Tailored interventions based on sputum eosinophils versus clinical symptoms for asthma in children and adults

BACKGROUND Asthma severity and control can be measured both subjectively and objectively. Sputum analysis for evaluation of percentage of sputum eosinophilia directly measures airway inflammation, and is one method of objectively monitoring asthma. Interventions for asthma therapies have been traditionally based on symptoms and spirometry. OBJECTIVES To evaluate the efficacy of tailoring asthma interventions based on sputum analysis in comparison to clinical symptoms (with or without spirometry/peak flow) for asthma related outcomes in children and adults. SEARCH STRATEGY We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles. The last search was on 31 October 2006. SELECTION CRITERIA All randomised controlled comparisons of adjustment of asthma therapy based on sputum eosinophils compared to traditional methods (primarily clinical symptoms and spirometry/peak flow). DATA COLLECTION AND ANALYSIS Results of searches were reviewed against pre-determined criteria for inclusion. Three sets of reviewers selected relevant studies.Two review authors independently assessed trial quality extracted data. Authors were contacted for further information but none were received. Data was analysed as "treatment received" and sensitivity analyses performed. MAIN RESULTS Three adult studies were included; these studies were clinically and methodologically heterogenous (use of medications, cut off for percentage of sputum eosinophils and definition of asthma exacerbation). There were no eligible paediatric studies. Of 246 participants randomised, 221 completed the trials. In the meta-analysis, a significant reduction in number of participants who had one or more asthma exacerbations occurred when treatment was based on sputum eosinophils in comparison to clinical symptoms; pooled odds ratio (OR) was 0.49 (95% CI 0.28 to 0.87); number needed to treat to benefit (NNTB) was 6 (95% CI 4 to 32).There were also differences between groups in the rate of exacerbation (any exacerbation per year) and severity of exacerbations defined by requirement for use of oral corticosteroids but the reduction in hospitalisations was not statistically significant. Data for clinical symptoms, quality of life and spirometry were not significantly different between groups. The mean dose of inhaled corticosteroids per day was similar in both groups and no adverse events were reported. However sputum induction was not always possible. AUTHORS' CONCLUSIONS Tailored asthma interventions based on sputum eosinophils is beneficial in reducing the frequency of asthma exacerbations in adults with asthma. This review supports the use of sputum eosinophils to tailor asthma therapy for adults with frequent exacerbations and severe asthma. Further studies need to be undertaken to strengthen these results and no conclusion can be drawn for children with asthma.

Understanding and impacting the practice of business process management

This presentation will explore how BPM research can seamlessly combine the academic requirement of rigor with the aim to impact the practice of Business Process Management. After a brief introduction into the research agendas as they are perceived by different BPM communities, two research projects will be discussed that illustrate how empirically-informed quantitative and qualitative research, combined with design science, can lead to outcomes that BPM practitioners are willing to adopt. The first project studies the practice of process modeling using Information Systems theory, and demonstrates how a better understanding of this practice can inform the design of modeling notations and methods. The second project studies the adoption of process management within organizations, and leads to models of how organizations can incrementally transition to greater levels of BPM maturity. The presentation will conclude with recommendations for how the BPM research and practitioner communities can increasingly benefit from each other.

