Age-related differences in exercise and quality of life among breast cancer survivors

Purpose: Physical activity has become a focus of cancer recovery research as it has the potential to reduce treatment-related burden and optimize health-related quality of life (HRQoL). However, the potential for physical activity to influence recovery may be age-dependent. This paper describes physical activity levels and HRQoL among younger and older women after surgery for breast cancer and explores the correlates of physical inactivity. Methods: A population-based sample of breast cancer patients diagnosed in South-East Queensland, Australia, (n=287) were assessed once every three months, from 6 to 18 months post-surgery. The Functional Assessment of Cancer Therapy-Breast questionnaire (FACTB+4) and items from the Behavioral Risk Factor Surveillance System (BRFSS) questionnaire were used to measure HRQoL and physical activity, respectively. Physical activity was assigned metabolic equivalent task (MET) values, and categorized as < 3, 3 to 17.9 and 18+ MET-hours/weeks. Descriptive statistics, generalized linear models with age stratification (<50 years versus 50+ years), and logistic regression were used for analyses (p=0.05, two-tailed). Results: Younger women who engaged in 3 or more MET-hours/week of physical activity reported a higher HRQoL at 18 months compared to their more sedentary counterparts (p<0.05). Older women reported similar HRQoL irrespective of activity level and consistently reported clinically higher HRQoL than younger women. Increasing age, being overweight or obese, and restricting use of the treated side at six months post-surgery increased the likelihood of sedentary behavior (OR>3, p<0.05). Conclusions: Age influences the potential to observe HRQoL benefits related to physical activity participation. These results also provide relevant information for the design of exercise interventions for breast cancer survivors and highlights that some groups of women are at greater risk of long-term sedentary behavior.

Factors related to the presentation of thin and thick nodular melanoma from a population-based cancer registry in Queensland Australia

Purpose: Worldwide, the incidence of thick melanoma has not declined, and the nodular melanoma (NM) subtype accounts for nearly 40% of newly-diagnosed thick melanoma. To assess differences between patients with thin (≤2.00 mm) and thick (≥2.01 mm) nodular melanoma, we evaluated factors such as demographics, melanoma detection patterns, tumor visibility, and physician screening for NM alone and compared clinical presentation and anatomic location of NM with superficial spreading melanoma (SSM). Methods We utilized data from a large population-based study of Queensland (Australia) residents diagnosed with melanoma. Queensland residents aged 20 to 75 years with histologically confirmed first primary invasive cutaneous melanoma were eligible for the study, and all questionnaires were conducted by telephone (response rate 77.9%). Results During this four-year period, 369 patients with nodular melanoma were interviewed, of whom 56.7% were diagnosed with tumors ≤ 2.00 mm. Men, older individuals, and those who had not been screened by a physician in the past three years were more likely to have nodular tumors of greater thickness. Thickest nodular melanoma (4 mm+) was also most common in persons who had not been screened by a doctor within the past three years (OR 3.75; 95% CI 1.47-9.59). Forty-six percent of patients with thin nodular melanoma (≤ 2.00 mm) reported a change in color, compared with 64% of patients with thin SSM and 26% of patients with thick nodular melanoma (>2.00 mm). Conclusion Awareness of factors related to earlier detection of potentially fatal nodular melanomas, including the benefits of a physician examination, should be useful in enhancing public and professional education strategies. Particular awareness of clinical warning signs associated with thin nodular melanoma should allow for more prompt diagnosis and treatment of this subtype.

Influence of presbyopic corrections on driving-related eye and head movements

Purpose: To investigate whether wearing different presbyopic vision corrections alters the pattern of eye and head movements when viewing and responding to driving-related traffic scenes. Methods: Participants included 20 presbyopes (mean age: 56.1 ± 5.7 years) who had no experience of wearing presbyopic vision corrections, apart from single vision (SV) reading spectacles. Each participant wore five different vision corrections: distance SV lenses, progressive addition spectacle lenses (PAL), bifocal spectacle lenses (BIF), monovision (MV) and multifocal contact lenses (MTF CL). For each visual condition, participants were required to view videotape recordings of traffic scenes, track a reference vehicle, and identify a series of peripherally presented targets. Digital numerical display panels were also included as near visual stimuli (simulating the visual displays of a vehicle speedometer and radio). Eye and head movements were measured, and the accuracy of target recognition was also recorded. Results: The path length of eye movements while viewing and responding to driving-related traffic scenes was significantly longer when wearing BIF and PAL than MV and MTF CL (both p ≤ 0.013). The path length of head movements was greater with SV, BIF, and PAL than MV and MTF CL (all p < 0.001). Target recognition and brake response times were not significantly affected by vision correction, whereas target recognition was less accurate when the near stimulus was located at eccentricities inferiorly and to the left, rather than directly below the primary position of gaze (p = 0.008), regardless of vision correction. Conclusions: Different presbyopic vision corrections alter eye and head movement patterns. The longer path length of eye and head movements and greater number of saccades associated with the spectacle presbyopic corrections may affect some aspects of driving performance.

