How important is length? : mechanical testing and measurement of a cemented, polished, tapered femoral implant

Total hip arthroplasty (THA) has a proven clinical record for providing pain relief and return of function to patients with disabling arthritis. There are many successful options for femoral implant design and fixation. Cemented, polished, tapered femoral implants have been shown to have excellent results in national joint registries and long-term clinical series. These implants are usually 150mm long at their lateral aspect. Due to their length, these implants cannot always be offered to patients due to variations in femoral anatomy. Polished, tapered implants as short as 95mm exist, however their small proximal geometry (neck offset and body size) limit their use to smaller stature patients. There is a group of patients in which a shorter implant with a maintained proximal body size would be advantageous. There are also potential benefits to a shorter implant in standard patient populations such as reduced bone removal due to reduced reaming, favourable loading of the proximal femur, and the ability to revise into good proximal bone stock if required. These factors potentially make a shorter implant an option for all patient populations. The role of implant length in determining the stability of a cemented, polished, tapered femoral implant is not well defined by the literature. Before changes in implant design can be made, a better understanding of the role of each region in determining performance is required. The aim of the thesis was to describe how implant length affects the stability of a cemented, polished, tapered femoral implant. This has been determined through an extensive body of laboratory testing. The major findings are that for a given proximal body size, a reduction in implant length has no effect on the torsional stability of a polished, tapered design, while a small reduction in axial stability should be expected. These findings are important because the literature suggests that torsional stability is the major determinant of long-term clinical performance of a THA system. Furthermore, a polished, tapered design is known to be forgiving of cement-implant interface micromotion due to the favourable wear characteristics. Together these findings suggest that a shorter polished, tapered implant may be well tolerated. The effect of a change in implant length on the geometric characteristics of polished, tapered design were also determined and applied to the mechanical testing. Importantly, interface area does play a role in stability of the system; however it is the distribution of the interface and not the magnitude of the area that defines stability. Taper angle (at least in the range of angles seen in this work) was shown not to be a determinant of axial or torsional stability. A range of implants were tested, comparing variations in length, neck offset and indication (primary versus cement-in-cement revision). At their manufactured length, the 125mm implants were similar to their longer 150mm counterparts suggesting that they may be similarly well tolerated in the clinical environment. However, the slimmer cement-in-cement revision implant was shown to have a poorer mechanical performance, suggesting their use in higher demand patients may be hazardous. An implant length of 125mm has been shown to be quite stable and the results suggest that a further reduction to 100mm may be tolerated. However, further work is required. A shorter implant with maintained proximal body size would be useful for the group of patients who are unable to access the current standard length implants due to variations in femoral anatomy. Extending the findings further, the similar function with potential benefits of a shorter implant make their application to all patients appealing.

Application of a human bone engineering platform to an in vitro and in vivo breast cancer metastasis model

Breast cancer in its advanced stage has a high predilection to the skeleton. Currently, treatment options of breast cancer-related bone metastasis are restricted to only palliative therapeutic modalities. This is due to the fact that mechanisms regarding the breast cancer celI-bone colonisation as well as the interactions of breast cancer cells with the bone microenvironment are not fully understood, yet. This might be explained through a lack of appropriate in vitro and in vivo models that are currently addressing the above mentioned issue. Hence the hypothesis that the translation of a bone tissue engineering platform could lead to improved and more physiological in vitro and in vivo model systems in order to investigate breast cancer related bone colonisation was embraced in this PhD thesis. Therefore the first objective was to develop an in vitro model system that mimics human mineralised bone matrix to the highest possible extent to examine the specific biological question, how the human bone matrix influences breast cancer cell behaviour. Thus, primary human osteoblasts were isolated from human bone and cultured under osteogenic conditions. Upon ammonium hydroxide treatment, a cell-free intact mineralised human bone matrix was left behind. Analyses revealed a similar protein and mineral composition of the decellularised osteoblast matrix to human bone. Seeding of a panel of breast cancer cells onto the bone mimicking matrix as well as reference substrates like standard tissue culture plastic and collagen coated tissue culture plastic revealed substrate specific differences of cellular behaviour. Analyses of attachment, alignment, migration, proliferation, invasion, as well as downstream signalling pathways showed that these cellular properties were influenced through the osteoblast matrix. The second objective of this PhD project was the development of a human ectopic bone model in NOD/SCID mice using medical grade polycaprolactone tricalcium phosphate (mPCL-TCP) scaffold. Human osteoblasts and mesenchymal stem cells were seeded onto an mPCL-TCP scaffold, fabricated using a fused deposition modelling technique. After subcutaneous implantation in conjunction with the bone morphogenetic protein 7, limited bone formation was observed due to the mechanical properties of the applied scaffold and restricted integration into the soft tissue of flank of NOD/SCID mice. Thus, a different scaffold fabrication technique was chosen using the same polymer. Electrospun tubular scaffolds were seeded with human osteoblasts, as they showed previously the highest amount of bone formation and implanted into the flanks of NOD/SCID mice. Ectopic bone formation with sufficient vascularisation could be observed. After implantation of breast cancer cells using a polyethylene glycol hydrogel in close proximity to the newly formed bone, macroscopic communication between the newly formed bone and the tumour could be observed. Taken together, this PhD project showed that bone tissue engineering platforms could be used to develop an in vitro and in vivo model system to study cancer cell colonisation in the bone microenvironment.

