Neutrophil gelatinase-associated lipocalin (NGAL) an early-screening biomarker for ovarian cancer : NGAL is associated with epidermal growth factor-induced epithelio-mesenchymal transition

The expression of neutrophil gelatinase-associated lipocalin (NGAL) has been shown to be upregulated in ovarian cancer cells. In this study, we report that the expression of immunoreactive NGAL (irNGAL) in ovarian tumors changes with disease grade and that this change is reflected in the concentration of NGAL in peripheral blood. A total of 59 ovarian tissues including normal, benign, borderline malignant and grades 1, 2 and 3 malignant were analyzed using immunohistochemistry. irNGAL was not present in normal ovaries and the NGAL expression was weak to moderate in benign tissues. Both borderline and grade 1 tumors displayed the highest amount of NGAL expression with moderate to strong staining, whereas in grade 2 and 3 tumors, the extent of staining was significantly less (p < 0.01) and staining intensity was weak to moderate. Staining in all cases was confined to the epithelium. NGAL expression was analyzed by ELISA in 62 serum specimens from normal and different grades of cancer patients. Compared to control samples, the NGAL concentration was 2 and 2.6-fold higher in the serum of patients with benign tumors and cancer patients with grade 1 tumors (p < 0.05) and that result was consistent with the expression of NGAL performed by Western blot. NGAL expression was evaluated by Western blot in an immortalized normal ovarian cell line (IOSE29) as well as ovarian cancer cell lines. Moderate to strong expression of NGAL was observed in epithelial ovarian cancer cell lines SKOV3 and OVCA433 while no expression of NGAL was evident in normal IOSE29 and mesenchyme-like OVHS1, PEO.36 and HEY cell lines. NGAL expression was downregulated in ovarian cancer cell lines undergoing epithelio-mesenchymal transition (EMT) induced by epidermal growth factor (EGF). Down-regulation of NGAL expression correlated with the upregulation of vimentin expression, enhanced cell dispersion and downregulation of E-cadherin expression, some of the hallmarks of EMT. EGF-induced EMT phenotypes were inhibited in the presence of AG1478, an inhibitor of EGF receptor tyrosine kinase activity. These data indicate that NGAL may be a good marker to monitor changes of benign to premalignant and malignant ovarian tumors and that the molecule may be involved in the progression of epithelial ovarian malignancies.

Vimentin expression in cervical carcinomas : association with invasive and migratory potential

Vimentin is an intermediate filament protein normally expressed in mesenchymal cells, but evidence is accumulating in the literature which suggests that the aberrant expression of vimentin in epithelial cancer cells might be related to local invasiveness and metastatic potential. Vimentin expression has previously been associated with invasive properties in an in vitro model consisting of a set of HPV-33-transformed cervical keratinocyte cell lines. In the present study, in order to emphasize those in vitro findings, the expression of vimentin has been investigated in cervical neoplasms of different grades, using immunohistochemistry. A clear association is reported between vimentin expression and metastatic progression, since vimentin was detected in all invasive carcinomas and lymph node metastases, but not in CIN III lesions. These in vivo results are compared with present and previous data obtained in vitro on cervical keratinocyte cell lines, where vimentin expression also correlated with in vitro invasiveness.

A natural oil-based emulsion containing allantoin versus aqueous cream for managing radiation-induced skin reactions in patients with cancer : a phase III double-blind randomised controlled trial