An investigation into how work-related road safety can be enhanced

Despite the facts that vehicle incidents continue to be the most common mechanism for Australian compensated fatalities and that employers have statutory obligations to provide safe workplaces, very few organisations are proactively and comprehensively managing their work-related road risks. Unfortunately, limited guidance is provided in the existing literature to assist practitioners in managing work-related road risks. The current research addresses this gap in the literature. To explore how work-related road safety can be enhanced, three studies were conducted. Study one explored the effectiveness of a range of risk management initiatives and whether comprehensive risk management practices were associated with safety outcomes. Study two explored barriers to, and facilitators for, accepting risk management initiatives. Study three explored the influence of organisational factors on road safety outcomes to identify optimal work environments for managing road risks. To maximise the research sample and increase generalisability, the studies were designed to allow data collection to be conducted simultaneously drawing upon the same sample obtained from four Australian organisations. Data was collected via four methods. A structured document review of published articles was conducted to identify what outcomes have been observed in previously investigated work-related road safety initiatives. The documents reviewed collectively assessed the effectiveness of 19 work-related road safety initiatives. Audits of organisational practices and process operating within the four researched organisations were conducted to identify whether organisations with comprehensive work-related road risk management practices and processes have better safety outcomes than organisations with limited risk management practices and processes. Interviews were conducted with a sample of 24 participants, comprising 16 employees and eight managers. The interviews were conducted to identify what barriers and facilitators within organisations are involved in implementing work-related road safety initiatives and whether differences in fleet safety climate, stage of change and safety ownership relate to work-related road safety outcomes. Finally, questionnaires were administered to a sample of 679 participants. The questionnaires were conducted to identify which initiatives are perceived by employees to be effective in managing work-related road risks and whether differences in fleet safety climate, stage of change and safety ownership relate to work-related road safety outcomes. Seven research questions were addressed in the current research project. The key findings with respect to each of the research questions are presented below. Research question one: What outcomes have been observed in previously investigated work-related road safety initiatives? The structured document review indicated that initiatives found to be positively associated with occupational road safety both during and after the intervention period included: a pay rise; driver training; group discussions; enlisting employees as community road safety change agents; safety reminders; and group and individual rewards. Research question two: Which initiatives are perceived by employees to be effective in managing work-related road risks? Questionnaire findings revealed that employees believed occupational road risks could best be managed through making vehicle safety features standard, providing practical driver skills training and through investigating serious vehicle incidents. In comparison, employees believed initiatives including signing a promise card commitment to drive safely, advertising the organisation’s phone number on vehicles and consideration of driving competency in staff selection process would have limited effectiveness in managing occupational road safety. Research question three: Do organisations with comprehensive work-related road risk management practices and processes have better safety outcomes than organisations with limited risk management practices and processes? The audit identified a difference among the organisations in their management of work-related road risks. Comprehensive risk management practices were associated with employees engaging in overall safer driving behaviours, committing less driving errors, and experiencing less fatigue and distraction issues when driving. Given that only four organisations participated in this research, these findings should only be considered as preliminary. Further research should be conducted to explore the relationship between comprehensiveness of risk management practices and road safety outcomes with a larger sample of organisations. Research question four: What barriers and facilitators within organisations are involved in implementing work-related road safety initiatives? The interviews identified that employees perceived six organisational characteristics as potential barriers to implementing work-related road safety initiatives. These included: prioritisation of production over safety; complacency towards work-related road risks; insufficient resources; diversity; limited employee input in safety decisions; and a perception that road safety initiatives were an unnecessary burden. In comparison, employees perceived three organisational characteristics as potential facilitators to implementing work-related road safety initiatives. These included: management commitment; the presence of existing systems that could support the implementation of initiatives; and supportive relationships. Research question five: Do differences in fleet safety climate relate to work-related road safety outcomes? The interviews and questionnaires identified that organisational climates with high management commitment, support for managing work demands, appropriate safety rules and safety communication were associated with employees who engaged in safer driving behaviours. Regression analyses indicated that as participants’ perceptions of safety climate increased, the corresponding likelihood of them engaging in safer driving behaviours increased. Fleet safety climate was perceived to influence road safety outcomes through several avenues. Some of these included: the allocation of sufficient resources to manage occupational road risks; fostering a supportive environment of mutual responsibility; resolving safety issues openly and fairly; clearly communicating to employees that safety is the top priority; and developing appropriate work-related road safety policies and procedures. Research question six: Do differences in stage of change relate to work-related road safety outcomes? The interviews and questionnaires identified that participants’ perceptions of initiative effectiveness were found to vary with respect to their individual stage of readiness, with stage-matched initiatives being perceived most effective. In regards to safety outcomes, regression analyses identified that as participants’ progress through the stages of change, the corresponding likelihood of them being involved in vehicle crashes decreases. Research question seven: Do differences in safety ownership relate to work-related road safety outcomes? The interviews and questionnaires revealed that management of road risks is often given less attention than other areas of health and safety management in organisations. In regards to safety outcomes, regression analyses identified that perceived authority and perceived shared ownership both emerged as significant independent predictors of self-reported driving behaviours pertaining to fatigue and distractions. The regression models indicated that as participants’ perceptions of the authority of the person managing road risks increases, and perceptions of shared ownership of safety tasks increases, the corresponding likelihood of them engaging in driving while fatigued or multitasking while driving decreases. Based on the findings from the current research, the author makes several recommendations to assist practitioners in developing proactive and comprehensive approaches to managing occupational road risks. The author also suggests several avenues for future research in the area of work-related road safety.

