Development and validation of a ultra performance LC-ESI/MS method for analysis of metabolic phenotypes of healthy men in day and night urine samples

Ultra-performance LC coupled to quadrupole TOF/MS (UPLC-QTOF/MS) in positive and negative ESI was developed and validated to analyze metabolite profiles for urine from healthy men during the day and at night. Data analysis using principal components analysis (PCA) revealed differences between metabolic phenotypes of urine in healthy men during the day and at night. Positive ions with mass-to-charge ratio (m/z) 310.24 (5.35 min), 286.24 (4.74 min) and 310.24 (5.63 min) were elevated in the urine from healthy men at night compared to that during the day. Negative ions elevated in day urine samples of healthy men included m/z 167.02 (0.66 min), 263.12 (2.55 min) and 191.03 (0.73 min), whilst ions m/z 212.01 (4.77 min) were at a lower concentration in urine of healthy men during the day compared to that at night. The ions m/z 212.01 (4.77 min), 191.03 (0.73 min) and 310.24 (5.35 min) preliminarily correspond to indoxyl sulfate, citric acid and N-acetylneuraminic acid, providing further support for an involvement of phenotypic difference in urine of healthy men in day and night samples, which may be associated with notably different activities of gut microbiota, velocity of tricarboxylic acid cycle and activity of sialic acid biosynthesis in healthy men as regulated by circadian rhythm of the mammalian bioclock.

Development and validation of an instrument to measure organizational cultures' support of business process management

The purpose of Business Process Management (BPM) is to increase the efficiency and effectiveness of organizational processes through improvement and innovation. Despite a common understanding that culture is an important element in these efforts, there is a dearth of theoretical and empirical research on culture as a facilitator of successful BPM. We develop the BPM culture construct and propose a validated instrument with which to measure organizational cultures’ support of BPM. The operationalization of the BPM culture concept provides a theoretical foundation for future research and a tool to assist organizations in developing a cultural environment that supports successful BPM.

Locked nucleic acid (LNA) single nucleotide polymorphism (SNP) genotype analysis and validation using real-time PCR

With an increased emphasis on genotyping of single nucleotide polymorphisms (SNPs) in disease association studies, the genotyping platform of choice is constantly evolving. In addition, the development of more specific SNP assays and appropriate genotype validation applications is becoming increasingly critical to elucidate ambiguous genotypes. In this study, we have used SNP specific Locked Nucleic Acid (LNA) hybridization probes on a real-time PCR platform to genotype an association cohort and propose three criteria to address ambiguous genotypes. Based on the kinetic properties of PCR amplification, the three criteria address PCR amplification efficiency, the net fluorescent difference between maximal and minimal fluorescent signals and the beginning of the exponential growth phase of the reaction. Initially observed SNP allelic discrimination curves were confirmed by DNA sequencing (n = 50) and application of our three genotype criteria corroborated both sequencing and observed real-time PCR results. In addition, the tested Caucasian association cohort was in Hardy-Weinberg equilibrium and observed allele frequencies were very similar to two independently tested Caucasian association cohorts for the same tested SNP. We present here a novel approach to effectively determine ambiguous genotypes generated from a real-time PCR platform. Application of our three novel criteria provides an easy to use semi-automated genotype confirmation protocol.

Optimal catalyst thickness in titanium dioxide fixed film reactors: Mathematical modelling and experimental validation

The use of immobilised TiO2 for the purification of polluted water streams introduces the necessity to evaluate the effect of mechanisms such as the transport of pollutants from the bulk of the liquid to the catalyst surface and the transport phenomena inside the porous film. Experimental results of the effects of film thickness on the observed reaction rate for both liquid-side and support-side illumination are here compared with the predictions of a one-dimensional mathematical model of the porous photocatalytic slab. Good agreement was observed between the experimentally obtained photodegradation of phenol and its by-products, and the corresponding model predictions. The results have confirmed that an optimal catalyst thickness exists and, for the films employed here, is 5 μm. Furthermore, the modelling results have highlighted the fact that porosity, together with the intrinsic reaction kinetics are the parameters controlling the photocatalytic activity of the film. The former by influencing transport phenomena and light absorption characteristics, the latter by naturally dictating the rate of reaction.

