Multiple testing in spatial epidemiology: a Bayesian approach

In this work we aim to propose a new approach for preliminary epidemiological studies on Standardized Mortality Ratios (SMR) collected in many spatial regions. A preliminary study on SMRs aims to formulate hypotheses to be investigated via individual epidemiological studies that avoid bias carried on by aggregated analyses. Starting from collecting disease counts and calculating expected disease counts by means of reference population disease rates, in each area an SMR is derived as the MLE under the Poisson assumption on each observation. Such estimators have high standard errors in small areas, i.e. where the expected count is low either because of the low population underlying the area or the rarity of the disease under study. Disease mapping models and other techniques for screening disease rates among the map aiming to detect anomalies and possible high-risk areas have been proposed in literature according to the classic and the Bayesian paradigm. Our proposal is approaching this issue by a decision-oriented method, which focus on multiple testing control, without however leaving the preliminary study perspective that an analysis on SMR indicators is asked to. We implement the control of the FDR, a quantity largely used to address multiple comparisons problems in the eld of microarray data analysis but which is not usually employed in disease mapping. Controlling the FDR means providing an estimate of the FDR for a set of rejected null hypotheses. The small areas issue arises diculties in applying traditional methods for FDR estimation, that are usually based only on the p-values knowledge (Benjamini and Hochberg, 1995; Storey, 2003). Tests evaluated by a traditional p-value provide weak power in small areas, where the expected number of disease cases is small. Moreover tests cannot be assumed as independent when spatial correlation between SMRs is expected, neither they are identical distributed when population underlying the map is heterogeneous. The Bayesian paradigm oers a way to overcome the inappropriateness of p-values based methods. Another peculiarity of the present work is to propose a hierarchical full Bayesian model for FDR estimation in testing many null hypothesis of absence of risk.We will use concepts of Bayesian models for disease mapping, referring in particular to the Besag York and Mollié model (1991) often used in practice for its exible prior assumption on the risks distribution across regions. The borrowing of strength between prior and likelihood typical of a hierarchical Bayesian model takes the advantage of evaluating a singular test (i.e. a test in a singular area) by means of all observations in the map under study, rather than just by means of the singular observation. This allows to improve the power test in small areas and addressing more appropriately the spatial correlation issue that suggests that relative risks are closer in spatially contiguous regions. The proposed model aims to estimate the FDR by means of the MCMC estimated posterior probabilities b i's of the null hypothesis (absence of risk) for each area. An estimate of the expected FDR conditional on data (\FDR) can be calculated in any set of b i's relative to areas declared at high-risk (where thenull hypothesis is rejected) by averaging the b i's themselves. The\FDR can be used to provide an easy decision rule for selecting high-risk areas, i.e. selecting as many as possible areas such that the\FDR is non-lower than a prexed value; we call them\FDR based decision (or selection) rules. The sensitivity and specicity of such rule depend on the accuracy of the FDR estimate, the over-estimation of FDR causing a loss of power and the under-estimation of FDR producing a loss of specicity. Moreover, our model has the interesting feature of still being able to provide an estimate of relative risk values as in the Besag York and Mollié model (1991). A simulation study to evaluate the model performance in FDR estimation accuracy, sensitivity and specificity of the decision rule, and goodness of estimation of relative risks, was set up. We chose a real map from which we generated several spatial scenarios whose counts of disease vary according to the spatial correlation degree, the size areas, the number of areas where the null hypothesis is true and the risk level in the latter areas. In summarizing simulation results we will always consider the FDR estimation in sets constituted by all b i's selected lower than a threshold t. We will show graphs of the\FDR and the true FDR (known by simulation) plotted against a threshold t to assess the FDR estimation. Varying the threshold we can learn which FDR values can be accurately estimated by the practitioner willing to apply the model (by the closeness between\FDR and true FDR). By plotting the calculated sensitivity and specicity (both known by simulation) vs the\FDR we can check the sensitivity and specicity of the corresponding\FDR based decision rules. For investigating the over-smoothing level of relative risk estimates we will compare box-plots of such estimates in high-risk areas (known by simulation), obtained by both our model and the classic Besag York Mollié model. All the summary tools are worked out for all simulated scenarios (in total 54 scenarios). Results show that FDR is well estimated (in the worst case we get an overestimation, hence a conservative FDR control) in small areas, low risk levels and spatially correlated risks scenarios, that are our primary aims. In such scenarios we have good estimates of the FDR for all values less or equal than 0.10. The sensitivity of\FDR based decision rules is generally low but specicity is high. In such scenario the use of\FDR = 0:05 or\FDR = 0:10 based selection rule can be suggested. In cases where the number of true alternative hypotheses (number of true high-risk areas) is small, also FDR = 0:15 values are well estimated, and \FDR = 0:15 based decision rules gains power maintaining an high specicity. On the other hand, in non-small areas and non-small risk level scenarios the FDR is under-estimated unless for very small values of it (much lower than 0.05); this resulting in a loss of specicity of a\FDR = 0:05 based decision rule. In such scenario\FDR = 0:05 or, even worse,\FDR = 0:1 based decision rules cannot be suggested because the true FDR is actually much higher. As regards the relative risk estimation, our model achieves almost the same results of the classic Besag York Molliè model. For this reason, our model is interesting for its ability to perform both the estimation of relative risk values and the FDR control, except for non-small areas and large risk level scenarios. A case of study is nally presented to show how the method can be used in epidemiology.