Near infrared spectroscopy for non-destructive evaluation of articular cartilage

There is a need for an accurate real-time quantitative system that would enhance decision-making in the treatment of osteoarthritis. To achieve this objective, significant research is required that will enable articular cartilage properties to be measured and categorized for health and functionality without the need for laboratory tests involving biopsies for pathological evaluation. Such a system would provide the capability of access to the internal condition of the cartilage matrix and thus extend the vision-based arthroscopy that is currently used beyond the subjective evaluation of surgeons. The system required must be able to non-destructively probe the entire thickness of the cartilage and its immediate subchondral bone layer. In this thesis, near infrared spectroscopy is investigated for the purpose mentioned above. The aim is to relate it to the structure and load bearing properties of the cartilage matrix to the near infrared absorption spectrum and establish functional relationships that will provide objective, quantitative and repeatable categorization of cartilage condition outside the area of visible degradation in a joint. Based on results from traditional mechanical testing, their innovative interpretation and relationship with spectroscopic data, new parameters were developed. These were then evaluated for their consistency in discriminating between healthy viable and degraded cartilage. The mechanical and physico-chemical properties were related to specific regions of the near infrared absorption spectrum that were identified as part of the research conducted for this thesis. The relationships between the tissue's near infrared spectral response and the new parameters were modeled using multivariate statistical techniques based on partial least squares regression (PLSR). With significantly high levels of statistical correlation, the modeled relationships were demonstrated to possess considerable potential in predicting the properties of unknown tissue samples in a quick and non-destructive manner. In order to adapt near infrared spectroscopy for clinical applications, a balance between probe diameter and the number of active transmit-receive optic fibres must be optimized. This was achieved in the course of this research, resulting in an optimal probe configuration that could be adapted for joint tissue evaluation. Furthermore, as a proof-of-concept, a protocol for obtaining the new parameters from the near infrared absorption spectra of cartilage was developed and implemented in a graphical user interface (GUI)-based software, and used to assess cartilage-on-bone samples in vitro. This conceptual implementation has been demonstrated, in part by the individual parametric relationship with the near infrared absorption spectrum, the capacity of the proposed system to facilitate real-time, non-destructive evaluation of cartilage matrix integrity. In summary, the potential of the optical near infrared spectroscopy for evaluating articular cartilage and bone laminate has been demonstrated in this thesis. The approach could have a spin-off for other soft tissues and organs of the body. It builds on the earlier work of the group at QUT, enhancing the near infrared component of the ongoing research on developing a tool for cartilage evaluation that goes beyond visual and subjective methods.

Prevalence of breast cancer treatment sequelae over 6 years of follow-up

Background: There is a need to better describe and understand the prevalence of breast cancer treatment-related adverse effects amenable to physical therapy and rehabilitative exercise. Prior studies have been limited to single issues and lacked long term follow-up. The Pulling Through Study provides data on prevalence of adverse effects in breast cancer survivors followed over six years. Methods: A population-based sample of Australian women (n=287) diagnosed with invasive, unilateral breast cancer was followed for a median of 6.6 years and prospectively assessed for treatment-related complications at 6, 12, 18 months, and 6 years post-diagnosis. Assessments included post-surgical complications, skin or tissue reaction to radiation therapy, upper-body symptoms, lymphedema, 10% weight gain, fatigue, and upper-quadrant function. The proportion of women with positive indication for each complication and one or more complication was estimated using all available data at each time point. Women were only considered to have a specific complication if they reported the highest two levels of the Likert scale for self-reported issues. Results: At six years post-diagnosis over 60% of women experienced one or more side effects amenable to rehabilitative intervention. The proportion of women experiencing 3 or more side effects decreased throughout follow-up, while the proportion experiencing no side effects remained stable around 40% from 12 months to six years. Weight gain was the only complication to increase in prevalence over time. Conclusion: These data support the development of a multi-disciplinary prospective surveillance approach for the purposes of managing and treating adverse effects in breast cancer survivors.

