Impact of extracellular matrix derived from osteoarthritis subchondral bone osteoblasts on osteocytes : role of integrinβ1 and focal adhesion kinase signaling cues

INTRODUCTION: Our recent study indicated that subchondral bone pathogenesis in osteoarthritis (OA) is associated with osteocyte morphology and phenotypic abnormalities. However, the mechanism underlying this abnormality needs to be identified. In this study we investigated the effect of extracellular matrix (ECM) produced from normal and OA bone on osteocytic cells function. METHODS: De-cellularized matrices, resembling the bone provisional ECM secreted from primary human subchondral bone osteoblasts (SBOs) of normal and OA patients were used as a model to study the effect on osteocytic cells. Osteocytic cells (MLOY4 osteocyte cell line) cultured on normal and OA derived ECMs were analyzed by confocal microscopy, scanning electron microscopy (SEM), cell attachment assays, zymography, apoptosis assays, qRT-PCR and western blotting. The role of integrinβ1 and focal adhesion kinase (FAK) signaling pathways during these interactions were monitored using appropriate blocking antibodies. RESULTS: The ECM produced by OA SBOs contained less mineral content, showed altered organization of matrix proteins and matrix structure compared with the matrices produced by normal SBOs. Culture of osteocytic cells on these defective OA ECM resulted in a decrease of integrinβ1 expression and the de-activation of FAK cell signaling pathway, which subsequently affected the initial osteocytic cell's attachment and functions including morphological abnormalities of cytoskeletal structures, focal adhesions, increased apoptosis, altered osteocyte specific gene expression and increased Matrix metalloproteinases (MMP-2) and -9 expression. CONCLUSION: This study provides new insights in understanding how altered OA bone matrix can lead to the abnormal osteocyte phenotypic changes, which is typical in OA pathogenesis.

Weak key-IV pairs in the A5/1 stream cipher

A5/1 is a shift register based stream cipher which provides privacy for the GSM system. In this paper, we analyse the loading of the secret key and IV during the initialisation process of A5/1. We demonstrate the existence of weak key-IV pairs in the A5/1 cipher due to this loading process; these weak key-IV pairs may generate one, two or three registers containing all-zero values, which may lead in turn to weak keystream sequences. In the case where two or three registers contain only zeros, we describe a distinguisher which leads to a complete decryption of the affected messages.

Earnings management and the role of the audit committee: an investigation of the influence of cross-listing and government officials on the audit committee

This paper extends research on the corporate governance practices of transitional economies by examining whether the ability of the audit committee to constrain earnings management in Chinese firms is associated with the listing environment and the presence of government officials on the audit committee. Despite considerable regulatory reforms by the Chinese Securities Regulatory Commission, there remain incentives for Chinese firms to manage earnings. However, government initiatives to encourage domestic firms to cross-list on the Hong Kong Stock Exchange are accompanied by improved governance. We find that the expertise and independence of the audit committee for cross-listed (CL) Chinese firms are associated with lower abnormal accruals, our measure of earnings management. Both domestic only listed firms and CL Chinese firms appoint government officials as independent members on the audit committee. However, due to the political connection between government officials and the controlling shareholder (the State), these appointments can severely mitigate audit committee independence. Subsequently, we find a significant and positive association between audit committee independence and experience and earnings management when there are government officials on the audit committee.

Computer simulation of the fatigue behaviour of roof cladding during the passage of a tropical cyclone

This paper describes the development of an analytical model used to simulate the fatigue behaviour of roof cladding during the passage of a tropical cyclone. The model incorporated into a computer program uses wind pressure data from wind tunnel tests in combination with time history information on wind speed and direction during a tropical cyclone, and experimental fatigue characteristics data of roof claddings. The wind pressure data is analysed using a rainflow form of analysis, and a fatigue damage index calculated using a modified form of Miner's rule. Some of the results obtained to date and their significance in relation to the review of current fatigue tests are presented. The model appears to be reasonable for comparative estimation of fatigue life, but an improvement of Miner's rule is required for the prediction of actual fatigue life.

Cyclone intensity categories

The weather forecast centers in Australia and many other countries use a scale of cyclone intensity categories (categories 1-5) in their cyclone advisories, which are considered to be indicative of the cyclone damage potential. However, this scale is mainly based on maximum gust wind speeds. In a recent research project involving computer modeling of cyclonic wind forces on roof claddings and fatigue damage to claddings, it was found that cyclone damage not only depends on the maximum gust wind speed, but also on two other cyclone parameters, namely, the forward speed and radius to maximum winds. This paper describes the computer model used in predicting the cyclone damage to claddings and investigates the damage potential of a cyclone as a function of all the relevant cyclone parameters, based on which it attempts to refine the current scale of cyclone intensity categories.

