The acute adaptations of normal and pathological human Achilles tendons to eccentric and concentric exercise

Eccentric exercise is the conservative treatment of choice for mid-portion Achilles tendinopathy. While there is a growing body of evidence supporting the medium to long term efficacy of eccentric exercise in Achilles tendinopathy treatment, very few studies have investigated the short term response of the tendon to eccentric exercise. Moreover, the mechanisms through which tendinopathy symptom resolution occurs remain to be established. The primary purpose of this thesis was to investigate the acute adaptations of the Achilles tendon to, and the biomechanical characteristics of, the eccentric exercise protocol used for Achilles tendinopathy rehabilitation and a concentric equivalent. The research was conducted with an orientation towards exploring potential mechanisms through which eccentric exercise may bring about a resolution of tendinopathy symptoms. Specifically, the morphology of tendinopathic and normal Achilles tendons was monitored using high resolution sonography prior to and following eccentric and concentric exercise, to facilitate comparison between the treatment of choice and a similar alternative. To date, the only proposed mechanism through which eccentric exercise is thought to result in symptom resolution is the increased variability in motor output force observed during eccentric exercise. This thesis expanded upon prior work by investigating the variability in motor output force recorded during eccentric and concentric exercises, when performed at two different knee joint angles, by limbs with and without symptomatic tendinopathy. The methodological phase of the research focused on establishing the reliability of measures of tendon thickness, tendon echogenicity, electromyography (EMG) of the Triceps Surae and the standard deviation (SD) and power spectral density (PSD) of the vertical ground reaction force (VGRF). These analyses facilitated comparison between the error in the measurements and experimental differences identified as statistically significant, so that the importance and meaning of the experimental differences could be established. One potential limitation of monitoring the morphological response of the Achilles tendon to exercise loading is that the Achilles tendon is continually exposed to additional loading as participants complete the walking required to carry out their necessary daily tasks. The specific purpose of the last experiment in the methodological phase was to evaluate the effect of incidental walking activity on Achilles tendon morphology. The results of this study indicated that walking activity could decrease Achilles tendon thickness (negative diametral strain) and that the decrease in thickness was dependent on both the amount of walking completed and the proximity of walking activity to the sonographic examination. Thus, incidental walking activity was identified as a potentially confounding factor for future experiments which endeavoured to monitor changes in tendon thickness with exercise loading. In the experimental phase of this thesis the thickness of Achilles tendons was monitored prior to and following isolated eccentric and concentric exercise. The initial pilot study demonstrated that eccentric exercise resulted in a greater acute decrease in Achilles tendon thickness (greater diametral strain) compared to an equivalent concentric exercise, in participants with no history of Achilles tendon pain. This experiment was then expanded to incorporate participants with unilateral Achilles tendinopathy. The major finding of this experiment was that the acute decrease in Achilles tendon thickness observed following eccentric exercise was modified by the presence of tendinopathy, with a smaller decrease (less diametral strain) noted for tendinopathic compared to healthy control tendon. Based on in vitro evidence a decrease in tendon thickness is believed to reflect extrusion of fluid from the tendon with loading. This process would appear to be limited by the presence of pathology and is hypothesised to be a result of the changes in tendon structure associated with tendinopathy. Load induced fluid movement may be important to the maintenance of tendon homeostasis and structure as it has the potential to enhance molecular movement and stimulate tendon remodelling. On this basis eccentric exercise may be more beneficial to the tendon than concentric exercise. Finally, EMG and motor output force variability (SD and PSD of VGRF) were investigated while participants with and without tendinopathy performed the eccentric and concentric exercises. Although between condition differences were identified as statistically significant for a number of force variability parameters, the differences were not greater than the limits of agreement for repeated measures. Consequently the meaning and importance of these findings were questioned. Interestingly, the EMG amplitude of all three Triceps Surae muscles did not vary with knee joint angle during the performance of eccentric exercise. This raises questions pertaining to the functional importance of performing the eccentric exercise protocol at each of the two knee joint angles as it is currently prescribed. EMG amplitude was significantly greater during concentric compared to eccentric muscle actions. Differences in the muscle activation patterns may result in different stress distributions within the tendon and be related to the different diametral strain responses observed for eccentric and concentric muscle actions.