Purpose To investigate the effects of a natural oil-based emulsion containing allantoin versus aqueous cream for preventing and managing radiation induced skin reactions (RISR). Methods and Materials A total of 174 patients were randomised and participated in the study. Patients either received Cream 1 (the natural oil-based emulsion containing allantoin) or Cream 2 (aqueous cream). Skin toxicity, pain, itching and skin-related quality of life scores were collected for up to four weeks after radiation treatment. Results Patients who received Cream 1 had a significantly lower average level of Common Toxicity Criteria at week 3 (p<0.05), but had statistically higher average levels of skin toxicity at weeks 7, 8 and 9 (all p<0.001). Similar results were observed when skin toxicity was analysed by grades. With regards to pain, patients in the Cream 2 group had a significantly higher average level of worst pain (p<0.05) and itching (p=0.046) compared to the Cream 1 group at week 3, however these differences were not observed at other weeks. In addition, there was a strong trend for Cream 2 to reduce the incidence of grade 2 or more skin toxicity in comparison to Cream 1 (p=0.056). Overall, more participants in the Cream 1 group were required to use another topical treatment at weeks 8 (p=0.049) and 9 (p=0.01). Conclusion The natural oil-based emulsion containing allantoin appears to have similar effects for managing skin toxicity compared to aqueous cream up to week 5, however, it becomes significantly less effective at later weeks into the radiation treatment and beyond treatment completion (week 6 and beyond). There were no major differences in pain, itching and skin-related quality of life. In light of these results, clinicians and patients can base their decision on costs and preferences. Overall, aqueous cream appears to be a more preferred option.

Biological performance of a polycaprolactone-based scaffold plus recombinant human morphogenetic protein-2 (rhBMP-2) in an ovine thoracic interbody fusion model

PURPOSE. We develop a sheep thoracic spine interbody fusion model to study the suitability of polycaprolactone-based scaffold and recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute within the thoracic spine. The surgical approach is a mini- open thoracotomy with relevance to minimally invasive deformity correction surgery for adolescent idiopathic scoliosis. To date there are no studies examining the use of this biodegradable implant in combination with biologics in a sheep thoracic spine model. METHODS. In the present study, six sheep underwent a 3-level (T6/7, T8/9 and T10/11) discectomy with randomly allocated implantation of a different graft substitute at each of the three levels; (i) calcium phosphate (CaP) coated polycaprolactone-based scaffold plus 0.54μg rhBMP-2, (ii) CaP coated PCL- based scaffold alone or (iii) autograft (mulched rib head). Fusion was assessed at six months post-surgery. RESULTS. Computed Tomographic scanning demonstrated higher fusion grades in the rhBMP-2 plus PCL- based scaffold group in comparison to either PCL-based scaffold alone or autograft. These results were supported by histological evaluations of the respective groups. Biomechanical testing revealed significantly higher stiffness for the rhBMP-2 plus PCL- based scaffold group in all loading directions in comparison to the other two groups. CONCLUSION. The results of this study demonstrate that rhBMP-2 plus PCL- based scaffold is a viable bone graft substitute, providing an optimal environment for thoracic interbody spinal fusion in a large animal model.

6 versus 12 month performance of polycaprolactone-based scaffold plus recombinant human morphogenetic protein-2 (rhBMP-2) in an ovine thoracic interbody fusion model

Introduction Well-designed biodegradable scaffolds in combination with bone growth factors offer a valuable alternative to the current gold standard autograft in spinal fusion surgery Yong et al. (2013). Here we report on 6- vs 12- month data set evaluating the longitudinal performance of a CaP coated polycaprolactone (PCL) scaffold loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute within a large preclinical animal model. Methods Twelve sheep underwent a 3-level (T6/7, T8/9 and T10/11) discectomy with randomly allocated implantation of a different graft substitute at each of the three levels; (i) calcium phosphate (CaP) coated polycaprolactone based scaffold plus 0.54µg rhBMP-2, (ii) CaP coated PCL- based scaffold alone or (iii) autograft (mulched rib head). Fusion assessments were performed via high resolution clinical computed tomography and histological evaluation were undertaken at six (n=6) and twelve (n=6) months post-surgery using the Sucato grading system (Sucato et al. 2004). Results The computed tomography fusion grades of the 6- and 12- months in the rhBMP-2 plus PCL- based scaffold group were 1.9 and 2.1 respectively, in the autograft group 1.9 and 1.3 respectively, and in the scaffold alone group 0.9 and 1.17 respectively. There were no statistically significant differences in the fusion scores between 6- and 12- month for the rhBMP plus PCL- based scaffold or PCL – based scaffold alone group however there was a significant reduction in scores in the autograft group. These scores were seen to correlate with histological evaluations of the respective groups. Conclusions The results of this study demonstrate the efficacy of scaffold-based delivery of rhBMP-2 in promoting higher fusion grades at 6- and 12- months in comparison to the scaffold alone or autograft group within the same time frame. Fusion grades achieved at six months using PCL+rhBMP-2 are not significantly increased at twelve months post-surgery.

