Cell invasion with proliferation mechanisms motivated by time-lapse data

Cell invasion involves a population of cells which are motile and proliferative. Traditional discrete models of proliferation involve agents depositing daughter agents on nearest- neighbor lattice sites. Motivated by time-lapse images of cell invasion, we propose and analyze two new discrete proliferation models in the context of an exclusion process with an undirected motility mechanism. These discrete models are related to a family of reaction- diffusion equations and can be used to make predictions over a range of scales appropriate for interpreting experimental data. The new proliferation mechanisms are biologically relevant and mathematically convenient as the continuum-discrete relationship is more robust for the new proliferation mechanisms relative to traditional approaches.

Migration of breast cancer cells : understanding the roles of volume exclusion and cell-to-cell adhesion

We study MCF-7 breast cancer cell movement in a transwell apparatus. Various experimental conditions lead to a variety of monotone and nonmonotone responses which are difficult to interpret. We anticipate that the experimental results could be caused by cell-to-cell adhesion or volume exclusion. Without any modeling, it is impossible to understand the relative roles played by these two mechanisms. A lattice-based exclusion process random-walk model incorporating agent-to-agent adhesion is applied to the experimental system. Our combined experimental and modeling approach shows that a low value of cell-to-cell adhesion strength provides the best explanation of the experimental data suggesting that volume exclusion plays a more important role than cell-to-cell adhesion. This combined experimental and modeling study gives insight into the cell-level details and design of transwell assays.

Self-narratives of children : using digital journals

This paper takes the position that children are at risk of being marginalised when research methods are not tailored to their requirements. In particular, children who are negotiating early adolescence are presented as an ideal group for involvement with narrative research approaches that attempt to be flexible and creative. With the premise that the need to juggle multiple realities within complex societal structures is challenging and isolating for such children, narrative methods offer a promising mode of access to their individual realities. Children's own self-narratives in the form of email journal entries are proposed as research tools that can help to minimise issues arising from resistance to adults and problems of shared vocabulary that may occur using more traditional methods. Digital journaling, as a means of capturing self-narratives, can provide a convenient space for young people to generate and share their own personal accounts of their lives and their experiences that can also serve to inform others. Guidelines are offered for how to manage a journaling project that is not reliant on children's physical presence within school settings. Digital journals are thus described as multi-function mechanisms that can support personal growth as well as promote shared understandings and social fairness between adults and children.

Associations among smoking status, lifestyle and lipoprotein subclasses

BACKGROUND: The relationship between cigarette smoking and cardiovascular disease is well established, yet the underlying mechanisms remain unclear. Although smokers have a more atherogenic lipid profile, this may be mediated by other lifestyle-related factors. Analysis of lipoprotein subclasses by the use of nuclear magnetic resonance spectroscopy (NMR) may improve characterisation of lipoprotein abnormalities. OBJECTIVE: We used NMR spectroscopy to investigate the relationships between smoking status, lifestyle-related risk factors, and lipoproteins in a contemporary cohort. METHODS: A total of 612 participants (360 women) aged 40–69 years at baseline (199021994) enrolled in the Melbourne Collaborative Cohort Study had plasma lipoproteins measured with NMR. Data were analysed separately by sex. RESULTS: After adjusting for lifestyle-related risk factors, including alcohol and dietary intake, physical activity, and weight, mean total low-density lipoprotein (LDL) particle concentration was greater for female smokers than nonsmokers. Both medium- and small-LDL particle concentrations contributed to this difference. Total high-density lipoprotein (HDL) and large-HDL particle concentrations were lower for female smokers than nonsmokers. The proportion with low HDL particle number was greater for female smokers than nonsmokers. For men, there were few smoking-related differences in lipoprotein measures. CONCLUSION: Female smokers have a more atherogenic lipoprotein profile than nonsmokers. This difference is independent of other lifestyle-related risk factors. Lipoprotein profiles did not differ greatly between male smokers and nonsmokers.

Effects of opening in the cross girders of the flat bottom rail wagons to the load transferring mechanisms when used as road bridge deck

A Flat Bed Rail Wagon (FBRW) has been proposed as an alternative solution for replacing bridges on low traffic volume roads. The subject matter for this paper is to investigate the impediment to load transfer from cross girders to main girder, through visually identifiable structural flaws. Namely, the effect of having large openings at close proximity to the connection of the main girder to the cross girder of a FBRW was examined. It was clear that openings locally reduce the section modulus of the secondary members; however it was unclear how these reductions would affect the load transfer to the main girder. The results are presented through modeling grillage action for which the loads applied onto the FBRW were distributed through cross girders to the main girder.

