Accelerated Partial Breast Irradiation (APBI) : a review of available techniques

Breast conservation therapy (BCT) is the procedure of choice for the management of the early stage breast cancer. However, its utilization has not been maximized because of logistics issues associated with the protracted treatment involved with the radiation treatment. Accelerated Partial Breast Irradiation (APBI) is an approach that treats only the lumpectomy bed plus a 1-2 cm margin, rather than the whole breast. Hence because of the small volume of irradiation a higher dose can be delivered in a shorter period of time. There has been growing interest for APBI and various approaches have been developed under phase I-III clinical studies; these include multicatheter interstitial brachytherapy, balloon catheter brachytherapy, conformal external beam radiation therapy and intra-operative radiation therapy (IORT). Balloon-based brachytherapy approaches include Mammosite, Axxent electronic brachytherapy and Contura, Hybrid brachytherapy devices include SAVI and ClearPath. This paper reviews the different techniques, identifying the weaknesses and strength of each approach and proposes a direction for future research and development. It is evident that APBI will play a role in the management of a selected group of early breast cancer. However, the relative role of the different techniques is yet to be clearly identified.

Automatic generation of assertions to detect potential security vulnerabilities in C programs that use union and pointer types

Type unions, pointer variables and function pointers are a long standing source of subtle security bugs in C program code. Their use can lead to hard-to-diagnose crashes or exploitable vulnerabilities that allow an attacker to attain privileged access over classified data. This paper describes an automatable framework for detecting such weaknesses in C programs statically, where possible, and for generating assertions that will detect them dynamically, in other cases. Exclusively based on analysis of the source code, it identifies required assertions using a type inference system supported by a custom made symbol table. In our preliminary findings, our type system was able to infer the correct type of unions in different scopes, without manual code annotations or rewriting. Whenever an evaluation is not possible or is difficult to resolve, appropriate runtime assertions are formed and inserted into the source code. The approach is demonstrated via a prototype C analysis tool.

Remaining useful life prediction using elliptical basis function network and Markov Chain

This paper presents a novel method for remaining useful life prediction using the Elliptical Basis Function (EBF) network and a Markov chain. The EBF structure is trained by a modified Expectation-Maximization (EM) algorithm in order to take into account the missing covariate set. No explicit extrapolation is needed for internal covariates while a Markov chain is constructed to represent the evolution of external covariates in the study. The estimated external and the unknown internal covariates constitute an incomplete covariate set which are then used and analyzed by the EBF network to provide survival information of the asset. It is shown in the case study that the method slightly underestimates the remaining useful life of an asset which is a desirable result for early maintenance decision and resource planning.

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.

Caveat Anicula! Beware of the Quiet Little Old Ladies : Demographics, Pharmacotherapy, Survival and Readmissions in a 10 Year Cohort of Heart Failure Patients with Preserved Systolic Function

Objective--To determine whether heart failure with preserved systolic function (HFPSF) has different natural history from left ventricular systolic dysfunction (LVSD). Design and setting--A retrospective analysis of 10 years of data (for patients admitted between 1 July 1994 and 30 June 2004, and with a study census date of 30 June 2005) routinely collected as part of clinical practice in a large tertiary referral hospital.Main outcome measures-- Sociodemographic characteristics, diagnostic features, comorbid conditions, pharmacotherapies, readmission rates and survival.Results--Of the 2961 patients admitted with chronic heart failure, 753 had echocardiograms available for this analysis. Of these, 189 (25%) had normal left ventricular size and systolic function. In comparison to patients with LVSD, those with HFPSF were more often female (62.4% v 38.5%; P = 0.001), had less social support, and were more likely to live in nursing homes (17.9% v 7.6%; P < 0.001), and had a greater prevalence of renal impairment (86.7% v 6.2%; P = 0.004), anaemia (34.3% v 6.3%; P = 0.013) and atrial fibrillation (51.3% v 47.1%; P = 0.008), but significantly less ischaemic heart disease (53.4% v 81.2%; P = 0.001). Patients with HFPSF were less likely to be prescribed an angiotensin-converting enzyme inhibitor (61.9% v 72.5%; P = 0.008); carvedilol was used more frequently in LVSD (1.5% v 8.8%; P < 0.001). Readmission rates were higher in the HFPSF group (median, 2 v 1.5 admissions; P = 0.032), particularly for malignancy (4.2% v 1.8%; P < 0.001) and anaemia (3.9% v 2.3%; P < 0.001). Both groups had the same poor survival rate (P = 0.912). Conclusions--Patients with HFPSF were predominantly older women with less social support and higher readmission rates for associated comorbid illnesses. We therefore propose that reduced survival in HFPSF may relate more to comorbid conditions than suboptimal cardiac management.