Diophantine equations as a context for technology-enhanced training in conjecturing and proving

Solving indeterminate algebraic equations in integers is a classic topic in the mathematics curricula across grades. At the undergraduate level, the study of solutions of non-linear equations of this kind can be motivated by the use of technology. This article shows how the unity of geometric contextualization and spreadsheet-based amplification of this topic can provide a discovery experience for prospective secondary teachers and information technology students. Such experience can be extended to include a transition from a computationally driven conjecturing to a formal proof based on a number of simple yet useful techniques.

Intervertebral staple grading system with micro-CT

Introduction Intervertebral stapling is a leading method of fusionless scoliosis treatment which attempts to control growth by applying pressure to the convex side of a scoliotic curve in accordance with the Hueter-Volkmann principle. In addition to that, staples have the potential to damage surrounding bone during insertion and subsequent loading. The aim of this study was to assess the extent of bony structural damage including epiphyseal injury as a result of intervertebral stapling using an in vitro bovine model. Materials and Methods Thoracic spines from 6-8 week old calves were dissected and divided into motion segments including levels T4-T11 (n=14). Each segment was potted in polymethylemethacrylate. An Instron Biaxial materials testing machine with a custom made jig was used for testing. The segments were tested in flexion/extension, lateral bending and axial rotation at 37⁰C and 100% humidity, using moment control to a maximum 1.75 Nm with a loading rate of 0.3 Nm per second for 10 cycles. The segments were initially tested uninstrumented with data collected from the tenth load cycle. Next an anterolateral 4-prong Shape Memory Alloy (SMA) staple (Medtronic Sofamor Danek, USA) was inserted into each segment. Biomechanical testing was repeated as before. The staples were cut in half with a diamond saw and carefully removed. Micro-CT scans were performed and sagittal, transverse and coronal reformatted images were produced using ImageJ (NIH, USA).The specimens were divided into 3 grades (0, 1 and 2) according to the number of epiphyses damaged by the staple prongs. Results: There were 9 (65%) segments with grade 1 staple insertions and 5 (35%) segments with grade 2 insertions. There were no grade 0 staples. Grade 2 spines had a higher stiffness level than grade 1 spines, in all axes of movement, by 28% (p=0.004). This was most noted in flexion/extension with an increase of 49% (p=0.042), followed by non-significant change in lateral bending 19% (p=0.129) and axial rotation 8% (p=0.456) stiffness. The cross sectional area of bone destruction from the prongs was only 0.4% larger in the grade 2 group compared to the grade 1 group (p=0.961). Conclusion Intervertebral staples cause epiphyseal damage. There is a difference in stiffness between grade 1 and grade 2 staple insertion segments in flexion/extension only. There is no difference in the cross section of bone destruction as a result of prong insertion and segment motion.

