Incentive-based interventions for increasing physical activity and fitness

This is the protocol for a review and there is no abstract. The objectives are as follows: The main aim of the review is to determine the effectiveness of using incentive-based approaches (IBAs) (financial and non-financial) to increase physical activity in community-dwelling children and adults. A secondary objective will be to address the use of incentives to improve cardiovascular and metabolic fitness. A final objective will be to explore: - whether there are any adverse effects associated with the use of IBAs for increasing physical activity; - whether there are any differential effects of IBAs within and between study populations by age, gender, education, inequalities and health status; and - whether the use of disincentive/aversive approaches leads to a reduction in sedentary behaviour.

The correlation between electric field emission phenomenon and Schottky contact reverse bias characteristics in nanostructured systems

Two different morphologies of nanotextured molybdenum oxide were deposited by thermal evaporation. By measuring their field emission (FE) properties, an enhancement factor was extracted. Subsequently, these films were coated with a thin layer of Pt to form Schottky contacts. The current-voltage (I-V) characteristics showed low magnitude reverse breakdown voltages, which we attributed to the localized electric field enhancement. An enhancement factor was obtained from the I-V curves. We will show that the enhancement factor extracted from the I-V curves is in good agreement with the enhancement factor extracted from the FE measurements.

Managing memory and reducing I/O cost for correlation matrix calculation in bioinformatics

The generation of a correlation matrix from a large set of long gene sequences is a common requirement in many bioinformatics problems such as phylogenetic analysis. The generation is not only computationally intensive but also requires significant memory resources as, typically, few gene sequences can be simultaneously stored in primary memory. The standard practice in such computation is to use frequent input/output (I/O) operations. Therefore, minimizing the number of these operations will yield much faster run-times. This paper develops an approach for the faster and scalable computing of large-size correlation matrices through the full use of available memory and a reduced number of I/O operations. The approach is scalable in the sense that the same algorithms can be executed on different computing platforms with different amounts of memory and can be applied to different problems with different correlation matrix sizes. The significant performance improvement of the approach over the existing approaches is demonstrated through benchmark examples.

Engineering the fitness of older patients for chemotherapy : an exploration of Comprehensive Geriatric Assessment in practice

Clinicians often report that currently available methods to assess older patients, including standard clinical consultations, do not elicit the information necessary to make an appropriate cancer treatment recommendation for older cancer patients. An increasingly popular way of assessing the potential of older patients to cope with chemotherapy is a Comprehensive Geriatric Assessment. What constitutes Comprehensive Geriatric Assessment, however, is open to interpretation and varies from one setting to another. Furthermore, Comprehensive Geriatric Assessment’s usefulness as a predictor of fitness for chemotherapy and as a determinant of actual treatment is not well understood. In this article, we analyse how Comprehensive Geriatric Assessment was developed for use in a large cancer service in an Australian capital city. Drawing upon Actor–Network Theory, our findings reveal how, during its development, Comprehensive Geriatric Assessment was made both a tool and a science. Furthermore, we briefly explore the tensions that we experienced as scholars who analyse medico-scientific practices and as practitioner–designers charged with improving the very tools we critique. Our study contributes towards geriatric oncology by scrutinising the medicalisation of ageing, unravelling the practices of standardisation and illuminating the multiplicity of ‘fitness for chemotherapy’.

