| 1. |
- Hedlund, Johanna, 1988-
(författare)
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The environment knows no borders : Investigating the collective challenge of governing policy issue interdependencies
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Many of today’s most pressing environmental problems cross-cut jurisdictional, geographical, and administrative boundaries, creating interdependencies between different locations and between policy issues that no single actor can address alone. In practice, however, environmental policy is still often contained within the traditional responsibilities of the public sector and frequently judged ineffective, particularly in the European context. Whether and how interdependencies are actually associated with collaboration between policy actors has remained difficult to establish. This cumulative thesis focuses on interdependent environmental challenges that policy actors need to manage. Specifically, this thesis describes and analyses policy issue interdependencies and how they align with the collaborations of policy actors. In addition, this thesis explores how policy issue interdependencies can be revealed, concretised, and analysed. Interdependencies are effectively represented by networks, both as conceptual models and as analytical methods. Therefore, the studies in this thesis use a multilevel network model to explore the structural alignment between interdependencies and collaboration through the perspective of institutional fit.This thesis reports findings from two research projects. The first project focuses on policy issue interdependencies relating to regional water degradation. This project describes and analyses these interdependencies in relation to collaborative networks across administrative boundaries (Papers I–III). The second project focuses on climate change impacts that propagate through food trade dependencies. This project contributes insights into the effect of climate change on food trade networks that cross national borders, illustrating a need for global climate adaptation (Paper IV).Paper I introduces a methodological procedure for assessing policy issue interdependencies and develops policy issue networks by identifying overlapping causal relationships between policy issues and their environmental targets. By applying the procedure empirically to water governance, the paper shows that policy issue interdependencies vary in degree and type. Paper II combines the policy issue networks from Paper I with collaborative networks of policy actors in a multilevel network to analyse the impact policy issue interdependencies have on who policy actors select for collaborative partners and to clarify if and how patterns of collaboration among actors are formed. Paper III differentiates reinforcing and counteracting policy issue interdependencies and studies how these impact the perceptions and collaborations of the actors. Paper IV, shifting the focus to the global level, analyses climate change impacts related to food trade dependencies across national borders. Specifically, Paper IV investigates the impact of climate change on the structure of global food trade networks and therefore contributes a baseline scenario analysis for future studies that investigate policy issue interdependencies and policy actor collaborations on the global level.
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| 2. |
- Högstedt, Alexandra, 1993-
(författare)
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Microvascular effects of insulin in the skin
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The microcirculation in the skin is essential for skin homeostasis. In instances of altered microvascular function, that may be the result of insulin resistance, tissue morbidity may ensue. The underlying mechanisms are however complex and not fully understood. By studying the physiological effects of insulin in the skin, the understanding of the complex interplay between glucose metabolism and skin microcirculation can be improved. The general aim of this thesis was to develop an experimental in vivo model to study metabolic and microvascular responses to insulin in the skin in healthy subjects. Microdialysis is a suiting technique as it allows for both local delivery of drugs and simultaneous monitoring of the local metabolic and vascular effects in the very same tissue compartment. The effects of local and systemic insulin provocation on skin blood flow and metabolism were investigated using microdialysis urea clearance and laser speckle contrast imaging (paper I). An insulin dependent increase in skin blood flow was observed, presumably induced through the nitric oxide pathway (paper II). Investigating the protein expression during an oral glucose provocation using proteomic approaches however indicates interactions with other pathways, such as the renin-angiotensin system and the kallikrein-kinin system (paper IV). Paper III also investigated methodological concerns regarding the sampling of insulin using microdialysis. This in vivo model can, in the future, be applied to assess the microvascular effects of insulin in the skin in different patient groups, including those with micro-vascular dysfunction due to, for instance, insulin resistance.