Addressing childhood obesity through increased physical activity

Obesity is affecting an increasing proportion of children globally. Despite an appreciation that physical activity is essential for the normal growth and development of children and prevents obesity and obesity-related health problems, too few children are physically active. A concurrent problem is that today’s young people spend more time than previous generations did in sedentary pursuits, including watching television and engaging in screen-based games. Active behavior has been displaced by these inactive recreational choices, which has contributed to reductions in activity-related energy expenditure. Implementation of multifactorial solutions considered to offer the best chance of combating these trends is urgently required to redress the energy imbalance that characterizes obesity. The counterproductive ‘shame and blame’ mentality that apportions responsibility for the childhood obesity problem to sufferers, their parents, teachers or health-care providers needs to be changed. Instead, these groups should offer constant support and encouragement to promote appropriate physical activity in children. Failure to provide activity opportunities will increase the likelihood that the children of today will live less healthy (and possibly shorter)lives than their parents.

The effects of muscle fatigue on knee function during landing

The human knee acts as a sophisticated shock absorber during landing movements. The ability of the knee to perform this function in the real world is remarkable given that the context of the landing movement may vary widely between performances. For this reason, humans must be capable of rapidly adjusting the mechanical properties of the knee under impact load in order to satisfy many competing demands. However, the processes involved in regulating these properties in response to changing constraints remain poorly understood. In particular, the effects of muscle fatigue on knee function during step landing are yet to be fully explored. Fatigue of the knee muscles is significant for 2 reasons. First, it is thought to have detrimental effects on the ability of the knee to act as a shock absorber and is considered a risk factor for knee injury. Second, fatigue of knee muscles provides a unique opportunity to examine the mechanisms by which healthy individuals alter knee function. A review of the literature revealed that the effect of fatigue on knee function during landing has been assessed by comparing pre and postfatigue measurements, with fatigue induced by a voluntary exercise protocol. The information is limited by inconsistent results with key measures, such as knee stiffness, showing varying results following fatigue, including increased stiffness, decreased stiffness or failure to detect any change in some experiments. Further consideration of the literature questions the validity of the models used to induce and measure fatigue, as well as the pre-post study design, which may explain the lack of consensus in the results. These limitations cast doubt on the usefulness of the available information and identify a need to investigate alternative approaches. Based on the results of this review, the aims of this thesis were to: • evaluate the methodological procedures used in validation of a fatigue model • investigate the adaptation and regulation of post-impact knee mechanics during repeated step landings • use this new information to test the effects of fatigue on knee function during a step-landing task. To address the aims of the thesis, 3 related experiments were conducted that collected kinetic, kinematic and electromyographic data from 3 separate samples of healthy male participants. The methodologies involved optoelectronic motion capture (VICON), isokinetic dynamometry (System3 Pro, BIODEX) and wireless surface electromyography (Zerowire, Aurion, Italy). Fatigue indicators and knee function measures used in each experiment were derived from the data. Study 1 compared the validity and reliability of repetitive stepping and isokinetic contractions with respect to fatigue of the quadriceps and hamstrings. Fifteen participants performed 50 repetitions of each exercise twice in randomised order, over 4 sessions. Sessions were separated by a minimum of 1 week’s rest, to ensure full recovery. Validity and reliability depended on a complex interaction between the exercise protocol, the fatigue indicator, the individual and the muscle of interest. Nevertheless, differences between exercise protocols indicated that stepping was less effective in eliciting valid and reliable changes in peak power and spectral compression, compared with isokinetic exercise. A key finding was that fatigue progressed in a biphasic pattern during both exercises. The point separating the 2 phases, known as the transition point, demonstrated superior between-test reliability during the isokinetic protocol, compared with stepping. However, a correction factor should be used to accurately apply this technique to the study of fatigue during landing. Study 2 examined alterations in knee function during repeated landings, with a different sample (N =12) performing 60 consecutive step landing trials. Each landing trial was separated by 1-minute rest periods. The results provided new information in relation to the pre-post study design in the context of detecting adjustments in knee function during landing. First, participants significantly increased or decreased pre-impact muscle activity or post-impact mechanics despite environmental and task constraints remaining unchanged. This is the 1st study to demonstrate this effect in healthy individuals without external feedback on performance. Second, single-subject analysis was more effective in detecting alterations in knee function compared to group-level analysis. Finally, repeated landing trials did not reduce inter-trial variability of knee function in some participants, contrary to assumptions underpinning previous studies. The results of studies 1 and 2 were used to modify the design of Study 3 relative to previous research. These alterations included a modified isokinetic fatigue protocol, multiple pre-fatigue measurements and singlesubject analysis to detect fatigue-related changes in knee function. The study design incorporated new analytical approaches to investigate fatiguerelated alterations in knee function during landing. Participants (N = 16) were measured during multiple pre-fatigue baseline trial blocks prior to the fatigue model. A final block of landing trials was recorded once the participant met the operational fatigue definition that was identified in Study 1. The analysis revealed that the effects of fatigue in this context are heavily dependent on the compensatory response of the individual. A continuum of responses was observed within the sample for each knee function measure. Overall, preimpact preparation and post-impact mechanics of the knee were altered with highly individualised patterns. Moreover, participants used a range of active or passive pre-impact strategies to adapt post-impact mechanics in response to quadriceps fatigue. The unique patterns identified in the data represented an optimisation of knee function based on priorities of the individual. The findings of these studies explain the lack of consensus within the literature regarding the effects of fatigue on knee function during landing. First, functional fatigue protocols lack validity in inducing fatigue-related changes in mechanical output and spectral compression of surface electromyography (sEMG) signals, compared with isokinetic exercise. Second, fatigue-related changes in knee function during landing are confounded by inter-individual variation, which limits the sensitivity of group-level analysis. By addressing these limitations, the 3rd study demonstrated the efficacies of new experimental and analytical approaches to observe fatigue-related alterations in knee function during landing. Consequently, this thesis provides new perspectives into the effects of fatigue in knee function during landing. In conclusion: • The effects of fatigue on knee function during landing depend on the response of the individual, with considerable variation present between study participants, despite similar physical characteristics. • In healthy males, adaptation of pre-impact muscle activity and postimpact knee mechanics is unique to the individual and reflects their own optimisation of demands such as energy expenditure, joint stability, sensory information and loading of knee structures. • The results of these studies should guide future exploration of adaptations in knee function to fatigue. However, research in this area should continue with reduced emphasis on the directional response of the population and a greater focus on individual adaptations of knee function.