Predicting fitness for chemotherapy in older cancer patients

Background: The Vulnerable Elders Survey-13 (VES-13) is increasingly used to screen for older patients who can proceed to intensive chemotherapy without further comprehensive assessment. This study compared the VES-13 determination of fitness for treatment with the oncologist's assessments of fitness. Method: Sample: Consecutive series of solid tumour patients ≥65 years (n=175; M=72; range=65-86) from an Australian cancer centre. Patients were screened with the VES-13 before proceeding to usual treatment. Blinded to screening, oncologists concurrently predicted patient fitness for chemotherapy. A sample of 175 can detect, with 90% power, kappa coefficients of agreement between VES-13 and oncologists’ assessments >0.90 ("almost perfect agreement"). Separate backward stepwise logistic regression analyses assessed potential predictors of VES-13 and oncologists’ ratings of fitness. Results: Kappa coefficient for agreement between VES-13 and oncologists’ ratings of fitness was 0.41 (p<0.001). VES-13 and oncologists’ assessments agreed in 71% of ratings. VES-13 sensitivity = 83.3%; specificity = 57%; positive predictive value = 69%; negative predictive value = 75%. Logistic regression modelling indicated that the odds of being vulnerable to chemotherapy (VES-13) increased with increasing depression (OR=1.42; 95% CI: 1.18, 1.71) and decreased with increased functional independence assessed on the Bartel Index (OR=0.82; CI: 0.74, 0.92) and Lawton instrumental activities of daily living (OR=0.44; CI: 0.30, 0.65); RSquare=.65. Similarly, the odds of a patient being vulnerable to chemotherapy, when assessed by physicians, increased with increasing age (OR=1.15; CI: 1.07, 1.23) and depression (OR=1.23; CI: 1.06, 1.43), and decreased with increasing functional independence (OR=0.91; CI: 0.85, 0.98); RSquare=.32. Conclusions: Our data indicate moderate agreement between VES-13 and clinician assessments of patients’ fitness for chemotherapy. Current ‘one-step’ screening processes to determine fitness have limits. Nonetheless, screening tools do have the potential for modification and enhanced predictive properties in cancer care by adding relevant items, thus enabling fit patients to be immediately referred for chemotherapy.

Comprehensive assessment of the fitness of older people for chemotherapy

Purpose: To present the results of a mixed-method study comparing the level of agreement of a two-phased, nurse-administered Comprehensive Geriatric Assessment (CGA) with current methods that assess the fitness for chemotherapy of older cancer patients. A nurse-led model of multidisciplinary cancer care based on the results is also described. Methods: The two phases comprised initial screening by a nurse with the Vulnerable Elders Survey-13 [VES-13], followed by nurse administration of a detailed CGA. Both phases were linked to a computerised algorithm categorising the patient as ‘fit’, ‘vulnerable’ or ‘frail’. The study determined the level of agreement between VES-13- and CGA-determined categories; and between the CGA and the physicians’ assessments. It also compared the CGA’s predictive abilities in terms of subsequent treatment toxicity; while interviews determined the acceptability of the nurse-led procedure from key stakeholders' perspectives. Results: Data collection was completed in December 2011. The results will be presented at the conference. A consecutive-series n=170 will be enrolled, 33% of whom are ‘fit’; 33% ‘vulnerable’; and 33% ‘too frail’ for treatment. This sample can detect, with 90% power, kappa coefficients of agreement of ≥ 0.70 or higher (“substantial agreement”). Fitness sub-group comparisons of agreement between the medical oncologist and the nurse assessments can detect kappa estimates of Κ ≥ 0.80 with the same power. Conclusion: The results have informed a nurse-led model of cancer care. It meets a clear need to develop, implement and test a nurse-led, robust, evidence-based, clinically-justifiable and economically-feasible CGA process that has relevance in national and international contexts.

Quantifying spatial structure in experimental observations and agent-based simulations using pair-correlation functions

We define a pair-correlation function that can be used to characterize spatiotemporal patterning in experimental images and snapshots from discrete simulations. Unlike previous pair-correlation functions, the pair-correlation functions developed here depend on the location and size of objects. The pair-correlation function can be used to indicate complete spatial randomness, aggregation or segregation over a range of length scales, and quantifies spatial structures such as the shape, size and distribution of clusters. Comparing pair-correlation data for various experimental and simulation images illustrates their potential use as a summary statistic for calibrating discrete models of various physical processes.

