Altered cell interactions of subchondral bone osteoblasts and articular chondrocytes in osteoarthritis is through the mediation of ERK1/2 phosphorylation

Introduction: Osteoarthritis (OA) is the most common musculoskeletal disorder and represents a major health burden to society. In the course of the pathological development of OA, articular cartilage chondrocytes (ACCs) undergo a typical phenotype changes characterized by the expression of hypertrophic differentiation markers. Also, the adjacent subchondral bone shows signs of abnormal mineral density and enhanced production of bone turnover markers, indicative of osteoblast dysfunction. However, the mechanism(s) by which these changes occur during the OA development are not completely understood. Materials and Methods: ACCs and subchondral bone osteoblasts (SBOs) were harvested from OA and healthy patients for the cross-talk studies between normal and OA ACCs and SBOs. The involvement of mitogen activated protein kinase (MAPK) signalling pathway during the cell-cell interactions was analysed by zymography, ELISA and western blotting methods. Results: The direct and in-direct co-culture studies showed that OA (ACCs and SBOs) cells induced osteoarthritic changes of normal (ACC and SBOs) cells. This altered cell interaction induced by OA cells significantly aggravated the proteolytic activity, which resulted cartilage degeneration. The altered cell interaction appeared to significantly activate ERK 1/2 phosphorylation and inhibition of MAPK-ERK 1/2 pathway reversed the osteoarthrtitic phenotypic changes. Discussion and Conclusion: Our study has demonstrated that the altered bi-directional communication of SBOs and ACCs are critical for initiation and progression of OA related changes and that this process is mediated by MAPK signalling pathways. Targeting these altered interactions by the use of MAPK inhibitors may provide the scientific rationale for the development of novel therapeutic strategies in the treatment and management of OA related disorders.

Organization and management of police

To understand the nature of police organisations and their management in an Australian context it is necessary to appreciate the recent history of policing at least in the last 30 years. In doing so an overall perspective is gained on the various reform efforts and organisational changes that have taken place in Australian policing. With this police reform perspective clearly in mind it then becomes possible to appreciate that the organization and management of the institution of policing in Australia is nested within the larger framework of ‘governance’. Hence, this notion of governance will be used as the key focal point around which to understand how police organizations manage their mission in the Australian context. Finally, the chapter discusses the inevitable ‘tension spaces’ that arise in policing and the need for police organizations to better manage such complexities.

Design and design thinking in business and management education and development

Design and design thinking have been identified as making valuable contributions to business and management and the numbers of higher education programs that teach design thinking to business students, managers and executives are growing. However multiple definitions of design thinking and the range of perspectives have created some confusion about potential pathways. This paper examines notions of design and design thinking and uses these definitions to identify themes in higher educational programs. We present the findings from an initial exploratory investigation of design and design thinking in higher education business programs and define four distinct educational approaches around human centred innovation, integrative thinking, design management and design as strategy. Potential directions for management education programs are presented.

It’s okay to ask : development and pilot testing of a question prompt list for patients with brain tumours

Background: Previous research identified that primary brain tumour patients have significant psychological morbidity and unmet needs, particularly the need for more information and support. However, the utility of strategies to improve information provision in this setting is unknown. This study involved the development and piloting of a brain tumour specific question prompt list (QPL). A QPL is a list of questions patients may find useful to ask their health professionals, and is designed to facilitate communication and information exchange. Methods: Thematic analysis of QPLs developed for other chronic diseases and brain tumour specific patient resources informed a draft QPL. Subsequent refinement of the QPL involved an iterative process of interviews and review with 12 recently diagnosed patients and six caregivers. Final revisions were made following readability analyses and review by health professionals. Piloting of the QPL is underway using a non-randomised control group trial with patients undergoing treatment for a primary brain tumour in Brisbane, Queensland. Following baseline interviews, consenting participants are provided with the QPL or standard information materials. Follow-up interviews four to 6 weeks later allow assessment of the acceptability of the QPL, how it is used by patients, impact on information needs, and feasibility of recruitment, implementation and outcome assessment. Results: The final QPL was determined to be readable at the sixth grade level. It contains seven sections: diagnosis, prognosis, symptoms and changes, the health professional team, support, treatment and management, and post-treatment concerns. At this time, fourteen participants have been recruited for the pilot, and data collection completed for eleven. Data collection and preliminary analysis are expected to be completed by and presented at the conference. Conclusions: If acceptable to participants, the QPL may encourage patients, doctors and nurses to communicate more effectively, reducing unmet information needs and ultimately improving psychological wellbeing.

