Gene transfer vectors targeted to human prostate cancer : do we need better preclinical testing systems?

Destruction of cancer cells by genetically modified viral and nonviral vectors has been the aim of many research programs. The ability to target cytotoxic gene therapies to the cells of interest is an essential prerequisite, and the treatment has always had the potential to provide better and more long-lasting therapy than existing chemotherapies. However, the potency of these infectious agents requires effective testing systems, in which hypotheses can be explored both in vitro and in vivo before the establishment of clinical trials in humans. The real prospect of off-target effects should be eliminated in the preclinical stage, if current prejudices against such therapies are to be overcome. In this review we have set out, using adenoviral vectors as a commonly used example, to discuss some of the key parameters required to develop more effective testing, and to critically assess the current cellular models for the development and testing of prostate cancer biotherapy. Only by developing models that more closely mirror human tissues will we be able to translate literature publications into clinical trials and hence into acceptable alternative treatments for the most commonly diagnosed cancer in humans.

Experimental studies of the shear behavior and strength of LiteSteel beams with stiffened web openings

Abstract: LiteSteel beam (LSB) is a new cold-formed steel hollow flange channel section produced using a patented manufacturing process. It is commonly used as flexural members in residential, industrial and commercial buildings. Current practice in flooring systems is to include openings in the web element of floor joists or bearers so that building services can be located within them. Test results have shown that the shear capacity of LSBs can be reduced considerably by the inclusion of web openings. A cost effective method of eliminating the detrimental effects of a large web opening is to attach suitable stiffeners around the web openings of LSBs. A detailed experimental study consisting of 17 shear tests was therefore undertaken to investigate the shear behaviour and strength of LSBs with stiffened circular web openings. Both plate and stud stiffeners with varying sizes and thicknesses were attached to the web elements of LSBs using a number of screw-fastening arrangements in order to develop a suitable stiffening arrangement for LSBs. Simply supported test specimens of LSBs with an aspect ratio of 1.5 were loaded at mid-span until failure. This paper presents the details of this experimental study of LSBs with stiffened web openings, and the results of their shear capacities and associated behavioural characteristics. Suitable screw-fastened plate stiffener arrangements have been recommended in order to restore the original shear capacity of LSBs.

Suitable stiffening systems for LiteSteel beams with web openings subjected to shear

Abstract: LiteSteel beam (LSB) is a new cold-formed steel hollow flange channel section produced using a simultaneous cold-forming and dual electric resistance welding process. It is commonly used as floor joists and bearers with web openings in residential, industrial and commercial buildings. Their shear strengths are considerably reduced when web openings are included for the purpose of locating building services. A cost effective method of eliminating the detrimental effects of a large web opening is to attach suitable stiffeners around the web openings of LSBs. Experimental and numerical studies were undertaken to investigate the shear behaviour and strength of LSBs with circular web openings reinforced using plate, stud, transverse and sleeve stiffeners with varying sizes and thicknesses. Both welding and varying screw-fastening arrangements were used to attach these stiffeners to the web of LSBs. Finite element models of LSBs with stiffened web openings in shear were developed to simulate their shear behaviour and strength of LSBs. They were then validated by comparing the results with experimental test results and used in a detailed parametric study. These studies have shown that plate stiffeners were the most suitable, however, their use based on the current American standards was found to be inadequate. Suitable screw-fastened plate stiffener arrangements with optimum thicknesses have been proposed for LSBs with web openings to restore their original shear capacity. This paper presents the details of the numerical study and the results.

An analytical method for assessing stage-specific drug activity in Plasmodium vivax malaria : implications for ex vivo drug susceptibility testing

The emergence of highly chloroquine (CQ) resistant P. vivax in Southeast Asia has created an urgent need for an improved understanding of the mechanisms of drug resistance in these parasites, the development of robust tools for defining the spread of resistance, and the discovery of new antimalarial agents. The ex vivo Schizont Maturation Test (SMT), originally developed for the study of P. falciparum, has been modified for P. vivax. We retrospectively analysed the results from 760 parasite isolates assessed by the modified SMT to investigate the relationship between parasite growth dynamics and parasite susceptibility to antimalarial drugs. Previous observations of the stage-specific activity of CQ against P. vivax were confirmed, and shown to have profound consequences for interpretation of the assay. Using a nonlinear model we show increased duration of the assay and a higher proportion of ring stages in the initial blood sample were associated with decreased effective concentration (EC50) values of CQ, and identify a threshold where these associations no longer hold. Thus, starting composition of parasites in the SMT and duration of the assay can have a profound effect on the calculated EC50 for CQ. Our findings indicate that EC50 values from assays with a duration less than 34 hours do not truly reflect the sensitivity of the parasite to CQ, nor an assay where the proportion of ring stage parasites at the start of the assay does not exceed 66%. Application of this threshold modelling approach suggests that similar issues may occur for susceptibility testing of amodiaquine and mefloquine. The statistical methodology which has been developed also provides a novel means of detecting stage-specific drug activity for new antimalarials.

