Generation of a recombinant Gag virus-like-particle panel for the evaluation of p24 antigen detection by diagnostic HIV tests.

BACKGROUND Detection of HIV-1 p24 antigen permits early identification of primary HIV infection and timely intervention to limit further spread of the infection. Principally, HIV screening should equally detect all viral variants, but reagents for a standardised test evaluation are limited. Therefore, we aimed to create an inexhaustible panel of diverse HIV-1 p24 antigens. METHODS We generated a panel of 43 recombinantly expressed virus-like particles (VLPs), containing the structural Gag proteins of HIV-1 subtypes A-H and circulating recombinant forms (CRF) CRF01_AE, CRF02_AG, CRF12_BF, CRF20_BG and group O. Eleven 4th generation antigen/antibody tests and five antigen-only tests were evaluated for their ability to detect VLPs diluted in human plasma to p24 concentrations equivalent to 50, 10 and 2 IU/ml of the WHO p24 standard. Three tests were also evaluated for their ability to detect p24 after heat-denaturation for immune-complex disruption, a pre-requisite for ultrasensitive p24 detection. RESULTS Our VLP panel exhibited an average intra-clade p24 diversity of 6.7%. Among the 4th generation tests, the Abbott Architect and Siemens Enzygnost Integral 4 had the highest sensitivity of 97.7% and 93%, respectively. Alere Determine Combo and BioRad Access were least sensitive with 10.1% and 40.3%, respectively. Antigen-only tests were slightly more sensitive than combination tests. Almost all tests detected the WHO HIV-1 p24 standard at a concentration of 2 IU/ml, but their ability to detect this input for different subtypes varied greatly. Heat-treatment lowered overall detectability of HIV-1 p24 in two of the three tests, but only few VLPs had a more than 3-fold loss in p24 detection. CONCLUSIONS The HIV-1 Gag subtype panel has a broad diversity and proved useful for a standardised evaluation of the detection limit and breadth of subtype detection of p24 antigen-detecting tests. Several tests exhibited problems, particularly with non-B subtypes.

Developing an alternative response format for the script concordance test

Introduction: Clinical reasoning is essential for the practice of medicine. In theory of development of medical expertise it is stated, that clinical reasoning starts from analytical processes namely the storage of isolated facts and the logical application of the ‘rules’ of diagnosis. Then the learners successively develop so called semantic networks and illness-scripts which finally are used in an intuitive non-analytic fashion [1], [2]. The script concordance test (SCT) is an example for assessing clinical reasoning [3]. However the aggregate scoring [3] of the SCT is recognized as problematic [4]. The SCT`s scoring leads to logical inconsistencies and is likely to reflect construct-irrelevant differences in examinees’ response styles [4]. Also the expert panel judgments might lead to an unintended error of measurement [4]. In this PhD project the following research questions will be addressed: 1. How does a format look like to assess clinical reasoning (similar to the SCT but) with multiple true-false questions or other formats with unambiguous correct answers, and by this address the above mentioned pitfalls in traditional scoring of the SCT? 2. How well does this format fulfill the Ottawa criteria for good assessment, with special regards to educational and catalytic effects [5]? Methods: 1. In a first study it shall be assessed whether designing a new format using multiple true-false items to assess clinical reasoning similar to the SCT-format is arguable in a theoretically and practically sound fashion. For this study focus groups or interviews with assessment experts and students will be undertaken. 2. In an study using focus groups and psychometric data Norcini`s and colleagues Criteria for Good Assessment [5] shall be determined for the new format in a real assessment. Furthermore the scoring method for this new format shall be optimized using real and simulated data.

Measuring color differences in automotive samples with lightness flop: a test of the AUDI2000 color-difference formula

From a set of gonioapparent automotive samples from different manufacturers we selected 28 low-chroma color pairs with relatively small color differences predominantly in lightness. These color pairs were visually assessed with a gray scale at six different viewing angles by a panel of 10 observers. Using the Standardized Residual Sum of Squares (STRESS) index, the results of our visual experiment were tested against predictions made by 12 modern color-difference formulas. From a weighted STRESS index accounting for the uncertainty in visual assessments, the best prediction of our whole experiment was achieved using AUDI2000, CAM02-SCD, CAM02-UCS and OSA-GP-Euclidean color-difference formulas, which were no statistically significant different among them. A two-step optimization of the original AUDI2000 color-difference formula resulted in a modified AUDI2000 formula which performed both, significantly better than the original formula and below the experimental inter-observer variability. Nevertheless the proposal of a new revised AUDI2000 color-difference formula requires additional experimental data.

