Systemic Design for Sustainable Healthcare. Designing for the treatment of chronic diseases

Health systems are facing significant societal and organizational challenges that require enhancing their resilience and sustainability. Public expenditure on health care and long-term care is expected to increase: health systems are searching for new solutions to controlling spending, implementing the use of available technology and engaging patients in prevention and self-care. The transition toward more sustainable health systems is both delicate and complex, and it needs radical changes of perspective as regards the patients’ role and the holistic and multi-disciplinary approach to health care. Over the past years, interest in what is called “Sustainable Healthcare” has grown globally: there is no common definition, but all the approaches to this emerging domain focus on making health care environmentally, economically and socially viable. Although design could successfully address some crucial environmental issues of health care (from waste reduction to resource optimization), design research made almost no contribution to this field. The present work aims at investigating the role of design towards Sustainable Healthcare, to propose, through case study experience, a systemic vision of the topic. Specifically, the research addressed the environmental issues of chronic haemodialysis, a life-saving treatment for people suffering from Chronic Kidney Disease. Medical treatments imply significant challenges because of their technical and operational complexity, that is further complicated by strict regulations and the presence of several users. Design should address environmental sustainability in such a complex system while maintaining the focus on user-centred care. Traditional design approaches cannot tackle the complexity of health care; therefore, a holistic approach is needed. Systemic Design integrates systems thinking and human-centred design methodologies to support designers working on complex design projects in multi-stakeholder and multi-environment systems. The doctoral research is deeply rooted in the framework of Systemic Design, aiming at defining how design strategies can improve the environmental sustainability of medical products, services, and systems, considering its close relationship with the social (people empowerment) and economic (feasibility) aspects. The first part of the research focused on the definition of all the items which make up the system, and the users that directly or indirectly interact with them. Four system items have been identified: products (packaging, disposables, devices), equipment (dialysis machine), treatment (haemodialysis as a whole) and local environment (policy and management strategies). In the second part different approaches, borrowed from sustainable design and human-centred design, have been combined to analyse each item. In order to establish a general frame, three different dialysis units and hospitals based in different European countries (Italy, Sweden, Denmark) were compared. This comprehensive analysis allowed to set specific guidelines for dialysis products, equipment, and treatment. The comparison of three international case studies highlighted how design should work on product and equipment to improve environmental sustainability on a global scale while addressing local systems and their specific needs to improve sustainability on a local level. The outcome of the research is a set of design strategies for the healthcare sector that take into account the technical, operational, social and environmental requirements of chronic treatments. This final result aims at providing a practical tool for designers and health stakeholders to address the design of new solutions for Sustainable Healthcare, considering the needs of direct and indirect users

A genomic analysis using RNA-Seq to investigate the adaptation of the psychrophilic diatom Fragilariopsis cylindrus to the polar environment

Diatoms are unicellular photosynthetic eukaryotes with a silicate cell wall. They often dominate polar marine ecosystems, driving the major biogeochemical cycles in these areas. The obligate psychrophilic diatom Fragilariopsis cylindrus is a keystone species in the Southern Ocean. It thrives both in open waters and sea ice and has become a model for studying eukaryotic microalgal adaptations to polar marine conditions. The aim of this thesis was to identify how the genome of F. cylindrus has evolved to cope with marine environmental conditions of the Southern Ocean. To identify key genes, comparative genomics, high-throughput transcriptome sequencing and reverse genetics were applied. Comparative genomics with the sequenced mesophilic diatoms Phaeodactylum tricornutum and Thalassiosira pseudonana was combined with genome-wide RNA-Seq transcriptome analysis, leading to the discovery a new bacteria-like rhodopsin not present in other sequenced diatoms. The characterisation of a bacteria-like rhodopsin in F. cylindrus was conducted by applying reverse genetics tools. The genome was characterised by a low G+C content, which affected codon usage. High sequence polymorphism resulted in pronounced unequal expression of putative heterozygous allelic gene copies in response to six different conditions. RNA-Seq detected transcriptional activity for 95% of the 27,137 predicted genes and > 4 fold expression changes between 55% of putative alleles. The most significant transcriptional changes were detected during prolonged darkness affecting 70% of genes and 30% of RNA-Seq reads mapped to unannotated regions of the genome. Two rhodopsin alleles showed unequal bi-allelic expression in response to iron starvation and heterologous expression in Xenopus laevis oocytes experimentally confirmed light-driven proton pumping for the iron-induced rhodopsin allele, suggesting significance for the adaptation of F. cylindrus to environmental conditions of the Southern Ocean. These data show how the polar environment can shape the genome of a eukaryotic phytoplankton in unprecedented detail. High numbers of species-specific genes resulting in expansion of gene and protein families, low G+C likely enabling efficient translation at low temperatures and a high degree of heterozygosity combined with unequal bi-allelic expression, may provide an adaptive strategy to polar conditions by conferring metabolic flexibility and capacity to adapt to a rapidly changing environment

New Perspective in Atrial Fibrillation

In spite of the large volume of associated research, the pathophysiological mechanisms involved in atrial fibrillation (AF) onset and recurrence remain uncertain. This may explain why the performances of thromboembolic and bleeding prediction scores in AF patients are limited. In the past few years, the concept of atrial cardiopathy has emerged as a promising lead to connect AF to stroke, heart failure, and inflammatory processes: indeed, all of the mechanisms associated with atrial remodeling and the development of atrial cardiopathy are also likely to promote the development of AF. This recent concept of atrial cardiopathy suggests that the real trigger of stroke may be an abnormal atrial substrate rather than atrial rhythm itself. In this setting, AF could be seen as a symptom of atrial cardiopathy rather than a risk factor of stroke. In the absence of validated clinical markers of atrial cardiopathy, the search for the mechanism of AF remains the cornerstone of cardioembolic stroke prevention for now.The aim of this Special Issue is to gather basic research as well as pathophysiological and epidemiological papers focused on the relationship between atrial substrates and atrial fibrillation onset, recurrence, and outcomes