Costrutti ed Applicazioni di Programmazione Generica in Linguaggi Object-Oriented

Generic programming is likely to become a new challenge for a critical mass of developers. Therefore, it is crucial to refine the support for generic programming in mainstream Object-Oriented languages — both at the design and at the implementation level — as well as to suggest novel ways to exploit the additional degree of expressiveness made available by genericity. This study is meant to provide a contribution towards bringing Java genericity to a more mature stage with respect to mainstream programming practice, by increasing the effectiveness of its implementation, and by revealing its full expressive power in real world scenario. With respect to the current research setting, the main contribution of the thesis is twofold. First, we propose a revised implementation for Java generics that greatly increases the expressiveness of the Java platform by adding reification support for generic types. Secondly, we show how Java genericity can be leveraged in a real world case-study in the context of the multi-paradigm language integration. Several approaches have been proposed in order to overcome the lack of reification of generic types in the Java programming language. Existing approaches tackle the problem of reification of generic types by defining new translation techniques which would allow for a runtime representation of generics and wildcards. Unfortunately most approaches suffer from several problems: heterogeneous translations are known to be problematic when considering reification of generic methods and wildcards. On the other hand, more sophisticated techniques requiring changes in the Java runtime, supports reified generics through a true language extension (where clauses) so that backward compatibility is compromised. In this thesis we develop a sophisticated type-passing technique for addressing the problem of reification of generic types in the Java programming language; this approach — first pioneered by the so called EGO translator — is here turned into a full-blown solution which reifies generic types inside the Java Virtual Machine (JVM) itself, thus overcoming both performance penalties and compatibility issues of the original EGO translator. Java-Prolog integration Integrating Object-Oriented and declarative programming has been the subject of several researches and corresponding technologies. Such proposals come in two flavours, either attempting at joining the two paradigms, or simply providing an interface library for accessing Prolog declarative features from a mainstream Object-Oriented languages such as Java. Both solutions have however drawbacks: in the case of hybrid languages featuring both Object-Oriented and logic traits, such resulting language is typically too complex, thus making mainstream application development an harder task; in the case of library-based integration approaches there is no true language integration, and some “boilerplate code” has to be implemented to fix the paradigm mismatch. In this thesis we develop a framework called PatJ which promotes seamless exploitation of Prolog programming in Java. A sophisticated usage of generics/wildcards allows to define a precise mapping between Object-Oriented and declarative features. PatJ defines a hierarchy of classes where the bidirectional semantics of Prolog terms is modelled directly at the level of the Java generic type-system.

Effectiveness of individual resource-oriented joint protection education in people with rheumatoid arthritis. A randomized controlled trial

the modern joint protection (JP) concept for people with rheumatoid arthritis (RA) is an active coping strategy to improve daily tasks and role performance by changing working methods and using assistive devices. Effective group JP education includes psycho-educational interventions. The Pictorial Representation of Illness and Self Measure (PRISM) is an interactive hands-on-tool, assessing (a) the individual's perceived burden of illness and (b) relevant individual resources. Both issues are important for intrinsic motivation to take action and change behaviour. This study compared individual conventional JP education (C-JP) with PRISM-based JP education (PRISM-JP).