Energy consumption, economic growth and prices: A reassessment using panel VECM for developed and developing countries

This paper reinvestigates the energy consumption-GDP growth nexus in a panel error correction model using data on 20 net energy importers and exporters from 1971 to 2002. Among the energy exporters, there was bidirectional causality between economic growth and energy consumption in the developed countries in both the short and long run, while in the developing countries energy consumption stimulates growth only in the short run. The former result is also found for energy importers and the latter result exists only for the developed countries within this category. In addition, compared to the developing countries, the developed countries' elasticity response in terms of economic growth from an increase in energy consumption is larger although its income elasticity is lower and less than unitary. Lastly. the implications for energy policy calling for a more holistic approach are discussed. (c) 2006 Elsevier Ltd. All rights reserved.

Stock market efficiency, the small firm effect and cointegration

The cointegration methodology commonly used for testing the efficiency of the foreign exchange market is applied to a sample of UK share prices. Specifically we test for static market efficiency in the share prices of small and large firms, using monthly data from January 1975 to December 1989. The empirical findings provide evidence of market efficiency for portfolios of large firms but of inefficiency for small firm portfolios. These results are indicative of a small firm effect in the UK stock market.

An econometric analysis of international tourism demand in Hong Kong : a cointegration and error correction approach

The purpose of this study is to develop econometric models to better understand the economic factors affecting inbound tourist flows from each of six origin countries that contribute to Hong Kong’s international tourism demand. To this end, we test alternative cointegration and error correction approaches to examine the economic determinants of tourist flows to Hong Kong, and to produce accurate econometric forecasts of inbound tourism demand. Our empirical findings show that permanent income is the most significant determinant of tourism demand in all models. The variables of own price, weighted substitute prices, trade volume, the share price index (as an indicator of changes in wealth in origin countries), and a dummy variable representing the Beijing incident (1989) are also found to be important determinants for some origin countries. The average long-run income and own price elasticity was measured at 2.66 and – 1.02, respectively. It was hypothesised that permanent income is a better explanatory variable of long-haul tourism demand than current income. A novel approach (grid search process) has been used to empirically derive the weights to be attached to the lagged income variable for estimating permanent income. The results indicate that permanent income, estimated with empirically determined relatively small weighting factors, was capable of producing better results than the current income variable in explaining long-haul tourism demand. This finding suggests that the use of current income in previous empirical tourism demand studies may have produced inaccurate results. The share price index, as a measure of wealth, was also found to be significant in two models. Studies of tourism demand rarely include wealth as an explanatory forecasting long-haul tourism demand. However, finding a satisfactory proxy for wealth common to different countries is problematic. This study indicates with the ECM (Error Correction Models) based on the Engle-Granger (1987) approach produce more accurate forecasts than ECM based on Pesaran and Shin (1998) and Johansen (1988, 1991, 1995) approaches for all of the long-haul markets and Japan. Overall, ECM produce better forecasts than the OLS, ARIMA and NAÏVE models, indicating the superiority of the application of a cointegration approach for tourism demand forecasting. The results show that permanent income is the most important explanatory variable for tourism demand from all countries but there are substantial variations between countries with the long-run elasticity ranging between 1.1 for the U.S. and 5.3 for U.K. Price is the next most important variable with the long-run elasticities ranging between -0.8 for Japan and -1.3 for Germany and short-run elasticities ranging between – 0.14 for Germany and -0.7 for Taiwan. The fastest growing market is Mainland China. The findings have implications for policies and strategies on investment, marketing promotion and pricing.

The appraisal and management of multi-storey dwelling blocks using large concrete panel systems

This exploratory study is concerned with the integrated appraisal of multi-storey dwelling blocks which incorporate large concrete panel systems (LPS). The first step was to look at U.K. multi-storey dwelling stock in general, and under the management of Birmingham City Council in particular. The information has been taken from the databases of three departments in the City of Birmingham, and rearranged in a new database using a suite of PC software called `PROXIMA' for clarity and analysis. One hundred of their stock were built large concrete panel system. Thirteen LPS blocks were chosen for the purpose of this study as case-studies depending mainly on the height and age factors of the block. A new integrated appraisal technique has been created for the LPS dwelling blocks, which takes into account the most physical and social factors affecting the condition and acceptability of these blocks. This appraisal technique is built up in a hierarchical form moving from the general approach to particular elements (a tree model). It comprises two main approaches; physical and social. In the physical approach, the building is viewed as a series of manageable elements and sub-elements to cover every single physical or environmental factor of the block, in which the condition of the block is analysed. A quality score system has been developed which depends mainly on the qualitative and quantitative conditions of each category in the appraisal tree model, and leads to physical ranking order of the study blocks. In the social appraisal approach, the residents' satisfaction and attitude toward their multi-storey dwelling block was analysed in relation to: a. biographical and housing related characteristics; and b. social, physical and environmental factors associated with this sort of dwelling, block and estate in general.The random sample consisted of 268 residents living in the 13 case study blocks. Data collected was analysed using frequency counts, percentages, means, standard deviations, Kendall's tue, r-correlation coefficients, t-test, analysis of variance (ANOVA) and multiple regression analysis. The analysis showed a marginally positive satisfaction and attitude towards living in the block. The five most significant factors associated with the residents' satisfaction and attitude in descending order were: the estate, in general; the service categories in the block, including heating system and lift services; vandalism; the neighbours; and the security system of the block. An important attribute of this method, is that it is relatively inexpensive to implement, especially when compared to alternatives adopted by some local authorities and the BRE. It is designed to save time, money and effort, to aid decision making, and to provide ranked priority to the multi-storey dwelling stock, in addition to many other advantages. A series of solution options to the problems of the block was sought for selection and testing before implementation. The traditional solutions have usually resulted in either demolition or costly physical maintenance and social improvement of the blocks. However, a new solution has now emerged, which is particularly suited to structurally sound units. The solution of `re-cycling' might incorporate the reuse of an entire block or part of it, by removing panels, slabs and so forth from the upper floors in order to reconstruct them as low-rise accommodations.

