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.

The Politics and Legality of Prisoner Disenfranchisement in Australian Federal Elections

To remove the right of prisoners to vote does many things. … It signals that whatever the prisoner says is not of interest to those at the top, that you are not interested in talking to them or even listening to them, that you want to exclude them and that you have no interest in knowing about them. INTRODUCTION In June 2006, Australia passed legislation disenfranchising all prisoners serving full-time custodial sentences from voting in federal elections. This followed a succession of changes dating from 1983 that alternately extended and restricted the prisoner franchise. In 1989 and 1995, the Australian Labor Party (ALP) federal government prepared draft legislation removing any restrictions on prisoner voting rights in federal elections; the measures were defeated and withdrawn. With the 2006 legislation, the Howard Coalition government (composed of the Liberal and National parties) successfully achieved the total disenfranchisement it first sought in 1998. This chapter examines the politics and legality of the 2006 disenfranchisement. This will be approached, first, by briefly outlining the key provisions of the Commonwealth Electoral Act 1918, offering a short legislative history of prisoner franchise, and examining some of the key constitutional issues. Second, the 2006 disenfranchisement introduced in the Electoral and Referendum (Electoral Integrity and Other Measures) Act 2006 will be examined in greater detail, particularly in terms of the manner in which it was achieved and the arguments that were mobilized both in support of and against the change.

Structural characterization of glycerophospholipids by combinations of ozone- and collision-induced dissociation mass spectrometry: The next step towards "top-down" lipidomics

The complete structural elucidation of complex lipids, including glycerophospholipids, using only mass spectrometry represents a major challenge to contemporary analytical technologies. Here, we demonstrate that product ions arising from the collision-induced dissociation (CID) of the [M + Na] + adduct ions of phospholipids can be isolated and subjected to subsequent gas-phase ozonolysis-known as ozone-induced dissociation (OzID)-in a linear ion-trap mass spectrometer. The resulting CID/OzID experiment yields abundant product ions that are characteristic of the acyl substitution on the glycerol backbone (i.e., sn-position). This approach is shown to differentiate sn-positional isomers, such as the regioisomeric phosphatidylcholine pair of PC 16:0/18:1 and PC 18:1/16:0. Importantly, CID/OzID provides a sensitive diagnostic for the existence of an isomeric mixture in a given sample. This is of very high value for the analysis of tissue extracts since CID/OzID analyses can reveal changes in the relative abundance of isomeric constituents even within different tissues from the same animal. Finally, we demonstrate the ability to assign carbon-carbon double bond positions to individual acyl chains at specific backbone positions by adding subsequent CID and/or OzID steps to the workflow and that this can be achieved in a single step using a hybrid triple quadrupole-linear ion trap mass spectrometer. This unique approach represents the most complete and specific structural analysis of lipids by mass spectrometry demonstrated to date and is a significant step towards comprehensive top-down lipidomics. This journal is © The Royal Society of Chemistry 2014. Grant Number ARC/DP0986628, ARC/FT110100249, ARC/LP110200648

Nutritional influences over the life course on lean body mass of individuals in developing countries

The double burden of childhood undernutrition and adult-onset adiposity in transitioning societies poses a significant public health challenge. The development of suboptimal lean body mass (LBM) could partly explain the link between these two forms of malnutrition. This review examines the evidence on both the role of nutrition in “developmental programming” of LBM and the nutritional influences that affect LBM throughout the life course. Studies from developing countries assessing the relationship of early nutrition with later LBM provide important insights. Overall, the evidence is consistent in suggesting a positive association of early nutritional status (indicated by birth weight and growth during first 2 years) with LBM in later life. Evidence on the impact of maternal nutritional supplementation during pregnancy on later LBM is inconsistent. In addition, the role of nutrients (protein, zinc, calcium, vitamin D) that can affect LBM throughout the life course is described. Promoting optimal intakes of these important nutrients throughout the life course is important for reducing childhood undernutrition as well as for improving the LBM of adults.

The role of parents and non-parents in the supervision of learner drivers in Australia

The purpose of this study was to contrast the role of parental and non-parental (sibling, other family and non-family) supervisors in the supervision of learner drivers in graduated driver licensing systems. The sample consisted of 522 supervisors from the Australian states of Queensland (n = 204, 39%) and New South Wales (n = 318, 61%). The learner licence requirements in these two states are similar, although learners in Queensland are required to accrue 100 h of supervision in a log book while those in New South Wales are required to accrue 120 h. Approximately 50 per cent of the sample (n = 255) were parents of the learner driver while the remainder of the sample were either siblings (n = 72, 13.8%), other family members (n = 153, 29.3%) or non-family (n = 114, 21.8%). Parents were more likely than siblings, other family or non-family members to be the primary supervisor of the learner driver. Siblings provided fewer hours of practice when compared with other supervisor types while the median and mode suggest that parents provided the most hours of practice to learner drivers. This study demonstrates that non-parental supervisors, such as siblings, other family members and non-family, at least in jurisdictions that require 100 or 120 h of practice, are important in facilitating learner drivers to accumulate sufficient supervised driving practice.

