The port-Hamiltonian framework as a comprehensive approach to model and simulate complex systems

This thesis describes modelling tools and methods suited for complex systems (systems that typically are represented by a plurality of models). The basic idea is that all models representing the system should be linked by well-defined model operations in order to build a structured repository of information, a hierarchy of models. The port-Hamiltonian framework is a good candidate to solve this kind of problems as it supports the most important model operations natively. The thesis in particular addresses the problem of integrating distributed parameter systems in a model hierarchy, and shows two possible mechanisms to do that: a finite-element discretization in port-Hamiltonian form, and a structure-preserving model order reduction for discretized models obtainable from commercial finite-element packages.

Metaheuristics for Search Problems in Genomics - New Algorithms and Applications

In this thesis we made the first steps towards the systematic application of a methodology for automatically building formal models of complex biological systems. Such a methodology could be useful also to design artificial systems possessing desirable properties such as robustness and evolvability. The approach we follow in this thesis is to manipulate formal models by means of adaptive search methods called metaheuristics. In the first part of the thesis we develop state-of-the-art hybrid metaheuristic algorithms to tackle two important problems in genomics, namely, the Haplotype Inference by parsimony and the Founder Sequence Reconstruction Problem. We compare our algorithms with other effective techniques in the literature, we show strength and limitations of our approaches to various problem formulations and, finally, we propose further enhancements that could possibly improve the performance of our algorithms and widen their applicability. In the second part, we concentrate on Boolean network (BN) models of gene regulatory networks (GRNs). We detail our automatic design methodology and apply it to four use cases which correspond to different design criteria and address some limitations of GRN modeling by BNs. Finally, we tackle the Density Classification Problem with the aim of showing the learning capabilities of BNs. Experimental evaluation of this methodology shows its efficacy in producing network that meet our design criteria. Our results, coherently to what has been found in other works, also suggest that networks manipulated by a search process exhibit a mixture of characteristics typical of different dynamical regimes.

Patent Strategies and R&D in Complex Product Industries

The study aims at providing a framework conceptualizing patenting activities under the condition of intellectual property rights fragmentation. Such a framework has to deal with the interrelated problems of technological complexity in the modern patent landscape. In that respect, ex-post licensing agreements have been incorporated into the analysis. More precisely, by consolidating the right to use patents required for commercialization of a product, private market solutions, such as cross-licensing agreements and patent pools help firms to overcome problems triggered by the intellectual property rights fragmentation. Thereby, private bargaining between parties as such cannot be isolated from the legal framework. A result of this analysis is that policies ignoring market solutions and only focusing on static gains can mitigate the dynamic efficiency gains as induced by the patent system. The evidence found in this thesis supports the opinion that legal reforms that aim to decrease the degree of patent protection or to lift it all together can hamper the functioning of the current system.

Complex chemical dynamics through engineering-like methods

Most of the problems in modern structural design can be described with a set of equation; solutions of these mathematical models can lead the engineer and designer to get info during the design stage. The same holds true for physical-chemistry; this branch of chemistry uses mathematics and physics in order to explain real chemical phenomena. In this work two extremely different chemical processes will be studied; the dynamic of an artificial molecular motor and the generation and propagation of the nervous signals between excitable cells and tissues like neurons and axons. These two processes, in spite of their chemical and physical differences, can be both described successfully by partial differential equations, that are, respectively the Fokker-Planck equation and the Hodgkin and Huxley model. With the aid of an advanced engineering software these two processes have been modeled and simulated in order to extract a lot of physical informations about them and to predict a lot of properties that can be, in future, extremely useful during the design stage of both molecular motors and devices which rely their actions on the nervous communications between active fibres.

Fast and accurate numerical solutions in some problems of particle and radiation transport: synthetic acceleration for the method of short characteristics, Doppler-broadened scattering kernel, remote sensing of the cryosphere

The aim of this work is to present various aspects of numerical simulation of particle and radiation transport for industrial and environmental protection applications, to enable the analysis of complex physical processes in a fast, reliable, and efficient way. In the first part we deal with speed-up of numerical simulation of neutron transport for nuclear reactor core analysis. The convergence properties of the source iteration scheme of the Method of Characteristics applied to be heterogeneous structured geometries has been enhanced by means of Boundary Projection Acceleration, enabling the study of 2D and 3D geometries with transport theory without spatial homogenization. The computational performances have been verified with the C5G7 2D and 3D benchmarks, showing a sensible reduction of iterations and CPU time. The second part is devoted to the study of temperature-dependent elastic scattering of neutrons for heavy isotopes near to the thermal zone. A numerical computation of the Doppler convolution of the elastic scattering kernel based on the gas model is presented, for a general energy dependent cross section and scattering law in the center of mass system. The range of integration has been optimized employing a numerical cutoff, allowing a faster numerical evaluation of the convolution integral. Legendre moments of the transfer kernel are subsequently obtained by direct quadrature and a numerical analysis of the convergence is presented. In the third part we focus our attention to remote sensing applications of radiative transfer employed to investigate the Earth's cryosphere. The photon transport equation is applied to simulate reflectivity of glaciers varying the age of the layer of snow or ice, its thickness, the presence or not other underlying layers, the degree of dust included in the snow, creating a framework able to decipher spectral signals collected by orbiting detectors.