BRAF mutation testing algorithm for vemurafenib treatment in melanoma: recommendations from an expert panel.

The incidence of melanoma has increased rapidly over the past 30 years, and the disease is now the sixth most common cancer among men and women in the U.K. Many patients are diagnosed with or develop metastatic disease, and survival is substantially reduced in these patients. Mutations in the BRAF gene have been identified as key drivers of melanoma cells and are found in around 50% of cutaneous melanomas. Vemurafenib (Zelboraf(®) ; Roche Molecular Systems Inc., Pleasanton, CA, U.S.A.) is the first licensed inhibitor of mutated BRAF, and offers a new first-line option for patients with unresectable or metastatic melanoma who harbour BRAF mutations. Vemurafenib was developed in conjunction with a companion diagnostic, the cobas(®) 4800 BRAF V600 Mutation Test. The purpose of this paper is to make evidence-based recommendations to facilitate the implementation of BRAF mutation testing and targeted therapy in patients with metastatic melanoma in the U.K. The recommendations are the result of a meeting of an expert panel and have been reviewed by melanoma specialists and representatives of the National Cancer Research Network Clinical Study Group on behalf of the wider melanoma community. This article is intended to be a starting point for practical advice and recommendations, which will no doubt be updated as we gain further experience in personalizing therapy for patients with melanoma.

Refining the diagnosis and EGFR status of non-small cell lung carcinoma in biopsy and cytologic material, using a panel of mucin staining, TTF-1, cytokeratin 5/6, and P63, and EGFR mutation analysis.

INTRODUCTION: The dichotomization of non-small cell carcinoma (NSCLC) subtype into squamous (SQCC) and adenocarcinoma (ADC) has become important in recent years and is increasingly required with regard to management. The aim of this study was to determine the utility of a panel of commercially available antibodies in refining the diagnosis on small biopsies and also to determine whether cytologic material is suitable for somatic EGFR genotyping in a prospectively analyzed series of patients undergoing investigation for suspected lung cancer. METHODS: Thirty-two consecutive cases of NSCLC were first tested using a panel comprising cytokeratin 5/6, P63, thyroid transcription factor-1, 34betaE12, and a D-PAS stain for mucin, to determine their value in refining diagnosis of NSCLC. After this test phase, two further pathologists independently reviewed the cases using a refined panel that excluded 34betaE12 because of its low specificity for SQCC, and refinement of diagnosis and concordance were assessed. Ten cases of ADC, including eight derived from cytologic samples, were sent for EGFR mutation analysis. RESULTS: There was refinement of diagnosis in 65% of cases of NSCLC to either SQCC or ADC in the test phase. This included 10 of 13 cases where cell pellets had been prepared from transbronchial needle aspirates. Validation by two further pathologists with varying expertise in lung pathology confirmed increased refinement and concordance of diagnosis. All samples were adequate for analysis, and they all showed a wild-type EGFR genotype. CONCLUSION: A panel comprising cytokeratin 5/6, P63, thyroid transcription factor-1, and a D-PAS stain for mucin increases diagnostic accuracy and agreement between pathologists when faced with refining a diagnosis of NSCLC to SQCC or ADC. These small samples, even cell pellets derived from transbronchial needle aspirates, seem to be adequate for EGFR mutation analysis.

