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.

Transport of IgG across the blood-luminal barrier of the male reproductive tract of the rat and the effect of estradiol administration on reabsorption of fluid and IgG by the epididymal ducts

In rats immunized systemically with tetanus toxoid the concentration of specific anti-tetanus-toxoid-specific IgG in fluid from the rete testis and cauda epididymidis were respectively 0.6% and 1.4% the concentration in blood serum. The extratesticular duct system reabsorbed 97% of the IgG and 99% of the fluid leaving the rete, but estradiol administration affected the site of reabsorption. In untreated rats, the ductuli efferentes reabsorbed 94% of the IgG and 96% of the fluid leaving the rete, whereas estradiol-treated rats reabsorbed 83% of the IgG and 86% of the fluid, and the ductus epididymidis fully compensated for these different effects of estradiol on the ductuli efferentes. The concentrations of IgG in secretions of the seminal vesicles and prostate gland were lower (0.1% and 0.3% respectively of the titers in blood serum) than in fluids from the extratesticular ducts, and were not affected by the administration of estradiol. RT-PCR showed that Fcgrt (neonatal Fc receptor, also known as FcRn) is expressed in the reproductive ducts, where IgG is probably transported across epithelium, being particularly strong in the ductuli efferentes (where most IgG was reabsorbed) and distal caput epididymidis. It is concluded that IgG enters the rete testis and is concentrated only 2.5-fold along the extratesticular duct system, unlike spermatozoa, which are concentrated 95-fold. Further, the ductus epididymidis can recognize and compensate for changes in function of the ductuli efferentes.

An exploration of the technical, social and macro-societal pressures influencing the adoption of online social networking services by organisations

Measuring the business value that Internet technologies deliver for organisations has proven to be a difficult and elusive task, given their complexity and increased embeddedness within the value chain. Yet, despite the lack of empirical evidence that links the adoption of Information Technology (IT) with increased financial performance, many organisations continue to adopt new technologies at a rapid rate. This is evident in the widespread adoption of Web 2.0 online Social Networking Services (SNSs) such as Facebook, Twitter and YouTube. These new Internet based technologies, widely used for social purposes, are being employed by organisations to enhance their business communication processes. However, their use is yet to be correlated with an increase in business performance. Owing to the conflicting empirical evidence that links prior IT applications with increased business performance, IT, Information Systems (IS), and E-Business Model (EBM) research has increasingly looked to broader social and environmental factors as a means for examining and understanding the broader influences shaping IT, IS and E-Business (EB) adoption behaviour. Findings from these studies suggest that organisations adopt new technologies as a result of strong external pressures, rather than a clear measure of enhanced business value. In order to ascertain if this is the case with the adoption of SNSs, this study explores how organisations are creating value (and measuring that value) with the use of SNSs for business purposes, and the external pressures influencing their adoption. In doing so, it seeks to address two research questions: 1. What are the external pressures influencing organisations to adopt SNSs for business communication purposes? 2. Are SNSs providing increased business value for organisations, and if so, how is that value being captured and measured? Informed by the background literature fields of IT, IS, EBM, and Web 2.0, a three-tiered theoretical framework is developed that combines macro-societal, social and technological perspectives as possible causal mechanisms influencing the SNS adoption event. The macro societal view draws on the concept of Castells. (1996) network society and the behaviour of crowds, herds and swarms, to formulate a new explanatory concept of the network vortex. The social perspective draws on key components of institutional theory (DiMaggio & Powell, 1983, 1991), and the technical view draws from the organising vision concept developed by Swanson and Ramiller (1997). The study takes a critical realist approach, and conducts four stages of data collection and one stage of data coding and analysis. Stage 1 consisted of content analysis of websites and SNSs of many organisations, to identify the types of business purposes SNSs are being used for. Stage 2 also involved content analysis of organisational websites, in order to identify suitable sample organisations in which to conduct telephone interviews. Stage 3 consisted of conducting 18 in-depth, semi-structured telephone interviews within eight Australian organisations from the Media/Publishing and Galleries, Libraries, Archives and Museum (GLAM) industries. These sample organisations were considered leaders in the use of SNSs technologies. Stage 4 involved an SNS activity count of the organisations interviewed in Stage 3, in order to rate them as either Advanced Innovator (AI) organisations, or Learning Focussed (LF) organisations. A fifth stage of data coding and analysis of all four data collection stages was conducted, based on the theoretical framework developed for the study, and using QSR NVivo 8 software. The findings from this study reveal that SNSs have been adopted by organisations for the purpose of increasing business value, and as a result of strong social and macro-societal pressures. SNSs offer organisations a wide range of value enhancing opportunities that have broader benefits for customers and society. However, measuring the increased business value is difficult with traditional Return On Investment (ROI) mechanisms, ascertaining the need for new value capture and measurement rationales, to support the accountability of SNS adoption practices. The study also identified the presence of technical, social and macro-societal pressures, all of which influenced SNS adoption by organisations. These findings contribute important theoretical insight into the increased complexity of pressures influencing technology adoption rationales by organisations, and have important practical implications for practice, by reflecting the expanded global online networks in which organisations now operate. The limitations of the study include the small number of sample organisations in which interviews were conducted, its limited generalisability, and the small range of SNSs selected for the study. However, these were compensated in part by the expertise of the interviewees, and the global significance of the SNSs that were chosen. Future research could replicate the study to a larger sample from different industries, sectors and countries. It could also explore the life cycle of SNSs in a longitudinal study, and map how the technical, social and macro-societal pressures are emphasised through stages of the life cycle. The theoretical framework could also be applied to other social fad technology adoption studies.