The morphology of service bundling settings

The purpose of this paper is to advance our understanding of what contextual factors influence the service bundling process in an organizational setting. Although previous literature contains insights into the mechanisms underlying bundling and the artefacts for performing the bundling task itself, the body of knowledge seems to lack a comprehensive framework for analysing the actual scenario in which the bundling process is performed. This is required as the scenario will influence the bundling method and the IT support. We address this need by designing a morphological box for analysing bundling scenarios in different organizational settings. The factors featured in the box are systematised into a set of four categories of bundling layers which we identify from reviewing literature. The two core layers in the framework are the service bundling on a type level and on an instance level (i.e. configuration). To demonstrate the applicability and utility of the proposed morphological box, we apply it to assess the underlying differences and commonalities of two different bundling scenarios from the B2B and G2C sectors which stress the differences between bundling on a type and instance level. In addition, we identify several prospects for future research that can benefit from the proposed morphological box.

The expression, regulation and function of kallikrein 4 in prostate cancer

Prostate cancer is a significant health problem faced by aging men. Currently, diagnostic strategies for the detection of prostate cancer are either unreliable, yielding high numbers of false positive results, or too invasive to be used widely as screening tests. Furthermore, the current therapeutic strategies for the treatment of the disease carry considerable side effects. Although organ confined prostate cancer can be curable, most detectable clinical symptoms occur in advanced disease when primary tumour cells have metastasised to distant sites - usually lymph nodes and bone. Many growth factors and steroids assist the continued growth and maintenance of prostatic tumour cells. Of these mitogens, androgens are important in the development of the normal prostate but are also required to sustain the growth of prostate cancer cells in the early stage of the disease. Not only are androgens required in the early stage of disease, but also many other growth factors and hormones interact to cause uncontrolled proliferation of malignant cells. The early, androgen sensitive phase of disease is followed by an androgen insensitive phase, whereby androgens are no longer required to stimulate the growth of the tumour cells. Growth factors such as transforming growth factor  and  (TGF/), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), insulin-like growth factors (IGFs), Vitamin D and thyroid hormone have been suggested to be important at this stage of disease. Interestingly, some of the kallikrein family of genes, including prostate specific antigen (PSA), the current serum diagnostic marker for prostate cancer, are regulated by androgens and many of the aforementioned growth factors. The kallikrein gene family is a group of serine proteases that are involved in a diverse range of physiological processes: regulation of local blood flow, angiogenesis, tissue invasion and mitogenesis. The earliest members of the kallikrein gene family (KLK1-KLK3) have been strongly associated with general disease states, such as hypertension, inflammation, pancreatitis and renal disease, but are also linked to various cancers. Recently, this family was extended to include 15 genes (KLK1-15). Several newer members of the kallikrein family have been implicated in the carcinogenesis and tumour metastasis of hormone-dependent cancers such as prostate, breast, endometrial and ovarian cancer. The aims of this project were to investigate the expression of the newly identified kallikrein, KLK4, in benign and malignant prostate tissues, and prostate cancer cell lines. This thesis has demonstrated the elevated expression of KLK4 mRNA transcripts in malignant prostate tissue compared to benign prostates. Additionally, expression of the full length KLK4 transcript was detected in the androgen dependent prostate cancer cell line, LNCaP. Based on the above finding, the LNCaP cell line was chosen to assess the potential regulation of full length KLK4 by androgen, thyroid hormone and epidermal growth factor. KLK4 mRNA and protein was found to be up-regulated by androgen and a combination of androgen and thyroid hormone. Thyroid hormone alone produced no significant change in KLK4 mRNA or protein over the control. Epidermal growth factor treatment also resulted in elevated expression levels of KLK4 mRNA and protein. To assess the potential functional role(s) of KLK4/hK4 in processes associated with tumour progression, full length KLK4 was transfected into PC-3 cells - a prostate cancer cell line originally derived from a secondary bone lesion. The KLK4/hK4 over-expressing cells were assessed for their proliferation, migration, invasion and attachment properties. The KLK4 over-expressing clones exhibited a marked change in morphology, indicative of a more aggressive phenotype. The KLK4 clones were irregularly shaped with compromised adhesion to the growth surface. In contrast, the control cell lines (parent PC-3 and empty vector clones) retained a rounded morphology with obvious cell to cell adhesion, as well as significant adhesion to their growth surface. The KLK4 clones exhibited significantly greater attachment to Collagen I and IV than native PC-3s and empty vector controls. Over a 12 hour period, in comparison to the control cells, the KLK4 clones displayed an increase in migration towards PC-3 native conditioned media, a 3 fold increase towards conditioned media from an osteoblastic cell line (Saos-2) and no change in migration towards conditioned media from neonatal foreskin fibroblast cells or 20% foetal bovine serum. Furthermore, the increase in migration exhibited by the KLK4 clones was partially blocked by the serine protease inhibitor, aprotinin. The data presented in this thesis suggests that KLK4/hK4 is important in prostate carcinogenesis due to its over-expression in malignant prostate tissues, its regulation by hormones and growth factors associated with prostate disease and the functional consequences of over-expression of KLK4/hK4 in the PC-3 cell line. These results indicate that KLK4/hK4 may play an important role in tumour invasion and bone metastasis via increased attachment to the bone matrix protein, Collagen I, and enhanced migration due to soluble factors produced by osteoblast cells. This suggestion is further supported by the morphological changes displayed by the KLK4 over-expressing cells. Overall, this data suggests that KLK4/hK4 should be further studied to more fully investigate the potential value of KLK4/hK4 as a diagnostic/prognostic biomarker or in therapeutic applications.