Precast Prestressed Concrete Panel Subdecks in Skewed Bridges, Interim Report, 1990

Precast prestressed concrete panels have been used in bridge deck construction in Iowa and many other states. To investigate the performance of these panels at abutment or pier diaphragm locations for bridges with various skew angles, a research program involving both analytical and experimental aspects, is being conducted. This interim report presents the status of the research with respect to four tasks. Task 1 which involves a literature review and two surveys is essentially complete. Task 2 which involved field investigations of three Iowa bridges containing precast panel subdecks has been completed. Based on the findings of these investigations, future inspections are recommended to evaluate potential panel deterioration due to possible corrosion of the prestressed strands. Task 3 is the experimental program which has been established to monitor the behavior of five configurations of full scale composite deck slabs. Three dimensional test and instrumentation frameworks have been constructed to load and monitor the slab specimens. The first slab configuration representing an interior panel condition is being tested and preliminary results are presented for one of these tests in this interim report. Task 4 involves the analytical investigation of the experimental specimens. Finite element methods are being applied to analytically predict the behavior of the test specimens. The first test configuration of the interior panel condition has been analyzed for the same loads used in the laboratory, and the results are presented herein. Very good correlation between the analytical and experimental results has occurred.

Mathematical analysis of maximum power generated by photovoltaic systems and fitting curves for standard test conditions

The rural electrification is characterized by geographical dispersion of the population, low consumption, high investment by consumers and high cost. Moreover, solar radiation constitutes an inexhaustible source of energy and in its conversion into electricity photovoltaic panels are used. In this study, equations were adjusted to field conditions presented by the manufacturer for current and power of small photovoltaic systems. The mathematical analysis was performed on the photovoltaic rural system I- 100 from ISOFOTON, with power 300 Wp, located at the Experimental Farm Lageado of FCA/UNESP. For the development of such equations, the circuitry of photovoltaic cells has been studied to apply iterative numerical methods for the determination of electrical parameters and possible errors in the appropriate equations in the literature to reality. Therefore, a simulation of a photovoltaic panel was proposed through mathematical equations that were adjusted according to the data of local radiation. The results have presented equations that provide real answers to the user and may assist in the design of these systems, once calculated that the maximum power limit ensures a supply of energy generated. This real sizing helps establishing the possible applications of solar energy to the rural producer and informing the real possibilities of generating electricity from the sun.

Identifying stationary series in panels: A Monte Carlo evaluation of sequential panel selection methods

Sequential panel selection methods (spsms — procedures that sequentially use conventional panel unit root tests to identify I(0)I(0) time series in panels) are increasingly used in the empirical literature. We check the reliability of spsms by using Monte Carlo simulations based on generating directly the individual asymptotic pp values to be combined into the panel unit root tests, in this way isolating the classification abilities of the procedures from the small sample properties of the underlying univariate unit root tests. The simulations consider both independent and cross-dependent individual test statistics. Results suggest that spsms may offer advantages over time series tests only under special conditions.

Modified CADF and CIPS panel unit root statistics with standard chi-squared and normal limiting distributions

In an influential paper Pesaran ('A simple panel unit root test in presence of cross-section dependence', Journal of Applied Econometrics, Vol. 22, pp. 265-312, 2007) proposes two unit root tests for panels with a common factor structure. These are the CADF and CIPS test statistics, which are amongst the most popular test statistics in the literature. One feature of these statistics is that their limiting distributions are highly non-standard, making for relatively complicated implementation. In this paper, we take this feature as our starting point to develop modified CADF and CIPS test statistics that support standard chi-squared and normal inference.

An IV test for a unit root in generally trending and correlated panels

This paper proposes an IV-based panel unit root test that is general enough to accommodate general error serial and cross-section dependence, and a potentially nonlinear deterministic trend function. These allowances make the new test one of the most general around. It is also very simple to implement. Indeed, the IV statistic is asymptotically invariant to not only to all nuisance parameters characterizing the dependence of the errors and the true trend function, but also the deterministic specification of the fitted test regression.

The Trier Social Stress Test: principles and practice

Researchers interested in the neurobiology of the acute stress response in humans require a valid and reliable acute stressor that can be used under experimental conditions. The Trier Social Stress Test (TSST) provides such a testing platform. It induces stress by requiring participants to make an interview-style presentation, followed by a surprise mental arithmetic test, in front of an interview panel who do not provide feedback or encouragement. In this review, we outline the methodology of the TSST, and discuss key findings under conditions of health and stress-related disorder. The TSST has unveiled differences in males and females, as well as different age groups, in their neurobiological response to acute stress. The TSST has also deepened our understanding of how genotype may moderate the cognitive neurobiology of acute stress, and exciting new inroads have been made in understanding epigenetic contributions to the biological regulation of the acute stress response using the TSST. A number of innovative adaptations have been developed which allow for the TSST to be used in group settings, with children, in combination with brain imaging, and with virtual committees. Future applications may incorporate the emerging links between the gut microbiome and the stress response. Future research should also maximise use of behavioural data generated by the TSST. Alternative acute stress paradigms may have utility over the TSST in certain situations, such as those that require repeat testing. Nonetheless, we expect that the TSST remains the gold standard for examining the cognitive neurobiology of acute stress in humans.