Systems medicine and integrated care to combat chronic noncommunicable diseases

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

Field Sales Management Control: Towards a Multi-Level Theory

The purpose of this dissertation is to increase the understanding and knowledge of field sales management control systems (i.e. sales managers monitoring, directing, evaluating and rewarding activities) and their potential consequences on salespeople. This topic is important because research conducted in the past has indicated that the choice of control system type can on the other hand have desirable consequences, such as high levels of motivation and performance, and on the other hand leadto harmful unintended consequences, such as opportunistic or unethical behaviors. Despite the fact that marketing and sales management control systems have been under rigorous research for over two decades, it still is at a very early stage of development, and several inconsistencies can be found in the research results. This dissertation argues that these inconsistencies are mainly derived from misspecification of the level of analysis in the past research. These different levels of analysis (i.e. strategic, tactical, and operational levels) involve very different decision-making situations regarding the control and motivation of sales force, which should be taken into consideration when conceptualizing the control. Moreover, the study of salesperson consequences of a field sales management control system is actually a cross-level phenomenon, which means that at least two levels of analysis are simultaneously involved. The results of this dissertation confirm the need to re-conceptualize the field sales management control system concept. It provides empirical evidence for the assertion that control should be conceptualized with more details atthe tactical/operational level of analysis than at the strategic levelof analysis. Moreover, the results show that some controls are more efficiently communicated to field salespeople than others. It is proposed that this difference is due to different purposes of control; some controls aredesigned for influencing salespersons' behavior (aim at motivating) whereas some controls are designed to aid decision-making (aim at providing information). According to the empirical results of this dissertation, the both types of controls have an impact to the sales force, but this impactis not as strong as expected. The results obtained in this dissertation shed some light to the nature of field sales management control systems, and their consequences on salespeopl

Studies on coordination of systems development process

This thesis examines coordination of systems development process in a contemporary software producing organization. The thesis consists of a series of empirical studies in which the actions, conceptions and artifacts of practitioners are analyzed using a theory-building case study research approach. The three phases of the thesis provide empirical observations on different aspects of systemsdevelopment. In the first phase is examined the role of architecture in coordination and cost estimation in multi-site environment. The second phase involves two studies on the evolving requirement understanding process and how to measure this process. The third phase summarizes the first two phases and concentrates on the role of methods and how practitioners work with them. All the phases provide evidence that current systems development method approaches are too naïve in looking at the complexity of the real world. In practice, development is influenced by opportunity and other contingent factors. The systems development processis not coordinated using phases and tasks defined in methods providing universal mechanism for managing this process like most of the method approaches assume.Instead, the studies suggest that managing systems development process happens through coordinating development activities using methods as tools. These studies contribute to the systems development methods by emphasizing the support of communication and collaboration between systems development participants. Methods should not describe the development activities and phases in a detail level, butshould include the higher level guidance for practitioners on how to act in different systems development environments.

Involvement of family physicians in structured programs for chronic diseases or multi-morbidity in Switzerland.

The increasing prevalence of chronic diseases and multi-morbidity represents challenges for health systems worldwide. In that perspective, the current organization of healthcare delivery, fragmentation of care, limited use of evidence-based guidelines and patients'insufficient empowerment are some reasons explaining the current limited effectiveness of the management of chronically ill patients. Based on theoretical models such as the Chronic Care Model (CCM), initiatives targeting improvements in the care of patients with chronic diseases have been implemented worldwide since more than a decade. Their development in Switzerland, a health system where more than half of practices are still single handed [6], is only recent and infrequent. Structured programs for patients with chronic diseases or multimorbidity usually propose patient-centered interventions and consider an integrative multidisciplinary approach. Currently, little is known on the existence of such programs and on the role of family physicians (FPs)within these programs, in Switzerland. The objective of this study was to identify and describe current structured programs targeting chronic diseases or multi-morbidity in Switzerland. This may help in examining innovative approaches that are only developed locally but would deserve wider interest for further implementation. We conducted a telephone-based survey between June and November 2013 and contacted systematically key institutions, informants and stakeholders nationwide and in the 26 cantons...

Identifying the preferred subset of enzymatic profiles in nonlinear kinetic metabolic models via multiobjective global optimization and pareto filters

Optimization models in metabolic engineering and systems biology focus typically on optimizing a unique criterion, usually the synthesis rate of a metabolite of interest or the rate of growth. Connectivity and non-linear regulatory effects, however, make it necessary to consider multiple objectives in order to identify useful strategies that balance out different metabolic issues. This is a fundamental aspect, as optimization of maximum yield in a given condition may involve unrealistic values in other key processes. Due to the difficulties associated with detailed non-linear models, analysis using stoichiometric descriptions and linear optimization methods have become rather popular in systems biology. However, despite being useful, these approaches fail in capturing the intrinsic nonlinear nature of the underlying metabolic systems and the regulatory signals involved. Targeting more complex biological systems requires the application of global optimization methods to non-linear representations. In this work we address the multi-objective global optimization of metabolic networks that are described by a special class of models based on the power-law formalism: the generalized mass action (GMA) representation. Our goal is to develop global optimization methods capable of efficiently dealing with several biological criteria simultaneously. In order to overcome the numerical difficulties of dealing with multiple criteria in the optimization, we propose a heuristic approach based on the epsilon constraint method that reduces the computational burden of generating a set of Pareto optimal alternatives, each achieving a unique combination of objectives values. To facilitate the post-optimal analysis of these solutions and narrow down their number prior to being tested in the laboratory, we explore the use of Pareto filters that identify the preferred subset of enzymatic profiles. We demonstrate the usefulness of our approach by means of a case study that optimizes the ethanol production in the fermentation of Saccharomyces cerevisiae.