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| 3. |
- Iredahl, Fredrik, 1988-
(författare)
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Assessment of microvascular and metabolic responses in the skin
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The general aim of this project was to develop experimental in vivo models that allow for minimally invasive investigations of responses in the skin to microvascular and metabolic provocations. The cutaneous microvasculature has emerged as a valuable model and been proposed to mirror the microcirculation in other organs. Dysfunction in the cutaneous microcirculation has thus been linked to systemic diseases such as hypertension and diabetes mellitus. Models for investigating skin responses could facilitate the understanding of pathophysiological mechanisms as well as effects of drugs.In the first study, three optical measurement techniques (laser Doppler flowmetry (LDF), laser speckle contrast imaging (LSCI) and tissue viability imaging (TiVi)) were compared against each other and showed differences in their ability to detect microvascular responses to provocations in the skin. TiVi was found more sensitive for measurement of noradrenaline-induced vasoconstriction, while LSCI was more sensitive for measurement of vascular occlusion. In the second study, microvascular responses in the skin to iontophoresis of vasoactive drugs were found to depend on the drug delivery protocol. Perfusion half-life was defined and used to describe the decay in the microvascular response to a drug after iontophoresis. In the third study, the role of nitric oxide (NO) was assessed during iontophoresis of insulin. The results showed a NO-dependent vasodilation in the skin by insulin. In the fourth study the vasoactive and metabolic effects of insulin were studied after both local and endogenous administration. Local delivery of insulin increased skin blood flow, paralleled by increased skin concentrations of interstitial pyruvate and lactate, although no change in glucose concentration was observed. An oral glucose load resulted in an increased insulin concentration in the skin paralleled by an increase in blood flow, as measured using the microdialysis urea clearance technique, although no changes in perfusion was measured by LSCI.The thesis concludes that when studying skin microvascular responses, the choice of measurement technique and the drug delivery protocol has an impact on the measurement results, and should therefore be carefully considered. The thesis also concludes that insulin has metabolic and vasodilatory effects in the skin both when administered locally and as an endogenous response to an oral glucose load. The vasodilatory effect of insulin in the skin is mediated by nitric oxide.
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| 4. |
- Hedlund, Johanna
(författare)
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No environmental problem is an island : Aligning networks of transboundary collaboration to complex policy issue interdependencies
- 2019
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In recent times, societal and environmental problems have been exhibiting a growing interconnectedness and interdependency. Based on the idea of institutional fit, interdependency on a problem level should be preferably matched with governance arrangements for effective problem-solving. Still, we know little about the governance of consequential interdependencies across societal and environmental problems. Moreover, knowledge on how the governance of such interdependencies can be effective is even more limited. In governance contexts, actors break down societal and environmental problems into specific policy issues. When actors engage in policy issues that exhibit interdependency with other policy issues, such as resource extraction and environmental protection, they must seek governance arrangements that go beyond framings of single policy issues as detached from others. Transboundary, collaborative forms of governance are often undertaken by actors as a response to interdependencies between policy issues. This combination of interdependencies and transboundary dimensions consolidates high complexity. Despite extensive literature on collaboration as a governance form and a growing body of research on interdependency between policy issues, few studies integrate these to inform research on the effectiveness of such complex governance systems, where both perspectives are combined. Nor do such studies provide empirical evidence of why the effects of transboundary arrangements for governing interdependencies matter. Without such knowledge, transboundary collaboration can therefore occur without acknowledging which policy issues are interdependent, and in what way. This poses a risk of hampering its effectiveness to solve given policy issues, pertaining to a societal or environmental problem. On that account, this PhD thesis will investigate policy issue interdependencies in the transboundary collaborative governance of the Norrström water basin, situated in the Mideast of Sweden with its outlet in Stockholm. This is a novel approach to understand a key feature of environmental problems that makes them difficult to effectively address, and to further investigate the potential of collaborative governance as way to succeed in such endeavour. This licentiate thesis addresses this current research gap with the two following papers. Paper I introduces a methodological procedure for identifying and measuring interdependencies between policy issues based on their common, causal relationships. It thereby contributes to advancing the description of policy issues as an indicator of actors’ decision-making and governance effectiveness. Paper II places the policy issue interdependency networks developed in Paper I in relation to governance networks using a multilevel network approach. It analyzes the impact of policy issue interdependencies as exogenous drivers of collaborative governance, providing insights about the evolution of complex governance systems. With these papers, this thesis aims at a concretization and application of interdependent structures at the policy issue level and actor level respectively. It thereby meets an objective highlighted by previous research by integrating interdependent policy issues and collaborative governance, contributing to the study of complex governance systems through its formation, development and effectiveness.