Key influences on motivations for utility cycling (cycling for transport to and from places)

Issue addressed: Although increases in cycling in Brisbane are encouraging, bicycle mode share to work in the state of Queensland remains low. The aim of this qualitative study was to draw upon the lived experiences of Queensland cyclists to understand the main motivators for utility cycling (cycling as a means to get to and from places) and compare motivators between utility cyclists (those who cycle for utility as well as for recreation) and non-utility cyclists (those who cycle only for recreation). Methods: For an online survey, members of a bicycle group (831 utility cyclists and 931 non-utility cyclists, aged 18-90 years) were asked to describe, unprompted, what would motivate them to engage in utility cycling (more often). Responses were coded into themes within four levels of an ecological model. Results: Within an ecological model, built environment influences on motivation were grouped according to whether they related to appeal (safety), convenience (accessibility) or attractiveness (more amenities) and included adequate infrastructure for short trips, bikeway connectivity, end-of-trip facilities at public locations and easy and safe bicycle access to destinations outside of cities. A key social-cultural influence related to improved interactions among different road users. Conclusions: The built and social-cultural environments need to be more supportive of utility cycling before even current utility and non-utility cyclists will be motivated to engage (more often) in utility cycling. So what?: Additional government strategies and more and better infrastructure that support utility cycling beyond commuter cycling may encourage a utility cycling culture.

Hospitalisation of Indigenous children in the Northern Territory for lower respiratory illness in the first year of life

Objective To describe the epidemiology of acute lower respiratory infection (ALRI) and bronchiectasis in Northern Territory Indigenous infants hospitalised in the first year of life. Design A historical cohort study constructed from the NT Hospital Discharge Dataset and the NT Imm(u)nisation Register. Participants and setting All NT resident Indigenous infants, born 1 January 1999 to 31 December 2004, admitted to NT public hospitals and followed up to 12 months of age. Main outcome measures Incidence of ALRI and bronchiectasis (ICD-10-AM codes) and radiologically confirmed pneumonia (World Health Organization protocol). Results Data on 9295 infants, 8498 child-years of observation and 15 948 hospitalised episodes of care were analysed. ALRI incidence was 426.7 episodes per 1000 child-years (95% Cl, 416.2-437.2). Incidence rates were two times higher (relative risk, 2.12; 95% Cl, 1.98-2.27) for infants in Central Australia compared with those in the Top End. The median age at first admission for an ALRI was 4.6 months (interquartile range, 2.6-7.3). Bronchiolitis accounted for most of the disease burden, with a rate of 227 per 1000 child-years. The incidence of first diagnosis of bronchiectasis was 1.18 per 1000 child-years (95% Cl, 0.60-2.16). One or more key comorbidities were present in 1445 of the 3227 (44.8%) episodes of care for ALRI. Conclusions Rates of ALRI and bronchiectasis in NT Indigenous infants are excessive, with early onset, frequent repeat episodes, and a high prevalence of comorbidities. These high rates of disease demand urgent attention.

Tracking structural development through data modelling in highly able Grade 1 students

A 3-year longitudinal study Transforming Children’s Mathematical and Scientific Development integrates, through data modelling, a pedagogical approach focused on mathematical patterns and structural relationships with learning in science. As part of this study, a purposive sample of 21 highly able Grade 1 students was engaged in an innovative data modelling program. In the majority of students, representational development was observed. Their complex graphs depicting categorical and continuous data revealed a high level of structure and enabled identification of structural features critical to this development.