Influence of tilt and surface roughness on the outflow wind field of an impinging jet

A physical and numerical steady flow impinging jet has been used to simulate the bulk characteristics of a downburst-like wind field. The influence of downdraft tilt and surface roughness on the ensuing wall jet flow has been investigated. It was found that a simulated downdraft impinging the surface at a non-normal angle has the potential for causing larger structural loads than the normal impingement case. It was also found that for the current impinging jet simulations, surface roughness played a minor role in determining the storm maximum wind structure, but this influence increased as the wall jet diverged. However, through comparison with previous research it was found that the influence of surface roughness is Reynolds number dependent and therefore may differ from that reported herein for full-scale downburst cases. Using the current experimental results an empirical model has been developed for laboratory-scale impinging jet velocity structure that includes the influence of both jet tilt and surface roughness.

Comparison of high sensitivity troponin T and I assays in the diagnosis of non-ST elevation acute myocardial infarction in emergency patients with chest pain

Objectives: Concentrations of troponin measured with high sensitivity troponin assays are raised in a number of emergency department (ED) patients; however many are not diagnosed with acute myocardial infarction (AMI). Clinical comparisons between the early use (2 h after presentation) of high sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) assays for the diagnosis of AMI have not been reported. Design and methods: Early (0 h and 2 h) hs-cTnT and hs-cTnI assay results in 1571 ED patients with potential acute coronary syndrome (ACS) without ST elevation on electrocardiograph (ECG) were evaluated. The primary outcome was diagnosis of index MI adjudicated by cardiologists using the local cTnI assay results taken ≥6 h after presentation, ECGs and clinical information. Stored samples were later analysed with hs-cTnT and hs-cTnI assays. Results: The ROC analysis for AMI (204 patients; 13.0%) for hs-cTnT and hs-cTnI after 2 h was 0.95 (95% CI: 0.94–0.97) and 0.98 (95% CI: 0.97–0.99) respectively. The sensitivity, specificity, PLR, and NLR of hs-cTnT and hs-cTnI for AMI after 2 h were 94.1% (95% CI: 90.0–96.6) and 95.6% (95% CI: 91.8–97.7), 79.0% (95% CI: 76.8–81.1) and 92.5% (95% CI: 90.9–93.7), 4.48 (95% CI: 4.02–5.00) and 12.86 (95% CI: 10.51–15.31), and 0.07 (95% CI: 0.04–0.13) and 0.05 (95% CI:0.03–0.09) respectively. Conclusions: Exclusion of AMI 2 h after presentation in emergency patients with possible ACS can be achieved using hs-cTnT or hs-cTnI assays. Significant differences in specificity of these assays are relevant and if using the hs-cTnT assay, further clinical assessment in a larger proportion of patients would be required.

Framework of a process laboratory for the operational control of service processes

Service processes such as financial advice, booking a business trip or conducting a consulting project have emerged as units of analysis of high interest for the business process and service management communities in practice and academia. While the transactional nature of production processes is relatively well understood and deployed, the less predictable and highly interactive nature of service processes still lacks in many areas appropriate methodological grounding. This paper proposes a framework of a process laboratory as a new IT artefact in order to facilitate the holistic analysis and simulation of such service processes. Using financial services as an example, it will be shown how such a process laboratory can be used to reduce the complexity of service process analysis and facilitate operational service process control.

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

Conducting accelerometer-based activity assessments in field-based research

Purpose The purpose of this review is to address important methodological issues related to conducting accelerometer-based assessments of physical activity in free-living individuals. Methods We review the extant scientific literature for empirical information related to the following issues: product selection, number of accelerometers needed, placement of accelerometers, epoch length, and days of monitoring required to estimate habitual physical activity. We also discuss the various options related to distributing and collecting monitors and strategies to enhance compliance with the monitoring protocol. Results No definitive evidence exists currently to indicate that one make and model of accelerometer is more valid and reliable than another. Selection of accelerometer therefore remains primarily an issue of practicality, technical support, and comparability with other studies. Studies employing multiple accelerometers to estimate energy expenditure report only marginal improvements in explanatory power. Accelerometers are best placed on hip or the lower back. Although the issue of epoch length has not been studied in adults, the use of count cut points based on 1-min time intervals maybe inappropriate in children and may result in underestimation of physical activity. Among adults, 3–5 d of monitoring is required to reliably estimate habitual physical activity. Among children and adolescents, the number of monitoring days required ranges from 4 to 9 d, making it difficult to draw a definitive conclusion for this population. Face-to-face distribution and collection of accelerometers is probably the best option in field-based research, but delivery and return by express carrier or registered mail is a viable option. Conclusion Accelerometer-based activity assessments requires careful planning and the use of appropriate strategies to increase compliance.

