (speed and wagon load) and design (wheel diameter) parameters that affect the wheel-rail contact; the effect of these parameters has been found to be negligible to the performance of the two improved designs and the improved designs are in turn found far superior to the current designs of the CIRJs in terms of stress singularities and deformation under the passage of the loaded wheels. Therefore, these improved designs are expected to provide longer service life in relation to the CIRJs.

Physical performance profile of sub-elite juvenile Gaelic Games players and the prevalence of a Relative Age Effect (RAE)

Gaelic Games are the indigenous sports played in Ireland, the most popular being Gaelic football and hurling. The games are contact sports and the physical demands are thought to be similar to those of Australian Rules football, rugby union, rugby league, field hockey, and lacrosse (Delahunt et al., 2011). The difference in chronological age between children in a single age group is known as relative age and its consequences as the RAE, whereby younger players are disadvantaged (Del Campo et al., 2010). The purpose of this study was to describe the physical and performance profile of sub-elite juvenile Gaelic Games players and to establish if a RAE is present in this cohort and any influence physiological moderator variables may have on this. Following receipt of ethical approval (EHSREC11-45), six sub-elite county development squads (Under-14/15/16 age groups, male, n=115) volunteered to partake in the study. Anthropometric data including skin folds and girths were collected. A number of field tests of physical performance including 5 and 20m speed, vertical and broad jump distance, and an estimate of VO2max were carried out. Descriptive data are presented as Mean SD. Juvenile sub-elite Gaelic Games players aged 14.53 0.82 y were 172.87 7.63 cm tall, had a mass of 64.74 11.06 kg, a BMI of 21.57 2.82 kg.m-2 and 9.22 4.78 % body fat. Flexibility, measured by sit and reach was 33.62 6.86 cm and lower limb power measured by vertical and broad jump were 42.19 5.73 and 191.16 25.26 cm, respectively. Participant time to complete 5m, 20m and an agility test (T-Test) was 1.12 0.07, 3.31 0.30 and 9.31 0.55 s respectively. Participant’s estimated VO2max was 48.23 5.05 ml.kg.min-1. Chi-Square analysis of birth month by quartile (Q1 = January-March) revealed that a RAE was present in this cohort, whereby an over-representation of players born in Q1 compared with Q2, Q3 and Q4 was evident (2 = 14.078, df = 3, p = 0.003). Kruskal-Wallis analysis of the data revealed no significant difference in any of the performance parameters based on quartile of birth (Alpha level = 0.05).This study provides a physical performance profile of juvenile sub-elite Gaelic Games players, comparable with those of other sports such as soccer and rugby. This novel data can inform us of the physical requirements of the sport. The evidence of a RAE is similar to that observed in other contact sports such as soccer and rugby league (Carling et al, 2009; Till et al, 2010). Although a RAE exists in this cohort, this cannot be explained by any physical/physiological moderator variables. Carling C et al. (2009). Scandinavian Journal of Medicine and Science in Sport 19, 3-9. Delahunt E et al. (2011). Journal of Athletic Training 46, 241-5. Del Campo DG et al. (2010). Journal of Sport Science and Medicine 9, 190-198. Delorme N et al. (2010). European Journal of Sport Science 10, 91-96. Till K et al. (2010). Scandinavian Journal of Medicine and Science in Sports 20, 320-329.

Development of an eight gene expression profile implicating human breast tumours of all grade

The goal of improving systemic treatment of breast cancers is to evolve from treating every patient with non-specific cytotoxic chemotherapy/hormonal therapy, to a more individually-tailored direct treatment. Although anatomic staging and histological grade are important prognostic factors, they often fail to predict the clinical course of this disease. This study aimed to develop a gene expression profile associated with breast cancers of differing grades. We extracted mRNA from FFPE archival breast IDC tissue samples (Grades I–III), including benign tumours. Affymetrix GeneChip� Human Genome U133 Plus 2.0 Arrays were used to determine gene expression profiles and validated by Q-PCR. IHC was used to detect the AXIN2 protein in all tissues. From the array data, an independent group t-test revealed that 178 genes were significantly (P B 0.01) differentially expressed between three grades of malignant breast tumours when compared to benign tissues. From these results, eight genes were significantly differentially expressed in more than one comparison group and are involved in processes implicated in breast cancer development and/or progression. The two most implicated candidates genes were CLD10 and ESPTI1 as their gene expression profile from the microarray analysis was replicated in Q-PCR analyses of the original tumour samples as well as in an extended population. The IHC revealed a significant association between AXIN2 protein expression and ER status. It is readily acknowledged and established that significant differences exist in gene expression between different cancer grades. Expansion of this approach may lead to an improved ability to discriminate between cancer grade and other pathological factors.

