Medizinischer und gesundheitsökonomischer Nutzen der Untersuchung auf Helicobacter pylori-Besiedlung mittels 13C-Harnstoff-Atemtest in der Primärdiagnostik im Vergleich zu invasiven und nichtinvasiven diagnostischen Verfahren

Hintergrund: Helicobacter pylori (H. pylori) zählt trotz abnehmender Inzidenz zu den häufigsten bakteriellen Infektionskrankheiten des Menschen. Die Infektion mit H. pylori ist ein Risikofaktor für Krankheiten wie gastroduodenale Geschwüre, Magenkarzinomen und MALT (Mucosa Associated Lymphoid Tissue)-Lymphomen. Zur Diagnostik von H. pylori stehen verschiedene invasive und nichtinvasive Verfahren zur Verfügung. Der 13C-Harnstoff-Atemtest wird zur Kontrolle einer Eradikationstherapie empfohlen, kommt in der Primärdiagnostik von H. pylori derzeit jedoch nicht standardmäßig in Deutschland zum Einsatz. Fragestellung: Welchen medizinischen und gesundheitsökonomischen Nutzen hat die Untersuchung auf H. pylori-Besiedlung mittels 13C-Harnstoff-Atemtest in der Primärdiagnostik im Vergleich zu invasiven und nichtinvasiven diagnostischen Verfahren? Methodik: Basierend auf einer systematischen Literaturrecherche in Verbindung mit einer Handsuche werden Studien zur Testgüte und Kosten-Effektivität des 13C-Harnstoff-Atemtests im Vergleich zu anderen diagnostischen Verfahren zum primären Nachweis von H. pylori identifiziert. Es werden nur medizinische Studien eingeschlossen, die den 13C-Harnstoff-Atemtest direkt mit anderen H. pylori-Testverfahren vergleichen. Goldstandard ist eines oder eine Kombination der biopsiebasierten Testverfahren. Für die gesundheitsökonomische Beurteilung werden nur vollständige gesundheitsökonomische Evaluationsstudien einbezogen, bei denen die Kosten-Effektivität des 13C Harnstoff-Atemtests direkt mit anderen H. pylori-Testverfahren verglichen wird. Ergebnisse: Es werden 30 medizinische Studien für den vorliegenden Bericht eingeschlossen. Im Vergleich zum Immunglobulin G (IgG)-Test ist die Sensitivität des 13C-Harnstoff-Atemtests zwölfmal höher, sechsmal niedriger und einmal gleich, und die Spezifität 13-mal höher, dreimal niedriger und zweimal gleich. Im Vergleich zum Stuhl-Antigen-Test ist die Sensitivität des 13C-Harnstoff-Atemtests neunmal höher, dreimal niedriger und einmal gleich, und die Spezifität neunmal höher, zweimal niedriger und zweimal gleich. Im Vergleich zum Urease-Schnelltest sind die Sensitivität des 13C-Harnstoff-Atemtests viermal höher, dreimal niedriger und viermal gleich und die Spezifität fünfmal höher, fünfmal niedriger und einmal gleich. Im Vergleich mit der Histologie ist die Sensitivität des 13C-Harnstoff-Atemtests einmal höher und zweimal niedriger und die Spezifität zweimal höher und einmal niedriger. In je einem Vergleich zeigt sich kein Unterschied zwischen 13C-Harnstoff-Atemtest und 14C-Harnstoff-Atemtest, sowie eine niedrigere Sensitivität und höhere Spezifität im Vergleich zur Polymerase-Kettenreaktion (PCR). Inwieweit die beschriebenen Unterschiede statistisch signifikant sind, wird in sechs der 30 Studien angegeben. Es werden neun gesundheitsökonomische Evaluationen in dem vorliegenden Bericht berücksichtigt. Die Test-and-Treat-Strategie mittels 13C-Harnstoff-Atemtest wird in sechs Studien mit einem Test-and-Treat-Verfahren auf Basis der Serologie sowie in drei Studien mit einem Test-and-Treat-Verfahren auf Basis des Stuhl-Antigen-Tests verglichen. Dabei ist das Atemtestverfahren dreimal kosteneffektiv gegenüber der serologischen Methode und wird von der Stuhl-Antigen-Test-Strategie einmal dominiert. Vier Studien beinhalten einen Vergleich der Test-and -Treat-Strategie auf Basis des 13C-Harnstoff-Atemtests mit einer empirischen antisekretorischen Therapie, wobei sich das Atemtesverfahren zweimal als kosteneffektive Prozedur erweist und zwei Studien einen Vergleich mit einer empirischen Eradikationstherapie. In fünf Studien wird das Test-and-Treat-Verfahren mittels 13C-Harnstoff-Atemtest einer endoskopiebasierten Strategie gegenübergestellt. Zweimal dominiert die Atemteststrategie die endoskopische Prozedur und einmal wird sie von dieser Strategie dominiert. Diskussion:Sowohl die medizinischen als auch die ökonomischen Studien weisen mehr oder minder gravierende Mängel auf und liefern heterogene Ergebnisse. So werden in der Mehrzahl der medizinischen Studien keine Angaben zur statistischen Signifikanz der berichteten Unterschiede zwischen den jeweiligen Testverfahren gemacht. Im direkten Vergleich weist der 13C-Harnstoff-Atemtest überwiegend eine höhere Testgüte als der IgG und der Stuhl-Antigen-Test auf. Aus den Vergleichen mit dem Urease-Schnelltest lassen sich keine Tendenzen bezüglich der Sensitivität ableiten, wohingegen die Spezifität des 13C-Harnstoff-Atemtests höher einzuschätzen ist. Für die Vergleiche des 13C-Harnstoff-Atemtest mit der Histologie, dem 14C-Harnstoff-Atemtest und der PCR liegen zu wenige Ergebnisse vor. In der eingeschlossenen ökonomischen Literatur deuten einige Studienergebnisse auf eine Kosten-Effektivität der Test-and-Treat-Strategie mittels 13C-Harnstoff-Atemtest gegenüber dem Test-and-Treat-Verfahren auf Basis der Serologie und der empirischen antiskretorischen Therapie hin. Um Tendenzen bezüglich der Kosten-Effektivität der Atemteststrategie gegenüber der Test-and-Treat-Strategie mittels Stuhl-Antigen-Test sowie der empirischen Eradikationstherapie abzuleiten, mangelt es an validen Ergebnissen bzw. ökonomischer Evidenz. Die Untersuchungsresultate hinsichtlich eines Vergleichs mit endoskopiebasierten Verfahren fallen diesbezüglich zu heterogen aus. Insgesamt kann keines der ökonomischen Modelle der Komplexität des Managements von Patienten mit dyspeptischen Beschwerden gänzlich gerecht werden. Schlussfolgerungen/Empfehlungen: Zusammenfassend ist festzuhalten, dass die Studienlage zur medizinischen und ökonomischen Beurteilung des 13C-Harnstoff-Atemtests im Vergleich zu anderen diagnostischen Methoden nicht ausreichend ist, um den Atemtest als primärdiagnostisches Standardverfahren im Rahmen einer Test-and-Treat-Strategie beim Management von Patienten mit dyspeptischen Beschwerden für die deutsche Versorgungslandschaft insbesondere vor dem Hintergrund der Leitlinien der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten (DGVS) anstelle einer endoskopiebasierten Methode zu empfehlen.