Increased Langerhan cell density and corneal nerve damage in diabetic patients : role of immune mechanisms in human diabetic neuropathy

Aim/hypothesis Immune mechanisms have been proposed to play a role in the development of diabetic neuropathy. We employed in vivo corneal confocal microscopy (CCM) to quantify the presence and density of Langerhans cells (LCs) in relation to the extent of corneal nerve damage in Bowman's layer of the cornea in diabetic patients. Methods 128 diabetic patients aged 58±1 yrs with a differing severity of neuropathy based on Neuropathy Deficit Score (NDS—4.7±0.28) and 26 control subjects aged 53±3 yrs were examined. Subjects underwent a full neurological evaluation, evaluation of corneal sensation with non-contact corneal aesthesiometry (NCCA) and corneal nerve morphology using corneal confocal microscopy (CCM). Results The proportion of individuals with LCs was significantly increased in diabetic patients (73.8%) compared to control subjects (46.1%), P=0.001. Furthermore, LC density (no/mm2) was significantly increased in diabetic patients (17.73±1.45) compared to control subjects (6.94±1.58), P=0.001 and there was a significant correlation with age (r=0.162, P=0.047) and severity of neuropathy (r=−0.202, P=0.02). There was a progressive decrease in corneal sensation with increasing severity of neuropathy assessed using NDS in the diabetic patients (r=0.414, P=0.000). Corneal nerve fibre density (P<0.001), branch density (P<0.001) and length (P<0.001) were significantly decreased whilst tortuosity (P<0.01) was increased in diabetic patients with increasing severity of diabetic neuropathy. Conclusion Utilising in vivo corneal confocal microscopy we have demonstrated increased LCs in diabetic patients particularly in the earlier phases of corneal nerve damage suggestive of an immune mediated contribution to corneal nerve damage in diabetes.