WebPut : Efficient web-based data imputation

In this paper, we present WebPut, a prototype system that adopts a novel web-based approach to the data imputation problem. Towards this, Webput utilizes the available information in an incomplete database in conjunction with the data consistency principle. Moreover, WebPut extends effective Information Extraction (IE) methods for the purpose of formulating web search queries that are capable of effectively retrieving missing values with high accuracy. WebPut employs a confidence-based scheme that efficiently leverages our suite of data imputation queries to automatically select the most effective imputation query for each missing value. A greedy iterative algorithm is also proposed to schedule the imputation order of the different missing values in a database, and in turn the issuing of their corresponding imputation queries, for improving the accuracy and efficiency of WebPut. Experiments based on several real-world data collections demonstrate that WebPut outperforms existing approaches.

Are academics messy? Testing the broken windows theory with a field experiment in the work environment

We test the broken windows theory using a field experiment in a shared area of an academic workplace(the department common room). More specifically, we explore academics’ and postgraduate students’ behavior under an order condition (a clean environment) and a disorder condition (a messy environment). We find strong evidence that signs of disorderly behavior trigger littering: In 59% of the cases, subjects litter in the disorder treatment as compared to 18% in the order condition. These results remain robust in a multivariate analysis even when controlling for a large set of factors not directly examined by previous studies. Overall, when academic staff and postgraduate students observe that others have violated the social norm of keeping the common room clean, all else being equal, the probability of littering increases by around 40%.

Development and interrater reliability testing of a telephone interview training programme for Australian nurse interviewers

Summary Background The final phase of a three phase study analysing the implementation and impact of the nurse practitioner role in Australia (the Australian Nurse Practitioner Project or AUSPRAC) was undertaken in 2009, requiring nurse telephone interviewers to gather information about health outcomes directly from patients and their treating nurse practitioners. A team of several registered nurses was recruited and trained as telephone interviewers. The aim of this paper is to report on development and evaluation of the training process for telephone interviewers. Methods The training process involved planning the content and methods to be used in the training session; delivering the session; testing skills and understanding of interviewers post-training; collecting and analysing data to determine the degree to which the training process was successful in meeting objectives and post-training follow-up. All aspects of the training process were informed by established educational principles. Results Interrater reliability between interviewers was high for well-validated sections of the survey instrument resulting in 100% agreement between interviewers. Other sections with unvalidated questions showed lower agreement (between 75% and 90%). Overall the agreement between interviewers was 92%. Each interviewer was also measured against a specifically developed master script or gold standard and for this each interviewer achieved a percentage of correct answers of 94.7% or better. This equated to a Kappa value of 0.92 or better. Conclusion The telephone interviewer training process was very effective and achieved high interrater reliability. We argue that the high reliability was due to the use of well validated instruments and the carefully planned programme based on established educational principles. There is limited published literature on how to successfully operationalise educational principles and tailor them for specific research studies; this report addresses this knowledge gap.

QUT_Para at TREC 2012 Web Track : word associations for retrieving web documents

Many existing information retrieval models do not explicitly take into account in- formation about word associations. Our approach makes use of rst and second order relationships found in natural language, known as syntagmatic and paradigmatic associ- ations, respectively. This is achieved by using a formal model of word meaning within the query expansion process. On ad hoc retrieval, our approach achieves statistically sig- ni cant improvements in MAP (0.158) and P@20 (0.396) over our baseline model. The ERR@20 and nDCG@20 of our system was 0.249 and 0.192 respectively. Our results and discussion suggest that information about both syntagamtic and paradigmatic associa- tions can assist with improving retrieval eectiveness on ad hoc retrieval.