Using interaction data for improving the offline and online evaluation of search engines

This thesis investigates how web search evaluation can be improved using historical interaction data. Modern search engines combine offline and online evaluation approaches in a sequence of steps that a tested change needs to pass through to be accepted as an improvement and subsequently deployed. We refer to such a sequence of steps as an evaluation pipeline. In this thesis, we consider the evaluation pipeline to contain three sequential steps: an offline evaluation step, an online evaluation scheduling step, and an online evaluation step. In this thesis we show that historical user interaction data can aid in improving the accuracy or efficiency of each of the steps of the web search evaluation pipeline. As a result of these improvements, the overall efficiency of the entire evaluation pipeline is increased. Firstly, we investigate how user interaction data can be used to build accurate offline evaluation methods for query auto-completion mechanisms. We propose a family of offline evaluation metrics for query auto-completion that represents the effort the user has to spend in order to submit their query. The parameters of our proposed metrics are trained against a set of user interactions recorded in the search engine’s query logs. From our experimental study, we observe that our proposed metrics are significantly more correlated with an online user satisfaction indicator than the metrics proposed in the existing literature. Hence, fewer changes will pass the offline evaluation step to be rejected after the online evaluation step. As a result, this would allow us to achieve a higher efficiency of the entire evaluation pipeline. Secondly, we state the problem of the optimised scheduling of online experiments. We tackle this problem by considering a greedy scheduler that prioritises the evaluation queue according to the predicted likelihood of success of a particular experiment. This predictor is trained on a set of online experiments, and uses a diverse set of features to represent an online experiment. Our study demonstrates that a higher number of successful experiments per unit of time can be achieved by deploying such a scheduler on the second step of the evaluation pipeline. Consequently, we argue that the efficiency of the evaluation pipeline can be increased. Next, to improve the efficiency of the online evaluation step, we propose the Generalised Team Draft interleaving framework. Generalised Team Draft considers both the interleaving policy (how often a particular combination of results is shown) and click scoring (how important each click is) as parameters in a data-driven optimisation of the interleaving sensitivity. Further, Generalised Team Draft is applicable beyond domains with a list-based representation of results, i.e. in domains with a grid-based representation, such as image search. Our study using datasets of interleaving experiments performed both in document and image search domains demonstrates that Generalised Team Draft achieves the highest sensitivity. A higher sensitivity indicates that the interleaving experiments can be deployed for a shorter period of time or use a smaller sample of users. Importantly, Generalised Team Draft optimises the interleaving parameters w.r.t. historical interaction data recorded in the interleaving experiments. Finally, we propose to apply the sequential testing methods to reduce the mean deployment time for the interleaving experiments. We adapt two sequential tests for the interleaving experimentation. We demonstrate that one can achieve a significant decrease in experiment duration by using such sequential testing methods. The highest efficiency is achieved by the sequential tests that adjust their stopping thresholds using historical interaction data recorded in diagnostic experiments. Our further experimental study demonstrates that cumulative gains in the online experimentation efficiency can be achieved by combining the interleaving sensitivity optimisation approaches, including Generalised Team Draft, and the sequential testing approaches. Overall, the central contributions of this thesis are the proposed approaches to improve the accuracy or efficiency of the steps of the evaluation pipeline: the offline evaluation frameworks for the query auto-completion, an approach for the optimised scheduling of online experiments, a general framework for the efficient online interleaving evaluation, and a sequential testing approach for the online search evaluation. The experiments in this thesis are based on massive real-life datasets obtained from Yandex, a leading commercial search engine. These experiments demonstrate the potential of the proposed approaches to improve the efficiency of the evaluation pipeline.

