Weekly cisplatin concurrently with radiotherapy in head and neck squamous cell cancer : a retrospective analysis of a tertiary institute experience

Radiotherapy combined with three weekly 100 mg/m2 of cisplatin is the accepted standard of care in head and neck squamous cell carcinoma. However, this regimen is associated with severe toxicities with devastating effects on patients. Alternative protocols like weekly 40 mg/m2 have been used in an attempt to reduce toxicities. The main objective of the present study is to identify the dose intensities and toxicities of weekly cisplatin in patients treated in a tertiary centre over a 12 month period. Included patients had squamous cell carcinoma arising in the oral cavity, oropharynx, larynx, or hypopharynx. Patients were excluded if they had nasopharyngeal squamous cell carcinoma, distant metastasis or if they had prior treatment for head and neck cancer excluding neck dissection. During the study period, 52 patients met the inclusion criteria and their data were retrospectively obtained from the patients' database of St James hospital, Dublin. The median age of the study cohort was 54 years (range 33-73). Of the patients, 40 (76.9 %) were male and 12 (20.1 %) were female. The primary tumour sites were as follows: oral cavity and oropharynx in 38 (73 %), larynx in 10 (19 %), and hypopharynx in 4 (8 %). In total, 33 (63.5 %) patients had stage IV disease, while 19 (36.5 %) had stage III disease. Treatment was definitive in 35 (67 %) patients and adjuvant in 17 (35 %). Full-dose radiotherapy was achieved in 50 (96 %) patients. Only 22 (42.3 %) patients completed the intended six cycles of chemotherapy. Cumulative dose of 200 mg/m2 or more was reached in 37 (71 %) patients. The acute adverse effects included grades 3 and 4 mucositis, which occurred in 22 (43.3 %) and 6 patients (12 %), respectively. Grade 3 and 4 neutropenia occurred in six (11.5 %) and three (5.7 %) patients, respectively. The only other haematological toxicity was grade 3 anaemia in 20 (38.4 %) patients. There was no grade 3 or 4 renal toxicity among the study cohort, although grade 2 was observed in six (11.5 %) patients. Death occurred in one patient due to neutropenic septicaemia. In conclusion, weekly cisplatin is associated with moderate to severe toxicities and might lead to suboptimal chemotherapy delivery. More prospective clinical studies are required to determine the optimal chemoradiation regimen in head and neck squamous cell carcinoma.

Meta-analysis of individual patient data from randomized trials of chemotherapy plus cetuximab as first-line treatment for advanced non-small cell lung cancer

OBJECTIVES: Four randomized phase II/III trials investigated the addition of cetuximab to platinum-based, first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). A meta-analysis was performed to examine the benefit/risk ratio for the addition of cetuximab to chemotherapy. MATERIALS AND METHODS: The meta-analysis included individual patient efficacy data from 2018 patients and individual patient safety data from 1970 patients comprising respectively the combined intention-to-treat and safety populations of the four trials. The effect of adding cetuximab to chemotherapy was measured by hazard ratios (HRs) obtained using a Cox proportional hazards model and odds ratios calculated by logistic regression. Survival rates at 1 year were calculated. All applied models were stratified by trial. Tests on heterogeneity of treatment effects across the trials and sensitivity analyses were performed for all endpoints. RESULTS: The meta-analysis demonstrated that the addition of cetuximab to chemotherapy significantly improved overall survival (HR 0.88, p=0.009, median 10.3 vs 9.4 months), progression-free survival (HR 0.90, p=0.045, median 4.7 vs 4.5 months) and response (odds ratio 1.46, p<0.001, overall response rate 32.2% vs 24.4%) compared with chemotherapy alone. The safety profile of chemotherapy plus cetuximab in the meta-analysis population was confirmed as manageable. Neither trials nor patient subgroups defined by key baseline characteristics showed significant heterogeneity for any endpoint. CONCLUSION: The addition of cetuximab to platinum-based, first-line chemotherapy for advanced NSCLC significantly improved outcome for all efficacy endpoints with an acceptable safety profile, indicating a favorable benefit/risk ratio.