An overview of physical growth and maturation

An understanding of physical growth and maturation is relevant to many disciplines, including exercise and sport science, anthropology, human biology, medicine, psychology and education. Growth and maturation is governed by a complex interaction between genetic and environmental factors. There is increasing evidence that physical activity plays an important role in normal growth, development, health and well-being of children and youth, however, caution is required in the activity setting so that growth and maturation is not jeopardised. To appreciate the impact of physical activity and/or exercise on growth and maturation, a thorough understanding of the general principles of auxology is useful. Following an introduction to terminology, an overview of physical growth and development is provided in the context of morphological changes. Detailed information is provided regarding individual variability in growth and development along with sexual dimorphism. A small degree of sexual dimorphism exists at birth however striking differences develop during the pubertal years. Sexual dimorphism in body composition is largely regulated by endocrine factors with critical roles played by growth hormone and gonadal steroids.

Are Active Australia physical activity questions valid for older adults?

Objective The Active Australia Survey (AAS) is used for physical activity (PA) surveillance in the general Australian adult population, but its validity in older adults has not been evaluated. Our aim was to examine the convergent validity of the AAS questions in older adults. Design The AAS was validated against pedometer step counts as an objective measure of PA, self-reported physical function, and a step-test to assess cardiorespiratory fitness. Method Participants were community-dwelling adults, aged 65-89 y, with the ability to walk 100 m. They completed a self-administered AAS and the step-test in one interview. One week earlier, they completed the Short Form-36 physical function subscale. Between these two interviews, they each wore a YAMAX Digiwalker SW200 pedometer and recorded daily steps. Using the AAS data, daily walking minutes and total PA minutes (walking, moderate-intensity PA and vigorous-intensity PA) were compared with the validity measures using Spearman rank-order correlations. Fifty-three adults completed the study. Results Median daily walking minutes were 34.2 (interquartile range [IQR] 17.1, 60.0), and median daily total PA minutes were 68.6 (IQR 31.4, 113.6). Walking and total PA minutes were both moderately correlated with pedometer steps (Spearman correlation r=0.42, p=0.003, for each) but not with step-test seconds to completion (r=-0.11, p=0.44; r=-0.25, p=0.08, respectively). Total PA minutes were significantly correlated with physical function scores (r=0.39, p=0.004), but walking minutes were not (r=0.15, p=0.29). Conclusions This initial examination of the psychometric properties of the AAS for older adults suggests that this surveillance tool has acceptable convergent validity for ambulatory, community-dwelling older adults.

Physical function and health-related quality of life of older adults undergoing hospital rehabilitation : how strong is the association?

The purpose of this research is to report preliminary empirical evidence regarding the association between common physical performance measures and health-related quality of life (HRQoL) of hospitalized older adults recovering from illness and injury. Frequently, these patients do not return to premorbid levels of independence and physical ability. Rehabilitation for this population often focuses on improving physical functioning and mobility with the intention of maximizing their HRQoL for discharge and thereafter. For this reason, longitudinal use of physical performance measures as an indicator of improvement in physical functioning (and thus HRQoL) is common. Although this is a logical approach, there have been mixed results from previous investigations into the association between common measures of physical function and HRQoL amongst other adult patient populations.1,2 There has been no previous investigation reporting the association between HRQoL and a variety of common physical performance measures in hospitalized older adults.

Intelligent physical modelling systems - Why?

“What did you think you were doing?” Was the question posed by the conference organizers to me as the inventor and constructor of the first working Tangible Interfaces over 40 years ago. I think the question was intended to encourage me to talk about the underlying ideas and intentionality rather than describe an endless sequence of electronic bricks and that is what I shall do in this presentation. In the sixties the prevalent idea for a graphics interface was an analogue with sketching which was to somehow be understood by the computer as three dimensional form. I rebelled against this notion for reasons which I will explain in the presentation and instead came up with tangible physical three dimensional intelligent objects. I called these first prototypes “Intelligent Physical Modelling Systems” which is a really dumb name for an obvious concept. I am eternally grateful to Hiroshi Ishii for coining the term “Tangible User Interfaces” - the same idea but with a much smarter name. Another motivator was user involvement in the design process, and that led to the Generator (1979) project with Cedric Price for the world’s first intelligent building capable of organizing itself in response to the appetites of the users. The working model of that project is in MoMA. And the same motivation led to a self builders design kit (1980) for Walter Segal which facilitated self-builders to design their own houses. And indeed as the organizer’s question implied, the motivation and intentionality of these projects developed over the years in step with advancing technology. The speaker will attempt to articulate these changes with medical, psychological and educational examples. Much of this later work indeed stemming from the Media Lab where we are talking. Related topics such as “tangible thinking” and “intelligent teacups” will be introduced and the presentation will end with some speculations for the future. The presentation will be given against a background of images of early prototypes many of which have never been previously published.