The influence of rock fabric in the durability of two sandstones used in the Andalusian Architectural Heritage (Montoro and Ronda, Spain)

Natural stone has been a popular and reliable building material throughout history appearing in many historic monuments and in more recent buildings. Research into the intrinsic properties of specific stones is important because it gives us a greater understanding of the factors that limit and act on them. This can help prevent serious problems from occurring in our buildings bringing both esthetic benefits and financial savings. To this end, the main objective of this research has been to study the influence of the fabric and the mineral composition of two types of sandstone on their durability. The first is a red continental sandstone from the Buntsandstein Age called “Molinaza Roja”, which is quarried in Montoro (Cordoba). The second is quarried in Ronda (Malaga) and is sold under the trade name of “Arenisca Ronda”. It is a light pink-whitish calcarenite deposited during the Late Tortonian to Late Messinian. We characterized their petrological and petrophysical properties by studying their rock fabrics, porous systems and mechanical properties. In order to obtain a complete vision of the behavior of their rock fabrics, we also carried out two decay tests, the salt crystallization and the freeze–thaw tests. We then measured the effects on the textures of the altered samples during and after the decay tests and we evaluated the changes in the porous system. By comparing the results between intact and altered samples, we found that Arenisca Ronda is less durable because it has a high quantity of expandable clays (smectites) and a high percentage of pores in the 0.1–1 μm range, in which the pressure produced by salt crystallization is strongest. In Molinaza Roja the decay agents caused significant sanding due to loss of cohesion between the clasts, especially during the salt crystallization test. In both stones, the anisotropies (oriented textures) have an important role in their hydric and dynamic behavior and also affect their mechanical properties (especially in the compression resistance). No changes in color were detected.

Assisted reproductive technology – IVF treatment in Ireland: A study of couples with successful outcomes

Human Fertility 17(3):165-9 This article describes the experiences of twelve Irish couples who had successful IVF treatment in Ireland. Irish Medical guidelines specify that IVF may only be used when no other treatment is likely to be effective. This article is based on data drawn from a longitudinal research study by Cotter (2009) which tells the stories of 34 couples who sought fertility treatment. Initially, the women assumed that they would become pregnant when they stopped using contraception. As a couple, it was the ‘right time’ for them to have a child - they were ready, socially and financially. For several months they were patient, hoping it would happen naturally. With envy and some despair they watched as their friends had babies. Infertility came as a shock to most of them. They were reluctant to talk about it to anyone, and over time their anxieties were accompanied by feelings of regret, stigma and social exclusion. They finally sought medical treatment. The latter involved a series of diagnostic treatments, which eventually culminated in IVF which offered them a final chance of having a ‘child of their own’. While IVF can be clinically assessed in terms of cycle success rates, their stories showed treatment as a series of discoveries, as an extensive range of diagnostic tests and procedures helped to reveal to them where their problems might lie. They described their treatments as a series of sequential ‘hurdles’ that they had to overcome, which further strengthened their resolve to try IVF. Much more knowledgeable at that stage, they embraced IVF as a final challenge with single minded dedication while drawing on all their psychological and biological resources to promote a successful outcome. Of the 34 couples who took part in the study, twelve got pregnant. Unfortunately, two children died shortly after birth but eighteen babies survived (see Table I). The findings suggest that health policy should raise awareness of infertility, and advise women to become aware of it just as in the past, when health policy addressed contraception. Increased public knowledge would reduce the stigma attached to the inability to have a baby. In the Irish case, infertility diagnosis should be reviewed with a view to giving eligible couples earlier access to IVF.  