Investigation of molecular mechanisms regulating biomineralization of pearl oyster Pinctada maxima

Biomineralization is a process encompassing all mineral containing tissues produced within an organism. The most dynamic example of this process is the formation of the mollusk shell, comprising a variety of crystal phases and microstructures. The organic component incorporated within the shell is said to dictate this remarkable architecture. Subsequently, for the past decade considerable research have been undertaken to identify and characterize the protein components involved in biomineralization. Despite these efforts the general understanding of the process remains ambiguous. This study employs a novel molecular approach to further the elucidation of the shell biomineralization. A microarray platform has been custom generated (PmaxArray 1.0) from the pearl oyster Pinctada maxima. PmaxArray 1.0 consists of 4992 expressed sequence tags (ESTs) originating from the mantle, an organ involved in shell formation. This microarray has been used as the primary tool for three separate investigations in an effort to associate transcriptional gene expression from P. maxima to the process of shell biomineralization. The first investigation analyzes the spatial expression of ESTs throughout the mantle organ. The mantle was dissected into five discrete regions and each analyzed for gene expression with PmaxArray 1.0. Over 2000 ESTs were differentially expressed among the tissue sections, identifying five major expression regions. Three of these regions have been proposed to have shell formation functions belonging to nacre, prismatic calcite and periostracum. The spatial gene expression map was confirmed by in situ hybridization, localizing a subset of ESTs from each expression region to the same mantle area. Comparative sequence analysis of ESTs expressed in the proposed shell formation regions with the BLAST tool, revealed a number of the transcripts were novel while others showed significant sequence similarities to previously characterized shell formation genes. The second investigation correlates temporal EST expression during P. maxima larval ontogeny with transitions in shell mineralization during the same period. A timeline documenting the morphologicat microstructural and mineralogical shell characteristics of P. maxima throughout larval ontogeny has been established. Three different shell types were noted based on the physical characters and termed, prodissoconch I, prodissoconch 11 and dissoconch. PmaxArray 1.0 analyzed ESTs expression of animals throughout the larval development of P. maxima, noting up-regulation of 359 ESTs in association with the shell transitions from prodissoconch 1 to prodissoconch 11 to dissoconch. Comparative sequence analysis of these ESTs indicates a number of the transcripts are novel as well as showing significant sequence similarities between ESTs and known shell matrix associated genes and proteins. These ESTs are discussed in relation to the shell characters associated with their temporal expression. The third investigation uses PmaxArray 1.0 to analyze gene expression in the mantle tissue of P. maxima specimens exposed to sub-lethal concentrations of a shell-deforming toxin, tributyltin (TBT). The shell specific effects of TBT are used in this investigation to interpret differential expression of ESTs with respect to shell formation functions. A lethal and sublethal TBT concentration range was established for P. maxima, noting a concentration of 50 ng L- 1 TBT as sub-lethal over a 21 day period. Mantle tissue from P. maxima animals treated with 50 ng L- 1 TBT was assessed for differential EST expression with untreated control animals. A total of 102 ESTs were identified as differentially expressed in association with TBT exposure, comparative sequence identities included an up-regulation of immunity and detoxification related genes and down-regulation of several shell matrix genes. A number of transcripts encoding novel peptides were additionally identified. The potential actions of these genes are discussed with reference to TBT toxicity and shell biomineralization. This thesis has used a microarray platform to analyze gene expression in spatial, temporal and toxicity investigations, revealing the involvement of numerous gene transcripts in specific shell formation functions. Investigation of thousands of transcripts simultaneously has provided a holistic interpretation of the organic components regulating shell biomineralization.