The Politics of the Self: Psychedelic Assemblages, Psilocybin, and Subjectivity in the Anthropocene

This dissertation examines how psychedelic substances become drawn into particular sociohistorical and political arrangements, and how psychedelic experiences with psilocybin ‘magic mushrooms’ are used as tools of subjectivation. Guided by literatures in philosophy, critical theory, and the social sciences that focus on subjectivity, assemblage theory, and critical posthumanism, I argue that psychedelics are drawn into variegated assemblages, each of which conceptualizes the nature of psychedelics in highly specific ways that reflect implicit conceptions of the world and the self. In developing the concept of psychedelic assemblages, this research provides a window onto the politics of the self in the Anthropocene. Drawing on mixed and netnographic methods, I conducted 30 semi-structured interviews and acquired 100 experience reports from online forums, using this data to demonstrate how psychedelic mushroom experiences are used as technologies of the self, or practices that individuals engage as a means of changing their subjectivity. Among the changes in subjectivity provoked by psychedelic mushroom experiences, there are sometimes reports of changes in human-environment relations based on an enhanced connection or relationship with nature

The EASL–Lancet Liver Commission: protecting the next generation of Europeans against liver disease complications and premature mortality

n

3D Quantification and Description of the Developing Zebrafish Cranial Vasculature

Background: Zebrafish are an excellent model to study cardiovascular development and disease. Transgenic reporter lines and state-of-the-art microscopy allow 3D visualization of the vasculature in vivo. Previous studies relied on subjective visual interpretation of vascular topology without objective quantification. Thus, there is the need to develop analysis approaches that model and quantify the zebrafish vasculature to understand the effect of development, genetic manipulation or drug treatment. Aim: To establish an image analysis pipeline to extract quantitative 3D parameters describing the shape and topology of the zebrafish vasculature, and examine how these are impacted during development, disease, and by chemicals. Methods: Experiments were performed in zebrafish embryos, conforming with UK Home Office regulations. Image acquisition of transgenic zebrafish was performed using a Z.1 Zeiss light-sheet fluorescence microscope. Pre-processing, enhancement, registration, segmentation, and quantification methods were developed and optimised using open-source software, Fiji (Fiji 1.51p; National Institutes of Health, Bethesda, USA). Results: Motion correction was successfully applied using Scale Invariant Feature Transform (SIFT), and vascular enhancement based on vessel tubularity (Sato filter) exceeded general filter outcomes. Following evaluation and optimisation of a variety of segmentation methods, intensity-based segmentation (Otsu thresholding) was found to deliver the most reliable segmentation, allowing 3D vascular volume measurement. Following successful segmentation of the cerebral vasculature, a workflow to quantify left-right intra-sample symmetry was developed, finding no difference from 2-to-5dpf. Next, the first vascular inter-sample registration using a manual landmark-based approach was developed and it was found that conjugate direction search allowed automatic inter-sample registration. This enabled extraction of age-specific regions of similarity and variability between different individual embryos from 2-to-5dpf. A workflow was developed to quantify vascular network length, branching points, diameter, and complexity, showing reductions in zebrafish without blood flow. Also, I discovered and characterised a previously undescribed endothelial cell membrane behaviour termed kugeln. Conclusion: A workflow that successfully extracts the zebrafish vasculature and enables detailed quantification of a wide variety of vascular parameters was developed

Modelling the behaviour of granular material on the surface of asteroids and under different gravity conditions (e.g., Mars, the Moon)

This thesis, at the interface between the scientific disciplines of planetary science and granular physics, has two key components, both of which intend to increase our understanding of granular dynamics in varying gravitational conditions. The dynamics of granular materials are involved in the evolution of solid planets and small bodies in our Solar System, whose surfaces are generally covered with regolith. Understanding granular dynamics is also critical for the design and/or operations of landers, sampling devices and rovers to be included in space missions. The first component of this thesis is the validation of the hard-sphere discrete element method implementation in the N-body code pkdgrav to model the dynamics of granular material. By direct comparison with results from laboratory experiments, it is demonstrated that the hard-sphere discrete element method implementation in pkdgrav is valid for modelling granular material in dilute regimes and is capable of reproducing the complex dynamical behaviour of a specific dense system as well. The second component is focussed on the AstEx parabolic flight experiment. This experiment, with the aim of characterising the response of granular material to rotational shear forces in a microgravity environment, was designed, constructed, flown and the data were analysed as part of this thesis. It was found that the effect of constant shearing on a granular material in a direction perpendicular to the gravity field is not strongly influenced by gravity. The AstEx experiment has demonstrated, for the first time, that the efficiency of granular convection may decrease in the presence of a weak gravitational field, similar to that on the surface of small bodies. The first measurements of transient weakening of granular material after shear reversal in microgravity are also reported. Results suggest that the force contact network may be weaker in microgravity, although the influence of any change in the contact network is felt by the granular material over much larger distances. This may have important implications for our interpretation of asteroid surfaces. Continued advancement of our understanding of granular materials in varying gravitational conditions requires futher experiments and the development of the soft-sphere discrete element method implementation in pkdgrav in order to model the granular regimes that are inaccessbile to the hard-sphere implementation