Improved treatment of nicotine addiction and emerging pulmonary drug delivery

Nicotine addiction remains the leading cause of death and disease in developed and developing nations and a major cause of mortality around the world. Currently, nicotine replacement therapies (NRTs), bupropion, and varenicline are approved by the regulatory agencies as first-line treatments for nicotine addiction. Emerging evidence indicates that varenicline and bupropion have some therapeutic limitations for treating nicotine addiction with oral route of administration. Thus, continued investigation of innovative drug delivery for nicotine addiction remains a critical priority. This review will discuss some novel strategies and future directions for pulmonary drug delivery, an emerging route of administration for smoking cessation. It is anticipated that the advancement of knowledge on pulmonary drug delivery will provide better management for nicotine addiction and other addictive disorders.

Are plasmons responsible for the Raman signal enhancement observed with gold nanoparticle sensors?

The electromagnetic enhancement that occurs in surface enhanced Raman scattering (SERS) substrates containing gold nanoparticles (NPs) is believed to arise through the generation of localised surface plasmons. We present results that show no SERS signals are obtained when 25 nm diameter gold NPs layered quartz substrates exposed to 2-aminopyridine are illuminated with plasmon resonant 532 nm radiation, but SERS signals are observed when the same samples are illuminated with non-resonant 785 nm radiation.

Factors influencing health behaviours of younger women after menopause-inducing cancer treatment

Objective To investigate the health promotion and risk reduction behaviors of younger women previously treated for cancer. Design and Sample Guided by the Precede-Proceed framework, a mixed-method descriptive investigation of the health behaviors of younger women with cancer treatment-induced menopause in one health jurisdiction in Australia was undertaken. Measures This article reports the results of the qualitative interview component of the study. Results Of the 85 women who responded to surveys that quantified their health behaviors, 22 consented to interviews that explored how and why these behaviors might occur. Conclusions Several predisposing, enabling and reinforcing factors that influenced participants will or ability to engage with health-promoting behaviors after cancer treatment were identified in the interviews. These include entrenched precancer diagnosis health behaviors, the disabilities resulting from cancer treatments, perceptions of risk, focused intervention by health professionals and the nature of participants social support. The results indicate a need for flexibility when planning public health initiatives to prepare this cohort for a healthy life after cancer, which accounts for their developmental, knowledge and posttreatment needs.

Facilitating first year students’ engagement with planning education : utilising student affinity for technology to increase cohort cohesion and decrease attrition

First year students overwhelmingly indicate that a strong interest in a field of study prompts them to enrol in university (McInnis et al 2000), yet over a quarter indicate that they have seriously considered dropping out of studies during their first year, with boredom most frequently cited by those domestic students who do depart before graduation (Coates and Ransom 2011). While it may be comforting to write off such withdrawals to the presumed apathy of youth, student “disquiet (in) their first year on campus may be a result of courses and institutions that do not match their needs and objectives, rather than any uncertainty or lack of purpose on their part” (James et al 1999). Voting with their mouse clicks, The current research investigate two conceptualized types of student participation in online discussion forums to increase understanding of student affinity for technology and its potential for fostering social network development amongst first year students.

Phenotypic Characterization of Prostate Cancer LNCaP Cells Cultured within a Bioengineered Microenvironment

Biophysical and biochemical properties of the microenvironment regulate cellular responses such as growth, differentiation, morphogenesis and migration in normal and cancer cells. Since two-dimensional (2D) cultures lack the essential characteristics of the native cellular microenvironment, three-dimensional (3D) cultures have been developed to better mimic the natural extracellular matrix. To date, 3D culture systems have relied mostly on collagen and Matrigel™ hydrogels, allowing only limited control over matrix stiffness, proteolytic degradability, and ligand density. In contrast, bioengineered hydrogels allow us to independently tune and systematically investigate the influence of these parameters on cell growth and differentiation. In this study, polyethylene glycol (PEG) hydrogels, functionalized with the Arginine-glycine-aspartic acid (RGD) motifs, common cell-binding motifs in extracellular matrix proteins, and matrix metalloproteinase (MMP) cleavage sites, were characterized regarding their stiffness, diffusive properties, and ability to support growth of androgen-dependent LNCaP prostate cancer cells. We found that the mechanical properties modulated the growth kinetics of LNCaP cells in the PEG hydrogel. At culture periods of 28 days, LNCaP cells underwent morphogenic changes, forming tumor-like structures in 3D culture, with hypoxic and apoptotic cores. We further compared protein and gene expression levels between 3D and 2D cultures upon stimulation with the synthetic androgen R1881. Interestingly, the kinetics of R1881 stimulated androgen receptor (AR) nuclear translocation differed between 2D and 3D cultures when observed by immunofluorescent staining. Furthermore, microarray studies revealed that changes in expression levels of androgen responsive genes upon R1881 treatment differed greatly between 2D and 3D cultures. Taken together, culturing LNCaP cells in the tunable PEG hydrogels reveals differences in the cellular responses to androgen stimulation between the 2D and 3D environments. Therefore, we suggest that the presented 3D culture system represents a powerful tool for high throughput prostate cancer drug testing that recapitulates tumor microenvironment. © 2012 Sieh et al.