Prostate radiotherapy treatment plan quality : effects of hip prostheses

Introduction This study aimed to examine the geometric and dosimetric results when radiotherapy treatment plans are designed for prostate cancer patients with hip prostheses. Methods Ten EBRT treatment plans for localised prostate cancer, in the presence of hip prostheses, were analysed and compared with a reference set of 196 treatment plans for localised prostate cancer in patients without prostheses. Crowe et al.’s TADA code [1] was used to extract treatment plan parameters and evaluate doses to target volumes and critical structures against recommended goals [2] and constraints [3, 4]. Results The need to avoid transmitting the radiation beam through the hip prostheses limited the range of gantry angles available for use in both the rotational (VMAT) and the non-rotational (3DCRT and IMRT) radiotherapy treatments. This geometric limitation (exemplified in the VMAT data shown in Fig. 1) reduced the overall quality of the treatment plans for patients with prostheses compared to the reference plans. All plans with prostheses failed the PTV dose homogeneity requirement [2], whereas only 4 % of the plans without prostheses failed this test. Several treatment plans for patients with hip prostheses also failed the QUANTEC requirements that less than 50 % of the rectum receive 50 Gy and less than 35 % of the rectum receive 60 Gy to keep the grade 3 toxicity rate below 10 % [3], or the Hansen and Roach requirement that less than 25 % of the bladder receive 75 Gy [4]. Discussion and conclusions The results of this study exemplify the difficulty of designing prostate radiotherapy treatment plans, where beams provide adequate doses to targeted tissues while avoiding nearby organs at risk, when the presence of hip prostheses limits the available treatment geometries. This work provides qualitative evidence of the compromised dose distributions that can result, in such cases.

Accelerometer data reduction : a comparison of four reduction algorithms on select outcome variables

Purpose Accelerometers are recognized as a valid and objective tool to assess free-living physical activity. Despite the widespread use of accelerometers, there is no standardized way to process and summarize data from them, which limits our ability to compare results across studies. This paper a) reviews decision rules researchers have used in the past, b) compares the impact of using different decision rules on a common data set, and c) identifies issues to consider for accelerometer data reduction. Methods The methods sections of studies published in 2003 and 2004 were reviewed to determine what decision rules previous researchers have used to identify wearing period, minimal wear requirement for a valid day, spurious data, number of days used to calculate the outcome variables, and extract bouts of moderate to vigorous physical activity (MVPA). For this study, four data reduction algorithms that employ different decision rules were used to analyze the same data set. Results The review showed that among studies that reported their decision rules, much variability was observed. Overall, the analyses suggested that using different algorithms impacted several important outcome variables. The most stringent algorithm yielded significantly lower wearing time, the lowest activity counts per minute and counts per day, and fewer minutes of MVPA per day. An exploratory sensitivity analysis revealed that the most stringent inclusion criterion had an impact on sample size and wearing time, which in turn affected many outcome variables. Conclusions These findings suggest that the decision rules employed to process accelerometer data have a significant impact on important outcome variables. Until guidelines are developed, it will remain difficult to compare findings across studies

Physical activity recognition from accelerometer data using a multi-scale ensemble method

Accurate and detailed measurement of an individual's physical activity is a key requirement for helping researchers understand the relationship between physical activity and health. Accelerometers have become the method of choice for measuring physical activity due to their small size, low cost, convenience and their ability to provide objective information about physical activity. However, interpreting accelerometer data once it has been collected can be challenging. In this work, we applied machine learning algorithms to the task of physical activity recognition from triaxial accelerometer data. We employed a simple but effective approach of dividing the accelerometer data into short non-overlapping windows, converting each window into a feature vector, and treating each feature vector as an i.i.d training instance for a supervised learning algorithm. In addition, we improved on this simple approach with a multi-scale ensemble method that did not need to commit to a single window size and was able to leverage the fact that physical activities produced time series with repetitive patterns and discriminative features for physical activity occurred at different temporal scales.

SPARC/osteonectin induces matrix metalloproteinase 2 activation in human breast cancer cell lines