Risk factors associated with negative in-vivo diagnostic results in bovine tuberculosis-infected cattle in Spain

BACKGROUND Despite great effort and investment incurred over decades to control bovine tuberculosis (bTB), it is still one of the most important zoonotic diseases in many areas of the world. Test-and-slaughter strategies, the basis of most bTB eradication programs carried out worldwide, have demonstrated its usefulness in the control of the disease. However, in certain countries, eradication has not been achieved due in part to limitations of currently available diagnostic tests. In this study, results of in-vivo and post-mortem diagnostic tests performed on 3,614 animals from 152 bTB-infected cattle herds (beef, dairy, and bullfighting) detected in 2007-2010 in the region of Castilla y León, Spain, were analyzed to identify factors associated with positive bacteriological results in cattle that were non-reactors to the single intradermal tuberculin test, to the interferon-gamma (IFN-γ) assay, or to both tests applied in parallel (Test negative/Culture + animals, T-/C+). The association of individual factors (age, productive type, and number of herd-tests performed since the disclosure of the outbreak) with the bacteriology outcome (positive/negative) was analyzed using a mixed multivariate logistic regression model. RESULTS The proportion of non-reactors with a positive post-mortem result ranged from 24.3% in the case of the SIT test to 12.9% (IFN-γ with 0.05 threshold) and 11.9% (95% CI 9.9-11.4%) using both tests in parallel. Older (>4.5 years) and bullfighting cattle were associated with increased odds of confirmed bTB infection by bacteriology, whereas dairy cattle showed a significantly lower risk. Ancillary use of IFN-γ assay reduced the proportion of T-/C + animals in high risk groups. CONCLUSIONS These results demonstrate the likelihood of positive bacteriological results in non-reactor cattle is influenced by individual epidemiological factors of tested animals. Increased surveillance on non-reactors with an increased probability of being false negative could be helpful to avoid bTB persistence, particularly in chronically infected herds. These findings may aid in the development of effective strategies for eradication of bTB in Spain.

Evaluación del desempeño de pruebas diagnósticas de tuberculosis en pacientes VIH positivo en dos hospitales públicos de Bogotá

La tuberculosis TB es una de las principales causas de muerte en el mundo en individuos con infección por VIH. En Colombia esta coinfección soporta una carga importante en la población general convirtiéndose en un problema de salud pública. En estos pacientes las pruebas diagnósticas tienen sensibilidad inferior y la enfermedad evoluciona con mayor frecuencia hacia formas diseminadas y rápidamente progresivas y su diagnóstico oportuno representa un reto en Salud. El objetivo de este proyecto es evaluar el desempeño de las pruebas diagnósticas convencionales y moleculares, para la detección de TB latente y activa pacientes con VIH, en dos hospitales públicos de Bogotá. Para TB latente se evaluó la concordancia entre las pruebas QuantiFERON-TB (QTF) y Tuberculina (PPD), sugiriendo superioridad del QTF sobre la PPD. Se evaluaron tres pruebas diagnósticas por su sensibilidad y especificidad, baciloscopia (BK), GenoType®MTBDR plus (Genotype) y PCR IS6110 teniendo como estándar de oro el cultivo. Los resultados de sensibilidad (S) y especificidad (E) de cada prueba con una prevalencia del 19,4 % de TB pulmonar y extrapulmonar en los pacientes que participaron del estudio fue: BK S: 64% E: 99,1%; Genotype S: 77,8% E: 94,5%; PCRIS6110 S: 73% E: 95,5%, de la misma forma se determinaron los valores predictivos positivos y negativos (VPP y VPN) BK: 88,9% y 94,8%, Genotype S: 77,8% E: 94,5%; PCRIS6110 S: 90% y 95,7%. Se concluyó bajo análisis de curva ROC que las pruebas muestran un rendimiento diagnóstico similar por separado en el diagnóstico de TB en pacientes con VIH, aumentando su rendimiento diagnostico cuando se combinan

Operationalizing the resource based view for nascent and young firms : developing scales for resource advantages and disadvantages