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| 5. |
- Alkusaibati, Wael, 1990-
(författare)
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Digitalized Co-production of Emergency Response : Using Volunteers as First Responders
- 2024
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Contemporary global challenges like global warming, rapid urban development, and the current unstable security situation, lead to an increase in large-scale crises (e.g., forest fires) alongside frequent smaller emergencies (e.g., house fires and traffic accidents). The increase in emergencies strains professional response organizations, necessitating additional resources. Civilian volunteers are therefore increasingly being integrated into the response system. The development is mediated by information and communication technologies (ICTs) which enable communication between professional responders (e.g., the municipal rescue services, the emergency medical services, the Public Swedish Answering Point) and citizens. While many studies focus on spontaneous volunteer activities emerging on social media, fewer examine organized volunteerism initiatives at the local emergency response level. Over a decade ago, a municipal rescue service in northern Sweden established an initiative recruiting volunteers as first responders and equipping them with basic response tools. The volunteers undergo training in tasks such as cardiopulmonary resuscitation (CPR) and fire extinguishing. They are dispatched to predefined response tasks using simple ICT applications like SMS lists or mobile apps. This initiative has expanded to other areas due to perceived benefits such as shorter response times and reduced casualties and material damage. The phenomenon can be labelled as an emerging form of ICT-enabled or digitalized co-production of public services. However, previous research indicates a research gap in understanding, describing, and defining this type of co-production. The overall aim of the thesis is to describe how these ICT-enabled initiatives emerge and develop over time and identify the related effects on the response system. This is expected to provide recommendations on how they can be developed and supported. This aim is divided into three specific objectives, where each has been addressed through a research paper: 1- identifying how the existing literature describes ICT-enabled/digitalized volunteerism in large- and small-scale emergencies, 2- identifying how these initiatives emerge and operate, and can be maintained in small-scale emergencies, introducing more systematized knowledge on this concept, 3- initially evaluating the contributions of volunteers in the initiatives. Leaning on a case study approach inspired by action research, a combination of data collection methods has been adopted, e.g., a literature review, interviews, and incident reports filled out by volunteers. For the data analysis, the theoretical lens of ICT-enabled/digitalized co-production of public services has been applied. The first paper is a literature review study that examines digitally enabled volunteering activities in crises and small-scale emergencies. It highlights the prevalence of studies on volunteers using social media for crowdsourcing in crises, often termed digitalized volunteerism which entails virtual and, or physical contributions by volunteers to the response efforts. In contrast, fewer studies focus on volunteers' role in local small-scale emergencies, labelled as "hybrid" ICT-enabled or digitalized coproduction. The term hybrid here refers to the loose affiliation of the volunteers where they collaborate with the rescue services but are not officially associated through binding contracts. Hence, they are in between spontaneous and organized volunteerism. Both volunteering modes support professional response systems and display similar needs for steering, financial support, coordination, and integration of ICT artifacts. However, crises require increased coordination to manage uncertainties, risks, and data overload effectively. The second paper presents three models describing the emergence of hybrid digitalized co-production initiatives in urban and rural areas, as defined in Paper 1, along with how national authorities can support them. These models i.e., Rural, Urban, and National consist of three phases: Recruitment, Response, and Maintenance. Each model exhibits distinct characteristics. In rural areas for example, there is a need for more regular training due to low alerting frequency, and the possibility of using simple dispatch ICTs as cost-effective solutions. Conversely, urban areas have more alerts, necessitating more advanced ICTs, with less emphasis on regular training compared to rural areas. At the macro-level, the national model highlights roles that national actors can play such as facilitating a joint Application Programming Interface (API), joint insurance solutions, and an ICT system that can register incoming and active volunteers. The third paper is an initial evaluation of these initiatives at emergency sites, focusing on ICT-enabled dispatch, estimated response times, tasks performed, and collaboration with professionals, to assess the effects of using volunteers. This approach contrasts with previous studies that took an overall perspective and only used qualitative data. A total of 53 incident reports were collected from volunteers, revealing that volunteers arrived before professionals in twothirds of incidents, contributing to an average gain of 5 minutes. Additionally, volunteers performed a broader range of tasks than previously described, and often continued collaboration with professionals on-site, despite the initial expectation of handing over tasks upon the arrival of professional response actors. Also, comparing this data with the rural model from Paper 2, similarities and differences emerged. For instance, there was a higher number of alerts, and the basic ICTs used for dispatch were deemed insufficient, contrary to the model's perception. The thesis’ scientific contribution is a clearer conception of digitalized co-production of, above all, local emergency response as an emerging phenomenon. In the three papers, the ICT dispatch was identified as central and needs further development to enhance this co-production form. The thesis also sheds light on the need to integrate the initiatives into the official governmental frameworks. Furthermore, the thesis provides a primary understanding of how the concept works on the ground and provides an initial evaluation of the effects. In the practical field, the thesis offers insights into the importance of volunteers as additional resources to the official response systems, highlights challenges, hindrances, and enablers, and suggests potential solutions and improvements. Future work will include a further collection of incident reports for more reliable assessments and complementary interviews with volunteers. Also, the potential role of volunteers in larger crises, for example, as part of civil preparedness, will be further explored.