The Law and Governance of Water Resources : The Challenge of Sustainability

To achieve the sustainable use and development of water resources is a daunting challenge for both the global and local communities. It requires commitments by all groups within the international, national and local communities from their own particular, possibly conflicting, perspectives. Without a set of coherent legal arrangements designed to ensure effective governance of water resources, their sustainable use and development are unlikely to be achieved. This study looks at how the legal arrangements for managing water resources have evolved across the continents over hundreds of years; their relevance for contemporary society; how the norms of current international and national legal regimes are responding; and, most importantly, how legal rights and duties should be structured so as to achieve sustainability in the future.

Recognising the capacities of dynamic reconfiguration for the QoS assurance of running systems in concurrent and parallel environments

Recognizing the impact of reconfiguration on the QoS of running systems is especially necessary for choosing an appropriate approach to dealing with dynamic evolution of mission-critical or non-stop business systems. The rationale is that the impaired QoS caused by inappropriate use of dynamic approaches is unacceptable for such running systems. To predict in advance the impact, the challenge is two-fold. First, a unified benchmark is necessary to expose QoS problems of existing dynamic approaches. Second, an abstract representation is necessary to provide a basis for modeling and comparing the QoS of existing and new dynamic reconfiguration approaches. Our previous work [8] has successfully evaluated the QoS assurance capabilities of existing dynamic approaches and provided guidance of appropriate use of particular approaches. This paper reinvestigates our evaluations, extending them into concurrent and parallel environments by abstracting hardware and software conditions to design an evaluation context. We report the new evaluation results and conclude with updated impact analysis and guidance.

Assessing the impact of a food supplement on the nutritional status and body composition of HIV-infected Zambian women on ARVs

Background Zambia is a sub-Saharan country with one of the highest prevalence rates of HIV, currently estimated at 14%. Poor nutritional status due to both protein-energy and micronutrient malnutrition has worsened this situation. In an attempt to address this combined problem, the government has instigated a number of strategies, including the provision of antiretroviral (ARV) treatment coupled with the promotion of good nutrition. High-energy protein supplement (HEPS) is particularly promoted; however, the impact of this food supplement on the nutritional status of people living with HIV/AIDS (PLHA) beyond weight gain has not been assessed. Techniques for the assessment of nutritional status utilising objective measures of body composition are not commonly available in Zambia. The aim of this study is therefore to assess the impact of a food supplement on nutritional status using a comprehensive anthropometric protocol including measures of skinfold thickness and circumferences, plus the criterion deuterium dilution technique to assess total body water (TBW) and derive fat-free mass (FFM) and fat mass (FM). Methods/Design This community-based controlled and longitudinal study aims to recruit 200 HIV-infected females commencing ARV treatment at two clinics in Lusaka, Zambia. Data will be collected at four time points: baseline, 4-month, 8-month and 12-month follow-up visits. Outcome measures to be assessed include body height and weight, body mass index (BMI), body composition, CD4, viral load and micronutrient status. Discussion This protocol describes a study that will provide a longitudinal assessment of the impact of a food supplement on the nutritional status of HIV-infected females initiating ARVs using a range of anthropometric and body composition assessment techniques.

The importance of mosquito behavioural adaptations to malaria control in Africa

Over the past decade the use of long-lasting insecticidal nets (LLINs), in combination with improved drug therapies, indoor residual spraying (IRS) and better health infrastructure, has helped reduce malaria in many African countries for the first time in a generation. However, insecticide resistance in the vector is an evolving threat to these gains. We review emerging and historical data on behavioural resistance in response to LLINs and IRS. Overall the current literature suggests behavioural and species changes may be emerging, but the data are sparse and, at times unconvincing. However, preliminary modelling has demonstrated that behavioural resistance could have significant impacts on the effectiveness of malaria control. We propose seven recommendations to improve understanding of resistance in malaria vectors. Determining the public health impact of physiological and behavioural insecticide resistance is an urgent priority if we are to maintain the significant gains made in reducing malaria morbidity and mortality.