Developing transactive memory systems : theoretical contributions from a social identity perspective

Transactive memory system (TMS) theory explains how expertise is recognized and coordinated in teams. Extending current TMS research from a group information-processing perspective, our article presents a theoretical model that considers TMS development from a social identity perspective. We discuss how two features of communication (quantity and quality) important to TMS development are linked to TMS through the group identification mechanism of a shared common team identity. Informed by social identity theory, we also differentiate between intragroup and intergroup contexts and outline how, in multidisciplinary teams, professional identification and perceived equality of status among professional subgroups have a role to play in TMS development. We provide a theoretical discussion of future research directions aimed at testing and extending our model.

Physical activity patterns of inner-city elementary schoolchildren

Purpose This study aimed to objectively measure the physical activity (PA) characteristics of a racially and ethnically diverse sample of inner-city elementary schoolchildren and to examine the influence of sex, race/ethnicity, grade level, and weight status on PA. Methods A total of 470 students in grades 4-6 from six inner-city schools in Philadelphia wore an ActiGraph GT3X+ accelerometer (Actigraph, Pensacola, FL) for up to 7 d. The resultant data were uploaded to a customized Visual Basic EXCEL macro to determine the time spent in sedentary (SED), light-intensity PA (LPA), and moderate- to vigorous-intensity PA (MVPA). Results On average, students accumulated 48 min of MVPA daily. Expressed as a percentage of monitoring time, students were sedentary for 63% of the time, in LPA 31% of the time, and in MVPA 6% of the time. Across all race/ethnicity and grade level groups, boys exhibited significantly higher levels of MVPA than girls did; fifth-grade boys exhibited significantly lower MVPA levels than fourth-and sixth-grade boys did, and sixth-grade girls exhibited significantly lower MVPA levels than fourth-and fifth-grade girls did. Hispanic children exhibited lower levels of MVPA than children from other racial/ethnic groups did, and overweight and obese children exhibited significantly lower MVPA levels than children in the healthy weight range did. Across the entire sample, only 24.3% met the current public health guidelines for PA. Physical inactivity was significantly greater among females, Hispanics, and overweight and obese students. Conclusions Fewer than one in four inner-city schoolchildren accumulated the recommended 60 min of MVPA daily. These findings highlight the need for effective and sustainable programs to promote PA in inner-city youth.

LCC15-MB : a vimentin-positive human breast cancer cell line from a femoral bone metastasis

The LCC15-MB cell line was established from a femoral bone metastasis that arose in a 29-year-old woman initially diagnosed with an infiltrating ductal mammary adenocarcinoma. The tumor had a relatively high (8%) S-phase fraction and 1/23 positive lymph nodes (LN). Both the primary tumor and LN metastasis were positive for estrogen receptor (ER) and progesterone receptor (PgR), but lacked erbB2 expression. Approximately one year later, the patient presented with a 0.8 cm comedo-type intraductal mammary adenocarcinoma in the left breast that was negative for ER and PgR, but positive for erbB2. Thirty-five months after the initial diagnosis she was treated for acute skeletal metastasis, and stabilized with a hip replacement. At this time, tumor cells were removed from surplus involved bone, inoculated into cell culture, and developed into the LCC15-MB cell line. The bone metastasis was a poorly differentiated adenocarcinoma lacking ER, PgR, and erbB2, characteristics shared by the LCC15-MB cells, although ER can be re-expressed by treatment of the LCC15-MB cells for 5 days with 75 μM 5-aza-2'-deoxycytidine. The LCC15-MB cell line is tumorigenic when implanted subcutaneously in NCr nu/nu mice and produces long-bone metastases after intracardiac injection. Although the bone metastasis from which the LCC15-MB cell line was derived lacked vimentin (VIM) expression, the original primary tumor and lymph node metastasis were strongly VIM positive, as are LCC15-MB cells in vitro and in nude mice. The karyotype and isozyme profiles of LCC15-MB cells are consistent with its origin from a human female, with most chromosome counts in the hypertriploid range. Thirty-two marker chromosomes are present. These cells provide an in vitro/in vivo model in which to study the inter-relationships between ER, VIM, and bone metastasis in human breast cancer.

Calibration and validation of wearable monitors

Background Wearable monitors are increasingly being used to objectively monitor physical activity in research studies within the field of exercise science. Calibration and validation of these devices are vital to obtaining accurate data. This article is aimed primarily at the physical activity measurement specialist, although the end user who is conducting studies with these devices also may benefit from knowing about this topic. Best Practices Initially, wearable physical activity monitors should undergo unit calibration to ensure interinstrument reliability. The next step is to simultaneously collect both raw signal data (e.g., acceleration) from the wearable monitors and rates of energy expenditure, so that algorithms can be developed to convert the direct signals into energy expenditure. This process should use multiple wearable monitors and a large and diverse subject group and should include a wide range of physical activities commonly performed in daily life (from sedentary to vigorous). Future Directions New methods of calibration now use "pattern recognition" approaches to train the algorithms on various activities, and they provide estimates of energy expenditure that are much better than those previously available with the single-regression approach. Once a method of predicting energy expenditure has been established, the next step is to examine its predictive accuracy by cross-validating it in other populations. In this article, we attempt to summarize the best practices for calibration and validation of wearable physical activity monitors. Finally, we conclude with some ideas for future research ideas that will move the field of physical activity measurement forward.