186698 research outputs found
Sort by
The Importance of Neuroimaging Follow-Up in Bilirubin-Induced Encephalopathy: A Clinical Case Review
No full textIntroduction: Hyperbilirubinemia in newborns can lead to kernicterus, a severe form of neonatal encephalopathy caused by bilirubin toxicity. Despite timely interventions such as exchange transfusion, kernicterus can still develop, especially in high-risk infants. MRI is crucial for detecting early and evolving signs of bilirubin-induced brain damage. Case Report: We report a term newborn who developed severe hyperbilirubinemia and kernicterus despite receiving exchange transfusion. The infant presented on day 3 of life with jaundice, hypotonia, and feeding difficulties and had a bilirubin level of 51 mg/dL. After exchange transfusion, bilirubin levels normalized, but neurotoxicity persisted. Initial MRI at one month showed mild T1 hyperintensity in the hippocampi with no changes in the basal ganglia. At two months, T1 hyperintensities in the hippocampi partially resolved. By six months, MRI revealed T2 hyperintensities in the globus pallidus and hippocampal atrophy, consistent with kernicterus. Magnetic resonance spectroscopy (MRS) showed reduced N-acetylaspartate (NAA) levels, indicating neuronal loss. Discussion: MRI is essential in monitoring bilirubin-induced brain injury. In this case, early MRI findings showed mild hippocampal T1 hyperintensity, which resolved partially. At six months, T2 hyperintensities in the globus pallidus confirmed chronic bilirubin encephalopathy. MRS demonstrated a reduction in N-acetylaspartate, indicative of neuronal loss. Susceptibility-Weighted Imaging (SWI) showed no abnormalities, likely due to the myelination process in neonates. Conclusions: This case highlights the importance of repeated MRI in detecting bilirubin-induced brain damage. Early neuroimaging enables timely interventions and improves long-term neurodevelopmental outcomes in infants with severe hyperbilirubinemia
Quantum groups as global symmetries II. Coulomb gas construction
No full textWe study a conformal field theory that arises in the infinite-volume limit of a spin chain with Uq (s l2) global symmetry. Most operators in the theory are defect-ending operators which allows Uq (s l2) symmetry transformations to act on them in a consistent way. We use Coulomb gas techniques to construct correlation functions and compute all OPE coefficients of the model in closed form, as well as to prove that the properties imposed by the quantum group symmetry are indeed satisfied by the correlation functions. In particular, we treat the non-chiral operators present in the theory. Free boson realization elucidates the origin of the defects attached to the operators. We also comment on the role of quantum group in generalized minimal models
Colorectal cancer-infiltrating NK cell landscape analysis unravels tissue-resident PD-1+ NK cells in microsatellite instability tumors
No full textBackground: Natural killer (NK) cells are innate lymphocytes endowed with potent cytotoxic activity. The presence of tumor-associated NK cells has been correlated with better prognosis in several solid tumors including colorectal cancer (CRC). This malignant disease is the second cause of cancer death worldwide and is in urgent need for novel approaches to improve current immunotherapies. Since CRC microenvironment can induce NK cell dysfunction and hinder cancer control, understanding tumor-associated NK cell features is mandatory to fully unlock their immunotherapeutic potential. Purpose: Our study aims at elucidating the molecular and functional characteristics of tumor-associated NK cells in CRC focusing on the expression of immune checkpoints that critically regulate NK cell function. We performed an in-depth cytofluorimetric analysis of tumor-associated NK cells obtained by tissue dissociation of samples derived from 80 CRC patients comparing tumor with matched tumor-free tissue and peripheral blood, stratifying patients by tumor stage or MSI/MSS condition. Tumor tissue was also analyzed by immunohistochemistry. Results: NK cells expressing immune checkpoints (i.e., KIR, NKG2A and TIM-3) were significantly enriched in tumor compared to tumor-free tissue, and an increase in PD-1+ NK cells was observed in tumors compared to peripheral blood and tumor-free tissue, indicating TME-induced modulation. Notably, tumor-associated PD-1+ NK cells characterized MSI rather than MSS CRC. In addition, tumor-associated NK cells also expressed tissue residency markers (CD103 and/or CD49a) and displayed a distinct profile also including the PD-1+ NK cell subset in MSI CRC, possibly representing NK cells recruited from circulation, retained in tumors, and reconfigured by TME signals. Importantly, tissue resident NK cells adequately expressed activating NK receptors and cytotoxic molecules. Conclusions: These results suggest, together with an increased PD-L1 expression on MSI tumor cells, that the efficacy of immunotherapies in MSI CRC based on PD-1/PD-L1 blockade could also rely on a superior anti-tumor potential of PD-1+ NK cells. Conversely, MSS CRC, in which tumor-associated PD-1+ NK cells are scarce, could benefit more from immunotherapies blocking NKG2A and/or KIRs. Thus, novel approaches based on NK cell features related to CRC type, fully exploiting circulating and resident NK cell anti-tumor activity, could be key to next-generation therapies
Phenotypic and functional analysis of human Natural Killer lymphocytes in patients affected by haematological neoplasms treated with autologous T lymphocytes genetically modified with chimeric antigen-specific receptor