Age, muscle fatigue, and walking endurance in pre-menopausal women

Aging is associated with loss of endurance; however, aging is also associated with decreased fatigue during maximal isometric contractions. The aims of this study were to examine the relationship between age and walking endurance (WE) and maximal isometric fatigue (MIF) and to determine which metabolic/fitness components explain the expected age effects on WE and MIF. Subjects were 96 pre-menopausal women. Oxygen uptake (walking economy) was assessed during a 3-mph walk; aerobic capacity and WE by progressive treadmill test; knee extension strength by isometric contractions, MIF during a 90-s isometric plantar flexion (muscle metabolism measured by 31P MRS). Age was related to increased walking economy (low VO2, r = −0.19, P < 0.03) and muscle metabolic economy (force/ATP, 0.34, P = 0.01), and reduced MIF (−0.26, P < 0.03). However, age was associated with reduced WE (−0.28, P < 0.01). Multiple regression showed that muscle metabolic economy explained the age-related decrease in MIF (partial r for MIF and age −0.13, P = 0.35) whereas walking economy did not explain the age-related decrease in WE (partial r for WE and age −0.25, P < 0.02). Inclusion of VO2max and knee endurance strength accounted for the age-related decreased WE (partial r for WE and age = 0.03, P > 0.80). In premenopausal women, age is related to WE and MIF. In addition, these results support the hypothesis that age-related increases in metabolic economy may decrease MIF. However, decreased muscle strength and oxidative capacity are related to WE.

Simulated cataract and low contrast stimuli impair cognitive performance in older adults : implications for neuropsychological assessment and everyday function

Objective: To investigate how age-related declines in vision (particularly contrast sensitivity), simulated using cataract-goggles and low-contrast stimuli, influence the accuracy and speed of cognitive test performance in older adults. An additional aim was to investigate whether declines in vision differentially affect secondary more than primary memory. Method: Using a fully within-subjects design, 50 older drivers aged 66-87 years completed two tests of cognitive performance - letter matching (perceptual speed) and symbol recall (short-term memory) - under different viewing conditions that degraded visual input (low-contrast stimuli, cataract-goggles, and low-contrast stimuli combined with cataract-goggles, compared with normal viewing). However, presentation time was also manipulated for letter matching. Visual function, as measured using standard charts, was taken into account in statistical analyses. Results: Accuracy and speed for cognitive tasks were significantly impaired when visual input was degraded. Furthermore, cognitive performance was positively associated with contrast sensitivity. Presentation time did not influence cognitive performance, and visual gradation did not differentially influence primary and secondary memory. Conclusion: Age-related declines in visual function can impact on the accuracy and speed of cognitive performance, and therefore the cognitive abilities of older adults may be underestimated in neuropsychological testing. It is thus critical that visual function be assessed prior to testing, and that stimuli be adapted to older adults' sensory capabilities (e.g., by maximising stimuli contrast).