Flight validation of a feedforward gust-attenuation controller for an autonomous helicopter

This paper presents a practical scheme to control heave motion for hover and automatic landing of a Rotary-wing Unmanned Aerial Vehicle (RUAV) in the presence of strong horizontal gusts. A heave motion model is constructed for the purpose of capturing dynamic variations of thrust due to horizontal gusts. Through construction of an effective gust estimator, a feedback-feedforward controller is developed which uses available measurements from onboard sensors. The proposed controller dynamically and synchronously compensates for aerodynamic variations of heave motion, enhancing disturbance-attenuation capability of the RUAV. Simulation results justify the reliability and efficiency of the suggested gust estimator. Moreover, flight tests conducted on our Eagle helicopter verify suitability of the proposed control strategy for small RUAVs operating in a gusty environment.

Validation of a new tool to measure responsiveness and structure in the feeding context : the Authoritative Feeding Practices Questionnaire

How mothers interact with their toddlers around food lays the foundations for healthy eating and healthy weight gain in later life. This research involving 467 Australian first-time mothers of 2-year-old children resulted in the development of a new self-report tool, the Authoritative Feeding Practices Questionnaire, assessing maternal responsive feeding and mealtime structure. Secondary analysis of the NOURISH randomised controlled trial included theory-driven item selection, confirmatory factor analysis, evaluation of psychometric properties and construct validation. The result is a brief, reliable and valid new tool for evaluating the maternal feeding practices that support children to become healthy, independent eaters.

Development and validation of anthropometric prediction equations for estimation of lean body mass and appendicular lean soft tissue in Indian men and women

Lean body mass (LBM) and muscle mass remains difficult to quantify in large epidemiological studies due to non-availability of inexpensive methods. We therefore developed anthropometric prediction equations to estimate the LBM and appendicular lean soft tissue (ALST) using dual energy X-ray absorptiometry (DXA) as a reference method. Healthy volunteers (n= 2220; 36% females; age 18-79 y) representing a wide range of body mass index (14-44 kg/m2) participated in this study. Their LBM including ALST was assessed by DXA along with anthropometric measurements. The sample was divided into prediction (60%) and validation (40%) sets. In the prediction set, a number of prediction models were constructed using DXA measured LBM and ALST estimates as dependent variables and a combination of anthropometric indices as independent variables. These equations were cross-validated in the validation set. Simple equations using age, height and weight explained > 90% variation in the LBM and ALST in both men and women. Additional variables (hip and limb circumferences and sum of SFTs) increased the explained variation by 5-8% in the fully adjusted models predicting LBM and ALST. More complex equations using all the above anthropometric variables could predict the DXA measured LBM and ALST accurately as indicated by low standard error of the estimate (LBM: 1.47 kg and 1.63 kg for men and women, respectively) as well as good agreement by Bland Altman analyses. These equations could be a valuable tool in large epidemiological studies assessing these body compartments in Indians and other population groups with similar body composition.

Prognostic factors for malignant mesothelioma in 142 patients : validation of CALGB and EORTC prognostic scoring systems

