Distributed plasticity analysis of steel frame structures comprising non-compact sections

Application of 'advanced analysis' methods suitable for non-linear analysis and design of steel frame structures permits direct and accurate determination of ultimate system strengths, without resort to simplified elastic methods of analysis and semi-empirical specification equations. However, the application of advanced analysis methods has previously been restricted to steel frames comprising only compact sections that are not influenced by the effects of local buckling. A research project has been conducted with the aim of developing concentrated plasticity methods suitable for practical advanced analysis of steel frame structures comprising non-compact sections. A primary objective was to produce a comprehensive range of new distributed plasticity analytical benchmark solutions for verification of the concentrated plasticity methods. A distributed plasticity model was developed using shell finite elements to explicitly account for the effects of gradual yielding and spread of plasticity, initial geometric imperfections, residual stresses and local buckling deformations. The model was verified by comparison with large-scale steel frame test results and a variety of existing analytical benchmark solutions. This paper presents a description of the distributed plasticity model and details of the verification study.

Pseudo plastic zone analysis of steel frame structures comprising non-compact sections

Application of `advanced analysis' methods suitable for non-linear analysis and design of steel frame structures permits direct and accurate determination of ultimate system strengths, without resort to simplified elastic methods of analysis and semi-empirical specification equations. However, the application of advanced analysis methods has previously been restricted to steel frames comprising only compact sections that are not influenced by the effects of local buckling. A concentrated plasticity method suitable for practical advanced analysis of steel frame structures comprising non-compact sections is presented in this paper. The pseudo plastic zone method implicitly accounts for the effects of gradual cross-sectional yielding, longitudinal spread of plasticity, initial geometric imperfections, residual stresses, and local buckling. The accuracy and precision of the method for the analysis of steel frames comprising non-compact sections is established by comparison with a comprehensive range of analytical benchmark frame solutions. The pseudo plastic zone method is shown to be more accurate and precise than the conventional individual member design methods based on elastic analysis and specification equations.

Large-scale testing of steel frame structures comprising non-compact sections

Application of 'advanced analysis' methods suitable for non-linear analysis and design of steel frame structures permits direct and accurate determination of ultimate system strengths, without resort to simplified elastic methods of analysis and semi-empirical specification equations. However, the application of advanced analysis methods has previously been restricted to steel frames comprising only compact sections that are not influenced by the effects of local buckling. A research project has been conducted with the aim of developing concentrated plasticity methods suitable for practical advanced analysis of steel frame structures comprising non-compact sections. A series of large-scale tests were performed in order to provide experimental results for verification of the new analytical models. Each of the test frames comprised non-compact sections, and exhibited significant local buckling behaviour prior to failure. This paper presents details of the test program including the test specimens, set-up and instrumentation, procedure, and results.

2 Hour game jam at SLQ Garage Gamer - Live performance with crowd participation

The 2 hour game jam was performed as part of the State Library of Queensland 'Garage Gamer' series of events, summer 2013, at the SLQ exhibition. An aspect of the exhibition was the series of 'Level Up' game nights. We hosted the first of these - under the auspices of brIGDA, Game On. It was a party - but the focal point of the event was a live streamed 2 hour game jam. Game jams have become popular amongst the game development and design community in recent years, particularly with the growth of the Global Game Jam, a yearly event which brings thousands of game makers together across different sites in different countries. Other established jams take place on-line, for example the Ludum Dare challenge which as been running since 2002. Other challenges follow the same model in more intimate circumstances and it is now common to find institutions and groups holding their own small local game making jams. There are variations around the format, some jams are more competitive than others for example, but a common aspect is the creation of an intense creative crucible centred around team work and ‘accelerated game development’. Works (games) produced during these intense events often display more experimental qualities than those undertaken as commercial projects. In part this is because the typical jam is started with a conceptual design brief, perhaps a single word, or in the case of the specific game jam described in this paper, three words. Teams have to envision the challenge key word/s as a game design using whatever skills and technologies they can and produce a finished working game in the time given. Game jams thus provide design researchers with extraordinary fodder and recent years have also seen a number of projects which seek to illuminate the design process as seen in these events. For example, Gaydos, Harris and Martinez discuss the opportunity of the jam to expose students to principles of design process and design spaces (2011). Rouse muses on the game jam ‘as radical practice’ and a ‘corrective to game creation as it is normally practiced’. His observations about his own experience in a jam emphasise the same artistic endeavour forefronted earlier, where the experience is about creation that is divorced from the instrumental motivations of commercial game design (Rouse 2011) and where the focus is on process over product. Other participants remark on the social milieu of the event as a critical factor and the collaborative opportunity as a rich site to engage participants in design processes (Shin et al, 2012). Shin et al are particularly interested in the notion of the site of the process and the ramifications of participants being in the same location. They applaud the more localized event where there is an emphasis on local participation and collaboration. For other commentators, it is specifically the social experience in the place of the jam is the most important aspect (See Keogh 2011), not the material site but rather the physical embodied experience of ‘being there’ and being part of the event. Participants talk about game jams they have attended in a similar manner to those observations made by Dourish where the experience is layered on top of the physical space of the event (Dourish 2006). It is as if the event has taken on qualities of place where we find echoes of Tuan’s description of a particular site having an aura of history that makes it a very different place, redolent and evocative (Tuan 1977). The 2 hour game jam held during the SLQ Garage Gamer program was all about social experience.