Reshaping Rural Extension: Learning for Sustainability (LforS): An Integrative and Learning-Based Advisory Approach for Rural Extension with Small-Scale Farmers

This publication offers concrete suggestions for implementing an integrative and learning-oriented approach to agricultural extension with the goal of fostering sustainable development. It targets governmental and non-governmental organisations, development agencies, and extension staff working in the field of rural development. The book looks into the conditions and trends that influence extension today, and outlines new challenges and necessary adaptations. It offers a basic reflection on the goals, the criteria for success and the form of a state-of-the-art approach to extension. The core of the book consists of a presentation of Learning for Sustainability (LforS), an example of an integrative, learning-oriented approach that is based on three crucial elements: stakeholder dialogue, knowledge management, and organizational development. Awareness raising and capacity building, social mobilization, and monitoring & evaluation are additional building blocks. The structure and organisation of the LforS approach as well as a selection of appropriate methods and tools are presented. The authors also address key aspects of developing and managing a learning-oriented extension approach. The book illustrates how LforS can be implemented by presenting two case studies, one from Madagascar and one from Mongolia. It addresses conceptual questions and at the same time it is practice-oriented. In contrast to other extension approaches, LforS does not limit its focus to production-related aspects and the development of value chains: it also addresses livelihood issues in a broad sense. With its focus on learning processes LforS seeks to create a better understanding of the links between different spheres and different levels of decision-making; it also seeks to foster integration of the different actors’ perspectives.

International Service-Learning and the Development of Civic Identity: Understanding the Role of Short-Term International Service-Learning and its Influence on the Development of Civic Identity in College Students Using a Mixed Methodological Approach

Higher education has a responsibility to educate a democratic citizenry and recent research indicates civic engagement is on the decline in the United States. Through a mixed methodological approach, I demonstrate that the potential exists for well structured short-term international service-learning programming to develop college students’ civic identities. Quantitative analysis of questionnaire data, collected from American college students immediately prior to their participation in a short-term service-learning experience in Northern Ireland and again upon their return to the United States, revealed increases in civic accountability, political efficacy, justice oriented citizenship, and service-learning. Subsequent qualitative analysis of interview transcripts, student journals, and field notes suggested that facilitated critical reflection before, during, and after the experience promoted transformational learning. Emergent themes included: (a) responsibilities to others, (b) the value of international service-learning, (c) crosspollination of ideas, (d) stepping outside the daily routine to facilitate divergent thinking, and (e) the necessity of precursory thinking for sustaining transformations in thinking. The first theme, responsibilities to others, was further divided into subthemes of thinking beyond oneself, raising awareness of responsibility to others, and voting responsibly.

Facing the dreaded: does mindfulness facilitate coping with distressing experiences? A moderator analysis

Increasing evidence shows that mindfulness is positively related to mental health; however, the nature of this relationship is not fully understood. The current study used structural equation modeling to investigate the hypothesis that mindfulness moderates the association between the occurrence of unavoidable distressing experiences (UDE) and mental health. Participants from a community sample (N = 376) completed the Freiburg Mindfulness Inventory, the Positive and Negative Affect Scale, the Brief Symptom Inventory, the Inventory of Approach and Avoidance Motivation, and the Incongruence Scale. Results indicated that mindfulness moderated the association between unavoidable distressing events and psychopathological symptoms/negative affect. Thus, mindfulness may contribute to enhance the ability to cope with UDE and thus mitigate the detrimental effects of these experiences on mental health.

Object-Oriented Legacy System Trace-based Logic Testing

When reengineering legacy systems, it is crucial to assess if the legacy behavior has been preserved or how it changed due to the reengineering effort. Ideally if a legacy system is covered by tests, running the tests on the new version can identify potential differences or discrepancies. However, writing tests for an unknown and large system is difficult due to the lack of internal knowledge. It is especially difficult to bring the system to an appropriate state. Our solution is based on the acknowledgment that one of the few trustable piece of information available when approaching a legacy system is the running system itself. Our approach reifies the execution traces and uses logic programming to express tests on them. Thereby it eliminates the need to programatically bring the system in a particular state, and handles the test-writer a high-level abstraction mechanism to query the trace. The resulting system, called TESTLOG, was used on several real-world case studies to validate our claims.