The role of physical activity in the lives of people with lymphoedema following cancer treatment : a social constructionist study

Lymphoedema is a chronic condition predominantly affecting the limbs, although it can involve the trunk and other areas of the body. It is characterised by swelling due to excess accumulation of fluid in body tissues. Secondary lymphoedema, which arises following cancer treatment, is the more common form of lymphoedema in developed countries. At least 20% of those diagnosed with the most common cancers will develop lymphoedema. This is a concern in Australia as incidence of these cancers is increasing. Cancer survival rates are also increasing. Currently, this equates to 9 300 new cases of secondary lymphoedema diagnosed each year. Considerable physical and psychosocial impacts of lymphoedema have been reported and its subsequent impact on health-related quality of life can exacerbate other side effects of cancer treatment. Exercise following cancer treatment has been shown to significantly reduce the impact of treatment side effects, improve quality of life and physical status. While participating in exercise does not increase risk nor exacerbate existing lymphoedema, reductions in incidence of lymphoedema exacerbations and associated symptoms have been observed in women participating in regular weight lifting following breast cancer treatment. Despite these benefits, lymphoedema prevention and management advice cautions people with lymphoedema against „repetitive use. or „overuse. of their affected arm. It is possible that this advice creates a barrier to participation in physical activity; however, little is known about the relationship between physical activity and lymphoedema. In addition, the majority of studies examining the experiences of people living with lymphoedema and the impact of the condition have been predominantly conducted internationally and have focused on women following breast cancer. This study sought to explore firstly, how men and women construct their experience of living with lymphoedema following treatment for a range of cancers in the context of everyday life in Australia; and secondly, to analyse the role of physical activity in the lives of those living with lymphoedema following cancer treatment. A social constructivist grounded theory approach was taken to explore these objectives as it is acknowledged that human actions and the meanings associated with these actions are influenced by the interaction between the self and the social world. It is also acknowledged that the research process itself is a social construction between the researcher and participant. Purposive sampling techniques were used to recruit a total of 29 participants from a variety of sources. Telephone interviews and focus groups were conducted to collect data. Data were concurrently collected and analysed and analysis was conducted using the constant comparative method. The core category that developed in objective one was „sense of self‟. The self was defined by perceptions participants held of themselves and their identity prior to a lymphoedema diagnosis and changes to their perceptions and identity since diagnosis. Three conceptual categories which related to each other and to „sense of self‟ were developed through the process of coding that represented the process of how participants constructed their experiences living with secondary lymphoedema in the context of everyday life. Firstly, altered normalcy reflected the physical and psychosocial changes experienced and the effect it had on their lives. Secondly, „accidental journey‟ reflected participants‟ journey with the heath care system prior to diagnosis through to longer term management. Thirdly, renegotiating control revealed participants perceived control over lymphoedema and their ability to participate in daily activities previously enjoyed. These findings revealed the failure of the broader health system to recognise the significant and chronic nature of a lymphoedema diagnosis following cancer treatment with greater understanding, knowledge and support from health professionals being needed. The findings also reveal access to health professionals trained in lymphoedema management, a comprehensive approach encompassing both physical and psychosocial needs and provision of practical and meaningful guidelines supported by scientific evidence would contribute to improved treatment and management of the condition. The key findings for objective two were that people with lymphoedema define physical activity in different ways. Physical activity post-diagnosis was perceived as important by most for a variety of reasons ranging from everyday functioning, to physical and psychosocial health benefits. Issues relating to the impact of lymphoedema on physical activity related to the impact on peoples‟ ability to be physically active, confusion about acceptable forms of physical activity and barriers that lymphoedema presented to being physically active. A relationship between how people construct their experiences with lymphoedema and the role of physical activity was also established. The contribution of physical activity to the lives of people living with lymphoedema following cancer treatment appeared to be influenced by their sense of self as socially constructed through their experiences prior to diagnosis and following diagnosis with lymphoedema. The influence of pre-lymphoedema habits, norms and beliefs suggests the importance of effective health promotion messages to encourage physical activity among the general population and specific messages and guidelines particular to the needs of those diagnosed with lymphoedema following cancer treatment. The influence of participant.s social constructions on the lymphoedema experience highlights the importance of improving interactions between the overall health care system and patients, providing a clear treatment plan, providing evidence-based and clear advice about participation in appropriate physical activity, which in doing so will limit the physical and psychosocial effect of lymphoedema and providing comprehensive physical and psychosocial support to those living with the condition and their families. This study has contributed to a deep understanding of people.s experiences with lymphoedema following cancer treatment and the role of physical activity in the context of daily life in Australia. Findings from this study lead to recommendations for advocacy, a comprehensive approach to diagnosis, treatment and management, and specific areas for future research.