Early local functional changes in the human diabetic retina : a global flash multifocal electroretinogram study

Purpose: To investigate early functional changes of local retinal defects in type II diabetic patients using the global flash multifocal electroretinogram (MOFO mfERG). Methods: Thirty-eight diabetic patients and 14 age-matched controls were recruited. Nine of the diabetics were free from diabetic retinopathy (DR), while the remainder had mild to moderate non-proliferative diabetic retinopathy. The MOFO mfERG was performed at high (98%) and low (46%) contrast levels. MfERG responses were grouped into 35 regions for comparison with DR classification at those locations. Z-scores of the regional mfERG responses were compared across different types of DR defects. Results: The mfERG waveform consisted of the direct component (DC) and the induced component (IC). Local reduction in DC and IC amplitudes were found in diabetic patients with and without DR. With increasing severity of retinopathy, there was a further deterioration in amplitude of both components. Under MOFO mfERG paradigm, amplitude was a useful screening parameter. Conclusion: The MOFO mfERG can help in detecting early functional anomalies before the appearance of visible signs, and may assist in monitoring further functional deterioration in diabetic patients.

Homo- and heteronuclear meso,meso-(E)-Ethene-1,2-diyl-Linked Diporphyrins : preparation, X-ray crystal structure, electronic absorption and emission spectra and density functional theory calculations

Homo-and heteronuclear meso,meso-(E)-ethene-1,2-diyl-linked diporphyrins have been prepared by the Suzuki coupling of porphyrinylboronates and iodovinylporphyrins. Combinations comprising 5,10,15-triphenylporphyrin (TriPP) on both ends of the ethene-1,2-diyl bridge M 210 (M 2=H 2/Ni, Ni 2, Ni/Zn, H 4, H 2Zn, Zn 2) and 5,15-bis(3,5-di-tert-butylphenyl)porphyrinato-nickel(II) on one end and H 2, Ni, and ZnTriPP on the other (M 211), enable the first studies of this class of compounds possessing intrinsic polarity. The compounds were characterized by electronic absorption and steady state emission spectra, 1H NMR spectra, and for the Ni 2 bis(TriPP) complex Ni 210, single crystal X-ray structure determination. The crystal structure shows ruffled distortions of the porphyrin rings, typical of Ni II porphyrins, and the (E)-C 2H 2 bridge makes a dihedral angle of 50° with the mean planes of the macrocycles. The result is a stepped parallel arrangement of the porphyrin rings. The dihedral angles in the solid state reflect the interplay of steric and electronic effects of the bridge on interporphyrin communication. The emission spectra in particular, suggest energy transfer across the bridge is fast in conformations in which the bridge is nearly coplanar with the rings. Comparisons of the fluorescence behaviour of H 410 and H 2Ni10 show strong quenching of the free base fluorescence when the complex is excited at the lower energy component of the Soret band, a feature associated in the literature with more planar conformations. TDDFT calculations on the gas-phase optimized geometry of Ni 210 reproduce the features of the experimental electronic absorption spectrum within 0.1 eV. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Should athletes return to sport after applying Ice? A systematic review of the effect of local 3 cooling on functional performance