Physical and functional interaction of the archaeal single-stranded DNA-binding protein SSB with RNA polymerase

Archaeal transcription utilizes a complex multisubunit RNA polymerase and the basal transcription factors TBP and TF(II)B, closely resembling its eukaryal counterpart. We have uncovered a tight physical and functional interaction between RNA polymerase and the single-stranded DNA-binding protein SSB in Sulfolobus solfataricus. SSB stimulates transcription from promoters in vitro under TBP-limiting conditions and supports transcription in the absence of TBP. SSB also rescues transcription from repression by reconstituted chromatin. We demonstrate the potential for promoter melting by SSB, suggesting a plausible basis for the stimulation of transcription. This stimulation requires both the single-stranded DNA-binding domain and the acidic C-terminal tail of the SSB. The tail forms a stable interaction with RNA polymerase. These data reveal an unexpected role for single-stranded DNA-binding proteins in transcription in archaea.

Cancer-related symptom clusters for symptom management in outpatients after commencing adjuvant chemotherapy, at 6 months, and 12 months

Goals of work: The aim of this secondary data analysis was to investigate symptom clusters over time for symptom management of a patient group after commencing adjuvant chemotherapy. Materials and methods: A prospective longitudinal study of 219 cancer outpatients conducted within 1 month of commencing chemotherapy (T1), 6 months (T2), and 12 months (T3) later. Patients' distress levels were assessed for 42 physical symptoms on a clinician-modified Rotterdam Symptom Checklist. Symptom clusters were identified in exploratory factor analyses at each time. Symptom inclusion in clusters was determined from structure coefficients. Symptoms could be associated with multiple clusters. Stability over time was determined from symptom cluster composition and the proportion of symptoms in the initial symptom clusters replicated at later times. Main results Fatigue and daytime sleepiness were the most prevalent distressing symptoms over time. The median number of concurrent distressing symptoms approximated 7, over time. Five consistent clusters were identified at T1, 2, and T3. An additional two clusters were identified at 12 months, possibly due to less variation in distress levels. Weakness and fatigue were each associated with two, four, and five symptom clusters at T1, T2, and T3, respectively, potentially suggesting different causal mechanisms. Conclusion: Stability is a necessary attribute of symptom clusters, but definitional clarification is required. We propose that a core set of concurrent symptoms identifies each symptom cluster, signifying a common cause. Additional related symptoms may be included over time. Further longitudinal investigation is required to identify symptom clusters and the underlying causes.

MobileMums: A randomized controlled trial of an SMS-based physical activity intervention

Background Postnatal women (<12 months postpartum) are at increased risk of physical inactivity. Purpose To evaluate the efficacy and feasibility of a theory-based physical activity (PA) intervention delivered to postnatal women primarily via mobile telephone short message service (SMS). Methods Eighty-eight women were randomized to the intervention (n=45) or minimal contact control (n=43) condition. The 12-week intervention consisted of a face-to-face PA goal-setting consultation, a goal-setting magnet, three to five personally tailored SMS/week and a nominated support person who received two SMS per week. SMS content targeted constructs of social cognitive theory. Frequency (days/week) and duration (min/week) of PA participation and walking for exercise were assessed via self-report at baseline, 6 and 13 weeks. Results Intervention participants increased PA frequency by 1.82 days/week (SE±0.18) by 13 weeks (F(2,85)=4.46, p=0.038) and walking for exercise frequency by 1.08 days/ week (SE±0.24) by 13 weeks (F(2,85)=5.38, p=0.02). Positive trends were observed for duration (min/week) of PA and walking for exercise. Conclusions Intervention exposure resulted in increased frequency of PA and walking for exercise in postnatal women.