Experimental investigation of post-fire mechanical properties of cold-formed steels

Cold-formed steel members are widely used in residential, industrial and commercial buildings as primary load-bearing elements. During fire events, they will be exposed to elevated temperatures. If the general appearance of the structure is satisfactory after a fire event then the question that has to be answered is how the load bearing capacity of cold-formed steel members in these buildings has been affected. Hence after such fire events there is a need to evaluate the residual strength of these members. However, the post-fire behaviour of cold-formed steel members has not been investigated in the past. This means conservative decisions are likely to be made in relation to fire exposed cold-formed steel buildings. Therefore an experimental study was undertaken to investigate the post-fire mechanical properties of cold-formed steels. Tensile coupons taken from cold-formed steel sheets of three different steel grades and thicknesses were exposed to different elevated temperatures up to 800 oC, and were then allowed to cool down to ambient temperature before they were tested to failure. Tensile coupon tests were conducted to obtain their post-fire stress-strain curves and associated mechanical properties (yield stress, Young’s modulus, ultimate strength and ductility). It was found that the post-fire mechanical properties of cold-formed steels are reduced below the original ambient temperature mechanical properties if they had been exposed to temperatures exceeding 300 oC. Hence a new set of equations is proposed to predict the post-fire mechanical properties of cold-formed steels. Such post-fire mechanical property assessments allow structural and fire engineers to make an accurate prediction of the safety of fire exposed cold-formed steel buildings. This paper presents the details of this experimental study and the results of post-fire mechanical properties of cold-formed steels. It also includes the results of a post-fire evaluation of cold-formed steel walls.

Sibling bullying perpetration: Associations with gender, grade, peer perpetration, trait anger, and moral disengagement

This study investigated bullying amongst siblings in both traditional and cyber forms, and the associations of gender, grade, peer bullying perpetration, trait anger and moral disengagement. The participants were 455 children in grades 5 to 12 (262 girls and 177 boys with 16 unknown gender) who had a sibling. As the number of siblings who only bullied by technology was low, these associations were not able to be calculated. However, the findings showed that the percentage of sibling traditional bullying perpetration (31.6%) was higher than peer bullying perpetration (9.8%). Sibling bullies reported engaging in complex behaviours of perpetration and victimisation in both the physical and in cyber settings, although the number was small. Gender, trait anger, moral disengagement and bullying peers at school (but not grade) were all significantly associated with sibling traditional bullying perpetration. The implications of the findings are discussed for bullying intervention and prevention programs to understand childhood bullying in diverse contexts.

An integrated modeling and risk analysis tool for mine water interactions

Poor mine water management can lead to corporate, environmental and social risks. These risks become more pronounced as mining operations move into areas of water scarcity and/or increase climatic variability while also managing increased demand, lower ore grades and increased strip ratios. Therefore, it is vital that mine sites better understand these risks in order to implement management practices to address them. Systems models provide an effective approach to understand complex networks, particularly across multiple scales. Previous work has represented mine water interactions using systems model on a mine site scale. Here, we expand on that work by present an integrated tool that uses a systems modeling approach to represent mine water interactions on a site and regional scale and then analyses the risks associated with events stemming from those interactions. A case study is presented to represent three indicative corporate, environmental and social risks associated with a mine site that exists in a water scarce region. The tool is generic and flexible, and can be used in many scenarios to provide significant potential utility to the mining industry.