Book review of Wang, Y., & Pizam, A. (Eds). 2011. Destination Marketing and Management – Theories and Applications.

A contentious issue in the field of destination marketing has been the recent tendency by some authors to refer to destination marketing organisations (DMOs) as destination management organisations. This nomenclature infers control over destination resources, a level of influence that is in reality held by few DMOs. This issue of a lack of control over the destination ‘amalgam’ is acknowledged by a number of the contributors, including the editors and the discussion on destination competitiveness by J.R. Brent Ritchie and Geoffrey Crouch, and is perhaps best summed up by Alan Fyall in the concluding chapter: “...unless all elements are owned by the same body, then the ability to control and influence the direction, quality and development of the destination pose very real challenges’ (p. 343). The title of the text acknowledges both marketing and management, in relation to theories and applications. While there are insightful propositions about ideals of destination management, readers will find there is a lack of coverage of destination management in practise by DMOs. This represents fertile ground for future research.

Ionic liquid pre-treatment and fractionation of sugarcane bagasse for the production of bioethanol

Pretretament is an essential and expensive processing step for the manufacturing of ethanol from lignocellulosic raw materials. Ionic liquids are a new class of solvents that have the potential to be used as pretreatment agents. The attractive characteristics of ionic liquid pretreatment of lignocellulosics such as thermal stability, dissolution properties, fractionation potential, cellulose decrystallisation capacity and saccharification impact are investigated in this thesis. Dissolution of bagasse with 1-butyl-3-methylimidazolium chloride ([C4mim]Cl) at high temperatures (110 �‹C to 160 �‹C) is investigated as a pretreatment process. Material balances are reported and used along with enzymatic saccharification data to identify optimum pretreatment conditions (150 �‹C for 90 min). At these conditions, the dissolved and reprecipitated material is enriched in cellulose, has a low crystallinity and the cellulose component is efficiently hydrolysed (93 %, 3 h, 15 FPU). At pretreatment temperatures < 150 �‹C, the undissolved material has only slightly lower crystallinity than the starting. At pretreatment temperatures . 150 �‹C, the undissolved material has low crystallinity and when combined with the dissolved material has a saccharification rate and extent similar to completely dissolved material (100 %, 3h, 15 FPU). Complete dissolution is not necessary to maximize saccharification efficiency at temperatures . 150 �‹C. Fermentation of [C4mim]Cl-pretreated, enzyme-saccharified bagasse to ethanol is successfully conducted (85 % molar glucose-to-ethanol conversion efficiency). As compared to standard dilute acid pretreatment, the optimised [C4mim]Cl pretreatment achieves substantially higher ethanol yields (79 % cf. 52 %) in less than half the processing time (pretreatment, saccharification, fermentation). Fractionation of bagasse partially dissolved in [C4mim]Cl to a polysaccharide rich and a lignin rich fraction is attempted using aqueous biphasic systems (ABSs) and single phase systems with preferential precipitation. ABSs of ILs and concentrated aqueous inorganic salt solutions are achievable (e.g. [C4mim]Cl with 200 g L-1 NaOH), albeit they exhibit a number of technical problems including phase convergence (which increases with increasing biomass loading) and deprotonation of imidazolium ILs (5 % - 8 % mol). Single phase fractionation systems comprising lignin solvents / cellulose antisolvents, viz. NaOH (2M) and acetone in water (1:1, volume basis), afford solids with, respectively, 40 % mass and 29 % mass less lignin than water precipitated solids. However, this