High-resolution loss of heterozygosity screening implicates PTPRJ as a potential tumor suppressor gene that affects susceptibility to non-Hodgkin's Lymphoma

We employed a Hidden-Markov-Model (HMM) algorithm in loss of heterozygosity (LOH) analysis of high-density single nucleotide polymorphism (SNP) array data from Non-Hodgkin’s lymphoma (NHL) entities, follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). This revealed a high frequency of LOH over the chromosomal region 11p11.2, containing the gene encoding the protein tyrosine phosphatase receptor type J (PTPRJ). Although PTPRJ regulates components of key survival pathways in B-cells (i.e., BCR, MAPK, and PI3K signaling), its role in B-cell development is poorly understood. LOH of PTPRJ has been described in several types of cancer but not in any hematological malignancy. Interestingly, FL cases with LOH exhibited down-regulation of PTPRJ, in contrast no significant variation of expression was shown in DLBCLs. In addition, sequence screening in Exons 5 and 13 of PTPRJ identified the G973A (rs2270993), T1054C (rs2270992), A1182C (rs1566734), and G2971C (rs4752904) coding SNPs (cSNPs). The A1182 allele was significantly more frequent in FLs and in NHLs with LOH. Significant over-representation of the C1054 (rs2270992) and the C2971 (rs4752904) alleles were also observed in LOH cases. A haplotype analysis also revealed a significant lower frequency of haplotype GTCG in NHL cases, but it was only detected in cases with retention. Conversely, haplotype GCAC was over-representated in cases with LOH. Altogether, these results indicate that the inactivation of PTPRJ may be a common lymphomagenic mechanism in these NHL subtypes and that haplotypes in PTPRJ gene may play a role in susceptibility to NHL, by affecting activation of PTPRJ in these B-cell lymphomas.

A new method to detect loss of heterozygosity using cohort heterozygosity comparisons

Background Loss of heterozygosity (LOH) is an important marker for one of the 'two-hits' required for tumor suppressor gene inactivation. Traditional methods for mapping LOH regions require the comparison of both tumor and patient-matched normal DNA samples. However, for many archival samples, patient-matched normal DNA is not available leading to the under-utilization of this important resource in LOH studies. Here we describe a new method for LOH analysis that relies on the genome-wide comparison of heterozygosity of single nucleotide polymorphisms (SNPs) between cohorts of cases and un-matched healthy control samples. Regions of LOH are defined by consistent decreases in heterozygosity across a genetic region in the case cohort compared to the control cohort. Methods DNA was collected from 20 Follicular Lymphoma (FL) tumor samples, 20 Diffuse Large B-cell Lymphoma (DLBCL) tumor samples, neoplastic B-cells of 10 B-cell Chronic Lymphocytic Leukemia (B-CLL) patients and Buccal cell samples matched to 4 of these B-CLL patients. The cohort heterozygosity comparison method was developed and validated using LOH derived in a small cohort of B-CLL by traditional comparisons of tumor and normal DNA samples, and compared to the only alternative method for LOH analysis without patient matched controls. LOH candidate regions were then generated for enlarged cohorts of B-CLL, FL and DLBCL samples using our cohort heterozygosity comparison method in order to evaluate potential LOH candidate regions in these non-Hodgkin's lymphoma tumor subtypes. Results Using a small cohort of B-CLL samples with patient-matched normal DNA we have validated the utility of this method and shown that it displays more accuracy and sensitivity in detecting LOH candidate regions compared to the only alternative method, the Hidden Markov Model (HMM) method. Subsequently, using B-CLL, FL and DLBCL tumor samples we have utilised cohort heterozygosity comparisons to localise LOH candidate regions in these subtypes of non-Hodgkin's lymphoma. Detected LOH regions included both previously described regions of LOH as well as novel genomic candidate regions. Conclusions We have proven the efficacy of the use of cohort heterozygosity comparisons for genome-wide mapping of LOH and shown it to be in many ways superior to the HMM method. Additionally, the use of this method to analyse SNP microarray data from 3 common forms of non-Hodgkin's lymphoma yielded interesting tumor suppressor gene candidates, including the ETV3 gene that was highlighted in both B-CLL and FL.