Global analysis of serum microRNAs as potential biomarkers for lung adenocarcinoma

Early diagnosis and the ability to predict the most relevant treatment option for individuals is essential to improve clinical outcomes for non-small cell lung cancer (NSCLC) patients. Adenocarcinoma (ADC), a subtype of NSCLC, is the single biggest cancer killer and therefore an urgent need to identify minimally invasive biomarkers to enable early diagnosis. Recent studies, by ourselves and others, indicate that circulating miRNA s have potential as biomarkers. Here we applied global profiling approaches in serum from patients with ADC of the lung to explore if miRNA s have potential as diagnostic biomarkers. This study involved RNA isolation from 80 sera specimens including those from ADC patients (equal numbers of stages 1, 2, 3, and 4) and age- and gender-matched controls (n = 40 each). Six hundred and sixty-seven miRNA s were co-analyzed in these specimens using TaqMan low density arrays and qPCR validation using individual miRNA s. Overall, approximately 390 and 370 miRNA s were detected in ADC and control sera, respectively. A group of 6 miRNA s, miR-30c-1* (AU C = 0.74; P < 0.002), miR-616(AU C = 0.71; P = 0.001), miR-146b-3p (AU C = 0.82; P < 0.0001), miR-566 (AU C = 0.80; P < 0.0001), miR-550 (AU C = 0.72; P = 0.0006), and miR-939 (AU C = 0.82; P < 0.0001) was found to be present at substantially higher levels in ADC compared with control sera. Conversely, miR-339-5p and miR-656 were detected at substantially lower levels in ADC sera (co-analysis resulting in AU C = 0.6; P = 0.02). Differences in miRNA profile identified support circulating miRNA s having potential as diagnostic biomarkers for ADC. More extensive studies of ADC and control serum specimens are warranted to independently validate the potential clinical relevance of these miRNA s as minimally invasive biomarkers for ADC.

Blast response and failure analysis of pile foundations subjected to surface explosion

This paper presents the response of pile foundations to ground shocks induced by surface explosion using fully coupled and non-linear dynamic computer simulation techniques together with different material models for the explosive, air, soil and pile. It uses the Arbitrary Lagrange Euler coupling formulation with proper state material parameters and equations. Blast wave propagation in soil, horizontal pile deformation and pile damage are presented to facilitate failure evaluation of piles. Effects of end restraint of pile head and the number and spacing of piles within a group on their blast response and potential failure are investigated. The techniques developed and applied in this paper and its findings provide valuable information on the blast response and failure evaluation of piles and will provide guidance in their future analysis and design.

Vulnerability and damage analysis of reinforced concrete framed buildings subjected to near field blast events

Terrorists usually target high occupancy iconic and public buildings using vehicle borne incendiary devices in order to claim a maximum number of lives and cause extensive damage to public property. While initial casualties are due to direct shock by the explosion, collapse of structural elements may extensively increase the total figure. Most of these buildings have been or are built without consideration of their vulnerability to such events. Therefore, the vulnerability and residual capacity assessment of buildings to deliberately exploded bombs is important to provide mitigation strategies to protect the buildings' occupants and the property. Explosive loads and their effects on a building have therefore attracted significant attention in the recent past. Comprehensive and economical design strategies must be developed for future construction. This research investigates the response and damage of reinforced concrete (RC) framed buildings together with their load bearing key structural components to a near field blast event. Finite element method (FEM) based analysis was used to investigate the structural framing system and components for global stability, followed by a rigorous analysis of key structural components for damage evaluation using the codes SAP2000 and LS DYNA respectively. The research involved four important areas in structural engineering. They are blast load determination, numerical modelling with FEM techniques, material performance under high strain rate and non-linear dynamic structural analysis. The response and damage of a RC framed building for different blast load scenarios were investigated. The blast influence region for a two dimensional RC frame was investigated for different load conditions and identified the critical region for each loading case. Two types of design methods are recommended for RC columns to provide superior residual capacities. They are RC columns detailing with multi-layer steel reinforcement cages and a composite columns including a central structural steel core. These are to provide post blast gravity load resisting capacity compared to typical RC column against a catastrophic collapse. Overall, this research broadens the current knowledge of blast and residual capacity analysis of RC framed structures and recommends methods to evaluate and mitigate blast impact on key elements of multi-storey buildings.

