Cyclic strain disrupts endothelial network formation on Matrigel

Most forms of tissue healing depend critically on revascularisation. In soft tissues and in vitro, mechanical stimuli have been shown to promote vessel-forming activity. However, in bone defects, increased interfragmentary motion impairs vascular regeneration. Because these effects seem contradictory, we aimed to determine whether a range of mechanical stimuli exists in which angiogenesis is favoured. A series of cyclic strain magnitudes were applied to a Matrigel-based “tube formation” assay and the total lengths of networks formed by human microvascular endothelial cells measured at 24 h. Network lengths were reduced at all strain levels, compared to unstretched controls. However, the levels of pro-angiogenic matrix metalloproteases-2 and -9 in the corresponding conditioned media were unchanged by strain, and vascular endothelial growth factor was uniformly elevated in stretched conditions. By repeating the assay with the addition of conditioned media from mesenchymal stem cells cultivated in similar conditions, paracrine stimuli were shown to increase network lengths, but not to alter the negative effect of cyclic stretching. Together, these results demonstrate that directly applied periodic strains can inhibit endothelial organisation in vitro, and suggest that this may be due to physical disruption rather than biochemical modulation. Most importantly, the results indicate that the straining of endothelial cells and their assembly into vascular-like structures must be studied simultaneously to adequately characterise the mechanical influence on vessel formation.

An investigation of differences in crash characteristics between males and females involved in a fatigue-related crash or close call event

There is consensus among community and road safety agencies that driver fatigue is a major road safety issue and it is well known that excessive fatigue is linked with an increased risk of a motor vehicle crash. Previous research has implicated a wide variety of factors involved in fatigue-related crashes and the effects of these various factors in regard to crash risk can be interpreted as causal (i.e. alcohol and/or drugs may induce fatigue states) or additive (e.g. where a lack of sleep is combined with alcohol). As such, the purpose of this investigation was to examine self-report data to determine whether there are any differences in the prevalence, crash characteristics, and travel patterns of males and females involved in a fatigue-related crash or close call event. Such research is important to understand how fatigue related incidents occur within the typical driving patterns of men and women and it provides a starting point in order to explore if males and females experience and understand the risk of diving when tired in the same way. A representative sample of (N = 1,600) residents living in the Australian Capital Territory (ACT) and New South Wales (NSW), Australia, were surveyed regarding their experience of fatigue and their involvement in fatigue-related crashes and close call incidents. Results revealed that over 35% of participants reported having had a close call or crash due to driving when tired in the five years prior to the study being conducted. In addition, the results obtained revealed a number of interesting characteristics that provide preliminary evidence that gender differences do exist when examining the prevalence, crash characteristics, and travel patterns of males and females involved in a fatigue-related crash or close call event. It is argued that the results obtained can provide particularly useful information for the refinement and further development of appropriate countermeasures that better target this complex issue.

Postpartum fatigue and driving : relating experiences, thoughts and opinions 12 weeks post-birth

Fatigue in the postnatal period is such a common experience for most mothers that the term ‘postpartum fatigue’ (PPF) has been coined to describe it. When new mothers experience extreme fatigue, it follows that their physical health, mental health, and social-wellbeing is negatively affected. It is interesting to note that there is a distinct lack of empirical investigations focusing on the link between PPF and increased risk of injury; particularly when the links between fatigue and increased risk of road crashes are well documented. The purpose of this investigation was to undertake pilot research to develop an understanding of the duration of PPF and the performance impairments experienced by new mothers when involved in safety-sensitive activities, such as driving a motor vehicle. Semi-structured interviews were undertaken with women (N = 24) at 12 weeks postpartum living in South-east Queensland, Australia. Key themes were identified; with a particular emphasis towards understanding the link between the participant’s experience of postpartum fatigue and the impact this has on their overall cognitive and physiological functioning, as well as their experience of the driving task. Further, sleep/wake data was collected and using the Karolinska Sleepiness Scale (KSS) the potential crash risk for this group of mothers is discussed. It is proposed that the findings of this investigation could be used to improve current knowledge among new mothers and practitioners regarding the mechanisms and consequences of fatigue and to inform interventions that lead to a decreased risk of injury associated with postpartum fatigue.

An examination of the relationship between workload and fatigue within and across consecutive days of work: Is the relationshiop static or dynamic?

Cognitive-energetical theories of information processing were used to generate predictions regarding the relationship between workload and fatigue within and across consecutive days of work. Repeated measures were taken on board a naval vessel during a non-routine and a routine patrol. Data were analyzed using growth curve modeling. Fatigue demonstrated a non-monotonic relationship within days in both patrols – fatigue was high at midnight, started decreasing until noontime and then increased again. Fatigue increased across days towards the end of the non-routine patrol, but remained stable across days in the routine patrol. The relationship between workload and fatigue changed over consecutive days in the non-routine patrol. At the beginning of the patrol, low workload was associated with fatigue. At the end of the patrol, high workload was associated with fatigue. This relationship could not be tested in the routine patrol, however it demonstrated a non-monotonic relationship between workload and fatigue – low and high workloads were associated with the highest fatigue. These results suggest that the optimal level of workload can change over time and thus have implications for the management of fatigue.