Fractal dimension of dried foods : a correlation between microstructure and porosity

The quality of dried food is affected by a number of factors including quality of raw material, initial microstructure, and drying conditions. The structure of the food materials goes through deformations due to the simultaneous effect of heat and mass transfer during the drying process. Shrinkage and changes in porosity, microstructure and appearance are some of the most remarkable features that directly influence overall product quality. Porosity and microstructure are the important material properties in relation to the quality attributes of dried foods. Fractal dimension (FD) is a quantitative approach of measuring surface, pore characteristics, and microstructural changes [1]. However, in the field of fractal analysis, there is a lack of research in developing relationship between porosity, shrinkage and microstructure of different solid food materials in different drying process and conditions [2-4]. Establishing a correlation between microstructure and porosity through fractal dimension during convective drying is the main objective of this work.

Spectroscopic correlation analysis of NMR-based metabonomics in exercise science

Spectroscopic studies of complex clinical fluids have led to the application of a more holistic approach to their chemical analysis becoming more popular and widely employed. The efficient and effective interpretation of multidimensional spectroscopic data relies on many chemometric techniques and one such group of tools is represented by so-called correlation analysis methods. Typical of these techniques are two-dimensional correlation analysis and statistical total correlation spectroscopy (STOCSY). Whilst the former has largely been applied to optical spectroscopic analysis, STOCSY was developed and has been applied almost exclusively to NMR metabonomic studies. Using a 1H NMR study of human blood plasma, from subjects recovering from exhaustive exercise trials, the basic concepts and applications of these techniques are examined. Typical information from their application to NMR-based metabonomics is presented and their value in aiding interpretation of NMR data obtained from biological systems is illustrated. Major energy metabolites are identified in the NMR spectra and the dynamics of their appearance and removal from plasma during exercise recovery are illustrated and discussed. The complementary nature of two-dimensional correlation analysis and statistical total correlation spectroscopy are highlighted.

Tumour necrosis is an independent prognostic marker in non-small cell lung cancer : correlation with biological variables

Background Tumour necrosis (TN) is recognized to be a consequence of chronic cellular hypoxia. TN and hypoxia correlate with poor prognosis in solid tumours. Methods In a retrospective study the prognostic implications of the extent of TN was evaluated in non-small cell lung cancer (NSCLC) and correlated with clinicopathological variables and expression of epidermal growth factor receptor, Bcl-2, p53 and matrix metalloproteinase-9 (MMP-9). Tissue specimens from 178 surgically resected cases of stage I-IIIA NSCLC with curative intent were studied. The specimens were routinely processed, formalin-fixed and paraffin-embedded. TN was graded as extensive or either limited or absent by two independent observers; disagreements were resolved using a double-headed microscope. The degree of reproducibility was estimated by re-interpreting 40 randomly selected cases after a 4 month interval. Results Reproducibility was attained in 36/40 cases, Kappa score=0.8 P<0.001. TN correlated with T-stage (P=0.001), platelet count (P=0.004) and p53 expression (P=0.031). Near significant associations of TN with N-stage (P=0.063) and MMP-9 expression (P=0.058) were seen. No association was found with angiogenesis (P=0.98). On univariate (P=0.0016) and multivariate analysis (P=0.023) TN was prognostic. Conclusion These results indicate that extensive TN reflects an aggressive tumour phenotype in NSCLC and may improve the predictive power of the TMN staging system. The lack of association between TN and angiogenesis may be important although these variables were not evaluated on serial sections. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

Thromboxane synthase expression and correlation with VEGF and angiogenesis in non-small cell lung cancer

