International epidemiology of prostate cancer : geographical distribution and secular trends

This review outlines current international patterns in prostate cancer incidence and mortality rates and survival, including recent trends and a discussion of the possible impact of prostate-specific antigen (PSA) testing on the observed data. Internationally, prostate cancer is the second most common cancer diagnosed among men (behind lung cancer), and is the sixth most common cause of cancer death among men. Prostate cancer is particularly prevalent in developed countries such as the United States and the Scandinavian countries, with about a six-fold difference between high-incidence and low-incidence countries. Interpretation of trends in incidence and survival are complicated by the increasing impact of PSA testing, particularly in more developed countries. As Western influences become more pronounced in less developed countries, prostate cancer incidence rates in those countries are tending to increase, even though the prevalence of PSA testing is relatively low. Larger proportions of younger men are being diagnosed with prostate cancer and living longer following diagnosis of prostate cancer, which has many implications for health systems. Decreasing mortality rates are becoming widespread among more developed countries, although it is not clear whether this is due to earlier diagnosis (PSA testing), improved treatment, or some combination of these or other factors.

Doctors and their patients : A context for understanding the wish to hasten death

There is a paucity of research that has directly examined the role of the health professional in dealing with a terminally ill patient's wish to hasten death (WTHD) and the implications of this for the support and services needed in the care for a dying patient. Themes to emerge from a qualitative analysis of interviews conducted on doctors (n=24) involved in the treatment and care of terminally ill patients were (i) the doctors' experiences in caring for their patients (including themes of emotional demands/expectations, the duration of illness, and the availability of palliative care services); (ii) the doctors' perception of the care provided to their respective patients (comprising themes concerning satisfaction with the care for physical symptoms, for emotional symptoms, or overall care); (iii) the doctors' attitudes to euthanasia and (iv) the doctors' perception of their patients' views/beliefs regarding euthanasia and hastened death. When responses were categorised according to the patients' level of a WTHD, the theme concerning the prolonged nature of the patients' illnesses was prominent in the doctor group who had patients with the highest WTHD, whereas there was only a minority of responses concerning support from palliative care services and satisfaction with the level of emotional care in this group. This exploratory study presents a set of descriptive findings identifying themes among a small group of doctors who have been involved in the care of terminally ill cancer patients, to investigate factors that may be associated with the WTHD among these patients. The pattern of findings suggest that research investigating the doctor-patient interaction in this setting may add to our understanding of the problems (for patients and their doctors) that underpins the wish to hasten death in the terminally ill.

Terminally ill cancer patients’ wish to hasten death

This exploratory study investigated factors associated with the wish to hasten death among a sample of terminally ill cancer patients. Semi-structured interviews conducted on a total of 72 hospice and home palliative care patients were subjected to qualitative analysis using QSRNUDIST. The main themes to emerge suggested that patients with a high wish to hasten death had greater concerns with physical symptoms and psychologica l suffering, perceived themselves to be more of a burden to others, and experienced higher levels of demoralization, while also reporting less confidence in symptom control, fewer social supports, less satisfaction with life experiences and fewer religious beliefs when compared with patients who had a moderate or no wish to hasten death. The implications of these findings will be discussed.

Passive control of a bi-ventricular assist device : an experimental and numerical investigation