Analysis of traffic injury severity in Dhaka, Bangladesh

This research identifies roadway, traffic, and environmental factors that influence the injury severity of road traffic crashes in Dhaka. Dhaka provides a rather unusual driving risk environment to study, since virtually anyone can obtain a drivers’ license and very little traffic enforcement and fines are given when drivers violate traffic rules. To examine this city with presumed heightened crash severity risk, police reported crash data from 2007 to 2011 containing about 2714 road traffic crashes were collected. The injury severity of traffic crashes—recorded as either fatal, serious injury, or property damage only—were modeled using an ordered Probit model. Significant factors increasing the probability of fatal injuries include crashes along highways (65%), absence of a road divider (80%), crashes during night time (54%), and vehicle-pedestrian collisions (367%); whereas two-way traffic configuration (21%), and traffic police controlled schemes (41%) decrease the probability of fatalities. Both similarities and differences of the findings between crash risk in Dhaka and developed countries are discussed in policy relevant terms.

Sectional analysis of the pollutant wash-off process based on runoff hydrograph

The validity of using rainfall characteristics as lumped parameters for investigating the pollutant wash-off process such as first flush occurrence is questionable. This research study introduces an innovative concept of using sector parameters to investigate the relationship between the pollutant wash-off process and different sectors of the runoff hydrograph and rainfall hyetograph. The research outcomes indicated that rainfall depth and rainfall intensity are two key rainfall characteristics which influence the wash-off process compared to the antecedent dry period. Additionally, the rainfall pattern also plays a critical role in the wash-off process and is independent of the catchment characteristics. The knowledge created through this research study provides the ability to select appropriate rainfall events for stormwater quality treatment design based on the required treatment outcomes such as the need to target different sectors of the runoff hydrograph or pollutant species. The study outcomes can also contribute to enhancing stormwater quality modelling and prediction in view of the fact that conventional approaches to stormwater quality estimation is primarily based on rainfall intensity rather than considering other rainfall parameters or solely based on stochastic approaches irrespective of the characteristics of the rainfall event.

Multifunctional agriculture in policy and practice? A comparative analysis of Norway and Australia

Ideals of productivist agriculture in the Western world have faded as the unintended consequences of intensive agriculture and pastoralism have contributed to rural decline and environmental problems. In Norway and Australia, there has been an increasing acceptance of the equal importance of social and environmental sustainability as well as economic sustainability. Alongside this shift is a belief that primary production needs to move away from an intensive, productivist-based agriculture to one that may be defined as post-productivist. In this paper, we argue that the dualism of productivism and post-productivism as concepts on agricultural policy regimes are too simplistic and discuss whether multifunctional agriculture is a better concept for a comparison of rural primary production at two extreme points of the scale, the market-oriented, liberalistic Australian agriculture and the market-protected small-scale Norwegian agriculture. We argue that multifunctionality in Australia rates relatively weakly as an ideology or policy and even less as a discourse or practice and hence is situated toward a ‘weak’ end of a continuum of a level of multifunctional agriculture. In Norwegian agriculture, multifunctional agriculture has thrived within a protectionist setting with the support of the public, the state and agricultural actors. In this sense it is very clearly a policy, practice and discourse that aims to preserve and conserve rural spaces, the cultural landscape, the farming way of life and food safety. Norway is as such situated toward a ‘strong’ end of a continuum of a level of multifunctional agriculture.

