Characterisation of mesenchymal cells from osteophytes in osteoarthritis

Osteophytes form through the process of chondroid metamorphosis of fibrous tissue followed by endochondral ossification. Osteophytes have been found to consist of three different mesenchymal tissue regions including endochondral bone formation within cartilage residues, intra-membranous bone formation within fibrous tissue and bone formation within bone marrow spaces. All these features provide evidence of mesenchymal stem cells (MSC) involvement in osteophyte formation; nevertheless, it remains to be characterised. MSC from numerous mesenchymal tissues have been isolated but bone marrow remains the “ideal” due to the ease of ex vivo expansion and multilineage potential. However, the bone marrow stroma has a relatively low number of MSC, something that necessitates the need for long-term culture and extensive population doublings in order to obtain a sufficient number of cells for therapeutic applications. MSC in vitro have limited proliferative capacity and extensive passaging compromises differentiation potential. To overcome this barrier, tissue derived MSC are of strong interest for extensive study and characterisation, with a focus on their potential application in therapeutic tissue regeneration. To date, no MSC type cell has been isolated from osteophyte tissue, despite this tissue exhibiting all the hallmark features of a regenerative tissue. Therefore, this study aimed to isolate and characterise cells from osteophyte tissues in relation to their phenotype, differentiation potential, immuno-modulatory properties, proliferation, cellular ageing, longevity and chondrogenesis in in vitro defect model in comparison to patient matched bone marrow stromal cells (bMSC). Osteophyte derived cells were isolated from osteophyte tissue samples collected during knee replacement surgery. These cells were characterised by the expression of cell surface antigens, differentiation potential into mesenchymal lineages, growth kinetics and modulation of allo-immune responses. Multipotential stem cells were identified from all osteophyte samples namely osteophyte derived mesenchymal stem cells (oMSC). Extensively expanded cell cultures (passage 4 and 9 respectively) were used to confirm cytogenetic stability and study signs of cellular aging, telomere length and telomerase activity. Cultured cells at passage 4 were used to determine 84 pathway focused stem cell related gene expression profile. Micro mass pellets were cultured in chondrogenic differentiation media for 21 days for phenotypic and chondrogenic related gene expression. Secondly, cell pellets differentiated overnight were placed into articular cartilage defects and cultured for further 21 days in control medium and chondrogenic medium to study chondrogenesis and cell behaviour. The surface antigen expression of oMSC was consistent with that of mesenchymal stem cells, such as lacking the haematopoietic and common leukocyte markers (CD34, CD45) while expressing those related to adhesion (CD29, CD166, CD44) and stem cells (CD90, CD105, CD73). The proliferation capacity of oMSC in culture was superior to that of bMSC, and they readily differentiated into tissues of the mesenchymal lineages. oMSC also demonstrated the ability to suppress allogeneic T-cell proliferation, which was associated with the expression of tryptophan degrading enzyme indoleamine 2,3 dioxygenase (IDO). Cellular aging was more prominent in late passage bMSC than in oMSC. oMSC had longer telomere length in late passages compared with bMSC, although there was no significant difference in telomere lengths in the early passages in either cell type. Telomerase activity was detectable only in early passage oMSC and not in bMSC. In osteophyte tissues telomerase positive cells were found to be located peri vascularly and were Stro-1 positive. Eighty-four pathway-focused genes were investigated and only five genes (APC, CCND2, GJB2, NCAM and BMP2) were differentially expressed between bMSC and oMSC. Chondrogenically induced micro mass pellets of oMSC showed higher staining intensity for proteoglycans, aggrecan and collagen II. Differential expression of chondrogenic related genes showed up regulation of Aggrecan and Sox 9 in oMSC and collagen II in bMSC. The in vitro defect models of oMSC in control medium showed rounded and aggregated cells staining positively for proteoglycan and presence of some extracellular matrix. In contrast, defects with bMSC showed fragmentation and loss of cells, fibroblast-like cell morphology staining positively for proteoglycans. For defects maintained in chondrogenic medium, rounded, aggregated and proteoglycan positive cells were found in both oMSC and bMSC cultures. Extracellular matrix and cellular integration into newly formed matrix was evident only in oMSC defects. For analysis of chondrocyte hypertrophy, strong expression of type X collagen could be noticed in the pellet cultures and transplanted bMSC. In summary, this study demonstrated that osteophyte derived cells had similar properties to mesenchymal stem cells in the expression of antigen phenotype, differential potential and suppression of allo-immune response. Furthermore, when compared to bMSC, oMSC maintained a higher proliferative capacity due to a retained level of telomerase activity in vitro, which may account for the relatively longer telomeres delaying growth arrest by replicative senescence compared with bMSC. oMSC behaviour in defects supported chondrogenesis which implies that cells derived from regenerative tissue can be an alternative source of stem cells and have a potential clinical application for therapeutic stem cell based tissue regeneration.