Mapping the conditions of penal hope

This article examines the conditions of penal hope behind suggestions that the penal expansionism of the last three decades may be at a ‘turning point’. The article proceeds by outlining David Green’s (2013b) suggested catalysts of penal reform and considers how applicable they are in the Australian context. Green’s suggested catalysts are: the cycles and saturation thesis; shifts in the dominant conception of the offender; the global financial crisis (GFC) and budgetary constraints; the drop in crime; the emergence of the prisoner re‐entry movement; apparent shifts in public opinion; the influence of evangelical Christian ideas; and the Right on Crime initiative. The article then considers a number of other possible catalysts or forces: the role of trade unions; the role of courts; the emergence of recidivism as a political issue; the influence of ‘evidence based’/‘what works’ discourse; and the emergence of justice reinvestment (JR). The article concludes with some comments about the capacity of criminology and criminologists to contribute to penal reductionism, offering an optimistic assessment for the prospects of a reflexive criminology that engages in and engenders a wider politics around criminal justice issues.

Ureaplasma parvum undergoes selection in utero resulting in genetically diverse isolates colonising the chorioamnion of fetal sheep

Ureaplasmas are the microorganisms most frequently isolated from the amniotic fluid of pregnant women and can cause chronic intrauterine infections. These tiny bacteria are thought to undergo rapid evolution and exhibit a hypermutatable phenotype; however, little is known about how ureaplasmas respond to selective pressures in utero. Using an ovine model of chronic intra-amniotic infection, we investigated if exposure of ureaplasmas to sub-inhibitory concentrations of erythromycin could induce phenotypic or genetic indicators of macrolide resistance. At 55 days gestation, 12 pregnant ewes received an intra-amniotic injection of a non-clonal, clinical U. parvum strain, followed by: (i) erythromycin treatment (IM, 30 mg/kg/day, n=6); or (ii) saline (IM, n=6) at 100 days gestation. Fetuses were then delivered surgically at 125 days gestation. Despite injecting the same inoculum into all ewes, significant differences between amniotic fluid and chorioamnion ureaplasmas were detected following chronic intra-amniotic infection. Numerous polymorphisms were observed in domain V of the 23S rRNA gene of ureaplasmas isolated from the chorioamnion (but not the amniotic fluid), resulting in a mosaic-like sequence. Chorioamnion isolates also harboured the macrolide resistance genes erm(B) and msr(D) and were associated with variable roxithromycin minimum inhibitory concentrations. Remarkably, this variability occurred independently of exposure of ureaplasmas to erythromycin, suggesting that low-level erythromycin exposure does not induce ureaplasmal macrolide resistance in utero. Rather, the significant differences observed between amniotic fluid and chorioamnion ureaplasmas suggest that different anatomical sites may select for ureaplasma sub-types within non-clonal, clinical strains. This may have implications for the treatment of intrauterine ureaplasma infections.

How much information can be obtained from tracking the position of the leading edge in a scratch assay?

Moving cell fronts are an essential feature of wound healing, development and disease. The rate at which a cell front moves is driven, in part, by the cell motility, quantified in terms of the cell diffusivity $D$, and the cell proliferation rate �$\lambda$. Scratch assays are a commonly-reported procedure used to investigate the motion of cell fronts where an initial cell monolayer is scratched and the motion of the front is monitored over a short period of time, often less than 24 hours. The simplest way of quantifying a scratch assay is to monitor the progression of the leading edge. Leading edge data is very convenient since, unlike other methods, it is nondestructive and does not require labeling, tracking or counting individual cells amongst the population. In this work we study short time leading edge data in a scratch assay using a discrete mathematical model and automated image analysis with the aim of investigating whether such data allows us to reliably identify $D$ and $\lambda$�. Using a naıve calibration approach where we simply scan the relevant region of the ($D$;$\lambda$�) parameter space, we show that there are many choices of $D$ and $\lambda$� for which our model produces indistinguishable short time leading edge data. Therefore, without due care, it is impossible to estimate $D$ and $\lambda$� from this kind of data. To address this, we present a modified approach accounting for the fact that cell motility occurs over a much shorter time scale than proliferation. Using this information we divide the duration of the experiment into two periods, and we estimate $D$ using data from the first period, while we estimate �$\lambda$ using data from the second period. We confirm the accuracy of our approach using in silico data and a new set of in vitro data, which shows that our method recovers estimates of $D$ and $\lamdba$� that are consistent with previously-reported values except that that our approach is fast, inexpensive, nondestructive and avoids the need for cell labeling and cell counting.