Activation of the matrix metalloproteinase 2 (MMP-2) has been shown to play a major role in the proteolysis of extracellular matrix (ECM) associated with tumor invasion. Although the precise mechanism of this activation remains elusive, levels of the membrane type 1-MMP (MT1-MMP) at the cell surface and of the tissue inhibitor of MMP-2 (TIMP-2) appear to be two important determinants. Induction of MMP-2 activation in cells cultivated on collagen type I gels indicated that the ECM is important in the regulation of this process. In this study, we show that SPARC/osteonectin, a small ECM- associated matricellular glycoprotein, can induce MMP-2 activation in two invasive breast cancer cell lines (MDA-MB-231 and BT549) but not in a noninvasive counterpart (MCF7), which lacks MT1-MMP. Using a set of peptides from different regions of SPARC, we found that peptide 1.1 (corresponding to the NH2-terminal region of the protein) contained the activity that induced NIMP-2 activation. Despite the requirement for MT1-MMP, seen in MCF-7 cells transfected with MT1-MMP, the activation of MMP-2 by SPARC peptide 1.1 was not associated with increased steady-state levels of MT1-MMP mRNA or protein in either MT1-MMP-transfected MCF-7 cells or constitutively expressing MDA- MB-231 and BT549 cells. We did, however, detect decreased levels of TIMP-2 protein in the media of cells incubated with peptide 1.1 or recombinant SPARC; thus, the induction of MMP-2 activation by SPARC might be due in part to a diminution of TIMP-2 protein. We conclude that SPARC, and specifically its NH2-terminal domain, regulates the activation of MMP-2 at the cell surface and is therefore likely to contribute to the proteolytic pathways associated with tumor invasion.

Complex regulation of membrane-type matrix metalloproteinase expression and matrix metalloproteinase-2 activation by concanavalin A in MDA-MB-231 human breast cancer cells

Matrix Metalloproteinase-2 (MMP-2) is secreted as a zymogen, the activation of which has been associated with metastatic progression in human breast cancer (HBC). Concanavalin A (Con A) has been found to induce activation of MMP-2 in invasive HBC cell lines. Con A effects on the expression of mRNA for membrane-type matrix metalloproteinase (MT-MMP), a newly described cell surface-associated MMP, showed a close temporal correlation with induction of MMP-2 activation. It is surprising that MT-MMP mRNA is constitutively present in the uninduced MDA-MB-231 cell, despite a lack of MMP-2 activation. We have used actinomycin D to demonstrate a partial requirement for de novo gene expression in the induction of MMP-2 activation by Con A in MDA-MB-231 HBC cells. Furthermore, this transcriptional response to Con A appeared to require the continued presence of Con A for its manifestation. The nontranscriptional component of the Con A induction manifests rapidly, is quite substantial, and persists strongly despite actinomycin D abrogation of both constitutive and Con A-induced MT-MMP. Cycloheximide analyses suggest that protein synthesis may be involved in this rapid transcription-independent response. These studies suggest that Con A induces MMP-2-activation in part by up-regulation of MT-MMP expression but has a more complicated mode of action, involving additional nontranscriptional effects, which apparently require protein synthesis.

Examining the effects of early cost drivers on contingencies

The accuracy of early cost estimates is critical to the success of construction projects. The selected tender price (clients' building cost) is usually seen in previous research as a holistic dependent variable when examining early stage estimates. Unlike other components of construction cost, the amount of contingencies is decided by clients/consultants with consideration of early project information. Cost drivers of contingencies estimates are associated with uncertainty and complexity, and include project size, schedule, ground condition, construction site access, market condition and so on. A path analysis of 133 UK school building contracts was conducted to identify impacts of nine major cost drivers on the determination of contingencies by different clients/cost estimators. This research finds that gross floor area (GFA), schedule and requirement of air conditioning have statistically significant impacts on the contingency determination. The mediating role of schedule between gross floor area and contingencies (GFA→Schedule→Contingencies) was confirmed with the Soble test. The total effects of the three variables on contingencies estimates were obtained with the consideration of this indirect effect. The squared multiple correlation (SMC) of contingencies (=0.624) indicates the identified three variables can explain 62.4% variance of contingencies, and it is comparatively satisfactory considering the heterogeneity among different estimators, unknown estimating techniques and different projects

Factors regulating basement membrane invasion by tumor cells

Basement membranes serve as significant barriers to the passage of tumor cells but ones which metastatic cells can pass. This involves the production of a cascade of proteases leading to the activation of a specific collagenase that degrades the unique collagen network in basement membrane. Breast cancer cells, when estrogen dependent, show a requirement for estrogen for invasive activity. However, when these cells progress to an estrogen independent state and increased malignancy, they express an invasive phenotype constitutively. Studies with various anti-estrogens suggest that these responses are mediated via the estrogen receptor. Anti-estrogens lacking agonist activity suppress invasiveness as well as growth of the breast cancer cells.