Preferred Spatial Frequencies for Human Face Processing Are Associated with Optimal Class Discrimination in the Machine

Psychophysical studies suggest that humans preferentially use a narrow band of low spatial frequencies for face recognition. Here we asked whether artificial face recognition systems have an improved recognition performance at the same spatial frequencies as humans. To this end, we estimated recognition performance over a large database of face images by computing three discriminability measures: Fisher Linear Discriminant Analysis, Non-Parametric Discriminant Analysis, and Mutual Information. In order to address frequency dependence, discriminabilities were measured as a function of (filtered) image size. All three measures revealed a maximum at the same image sizes, where the spatial frequency content corresponds to the psychophysical found frequencies. Our results therefore support the notion that the critical band of spatial frequencies for face recognition in humans and machines follows from inherent properties of face images, and that the use of these frequencies is associated with optimal face recognition performance.

The multi-facets of sustainable nanotechnology : lessons from a nanosafety symposium

An international symposium for nanosafety was held recently at the Nanyang Technological University in Singapore. Topics relating to understanding nanomaterial properties, tools, and infrastructure required for predicting hazardous outcomes, measuring nanomaterial exposure levels, systems approach for risk assessment and public's perception of nanotechnology were covered. The need for a multidisciplinary approach, across both natural and social sciences, for developing sustainable nanotechnology solutions was heavily emphasized. This commentary highlights the major issues discussed and the commitment of the nanosafety research community in Singapore to contribute collectively to realise the vision of sustainable nanotechnology.

Data Envelopment Analysis and non-discretionary inputs : How to select the most suitable model using multi-criteria decision analysis

Within Data Envelopment Analysis, several alternative models allow for an environmental adjustment. The majority of them deliver divergent results. Decision makers face the difficult task of selecting the most suitable model. This study is performed to overcome this difficulty. By doing so, it fills a research gap. First, a two-step web-based survey is conducted. It aims (1) to identify the selection criteria, (2) to prioritize and weight the selection criteria with respect to the goal of selecting the most suitable model and (3) to collect the preferences about which model is preferable to fulfil each selection criterion. Second, Analytic Hierarchy Process is used to quantify the preferences expressed in the survey. Results show that the understandability, the applicability and the acceptability of the alternative models are valid selection criteria. The selection of the most suitable model depends on the preferences of the decision makers with regards to these criteria.

Multi-sided Böhm-Bawerk assignment markets: the core

[cat] En aquest treball introduïm la classe de "multi-sided Böhm-Bawerk assignment games", que generalitza la coneguda classe de jocs d’assignació de Böhm-Bawerk bilaterals a situacions amb un nombre arbitrari de sectors. Trobem els extrems del core de qualsevol multi-sided Böhm-Bawerk assignment game a partir d’un joc convex definit en el conjunt de sectors enlloc del conjunt de venedors i compradors. Addicionalment estudiem quan el core d’aquests jocs d’assignació és estable en el sentit de von Neumann-Morgenstern.

A survey of transposable element classification systems--a call for a fundamental update to meet the challenge of their diversity and complexity.

The increase of publicly available sequencing data has allowed for rapid progress in our understanding of genome composition. As new information becomes available we should constantly be updating and reanalyzing existing and newly acquired data. In this report we focus on transposable elements (TEs) which make up a significant portion of nearly all sequenced genomes. Our ability to accurately identify and classify these sequences is critical to understanding their impact on host genomes. At the same time, as we demonstrate in this report, problems with existing classification schemes have led to significant misunderstandings of the evolution of both TE sequences and their host genomes. In a pioneering publication Finnegan (1989) proposed classifying all TE sequences into two classes based on transposition mechanisms and structural features: the retrotransposons (class I) and the DNA transposons (class II). We have retraced how ideas regarding TE classification and annotation in both prokaryotic and eukaryotic scientific communities have changed over time. This has led us to observe that: (1) a number of TEs have convergent structural features and/or transposition mechanisms that have led to misleading conclusions regarding their classification, (2) the evolution of TEs is similar to that of viruses by having several unrelated origins, (3) there might be at least 8 classes and 12 orders of TEs including 10 novel orders. In an effort to address these classification issues we propose: (1) the outline of a universal TE classification, (2) a set of methods and classification rules that could be used by all scientific communities involved in the study of TEs, and (3) a 5-year schedule for the establishment of an International Committee for Taxonomy of Transposable Elements (ICTTE).