Applying ice or other forms of topical cooling is a popular method of treating sports injuries. It is commonplace for athletes to return to competitive activity, shortly or immediately after the application of a cold treatment. In this article, we examine the effect of local tissue cooling on outcomes relating to functional performance and to discuss their relevance to the sporting environment. A computerized literature search, citation tracking and hand search was performed up to April, 2011. Eligible studies were trials involving healthy human participants, describing the effects of cooling on outcomes relating to functional performance. Two reviewers independently assessed the validity of included trials and calculated effect sizes. Thirty five trials met the inclusion criteria; all had a high risk of bias. The mean sample size was 19. Meta-analyses were not undertaken due to clinical heterogeneity. The majority of studies used cooling durations >20 minutes. Strength (peak torque/force) was reported by 25 studies with approximately 75% recording a decrease in strength immediately following cooling. There was evidence from six studies that cooling adversely affected speed, power and agility-based running tasks; two studies found this was negated with a short rewarming period. There was conflicting evidence on the effect of cooling on isolated muscular endurance. A small number of studies found that cooling decreased upper limb dexterity and accuracy. The current evidence base suggests that athletes will probably be at a performance disadvantage if they return to activity immediately after cooling. This is based on cooling for longer than 20 minutes, which may exceed the durations employed in some sporting environments. In addition, some of the reported changes were clinically small and may only be relevant in elite sport. Until better evidence is available, practitioners should use short cooling applications and/or undertake a progressive warm up prior to returning to play.

Functional and advanced functional and causal relationship diagrams for remote condition monitoring

Analysing the condition of an asset is a big challenge as there can be many aspects which can contribute to the overall functional reliability of the asset that have to be considered. In this paper we propose a two-step functional and causal relationship diagram (FCRD) to address this problem. In the first step, the FCRD is designed to facilitate the analysis of the condition of an asset by evaluating the interdependence (functional and causal) relationships between different components of the asset with the help of a relationship diagram. This is followed by the advanced FCRD (AFCRD) which refines the information from the FCRD into a comprehensive and manageable format. This new two-step methodology for asset condition monitoring is tested and validated for the case of a water treatment plant. © IMechE 2012.

Molecules, morphology, and ecology indicate a recent, amphibious ancestry for echidnas

The semiaquatic platypus and terrestrial echidnas (spiny anteaters) are the only living egg-laying mammals (monotremes). The fossil record has provided few clues as to their origins and the evolution of their ecological specializations; however, recent reassignment of the Early Cretaceous Teinolophos and Steropodon to the platypus lineage implies that platypuses and echidnas diverged >112.5 million years ago, reinforcing the notion of monotremes as living fossils. This placement is based primarily on characters related to a single feature, the enlarged mandibular canal, which supplies blood vessels and dense electrosensory receptors to the platypus bill. Our reevaluation of the morphological data instead groups platypus and echidnas to the exclusion of Teinolophos and Steropodon and suggests that an enlarged mandibular canal is ancestral for monotremes (partly reversed in echidnas, in association with general mandibular reduction). A multigene evaluation of the echidna–platypus divergence using both a relaxed molecular clock and direct fossil calibrations reveals a recent split of 19–48 million years ago. Platypus-like monotremes (Monotrematum) predate this divergence, indicating that echidnas had aquatically foraging ancestors that reinvaded terrestrial ecosystems. This ecological shift and the associated radiation of echidnas represent a recent expansion of niche space despite potential competition from marsupials. Monotremes might have survived the invasion of marsupials into Australasia by exploiting ecological niches in which marsupials are restricted by their reproductive mode. Morphology, ecology, and molecular biology together indicate that Teinolophos and Steropodon are basal monotremes rather than platypus relatives, and that living monotremes are a relatively recent radiation.

The relationship between chronic disease self-efficacy and nutritional status, functional ability and quality of life in older adults at risk of hospital readmission