Prevalence of Staphylococcus aureus strains in an Australian cohort, 1989-2003 : evidence for the low prevalence of the toxic shock toxin and Panton-Valentine leukocidin genes

The purpose of this paper is to determine the prevalence of the toxic shock toxin gene (tst) and to enumerate the circulating strains of methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in Australian isolates collected over two decades. The aim was to subtype these strains using the binary genes pvl, cna, sdrE, pUB110 and pT181. Isolates were assayed using real-time polymerase chain reaction (PCR) for mecA, nuc, 16 S rRNA, eight single-nucleotide polymorphisms (SNPs) and for five binary genes. Two realtime PCR assays were developed for tst. The 90 MRSA isolates belonged to CC239 (39 in 1989, 38 in 1996 and ten in 2003), CC1 (two in 2003) and CC22 (one in 2003). The majority of the 210 MSSA isolates belonged to CC1 (26), CC5 (24) and CC78 (23). Only 18 isolates were tst-positive and only 15 were pvl-positive. Nine MSSA isolates belonged to five binary types of ST93, including two pvlpositive types. The proportion of tst-positive and pvl-positive isolates was low and no significant increase was demonstrated. Dominant MSSA clonal complexes were similar to those seen elsewhere, with the exception of CC78. CC239 MRSA (AUS-2/3) was the predominant MRSA but decreased significantly in prevalence, while CC22 (EMRSA-15) and CC1 (WA-1) emerged. Genetically diverse ST93 MSSA predated the emergence of ST93- MRSA (the Queensland clone).

Perceptions of aging across 26 cultures and their culture-level associates

College students (N = 3,435) in 26 cultures reported their perceptions of age-related changes in physical, cognitive, and socioemotional areas of functioning and rated societal views of aging within their culture. There was widespread cross-cultural consensus regarding the expected direction of aging trajectories with (1) perceived declines in societal views of aging, physical attractiveness, the ability to perform everyday tasks, and new learning, (2) perceived increases in wisdom, knowledge, and received respect, and (3) perceived stability in family authority and life satisfaction. Cross-cultural variations in aging perceptions were associated with culture-level indicators of population aging, education levels, values, and national character stereotypes. These associations were stronger for societal views on aging and perceptions of socioemotional changes than for perceptions of physical and cognitive changes. A consideration of culture-level variables also suggested that previously reported differences in aging perceptions between Asian and Western countries may be related to differences in population structure.

Sources of coding discrepancies in injury morbidity data: Implications for injury surveillance

Objective: To examine the sources of coding discrepancy for injury morbidity data and explore the implications of these sources for injury surveillance.-------- Method: An on-site medical record review and recoding study was conducted for 4373 injury-related hospital admissions across Australia. Codes from the original dataset were compared to the recoded data to explore the reliability of coded data aand sources of discrepancy.---------- Results: The most common reason for differences in coding overall was assigning the case to a different external cause category with 8.5% assigned to a different category. Differences in the specificity of codes assigned within a category accounted for 7.8% of coder difference. Differences in intent assignment accounted for 3.7% of the differences in code assignment.---------- Conclusions: In the situation where 8 percent of cases are misclassified by major category, the setting of injury targets on the basis of extent of burden is a somewhat blunt instrument Monitoring the effect of prevention programs aimed at reducing risk factors is not possible in datasets with this level of misclassification error in injury cause subcategories. Future research is needed to build the evidence base around the quality and utility of the ICD classification system and application of use of this for injury surveillance in the hospital environment.