Effect of coffee combining green coffee bean constituents with typical roasting products on the Nrf2/ARE pathway in vitro and in vivo

This study investigated Nrf2-activating properties of a coffee blend combining raw coffee bean constituents with 5-O-caffeoylquinic acid (CGA) as a lead component with typical roasting products such as N-methylpyridinium (NMP). In cell culture (HT29) the respective coffee extract (CN-CE) increased nuclear Nrf2 translocation and enhanced the transcription of ARE-dependent genes as exemplified for NAD(P)H:quinone oxidoreductase and glutathione-S-transferase (GST)A1, reflected in the protein level by an increase in GST enzyme activity. In a pilot human intervention study (29 healthy volunteers), daily consumption of 750 mL of CN-coffee for 4 weeks increased Nrf2 transcription in peripheral blood lymphocytes on average. However, the transcriptional response pattern of Nrf2/ARE-dependent genes showed substantial interindividual variations. The presence of SNPs in the Nrf2-promoter, reported recently, as well as the detection of GSTT1*0 (null) genotypes in the study collective strengthens the hypothesis that coffee acts as a modulator of Nrf2-dependent gene response in humans, but genetic polymorphisms play an important role in the individual response pattern.

Improved ultra-performance liquid chromatography with electrospray ionization quadrupole-time-of-flight high-definition mass spectrometry method for the rapid analysis of the chemical constituents of a typical medical formula: Liuwei Dihuang Wan

Liuwei Dihuang Wan (LWD), a classic Chinese medicinal formulae, has been used to improve or restore declined functions related to aging and geriatric diseases, such as impaired mobility, vision, hearing, cognition and memory. It has attracted increasingly much attention as one of the most popular and valuable herbal medicines. However, the systematic analysis of the chemical constituents of LDW is difficult and thus has not been well established. In this paper, a rapid, sensitive and reliable ultra-performance liquid chromatography with electrospray ionization quadrupole time-of-flight high-definition mass spectrometry (UPLC-ESI-Q-TOF-MS) method with automated MetaboLynx analysis in positive and negative ion mode was established to characterize the chemical constituents of LDW. The analysis was performed on a Waters UPLCTM HSS T3 using a gradient elution system. MS/MS fragmentation behavior was proposed for aiding the structural identification of the components. Under the optimized conditions, a total of 50 peaks were tentatively characterized by comparing the retention time and MS data. It is concluded that a rapid and robust platform based on UPLC-ESI-Q-TOF-MS has been successfully developed for globally identifying multiple-constituents of traditional Chinese medicine prescriptions. This is the first report on systematic analysis of the chemical constituents of LDW. This article is protected by copyright. All rights reserved.

A typical migraine susceptibility region localizes to chromosome 1q31

Migraine (with and without aura) is a prevalent neurovascular disease that shows strong familial aggregation, although the number of genes involved and the mode of inheritance is not clear. Some insight into the disease has been gained from genetic studies into a rare and very severe migraine subtype known as familial hemiplegic migraine (FHM). In this study, we took a family-based linkage and association approach to investigate the FHM susceptibility region on chromosome 1q31 for involvement in typical migraine susceptibility in affected Australian pedigrees. Initial multipoint ALLEGRO analysis provided strong evidence for linkage of Chrlq31 markers to typical migraine in a large multigenerational pedigree. The 1-LOD* unit support interval for suggestive linkage spanned approximately 18 cM with a maximum allele sharing LOD* score of 3.36 obtained for marker D1S2782 (P=0.00004). Subsequent analysis of an independent sample of 82 affected pedigrees added support to the initial findings with a maximum LOD* of 1.24 (P=0.008). Utilising the independent sample of 82 pedigrees, we also performed a family-based association test. Results of this analysis indicated distortion of allele transmission at marker D1S249 [global chi2 (5) of 15.00, P=0.010] in these pedigrees. These positive linkage and association results will need further confirmation by independent researchers. However, overall they provide good evidence for the existence of a typical migraine locus near these markers on Chrlq3l, and reinforce the idea that an FHM gene in this genomic region may also contribute to susceptibility to the more common forms of migraine.

Ultimate load behaviour of box-columns under combined loading of axial compression and torsion

This paper describes a study of the theoretical and experimental behaviour of box-columns of varying b/t ratios under loadings of axial compression and torsion and their combinations. Details of the testing rigs and the testing methods, the results obtained such as the load-deflection curves and the interaction diagrams, and experimental observations regarding the behaviour of box-models and the types of local plastic mechanisms associated with each type of loading are presented. A simplified rigid-plastic analysis is carried out to study the collapse behaviour of box-columns under these loadings, based on the observed plastic mechanisms, and the results are compared with those of experiments.

Single-nucleotide polymorphism alleles in the insulin receptor gene are associated with typical migraine

We have identified a migraine locus on chromosome 19p13.3/2 using linkage and association analysis. We isolated 48 single-nucleotide polymorphisms within the locus, of which we genotyped 24 in a Caucasian population comprising 827 unrelated cases and 765 controls. Five single-nucleotide polymorphisms within the insulin receptor gene showed significant association with migraine. This association was independently replicated in a case-control population collected separately. We used experiments with insulin receptor RNA and protein to investigate functionality for the migraine-associated single-nucleotide polymorphisms. We suggest possible functions for the insulin receptor in migraine pathogenesis.