Determining the psychosocial predictors of living, living-related, and posthumous organ donation

The worldwide organ shortage occurs despite people’s positive organ donation attitudes. The discrepancy between attitudes and behaviour is evident in Australia particularly, with widespread public support for organ donation but low donation and communication rates. This problem is compounded further by the paucity of theoretically based research to improve our understanding of people’s organ donation decisions. This program of research contributes to our knowledge of individual decision making processes for three aspects of organ donation: (1) posthumous (upon death) donation, (2) living donation (to a known and unknown recipient), and (3) providing consent for donation by communicating donation wishes on an organ donor consent register (registering) and discussing the donation decision with significant others (discussing). The research program used extended versions of the Theory of Planned Behaviour (TPB) and the Prototype/Willingness Model (PWM), incorporating additional influences (moral norm, self-identity, organ recipient prototypes), to explicate the relationship between people’s positive attitudes and low rates of organ donation behaviours. Adopting the TPB and PWM (and their extensions) as a theoretical basis overcomes several key limitations of the extant organ donation literature including the often atheoretical nature of organ donation research, thefocus on individual difference factors to construct organ donor profiles and the omission of important psychosocial influences (e.g., control perceptions, moral values) that may impact on people’s decision-making in this context. In addition, the use of the TPB and PWM adds further to our understanding of the decision making process for communicating organ donation wishes. Specifically, the extent to which people’s registering and discussing decisions may be explained by a reasoned and/or a reactive decision making pathway is examined (Stage 3) with the novel application of the TPB augmented with the social reaction pathway in the PWM. This program of research was conducted in three discrete stages: a qualitative stage (Stage 1), a quantitative stage with extended models (Stage 2), and a quantitative stage with augmented models (Stage 3). The findings of the research program are reported in nine papers which are presented according to the three aspects of organ donation examined (posthumous donation, living donation, and providing consent for donation by registering or discussing the donation preference). Stage One of the research program comprised qualitative focus groups/interviews with university students and community members (N = 54) (Papers 1 and 2). Drawing broadly on the TPB framework (Paper 1), content analysed responses revealed people’s commonly held beliefs about the advantages and disadvantages (e.g., prolonging/saving life), important people or groups (e.g., family), and barriers and motivators (e.g., a family’s objection to donation), related to living and posthumous organ donation. Guided by a PWM perspective, Paper Two identified people’s commonly held perceptions of organ donors (e.g., altruistic and giving), non-donors (e.g., self-absorbed and unaware), and transplant recipients (e.g., unfortunate, and in some cases responsible/blameworthy for their predicament). Stage Two encompassed quantitative examinations of people’s decision makingfor living (Papers 3 and 4) and posthumous (Paper 5) organ donation, and for registering and discussing donation wishes (Papers 6 to 8) to test extensions to both the TPB and PWM. Comparisons of health students’ (N = 487) motivations and willingness for living related and anonymous donation (Paper 3) revealed that a person’s donor identity, attitude, past blood donation, and knowing a posthumous donor were four common determinants of willingness, with the results highlighting students’ identification as a living donor as an important motive. An extended PWM is presented in Papers Four and Five. University students’ (N = 284) willingness for living related and anonymous donation was tested in Paper Four with attitude, subjective norm, donor prototype similarity, and moral norm (but not donor prototype favourability) predicting students’ willingness to donate organs in both living situations. Students’ and community members’ (N = 471) posthumous organ donation willingness was assessed in Paper Five with attitude, subjective norm, past behaviour, moral norm, self-identity, and prior blood donation all significantly directly predicting posthumous donation willingness, with only an indirect role for organ donor prototype evaluations. The results of two studies examining people’s decisions to register and/or discuss their organ donation wishes are reported in Paper Six. People’s (N = 24) commonly held beliefs about communicating their organ donation wishes were explored initially in a TPB based qualitative elicitation study. The TPB belief determinants of intentions to register and discuss the donation preference were then assessed for people who had not previously communicated their donation wishes (N = 123). Behavioural and normative beliefs were important determinants of registering and discussing intentions; however, control beliefs influenced people’s registering intentions only. Paper Seven represented the first empirical test of the role of organ transplant recipient prototypes (i.e., perceptions of organ transplant recipients) in people’s (N = 465) decisions to register consent for organ donation. Two factors, Substance Use and Responsibility, were identified and Responsibility predicted people’s organ donor registration status. Results demonstrated that unregistered respondents were the most likely to evaluate transplant recipients negatively. Paper Eight established the role of organ donor prototype evaluations, within an extended TPB model, in predicting students’ and community members’ registering (n = 359) and discussing (n = 282) decisions. Results supported the utility of an extended TPB and suggested a role for donor prototype evaluations in predicting people’s discussing intentions only. Strong intentions to discuss donation wishes increased the likelihood that respondents reported discussing their decision 1-month later. Stage Three of the research program comprised an examination of augmented models (Paper 9). A test of the TPB augmented with elements from the social reaction pathway in the PWM, and extensions to these models was conducted to explore whether people’s registering (N = 339) and discussing (N = 315) decisions are explained via a reasoned (intention) and/or social reaction (willingness) pathway. Results suggested that people’s decisions to communicate their organ donation wishes may be better explained via the reasoned pathway, particularly for registering consent; however, discussing also involves reactive elements. Overall, the current research program represents an important step toward clarifying the relationship between people’s positive organ donation attitudes but low rates of organ donation and communication behaviours. Support has been demonstrated for the use of extensions to two complementary theories, the TPB and PWM, which can inform future research aiming to explicate further the organ donation attitude-behaviour relationship. The focus on a range of organ donation behaviours enables the identification of key targets for future interventions encouraging people’s posthumous and living donation decisions, and communication of their organ donation preference.