UNICEF, Jakarta, Indonesia : Review of Satap Schools

A. Background and context 1. Education, particularly basic education (grades1-9), has been considered critical to promoting national economic growth and social well being1. Three factors that con-tribute to the above are: (i) Education increases human capital inherent in a labor force and thus increases productivity. It also increases capacity for working with others and builds community consensus to support national development. (ii) Education can in-crease the innovative capacity of a community to support social and economic growth—use of new technologies, products and services to promote growth and wellbeing. (iii) Education can facilitate knowledge transfer needed to understand the social and eco-nomic innovations and new processes, practices and values. Cognizant of the above benefits of education, the Millennium Development Goals (MDG) and the Education for All (EFA) declarations advocating universal basic education were formulated and ratified by UN member countries. 2. Achieving universal primary education (grade 6) may not be sufficient to maxim-ize the above noted socio-economic and cultural benefits. There is general consensus that basic literacy and numeracy up to grade 9 are essential foundational blocks for any good education system to support national development. Basic Education provides an educational achievement threshold that ensures the learning is retained. To achieve this, the donor partner led interventions and the UN declarations such as the MDG goals have sought universal access to basic education (grades 1-9). As many countries progress towards achieving the universal access targets, recent research evidence suggests that we need more than just access to basic education to impact on the na-tional development. Measuring basic education completion cycle, gross enrolment rate (GER) and participation rate etc., has to now include a focus on quality and relevance of the education2. 3. While the above research finding is generally accepted by the Government of In-donesia (GoI), unlike many other developing countries, Indonesia is geographically and linguistically complex and has the fourth largest education sector in the world. It has over 3000 islands, 17,000 ethnic groups and it takes as long as 7 hours to travel from east to west of the country and has multiple time differences. The education system has six years of primary education (grades 1-6), 3 years of junior secondary education (grades 7-9) and three years of senior secondary education (grades 10-12). Therefore, applying the findings of the above cited research in a country like Indonesia is a chal-lenge. Nevertheless, since the adoption of the National Education Law (2003)3 the GoI has made significant progress in improving access to and quality of basic education (grades 1-9). The 2011/12 national education statistics show the primary education (grades 1-6) completion rate was 99.3%, the net enrolment rate (NER) was 95.4% and the GER was 115.4%. This is a significant achievement considering the complexities faced within Indonesia. This increase in the primary education sub-sector, however, has not flowed onto the Junior Secondary School (JSS) education. The transition from pri-mary to JSS is still short of the GoI targets. In 2012, there were 146,826 primary schools feeding into 33,668 junior secondary schools. The transition rate from primary to secondary in 2011/12 was 78%. When considering district or sub-district level data the transition in poor districts could be less than the aggregated national rate. Poverty and lack of parents’ education, confounded by opportunity cost, are major obstacles to transitioning to JSS4. 4. Table 1 presents a summary of GoI initiatives to accelerate the transition to JSS. GoI, with assistance from the donor community, has built 2465 new regular JSS, mak-ing the total number of regular JSS 33,668. In addition, 57,825 new classrooms have been added to existing regular JSS. Also, in rural and remote areas 4136 Satu-Atap5 (SATAP) schools were built to increase access to JSS. These SATAP schools are the focus of this study as they provide education opportunities to the most marginalized, ru-ral, remote children who otherwise would not have access to JSS and consequently not complete basic education.

Experimental and numerical studies of fire exposed lipped channel columns subject to distortional buckling

Cold-formed steel sections are commonly used in low-rise commercial and residential buildings. During fire events, cold-formed steel structural elements in these buildings are exposed to elevated temperatures. Hence after such events there is a need to determine the residual strength of these structural elements. However, only limited information is available in relation to the residual strength of fire exposed cold-formed steel members. This research is aimed at investigating the residual distortional buckling capacities of fire exposed cold-formed steel lipped channel sections. A series of compression tests of fire exposed, short lipped channel columns made of varying steel grades and thicknesses was undertaken in this research. Test columns were exposed to different elevated temperatures up to 800 oC. They were then allowed to cool down at ambient temperature before they were tested to failure. Suitable finite element models of tested columns were also developed and validated using test results. The residual compression capacities of tested columns were predicted using the ambient temperature cold-formed steel design rules (AS/NZS 4600, AISI S100 and Direct Strength Method). Post-fire mechanical properties obtained from a previous study were used in this study. Comparison of results showed that ambient temperature design rules for compression members can be used to predict the residual compression capacities of fire exposed short or laterally restrained cold-formed steel columns provided the maximum temperature experienced by the columns can be estimated after a fire event. Such residual capacity assessments will allow structural and fire engineers to make an accurate prediction of the safety of buildings after fire events. This paper presents the details of these experimental and numerical studies and the results.