Background Thromboxane synthase (TXS) metabolizes prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with angiogenesis and poor outcome. TXS has been identified as a potential therapeutic target in NSCLC. This study examines a link between TXS expression, angiogenesis, and survival in NSCLC. Methods TXS and VEGF metabolite levels were measured in NSCLC serum samples (n=46) by EIA. TXB2 levels were correlated with VEGF. A 204-patient TMA was stained for TXS, VEGF, and CD-31 expression. Expression was correlated with a range of clinical parameters, including overall survival. TXS expression was correlated with VEGF and CD-31. Stable TXS clones were generated and the effect of overexpression on tumor growth and angiogenesis markers was examined in-vitro and in-vivo (xenograft mouse model). Results Serum TXB2 levels were correlated with VEGF (p<0.05). TXS and VEGF were expressed to a varying degree in NSCLC tissue. TXS was associated with VEGF (p<0.0001) and microvessel density (CD-31; p<0.05). TXS and VEGF expression levels were higher in adenocarcinoma (p<0.0001) and female patients (p<0.05). Stable overexpression of TXS increased VEGF secretion in-vitro. While no significant association with patient survival was observed for either TXS or VEGF in our patient cohort, TXS overexpression significantly (p<0.05) increased tumor growth in-vivo. TXS overexpression was also associated with higher levels of VEGF, microvessel density, and reduced apoptosis in xenograft tumors. Conclusion TXS promotes tumor growth in-vivo in NSCLC, an effect which is at least partly mediated through increased tumor angiogenesis.

Distinguishing between mechanisms of cell aggregation using pair-correlation functions

Many cell types form clumps or aggregates when cultured in vitro through a variety of mechanisms including rapid cell proliferation, chemotaxis, or direct cell-to-cell contact. In this paper we develop an agent-based model to explore the formation of aggregates in cultures where cells are initially distributed uniformly, at random, on a two-dimensional substrate. Our model includes unbiased random cell motion, together with two mechanisms which can produce cell aggregates: (i) rapid cell proliferation, and (ii) a biased cell motility mechanism where cells can sense other cells within a finite range, and will tend to move towards areas with higher numbers of cells. We then introduce a pair-correlation function which allows us to quantify aspects of the spatial patterns produced by our agent-based model. In particular, these pair-correlation functions are able to detect differences between domains populated uniformly at random (i.e. at the exclusion complete spatial randomness (ECSR) state) and those where the proliferation and biased motion rules have been employed - even when such differences are not obvious to the naked eye. The pair-correlation function can also detect the emergence of a characteristic inter-aggregate distance which occurs when the biased motion mechanism is dominant, and is not observed when cell proliferation is the main mechanism of aggregate formation. This suggests that applying the pair-correlation function to experimental images of cell aggregates may provide information about the mechanism associated with observed aggregates. As a proof of concept, we perform such analysis for images of cancer cell aggregates, which are known to be associated with rapid proliferation. The results of our analysis are consistent with the predictions of the proliferation-based simulations, which supports the potential usefulness of pair correlation functions for providing insight into the mechanisms of aggregate formation.

Reliability and validity of physical fitness field tests for adults aged 55 to 70 years

The aim of this study was to examine the reliability and validity of field tests for assessing physical function in mid-aged and young-old people (55-70 y). Tests were selected that required minimal space and equipment and could be implemented in multiple field settings such as a general practitioner's office. Nineteen participants completed 2 field and I laboratory testing sessions. Intra-class correlations showed good reliability for the tests of upper body strength (lift and reach, R=.66), lower body strength (sit to stand, R=.80) and functional capacity (Canadian Step Test, R=.92), but not for leg power (single timed chair rise, R=.28). There was also good reliability for the balance test during 3 stances: parallel (94.7% agreement), semi-tandem (73.7%), and tandem (52.6%). Comparison of field test results with objective laboratory measures found good validity for the sit to stand (cf 1RM leg press, Pearson r=.68, p <.05), and for the step test (cf PWC140, r = -.60, p <.001), but not for the lift and reach (cf 1RM bench press, r=.43, p >.05), balance (r=-.13, -.18, .23) and rate of force development tests (r=-.28). It was concluded that the lower body strength and cardiovascular function tests were appropriate for use in field settings with mid-aged and young-old adults.