An EEG approach to the neurodevelopmental hypothesis of schizophrenia studying schizophrenics, normal controls and adolescents

Based on an integrative brain model which focuses on memory-driven and EEG state-dependent information processing for the organisation of behaviour, we used the developmental changes of the awake EEG to further investigate the hypothesis that neurodevelopmental abnormalities (deviations in organisation and reorganisation of cortico-cortical connectivity during development) are involved in the pathogenesis of schizophrenia. First-episode, neuroleptic-naive schizophrenics and their matched controls and three age groups of normal adolescents were studied (total: 70 subjects). 19-channel EEG delta-theta, alpha and beta spectral band centroid frequencies during resting (baseline) and after verbal stimuli were used as measure of the level of attained complexity and momentary excitability of the neuronal network (working memory). Schizophrenics compared with all control groups showed lower delta-theta activity centroids and higher alpha and beta activity centroids. Reactivity centroids (centroid after stimulus minus centroid during resting) were used as measure of update of working memory. Schizophrenics showed partial similarities in delta-theta and beta reactivity centroids with the 11-year olds and in alpha reactivity centroids with the 13-year olds. Within the framework of our model, the results suggest multifactorially elicited imbalances in the level of excitability of neuronal networks in schizophrenia, resulting in network activation at dissociated complexity levels, partially regressed and partially prematurely developed. It is hypothesised that activation of age- and/or state-inadequate representations for coping with realities becomes manifest as productive schizophrenic symptoms. Thus, the results support some aspects of the neurodevelopmental hypothesis.

Learning for Sustainability - LforS: An extension approach in small scale farming

Description of LforS as a integrativ and learning oriented extension approach

Practical Object-Oriented Back-in-Time Debugging

Back-in-time debuggers are extremely useful tools for identifying the causes of bugs, as they allow us to inspect the past states of objects no longer present in the current execution stack. Unfortunately the "omniscient" approaches that try to remember all previous states are impractical because they either consume too much space or they are far too slow. Several approaches rely on heuristics to limit these penalties, but they ultimately end up throwing out too much relevant information. In this paper we propose a practical approach to back-in-time debugging that attempts to keep track of only the relevant past data. In contrast to other approaches, we keep object history information together with the regular objects in the application memory. Although seemingly counter-intuitive, this approach has the effect that past data that is not reachable from current application objects (and hence, no longer relevant) is automatically garbage collected. In this paper we describe the technical details of our approach, and we present benchmarks that demonstrate that memory consumption stays within practical bounds. Furthermore since our approach works at the virtual machine level, the performance penalty is significantly better than with other approaches.

The role of specialisation in the promotion of young football talents: A person-oriented study

This paper investigates the controversial question whether it is more effective to promote specialisation in a specific sport at the beginning of a career or whether to encourage a broad range of sports when promoting competitive sports talents in order for them to achieve a high level of performance in adulthood. The issue of promoting talents depends on human developmental processes and therefore raises developmental scientific questions. Based on recent, dynamic-interactionist concepts of development, we assume a person-oriented approach focussing on the person as a whole rather than individual features. Theoretical considerations lead to four interacting factors being summarised to form a subsystem: childhood training. The relative weights of these factors lead to patterns. By relating these to a performance criterion at the age of peak performance, particularly promising developmental patterns may be identified. One hundred fifty-nine former Swiss football talents were retrospectively interviewed about their career and the data analysed using the LICUR method. Two early career patterns were identified as having a favourable influence on adult performance. Both are characterised by an above-average amount of in-club training. One pattern also exhibits an above-average amount of informal football played outside the club, the other above-average scores for activity in other sports. Hence, comprehensive training and practice inside and outside the club form the basis for subsequent football expertise.