Fire performance and design of cold-formed steel wall systems

Traditionally, the fire resistance rating of Light gauge steel frame (LSF) wall systems is based on approximate prescriptive methods developed using limited fire tests. These fire tests are conducted using standard fire time-temperature curve given in ISO 834. However, in recent times fire has become a major disaster in buildings due to the increase in fire loads as a result of modern furniture and lightweight construction, which make use of thermoplastics materials, synthetic foams and fabrics. Therefore a detailed research study into the performance of load bearing LSF wall systems under both standard and realistic design fires on one side was undertaken to develop improved fire design rules. This study included both full scale fire tests and numerical studies of eight different LSF wall systems conducted for both the standard fire curve and the recently developed realistic design fire curves. The use of previous fire design rules developed for LSF walls subjected to non-uniform elevated temperature distributions based on AISI design manual and Eurocode 3 Parts 1.2 and 1.3 was investigated first. New simplified fire design rules based on AS/NZS 4600, North American Specification and Eurocode 3 Part 1.3 were then proposed with suitable allowances for the interaction effects of compression and bending actions. The importance of considering thermal bowing, magnified thermal bowing and neutral axis shift in the fire design was also investigated and their effects were included. A spread sheet based design tool was developed based on the new design rules to predict the failure load ratio versus time and temperature curves for varying LSF wall configurations. The accuracy of the proposed design rules was verified using the fire test and finite element analysis results for various wall configurations, steel grades, thicknesses and load ratios under both standard and realistic design fire conditions. A simplified method was also proposed to predict the fire resistance rating of LSF walls based on two sets of equations developed for the load ratio-hot flange temperature and the time-temperature relationships. This paper presents the details of this study on LSF wall systems under fire conditions and the results.

Fire performance of LSF wall panels using numerical parametric studies

Light Gauge Steel Framing (LSF) walls made of cold-formed and thin-walled steel lipped channel studs with plasterboard linings on both sides are commonly used in commercial, industrial and residential buildings. However, there is limited data about their structural and thermal performances under fire conditions. Recent research at the Queensland University of Technology has investigated the structural and thermal behaviour of load bearing LSF wall systems. In this research a series of full scale fire tests was conducted first to evaluate the performance of LSF wall systems with eight different wall configurations under standard fire conditions. Finite element models of LSF walls were then developed, analysed under transient and steady state conditions, and validated using full scale fire tests. This paper presents the details of an investigation into the fire performance of LSF wall panels based on an extensive finite element analysis based parametric study. The LSF wall panels with eight different plasterboard-insulation configurations were considered under standard fire conditions. Effects of varying steel grades, steel thicknesses, screw spacing, plasterboard restraint, insulation materials and load ratio on the fire performance of LSF walls were investigated and the results of extensive fire performance data are presented in the form of load ratio versus time and critical hot flange (failure) temperature curves.

Post-fire mechanical properties of cold-formed steels

Cold-formed steel members have been widely used in residential, industrial and commercial buildings as primary load-bearing and non-load bearing structural elements. These buildings must be properly evaluated after a fire event to assess the nature and extent of structural damage. If the general appearance of the structure is satisfactory after a fire event then the question that has to be answered is how the structural capacity of cold-formed steel members in these buildings has been affected. Elevated temperatures during a fire event affect the structural performance of cold-formed steel members even after cooling down to ambient temperature due to the possible detrimental changes in their mechanical properties. However, the post-fire behaviour of cold-formed steel members has not been investigated in the past and hence there is a need to investigate the post-fire mechanical properties of cold-formed steels. Therefore an experimental study was undertaken at the Queensland University of Technology to understand the residual mechanical properties of cold-formed steels after fire events. Tensile coupon tests were conducted on three different steel grades and thicknesses to obtain their stress-strain curves and relevant mechanical properties after cooling them down from different elevated temperatures. It was found that the post-fire mechanical properties of cold-formed steels are different to the original ambient temperature mechanical properties. Hence a new set of equations is proposed to predict the reduced mechanical properties of cold-formed steels after a fire event.