Semiparametric analysis of complex longitudinal data

Event history data consist of the longitudinal records of event occurrence times. Recurrent event data and panel count data are two common types of event history data that occur in many areas, such as medical studies and social sciences. A great deal of literature has been established for their analyses. Nevertheless, only limited research exists on the variable selection for recurrent event data and panel count data. The existing methods can be seen as direct generalizations of the available penalized procedures for linear models, but may not perform as well as expected due to the complex structure of event history data. The first and second parts of this dissertation then discuss simultaneous parameter estimation and variable selection for event history data. We present a new variable selection method with a new penalty function, which will be referred to as the broken adaptive ridge regression approach. In addition to the establishment of the oracle property, we also show that the proposed variable selection method has the clustering or grouping effect when covariates are highly correlated. Furthermore, the numerical studies are performed and indicate that the method works well for practical situations and can outperform the existing methods. Applications to real data are provided. Most of the existing studies of longitudinal data assume that covariates can be observed at the same observation times for the response variable, and the observation process is independent of the response variable completely or given covariates. In practice, the response variables and covariates are sometimes observed intermittently at different time points, leading to sparse asynchronous longitudinal data. The observation process may also be related to the response variable even given covariates and sometimes both issues can even occur at the same time. Although each of the two issues has been developed to address in literature, it does not seem to exist an established approach that can deal with both together. To address both issues simultaneously, the third part of this dissertation proposes a flexible semiparametric transformation conditional model and a kernel-weighted estimating equation based approach. The proposed estimators of regression parameters are shown to be consistent and asymptotically follow the normal distribution. For the assessment of the finite sample performance of the proposed method, an extensive simulation study is carried out and suggests that it performs well for practical situations. The approach is applied to a prospective HIV study that motivated this investigation.Includes bibliographical reference

Flexible estimation of temporal point processes and graphs

Handling complex data types with spatial structures, temporal dependencies, or discrete values, is generally a challenge in statistics and machine learning. In the recent years, there has been an increasing need of methodological and theoretical work to analyse non-standard data types, for instance, data collected on protein structures, genes interactions, social networks or physical sensors. In this thesis, I will propose a methodology and provide theoretical guarantees for analysing two general types of discrete data emerging from interactive phenomena, namely temporal point processes and graphs. On the one hand, temporal point processes are stochastic processes used to model event data, i.e., data that comes as discrete points in time or space where some phenomenon occurs. Some of the most successful applications of these discrete processes include online messages, financial transactions, earthquake strikes, and neuronal spikes. The popularity of these processes notably comes from their ability to model unobserved interactions and dependencies between temporally and spatially distant events. However, statistical methods for point processes generally rely on estimating a latent, unobserved, stochastic intensity process. In this context, designing flexible models and consistent estimation methods is often a challenging task. On the other hand, graphs are structures made of nodes (or agents) and edges (or links), where an edge represents an interaction or relationship between two nodes. Graphs are ubiquitous to model real-world social, transport, and mobility networks, where edges can correspond to virtual exchanges, physical connections between places, or migrations across geographical areas. Besides, graphs are used to represent correlations and lead-lag relationships between time series, and local dependence between random objects. Graphs are typical examples of non-Euclidean data, where adequate distance measures, similarity functions, and generative models need to be formalised. In the deep learning community, graphs have become particularly popular within the field of geometric deep learning. Structure and dependence can both be modelled by temporal point processes and graphs, although predominantly, the former act on the temporal domain while the latter conceptualise spatial interactions. Nonetheless, some statistical models combine graphs and point processes in order to account for both spatial and temporal dependencies. For instance, temporal point processes have been used to model the birth times of edges and nodes in temporal graphs. Moreover, some multivariate point processes models have a latent graph parameter governing the pairwise causal relationships between the components of the process. In this thesis, I will notably study such a model, called the Hawkes model, as well as graphs evolving in time. This thesis aims at designing inference methods that provide flexibility in the contexts of temporal point processes and graphs. This manuscript is presented in an integrated format, with four main chapters and two appendices. Chapters 2 and 3 are dedicated to the study of Bayesian nonparametric inference methods in the generalised Hawkes point process model. While Chapter 2 provides theoretical guarantees for existing methods, Chapter 3 also proposes, analyses, and evaluates a novel variational Bayes methodology. The other main chapters introduce and study model-free inference approaches for two estimation problems on graphs, namely spectral methods for the signed graph clustering problem in Chapter 4, and a deep learning algorithm for the network change point detection task on temporal graphs in Chapter 5. Additionally, Chapter 1 provides an introduction and background preliminaries on point processes and graphs. Chapter 6 concludes this thesis with a summary and critical thinking on the works in this manuscript, and proposals for future research. Finally, the appendices contain two supplementary papers. The first one, in Appendix A, initiated after the COVID-19 outbreak in March 2020, is an application of a discrete-time Hawkes model to COVID-related deaths counts during the first wave of the pandemic. The second work, in Appendix B, was conducted during an internship at Amazon Research in 2021, and proposes an explainability method for anomaly detection models acting on multivariate time series