Health-related quality of life in obese children and adolescents

Objective: This review addresses the effect of overweight and obese weight status on pediatric health-related quality of life (HRQOL). Method: Web of Science, Medline, CINAHL, Cochrane Library, EMBASE, AMED and PubMed were searched for peer-reviewed studies in English reporting HRQOL and weight status in youth (<21 years), published before March 2008. Results: Twenty-eight articles were identified. Regression of HRQOL against body mass index (BMI) using pooled data from 13 studies utilizing the Pediatric Quality of Life Inventory identified an inverse relationship between BMI and pediatric HRQOL (r=−0.7, P=0.008), with impairments in physical and social functioning consistently reported. HRQOL seemed to improve with weight loss, but randomized controlled trials were few and lacked long-term follow-up. Conclusions: Little is known about the factors associated with reduced HRQOL among overweight or obese youth, although gender, age and obesity-related co-morbidities may play a role. Few studies have examined the differences in HRQOL between community and treatment-seeking samples. Pooled regressions suggest pediatric self-reported HRQOL can be predicted from parent proxy reports, although parents of obese youths tend to perceive worse HRQOL than children do about themselves. Thus, future research should include both pediatric and parent proxy perspectives.

Kallikrein-related peptidase 4 activation of protease-activated receptor family members and association with prostate cancer

Two areas of particular importance in prostate cancer progression are primary tumour development and metastasis. These processes involve a number of physiological events, the mediators of which are still being discovered and characterised. Serine proteases have been shown to play a major role in cancer invasion and metastasis. The recently discovered phenomenon of their activation of a receptor family known as the protease activated receptors (PARs) has extended their physiological role to that of signaling molecule. Several serine proteases are expressed by malignant prostate cancer cells, including members of the kallikreinrelated peptidase (KLK) serine protease family, and increasingly these are being shown to be associated with prostate cancer progression. KLK4 is highly expressed in the prostate and expression levels increase during prostate cancer progression. Critically, recent studies have implicated KLK4 in processes associated with cancer. For example, the ectopic over-expression of KLK4 in prostate cancer cell lines results in an increased ability of these cells to form colonies, proliferate and migrate. In addition, it has been demonstrated that KLK4 is a potential mediator of cellular interactions between prostate cancer cells and osteoblasts (bone forming cells). The ability of KLK4 to influence cellular behaviour is believed to be through the selective cleavage of specific substrates. Identification of relevant in vivo substrates of KLK4 is critical to understanding the pathophysiological roles of this enzyme. Significantly, recent reports have demonstrated that several members of the KLK family are able to activate PARs. The PARs are relatively new members of the seven transmembrane domain containing G protein coupled receptor (GPCR) family. PARs are activated through proteolytic cleavage of their N-terminus by serine proteases, the resulting nascent N-terminal binds intramolecularly to initiate receptor activation. PARs are involved in a number of patho-physiological processes, including vascular repair and inflammation, and a growing body of evidence suggests roles in cancer. While expression of PAR family members has been documented in several types of cancers, including prostate, the role of these GPCRs in prostate cancer development and progression is yet to be examined. Interestingly, several studies have suggested potential roles in cellular invasion through the induction of cytoskeletal reorganisation and expression of basement membrane-degrading enzymes. Accordingly, this program of research focussed on the activation of the PARs by the prostate cancer associated enzyme KLK4, cellular processing of activated PARs and the expression pattern of receptor and agonist in prostate cancer. For these studies KLK4 was purified from the conditioned media of stably transfected Sf9 insect cells expressing a construct containing the complete human KLK4 coding sequence in frame with a V5 epitope and poly-histidine encoding sequences. The first aspect of this study was the further characterisation of this recombinant zymogen form of KLK4. The recombinant KLK4 zymogen was demonstrated to be activatable by the metalloendopeptidase thermolysin and amino terminal sequencing indicated that thermolysin activated KLK4 had the predicted N-terminus of mature active KLK4 (31IINED). Critically, removal of the pro-region successfully generated a catalytically active enzyme, with comparable activity to a previously published recombinant KLK4 produced from S2 insect cells. The second aspect of this study was the activation of the PARs by KLK4 and the initiation of signal transduction. This study demonstrated that KLK4 can activate PAR-1 and PAR-2 to mobilise intracellular Ca2+, but failed to activate PAR-4. Further, KLK4 activated PAR-1 and PAR-2 over distinct concentration ranges, with KLK4 activation and mobilisation of Ca2+ demonstrating higher efficacy through PAR-2. Thus, the remainder of this study focussed on PAR-2. KLK4 was demonstrated to directly cleave a synthetic peptide that mimicked the PAR-2 Nterminal activation sequence. Further, KLK4 mediated Ca2+ mobilisation through PAR-2 was accompanied by the initiation of the extra-cellular regulated kinase (ERK) cascade. The specificity of intracellular signaling mediated through PAR-2 by KLK4 activation was demonstrated by siRNA mediated protein depletion, with a reduction in PAR-2 protein levels correlating to a reduction in KLK4 mediated Ca2+mobilisation and ERK phosphorylation. The third aspect of this study examined cellular processing of KLK4 activated PAR- 2 in a prostate cancer cell line. PAR-2 was demonstrated to be expressed by five prostate derived cell lines including the prostate cancer cell line PC-3. It was also demonstrated by flow cytometry and confocal microscopy analyses that activation of PC-3 cell surface PAR-2 by KLK4 leads to internalisation of this receptor in a time dependent manner. Critically, in vivo relevance of the interaction between KLK4 and PAR-2 was established by the observation of the co-expression of receptor and agonist in primary prostate cancer and prostate cancer bone lesion samples by immunohistochemical analysis. Based on the results of this study a number of exciting future studies have been proposed, including, delineating differences in KLK4 cellular signaling via PAR-1 and PAR-2 and the role of PAR-1 and PAR-2 activation by KLK4 in prostate cancer cells and bone cells in prostate cancer progression.