Assessing the discipline : an analysis of Australian journalism review articles 2000-2010

In recent years, there has been much discussion about the quality of research published by Australian journalism academics, without much empirical evidence about what kind of work the field actually engages in. This paper attempts to map the relatively young field of Australian journalism research by presenting the results of a comprehensive meta-analysis of articles published in the Australian Journalism Review between 2000 and 2010. Our findings show that, contrary to evidence elsewhere, a gender balance exists in terms of absolute numbers of authors, although a "glass-ceiling effect" is still discernible. Queensland universities dominate the publications, and most studies employ qualitative rather than quantitative methods. Journalism education is the most popular topic, yet a large variety of topics are evident overall. Despite a heavy focus on Australia, and to a smaller extent New Zealand, the journal also displays a sizeable international touch.

Representations of foreign places outside the news : an analysis of Australian newspaper travel sections

Despite continued growth over recent decades, travel journalism has so far gained little attention in journalism research, with scholars often ridiculing it and other forms of lifestyle journalism as not being real journalism. This paper aims to the shift the focus by arguing that non-news journalism is increasingly important as a site for research. It reports the results from a content analysis of Australian newspaper travel sections and examines the role they play in mediating foreign places. The results demonstrate that travel stories can be mostly classed as service stories in that they focus on destinations which are already popular with Australians. At the same time they report very little about local cultures at the destinations, demonstrating a focus on the tourist experience and a missed opportunity for improving inter-cultural understanding. A visual analysis of photographs shows stereotypical portrayals of destinations broadly in line with tourism promotion materials.

Formal analysis of security properties in trusted computing protocols

This research introduces a general methodology in order to create a Coloured Petri Net (CPN) model of a security protocol. Then standard or user-defined security properties of the created CPN model are identified. After adding an attacker model to the protocol model, the security property is verified using state space method. This approach is applied to analyse a number of trusted computing protocols. The results show the applicability of proposed method to analyse both standard and user-defined properties.

The tertiary debate : a case study analysis of factors considered when applying for university entry by traditional age school leavers in Brisbane

Many interacting factors contribute to a student's choice of a university. This study takes a systems perspective of the choice and develops a Bayesian Network to represent and quantify these factors and their interactions. The systems model is illustrated through a small study of traditional school leavers in Australia, and highlights similarities and differences between universities' perceptions of student choices, students' perceptions of factors that they should consider and how students really make choices. The study shows the range of information that can be gained from this approach, including identification of important factors and scenario assessment.

Observability analysis of electric networks considering branch impedance

This paper presents an analytical method to analyze the effect of X to R ratio as well as impedance value of branches on observability of a network based on un-decoupled formulation of state estimation (SE) and null space of matrices. The results showed that the X to R ratio of branches had no effect on the observability of networks. In addition, it was shown that observability of some networks was affected by impedance values while some others were not affected. In addition, for branch observability analysis of radial network, a simple and quick method is developed. Illustrative examples of the network under transmission and distribution voltages demonstrate the effectiveness of the proposed methods.

New suburbs in the making? Locating master planned estates in a comparative analysis of suburbs in South-East Queensland

In urban scholarship Master Planned Estates (MPEs) are viewed as illustrative of broader changes to the urban environment and characterised as homogenous, affluent enclaves where community life is largely orchestrated by the developer. Yet no study has fully considered if, and to what extent, MPEs can be distinguished from other suburb types in terms of their residential composition and their levels of sociability and community attachment. In this article, we empirically test if MPEs are different from ‘conventional’ suburbs by examining them structurally in terms of their demographic and socio-economic characteristics, as well as in terms of their key community social processes. Using data from a 2008 study of 148 suburbs across Brisbane, Australia (which includes data from two MPEs), we undertake a comparative analysis of suburbs and examine the density of neighbour networks, residents' reports of place attachment and cohesion and neighbourly contact in MPEs compared to other residential suburbs. Our findings suggest that MPEs are not distinct in terms of their degree of homogeneity and socio-economic characteristics, but that connections among residents are lower than other suburbs despite—or perhaps because of—the active interventions of the developer.