Principal Topic: It is well known that most new ventures suffer from a significant lack of resources, which increases the risk of failure (Shepherd, Douglas and Shanley, 2000) and makes it difficult to attract stakeholders and financing for the venture (Bhide & Stevenson, 1999). The Resource-Based View (RBV) (Barney, 1991; Wernerfelt, 1984) is a dominant theoretical base increasingly drawn on within Strategic Management. While theoretical contributions applying RBV in the domain of entrepreneurship can arguably be traced back to Penrose (1959), there has been renewed attention recently (e.g. Alvarez & Busenitz, 2001; Alvarez & Barney, 2004). This said, empirical work is in its infancy. In part, this may be due to a lack of well developed measuring instruments for testing ideas derived from RBV. The purpose of this study is to develop a measurement scales that can serve to assist such empirical investigations. In so doing we will try to overcome three deficiencies in current empirical measures used for the application of RBV to the entrepreneurship arena. First, measures for resource characteristics and configurations associated with typical competitive advantages found in entrepreneurial firms need to be developed. These include such things as alertness and industry knowledge (Kirzner, 1973), flexibility (Ebben & Johnson, 2005), strong networks (Lee et al., 2001) and within knowledge intensive contexts, unique technical expertise (Wiklund and Shepard, 2003). Second, the RBV has the important limitations of being relatively static and modelled on large, established firms. In that context, traditional RBV focuses on competitive advantages. However, newly established firms often face disadvantages, especially those associated with the liabilities of newness (Aldrich & Auster, 1986). It is therefore important in entrepreneurial contexts to expand to an investigation of responses to competitive disadvantage through an RBV lens. Conversely, recent research has suggested that resource constraints actually have a positive effect on firm growth and performance under some circumstances (e.g., George, 2005; Katila & Shane, 2005; Mishina et al., 2004; Mosakowski, 2002; cf. also Baker & Nelson, 2005). Third, current empirical applications of RBV measured levels or amounts of particular resources available to a firm. They infer that these resources deliver firms competitive advantage by establishing a relationship between these resource levels and performance (e.g. via regression on profitability). However, there is the opportunity to directly measure the characteristics of resource configurations that deliver competitive advantage, such as Barney´s well known VRIO (Valuable, Rare, Inimitable and Organized) framework (Barney, 1997). Key Propositions and Methods: The aim of our study is to develop and test scales for measuring resource advantages (and disadvantages) and inimitability for entrepreneurial firms. The study proceeds in three stages. The first stage developed our initial scales based on earlier literature. Where possible, we adapt scales based on previous work. The first block of the scales related to the level of resource advantages and disadvantages. Respondents were asked the degree to which each resource category represented an advantage or disadvantage relative to other businesses in their industry on a 5 point response scale: Major Disadvantage, Slight Disadvantage, No Advantage or Disadvantage, Slight Advantage and Major Advantage. Items were developed as follows. Network capabilities (3 items) were adapted from (Madsen, Alsos, Borch, Ljunggren & Brastad, 2006). Knowledge resources marketing expertise / customer service (3 items) and technical expertise (3 items) were adapted from Wiklund and Shepard (2003). flexibility (2 items), costs (4 items) were adapted from JIBS B97. New scales were developed for industry knowledge / alertness (3 items) and product / service advantages. The second block asked the respondent to nominate the most important resource advantage (and disadvantage) of the firm. For the advantage, they were then asked four questions to determine how easy it would be for other firms to imitate and/or substitute this resource on a 5 point likert scale. For the disadvantage, they were asked corresponding questions related to overcoming this disadvantage. The second stage involved two pre-tests of the instrument to refine the scales. The first was an on-line convenience sample of 38 respondents. The second pre-test was a telephone interview with a random sample of 31 Nascent firms and 47 Young firms (< 3 years in operation) generated using a PSED method of randomly calling households (Gartner et al. 2004). Several items were dropped or reworded based on the pre-tests. The third stage (currently in progress) is part of Wave 1 of CAUSEE (Nascent Firms) and FEDP (Young Firms), a PSED type study being conducted in Australia. The scales will be tested and analysed with a random sample of approximately 700 Nascent and Young firms respectively. In addition, a judgement sample of approximately 100 high potential businesses in each category will be included. Findings and Implications: The paper will report the results of the main study (stage 3 – currently data collection is in progress) will allow comparison of the level of resource advantage / disadvantage across various sub-groups of the population. Of particular interest will be a comparison of the high potential firms with the random sample. Based on the smaller pre-tests (N=38 and N=78) the factor structure of the items confirmed the distinctiveness of the constructs. The reliabilities are within an acceptable range: Cronbach alpha ranged from 0.701 to 0.927. The study will provide an opportunity for researchers to better operationalize RBV theory in studies within the domain of entrepreneurship. This is a fundamental requirement for the ability to test hypotheses derived from RBV in systematic, large scale research studies.