The relationship between subjective appetite sensations, markers of inflammation and appetite in dialysis patients

Background: Poor appetite is a marker of morbidity and mortality in hemodialysis patients, making it an important area for research. Visual analog scales (VAS) can capture a range of subjective sensations related to appetite (such as hunger, desire to eat or fullness), but have not been commonly used to measure appetite in dialysis patients. The aim of this study was to explore the association between retrospective ratings of appetite using VAS and a range of clinical variables as well as biomarkers of appetite in hemodialysis patients.----- Methods: 28 hemodialysis patients (mean age 61±17y, 50% male, median dialysis vintage 19.5(4-101) months) rated their appetite using VAS for hunger, fullness and desire to eat and a 5-point categorical scale measuring general appetite. Blood levels of the appetite peptides leptin, ghrelin and peptide YY were also measured.----- Results: Hunger ratings measured by VAS were significantly (p<0.05) correlated with a range of clinical, nutritional and inflammatory markers: age (r=-0.376), co-morbidities, (r=-0.380) PG-SGA score (r=-0.451), weight (r=-0.375), fat-free mass (r=-0.435), C-Reactive Protein (CRP) (r=-0.383) and Intercellular adhesion molecule (sICAM-1) (r=-0.387). There was a consistent relationship between VAS and appetite on a 5-point categorical scale for questions of hunger, and a similar trend for desire to eat, but not for fullness. Neither method of measuring subjective appetite correlated with appetite peptides.----- Conclusions: Retrospective ratings of hunger on a VAS are associated with a range of clinical variables and further studies are warranted to support their use as a method of measuring appetite in dialysis patients.

The nature and extent of policing alcohol related crime and reducing violence in and around late night entertainment areas