Copper-containing mesoporous bioactive glass scaffolds with multifunctional properties of angiogenesis capacity, osteostimulation and antibacterial activity

It is of great importance to develop multifunctional bioactive scaffolds, which combine angiogenesis capacity, osteostimulation, and antibacterial properties for regenerating lost bone tissues. In order to achieve this aim, we prepared copper (Cu)-containing mesoporous bioactive glass (Cu-MBG) scaffolds with interconnective large pores (several hundred micrometer) and well-ordered mesopore channels (around 5 nm). Both Cu-MBG scaffolds and their ionic extracts could stimulate hypoxia-inducible factor (HIF)-1a and vascular endothelial growth factor(VEGF) expression in human bone marrow stromal cells(hBMSCs). In addition, both Cu-MBG scaffolds and their ionic extracts significantly promoted the osteogenic differentiation of hBMSCs by improving their bone-related gene expression (alkaline phosphatase (ALP), osteopontin(OPN) and osteocalcin (OCN)). Furthermore, Cu-MBG scaffolds could maintain a sustained release of ibuprofen and significantly inhibited the viability of bacteria. This study indicates that the incorporation of Cu2þ ions into MBG scaffolds significantly enhances hypoxia-like tissue reaction leading to the coupling of angiogenesis and osteogenesis. Cu2þ ions play an important role to offer the multifunctional properties of MBG scaffold system. This study has demonstrated that it is possible to develop multifunctional scaffolds by combining enhanced angiogenesis potential, osteostimulation, and antibacterial properties for the treatment of large bone defects.

Experimental study on mechanical properties of pumpkin tissue

Purpose: The purpose of this study was to calculate mechanical properties of tough skinned vegetables as a part of Finite Element Modelling (FEM) and simulation of tissue damage during mechanical peeling of tough skinned vegetables. Design/methodology: There are some previous studies on mechanical properties of fruits and vegetables however, behaviour of tissue under different processing operations will be different. In this study indentation test was performed on Peel, Flesh and Unpeeled samples of pumpkin as a tough skinned vegetable. Additionally, the test performed in three different loading rates for peel: 1.25, 10, 20 mm/min and 20 mm/min for flesh and unpeeled samples respectively. The spherical end indenter with 8mm diameter used for the experimental tests. Samples prepare from defect free and ripped pumpkin purchased from local shops in Brisbane, Australia. Humidity and temperature were 20-55% and 20-250C respectively. Findings: Consequently, force deformation and stress and strain of samples were calculated and shown in presented figures. Relative contribution (%) of skin to different mechanical properties is computed and compared with data available from literature. According the results, peel samples had the highest value of rupture force (291N) and as well as highest value of firmness (1411Nm-1). Research limitations/implications: The proposed study focused on one type of tough skinned vegetables and one variety of pumpkin however, more tests will give better understandings of behaviours of tissue. Additionally, the behaviours of peel, unpeeled and flesh samples in different speed of loading will provide more details of tissue damages during mechanical loading. Originality/value: Mechanical properties of pumpkin tissue calculated using the results of indentation test, specifically the behaviours of peel, flesh and unpeeled samples were explored which is a new approach in Finite Element Modelling (FEM) of food processes. Keywords: Finite Element Modelling (FEM), relative contribution, firmness, toughness and rupture force.

Factors affecting antihypertensive treatment adherence : a Saudi Arabian perspective

Hypertension is a global health issue among the adult population. Adherence to antihypertensive medications is an effective step for better control of blood pressure and preventing the risk of complications. Several factors support or hinder hypertensive patients’ adherence. Objectives: This article reviews the factors affecting adherence to antihypertensive treatments, and reflects on these factors from a Saudi Arabian perspective. Methods: Papers and studies about antihypertensive medication adherence were reviewed from different databases including MEDLINE, PubMed, ScienceDirect and Google scholar. Results: Factors affecting antihypertensive treatments adherence are classified into three domains: Patient (e.g. sociodemographic, individual knowledge and skills), Health System, and Provider related factors.