For the last two decades heart disease has been the highest single cause of death for the human population. With an alarming number of patients requiring heart transplant, and donations not able to satisfy the demand, treatment looks to mechanical alternatives. Rotary Ventricular Assist Devices, VADs, are miniature pumps which can be implanted alongside the heart to assist its pumping function. These constant flow devices are smaller, more efficient and promise a longer operational life than more traditional pulsatile VADs. The development of rotary VADs has focused on single pumps assisting the left ventricle only to supply blood for the body. In many patients however, failure of both ventricles demands that an additional pulsatile device be used to support the failing right ventricle. This condition renders them hospital bound while they wait for an unlikely heart donation. Reported attempts to use two rotary pumps to support both ventricles concurrently have warned of inherent haemodynamic instability. Poor balancing of the pumps’ flow rates quickly leads to vascular congestion increasing the risk of oedema and ventricular ‘suckdown’ occluding the inlet to the pump. This thesis introduces a novel Bi-Ventricular Assist Device (BiVAD) configuration where the pump outputs are passively balanced by vascular pressure. The BiVAD consists of two rotary pumps straddling the mechanical passive controller. Fluctuations in vascular pressure induce small deflections within both pumps adjusting their outputs allowing them to maintain arterial pressure. To optimise the passive controller’s interaction with the circulation, the controller’s dynamic response is optimised with a spring, mass, damper arrangement. This two part study presents a comprehensive assessment of the prototype’s ‘viability’ as a support device. Its ‘viability’ was considered based on its sensitivity to pathogenic haemodynamics and the ability of the passive response to maintain healthy circulation. The first part of the study is an experimental investigation where a prototype device was designed and built, and then tested in a pulsatile mock circulation loop. The BiVAD was subjected to a range of haemodynamic imbalances as well as a dynamic analysis to assess the functionality of the mechanical damper. The second part introduces the development of a numerical program to simulate human circulation supported by the passively controlled BiVAD. Both investigations showed that the prototype was able to mimic the native baroreceptor response. Simulating hypertension, poor flow balancing and subsequent ventricular failure during BiVAD support allowed the passive controller’s response to be assessed. Triggered by the resulting pressure imbalance, the controller responded by passively adjusting the VAD outputs in order to maintain healthy arterial pressures. This baroreceptor-like response demonstrated the inherent stability of the auto regulating BiVAD prototype. Simulating pulmonary hypertension in the more observable numerical model, however, revealed a serious issue with the passive response. The subsequent decrease in venous return into the left heart went unnoticed by the passive controller. Meanwhile the coupled nature of the passive response not only decreased RVAD output to reduce pulmonary arterial pressure, but it also increased LVAD output. Consequently, the LVAD increased fluid evacuation from the left ventricle, LV, and so actually accelerated the onset of LV collapse. It was concluded that despite the inherently stable baroreceptor-like response of the passive controller, its lack of sensitivity to venous return made it unviable in its present configuration. The study revealed a number of other important findings. Perhaps the most significant was that the reduced pulse experienced during constant flow support unbalanced the ratio of effective resistances of both vascular circuits. Even during steady rotary support therefore, the resulting ventricle volume imbalance increased the likelihood of suckdown. Additionally, mechanical damping of the passive controller’s response successfully filtered out pressure fluctuations from residual ventricular function. Finally, the importance of recognising inertial contributions to blood flow in the atria and ventricles in a numerical simulation were highlighted. This thesis documents the first attempt to create a fully auto regulated rotary cardiac assist device. Initial results encourage development of an inlet configuration sensitive to low flow such as collapsible inlet cannulae. Combining this with the existing baroreceptor-like response of the passive controller will render a highly stable passively controlled BiVAD configuration. The prototype controller’s passive interaction with the vasculature is a significant step towards a highly stable new generation of artificial heart.

The effect of bone graft type on fusion rates following anterior thoracoscopic scoliosis correction

Bone graft is generally considered fundamental in achieving solid fusion in scoliosis correction and pseudarthrosis following instrumentation may predispose to implant failure. In thoracoscopic anterior-instrumented scoliosis surgery, autologous rib or iliac crest graft has been utilised traditionally but both techniques increase operative duration and cause donor site morbidity. Allograft bone and bone morphogenetic protein (BMP) alternatives may improve fusion rates but this remains controversial. This study's objective was to compare two-year postoperative fusion rates in a series of patients who underwent thoracoscopic anterior instrumentation for thoracic scoliosis utilising various bone graft types.

Continuation rates and reasons for removal among Implanon® users accessing two family planning clinics in Queensland, Australia

Background - This study examined demographic profile, continuation rates and reasons for removal among Implanon^® users accessing two family planning clinics in Queensland, Australia. Study Design - A retrospective chart audit of 976 women who attended for implant insertion over a 3-year period between May 2001 and May 2004. Results - Continuation rates showed that at 6 months after insertion, 94% of women continued, 74% continued at 1 year and 50% continued at 2 years. Metropolitan women were more likely than rural women to discontinue use because of dissatisfaction with bleeding patterns. Cox regression analysis showed that those attending the regional clinic experienced significantly shorter time to removal. Conclusions - Implanon® continuation rates and reasons for removal differ between clinics in metropolitan and rural locations. A cooling-off period did not affect the likelihood of continuation with Implanon®. Preinsertion counselling should emphasize potential changes in bleeding patterns.