TMS Algarve 2022: sustainability challenges in tourism, hospitality and management – Tourism & Management Studies International Conference 16 - 19 November - Olhão, Portugal: Programme and abstracts

Book of abstracts of the TMS Algarve 2022 (Tourism & Management Studies International Conference) entitled Sustainability Challenges in Tourism, Hospitality and Management, held on Real Marina Hotel & Spa, Olhão, Portugal, 16-19 November 2022info:eu-repo/semantics/publishedVersio

Micro-costing study of rituximab subcutaneous injection versus intravenous infusion in dutch setting

Background: Rituximab for subcutaneous (SC) administration has recently been approved for use in common forms of diffuse large B-cell lymphoma (DLBCL). This form of rituximab is supplied in ready-to-use vials that do not require individual dose adjustment. It is expected that SC-injection will shorten the treatment time per administration of rituximab in comparison with currently available intravenous (IV) infusion. Aims: The goal of this study is to identify and compare all direct costs of IV and SC rituximab given to the DLBCL patients in the Netherlands. Methods: Using a prospective, observational, bottom up, micro-costing study we collected primary data on the direct medical costs of the preparation, administration and acquisition of rituximab. Drug costs and spillage, labor costs, material costs and remaining daycare costs were identified using standardized forms, structured using guideline prices and compared for the IV and SC forms of rituximab. Results: Measurements were done on 53 administrations (33 IV and 20 SC). The mean total costs of the IV infusion were €2174, and €1907 for the SC injection. The estimated difference of €267 per administration was mainly due to spillage costs and differences in chair time, related daycare costs and drug costs. Summary and Conclusions: Rituximab administered in the form of SC injection is less costly than its IV form. Taking into account their equal effectiveness, favorable pharmacoeconomic profile of SC rituximab can result in significant savings when transferred to the total DLBCL population in the Netherlands

Trial efficacy vs real world effectiveness in first line treatment of multiple myeloma