Venture idea newness, relatedness and performance in nascent ventures

Principal Topic The study of the origin and characteristics of venture ideas - or ''opportunities'' as they are often called - and their contextual fit are key research goals in entrepreneurship (Davidsson, 2004). We define venture idea as ''the core ideas of an entrepreneur about what to sell, how to sell, whom to sell and how an entrepreneur acquire or produce the product or service which he/she sells'' for the purpose of this study. When realized the venture idea becomes a ''business model''. Even though venture ideas are central to entrepreneurship yet its characteristics and their effect to the entrepreneurial process is mysterious. According to Schumpeter (1934) entrepreneurs could creatively destruct the existing market condition by introducing new product/service, new production methods, new markets, and new sources of supply and reorganization of industries. The introduction, development and use of new ideas are generally called as ''innovation'' (Damanpour & Wischnevsky, 2006) and ''newness'' is a property of innovation and is a relative term which means that the degree of unfamiliarity of venture idea either to a firm or to a market. However Schumpeter's (1934) discusses five different types of newness, indicating that type of newness is an important issue. More recently, Shane and Venkataraman (2000) called for research taking into consideration not only the variation of characteristics of individuals but also heterogeneity of venture ideas, Empirically, Samuelson (2001, 2004) investigated process differences between innovative venture ideas and imitative venture ideas. However, he used only a crude dichotomy regarding the venture idea newness. According to Davidsson, (2004) as entrepreneurs could introduce new economic activities ranging from pure imitation to being new to the entire world market, highlighting that newness is a matter of degree. Dahlqvist (2007) examined the venture idea newness and made and attempt at more refined assessment of the degree and type of newness of venture idea. Building on these predecessors our study refines the assessment of venture idea newness by measuring the degree of venture idea newness (new to the world, new to the market, substantially improved while not entirely new, and imitation) for four different types of newness (product/service, method of production, method of promotion, and customer/target market). We then related type and degree of newness to the pace of progress in nascent venturing process. We hypothesize that newness will slow down the business creation process. Shane & Venkataraman (2000) introduced entrepreneurship as the nexus of opportunities and individuals. In line with this some scholars has investigated the relationship between individuals and opportunities. For example Shane (2000) investigates the relatedness between individuals' prior knowledge and identification of opportunities. Shepherd & DeTinne (2005) identified that there is a positive relationship between potential financial reward and the identification of innovative venture ideas. Sarasvathy's 'Effectuation Theory'' assumes high degree of relatedness with founders' skills, knowledge and resources in the selection of venture ideas. However entrepreneurship literature is scant with analyses of how this relatedness affects to the progress of venturing process. Therefore, we assess the venture ideas' degree of relatedness to prior knowledge and resources, and relate these, too, to the pace of progress in nascent venturing process. We hypothesize that relatedness will increase the speed of business creation. Methodology For this study we will compare early findings from data collected through the Comprehensive Australian Study of Entrepreneurial Emergence (CAUSEE). CAUSEE is a longitudinal study whose primary objective is to uncover the factors that initiate, hinder and facilitate the process of emergence and development of new firms. Data were collected from a representative sample of some 30,000 households in Australia using random digit dialing (RDD) telephone survey interviews. Through the first round of data collection identified 600 entrepreneurs who are currently involved in the business start-up process. The unit of the analysis is the emerging venture, with the respondent acting as its spokesperson. The study methodology allows researchers to identify ventures in early stages of creation and to longitudinally follow their progression through data collection periods over time. Our measures of newness build on previous work by Dahlqvist (2007). Our adapted version was developed over two pre-tests with about 80 participants in each. The measures of relatedness were developed through the two rounds of pre-testing. The pace of progress in the venture creation process is assessed with the help of time-stamped gestation activities; a technique developed in the Panel Study of Entrepreneurial Dynamics (PSED). Results and Implications We hypothesized that venture idea newness slows down the venturing process whereas relatedness facilitates the venturing process. Results of 600 nascent entrepreneurs in Australia indicated that there is marginal support for the hypothesis that relatedness assists the gestation progress. Newness is significant but is the opposite sign to the hypothesized. The results give number of implications for researchers, business founders, consultants and policy makers in terms of better knowledge of the venture creation process.

Simple Serological Assays for Detecting Rice Tungro Viruses

An attempt was made to produce sensitive and specific polyclonal antisera against the viruses causing rice tungro disease, and to assess their potential for use in simple diagnostic tests. Using a multiple, sequential injection procedure, seven batches of polyclonal antisera against rice tungro bacilliform virus (RTBV) and rice tungro spherical virus (RTSV) were produced. These were characterized for their sensitivity and specificity using ring-interface precipitin test and double antibody sandwich (DAS) ELISA. Thirty-one weeks after the first immunization, antiserum batch B6b for RTBV showed the highest ring interface titer (DEP = 1:1920). For RTSV, batches S3, S4b and S5b all had similar titres (DEP = 1:640). In DAS-ELISA, however, significant differences among purified antisera (IgG) batches were observed only at IgG dilution of 10-3. At that dilution, IgGB4b showed the greatest sensitivity, while IgGS3 showed greatest sensitivity for RTSV. When all IgG batches were tested against 11 tungro field isolates (dual RTBV-RTSV infections) at sample dilution of 1:10, IgGB4b and IgGB6b for RTBV and IgGS3 and IgGS6b for RTSV performed equally well. However, after cross adsorption with healthy plant extracts in a specially prepared healthy plant-Sepharose affinity column, only IgGB6b could be used specifically to detect RTBV in a simple tissue-print assay.

