Special Issue on 'Computational Modelling in Medicine': Guest editor introduction.

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Old and new The experience of the Brazil Architecture Office in intervention programs in historical buildings and sites

Reaching near 30 years of activity, Brazil Architecture establishes a work path among top state-of-the-art architectural Brazilian producers. Back tracking the architects’ progress has shown us that early projects fell under FAU’s current ideology during their student years. As new references yielded ideas and time was passing by Brazil Architecture kept on leading its own character and trends into the architectonic language. The importance of programs involving architectonic and historic site interventions are a highlight among the office’s history, as 40 projects, from almost 200, bring into discussion matters of memory and contemporaneity plus the relations between the new and the old. The counterpart aspect added the conviviality of the new together with the old shall be the motto for the whole production being built, from learning at the Pompeia Commerce Social Service (Serviço Social do Comércio – Sesc Pompéia, São Paulo, Brazil), then consolidated throughout the Rodin Museum and finally reaching maturity by the building of the Bread Museum. As they are still relatively young, it nevertheless points towards new chapters yet to be written in future years.La trayectoria trazada por Brasil Arquitectura a lo largo de cerca de treinta años de actuación pone la obra de esa oficina en un lugar destacado en la producción arquitectónica brasileña actual. La revisión del camino de los arquitectos nos muestra que los primeros proyectos se quedaban bajo el ideario difundido por la FAU en los tiempos en los que eran estudiantes. Con el pasar de los años, y con la asimilación de nuevas referencias, Brasil Arquitetura siguió construyendo un lenguaje arquitectónico propio. La importancia de los programas que involucran la intervención en el patrimonio histórico y arquitectónico se observa en la evolución de la oficina, pues, de los cerca de 200 proyectos realizados, aproximadamente cuarenta son los que traen a discusión las cuestiones de memoria y contemporaneidad, además de la relación entre nuevo y viejo. La postura de contraposición y convivencia de lo antiguo con lo nuevo debe ser el mote de toda una producción que se viene construyendo desde la enseñanza en el Servicio Social del Comercio Pompéia (SESC), consolidándose con el Museo Rodin y, por siguiente, logrando experiencia con la obra del Museo del Pan. Aunque la oficina es relativamente joven, todo lleva a creer que faltan más capítulos aún por escribir en los años veniderosA trajetória traçada pelo Brasil Arquitetura ao longo dos quase 30 anos de atuação insere a obra do escritório com relativo destaque na produção arquitetônica brasileira atual. A revisão do percurso dos arquitetos nos mostra que os primeiros projetos estão presos ao ideário propagado na FAU no momento em que eram estudantes. Com o decorrer do tempo e após a assimilação de novas referências, o Brasil Arquitetura vai construindo uma linguagem arquitetônica própria. A importância dos programas que envolvem a intervenção no patrimônio histórico e arquitetônico na evolução do escritório salta aos olhos, pois, de quase 200 projetos realizados, cerca de 40 são projetos que colocam em discussão as questões de memória e contemporaneidade e a relação do novo e do velho. A postura de contraposição e convivência do antigo com o novo será o mote de toda uma produção que vem sendo construída desde o aprendizado no Serviço Social do Comércio (Sesc) Pompéia, consolidando-se com o Museu Rodin e atingindo a maturidade com a obra do Museu do Pão. Como são relativamente jovens, tudo leva a crer que outros capítulos ainda serão escritos nos anos vindouro

Biomechanics-based in silico medicine: The manifesto of a new science

In this perspective article we discuss the role of contemporary biomechanics in the light of recent applications such as the development of the so-called Virtual Physiological Human technologies for physiology-based in silico medicine. In order to build Virtual Physiological Human (VPH) models, computer models that capture and integrate the complex systemic dynamics of living organisms across radically different space–time scales, we need to re-formulate a vast body of existing biology and physiology knowledge so that it is formulated as a quantitative hypothesis, which can be expressed in mathematical terms. Once the predictive accuracy of these models is confirmed against controlled experiments and against clinical observations, we will have VPH model that can reliably predict certain quantitative changes in health status of a given patient, but also, more important, we will have a theory, in the true meaning this word has in the scientific method. In this scenario, biomechanics plays a very important role, biomechanics is one of the few areas of life sciences where we attempt to build full mechanistic explanations based on quantitative observations, in other words, we investigate living organisms like physical systems. This is in our opinion a Copernican revolution, around which the scope of biomechanics should be re-defined. Thus, we propose a new definition for our research domain “Biomechanics is the study of living organisms as mechanistic systems”

Policy needs and options for a common approach towards modelling and simulation of human physiology and diseases with a focus on the virtual physiological human.