delignification imparts little increase in saccharification rates and extents of these solids. An alternative single phase fractionation system is achieved simply by using water as an antisolvent. Regulating the water : IL ratio results in a solution that precipitates cellulose and maintains lignin in solution (0.5 water : IL mass ratio) in both [C4mim]Cl and 1-ethyl-3-methylimidazolium acetate ([C2mim]OAc)). This water based fractionation is applied in three IL pretreatments on bagasse ([C4mim]Cl, 1-ethyl-3-methyl imidazolium chloride ([C2mim]Cl) and [C2mim]OAc). Lignin removal of 10 %, 50 % and 60 % mass respectively is achieved although only 0.3 %, 1.5 % and 11.7 % is recoverable even after ample water addition (3.5 water : IL mass ratio) and acidification (pH . 1). In addition the recovered lignin fraction contains 70 % mass hemicelluloses. The delignified, cellulose-rich bagasse recovered from these three ILs is exposed to enzyme saccharification. The saccharification (24 h, 15 FPU) of the cellulose mass in starting bagasse, achieved by these pretreatments rank as: [C2mim]OAc (83 %)>>[C2mim]Cl (53 %)=[C4mim]Cl(53%). Mass balance determinations accounted for 97 % of starting bagasse mass for the [C4mim]Cl pretreatment , 81 % for [C2mim]Cl and 79 %for [C2mim]OAc. For all three IL treatments, the remaining bagasse mass (not accounted for by mass balance determinations) is mainly (more than half) lignin that is not recoverable from the liquid fraction. After pretreatment, 100 % mass of both ions of all three ILs were recovered in the liquid fraction. Compositional characteristics of [C2mim]OAc treated solids such as low lignin, low acetyl group content and preservation of arabinosyl groups are opposite to those of chloride IL treated solids. The former biomass characteristics resemble those imparted by aqueous alkali pretreatment while the latter resemble those of aqueous acid pretreatments. The 100 % mass recovery of cellulose in [C2mim]OAc as opposed to 53 % mass recovery in [C2mim]Cl further demonstrates this since the cellulose glycosidic bonds are protected under alkali conditions. The alkyl chain length decrease in the imidazolium cation of these ILs imparts higher rates of dissolution and losses, and increases the severity of the treatment without changing the chemistry involved.

Modification of advanced programmatic risk analysis and management model for the whole project life cycle’s risks

The advanced programmatic risk analysis and management model (APRAM) is one of the recently developed methods that can be used for risk analysis and management purposes considering schedule, cost, and quality risks simultaneously. However, this model considers those failure risks that occur only over the design and construction phases of a project’s life cycle. While it can be sufficient for some projects for which the required cost during the operating life is much less than the budget required over the construction period, it should be modified in relation to infrastructure projects because the associated costs during the operating life cycle are significant. In this paper, a modified APRAM is proposed, which can consider potential risks that might occur over the entire life cycle of the project, including technical and managerial failure risks. Therefore, the modified model can be used as an efficient decision-support tool for construction managers in the housing industry in which various alternatives might be technically available. The modified method is demonstrated by using a real building project, and this demonstration shows that it can be employed efficiently by construction managers. The Delphi method was applied in order to figure out the failure events and their associated probabilities. The results show that although the initial cost of a cold-formed steel structural system is higher than a conventional construction system, the former’s failure cost is much lower than the latter’s