Background: Large randomized clinical trials (RCT) are the foundation of the registration of newly developed drugs. A potential problem with RCTs is that the inclusion/exclusion criteria will make the population different from the actual population treated in real life. Hence, it is important to understand how the results from the RCT can be generalized to a general population. Aims: The primary aim of the present study was to assess the generalizability of the large 1st line RCTs in Multiple Myeloma (MM) to the Nordic setting and to understand potential difference and magnitude in outcomes between RCTs and patients treated in standard care in the Nordics. Methods: A retrospective analysis was performed on an incident cohort of 2960 MM-patients from 24 hospitals in Denmark, Finland, Norway and Sweden. The database contained information on patient baseline characteristics, treatments and outcomes. Data from relevant 1st line MM RCTs was selected from the treatment MP (Waage, A., et al., Blood. 2010], MPT (Waage, A., et al., Blood. 2010) and VMP (San Miguel, J.F., et al., N Engl J Med, 2008) and baseline characteristics were compared to newly diagnosed Nordic MM treated patients. Potential difference in response and overall survival (OS) was estimated by adjusting the RWE population to the RCT population using matching adjusted indirect comparisons. Patients were matched on age (median approximated to mean), gender, calcium, beta2-microglobulin and ISS score 3. These variables were selected because they were reported in all trials and have previously been identified as having prognostic value. Results: Patients in the Nordic database treated with MP (n=880) had a response rate of (PD, NR, PR, VGPR, ≥nCR) of (13%, 39%, 38%, 6%, 4%). After matching (n=347), the response rate was slightly worse (12%, 43%, 36%, 6%, 3%). This can be compared to the response rate from the RCT of (7%, 53%, 33%, 3%, 4%). OS for Nordic MP treated patients was 2.67 years (2.25-3.17). After matching the OS was 3.37 years (2.86-3.96) and this can be compared to the trial with OS 2.40 years (2.23-2.66). Patients treated with MPT (n=283) in the Nordic countries had a response rate of (5%, 14%, 52%, 20%, 9%). After matching (n=179) the response rate was slightly changed to (6%, 20%, 50%, 13% 11%). The corresponding RCT response results were 14%, 29%, 34%, 10%, and 13% respectively. OS for Nordic MPT treated patients was 4.15 years (3.73- 4.74). After matching the OS was 4.28 years (3.98-NA) years and compared to 2.42 years (2.08-3.17) OS observed in the corresponding trial. Patients treated with VMP (n=59) in the Nordic countries had a response rate of (4%, 5%, 40%, 18%, 33%). After matching (n=31) the response rate was improved to (8%, 11%, 28%, 8%, 45%). This corresponding response rates shown in the trial are 1%, 23%, 33%, 8%, and 33% respectively. OS for Nordic MP treated patients was 4.86 years (3.79-NA). After matching the OS was 4.86 years (4.86-NA) and this can be compared to the trial with OS 4.70 years. Summary and Conclusions: Surprisingly Nordic treated MM patients do very well compared to, and even better than, patients treated in RCTs. Since the OS for all tested treatments improves after matching to the RCT baseline characteristics, patients recruited to the RCTs seems to be a bit better than ordinary Nordic patents. The database used in the present study, and the used method, can be valuable for generalizing the results to the Nordic setting and estimating potential difference for future RCTs and Nordic MM treated patients. Future research should include different data cuts to see whether the analyses are biased by differences subsequent treatments applied in RCTs and clinical practice

Sustainable agriculture and rural development in terms of the republic of Serbia strategic goals realization within the Danube region. Achieving regional competitiveness

International Scientific Conference „SUSTAINABLE AGRICULTURE AND RURAL DEVELOPMENT IN TERMS OF THE REPUBLIC OF SERBIA STRATEGIC GOALS REALIZATION WITHIN THE DANUBE REGION -achieving regional competitiveness“, which was held in period 5-7th December 2013 in Topola, the Republic of Serbia, through number of presented papers mainly provides an overview of results of scientific research on the integrated and interdisciplinary project no. III 46006 „SUSTAINABLE AGRICULTURE AND RURAL DEVELOPMENT IN TERMS OF THE REPUBLIC OF SERBIA STRATEGIC GOALS REALIZATION WITHIN THE DANUBE REGION“. International Scientific Conference „SUSTAINABLE AGRICULTURE AND RURAL DEVELOPMENT IN TERMS OF THE REPUBLIC OF SERBIA STRATEGIC GOALS REALIZATION WITHIN THE DANUBE REGION - achieving regional competitiveness“, gathered number of scientific workers and experts from many countries. Besides the authors from Serbia in Thematic Proceedings are also presented the papers of authors from Bosnia and Herzegovina, Macedonia, Romania, Russia, Moldova, Slovakia, Ukraine, Germany, the Netherlands, Japan and Austria. After all 92 papers were positively reviewed by the reviewers and presented on the International Scientific Conference, they were published in the Thematic Proceedings. Proceedings publisher was Institute of Agricultural Economics Belgrade, together with 34 eminent scientific-educational institutions from Serbia and abroad. In the Plenary Section were presented 3 papers which gave significant contributions to International Scientific Conference. Rest of the papers are systematized in 3 thematic sections: IKNOWLEDGE ECONOMY AND HUMAN CAPITAL IN THE FUNCTION OF IMPROVING REGIONAL COMPETITIVENESS (45 papers); II BIOREGIONALISM AND PERMACULTURE AS A CONCEPTS OF CONSERVATION OF ECOLOGICAL SPECIFICITIES OF RURAL AREAS (27 papers); III THE CONSTRUCTION OF AGRO-REGIONAL IDENTITY THROUGH INSTITUTIONAL REFORM (17 papers)