The value of respect in human research ethics: A conceptual analysis and a practical guide

In order to continue to maintain public trust and confidence in human research, participants must be treated with respect. Researchers and Human Research Ethics Committee members need to be aware that modern considerations of this value include: the need for a valid consenting process, the protection of participants who have their capacity for consent compromised; the promotion of dignity for participants; and the effects that human research may have on cultures and communities. This paper explains the prominence of respect as a value when considering the ethics of human research and provides practical advice for both researchers and Human Research Ethics Committee members in developing respectful research practices.

Engendering the responsibility to protect : women and the prevention of mass atrocities

This article explores the relationship between the Responsibility to Protect (R2P) and the pursuit of the so-called ‘Women, Peace and Security’ (WPS) agenda at the UN. We ask whether the two agendas should continue to be pursued separately or whether each can make a useful contribution to the other. We argue that while the history of R2P has not included language that deliberately evokes the protection of women and the promotion of gender in preventing genocide and mass atrocities, this does not preclude the R2P and WPS agendas becoming mutually reinforcing. The article identifies cross-cutting areas where the two agendas may be leveraged for the UN and member states to address the concerns of women as both actors in need of protection and active agents in preventing and responding to genocide and mass atrocities, namely in the areas of early warning.

Do nursing students have the recall of bioscience necessary to study pharmacology?

Background: For medical and allied health students, bioscience knowledge underpins the successful scaffolding of learning in their developmental and advanced level units. Many of these students complete theory-based Bioscience units, followed by a unit in Pharmacology, which specifically requires knowledge of anatomy, physiology and microbiology. In general, studies of recall report relatively large losses over short retention intervals (months), which accumulate, but level off, for longer retention intervals (years) (Custers, 2010). However, there are no studies that specifically test the recall of bioscience knowledge by allied health students. Methods: We are tracking the recall of bioscience in nursing students prior to, and during, their Pharmacology unit. In each semester, students complete short, basic, knowledge-based MCQ quizzes on concepts from (i) the gastrointestinal system and (ii) fundamental microbiology. Students were given 5 days warning about the microbiology quizzes but were given no warning prior to the gastrointestinal system quiz. Performance in these quizzes was compared to individual student’s results in the final examination on these topics in the first semester of their degree. Results: At the start of the study, the nursing students performed better in the exam MCQs on the gastrointestinal system than on microbiology. In the exam, the students’ mean marks for the gastrointestinal system ranged from 69–83%, and this was successively reduced to 63%, 53% and 49% after 4, 9 and 16 months, respectively. The mean exam marks for microbiology was 48–58%, and this did not change significantly after 4 (63%), 9 (59%) or 16 months (47%). This suggests that warning the nursing students that they were to be quizzed on microbiology may have helped their recall. However, after 16 months regardless of the subject, the nursing students undertaking the Pharmacology unit recalled less than half of the bioscience quiz answers. Conclusions: Nursing students may not have the recall of bioscience necessary to study pharmacology, and this may limit their success in pharmacology. Reference: Custers, E. J. F. M. (2010). Long-term retention of basic science knowledge: a review study. Advances in Health Science Education, 15, 109–128.

Children’s physical activity, health and physical education in isolated rural contexts : the views of parent educators in Queensland

This paper describes the views of parent educators of their children’s levels and types of physical activity. The study was conducted at two mini-schools in western Queensland. These are occasion where students who undertake formal education through various Schools Distance Education, come together for a week of educational activity. Parents (mostly mothers) were interviewed using a semi-structured approach. The interview data were then analysed for dominant themes using a constant comparison method. The emergent themes related to nutrition and physical activity. Within the physical activity theme, notions of the great outdoors, work and organised sport skill development also emerged.

Speaking too soon : the sabotage of bail reform in New South Wales

Within just over one month of coming into operation in May 2014, the new Bail Act 2013 (NSW), a product of long-term law reform consideration, was reviewed and then amended after talk-back radio ‘shock jock’ and tabloid newspaper outcry over three cases. This article examines the media triggers, the main arguments of the review conducted by former New South Wales (NSW) Attorney General John Hatzistergos, and the amendments, with our analysis of the judicial interpretation of the Act thus far providing relevant background. We argue that the amendments are premature, unnecessary, create complexity and confusion, and, quite possibly, will have unintended consequences: in short, they are a mess. The whole process of reversal is an example of law and order politics driven by the shock jocks and tabloid media, the views of which, are based on fundamental misconceptions of the purpose of bail and its place in the criminal process, resulting in a conflation of accusation, guilt and punishment. Other consequences of the review and amendments process recognised in this article include the denigration of judicial expertise and lack of concern with evidence and process; the disproportionate influence of the shock jocks, tabloids and Police Association of NSW on policy formation; the practice of using retired politicians to produce ‘quick fix’ reviews; and the political failure to understand and defend fundamental legal principles that benefit us all and are central to the maintenance of a democratic society and the rule of law. The article concludes with some discussion of ways in which media and political debate might be conducted to produce more balanced outcomes.