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| 6. |
- Ghaviha, Nima, 1987-
(författare)
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Energy Optimal Operation of Electric Trains : Development of a Driver Advisory System
- 2016
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The electric traction system used in trains is the most energy efficient traction system in the transportation sector. Moreover, it has the least NOx and CO2 emissions in comparison to other transportation systems (e.g. busses, passenger cars, airplanes, etc.). On the other hand, they are extremely expensive, mainly due to high installation and maintenance cost of the catenary system, including e.g. overhead lines and substations. Consequently, the share of electrified lines is only slightly higher than non-electrified lines. For instance in Europe, 60% of the railway networks are electrified, and the percentage is much lower in other continents. Battery driven trains are a new generation of electric trains that can overcome such high costs while keeping CO2 emissions and energy consumption low.At the moment, there are only two battery driven electric trains developed and both of the trains are passenger electric multiple units (EMUs). An EMU is an electric train with a traction system in more than one wagon, in contrast to loco-haul electric trains which have a traction system in one wagon only. Energy management during the operation of battery driven trains is a crucial task, as energy optimal operation of trains considering the optimal use of batteries can increase both the operating time and the lifetime of batteries. Energy efficient train operation is realized using driver advisory systems (DAS) that instructs drivers on how to drive trains for minimum energy consumption. The aim of this research is to propose an algorithm for speed profile optimization of both EMUs and battery driven EMUs. The desired algorithm should be suitable as a core component for an online DAS with short response time.Several approaches are proposed in the literature for speed profile optimization of electric trains, and a few of these have been proposed for speed profile optimization of battery driven electric trains. The trains modeled in almost all of the approaches are trains using a notch system for controlling tractive effort. The proposed solution in this research project is to use discrete dynamic programming (DP) to find the optimum speed profile. The application of DP is studied for speed profile optimization of EMUs with a notch system as well as EMUs with a smooth gliding handle for controlling tractive effort. The problem is solved for both normal EMUs and battery driven EMUs.The results of this research show that DP can provide accurate results in a reasonably short time. Moreover, the proposed algorithm can be used as a base for a DAS with fast response time (real-time).
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| 7. |
- Goodness, Julie, 1985-
(författare)
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Shaping urban environments through human selection for plant traits
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cities, as home to the majority of the world’s people, are significant sites for addressing challenges of achieving sustainability and securing human wellbeing. Urban environments are complex social-ecological systems, and meeting these challenges requires better understandings of the interactions of social and ecological elements. While there are many possible lenses through which to study social-ecological systems, this thesis examines the potential of a traits approach as one way to link ecological elements to social values. In ecology, functional traits have been defined as the characteristics of organisms that determine how organisms respond to the environment, and how they affect ecosystem processes, functions, and services. While functional traits have an established history of being linked to ecosystem processes and functions, they have only recently been extended to social aspects through the operationalization of the ecosystem services concept. As such, there is a distinct gap in identifying traits that are relevant and important to people. This interdisciplinary thesis attempts to bridge some of this lacuna, through empirical studies conducted in two cities: Cape Town, South Africa, and Stockholm, Sweden. Paper 1 addresses connections between traits and social values generally across cities through a literature review that examines connections between traits and cultural ecosystem services. Paper 2 explores preferences for traits and reasons for plant selection in the context of Cape Town. Paper 3 examines vegetation patterns and the expression of socially-valued traits across different land cover and land use classes in Stockholm. Paper 4 serves as a synthesis and comparison piece between Cape Town and Stockholm, and brings together social data on plant preferences and ecological data on plant patterns gathered in both locations under two different projects. Overall, responses from social surveys of preferences suggest that people actively select for a variety of different plant traits in the urban environment, and have a multitude of reasons for selecting the plants that they do, related both to qualities of the plants themselves, as well as broader external factors at multiple scales. Vegetation surveys of plant patterns suggest that trait preferences may be inscribed by people in the landscape, though to differing degrees. Using traits as an approach to link ecological elements to social values exhibits advantages in that traits are a spatial unit that is easily understood by citizens and environmental managers. However, it presents limitations in terms of scale, as traits are most useful in connecting to pin-point characteristics in the landscape, and social values associated with broader scales may be overlooked. Collectively, however, the papers in this thesis suggest that traits may serve as one useful approach for discerning human values in the urban landscape, and can be used as indicators of social function. In management applications, particular traits can be incorporated into landscaping interventions to provide for urban areas of greater social meaning. In this way, traits may serve as one tool within the evolving toolbox of social-ecological system study, and thus can contribute to future urban landscapes that exhibit robust social and ecological function.