Gelatinase A (MMP-2) activation by skin fibroblasts : dependence on MT1-MMP expression and fibrillar collagen form

The respective requirements of collagen and MT1-MMP in the activation of MMP-2 by primary fibroblast cultures were explored further. Three-dimensional gels enriched in human collagen types I and III or composed of recombinant human type II or III collagen, caused increased MT1-MMP production (mRNA and protein) and induced MMP-2 activation. Only marginal induction was seen with dried monomeric collagen confirming the need for collagen fibrillar organisation for activation. To our surprise, relatively low amounts (as low as 25 μg/ml) of acid soluble type I collagen added to fibroblast cultures also induced potent MMP-2 activation. However, the requirement for collagen fibril formation by the added collagen was indicated by the inhibition seen when the collagen was pre-incubated with a fibril-blocking peptide, and the reduced activation seen with alkali-treated collagen preparations known to have impaired fibrilisation. Pre-treatment of the collagen with sodium periodate also abrogated MMP-2 activation induction. Further evidence of the requirement for collagen fibril formation was provided by the lack of activation when type IV collagen, which does not form collagen fibrils, was added in the cultures. Fibroblasts derived from MT1-MMP-deficient mice were unable to activate MMP-2 in response to either three-dimensional collagen gel or added collagen solutions, compared to their littermate controls. Collectively, these data indicate that the fibrillar structure of collagen and MT1-MMP are essential for the MMP-2 activational response in fibroblasts.

Motor Accident Insurance Act 1994 - compulsory conferences and offers to settle

In Lindsay v Aumaali [2004] QDC 028 the Court considered whether it could, in effect, postpone the requirement for a compulsory conference under s51A of the Moror Accident insurance Act 1994 (Qld) or the exchange of final offers under s51C of the Act until after the start of proceedings.

Entrepreneurship education in non-business schools : best practice for Australian contexts of knowledge and innovation communities (Final Report)

In the current era of global economic instability, business and industry have already identified a widening gap between graduate skills and employability. An important element of this is the lack of entrepreneurial skills in graduates. This Teaching Fellowship investigated two sides of a story about entrepreneurial skills and their teaching. Senior players in the innovation commercialisation industry, a high profile entrepreneurial sector, were surveyed to gauge their needs and experiences of graduates they employ. International contexts of entrepreneurship education were investigated to explore how their teaching programs impart the skills of entrepreneurship. Such knowledge is an essential for the design of education programs that can deliver the entrepreneurial skills deemed important by industry for future sustainability. Two programs of entrepreneurship education are being implemented at QUT that draw on the best practice exemplars investigated during this Fellowship. The QUT Innovation Space (QIS) focuses on capturing the innovation and creativity of students, staff and others. The QIS is a physical and virtual meeting and networking space; a connected community enhancing the engagement of participants. The Q_Hatchery is still embryonic; but it is intended to be an innovation community that brings together nascent entrepreneurial businesses to collaborate, train and support each other. There is a niche between concept product and business incubator where an experiential learning environment for otherwise isolated ‘garage-at-home’ businesses could improve success rates. The QIS and the Q_Hatchery serve as living research laboratories to trial the concepts emerging from the skills survey. The survey of skills requirements of the innovation commercialisation industry has produced a large and high quality data set still being explored. Work experience as an employability factor has already emerged as an industry requirement that provides employee maturity. Exploratory factor analysis of the skills topics surveyed has led to a process-based conceptual model for teaching and learning higher-order entrepreneurial skills. Two foundational skills domains (Knowledge, Awareness) are proposed as prerequisites which allow individuals with a suite of early stage entrepreneurial and behavioural skills (Pre-leadership) to further leverage their careers into a leadership role in industry with development of skills around higher order elements of entrepreneurship, management in new business ventures and progressing winning technologies to market. The next stage of the analysis is to test the proposed model through structured equation modelling. Another factor that emerged quickly from the survey analysis broadens the generic concept of team skills currently voiced in Australian policy documents discussing the employability agenda. While there was recognition of the role of sharing, creating and using knowledge in a team-based interdisciplinary context, the adoption and adaptation of behaviours and attitudes of other team members of different disciplinary backgrounds (interprofessionalism) featured as an issue. Most undergraduates are taught and undertake teamwork in silos and, thus, seldom experience a true real-world interdisciplinary environment. Enhancing the entrepreneurial capacity of Australian industry is essential for the economic health of the country and can only be achieved by addressing the lack of entrepreneurial skills in graduates from the higher education system. This Fellowship has attempted to address this deficiency by identifying the skills requirements and providing frameworks for their teaching.