What about me? Avoiding fatigue and gaining personal time in the work to leisure transition in work-life balance initiatives

Fatigue and overwork are problems experienced by numerous employees in many industry sectors. Focusing on improving work-life balance can frame the ‘problem’ of long work hours to resolve working time duration issues. Flexible work options through re-organising working time arrangements is key to developing an organisational response for delivering work-life balance and usually involves changing the internal structure of work time. This study examines the effect of compressed long weekly working hours and the consequent ‘long break’ on work-life balance. Using Spillover theory and Border theory, this research considers organisational and personal determinants of overwork and fatigue. It concludes compressed long work hours with a long break provide better work-life balance. Further, a long break allows gaining ‘personal time’ and overcoming fatigue.

Experimental and theoretical studies of the redox potentials of cyclic nitroxides

The redox potentials of 25 cyclic nitroxides from four different structural classes (pyrrolidine, piperidine, isoindoline, and azaphenalene) were determined experimentally by cyclic voltammetry in acetonitrile, and also via high-level ab initio molecular orbital calculations. It is shown that the potentials are influenced by the type of ring system, ring substituents and/or groups surrounding the radical moiety. For the pyrrolidine, piperidine, and isoindolines there is excellent agreement (mean absolute deviation of 0.05 V) between the calculated and experimental oxidation potentials; for the azaphenalenes, however, there is an extraordinary discrepancy (mean absolute deviation of 0.60 V), implying that their one-electron oxidation might involve additional processes not considered in the theoretical calculations. This recently developed azaphenalene class of nitroxide represents a new variant of a nitroxide ring fused to an aromatic system and details of the synthesis of five derivatives involving differing aryl substitution are also presented.

Accelerated computation of cyclic steady state for simulated-moving-bed processes

Industrial applications of the simulated-moving-bed (SMB) chromatographic technology have brought an emergent demand to improve the SMB process operation for higher efficiency and better robustness. Improved process modelling and more-efficient model computation will pave a path to meet this demand. However, the SMB unit operation exhibits complex dynamics, leading to challenges in SMB process modelling and model computation. One of the significant problems is how to quickly obtain the steady state of an SMB process model, as process metrics at the steady state are critical for process design and real-time control. The conventional computation method, which solves the process model cycle by cycle and takes the solution only when a cyclic steady state is reached after a certain number of switching, is computationally expensive. Adopting the concept of quasi-envelope (QE), this work treats the SMB operation as a pseudo-oscillatory process because of its large number of continuous switching. Then, an innovative QE computation scheme is developed to quickly obtain the steady state solution of an SMB model for any arbitrary initial condition. The QE computation scheme allows larger steps to be taken for predicting the slow change of the starting state within each switching. Incorporating with the wavelet-based technique, this scheme is demonstrated to be effective and efficient for an SMB sugar separation process. Moreover, investigations are also carried out on when the computation scheme should be activated and how the convergence of the scheme is affected by a variable stepsize.

Managing driver fatigue : education or motivation?

Fatigue has been recognised as the primary contributing factor in approximately 15% of all fatal road crashes in Australia. To develop effective countermeasures for managing fatigue, this study investigates why drivers continue to drive when sleepy, and driver perceptions and behaviours in regards to countermeasures. Based on responses from 305 Australian drivers, it was identified that the major reasons why these participants continued to drive when sleepy were: wanting to get to their destination; being close to home; and time factors. Participants’ perceptions and use of 18 fatigue countermeasures were investigated. It was found that participants perceived the safest strategies, including stopping and sleeping, swapping drivers and stopping for a quick nap, to be the most effective countermeasures. However, it appeared that their knowledge of safe countermeasures did not translate into their use of these strategies. For example, although the drivers perceived stopping for a quick nap to be an effective countermeasure, they reported more frequent use of less safe methods such as stopping to eat or drink and winding down the window. This finding suggests that, while practitioners should continue educating drivers, they may need a greater focus on motivating drivers to implement safe fatigue countermeasures.

Cochrane review summary for cancer nursing : drug therapy for cancer-related fatigue

Cancer-related fatigue (CRF) is one of themost debilitating symptoms in patients with cancer. It is prevalent at the time of diagnosis and during and after antineoplastic treatment and in patients with advanced disease. The multifactorial and complex nature of CRF makes it challenging for health professionals to identify a clear underlying mechanism and manage this symptom effectively. Often, the management plan for CRF (whether pharmacological or nonpharmacological) can be further complicated by the coexistence of other symptoms. This systematic review1 is therefore important in informing health professionals on the effectiveness of pharmacological management for CRF.

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.