Hepatitis C, mental health and equity of access to antiviral therapy : a systematic narrative review

Introduction Access to hepatitis C (hereafter HCV) antiviral therapy has commonly excluded populations with mental health and substance use disorders because they were considered as having contraindications to treatment, particularly due to the neuropsychiatric effects of interferon that can occur in some patients. In this review we examined access to HCV interferon antiviral therapy by populations with mental health and substance use problems to identify the evidence and reasons for exclusion. Methods We searched the following major electronic databases for relevant articles: PsycINFO, Medline, CINAHL, Scopus, Google Scholar. The inclusion criteria comprised studies of adults aged 18 years and older, peer-reviewed articles, date range of (2002--2012) to include articles since the introduction of pegylated interferon with ribarvirin, and English language. The exclusion criteria included articles about HCV populations with medical co-morbidities, such as hepatitis B (hereafter HBV) and human immunodeficiency virus (hereafter HIV), because the clinical treatment, pathways and psychosocial morbidity differ from populations with only HCV. We identified 182 articles, and of these 13 met the eligibility criteria. Using an approach of systematic narrative review we identified major themes in the literature. Results Three main themes were identified including: (1) pre-treatment and preparation for antiviral therapy, (2) adherence and treatment completion, and (3) clinical outcomes. Each of these themes was critically discussed in terms of access by patients with mental health and substance use co-morbidities demonstrating that current research evidence clearly demonstrates that people with HCV, mental health and substance use co-morbidities have similar clinical outcomes to those without these co-morbidities. Conclusions While research evidence is largely supportive of increased access to interferon by people with HCV, mental health and substance use co-morbidities, there is substantial further work required to translate evidence into clinical practice. Further to this, we conclude that a reconsideration of the appropriateness of the tertiary health service model of care for interferon management is required and exploration of the potential for increased HCV care in primary health care settings.

Monitoring style drift : evidence from U.S. Equity funds

This thesis examines the stewardship and investment style monitoring by managers and boards of U.S. equity funds. Results indicate that complying with a fund’s declared style, especially in value-growth dimension, remains a challenge for fund managers and boards, and that style-based investors should be aware of the risk of style drift since fund managers and boards do not always monitor the fund’s investment style as stated in the prospectus. Results also show that the quality of fund stewardship, as reflected by fund board quality, corporate culture, manager compensation, regulatory history, and fees are effective in ensuring that fund managers and boards perform their fiduciary obligation by increasing monitoring of the fund investment style.