Sustainable agriculture and rural development in terms of the republic of Serbia strategic goals realization within the Danube region. Achieving regional competitiveness

International Scientific Conference „SUSTAINABLE AGRICULTURE AND RURAL DEVELOPMENT IN TERMS OF THE REPUBLIC OF SERBIA STRATEGIC GOALS REALIZATION WITHIN THE DANUBE REGION -achieving regional competitiveness“, which was held in period 5-7th December 2013 in Topola, the Republic of Serbia, through number of presented papers mainly provides an overview of results of scientific research on the integrated and interdisciplinary project no. III 46006 „SUSTAINABLE AGRICULTURE AND RURAL DEVELOPMENT IN TERMS OF THE REPUBLIC OF SERBIA STRATEGIC GOALS REALIZATION WITHIN THE DANUBE REGION“. International Scientific Conference „SUSTAINABLE AGRICULTURE AND RURAL DEVELOPMENT IN TERMS OF THE REPUBLIC OF SERBIA STRATEGIC GOALS REALIZATION WITHIN THE DANUBE REGION - achieving regional competitiveness“, gathered number of scientific workers and experts from many countries. Besides the authors from Serbia in Thematic Proceedings are also presented the papers of authors from Bosnia and Herzegovina, Macedonia, Romania, Russia, Moldova, Slovakia, Ukraine, Germany, the Netherlands, Japan and Austria. After all 92 papers were positively reviewed by the reviewers and presented on the International Scientific Conference, they were published in the Thematic Proceedings. Proceedings publisher was Institute of Agricultural Economics Belgrade, together with 34 eminent scientific-educational institutions from Serbia and abroad. In the Plenary Section were presented 3 papers which gave significant contributions to International Scientific Conference. Rest of the papers are systematized in 3 thematic sections: IKNOWLEDGE ECONOMY AND HUMAN CAPITAL IN THE FUNCTION OF IMPROVING REGIONAL COMPETITIVENESS (45 papers); II BIOREGIONALISM AND PERMACULTURE AS A CONCEPTS OF CONSERVATION OF ECOLOGICAL SPECIFICITIES OF RURAL AREAS (27 papers); III THE CONSTRUCTION OF AGRO-REGIONAL IDENTITY THROUGH INSTITUTIONAL REFORM (17 papers)

Proceedings of the II International Congress on Interdisciplinarity in Social and Human Sciences

Interdisciplinarity is the main topic and the main goal of this conference. Since the sixteen century with the creation of the first Academy of Sciences, in Napoles (Italy) (1568), and before that with the creation of the Fine Arts Academies, the world of science and arts began to work independently, on the contrary of the Academy of Plato, in Classical Antiquity, where science, art and sport went interconnected. Over time, specific sciences began to be independent, and the specificity of sciences caused an increased difficulty in mutual understanding. The same trend has affected the Human and Social Sciences. Each of the specific sciences gave rise to a wide range of particular fields. This has the advantage of allowing the deepening of specialised knowledge, but it means that there is often only a piecemeal approach of the research object, not taking into account its overall complexity. So, it is important to work for a better understanding of the scientific phenomena with the complementarity of the different sciences, in an interdisciplinary perspective. With this growing specialisation of sciences, Interdisciplinarity acquired more relevance for scientists to find more encompassing and useful answers for their research questions. CIEO (Research Centre for Spatial and Organizational Dynamics) organises this conference, being Interdisciplinarity an important issue.info:eu-repo/semantics/acceptedVersio