Preliminary reliability and validity testing of a self-efficacy questionnaire for Chinese family caregivers

Objectives: To develop and test preliminary reliability and validity of a Self-Efficacy Questionnaire for Chinese Family Caregivers (SEQCFC). Methods: A cross-sectional survey of 196 family caregivers (CGs) of people with dementia (CGs) was conducted to determine the factor structure of a SEQCFC of people with dementia. Following factor analyses, preliminary testing was performed, including internal consistency, 4-week test retest reliability, and construct and convergent validity. Results: Factor analyses with direct oblimin rotation were performed. Eight items were removed and five subscales(selfefficacy for gathering information about treatment, symptoms and health care; obtaining support; responding to behaviour disturbances; managing household, personal and medical care; and managing distress associated with caregiving) were identified. The Cronbach’s alpha coefficients for the whole scale and for each subscale were all over 0.80. The 4-week testretest reliabilities for the whole scale and for each subscale ranged from 0.64 to 0.85. The convergent validity was acceptable. Conclusions: Evidence for the preliminary testing of the SEQCFC was encouraging. A future follow-up study using confirmatory factor analysis with a new sample from different recruitment centres in Shanghai will be conducted. Future psychometric property testings of the questionnaire will be required for CGs from other regions of mainland China.

Numerical modelling and full scale testing of load bearing steel walls under real fires

Fire safety has become an important part in structural design due to the ever increasing loss of properties and lives during fires. Fire rating of load bearing wall systems made of Light gauge Steel Frames (LSF) is determined using fire tests based on the standard time-temperature curve given in ISO 834. However, modern residential buildings make use of thermoplastic materials, which mean considerably high fuel loads. Hence a detailed fire research study into the performance of load bearing LSF walls was undertaken using a series of realistic design fire curves developed based on Eurocode parametric curves and Barnett’s BFD curves. It included both full scale fire tests and numerical studies of LSF walls without any insulation, and the recently developed externally insulated composite panels. This paper presents the details of fire tests first, and then the numerical models of tested LSF wall studs. It shows that suitable finite element models can be developed to predict the fire rating of load bearing walls under real fire conditions. The paper also describes the structural and fire performances of externally insulated LSF walls in comparison to the non-insulated walls under real fires, and highlights the effects of standard and real fire curves on fire performance of LSF walls.

Improving the moment capacities of hollow flange cold-formed Litesteel Beams using web stiffeners

The LiteSteel Beam (LSB) is a new hollow flange section developed in Australia with a unique geometry consisting of torsionally rigid rectangular hollow flanges and a relatively slender web. The LSB is subjected to a relatively new Lateral Distortional Buckling (LDB) mode when used as flexural members. Unlike the commonly observed lateral torsional buckling, lateral distortional buckling of LSBs is characterised by cross sectional change due to web distortion. Lateral distortional buckling causes significant moment capacity reduction for LSBs with intermediate spans. Therefore a detailed investigation was undertaken to determine the methods of reducing the effects of lateral distortional buckling in LSB flexural members. For this purpose the use of web stiffeners was investigated using finite element analyses of LSBs with different web stiffener spacing and sizes. It was found that the use of 5 mm steel plate stiffeners welded or screwed to the inner faces of the top and bottom flanges at third span points considerably reduced the lateral distortional buckling effects in LSBs. Suitable design rules were then developed to calculate the enhanced elastic lateral distortional buckling moments and the higher ultimate moment capacities of LSBs with the chosen web stiffener arrangement. This paper presents the details of this investigation and the results.

A taxonomy of model-based testing approaches

Model-based testing (MBT) relies on models of a system under test and/or its environment to derive test cases for the system. This paper discusses the process of MBT and defines a taxonomy that covers the key aspects of MBT approaches. It is intended to help with understanding the characteristics, similarities and differences of those approaches, and with classifying the approach used in a particular MBT tool. To illustrate the taxonomy, a description of how three different examples of MBT tools fit into the taxonomy is provided.

K from zeolite : glasshouse trial for testing K availability to the plants

MesoLite, a zeolite material manufactured by NanoChem Holdings Pty Ltd is made by caustic reaction of kaolin at temperatures between 80-95°C. This material has a moderate surface area (9~12 m2/g) and very high cation exchange capacity (500meq/100g). To measure the availability of K in K-MesoLite to plants, wheat was grown with K-MesoLite or a soluble fertiliser (e.g. KCl) in non-leached pots in a glasshouse. The weights and elemental compositions of the plants were compared after four weeks growth. Plants grown with K-MesoLite were slightly larger than those grown with KCl. The elemental compositions of the plants were similar except for Si, which was significantly higher in the plants grown with K-MesoLite than in those fertilised with KCl. K from K-MesoLite is readily available to plants.

A novel testing system for a Cycloidal drive

At present, for mechanical power transmission, Cycloidal drives are most preferred - for compact, high transmission ratio speed reduction, especially for robot joints and manipulator applications. Research on drive-train dynamics of Cycloidal drives is not well-established. This paper presents a testing rig for Cycloidal drives, which would produce data for development of mathematical models and investigation of drive-train dynamics, further aiding in optimising its design