Off-pump extraanatomic aortic bypass for the treatment of complex aortic coarctation and hypoplastic aortic arch

BACKGROUND: Despite advances in surgical and interventional techniques, the optimal surgical treatment of severe aortic (re) coarctation and hypoplastic aortic arch is still controversial. Anatomic repair may require extensive dissection, cardiopulmonary bypass, and deep hypothermic circulatory arrest with their inherent risks. The aim of this study was to analyze the outcome of off-pump extraanatomic aortic bypass as a surgical alternative to local repair. METHODS: From February 2000 to December 2005, ten consecutive patients (median age 20 years; range, 11 to 38 years) with severe aortic (re) coarctation (n = 4) and (or) hypoplastic aortic arch (n = 7) underwent off-pump extraanatomic aortic bypass through median sternotomy. All but three patients had undergone previous surgery for coarctation and angioplasty or stenting. Three patients underwent concomitant replacement of the ascending aorta because of an aneurysm using cardiopulmonary bypass. RESULTS: Postoperative hospital course was uneventful in all patients. There was no perioperative mortality or significant morbidity. During a mean follow-up of 48 +/- 22 months no patient required additional procedures. All patients were free of symptoms; no patient showed signs of heart failure after follow-up. At last follow-up, no patient presented with claudication, nor any patient experienced orthostatic problems due to a steal phenomenon. During follow-up, hypertension resolved in all patients with residual mild hypertension in two patients. CONCLUSIONS: Off-pump extraanatomic aortic bypass is an attractive treatment option for complex aortic (re) coarctation and hypoplastic aortic arch. Perioperative risks are minimized, hypertension is influenced favorably, and midterm survival is event-free.

Defining Goals and Learning Objectives for a Longitudinal Clerkship in the Complex Context of Health Care

In autumn 2007 the Swiss Medical School of Berne (Switzerland) implemented mandatory short-term clerkships in primary health care for all undergraduate medical students. Students studying for a Bachelor degree complete 8 half-days per year in the office of a general practitioner, while students studying for a Masters complete a three-week clerkship. Every student completes his clerkships in the same GP office during his four years of study. The purpose of this paper is to show how the goals and learning objectives were developed and evaluated. Method:A working group of general practitioners and faculty had the task of defining goals and learning objectives for a specific training program within the complex context of primary health care. The group based its work on various national and international publications. An evaluation of the program, a list of minimum requirements for the clerkships, an oral exam in the first year and an OSCE assignment in the third year assessed achievement of the learning objectives. Results: The findings present the goals and principal learning objectives for these clerkships, the results of the evaluation and the achievement of minimum requirements. Most of the defined learning objectives were taught and duly learned by students. Some learning objectives proved to be incompatible in the context of ambulatory primary care and had to be adjusted accordingly. Discussion: The learning objectives were evaluated and adapted to address students’ and teachers’ needs and the requirements of the medical school. The achievement of minimum requirements (and hence of the learning objectives) for clerkships has been mandatory since 2008. Further evaluations will show whether additional learning objectives need to be adopte

Plate fixation of extra-articular fractures of the proximal phalanx: do new implants cause less problems?

BACKGROUND Limited range of finger motion is a frequent complication after plate fixation of phalangeal fractures. The purpose of this study was to evaluate the results of plate fixation of extra-articular fractures of the proximal phalanx using current low-profile mini-fragment-systems. METHODS From 2006 to 2012, 32 patients with 36 extra-articular fractures of the proximal phalanx of the triphalangeal fingers were treated with open reduction and plate fixation (ORPF) using 1.2 and 1.5 mm mini-fragment systems. Patients presenting with open fractures grade 2 and 3 or relevant laceration of adjacent structures were excluded from the study. We retrospectively evaluated the rate of mal-union or non-union after ORPF, the need for revision surgery, for plate removal, and for tenolysis. Data were analyzed for further complications with regard to infections or complex regional pain syndrome (CRPS). RESULTS No infections were noted. Five patients developed transient symptoms of CRPS. Six weeks postoperatively, total active finger motion (TAM) averaged 183°, and all 32 patients underwent formal hand therapy. At the latest follow-up or at the time of plate removal, respectively, the mean TAM improved to 213°. Extension lag of proximal interphalangeal joints was found in 67 % of all fractured fingers. Secondary surgery was necessary in 14 of 32 patients (2 corrective osteotomies, 12 plate removals including 7 procedures explicitly because of reduced mobility). CONCLUSIONS Despite of new implant designs significant problems persist. Adhesions of extensor tendons leading to limited range of finger motion are still the most frequent complications after ORPF of proximal phalangeal fractures, even in absence of significant soft-tissue damage. LEVEL OF EVIDENCE Therapeutic, Retrospective, Level IV.