Infertility in Australia circa 1980 : an historical population perspective on the uptake of fertility treatment by Australian women born in 1946-51

Objective: To estimate the prevalence of lifetime infertility in Australian women born in 1946-51 and examine their uptake of treatment. Methods: Participants in the Australian Longitudinal Study on Women's Health born in 1946-51 (n=13,715) completed up to four mailed surveys from 1996 to 2004. The odds of infertility were estimated using logistic regression with adjustment for socio-demographic and reproductive factors. Results: Among participants, 92.1% had been pregnant. For women who had been pregnant (n=12738): 56.5% had at least one birth but no pregnancy loss (miscarriage and/or termination); 39.9% experienced both birth and loss; and 3.6% had a loss only. The lifetime prevalence of infertility was 11.0%. Among women who reported infertility (n=1511), 41.7% used treatment. Women had higher odds of infertility when they had reproductive histories of losses only (OR range 9.0-43.5) or had never been pregnant (OR=15.7, 95%CI 11.8-20.8); and higher odds for treatment: losses only (OR range 2.5-9.8); or never pregnant (1.96, 1.28-3.00). Women who delayed their first birth until aged 30+ years had higher odds of treatment (OR range 3.2-4.3). Conclusions: About one in ten women experienced infertility and almost half used some form of treatment, especially those attempting pregnancy after 1980. Older first time mothers had an increased uptake of treatment as assisted reproductive technologies (ART) developed. Implications: This study provided evidence of the early uptake of treatment prior to 1979 when the national register of invasive ART was developed and later uptake prior to 1998 when data on non-invasive ART were first collected.

Infertility, medical advice and treatment with fertility hormones and/or in vitro fertilisation: a population perspective from the Australian Longitudinal Study on Women's Health

OBJECTIVE: To identify the factors associated with infertility, seeking advice and treatment with fertility hormones and/or in vitro fertilisation (IVF) among a general population of women. METHODS: Participants in the Australian Longitudinal Study on Women's Health aged 28-33 years in 2006 had completed up to four mailed surveys over 10 years (n=9,145). Parsimonious multivariate logistic regression was used to identify the socio-demographic, biological (including reproductive histories), and behavioural factors associated with infertility, advice and hormonal/IVF treatment. RESULTS: For women who had tried to conceive or had been pregnant (n=5,936), 17% reported infertility. Among women with infertility (n=1031), 72% (n=728) sought advice but only 50% (n=356) used hormonal/IVF treatment. Women had higher odds of infertility when: they had never been pregnant (OR=7.2, 95% CI 5.6-9.1) or had a history of miscarriage (OR range=1.5-4.0) than those who had given birth (and never had a miscarriage or termination). CONCLUSION: Only one-third of women with infertility used hormonal and/or IVF treatment. Women with PCOS or endometriosis were the most proactive in having sought advice and used hormonal/IVF treatment. IMPLICATIONS: Raised awareness of age-related declining fertility is important for partnered women aged approximately 30 years to encourage pregnancy during their prime reproductive years and reduce the risk of infertility.

Early users of fertility treatment with hormones and IVF : women who live in major cities and have private health insurance

Objective: To identify early users (women aged <34 years) of fertility treatment with hormones and in vitro fertilisation (IVF). Methods: A cross-sectional survey of infertile women from fertility clinics (n=59) and from the community (Australian Longitudinal Study on Women's Health participants) who had (n=121) or had not (n=110) used hormones/IVF as treatment for infertility. Associations between socio-demographic, reproductive and lifestyle factors, medical conditions and recurrent symptoms and using treatment (or not) were analysed using multivariable logistic regression. Results: Among infertile women who had used treatment (community vs clinic), women from clinics had lower odds of living outside major cities, using hormones only, i.e., not IVF, or recurrent headaches/migraines, severe tiredness, or stiff/painful joints; and higher odds of recent diagnoses of urinary tract infection or anxiety disorder. Compared to infertile women who had not used treatment, women from clinics had lower odds of living outside major cities, recurrent allergies or severe tiredness; and higher odds of having private health insurance for hospital or ancillary services, recent diagnosis of polycystic ovary syndrome or recurrent constipation. Conclusions: Compared to infertile women in the community, living in major cities and having private health insurance are associated with early use of treatment for infertility at specialist clinics by women aged <34 years. Implications: These results provided evidence of inequity of services for infertile women.