The misuse of alcohol is well documented in Australia and has been associated with disorders and harms that often require police attention. The extent of alcohol-related incidents requiring police attention has been recorded as substantial in some Australian cities (Arro, Crook, & Fenton, 1992; Davey & French, 1995; Ireland & Thommeny, 1993). A significant proportion of harmful drinking occurs in and around licensed premises (Jochelson, 1997; Stockwell, Masters, Phillips, Daly, Gahegan, Midford, & Philp, 1998; Borges, Cherpitel, & Rosovsky, 1998) and most of these incidents are not reported to police (Bryant & Williams, 2000; Lister, Hobbs, Hall, & Winlow, 2000). Alcohol-related incidents have also been found to be concentrated in certain places at certain times (Jochelson, 1997) and therefore manipulating the context in which these incidents occur may provide a means to prevent and reduce the harm associated with alcohol misuse. One of the major objectives of the present program of research was to investigate the occurrence and resource impact of alcohol-related incidents on operational (general duties) policing across a large geographical area. A second objective of the thesis was to examine the characteristics and temporal/spatial dynamics of police attended alcohol incidents in the context of Place Based theories of crime. It was envisaged that this approach would reveal the patterns of the most prevalent offences and demonstrate the relevance of Place Based theories of crime to understanding these patterns. In addition, the role of alcohol, time and place were also explored in order to examine the association between non criminal traffic offences and other types of criminal offences. A final objective of the thesis was to examine the impact of a situational crime prevention strategy that had been initiated to reduce the violence and disorder associated with late-night liquor trading premises. The program of research in this doctorate thesis has been undertaken through the presentation of published papers. The research was conducted in three stages which produced six manuscripts, five of which were submitted to peer reviewed journals and one that was published in a peer reviewed conference proceedings. Stage One included two studies (Studies 1 & 2) both of which involved a cross sectional approach to examine the prevalence and characteristics of alcohol-related incidents requiring police attendance across three large geographical areas that included metropolitan cities, provincial regions and rural areas. Stage Two of the program of research also comprised two cross sectional quantitative studies (Studies 3 & 4) that investigated the temporal and spatial dynamics of the major offence categories attended by operational police in a specific Police District (Gold Coast). Stage Three of the program of research involved two studies (Studies 5 & 6) that assessed the effectiveness of a situational crime prevention strategy. The studies employed a pre-post design to assess the impact on crime, disorder and violence by preventing patrons from entering late-night liquor trading premises between 3 a.m. and 5 a.m. (lockout policy). Although Study Five was solely quantitative in nature, Study Six included both quantitative and qualitative aspects. The approach adopted in Study Six, therefore facilitated not only a quantative comparison of the impact of the lockout policy on different policing areas, but also enabled the processes related to the implementation of the lockout policy to be examined. The thesis reports a program of research involving a common data collection method which then involved a series of studies being conducted to explore different aspects of the data. The data was collected from three sources. Firstly a pilot phase was undertaken to provide participants with training. Secondly a main study period was undertaken immediately following the pilot phase. The first and second sources of data were collected between 29th March 2004 and 2nd May 2004. Thirdly, additional data was collected between the 1st April 2005 and 31st May 2005. Participants in the current program of research were first response operational police officers who completed a modified activity log over a 9 week period (4 week pilot phase & 5 week survey study phase), identifying the type, prevalence and characteristics of alcohol-related incidents that were attended. During the study period police officers attended 31,090 alcohol-related incidents. Studies One and Two revealed that a substantial proportion of current police work involves attendance at alcohol-related incidents (i.e., 25% largely involving young males aged between 17 and 24 years). The most common incidents police attended were vehicle and/or traffic matters, disturbances and offences against property. The major category of offences most likely to involve alcohol included vehicle/traffic matters, disturbances and offences against the person (e.g., common & serious assaults). These events were most likely to occur in the late evenings and early hours of the morning on the weekends, and importantly, usually took longer for police to complete than non alcohol-related incidents. The findings in Studies Three and Four suggest that serious traffic offences, disturbances and offences against the person share similar characteristics and occur in concentrated places at similar times. In addition, it was found that time, place and incident type all have an influence on whether an incident attended by a police officer is alcohol-related. Alcohol-related incidents are more likely to occur in particular locations in the late evenings and early mornings on the weekends. In particular, there was a strong association between the occurrence of alcohol-related disturbances and alcohol-related serious traffic offences in regards to place and time. In general, stealing and property offences were not alcohol-related and occurred in daylight hours during weekdays. The results of Studies Five and Six were mixed. A number of alcohol-related offences requiring police attention were significantly reduced for some policing areas and for some types of offences following the implementation of the lockout policy. However, in some locations the lockout policy appeared to have a negative or minimal impact. Interviews with licensees revealed that although all were initially opposed to the lockout policy as they believed it would have a negative impact on business, most perceived some benefits from its introduction. Some of the benefits included, improved patron safety and the development of better business strategies to increase patron numbers. In conclusion, the overall findings of the six studies highlight the pervasive nature of alcohol across a range of criminal incidents, demonstrating the tremendous impact alcohol-related incidents have on police. The findings also demonstrate the importance of time and place in predicting the occurrence of alcohol-related offences. Although this program of research did not set out to test Place Based theories of crime, these theories were used to inform the interpretation of findings. The findings in the current research program provide evidence for the relevance of Place Based theories of crime to understanding the factors contributing to violence and disorder, and designing relevant crime prevention strategies. For instance, the results in Studies Five and Six provide supportive evidence that this novel lockout initiative can be beneficial for public safety by reducing some types of offences in particular areas in and around late-night liquor trading premises. Finally, intelligent-led policing initiatives based on problem oriented policing, such as the lockout policy examined in this thesis, have potential as a major crime prevention technique to reduce specific types of alcohol-related offences.