Flexibility Properties in Complex Analysis and Affine Algebraic Geometry

In the last decades affine algebraic varieties and Stein manifolds with big (infinite-dimensional) automorphism groups have been intensively studied. Several notions expressing that the automorphisms group is big have been proposed. All of them imply that the manifold in question is an Oka–Forstnerič manifold. This important notion has also recently merged from the intensive studies around the homotopy principle in Complex Analysis. This homotopy principle, which goes back to the 1930s, has had an enormous impact on the development of the area of Several Complex Variables and the number of its applications is constantly growing. In this overview chapter we present three classes of properties: (1) density property, (2) flexibility, and (3) Oka–Forstnerič. For each class we give the relevant definitions, its most significant features and explain the known implications between all these properties. Many difficult mathematical problems could be solved by applying the developed theory, we indicate some of the most spectacular ones.

[Smoking and digestive tract: a complex relationship. Part 2: Intestinal microblota and cigarette smoking]

The digestive tract is colonized from birth by a bacterial population called the microbiota which influences the development of the immune system. Modifications in its composition are associated with problems such as obesity or inflammatory bowel diseases. Antibiotics are known to influence the intestinal microbiota but other environmental factors such as cigarette smoking also seem to have an impact on its composition. This influence might partly explain weight gain which is observed after smoking cessation. Indeed there is a modification of the gut microbiota which becomes similar to that of obese people with a microbiotical profile which is more efficient to extract calories from ingested food. These new findings open new fields of diagnostic and therapeutic approaches through the regulation of the microbiota.

Using the contribution matrix to evaluate complex study limitations in a network meta-analysis: a case study of bipolar maintenance pharmacotherapy review.

BACKGROUND Limitations in the primary studies constitute one important factor to be considered in the grading of recommendations assessment, development, and evaluation (GRADE) system of rating quality of evidence. However, in the network meta-analysis (NMA), such evaluation poses a special challenge because each network estimate receives different amounts of contributions from various studies via direct as well as indirect routes and because some biases have directions whose repercussion in the network can be complicated. FINDINGS In this report we use the NMA of maintenance pharmacotherapy of bipolar disorder (17 interventions, 33 studies) and demonstrate how to quantitatively evaluate the impact of study limitations using netweight, a STATA command for NMA. For each network estimate, the percentage of contributions from direct comparisons at high, moderate or low risk of bias were quantified, respectively. This method has proven flexible enough to accommodate complex biases with direction, such as the one due to the enrichment design seen in some trials of bipolar maintenance pharmacotherapy. CONCLUSIONS Using netweight, therefore, we can evaluate in a transparent and quantitative manner how study limitations of individual studies in the NMA impact on the quality of evidence of each network estimate, even when such limitations have clear directions.

Counselors' education in complex contexts with special reference to Latin America

This paper makes reference to the importance lying, at present, on the professional education of counselors. It goes through the history of the different pre-scientific and scientific stages of counseling, and it points out the main representatives in Latin America . It also shows the current state of the specialization, taking as an antecedent some in-depth, widely encompassing research carried out in the European Union in this area. Coincidences and differences are exposed here in terms of professional profiles, university degrees, institutional dependence, up-dating processes and modes of intervention. The current state of postgraduate studies at university is also touched upon, and the different proposals for further education in Latin America are analyzed as well as their dependence upon an undergraduate degree in Psychology, Educational Sciences or Psycho-pedagogy. Finally, this paper places counseling within the complexity and the need to provide all-encompassing and integrative answers which require a wide and deep enough education so as to answer all these issues and problems.

Counselors' education in complex contexts with special reference to Latin America

This paper makes reference to the importance lying, at present, on the professional education of counselors. It goes through the history of the different pre-scientific and scientific stages of counseling, and it points out the main representatives in Latin America . It also shows the current state of the specialization, taking as an antecedent some in-depth, widely encompassing research carried out in the European Union in this area. Coincidences and differences are exposed here in terms of professional profiles, university degrees, institutional dependence, up-dating processes and modes of intervention. The current state of postgraduate studies at university is also touched upon, and the different proposals for further education in Latin America are analyzed as well as their dependence upon an undergraduate degree in Psychology, Educational Sciences or Psycho-pedagogy. Finally, this paper places counseling within the complexity and the need to provide all-encompassing and integrative answers which require a wide and deep enough education so as to answer all these issues and problems.

Counselors' education in complex contexts with special reference to Latin America

This paper makes reference to the importance lying, at present, on the professional education of counselors. It goes through the history of the different pre-scientific and scientific stages of counseling, and it points out the main representatives in Latin America . It also shows the current state of the specialization, taking as an antecedent some in-depth, widely encompassing research carried out in the European Union in this area. Coincidences and differences are exposed here in terms of professional profiles, university degrees, institutional dependence, up-dating processes and modes of intervention. The current state of postgraduate studies at university is also touched upon, and the different proposals for further education in Latin America are analyzed as well as their dependence upon an undergraduate degree in Psychology, Educational Sciences or Psycho-pedagogy. Finally, this paper places counseling within the complexity and the need to provide all-encompassing and integrative answers which require a wide and deep enough education so as to answer all these issues and problems.