Surgical resection for non-small cell lung cancer : clinical features and outcomes for a consecutive series at an Irish tertiary referral centre

Background: Few patients diagnosed with lung cancer are still alive 5 years after diagnosis. The aim of the current study was to conduct a 10-year review of a consecutive series of patients undergoing curative-intent surgical resection at the largest tertiary referral centre to identify prognostic factors. Methods: Case records of all patients operated on for lung cancer between 1998 and 2008 were reviewed. The clinical features and outcomes of all patients with non-small cell lung cancer (NSCLC) stage I-IV were recorded. Results: A total of 654 patients underwent surgical resection with curative intent during the study period. Median overall survival for the entire cohort was 37 months. The median age at operation was 66 years, with males accounting for 62.7 %. Squamous cell type was the most common histological subtype, and lobectomies were performed in 76.5 % of surgical resections. Pneumonectomy rates decreased significantly in the latter half of the study (25 vs. 16.3 %), while sub-anatomical resection more than doubled (2 vs. 5 %) (p < 0.005). Clinico-pathological characteristics associated with improved survival by univariate analysis include younger age, female sex, smaller tumour size, smoking status, lobectomy, lower T and N status and less advanced pathological stage. Age, gender, smoking status and tumour size, as well as T and N descriptors have emerged as independent prognostic factors by multivariate analysis. Conclusion: We identified several factors that predicted outcome for NSCLC patients undergoing curative-intent surgical resection. Survival rates in our series are comparable to those reported from other thoracic surgery centres. © 2012 Royal Academy of Medicine in Ireland.

Designing for participation in local suburban communications

People have difficulty accessing means to easily publicise and discuss their ideas and concerns with their local community. The aim of this research has been to design and evaluate capacity for Internet technologies coupled with public displays to engage a diverse range of community members in the making of a shared local suburban communications network. The research problem relates to the challenges of community building, in particular discovering mechanisms that work to engage a target community and motivate participation. In an effort to understand genuine participation and barriers to use, the study was embedded in a local community and purposely longitudinal. This research contributes knowledge about the limitations of public displays to increase visibility of local communications, the need for long-term and networked visibility of community-building communications, the integral role of community facilitators, and the challenges of sustaining shared communications.

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.

Epigenetics underpinning the regulation of the CXC (ELR+) chemokines in non-small cell lung cancer

Background: Angiogenesis may play a role in the pathogenesis of Non-Small Cell Lung cancer (NSCLC). The CXC (ELR+) chemokine family are powerful promoters of the angiogenic response. Methods: The expression of the CXC (ELR+) family members (CXCL1-3/GROα-γ, CXCL8/IL-8, CXCR1/2) was examined in a series of resected fresh frozen NSCLC tumours. Additionally, the expression and epigenetic regulation of these chemokines was examined in normal bronchial epithelial and NSCLC cell lines. Results: Overall, expression of the chemokine ligands (CXCL1, 2, 8) and their receptors (CXCR1/2) were down regulated in tumour samples compared with normal, with the exception of CXCL3. CXCL8 and CXCR1/2 were found to be epigenetically regulated by histone post-translational modifications. Recombinant CXCL8 did not stimulate cell growth in either a normal bronchial epithelial or a squamous carcinoma cell line (SKMES-1). However, an increase was observed at 72 hours post treatment in an adenocarcinoma cell line. Conclusions: CXC (ELR+) chemokines are dysregulated in NSCLC. The balance of these chemokines may be critical in the tumour microenvironment and requires further elucidation. It remains to be seen if epigenetic targeting of these pathways is a viable therapeutic option in lung cancer treatment. © 2011 Baird et al.

IL-23 is pro-proliferative, epigenetically regulated and modulated by chemotherapy in non-small cell lung cancer

Background IL-23 is a member of the IL-6 super-family and plays key roles in cancer. Very little is currently known about the role of IL-23 in non-small cell lung cancer (NSCLC). Methods RT-PCR and chromatin immunopreciptiation (ChIP) were used to examine the levels, epigenetic regulation and effects of various drugs (DNA methyltransferase inhibitors, Histone Deacetylase inhibitors and Gemcitabine) on IL-23 expression in NSCLC cells and macrophages. The effects of recombinant IL-23 protein on cellular proliferation were examined by MTT assay. Statistical analysis consisted of Student's t-test or one way analysis of variance (ANOVA) where groups in the experiment were three or more. Results In a cohort of primary non-small cell lung cancer (NSCLC) tumours, IL-23A expression was significantly elevated in patient tumour samples (p<0.05). IL-23A expression is epigenetically regulated through histone post-translational modifications and DNA CpG methylation. Gemcitabine, a chemotherapy drug indicated for first-line treatment of NSCLC also induced IL-23A expression. Recombinant IL-23 significantly increased cellular proliferation in NSCLC cell lines. Conclusions These results may therefore have important implications for treating NSCLC patients with either epigenetic targeted therapies or Gemcitabine. © 2012 Elsevier Ireland Ltd.