Background The incidence of malignant mesothelioma is increasing. There is the perception that survival is worse in the UK than in other countries. However, it is important to compare survival in different series based on accurate prognostic data. The European Organisation for Research and Treatment of Cancer (EORTC) and the Cancer and Leukaemia Group B (CALGB) have recently published prognostic scoring systems. We have assessed the prognostic variables, validated the EORTC and CALGB prognostic groups, and evaluated survival in a series of 142 patients. Methods Case notes of 142 consecutive patients presenting in Leicester since 1988 were reviewed. Univariate analysis of prognostic variables was performed using a Cox proportional hazards regression model. Statistically significant variables were analysed further in a forward, stepwise multivariate model. EORTC and CALGB prognostic groups were derived, Kaplan-Meier survival curves plotted, and survival rates were calculated from life tables. Results Significant poor prognostic factors in univariate analysis included male sex, older age, weight loss, chest pain, poor performance status, low haemoglobin, leukocytosis, thrombocytosis, and non-epithelial cell type (p<0.05). The prognostic significance of cell type, haemoglobin, white cell count, performance status, and sex were retained in the multivariate model. Overall median survival was 5.9 (range 0-34.3) months. One and two year survival rates were 21.3% (95% CI 13.9 to 28.7) and 3.5% (0 to 8.5), respectively. Median, one, and two year survival data within prognostic groups in Leicester were equivalent to the EORTC and CALGB series. Survival curves were successfully stratified by the prognostic groups. Conclusions This study validates the EORTC and CALGB prognostic scoring systems which should be used both in the assessment of survival data of series in different countries and in the stratification of patients into randomised clinical studies.

Validation of the interRAI Cognitive Performance Scale against independent clinical diagnosis and the Mini-Mental State Examination in older hospitalized patients

Objective To compare the diagnostic accuracy of the interRAI Acute Care (AC) Cognitive Performance Scale (CPS2) and the Mini-Mental State Examination (MMSE), against independent clinical diagnosis for detecting dementia in older hospitalized patients. Design, Setting, and Participants The study was part of a prospective observational cohort study of patients aged ≥70 years admitted to four acute hospitals in Queensland, Australia, between 2008 and 2010. Recruitment was consecutive and patients expected to remain in hospital for ≥48 hours were eligible to participate. Data for 462 patients were available for this study. Measurements Trained research nurses completed comprehensive geriatric assessments and administered the interRAI AC and MMSE to patients. Two physicians independently reviewed patients’ medical records and assessments to establish the diagnosis of dementia. Indicators of diagnostic accuracy included sensitivity, specificity, predictive values, likelihood ratios and areas under receiver (AUC) operating characteristic curves. Results 85 patients (18.4%) were considered to have dementia according to independent clinical diagnosis. The sensitivity of the CPS2 [0.68 (95%CI: 0.58–0.77)] was not statistically different to the MMSE [0.75 (0.64–0.83)] in predicting physician diagnosed dementia. The AUCs for the 2 instruments were also not statistically different: CPS2 AUC = 0.83 (95%CI: 0.78–0.89) and MMSE AUC = 0.87 (95%CI: 0.83–0.91), while the CPS2 demonstrated higher specificity [0.92 95%CI: 0.89–0.95)] than the MMSE [0.82 (0.77–0.85)]. Agreement between the CPS2 and clinical diagnosis was substantial (87.4%; κ=0.61). Conclusion The CPS2 appears to be a reliable screening tool for assessing cognitive impairment in acutely unwell older hospitalized patients. These findings add to the growing body of evidence supporting the utility of the interRAI AC, within which the CPS2 is embedded. The interRAI AC offers the advantage of being able to accurately screen for both dementia and delirium without the need to use additional assessments, thus increasing assessment efficiency.

Colloidal drug probe : method development and validation for adhesion force measurement using atomic force microscopy

This study demonstrates a novel technique of preparing drug colloid probes to determine the adhesion force between the drug salbutamol sulphate (SS) and the surfaces of polymer microparticles to be used as carriers for the dispersion of drug particles from a dry powder inhaler (DPI) formulation. Initially model silica probes of approximately 4 μm size, similar to a drug particle used in DPI formulations, were coated with a saturated SS solution with the aid of capillary forces acting between the silica probe and the drug solution. The developed method of ensuring a smooth and uniform layer of SS on the silica probe was validated using X-Ray Photoelectron Spectroscopy (XPS) and Scanning Electron Microscopy (SEM). Using the same technique, silica microspheres preattached on the AFM cantilever were coated with SS. The adhesion forces between the silica probe and drug coated silica (drug probe) and polymer surfaces (hydrophilic and hydrophobic) were determined. Our experimental results showed that the technique for preparing the drug probe was robust and can be used to determine the adhesion force between hydrophilic/hydrophobic drug probe and carrier surfaces to gain a better understanding on drug carrier adhesion forces in DPI formulations.