Multi-sided Böhm-Bawerk assignment markets: the core

[cat] En aquest treball introduïm la classe de "multi-sided Böhm-Bawerk assignment games", que generalitza la coneguda classe de jocs d’assignació de Böhm-Bawerk bilaterals a situacions amb un nombre arbitrari de sectors. Trobem els extrems del core de qualsevol multi-sided Böhm-Bawerk assignment game a partir d’un joc convex definit en el conjunt de sectors enlloc del conjunt de venedors i compradors. Addicionalment estudiem quan el core d’aquests jocs d’assignació és estable en el sentit de von Neumann-Morgenstern.

Design of User Authentication System for Multi-operator wireless LANs

Langattomat lähiverkot ovat viime vuosikymmeninä saavuttaneet suuren suosion. Tässä työssä käsitellään käyttäjien todentamisjärjestelmän suunnittelua ja kehitystä langattomaan monioperaattoriverkkoon. Langattomassa monioperaattoriverkossa käyttäjillä on mahdollisuus käyttää eri operaattoreiden palveluita. Aluksi käsitellään olemassa olevia todentamismenetelmiä ja -järjestelmiä. minkä jälkeen kuvaillaan todentamisjärjestelmä langattomille monioperaattoriverkoille. Todentamisjärjestelmän ratkaisuvaihtoehtoja esitellään kaksi, niin sanotut moni- istunto - ja yksittäisistuntomalli. Moni-istuntomalli on normaali lähestymistapa käyttäjien todentamiseen tietokonejärjestelmissä. Siinä käyttäjän pitää tunnistautua ja todentaa itsensä jokaiselle verkon palvelulle erikseen. Yksittäisistuntomallissa pyritään parempaan luotettavuuteen ja käytettävyyteen. Siinä käyttäjä todentaa itsensä vain kerran ja voi sen jälkeen päästä useisiin palveluihin. Työn loppuosassa kuvaillaan suunnitellun järjestelmän toteutusta. Lisäksi ehdotetaan vaihtoehtoisia toteutustapoja, analysoidaan järjestelmän heikkouksia ja kerrotaan jatkokehitysmahdoillisuuksista.

Systems Medicine and Integrated Care to Combat Chronic Noncommunicable Diseases.

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

Statistical mechanics of multi-edge networks

Statistical properties of binary complex networks are well understood and recently many attempts have been made to extend this knowledge to weighted ones. There are, however, subtle yet important considerations to be made regarding the nature of the weights used in this generalization. Weights can be either continuous or discrete magnitudes, and in the latter case, they can additionally have undistinguishable or distinguishable nature. This fact has not been addressed in the literature insofar and has deep implications on the network statistics. In this work we face this problem introducing multiedge networks as graphs where multiple (distinguishable) connections between nodes are considered. We develop a statistical mechanics framework where it is possible to get information about the most relevant observables given a large spectrum of linear and nonlinear constraints including those depending both on the number of multiedges per link and their binary projection. The latter case is particularly interesting as we show that binary projections can be understood from multiedge processes. The implications of these results are important as many real-agent-based problems mapped onto graphs require this treatment for a proper characterization of their collective behavior.

2015 Update on Acute Adverse Reactions to Gadolinium based Contrast Agents in Cardiovascular MR. Large Multi-National and Multi-Ethnical Population Experience With 37788 Patients From the EuroCMR Registry.

OBJECTIVES: Specifically we aim to demonstrate that the results of our earlier safety data hold true in this much larger multi-national and multi-ethnical population. BACKGROUND: We sought to re-evaluate the frequency, manifestations, and severity of acute adverse reactions associated with administration of several gadolinium- based contrast agents during routine CMR on a European level. METHODS: Multi-centre, multi-national, and multi-ethnical registry with consecutive enrolment of patients in 57 European centres. RESULTS: During the current observation 37,788 doses of Gadolinium based contrast agent were administered to 37,788 patients. The mean dose was 24.7 ml (range 5-80 ml), which is equivalent to 0.123 mmol/kg (range 0.01 - 0.3 mmol/kg). Forty-five acute adverse reactions due to contrast administration occurred (0.12%). Most reactions were classified as mild (43 of 45) according to the American College of Radiology definition. The most frequent complaints following contrast administration were rashes and hives (15 of 45), followed by nausea (10 of 45) and flushes (10 of 45). The event rate ranged from 0.05% (linear non-ionic agent gadodiamide) to 0.42% (linear ionic agent gadobenate dimeglumine). Interestingly, we also found different event rates between the three main indications for CMR ranging from 0.05% (risk stratification in suspected CAD) to 0.22% (viability in known CAD). CONCLUSIONS: The current data indicate that the results of the earlier safety data hold true in this much larger multi-national and multi-ethnical population. Thus, the "off-label" use of Gadolinium based contrast in cardiovascular MR should be regarded as safe concerning the frequency, manifestation and severity of acute events.