Mechanical Ventilation and Acute Kidney Injury

Groeneveld, A.B.J. [Promotor]Gemke, R.J.B.J. [Promotor]Plötz, F.B. [Copromotor

Duality properties of indicatrices of knots

The bridge index and superbridge index of a knot are important invariants in knot theory. We define the bridge map of a knot conformation, which is closely related to these two invariants, and interpret it in terms of the tangent indicatrix of the knot conformation. Using the concepts of dual and derivative curves of spherical curves as introduced by Arnold, we show that the graph of the bridge map is the union of the binormal indicatrix, its antipodal curve, and some number of great circles. Similarly, we define the inflection map of a knot conformation, interpret it in terms of the binormal indicatrix, and express its graph in terms of the tangent indicatrix. This duality relationship is also studied for another dual pair of curves, the normal and Darboux indicatrices of a knot conformation. The analogous concepts are defined and results are derived for stick knots.Comment: 22 pages, 9 figure

Effects of fatty acids on T cell function: role in atherosclerosis

Fatty acids affect the pathogenesis of atherosclerosis, and accumulating evidence shows that fatty acids also modulate T cell functions and processes. This Review summarizes the effects of circulating fatty acids on the metabolism, activation, proliferation and polarization of T cells and how these changes influence the subsequent functions of T cells in the pathogenesis of atherosclerosis.T cells are among the most common cell types present in atherosclerotic plaques and are increasingly being recognized as a central mediator in atherosclerosis development and progression. At the same time, triglycerides and fatty acids have re-emerged as crucial risk factors for atherosclerosis. Triglycerides and fatty acids are important components of the milieu to which the T cell is exposed from the circulation to the plaque, and increasing evidence shows that fatty acids influence T cell function. In this Review, we discuss the effects of fatty acids on four components of the T cell response - metabolism, activation, proliferation and polarization - and the influence of these changes on the pathogenesis of atherosclerosis. We also discuss how quiescent T cells can undergo a type of metabolic reprogramming induced by exposure to fatty acids in the circulation that influences the subsequent functions of T cells after activation, such as in atherosclerotic plaques.Cardiolog

An infinite genus mapping class group and stable cohomology

We exhibit a finitely generated group \M whose rational homology is isomorphic to the rational stable homology of the mapping class group. It is defined as a mapping class group associated to a surface \su of infinite genus, and contains all the pure mapping class groups of compact surfaces of genus $g$ with $n$ boundary components, for any $g\geq 0$ and $n>0$. We construct a representation of \M into the restricted symplectic group ${\rm Sp_{res}}({\cal H}_r)$ of the real Hilbert space generated by the homology classes of non-separating circles on \su, which generalizes the classical symplectic representation of the mapping class groups. Moreover, we show that the first universal Chern class in H^2(\M,\Z) is the pull-back of the Pressley-Segal class on the restricted linear group ${\rm GL_{res}}({\cal H})$ via the inclusion ${\rm Sp_{res}}({\cal H}_r)\subset {\rm GL_{res}}({\cal H})$.Comment: 14p., 8 figures, to appear in Commun.Math.Phy

Serum Biomarkers of Vascular Involvement in Childhood Uveitis

Purpose: Nonanterior uveitis frequently involves the retinal vasculature; however, no molecular markers associated with the retinal vascular disease are currently known. In this study, we aimed to identify serum biomarker signatures associated with retinal vascular involvement in noninfectious pediatric uveitis. Methods: We performed a 384-plex targeted proteomic analysis of serum samples of 154 noninfectious pediatric uveitis patients diagnosed with nonanterior uveitis (n = 74), idiopathic chronic anterior uveitis (iCAU, n = 36), or juvenile idiopathic arthritis– associated uveitis (JIA-U, n = 44), as well as 22 noninflammatory pediatric controls. Data on retinal vascular involvement (i.e., papillitis, cystoid macular edema, retinal vasculitis, or retinal capillary leakage on optical coherence tomography and/or fluorescein angiography) were used to stratify cases in the nonanterior uveitis group. Results: In the analysis of nonanterior uveitis, we identified nine proteins significantly associated with retinal vascular involvement, including F13B, MYOM3, and PTPN9. These proteins were enriched through pathway enrichment analysis for the coagulation cascade. Comparing cases and controls, we identified 63 differentially expressed proteins, notably proteins involved in platelet biology and complement cascades, which could be primarily attributed to differences in serum proteomes between anterior uveitis and nonanterior uveitis groups. Conclusions: Serum proteins related to the coagulation and complement cascade are associated with retinal vascular involvement in pediatric uveitis patients. Our results indicate involvement of mediators that could interact with the microcirculation in pediatric uveitis and might serve as potential biomarkers in personalized medicine in the future. Translational Relevance: Our targeted proteomics analysis in serumof pediatric uveitis patients indicates involvement of mediators that could interact with the microcirculation in pediatric uveitis and might serve as potential biomarkers in personalized medicine in the future

Assessing the microcirculation with handheld vital microscopy in critically ill neonates and children: Evolution of the technique and its potential for critical care

Assuring adequate tissue oxygenation in the critically ill, but still developing child is challenging. Conventional hemodynamic monitoring techniques fall short in assessing tissue oxygenation as these are directed at the macrocirculation and indirect surrogates of tissue oxygenation. The introduction of handheld vital microscopy (HVM) has allowed for the direct visualization of the microcirculation and with this has offered insight into tissue oxygenation on a microcirculatory level. Since its introduction, technical improvements have been made to HVM, to both hardware and software, and guidelines have been developed through expert consensus on image assessment and analysis. Using HVM, the microcirculation of the skin, the buccal mucosa, and the sublingual mucosa of healthy and (critically) ill neonates and children have been visualized and investigated. Yet, integration of HVM in hemodynamic monitoring has been limited due to technical shortcomings. Only superficial microcirculatory beds can be visualized, inter-observer and intra-observer variabilities are not accounted for and image analysis happens offline and is semi-automated and time-consuming. More importantly, patients need to be cooperative or fully sedated to prevent pressure and movement artifacts, which is often not the case in children. Despite these shortcomings, observational research with HVM in neonates and children has revealed the following: (1) age-related developmental changes in the microcirculation, (2) loss of hemodynamic coherence, i.e., microcirculatory disturbances in the presence of a normal macrocirculation and, (3) microcirculatory disturbances which were independently associated with increased mortality risk. Although these observations underline the importance of microcirculatory monitoring, several steps have to be taken before integration in the decision process during critical care can happen. These steps include technological innovations to ease the use of HVM in the pediatric age group, measuring additional functional parameters of microvascular blood flow and integrated automated analysis software. As a next step, reference values for microcirculatory parameters need to be established, while also accounting for developmental changes. Finally, studies on microcirculatory guided therapies are necessary to assess whether the integration of microcirculatory monitoring will actually improve patient outcome. Nevertheless, HVM remains a promising, noninvasive tool to help physicians assure tissue oxygenation in the critically ill child