Validation of an instrument to measure governance and performance on collaborative infrastructure projects

Collaborative infrastructure projects use hybrid formal and informal governance structures to manage transactions. Based on previous desk-top research, the authors identified the key mechanisms underlying project governance, and posited the performance implications of the governance (Chen et al. 2012). The current paper extends that qualitative research by testing the veracity of those findings using data from 320 Australian construction organisations. The results provide, for the first time, reliable and valid scales to measure governance and performance of collaborative projects, and the relationship between them. The results confirm seven of seven hypothesised governance mechanisms; 30 of 43 hypothesised underlying actions; eight of eight hypothesised key performance indicators; and the dual importance of formal and informal governance. A startling finding of the study was that the implementation intensity of informal mechanisms (non-contractual conditions) is a greater predictor of project performance variance than that of formal mechanisms (contractual conditions). Further, contractual conditions do not directly impact project performance; instead their impact is mediated by the non-contractual features of a project. Obligations established under the contract are not sufficient to optimise project performance.

Validation of β-actin used as endogenous control for gene expression analysis in mechanobiology studies : amendments

We write in response to the letter by Liu et al. [1] commenting on our article, ‘‘Mesenchymal Stem Cells Regulate Angiogenesis According to Their Mechanical Environment’’ [2]. The study by Liu et al. demonstrates that the commonly used endogeneous reference gene (ERG), b-actin, is upregulated by mechanical loading, indicating a potential bias in the determined target gene expression when normalizing to b-actin, such as in our report on unchanged vascular endothelial growth factor (VEGF) and hypoxia-inducible factors (HIF)-1a mRNA levels in mechanically loaded mesenchymal stem cells (MSCs).

Consumer perceptions of trade show effectiveness : scale development and validation within a B2C context

Purpose This paper develops and estimates a model to measure consumer perceptions of trade show effectiveness. Design/methodology/approach Data were collected at three separate B2C trade shows. Study 1 (n=47) involved field interviews with data subjected to qualitative item generation and content analysis. Study 2 data (n=147) were subjected to exploratory factor analysis and item-total correlation to identify a preliminary factor structure for the effectiveness construct and to test for reliability. In Study 3 (n=592), confirmatory factor analysis was undertaken to more rigorously test the factor structure and generalise across industries. Validity testing was also performed. Findings A three-dimensional factor structure for assessing consumer visitors’ perceptions of trade show effectiveness was produced incorporating research, operational, and entertainment components. Research limitations/implications Data were collected in Australia and results may not generalise across cultural boundaries. Practical implications The resulting measurement model may be used as a reliable post-hoc diagnostic tool to identify areas of trade show effectiveness where specific performance improvements are needed. Results indicate that exhibitors and organisers of B2C trade shows should consider effectiveness as a multidimensional phenomenon with entertainment, product / industry research, and the facilitation of purchase decision-making processes and problem resolution being key objectives for consumer attendees. These elements of effectiveness should each be addressed by exhibitors and organisers in planning their displays and events. Originality/value This is the first study to provide an empirically valid model for assessing trade show effectiveness from the consumer visitor’s perspective.

Motion planning and stochastic control with experimental validation on a planetary rover

Motion planning for planetary rovers must consider control uncertainty in order to maintain the safety of the platform during navigation. Modelling such control uncertainty is difficult due to the complex interaction between the platform and its environment. In this paper, we propose a motion planning approach whereby the outcome of control actions is learned from experience and represented statistically using a Gaussian process regression model. This model is used to construct a control policy for navigation to a goal region in a terrain map built using an on-board RGB-D camera. The terrain includes flat ground, small rocks, and non-traversable rocks. We report the results of 200 simulated and 35 experimental trials that validate the approach and demonstrate the value of considering control uncertainty in maintaining platform safety.