Endothelin-1 is a novel prognostic factor in non-small cell lung cancer

Endothelin-1 (ET-1) is a potent vasoactive peptide and a hypoxia-inducible angiogenic growth factor associated with the development and growth of solid tumours. This study evaluated the expression of big endothelin-1 (big ET-1), a stable precursor of ET-1, and ET-1 in non-small cell lung cancer (NSCLC). Big ET-1 expression was evaluated in paraffin-embedded tissue sections from 10 NSCLC tumours using immunohistochemistry and in situ hybridisation. The production of big ET-1 and ET-1 was studied in six established NSCLC cell lines. The plasma concentrations of big ET-1 were measured in 30 patients with proven NSCLC prior to chemotherapy by means of a sandwich enzyme-linked immunoassay and compared to levels in 20 normal controls. Big ET-1 immunostaining was detected in the cancer cells of all tumours studied. Using in situ hybridisation, tumour cell big ET-1 mRNA expression was demonstrated in all samples. All six NSCLC cell lines expressed ET-1, with big ET-1 being detected in three. The median big ET-1 plasma level in patients with NSCLC was 5.4 pg/mL (range 0-22.7 pg/mL) and was significantly elevated compared to median big ET-1 plasma levels in controls, 2.1 pg/mL (1.2-13.4 pg/mL) (p=0.0001). Furthermore, patients with plasma big ET-1 levels above the normal range (upper tertile) had a worse outcome (p=0.01). In conclusion, big ET-1/ET-1 is expressed by resected NSCLC specimens and tumour cell lines. Plasma big ET-1 levels are elevated in NSCLC patients compared to controls with levels >7.8 pg/mL being associated with a worse outcome. The development of selective ET-1 antagonists such as Atrasentan indicates that ET-1 may be a therapeutic target in NSCLC. © 2004 Wichtig Editore.

Flapless dental implant surgery : a retrospective study of 1,241 consecutive implants

Purpose: The purpose of this study was to identify retrospectively the predictors of implant survival when the flapless protocol was used in two private dental practices. Materials and Methods: The collected data were initially computer searched to identify the patients; later, a hand search of patient records was carried out to identify all flapless implants consecutively inserted over the last 10 years. The demographic information gathered on statistical predictors included age, sex, periodontal and peri-implantitis status, smoking, details of implants inserted, implant locations, placement time after extraction, use of simultaneous guided hard and soft tissue regeneration procedures, loading protocols, type of prosthesis, and treatment outcomes (implant survival and complications). Excluded were any implants that required flaps or simultaneous guided hard and soft tissue regeneration procedures, and implants narrower than 3.25 mm. Results: A total of 1,241 implants had been placed in 472 patients. Life table analysis indicated cumulative 5-year and 10-year implant survival rates of 97.9% and 96.5%, respectively. Most of the failed implants occurred in the posterior maxilla (54%) in type 4 bone (74.0%), and 55.0% of failed implants had been placed in smokers. Conclusion: Flapless dental implant surgery can yield an implant survival rate comparable to that reported in other studies using traditional flap techniques.

Quality of life and survival in patients treated with radical chemoradiation alone for oesophageal cancer

Aims: To report cancer-specific and health-related quality-of-life outcomes in patients undergoing radical chemoradiation (CRT) alone for oesophageal cancer. Materials and methods: Between 1998 and 2005, 56 patients with oesophageal cancer received definitive radical CRT, due to local disease extent, poor general health, or patient choice. Data from European Organization for Research and Treatment of Cancer quality-of-life questionnaires QLQ-30 and QLQ-OES24 were collected prospectively. Questionnaires were completed at diagnosis, and at 3, 6 and 12 months after CRT where applicable. Results: The median follow-up was 18 months. The median overall survival was 14 months, with a 51, 26 and 13% 1-, 3- and 5-year survival, respectively. At 12 months after treatment there was a significant improvement compared with before treatment with respect to dysphagia and pain. Global health scores were not significantly affected. Conclusions: Considering the relatively short long-term survival for this cohort of patients, maximising the quality of those final months should be very carefully borne in mind from the outset. The health-related quality-of-life data reported herein helps to establish benchmarks for larger evaluation within randomised clinical trials. © 2007 The Royal College of Radiologists.

Reduced Thrombospondin-1 at presentation predicts disease progression in superficial bladder cancer

Objectives: Superficial bladder cancer (SBC) presents a difficult clinical dilemma at diagnosis as only a small subgroup of patients will subsequently develop invasive disease. Study of cancer biology has found that angiogenesis is central to growth and spread. This study examines the relationship between the angiogenic inhibitory factor Thrombospondin-1 (TSP-1) at initial presentation and subsequent progression of SBC. Methods: Using immunohistochemistry, 220 cases of SBC were examined for pattern and extent of expression of TSP-1 at initial presentation. Results: TSP-1 was detected in perivascular tissue, at the epithelial-stromal junction, in the stroma and in tumour cells and reduced perivascular TSP-1 staining at presentation was an independent predictive factor for the subsequent development of muscle invasive or metastatic disease. Conclusion: This adds further weight to the theory that TSP-1 plays a major part in the biology of bladder cancer possibly through the control of angiogenesis. © 2002 Elsevier Science B.V. All rights reserved.