Coming dissertations at Uppsala university
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Exploring Vascular Specialization at the Organotypic and Cellular Levels
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-543745
The lymphatic system is a unidirectional network that drains fluid and macromolecules, consisting of functionally specialized lymphatic capillaries and collecting vessels. Similarly, the blood vascular system is composed of the functionally arteries, capillaries, and veins, which together enable the distribution of oxygen and nutrients. Certain tissues exhibit organ-specific vascular adaptations, including hybrid vascular identities that combine features of different vessel types. In Paper I, I identified the penile cavernous sinusoids (pc-Ss) as a novel hybrid vascular bed that maintains both blood and lymphatic vessel-specific characteristics in both mice and humans. Notably, this highly specialized PROX1-positive vascular bed developed independently of the key lymphangiogenic growth factor VEGF-C, distinguishing it from other lymphatic and hybrid vessels analyzed so far.
The vascular system is continuously subjected to mechanical forces generated by fluid flow, including laminar and turbulent flows in different vessel segments. Unique to the lymphatic system, the oak leaf-shaped lymphatic endothelial cells (LECs) that line the capillaries and facilitate the uptake of interstitial fluid are primarily subjected to transmural flow and isotropic stretch, caused by fluid uptake-induced changes in vessel caliber. To investigate how capillary LECs adapt to these mechanical stressors at the cellular level, I established in Paper II in vitro models that mimic transmural flow and isotropic stretch. Using these models, in Paper III, I identified cyclic isotropic stretch as a driver of key features associated with capillary LECs in vivo, including prominent cellular overlaps and curvature of cell-cell contacts. We also found that dynamic remodeling of capillary LEC overlaps and the cytoskeleton is essential to maintaining monolayer integrity during isotropic stretch in vitro and in homeostasis in vivo. This process is mediated through a CDC42-dependent mechanism independent of integrin ß1.
In summary, this thesis provides new molecular and functional insights into organ-specific vascular heterogeneity, which may ultimately help identify targets for the development of improved therapies for conditions such as dysregulated penile vasculature or lymphedema. Furthermore, by applying new tools to study different mechanical forces in vitro, this thesis uncovers how publisherpus contribute to the functional specialization of LECs and regulate the homeostatic maintenance of lymphatic vessels - insights that may be applicable to other vascular beds.
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Reliability and prognostic value of systolic left ventricular function assessments by echocardiography following Acute Coronary Syndrome
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-542295
This thesis investigates the accuracy and prognostic utility of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) in acute coronary syndrome (ACS), analyzing data from Swedish myocardial infarction patients across four studies. The first paper evaluated the accuracy and reliability of LVEF recorded in the SWEDEHEART registry. Although good agreement was observed using Gwet’s weighted coefficient, unweighted metrics showed moderate consistency particularly for subnormal LVEF (<50%) with SWEDEHEART values tending to underestimate LVEF compared to the reference method. This highlights the need for caution when interpreting LVEF data from the years of inclusion (2008-2014).
In the second study, GLS was examined as a potential metric to improve risk prediction in ACS beyond LVEF. Although GLS was independently predictive of adverse outcomes, its additional prognostic value over LVEF for differentiating patients at risk was limited, particularly when systolic function was normal or mildly reduced. The third study reassessed LVEF and GLS one year post-myocardial infarction, finding that changes in GLS may offer improved prognostic insights in selected patients beyond initial LVEF and GLS values. Patients with improved systolic function showed comparable outcomes to those with stable normal function, while a small subset with deteriorating GLS faced elevated risk of heart failure (HF) hospitalization.
The final study explored the impact of adding LVEF and GLS to the GRACE 2.0 score for mortality risk stratification. Neither LVEF nor GLS significantly enhanced risk discrimination whereas the biomarker GDF-15 did improve predictive accuracy when combined with GRACE 2.0, suggesting that in ACS populations with predominantly normal ejection fraction, comorbidities and age, rather than myocardial dysfunction, influence mortality risk.
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Wealth, War and Modernization : Essays on Mexican Economic History
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-543205
This dissertation examines the intricate relationship between war, wealth accumulation, and economic modernization in Mexico from independence in 1810 to the mid-20th century. It challenges the notion of the Mexican 19th century as a "censored century", unknowable due to a lack of data, by employing a novel database of wills to reconstruct wealth inequality trends. In turn, those estimates can be used to highlight the changing political economy dynamics. The study reveals consistently high levels of wealth inequality, punctuated by fluctuations driven by political and economic forces.
Inequality, wars, and economic modernization are inexorably tied. Previous research has seen wars as great levelers. However, wars in 19th-century Mexico did not uniformly reduce inequality. Some conflicts, such as the War of Independence, destroyed wealth, while others, like the conflicts of the First Republic, enabled elite extraction and wealth accumulation. The evolution of inequality clarifies the political economy dynamics that shaped the formation of the Mexican state and its accumulation of state capacity. Constant warfare became an obstacle to the structural transformation of its economy.
Contrary to common sense, losing territory to the US in the aftermath of the Mexican-American War in 1848 ultimately strengthened the Mexican state. The resulting smaller, more manageable border enhanced the security and control of the territory. It facilitated demographic shifts that would translate into greater state capacity. The consolidation and strengthening of the state after nearly 60 years of warfare led to the modernization of the economy during the Porfiriato (1877–1910). The late 19th century saw the beginnings of industrialization in a context of state capture by economic elites, consolidating control over natural resources, banks, and infrastructure.
The Mexican Revolution (1910–1940), a reaction against the Porfirian elites, brought significant changes, but its impact on inequality was mixed. Initial reforms led to decreased income inequality, yet subsequent industrialization policies, particularly import substitution industrialization (ISI), contributed to its resurgence. Despite fostering economic growth, ISI created a "mesocratic distribution," favoring a growing middle class while exacerbating inequality between urban and rural areas.
This dissertation stresses the crucial role of political decisions and institutions in shaping inequality, demonstrating that economic forces alone do not determine the distribution of resources. By analyzing winners and losers across different historical periods, the thesis provides insights into the complex dynamics of inequality in a developing nation, offering lessons for contemporary policymaking to achieve equitable and sustainable development.