Health, Death, and Indigenous Australians in the Coronial system

This paper details research conducted in Queensland during the first year of operation of the new Coroners Act 2003. Information was gathered from all completed investigations between December 2003 and December 2004 across five categories of death: accidental, suicide, natural, medical and homicide. It was found that 25 percent of the total number of Indigenous deaths recorded in 2004 were reported to, and investigated by, the Coroner, in comparison to 9.4 percent of non-Indigenous deaths. Moreover, Indigenous people were found to be over-represented in each category of death, except in death in a medical setting, where they were absent.

Rates of change : digital distribution as a disruptive technology in the film industry

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Exploring donation decisions: Beliefs and preferences for organ donation in Australia

We explored common beliefs and preferences for posthumous and living organ donation in Australia where organ donation rates are low and little research exists. Content analysis of discussions revealed the advantage of prolonging/saving life whereas disadvantages differed according to donation context. A range of people/groups perceived to approve and disapprove of donation were identified. Barriers for posthumous donation included a family’s objection, with the type of organ needed important for living donation. Motivators included knowledge about potential organ recipients. Donation preferences favored loved ones, with weaker preferences for recipients who were perceived as morally questionable or responsible for their illness.

The role of extreme sports in lifestyle enhancement and wellness

Alternative sports are fast becoming the physical activity of choice. Participation rates are even outstripping more traditional activities such as golf. At their most extreme there is no second chance, the most likely outcome of a mismanaged error or accident is death. At this level participants enjoy activities such as B.A.S.E. (Buildings, Antennae, Space, Earth) jumping, big wave surfing, waterfall kayaking, extreme skiing, rope-free climbing and extreme mountaineering. Probably the most common explanation for participation in extreme sports is the notion that participation is just a matter of some people‟s need to take unnecessary risks. This study reports on findings that indicate a more positive experience. A phenomenological method was used via unstructured interviews with 15 extreme sports participants (ages 30 – 72 years) and other firsthand accounts. Extreme sport participants directly related their experience to personal transformations that spill over to life in general. Athletes report feelings of deep psychological wellbeing and meaningfulness. The extreme sport experience enables a participant to break through personal barriers and develop an understanding of their own resourcefulness and emotional, cognitive, physical and spiritual capabilities. Furthermore such a breakthrough also seems to trigger a change in personal philosophy or view on life. The extreme sport experience transforms a participant though not in terms of working towards an external (social or cultural) perception of identity or towards some constructed perception of an ideal self, but by touching something within.

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.

An empirical investigation of the level effect in Australian interest rates

An extensive literature examines the dynamics of interest rates, with particular attention given to the positive relationship between interest-rate volatility and the level of interest rates—the so-called level effect. This paper examines the interaction between the estimated level effect and competing parameterisations of interest-rate volatility for the Australian yield curve. We adopt a new methodology that estimates elasticity in a multivariate setting that explicitly accommodates the correlations that exist between various yield factors. Results show that significant correlations exist between the residuals of yield factors and that such correlations do indeed impact on model estimates. Within the multivariate setting, the level of the short rate is shown to be a crucial determinant of the conditional volatility of all three yield factors. Measures of model fit suggest that, in addition to the usual level effect, the incorporation of GARCH effects and possible regime shifts is important

Discrepancies between metabolic activity and DNA content as tool to assess cell proliferation in cancer research

Cell proliferation is a critical and frequently studied feature of molecular biology in cancer research. Therefore, various assays are available using different strategies to measure cell proliferation. Metabolic assays such as AlamarBlue, WST-1, and MTT, which were originally developed to determine cell toxicity, are being used to assess cell numbers. Additionally, proliferative activity can be determined by quantification of DNA content using fluorophores, such as CyQuant and PicoGreen. Referring to data published in high ranking cancer journals, 945 publications applied these assays over the past 14 years to examine the proliferative behaviour of diverse cell types. Within this study, mainly metabolic assays were used to quantify changes in cell growth yet these assays may not accurately reflect cellular proliferation rates due to a miscorrelation of metabolic activity and cell number. Testing this hypothesis, we compared metabolic activity of different cell types, human cancer cells and primary cells, over a time period of 4 days using AlamarBlue and fluorometric assays CyQuant and PicoGreen to determine their DNA content. Our results show certain discrepancies in terms of over-estimation of cell proliferation with respect to the metabolic assay in comparison to DNA binding fluorophores.