Motivation, development and validation of a new spectral greenness index : a spectral dimension related to foliage projective cover

A method is presented for the development of a regional Landsat-5 Thematic Mapper (TM) and Landsat-7 Enhanced Thematic Mapper plus (ETM+) spectral greenness index, coherent with a six-dimensional index set, based on a single ETM+ spectral image of a reference landscape. The first three indices of the set are determined by a polar transformation of the first three principal components of the reference image and relate to scene brightness, percent foliage projective cover (FPC) and water related features. The remaining three principal components, of diminishing significance with respect to the reference image, complete the set. The reference landscape, a 2200 km2 area containing a mix of cattle pasture, native woodland and forest, is located near Injune in South East Queensland, Australia. The indices developed from the reference image were tested using TM spectral images from 19 regionally dispersed areas in Queensland, representative of dissimilar landscapes containing woody vegetation ranging from tall closed forest to low open woodland. Examples of image transformations and two-dimensional feature space plots are used to demonstrate image interpretations related to the first three indices. Coherent, sensible, interpretations of landscape features in images composed of the first three indices can be made in terms of brightness (red), foliage cover (green) and water (blue). A limited comparison is made with similar existing indices. The proposed greenness index was found to be very strongly related to FPC and insensitive to smoke. A novel Bayesian, bounded space, modelling method, was used to validate the greenness index as a good predictor of FPC. Airborne LiDAR (Light Detection and Ranging) estimates of FPC along transects of the 19 sites provided the training and validation data. Other spectral indices from the set were found to be useful as model covariates that could improve FPC predictions. They act to adjust the greenness/FPC relationship to suit different spectral backgrounds. The inclusion of an external meteorological covariate showed that further improvements to regional-scale predictions of FPC could be gained over those based on spectral indices alone.

Age-related maculopathy : linking aetiology and pathophysiological changes to the ischaemia hypothesis

Age-related maculopathy (ARM) has remained a challenging topic with respect to its aetiology, pathomechanisms, early detection and treatment since the late 19th century when it was first described as its own entity. ARM was previously considered an inflammatory disease, a degenerative disease, a tumor and as the result of choroidal hemodynamic disturbances and ischaemia. The latter processes have been repeatedly suggested to have a key role in its development and progression. In vivo experiments under hypoxic conditions could be models for the ischaemic deficits in ARM. Recent research has also linked ARM with gene polymorphisms. It is however unclear what triggers a person's gene susceptibility. In this manuscript, a linking hypothesis between aetiological factors including ischaemia and genetics and the development of early clinicopathological changes in ARM is proposed. New clinical psychophysical and electrophysiological tests are introduced that can detect ARM at an early stage. Models of early ARM based upon hemodynamic, photoreceptor and post-receptoral deficits are described and the mechanisms by which ischaemia may be involved as a final common pathway are considered. In neovascular age-related macular degeneration (neovascular AMD), ischaemia is thought to promote release of vascular endothelial growth factor (VEGF) which induces chorioretinal neovascularisation. VEGF is critical in the maintenance of the healthy choriocapillaris. In the final section of the manuscript the documentation of the effect of new anti-VEGF treatments on retinal function in neovascular AMD is critically viewed.

Multivariate methods to identify cancer-related symptom clusters

Multivariate methods are required to assess the interrelationships among multiple, concurrent symptoms. We examined the conceptual and contextual appropriateness of commonly used multivariate methods for cancer symptom cluster identification. From 178 publications identified in an online database search of Medline, CINAHL, and PsycINFO, limited to articles published in English, 10 years prior to March 2007, 13 cross-sectional studies met the inclusion criteria. Conceptually, common factor analysis (FA) and hierarchical cluster analysis (HCA) are appropriate for symptom cluster identification, not principal component analysis. As a basis for new directions in symptom management, FA methods are more appropriate than HCA. Principal axis factoring or maximum likelihood factoring, the scree plot, oblique rotation, and clinical interpretation are recommended approaches to symptom cluster identification.

Signs, symptoms and comorbidities in contact lens-related microbial keratitis

Purpose: The aim of this study was to characterize the clinical signs, symptoms, and ocular and systemic comorbidities in a large case series of contact lens-related microbial keratitis. Methods: Two hundred ninety-seven cases of contact lens-related microbial keratitis, aged between 15 and 64 years were detected through surveillance of hospital and community based ophthalmic practitioners in Australia and New Zealand. Full clinical data were available for 190 cases and 90 were interviewed by telephone. Clinical data included the size, location, and degree of anterior chamber response. Symptom data were available from the practitioner and from participant self-report. Associations between symptoms and disease severity were evaluated. Data on ocular and systemic disease were collected from participants and practitioners. The frequency of comorbidities was compared between the different severities of disease and to population norms. Results: More severe disease was associated with greater symptom severity and pain was the most prevalent symptom reported. Ninety-one percent of cases showed progression of ocular symptoms after lens removal, and symptom progression was associated with all severities of disease. Twenty-five percent of cases reported prior episodes requiring emergency attention. Thyroid disease (p 0.05) and self-reported poor health (p 0.001) were more common in cases compared with age-matched population norms. Discussion: Information on the signs, symptoms, and comorbidities associated with contact lens-related microbial keratitis may be useful in patient education and for practitioners involved in the fitting of lenses and management of complications. Although pain was the most common symptom experienced, progression of symptoms despite lens removal was close to universal. Poor general health, particularly respiratory disease and thyroid disease was more common in cases than in the general population, which may prompt practitioners to recommend flexibility in wear schedules when in poor health or the selection of a lower risk wear schedule in at risk patients