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| 8. |
- Hirst, Catherine, 1989-
(författare)
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Iron in the Lena River basin, NE Russia : Insights from microscopy, spectroscopy and isotope analysis
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Iron is an important mediator of biotic and abiotic processes on the Earth’s surface, being an electron acceptor in organic matter degradation, a surface for organic matter and trace element adsorption, and a required element for enzymatic processes during primary production. Yet, the role of iron as a mediator of carbon and trace element cycling in high latitude, permafrost-dominated regions remains poorly investigated. The aim of this study was to characterise the chemical reactivity (by size separation, microscopy and spectroscopy) and sources (by isotope composition) of Fe in the Lena River and major tributaries, spanning a wide range in lithology, topography and climate. The Fe transported in the Lena River and major tributaries carries an integrated signal of Fe weathering processes across the permafrost-dominated terrain.A spatial sample set was collected during the post-spring flood period (July 2012, June 2013), from the main channel and tributaries draining contrasting topography and permafrost extent. Across the basin, Fe is mainly transported as chemically reactive ferrihydrite that spans the particulate (> 0.22 µm) and colloidal (0.22 µm – 1 kDa) fractions. The remaining Fe transported as poorly reactive detrital Fe in clays and crystalline oxides. Fe is transported in larger size fractions than the dissolved OM showing that Fe is not a major carrier of DOM. Nano-sized ferrihydrite was attached to OM in the particulate fraction, evidence of a Fe – OM particle association in the Lena River basin.Ferrihydrite shows distinct isotope values in particulate and colloidal fractions, showing that there is a difference in isotopic composition between different size fractions of the same mineral. A conceptual model was developed to understand ferrihydrite formation in the riparian zone of the Lena River and tributaries. Particulate ferrihydrite has isotope values lower than crustal values resulting from redox and organic-ligand promoted mineral dissolution and precipitation of Fe(II)aq to form coatings of ferrihydrite on particles in the riparian zone. Ferrihydrite colloids span a wider range of isotope values, higher than Fe particles, resulting from variations in the size and isotope composition of the Fe(II)aq pool transported in soil groundwaters, and the isotope fractionation factor for Fe oxidation and organic complexation.A temporal sample set was collected in the main channel between September 2012 – March 2013 and every three days during May 2015. The colloidal Fe shows distinct seasonal Fe isotope signatures and Fe fluxes, with isotope values lower than crustal during winter baseflow, overlying crustal values during spring flood and higher than crustal values during summer, attributed to changing sources and thus conditions for isotope fractionation. The combined understanding of Fe reactivity and isotope composition allows us to isolate the dominant sources of Fe entering the Lena River.