Successful Careers in Football – Findings of a Person-Oriented Study

A successful career in football is the result of the appropriate interaction between different aspects of an individual’s life, since the various areas and phases of one’s life depend on each other. An endogenous causal relationship exists throughout a person’s entire history (Mayer, 1990). In particular, their family, work and sports career must be tuned to each other. The transition from the initial stages of education (compulsory schooling) to vocational training, which coincides with the beginning of the selection for the national youth teams, is a particularly critical phase (Wylleman, Theeboom, & Lavallee, 2004). In order to do justice to the overall life situation of a young sports talent during this transition phase, we have adopted a holistic perspective and follow Bergman, Magnusson and El-Khouri (2003) in using a person-oriented and systemic approach. In doing so, our main focus lies on the person-environment system. This overall system is made up of various subsystems, consisting of several operating factors which interact with one another. The different levels to which these operating factors are expressed lead to observable patterns, which can be summarised in the form of types. Particularly promising types can therefore be identified and the developmental process can be described. Former players on the Swiss U16 to U21 national football teams, born between 1981 and 1987 (n=159), were interviewed concerning their careers, and the operating factors school/vocational training, family support and sports environment were examined. With the help of the LICUR method (Linking of Clusters after removal of Residue) (Bergman et al., 2003), developmental types were identified which were promising in terms of achieving top performance in adulthood. A range of developmental types and anti-types emerge for the transition from the under-15 phase to the over-16 phase. One particularly promising type is observed in the over-16 phase, for which the operating factors education, family support and participation in national U16 to U18 teams have slightly above-average scores, with scores that are well above average in the sports environment.

A Health- and Resource-Oriented Perspective on NSLBP

Nonspecific low back pain (NSLBP) is an important health issue of our time. Personal as well as economic factors, like suffering pain and experiencing disability on the one hand and enormous and still increasing costs to the economy and society on the other hand, display the importance of the matter. Tremendous research has been conducted in the last few decades on NSLBP. A PubMed search (June 17, 2013) on “low back pain” provided 22,980 hits, and when specifying for “low back pain, systematic review,” 3,134 hits were still generated. Most research has been done examining the development, risk factors, or therapeutic measures of NSLBP, but hardly any literature exists on resources related to NSLBP. The aims of this review are twofold. In order to shade light on the salutogenetic approach of NSLBP, and thus to focus on health instead of illness, the first aim is to facilitate the understanding of which therapeutic measures enhance the ability to cope with chronic NSLBP and enable (more) normal functioning in life. The second aim is to stimulate the understanding of resources protecting against the onset of NSLBP or against the development of chronic NSLBP and its resulting work absence.

Maximising the impact of research: the NCCR North-South approach: Fourth NCCR North-South Report on Effectiveness

Interest is growing in the impact that science can have on reducing poverty in the global South. If we understand impact as the “demonstrable contribution that excellent research makes to society and the economy”, the concept encompasses a variety of contributions of research-related knowledge and skills that benefit people and the environment. One reason for the growing interest in impact in this context is research councils’ increasing focus on documenting the social and environmental benefits of science, as indicated by the above quotation from the British research councils. Another reason is that research funding agencies from the private and public sectors are now more interested in social innovations for solving problems on the ground. Research can indeed influence policymakers’ views, policy development, funding patterns, and implementation or practice. This is promising for those who would like to improve – and prove – the influence research can have on policy and practice. It is also of importance for better understanding the intended and unintended effects of research. This report presents the NCCR North-South approach to increasing the impact of development-oriented research. It explains how we can maximise our impact and how we can assess whether our efforts have worked, based on six case studies from around the world. The report is of interest to all researchers who wish to respond to policy and practice from their point of view and who are keen on publicising their evidence. It is also relevant to those who teach how to maximise research impact.

Benefits and challenges in practice-oriented psychotherapy research in Germany: The TK and the QS-PSY-BAY projects of quality assurance in outpatient psychotherapy

Objective: Two patient-focused long-term research projects performed in the German outpatient psychotherapy system are focused on in this article. The TK (Techniker Krankenkasse) project is the first study to evaluate a quality assurance and feedback system with regard to its practical feasibility in German routine care. The other study (“Quality Assurance in Outpatient Psychotherapy in Bavaria”; QS-PSY-BAY) was designed to test a new approach for quality assurance in outpatient psychotherapy using electronic documentation of patient characteristics and outcome parameters. In addition this project provides the opportunity to analyze data on health-related costs for the patients undergoing outpatient psychotherapy. Method: Both projects and their results indicating high effect sizes are briefly described. Results: From the perspectives of the research teams, advisory boards and other stakeholders, the experiences with these projects are discussed focusing on obstacles, challenges, difficulties, and benefits in developing and implementing the studies. The triangle collaboration of therapists, researchers, and health insurance companies/health service institutions turned out to be fruitful in both studies. Conclusions: Despite some controversies between the partners the experiences indicate the importance of practiced-research collaborations to provide relevant information about the delivery of outpatient psychotherapy in the health system