Life is the result of an intricate systemic interaction between many processes occurring at radically different spatial and temporal scales. Every day, worldwide biomedical research and clinical practice produce a huge amount of information on such processes. However, this information being highly fragmented, its integration is largely left to the human actors who find this task increasingly and ever more demanding in a context where the information available continues to increase exponentially. Investments in the Virtual Physiological Human (VPH) research are largely motivated by the need for integration in healthcare. As all health information becomes digital, the complexity of health care will continue to evolve, translating into an ever increasing pressure which will result from a growing demand in parallel to limited budgets. Hence, the best way to achieve the dream of personalised, preventive, and participative medicine at sustainable costs will be through the integration of all available data, information and knowledge

A haptic-enabled multimodal interface for the planning of hip arthroplasty

Multimodal environments help fuse a diverse range of sensory modalities, which is particularly important when integrating the complex data involved in surgical preoperative planning. The authors apply a multimodal interface for preoperative planning of hip arthroplasty with a user interface that integrates immersive stereo displays and haptic modalities. This article overviews this multimodal application framework and discusses the benefits of incorporating the haptic modality in this area

Big Data, Big Knowledge: Big Data for Personalized Healthcare.

The idea that the purely phenomenological knowledge that we can extract by analyzing large amounts of data can be useful in healthcare seems to contradict the desire of VPH researchers to build detailed mechanistic models for individual patients. But in practice no model is ever entirely phenomenological or entirely mechanistic. We propose in this position paper that big data analytics can be successfully combined with VPH technologies to produce robust and effective in silico medicine solutions. In order to do this, big data technologies must be further developed to cope with some specific requirements that emerge from this application. Such requirements are: working with sensitive data; analytics of complex and heterogeneous data spaces, including nontextual information; distributed data management under security and performance constraints; specialized analytics to integrate bioinformatics and systems biology information with clinical observations at tissue, organ and organisms scales; and specialized analytics to define the "physiological envelope" during the daily life of each patient. These domain-specific requirements suggest a need for targeted funding, in which big data technologies for in silico medicine becomes the research priority

Comparative validation of two patient-specific modelling pipelines for predicting knee joint forces during level walking

Over the past few years, the use of computer models and simulations tailored to the patient's physiology to assist clinical decision-making has increased enormously. While several pipelines to develop personalized models exist, their adoption on a large scale is still limited due to the required niche computational skillset and the lengthy operations required. Novel toolboxes, such as STAPLE, promise to streamline and expedite the development of image-based skeletal lower limb models. STAPLE-generated models can be rapidly generated, with minimal user input, and present similar joint kinematics and kinetics compared to models developed employing the established INSIGNEO pipeline. Yet, it is unclear how much the observed discrepancies scale up and affect joint contact force predictions. In this study, we compared image-based musculoskeletal models developed (i) with the INSIGNEO pipeline and (ii) with a semi-automated pipeline that combines STAPLE and nmsBuilder, and assessed their accuracy against experimental implant data. Our results showed that both pipelines predicted similar total knee joint contact forces between one another in terms of profiles and average values, characterized by a moderately high level of agreement with the experimental data. Nonetheless, the Student t-test revealed statistically significant differences between both pipelines. Of note, the STAPLE-based pipeline required considerably less time than the INSIGNEO pipeline to generate a musculoskeletal model (i.e., 60 vs 160 min). This is likely to open up opportunities for the use of personalized musculoskeletal models in clinical practice, where time is of the essence

In silico clinical trials: how computer simulation will transform the biomedical industry

The term ‘in silico clinical trials indicates the use of individualised computer simulation in the development or regulatory evaluation of a medicinal product, medical device, or medical intervention. This review article summarises the research and technological roadmap developed by the Avicenna Support Action during an 18 month consensus process that involved 577 international experts from academia, the biomedical industry, the simulation industry, the regulatory world, etc. The roadmap documents early examples of in silico clinical trials, identifies relevant use cases for in silico clinical trial technologies over the entire development and assessment cycle for both pharmaceuticals and medical devices, identifies open challenges and barriers to a wider adoption and puts forward 36 recommendations for all relevant stakeholders to consider

The uncontrolled manifold theory could explain part of the inter-trial variability of knee contact force during level walking

Accurate predictions of joint contact forces through computer simulation of musculoskeletal dynamics can provide insight, in a non-invasive manner, into the joint loads of patients with osteoarthritis and healthy controls. The current approach to assume optimal control, in terms of metabolic energy expenditure, remains a major limitation of the prediction of muscle activation patterns that determine joint contact forces. Stochastically optimal muscle control, in the form of a stochastic component superimposed to the optimal control, could potentially explain the inter-trial variability as observed in measured knee contact forces during level walking. A probabilistic approach was used to predict sets of possible muscle activation patterns within a 5 and 10% limit from the optimal muscle activation pattern. The knee contact forces determined by both the optimal and stochastically optimal muscle activation patterns were compared to the corresponding knee contact force patterns measured by an instrumented implant. The range of muscle control patterns captured the inter-trial variability of knee contact forces for most of the gait cycle, suggesting that the probabilistic approach used here is representative of a stochastically optimal control that accounts for co-contraction, whereas during some time intervals a more explicit representation of the motor control strategy is required. These findings underline the importance of stochastically optimal muscle control in the prediction of knee forces within a multi-body dynamics approach