The challenge to know and control: Disease outbreak surveillance and alerts in China and India

Since the revisions to the International Health Regulations (IHR) in 2005, much attention has been turned to how states, particularly developing states, will address core capacity requirements. The question often examined is how states with poor health systems can strengthen their capacity to identify and verify public health emergencies of international concern. A core capacity requirement is that by 2012 states will have a surveillance and response network that operates from the local community to the national level. Much emphasis has turned to the health system capacity required for this task. In this article, I seek to understand the political capacity to perform this task. This article considers how the world's two most populous states,1 1. For the purposes of this paper, I use the word ‘state’ as a shorthand for the nation-state of China and India, or member state as used by the United Nations. View all notes China and India, have sought to communicate outbreak events in times of crisis and calm. I consider what this reporting performance tells us of their capacity to meet their IHR obligations given the two countries differing political institutions.

Common secure index for conjunctive keyword-based retrieval over encrypted data

We consider the following problem: users in a dynamic group store their encrypted documents on an untrusted server, and wish to retrieve documents containing some keywords without any loss of data confidentiality. In this paper, we investigate common secure indices which can make multi-users in a dynamic group to obtain securely the encrypted documents shared among the group members without re-encrypting them. We give a formal definition of common secure index for conjunctive keyword-based retrieval over encrypted data (CSI-CKR), define the security requirement for CSI-CKR, and construct a CSI-CKR based on dynamic accumulators, Paillier’s cryptosystem and blind signatures. The security of proposed scheme is proved under strong RSA and co-DDH assumptions.

How to strengthen any weakly unforgeable signature into a strongly unforgeable signature

Standard signature schemes are usually designed only to achieve weak unforgeability – i.e. preventing forgery of signatures on new messages not previously signed. However, most signature schemes are randomised and allow many possible signatures for a single message. In this case, it may be possible to produce a new signature on a previously signed message. Some applications require that this type of forgery also be prevented – this requirement is called strong unforgeability. At PKC2006, Boneh Shen and Waters presented an efficient transform based on any randomised trapdoor hash function which converts a weakly unforgeable signature into a strongly unforgeable signature and applied it to construct a strongly unforgeable signature based on the CDH problem. However, the transform of Boneh et al only applies to a class of so-called partitioned signatures. Although many schemes fall in this class, some do not, for example the DSA signature. Hence it is natural to ask whether one can obtain a truly generic efficient transform based on any randomised trapdoor hash function which converts any weakly unforgeable signature into a strongly unforgeable one. We answer this question in the positive by presenting a simple modification of the Boneh-Shen-Waters transform. Our modified transform uses two randomised trapdoor hash functions.