Improving the performance of model-order selection criteria by partial-model selection search

The traditional searching method for model-order selection in linear regression is a nested full-parameters-set searching procedure over the desired orders, which we call full-model order selection. On the other hand, a method for model-selection searches for the best sub-model within each order. In this paper, we propose using the model-selection searching method for model-order selection, which we call partial-model order selection. We show by simulations that the proposed searching method gives better accuracies than the traditional one, especially for low signal-to-noise ratios over a wide range of model-order selection criteria (both information theoretic based and bootstrap-based). Also, we show that for some models the performance of the bootstrap-based criterion improves significantly by using the proposed partial-model selection searching method. Index Terms— Model order estimation, model selection, information theoretic criteria, bootstrap 1. INTRODUCTION Several model-order selection criteria can be applied to find the optimal order. Some of the more commonly used information theoretic-based procedures include Akaike’s information criterion (AIC) [1], corrected Akaike (AICc) [2], minimum description length (MDL) [3], normalized maximum likelihood (NML) [4], Hannan-Quinn criterion (HQC) [5], conditional model-order estimation (CME) [6], and the efficient detection criterion (EDC) [7]. From a practical point of view, it is difficult to decide which model order selection criterion to use. Many of them perform reasonably well when the signal-to-noise ratio (SNR) is high. The discrepancies in their performance, however, become more evident when the SNR is low. In those situations, the performance of the given technique is not only determined by the model structure (say a polynomial trend versus a Fourier series) but, more importantly, by the relative values of the parameters within the model. This makes the comparison between the model-order selection algorithms difficult as within the same model with a given order one could find an example for which one of the methods performs favourably well or fails [6, 8]. Our aim is to improve the performance of the model order selection criteria in cases where the SNR is low by considering a model-selection searching procedure that takes into account not only the full-model order search but also a partial model order search within the given model order. Understandably, the improvement in the performance of the model order estimation is at the expense of additional computational complexity.

Executive function effects and numerical development in children : behavioural and ERP evidence from a numerical Stroop paradigm

Most research on numerical development in children is behavioural, focusing on accuracy and response time in different problem formats. However, Temple and Posner (1998) used ERPs and the numerical distance task with 5-year-olds to show that the development of numerical representations is difficult to disentangle from the development of the executive components of response organization and execution. Here we use the numerical Stroop paradigm (NSP) and ERPs to study possible executive interference in numerical processing tasks in 6–8-year-old children. In the NSP, the numerical magnitude of the digits is task-relevant and the physical size of the digits is task-irrelevant. We show that younger children are highly susceptible to interference from irrelevant physical information such as digit size, but that access to the numerical representation is almost as fast in young children as in adults. We argue that the developmental trajectories for executive function and numerical processing may act together to determine numerical development in young children.

Tips for generating a media release and media coverage : how the media ate up my research on Aussie horror movies

The focus of this paper is preparing research for dissemination by mainstream print, broadcast, and online media. While the rise of the blogosphere and social media is proving an effective way of reaching niche audiences, my own research reached such an audience through traditional media. The first major study of Australian horror cinema, my PhD thesis A Dark New World: Anatomy of Australian Horror Films, generated strong interest from horror movie fans, film scholars, and filmmakers. I worked closely with the Queensland University of Technology’s (QUT) public relations unit to write two separate media releases circulated on October 13, 2008 and October 14, 2009. This chapter reflects upon the process of working with the media and provides tips for reaching audiences, particularly in terms of strategically planning outcomes. It delves into the background of my study which would later influence my approach to the media, the process of drafting media releases, and key outcomes and benefits from popularising research. A key lesson from this experience is that redeveloping research for the media requires a sharp writing style, letting go of academic justification, catchy quotes, and an ability to distil complex details into easy-to-understand concepts. Although my study received strong media coverage, and I have since become a media commentator, my experiences also revealed a number of pitfalls that are likely to arise for other researchers keen on targeting media coverage.

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.