A longitudinal assessment of chronic wound fluid to detect biochemical indicators of healing

Chronic venous leg ulcers are a detrimental health issue plaguing our society, resulting in long term pain, immobility and decreased quality of life for a large proportion of sufferers. The frequency of these chronic wounds has led current research to focus on the wound environment to provide important information regarding the prolonged, fluctuated or static healing patterns of these wounds. Disruption to the normal wound healing process results in release of multiple factors in the wound environment that could correlate to wound chronicity. These biochemical factors can often be detected through non-invasively sampling chronic wound fluid (CWF) from the site of injury. Of note, whilst there are numerous studies comparing acute and chronic wound fluids, there have not been any reports in the literature employing a longitudinal study in order to track biochemical changes in wound fluid as patients transition from a non-healing to healed state. Initially the objective of this study was to identify biochemical changes in CWF associated with wound healing using a proteomic approach. The proteomic approach incorporated a multi-dimensional liquid chromatography fractionation technique coupled with mass spectrometry (MS) to enable identification of proteins present in lower concentrations in CWF. Not surprisingly, many of the proteins identified in wound fluid were acute phase proteins normally expressed during the inflammatory phase of healing. However, the number of proteins positively identified by MS was quite low. This was attributed to the diverse range in concentration of protein species in CWF making it challenging to detect the diagnostically relevant low molecular weight proteins. In view of this, SELDI-TOF MS was also explored as a means to target low molecular weight proteins in sequential patient CWF samples during the course of healing. Unfortunately, the results generated did not yield any peaks of interest that were altered as wounds transitioned to a healed state. During the course of proteomic assessment of CWF, it became evident that a fraction of non-proteinaceous compounds strongly absorbed at 280 nm. Subsequent analyses confirmed that most of these compounds were in fact part of the purine catabolic pathway, possessing distinctive aromatic rings and which results in high absorbance at 254 nm. The accumulation of these purinogenic compounds in CWF suggests that the wound bed is poorly oxygenated resulting in a switch to anaerobic metabolism and consequently ATP breakdown. In addition, the presence of the terminal purine catabolite, uric acid (UA), indicates that the enzyme xanthine oxidoreductase (XOR) catalyses the reaction of hypoxanthine to xanthine and finally to UA. More importantly, the studies provide evidence for the first time of the exogenous presence of XOR in CWF. XOR is the only enzyme in humans capable of catalysing the production of UA in conjunction with a burst of the highly reactive superoxide radical and other oxidants like H2O2. Excessive release of these free radicals in the wound environment can cause cellular damage disrupting the normal wound healing process. In view of this, a sensitive and specific assay was established for monitoring low concentrations of these catabolites in CWF. This procedure involved combining high performance liquid chromatography (HPLC) with tandem mass spectrometry and multiple reaction monitoring (MRM). This application was selective, using specific MRM transitions and HPLC separations for each analyte, making it ideal for the detection and quantitation of purine catabolites in CWF. The results demonstrated that elevated levels of UA were detected in wound fluid obtained from patients with clinically worse ulcers. This suggests that XOR is active in the wound site generating significant amounts of reactive oxygen species (ROS). In addition, analysis of the amount of purine precursors in wound fluid revealed elevated levels of purine precursors in wound fluid from patients with less severe ulcers. Taken together, the results generated in this thesis suggest that monitoring changes of purine catabolites in CWF is likely to provide valuable information regarding the healing patterns of chronic venous leg ulcers. XOR catalysis of purine precursors not only provides a method for monitoring the onset, prognosis and progress of chronic venous leg ulcers, but also provides a potential therapeutic target by inhibiting XOR, thus blocking UA and ROS production. Targeting a combination of these purinogenic compounds and XOR could lead to the development of novel point of care diagnostic tests. Therefore, further investigation of these processes during wound healing will be worthwhile and may assist in elucidating the pathogenesis of this disease state, which in turn may lead to the development of new diagnostics and therapies that target these processes.

Community-based asylum seekers’ use of primary health care services in Melbourne

Objective: To investigate primary health care service utilisation and health presentations among asylum seekers living in Melbourne. Design and setting: Retrospective audit of files of people who attended three Melbourne asylum-seeker health clinics between 1 July 2005 and 30 June 2006. Main outcome measures: Rates of reasons for the encounter, diagnostic tests or investigations required, treatments prescribed and referrals. Results: Data were collected from 998 consultations corresponding to 341 people. Eighty-eight per cent of visits involved people with no Medicare access, owing to their visa status. The most common reasons for the encounter were general and unspecified symptoms or problems (rate, 59.9 per 100 encounters; 95% CI, 55–65), followed by musculoskeletal conditions (27.1; 95% CI, 24–30), and psychological problems (26.5; 95% CI, 23–30). The rate of referrals was 18.3 per 100 encounters (95% CI, 16–21). Conclusions: The three clinics providing services to asylum seekers in Melbourne are delivering care to a considerable number of people with complex health needs. A substantial number of asylum seekers present to clinics with psychological and social problems. Most cannot access government-subsidised health care. This must be addressed urgently by policy change at the federal and state and territory levels.