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| 9. |
- Goodness, Julie
(författare)
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Linking functional traits and cultural ecosystem services in urban areas through human preferences
- 2016
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Urban areas are now the daily lived experience for the majority of the world’s people, and it is therefore important to explore what kind of ecological communities and corresponding ecosystem functions and services are being generated in these environments. Urban areas are shaped by a variety of factors, but arguably one of the most influential is that of people, in terms of how their preferences and active selective choices for biota play out in the landscape. A better understanding of these processes and dynamics can contribute toward better scientific knowledge as well as inform management decisions for creating more robust and resilient landscapes of ecosystem function and services. A functional traits approach, which links particular aspects of organisms related to fitness to ecosystem processes, functions, and services, may provide one way of interpreting the significance of biodiversity in the urban landscape. While this approach has traditionally linked traits to processes and functions, recently it has been conceptually extended to include services. Links between traits and provisioning, regulating, and supporting services have been well-characterized, but connections to cultural services have been less explored. This thesis addresses this critical information gap and how human preferences could be connected to the traits framework through an examination of the connections between functional traits and cultural ecosystem services. Paper I, a literature review, investigates scholarship outside the explicit field of functional traits to identify potential trait-cultural service linkages. It finds the strongest base of support for connections between traits and aesthetic benefits (particularly visual); though connections to spiritual, heritage, and wellbeing benefits are also identified. It suggests that what is considered a “functional trait” may need to be revisited in light of the expansion of to include not only ecosystem processes and functions, but services as well. The paper also explores how functional traits could be operationalized in a management context, with the development of trait-service indicators. Paper II builds upon the work of Paper I, and provides an empirical, case study interrogation of connections between traits and cultural ecosystem services in Cape Town, South Africa. It examines people’s expressed preferences for plant traits, and finds that traits related to visual and aesthetic appeal are described as the most common reason for selection, though traits related to use (e.g. as food) and low resource input are also cited. It also points to other factors beyond preference that may influence human selection for plants in the landscape. Together, these two papers provide a more detailed understanding of human preferences for traits in urban areas, and which traits may be connected to which services. This builds knowledge within the functional traits field and provides a basis for further study in research. It also points to trait-cultural ecosystem service connections that can be harnessed in management actions to select for trait combinations that will provide both ecosystem services and ecosystem resilience.
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| 10. |
- Grännö, O., et al.
(författare)
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Preclinical protein signatures in blood predict Crohn's disease and Ulcerative colitis several years before the diagnosis
- 2024
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 18:Suppl. 1, s. I660-I661
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: We aimed to identify protein signatures predictive of a future diagnosis of inflammatory bowel disease (IBD).Methods: We conducted a case-control study, nested within large population-based cohorts with biorepositories. Samples were obtained from individuals who later in life were diagnosed with IBD (preclinical cases) and compared with age and sex-matched individuals who remained free from IBD during follow-up (controls). Using proximity extension assays (Olink, Uppsala), we measured 176 proteins. We applied regularized logistic regression to identify protein signatures of preclinical disease in serum from the discovery cohort (n=312). Their performance was validated in an external preclinical cohort (n=222). The biological relevance of identified proteins was further assessed in an inception cohort (n=144). Finally, we used an IBD twin cohort (n=327) to examine the impact of genetic and shared environmental factors on identified proteins.Results: We identified 34 proteins associated with preclinical Crohn’s disease (CD) in the discovery cohort (Pfalse discovery rate <0.10), with 9 confirmed in the validation cohort (Pfalse discovery rate <0.05). For preclinical ulcerative colitis (UC), 45 proteins were identified and 12 validated (Fig. 1A-B). In the discovery cohort, a signature of 29 proteins differentiated preclinical CD cases from controls with an AUC of 0.85 (Fig. 1G). Its performance was confirmed when applied to the preclinical validation cohort (AUC=0.84, Fig. 1H). Moreover, the signature had excellent capacity to differentiate newly diagnosed CD from healthy controls in the inception cohort (AUC = 0.99, Fig. 1I). The preclinical UC signature had a significant, but albeit lower, predictive capacity in the discovery (AUC=0.77), validation (AUC=0.67) and inception cohort (AUC=0.90, Fig. 1G-I).15 of 17 proteins associated with preclinical IBD demonstrated significantly higher intra-pair correlation coefficients in healthy monozygotic- compared to dizygotic twin pairs, indicating an influence from genetic factors on the regulation of these protein markers. The preclinical signature for CD demonstrated an AUC of 0.87 when comparing twins with preclinical CD (n=10) to matched external healthy twins. However, its predictive capacity was lower when comparing preclinical CD twins with their healthy twin siblings (AUC=0.58), i.e., when accounting for genetic and shared environmental factors. The difference in AUC estimates in the twin cohort was not significant (P=0.07).
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