Quantifying the costs of drought : new evidence from life satisfaction data

We estimate the cost of droughts by matching rainfall data with individual life satisfaction. Our context is Australia over the period 2001 to 2004, which included a particularly severe drought. Using fixed-effect models, we find that a drought in spring has a detrimental effect on life satisfaction equivalent to an annual reduction in income of A$18,000. This effect, however, is only found for individuals living in rural areas. Using our estimates, we calculate that the predicted doubling of the frequency of spring droughts will lead to the equivalent loss in life satisfaction of just over 1% of GDP annually.

Estimating short and long-term residential demand for electricity : new evidence from Sri Lanka

This study investigates the short-run dynamics and long-run equilibrium relationship between residential electricity demand and factors influencing demand - per capita income, price of electricity, price of kerosene oil and price of liquefied petroleum gas - using annual data for Sri Lanka for the period, 1960-2007. The study uses unit root, cointegration and error-correction models. The long-run demand elasticities of income, own price and price of kerosene oil (substitute) were estimated to be 0.78, - 0.62, and 0.14 respectively. The short-run elasticities for the same variables were estimated to be 032, - 0.16 and 0.10 respectively. Liquefied petroleum (LP) gas is a substitute for electricity only in the short-run with an elasticity 0.09. The main findings of the paper support the following (1) increasing the price of electricity is not the most effective tool to reduce electricity consumption (2) existing subsidies on electricity consumption can be removed without reducing government revenue (3) the long-run income elasticity of demand shows that any future increase in household incomes is likely to significantly increase the demand for electricity and(4) any power generation plans which consider only current per capita consumption and population growth should be revised taking into account the potential future income increases in order to avoid power shortages ill the country.

Tax morale affects tax compliance : evidence from surveys and an artefactual field experiment

Our working hypotheses is that cross-cultural differences in tax compliance behaviour have foundations in the institutions of tax administration and citizen assessment of the quality of governance. Tax compliance being a complex behavioural issue. Its investigation requires use of a variety of methods and data sources. Results from artefactual field experiments conducted in countries with substantially different political histories and records of governance quality demondtrate that observed differences in tax compliance levels persist over alternative levels of enforcement. The experimental results are shown to be robust by replicating them for the same countries using survey response measures of tax compliance.

Driver behaviour and decision making at railway level crossings : An exploratory on-road case study

Crashes at rail level crossings represent a significant problem, both in Australia and worldwide. Advances in driving assessment methods, such as the provision of on-road instrumented test vehicles, now provide researchers with the opportunity to further understand driver behaviour at rail level crossings in ways not previously possible. This paper gives an overview of a recent on-road pilot study of driver behaviour at rail level crossings in which 25 participants drove a pre-determined route, incorporating 4 rail level crossings, using MUARC's instrumented On-Road Test Vehicle (ORTeV). Drivers provided verbal commentary whilst driving the route, and a range of other data were collected, including eye fixations, forward, cockpit and driver video, and vehicle data (speed, braking, steering wheel angle, lane tracking etc). Participants also completed a post trial cognitive task analysis interview. Extracts from the wider analyses are used to examine in depth driver behaviour at one of the rail level crossings encountered during the study. The analysis presented, along with the overall analysis undertaken, gives insight into the driver and wider systems factors that shape behaviour at rail level crossings, and highlights the utility of using a multi-method, instrumented vehicle approach for gathering data regarding driver behaviour in different contexts.