Background and significance: Older adults with chronic diseases are at increasing risk of hospital admission and readmission. Approximately 75% of adults have at least one chronic condition, and the odds of developing a chronic condition increases with age. Chronic diseases consume about 70% of the total Australian health expenditure, and about 59% of hospital events for chronic conditions are potentially preventable. These figures have brought to light the importance of the management of chronic disease among the growing older population. Many studies have endeavoured to develop effective chronic disease management programs by applying social cognitive theory. However, limited studies have focused on chronic disease self-management in older adults at high risk of hospital readmission. Moreover, although the majority of studies have covered wide and valuable outcome measures, there is scant evidence on examining the fundamental health outcomes such as nutritional status, functional status and health-related quality of life. Aim: The aim of this research was to test social cognitive theory in relation to self-efficacy in managing chronic disease and three health outcomes, namely nutritional status, functional status, and health-related quality of life, in older adults at high risk of hospital readmission. Methods: A cross-sectional study design was employed for this research. Three studies were undertaken. Study One examined the nutritional status and validation of a nutritional screening tool; Study Two explored the relationships between participants. characteristics, self-efficacy beliefs, and health outcomes based on the study.s hypothesized model; Study Three tested a theoretical model based on social cognitive theory, which examines potential mechanisms of the mediation effects of social support and self-efficacy beliefs. One hundred and fifty-seven patients aged 65 years and older with a medical admission and at least one risk factor for readmission were recruited. Data were collected from medical records on demographics, medical history, and from self-report questionnaires. The nutrition data were collected by two registered nurses. For Study One, a contingency table and the kappa statistic was used to determine the validity of the Malnutrition Screening Tool. In Study Two, standard multiple regression, hierarchical multiple regression and logistic regression were undertaken to determine the significant influential predictors for the three health outcome measures. For Study Three, a structural equation modelling approach was taken to test the hypothesized self-efficacy model. Results: The findings of Study One suggested that a high prevalence of malnutrition continues to be a concern in older adults as the prevalence of malnutrition was 20.6% according to the Subjective Global Assessment. Additionally, the findings confirmed that the Malnutrition Screening Tool is a valid nutritional screening tool for hospitalized older adults at risk of readmission when compared to the Subjective Global Assessment with high sensitivity (94%), and specificity (89%) and substantial agreement between these two methods (k = .74, p < .001; 95% CI .62-.86). Analysis data for Study Two found that depressive symptoms and perceived social support were the two strongest influential factors for self-efficacy in managing chronic disease in a hierarchical multiple regression. Results of multivariable regression models suggested advancing age, depressive symptoms and less tangible support were three important predictors for malnutrition. In terms of functional status, a standard regression model found that social support was the strongest predictor for the Instrumental Activities of Daily Living, followed by self-efficacy in managing chronic disease. The results of standard multiple regression revealed that the number of hospital readmission risk factors adversely affected the physical component score, while depressive symptoms and self-efficacy beliefs were two significant predictors for the mental component score. In Study Three, the results of the structural equation modelling found that self-efficacy partially mediated the effect of health characteristics and depression on health-related quality of life. The health characteristics had strong direct effects on functional status and body mass index. The results also indicated that social support partially mediated the relationship between health characteristics and functional status. With regard to the joint effects of social support and self-efficacy, social support fully mediated the effect of health characteristics on self-efficacy, and self-efficacy partially mediated the effect of social support on functional status and health-related quality of life. The results also demonstrated that the models fitted the data well with relative high variance explained by the models, implying the hypothesized constructs under discussion were highly relevant, and hence the application for social cognitive theory in this context was supported. Conclusion: This thesis highlights the applicability of social cognitive theory on chronic disease self-management in older adults at risk of hospital readmission. Further studies are recommended to validate and continue to extend the development of social cognitive theory on chronic disease self-management in older adults to improve their nutritional and functional status, and health-related quality of life.

Experimental and theoretical investigation of ligand effects on the synthesis of ZnO nanoparticles

ZnO nanoparticles with highly controllable particle sizes(less than 10 nm) were synthesized using organic capping ligands in Zn(Ac)2 ethanolic solution. The molecular structure of the ligands was found to have significant influence on the particle size. The multi-functional molecule tris(hydroxymethyl)-aminomethane (THMA) favoured smaller particle distributions compared with ligands possessing long hydrocarbon chains that are more frequently employed. The adsorption of capping ligands on ZnnOn crystal nuclei (where n = 4 or 18 molecular clusters of(0001) ZnO surfaces) was modelled by ab initio methods at the density functional theory (DFT) level. For the molecules examined, chemisorption proceeded via the formation of Zn...O, Zn...N, or Zn...S chemical bonds between the ligands and active Zn2+ sites on ZnO surfaces. The DFT results indicated that THMA binds more strongly to the ZnO surface than other ligands, suggesting that this molecule is very effective at stabilizing ZnO nanoparticle surfaces. This study, therefore, provides new insight into the correlation between the molecular structure of capping ligands and the morphology of metal oxide nanostructures formed in their presence.