Exercising QS: Quantitative skills in an exercise science course

This study seeks to bring the discipline of exercise science into the discussion of Quantitative Skills (QS) in Science. The author’s experiences of providing learning support to students and working with educators in the field are described, demonstrating the difficulty of encouraging students to address their skills deficit. A survey of students’ perceptions of their own QS and of that required for their course, demonstrates the difficulties faced by students who do not have the prescribed assumed knowledge for the course. Limited results from academics suggest that their perceptions of students’ QS deficits are even more dire than those of the under-prepared students.

The case for routine cervical mediastinoscopy prior to radical surgery for malignant pleural mesothelioma

Objectives: To assess whether cervical mediastinoscopy is necessary before radical resection of malignant pleural mesothelioma (MPM). Methods: Patients who underwent radical excision of MPM in a 48-month period were prospectively followed for evidence of disease recurrence and death. Histological evidence of extra pleural lymph node metastases was correlated with survival. Lymph node size at intraoperative lymphadenectomy was correlated with the presence of metastatic tumour. Results: The 55 patients who underwent radical resection (51 extra pleural pneumonectomies and 4 radical pleurectomies) comprised 50 men and 5 women with a median age of 58 years, range 41-70. Histological examination revealed 50 epithelioid, four biphasic and one sarcomatoid histology. Postoperative IMIG T stage was stage I 4, II 11, III 30 and IV 10. Postoperatively the 17 patients with metastases to the extra pleural lymph nodes had significantly shorter survival (median 4.4 months, 95% CI 3.2-5.4) than those without (median survival 16.3 months, 95% CI 11.6-21.0) P=0.012 Kaplan-Meier analysis. Seventy-seven extra pleural lymph nodes without metastases were measured with a mean long axis diameter of 16.9 mm (range 4-55) ; 22 positive nodes had a mean long axis diameter of 15.2 mm (range 6-30). In 15 of the 17 patients with positive extra pleural nodes, the nodes could have been biopsied at cervical mediastinoscopy. Conclusions: This study confirms that extra pleural nodal metastases are related to poor survival. Pathological nodal involvement cannot be predicted from nodal dimensions. These data suggest that all patients being considered for radical resection of MPM should preferentially undergo preoperative cervical mediastinoscopy irrespective of radiological findings. © 2003 Elsevier B.V. All rights reserved.

Ambiguity Acceptance Testing : A Comparison of the Ratio Test and Difference Test

Integer ambiguity resolution is an indispensable procedure for all high precision GNSS applications. The correctness of the estimated integer ambiguities is the key to achieving highly reliable positioning, but the solution cannot be validated with classical hypothesis testing methods. The integer aperture estimation theory unifies all existing ambiguity validation tests and provides a new prospective to review existing methods, which enables us to have a better understanding on the ambiguity validation problem. This contribution analyses two simple but efficient ambiguity validation test methods, ratio test and difference test, from three aspects: acceptance region, probability basis and numerical results. The major contribution of this paper can be summarized as: (1) The ratio test acceptance region is overlap of ellipsoids while the difference test acceptance region is overlap of half-spaces. (2) The probability basis of these two popular tests is firstly analyzed. The difference test is an approximation to optimal integer aperture, while the ratio test follows an exponential relationship in probability. (3) The limitations of the two tests are firstly identified. The two tests may under-evaluate the failure risk if the model is not strong enough or the float ambiguities fall in particular region. (4) Extensive numerical results are used to compare the performance of these two tests. The simulation results show the ratio test outperforms the difference test in some models while difference test performs better in other models. Particularly in the medium baseline kinematic model, the difference tests outperforms the ratio test, the superiority is independent on frequency number, observation noise, satellite geometry, while it depends on success rate and failure rate tolerance. Smaller failure rate leads to larger performance discrepancy.

Plasmodium falciparum parasites lacking histidine-rich protein 2 and 3 : a review and recommendations for accurate reporting

Malaria rapid diagnostic tests (RDTs) play a critical role in malaria case management, surveillance and case investigations. Test performance is largely determined by design and quality characteristics, such as detection sensitivity, specificity, and thermal stability. However, parasite characteristics such as variable or absent expression of antigens targeted by RDTs can also affect RDT performance. Plasmodium falciparum parasites lacking the PfHRP2 protein, the most common target antigen for detection of P. falciparum, have been reported in some regions. Therefore, accurately mapping the presence and prevalence of P. falciparum parasites lacking pfhrp2 would be an important step so that RDTs targeting alternative antigens, or microscopy, can be preferentially selected for use in such regions. Herein the available evidence and molecular basis for identifying malaria parasites lacking PfHRP2 is reviewed, and a set of recommended procedures to apply for future investigations for parasites lacking PfHRP2, is proposed.