The appropriateness of default investment options in defined contribution plans : Australian evidence

For participants in defined contribution (DC) plans who refrain from exercising investment choice, plan contributions are invested following the default investment option of their respective plans. Since default investment options of different plans vary widely in terms of their benchmark asset allocation, the most important determinant of investment performance, participants enrolled in these options face significantly different wealth outcomes at retirement. This paper simulates the terminal wealth outcomes under different static asset allocation strategies to evaluate their relative appeal as default investment choice in DC plans. We find that strategies with low or moderate allocation to stocks are consistently outperformed in terms of upside potential of exceeding the participant’s wealth accumulation target at retirement as well as downside risk of falling below that target outcome by aggressive strategies whose allocation to stocks approach 100%. The risk of extremely adverse wealth outcomes for plan participants also does not appear to be very sensitive to asset allocation. Our evidence suggests the appropriateness of strategies heavily tilted towards stocks to be nominated as default investment options in DC plans unless plan providers emphasize predictability of wealth outcomes over adequacy of retirement wealth.

Is there timing ability in currency markets? Evidence from ADR issuances

Is there timing ability in the exchange rate markets? We address this question by examining foreign firms' decisions to issue American Depositary Receipts (ADRs). Specifically, we test whether foreign firms consider currency market conditions in their ADR issuance decisions and, in doing so, display some ability to time their local exchange rate market. We study ADR issuances in the U.S. stock market between 1976 and 2003. We find that foreign firms tend to issue ADRs after their local currency has been abnormally strong against the U.S. dollar and before their local currency becomes abnormally weak. This evidence is statistically significant even after controlling for local and U.S. past and future stock market performance and predicable exchange rate movements. Currency market timing is especially significant i) for value companies, relatively small (yet absolutely large) companies issuing relatively large amounts of ADRs, companies with higher currency exposure, manufacturing companies, and emerging market companies, ii) during currency crises (when mispricings are rife) and after the integration of the issuer's local financial market with the world capital markets, iii) when the ADR issue raises capital for the issuing firm (Level III ADR), and iv) regardless of the identity of the underwriting investment bank. Currency market timing is also economically significant since it translates into total savings for the issuing firms of about $646 million (or 1.86% of the total capital-raising ADR issue volume). In contrast, we find no evidence of currency timing ability in a control sample made of non-capital raising ADRs (Level II ADRs). These findings suggest that some companies may have, at least occasionally, private information about foreign exchange.

Effects of lead exposure on hippocampal metabotropic glutamate receptor subtype 3 and 7 in developmental rats

Background A complete explanation of the mechanisms by which Pb2+ exerts toxic effects on developmental central nervous system remains unknown. Glutamate is critical to the developing brain through various subtypes of ionotropic or metabotropic glutamate receptors (mGluRs). Ionotropic N-methyl-D-aspartate receptors have been considered as a principal target in lead-induced neurotoxicity. The relationship between mGluR3/mGluR7 and synaptic plasticity had been verified by many recent studies. The present study aimed to examine the role of mGluR3/mGluR7 in lead-induced neurotoxicity. Methods Twenty-four adult and female rats were randomly selected and placed on control or 0.2% lead acetate during gestation and lactation. Blood lead and hippocampal lead levels of pups were analyzed at weaning to evaluate the actual lead content at the end of the exposure. Impairments of short -term memory and long-term memory of pups were assessed by tests using Morris water maze and by detection of hippocampal ultrastructural alterations on electron microscopy. The impact of lead exposure on mGluR3 and mGluR7 mRNA expression in hippocampal tissue of pups were investigated by quantitative real-time polymerase chain reaction and its potential role in lead neurotoxicity were discussed. Results Lead levels of blood and hippocampi in the lead-exposed rats were significantly higher than those in the controls (P < 0.001). In tests using Morris Water Maze, the overall decrease in goal latency and swimming distance was taken to indicate that controls had shorter latencies and distance than lead-exposed rats (P = 0.001 and P < 0.001 by repeated-measures analysis of variance). On transmission electron microscopy neuronal ultrastructural alterations were observed and the results of real-time polymerase chain reaction showed that exposure to 0.2% lead acetate did not substantially change gene expression of mGluR3 and mGluR7 mRNA compared with controls. Conclusion Exposure to lead before and after birth can damage short-term and long-term memory ability of young rats and hippocampal ultrastructure. However, the current study does not provide evidence that the expression of rat hippocampal mGluR3 and mGluR7 can be altered by systemic administration of lead during gestation and lactation, which are informative for the field of lead-induced developmental neurotoxicity noting that it seems not to be worthwhile to include mGluR3 and mGluR7 in future studies. Background