Phase III study of matrix metalloproteinase inhibitor prinomastat in non-small-cell lung cancer

Purpose: Matrix metalloproteinases (MMPs) degrade extracellular proteins and facilitate tumor growth, invasion, metastasis, and angiogenesis. This trial was undertaken to determine the effect of prinomastat, an inhibitor of selected MMPs, on the survival of patients with advanced non-small-cell lung cancer (NSCLC), when given in combination with gemcitabine-cisplatin chemotherapy. Patients and Methods: Chemotherapy-naive patients were randomly assigned to receive prinomastat 15 mg or placebo twice daily orally continuously, in combination with gemcitabine 1,250 mg/m2 days 1 and 8 plus cisplatin 75 mg/m2 day 1, every 21 days for up to six cycles. The planned sample size was 420 patients. Results: Study results at an interim analysis and lack of efficacy in another phase III trial prompted early closure of this study. There were 362 patients randomized (181 on prinomastat and 181 on placebo). One hundred thirty-four patients had stage IIIB disease with T4 primary tumor, 193 had stage IV disease, and 34 had recurrent disease (one enrolled patient was ineligible with stage IIIA disease). Overall response rates for the two treatment arms were similar (27% for prinomastat v 26% for placebo; P = .81). There was no difference in overall survival or time to progression; for prinomastat versus placebo patients, the median overall survival times were 11.5 versus 10.8 months (P = .82), 1-year survival rates were 43% v 38% (P = .45), and progression-free survival times were 6.1 v 5.5 months (P = .11), respectively. The toxicities of prinomastat were arthralgia, stiffness, and joint swelling. Treatment interruption was required in 38% of prinomastat patients and 12% of placebo patients. Conclusion: Prinomastat does not improve the outcome of chemotherapy in advanced NSCLC. © 2005 by American Society of Clinical Oncology.

A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/ cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer : a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1)

Background: Phase III studies suggest that non-small-cell lung cancer (NSCLC) patients treated with cisplatin-docetaxel may have higher response rates and better survival compared with other platinum-based regimens. We report the final results of a randomised phase III study of docetaxel and carboplatin versus MIC or MVP in patients with advanced NSCLC. Patients and methods: Patients with biopsy proven stage III-IV NSCLC not suitable for curative surgery or radiotherapy were randomised to receive four cycles of either DCb (docetaxel 75 mg/m 2, carboplatin AUC 6), or MIC/MVP (mitomycin 6 mg/m 2, ifosfamide 3 g/m 2 and cisplatin 50 mg/m 2 or mitomycin 6 mg/ m 2, vinblastine 6 mg/m 2 and cisplatin 50 mg/m 2, respectively), 3 weekly. The primary end point was survival, secondary end points included response rates, toxicity and quality of life. Results: The median follow-up was 17.4 months. Overall response rate was 32% for both arms (partial response = 31%, complete response = 1%); 32% of MIC/MVP and 26% of DCb patients had stable disease. One-year survival was 39% and 35% for DCb and MIC/MVP, respectively. Two-year survival was 13% with both arms. Grade 3/4 neutropenia (74% versus 43%, P < 0.005), infection (18% versus 9%, P = 0.01) and mucositis (5% versus 1%, P = 0.02) were more common with DCb than MIC/MVP. The MIC/MVP arm had significant worsening in overall EORTC score and global health status whereas the DCb arm showed no significant change. Conclusions: The combination of DCb had similar efficacy to MIC/MVP but quality of life was better maintained. © 2006 European Society for Medical Oncology.

Equity and Trusts in Principle [3rd ed.]

Equity and Trusts : in Principle, 3rd edition is updated and revised throughout. It addresses the principles of equity and trusts and provides a clear analysis of this area.