Lie group symmetry analysis for granular media stress equations

The Airy stress function, although frequently employed in classical linear elasticity, does not receive similar usage for granular media problems. For plane strain quasi-static deformations of a cohesionless Coulomb–Mohr granular solid, a single nonlinear partial differential equation is formulated for the Airy stress function by combining the equilibrium equations with the yield condition. This has certain advantages from the usual approach, in which two stress invariants and a stress angle are introduced, and a system of two partial differential equations is needed to describe the flow. In the present study, the symmetry analysis of differential equations is utilised for our single partial differential equation, and by computing an optimal system of one-dimensional Lie algebras, a complete set of group-invariant solutions is derived. By this it is meant that any group-invariant solution of the governing partial differential equation (provided it can be derived via the classical symmetries method) may be obtained as a member of this set by a suitable group transformation. For general values of the parameters (angle of internal friction and gravity g) it is found there are three distinct classes of solutions which correspond to granular flows considered previously in the literature. For the two limiting cases of high angle of internal friction and zero gravity, the governing partial differential equation admit larger families of Lie point symmetries, and from these symmetries, further solutions are derived, many of which are new. Furthermore, the majority of these solutions are exact, which is rare for granular flow, especially in the case of gravity driven flows.

An advanced implicit meshless approach for fractional partial differential equation in computational mechanics

Recently, the numerical modelling and simulation for fractional partial differential equations (FPDE), which have been found with widely applications in modern engineering and sciences, are attracting increased attentions. The current dominant numerical method for modelling of FPDE is the explicit Finite Difference Method (FDM), which is based on a pre-defined grid leading to inherited issues or shortcomings. This paper aims to develop an implicit meshless approach based on the radial basis functions (RBF) for numerical simulation of time fractional diffusion equations. The discrete system of equations is obtained by using the RBF meshless shape functions and the strong-forms. The stability and convergence of this meshless approach are then discussed and theoretically proven. Several numerical examples with different problem domains are used to validate and investigate accuracy and efficiency of the newly developed meshless formulation. The results obtained by the meshless formations are also compared with those obtained by FDM in terms of their accuracy and efficiency. It is concluded that the present meshless formulation is very effective for the modelling and simulation for FPDE.

Chlamydial infection of immune cells : altered function and implications for disease

Chlamydia trachomatis is an obligate intracellular bacterial pathogen that infects the genital and ocular mucosa of humans, causing infections that can lead to pelvic inflammatory disease, infertility, and blinding trachoma. C. pneumoniae is a respiratory pathogen that is the cause of 12–15% of community-acquired pneumonia. Both chlamydial species were believed to be restricted to the epithelia of the genital, ocular, and respiratory mucosa; however, increasing evidence suggests that both these pathogens can be isolated from peripheral blood of both healthy individuals and patients with inflammatory conditions such as coronary artery disease and asthma. Chlamydia can also be isolated from brain tissues of patients with degenerative neurological disorders such as Alzheimer’s disease and multiple sclerosis, and also from certain lymphomas. An increasing number of in vitro studies suggest that some chlamydial species can infect immune cells, at least at low levels. These infections may alter immune cell function in a way that promotes chlamydial persistence in the host and contributes to the progression of several chronic inflammatory diseases. In this paper, we review the evidence for the growth of Chlamydia in immune cells, particularly monocytes/macrophages and dendritic cells, and describe how infection may affect the function of these cells.

Multiple human single-stranded DNA binding proteins function in genome maintenance : structural, biochemical and functional analysis

DNA exists predominantly in a duplex form that is preserved via specific base pairing. This base pairing affords a considerable degree of protection against chemical or physical damage and preserves coding potential. However, there are many situations, e.g. during DNA damage and programmed cellular processes such as DNA replication and transcription, in which the DNA duplex is separated into two singlestranded DNA (ssDNA) strands. This ssDNA is vulnerable to attack by nucleases, binding by inappropriate proteins and chemical attack. It is very important to control the generation of ssDNA and protect it when it forms, and for this reason all cellular organisms and many viruses encode a ssDNA binding protein (SSB). All known SSBs use an oligosaccharide/oligonucleotide binding (OB)-fold domain for DNA binding. SSBs have multiple roles in binding and sequestering ssDNA, detecting DNA damage, stimulating strand-exchange proteins and helicases, and mediation of protein–protein interactions. Recently two additional human SSBs have been identified that are more closely related to bacterial and archaeal SSBs. Prior to this it was believed that replication protein A, RPA, was the only human equivalent of bacterial SSB. RPA is thought to be required for most aspects of DNA metabolism including DNA replication, recombination and repair. This review will discuss in further detail the biological pathways in which human SSBs function.