Distribution of benefits of irrigation induced technological changes and commodity markets : new evidence

A plethora of literature exists on irrigation development. However, only a few studies analyse the distributional issues associated with irrigation induced technological changes (IITC) in the context of commodity markets. Furthermore, these studies deal with only the theoretical arguments and to date no proper investigation has been conducted to examine the long-term benefits of adopting modern irrigation technology. This study investigates the long-term benefit changes of irrigation induced technological changes using data from Sri Lanka with reference to rice farming. The results show that (1) adopting modern technology on irrigation increases the overall social welfare through consumption of a larger quantity at a lower cost (2) the magnitude, sensitivity and distributional gains depend on the price elasticity of demand and supply as well as the size of the marketable surplus (3) non-farm sector gains are larger than farm sector gains (4) the distribution of the benefits among different types of producers depend on the magnitude of the expansion of the irrigated areas as well as the competition faced by traditional farmers (5) selective technological adoption and subsidies have a detrimental effect on the welfare of other producers who do not enjoy the same benefits (6) the short-term distributional effects are more severe than the long-term effects among different groups of farmers.

Academic rigour in science assessment tasks

The critical problem of student disengagement and underachievement in the middle years of schooling (Years 4 . 9) has focussed attention on the quality of educational programs in schools, in Australia and elsewhere. The loss of enthusiasm for science in the middle years is particularly problematic given the growing demand for science professionals. Reshaping middle years programs has included an emphasis on integrating Information and Communication Technologies (ICTs) and improving assessment practices to engage students in higher cognitive processes and enhance academic rigour. Understanding the nature of academic rigour and how to embed it in students. science assessment tasks that incorporate the use of ICTs could enable teachers to optimise the quality of the learning environment. However, academic rigour is not clearly described or defined in the literature and there is little empirical evidence upon which researchers and teachers could draw to enhance understandings. This study used a collective case study design to explore teachers' understandings of academic rigour within science assessment tasks. The research design is based on a conceptual framework that is underpinned by socio-cultural theory. Three methods were used to collect data from six middle years teachers and their students. These methods were a survey, focus group discussion with teachers and a group of students and individual semi-structured interviews with teachers. Findings of the case study revealed six criteria of academic rigour, namely, higher order thinking, alignment, building on prior knowledge, scaffolding, knowledge construction and creativity. Results showed that the middle years teachers held rich understandings of academic rigour that led to effective utilisation of ICTs in science assessment tasks. Findings also indicated that teachers could further enhance their understandings of academic rigour in some aspects of each of the criteria. In particular, this study found that academic rigour could have been further optimised by: promoting more thoughtful discourse and interaction to foster higher order thinking; increasing alignment between curriculum, pedagogy, and assessment, and students. prior knowledge; placing greater emphasis on identifying, activating and building on prior knowledge; better differentiating the level of scaffolding provided and applying it more judiciously; fostering creativity throughout tasks; enhancing teachers‟ content knowledge and pedagogical content knowledge, and providing more in-depth coverage of fewer topics to support knowledge construction. Key contributions of this study are a definition and a model which clarify the nature of academic rigour.

Nursing care of the mechanically ventilated patient: What does the evidence say?: Part two

The care of the mechanically ventilated patient is a fundamental component of a nurse's clinical practice in the intensive care unit (ICU). Published work relating to the numerous nursing issues of the care of the mechanically ventilated patient in the ICU is growing significantly, yet is fragmentary by nature. The purpose of this paper is to provide a single comprehensive examination of the evidence related to the care of the mechanically ventilated patient. In part one of this two-part paper, the evidence on nursing care of the mechanically ventilated patient was explored with specific focus on patient safety: particularly patient and equipment assessment. This article, part two, examines the evidence related to the mechanically ventilated patient's comfort: patient position, hygiene, management of stressors (such as communication, sleep disturbance and isolation), pain management and sedation.