No full textChimeric antigen receptor T cell therapy represents a novel perspective for patients with aggressive, chemotherapy-refractory B cell neoplasms. While CAR-T cells exhibit direct cytotoxic properties, other immune populations may also contribute to treatment response and complications. Macrophages and dendritic cells are recognized as key-mediators of CAR-T cell associated inflammatory toxicities, while emerging evidence suggests that regulatory T cells may hamper CAR-T cell efficacy. To investigate NK cell dynamics, we performed peripheral blood flow cytometry in 40 patients before and after CAR-T cell therapy for diffuse large B cell lymphoma. Our analysis revealed that early NKG2A+ KIR⌐ NK cells repopulate shortly after CAR-T infusion. Within the CD56dim subset, NKp46+ NK cells frequencies progressively increased overtime, while NK cells expressing the inhibitory receptor Siglec-7 were abruptly depleted. PD-1 was already detectable before lymphodepletion and increased thereafter, potentially reflecting NK cell activation or glucocorticoid treatment to mitigate inflammatory complications. Higher PD-1 levels were associated with severe inflammatory complications. Patients who achieved a response to therapy exhibited enriched populations of NKp46+, CD62L+ NK cells, likely with lower proportions of PD-1+ circulating NK cells. Overall, our findings suggest that NK cells undergo dynamic changes following CAR-T cell therapy, potentially driven by lymphodepleting chemotherapy and cytokines release. Further studies are needed to clarify their role in inflammatory complications and treatment outcomes
Computational study of retinal blood flow coupled to a global circulation model
No full textThis work focuses on the study of retinal blood flow, using computational models to simulate the interactions between ocular circulation and global systemic dynamics. The primary aim of this work is to develop a comprehensive multiscale mathematical model that can accurately represent the blood flow dynamics in the retina, considering the complex interplay between retinal circulation, intraocular pressure, and systemic factors such as cerebrospinal fluid pressure. These interactions are essential for gaining deeper insights into the regulation and behavior of retinal blood flow under normal and pathological conditions. The first chapter provides the physiological background necessary for understanding the intricacies of ocular circulation. It explains the structure and function of the visual apparatus, with particular focus on the vascular system. Detailed descriptions are provided for the retinal and choroidal circulations, both of which are responsible for supplying the retina with oxygen and nutrients, while also facilitating the removal of waste products.
The chapter further explores the relationship between ocular circulation and systemic circulation, particularly in the context of intraocular pressure (IOP), which plays a critical role in maintaining the shape of the eye and preventing damage. The dynamics of retinal vein pulsation, influenced by both IOP and intracranial pressure, are also discussed, as well as pathological conditions related to disturbances in retinal circulation.
The second chapter reviews the mathematical models that have been developed to simulate retinal blood flow. These models vary in their complexity, from simplified lumpedparameter models to more advanced 1D, 2D, and 3D models. Each model offers a different approach to representing the retinal vascular system and its hemodynamic behavior. The chapter critically examines the strengths and limitations of each. For example,
lumped-parameter models provide a global representation of blood flow, but lack spatial resolution, while 1D models offer a more detailed representation of blood flow along the length of vessels, and 3D models capture the full complexity of retinal vasculature but at the cost of higher computational demand. The chapter discusses how advancements in computational power and imaging technologies have contributed to the development of these models, enabling a more accurate understanding of retinal circulation.
The third chapter presents the global multiscale mathematical model developed by Müller and Toro, as detailed in their foundational works . This comprehensive model integrates the circulatory system with CSF dynamics, combining one-dimensional (1D) representations of major vessels with zero-dimensional (0D) models for microcirculation, heart and pulmonary circulation, and CSF compartments. This chapter provides a detailed explanation of the model’s structure, formulation, the physical laws and numerical techniques it incorporates. Chapter 4 builds upon the global circulation model described in Chapter 3, focusing on the integration of the retinal vascular network and IOP dynamics. This chapter details how the model is adapted to simulate blood flow specifically in the retina, incorporating both the IOP and the Starling Resistor (SR) model to represent retinal perfusion. The process begins with the segmentation and correction of the retinal vessels, ensuring accurate representation of the arterial and venous networks within the eye. Once the vasculature is properly defined, the IOP model is incorporated to simulate how intraocular pressure influences blood flow through the retinal vessels. Additionally, the SR model is applied to simulate retinal vein pulsation, accounting for changes in vessel diameter and pressure during the cardiac cycle, and reflecting the dynamic nature of retinal blood flow. Chapter 5 presents the results of the simulations performed using the models developed in the previous chapters. The chapter begins with an analysis of mass conservation across the different numerical methods employed in the simulations. This analysis ensures that the models accurately preserve mass throughout the system, which is critical for the validity of the simulation results. Following this, the results primarily focus on the validation of the model’s predictions against experimental and clinical data, with a particular emphasis on systemic and cerebral hemodynamics. The model’s blood flow predictions are compared with data from the literature to validate the accuracy of the simulations. For the retinal circulation, the chapter includes a comparison of the simulated curves and values with those available in the literature. This comparison helps to validate the model’s representation of retinal blood flow dynamics, particularly in terms of pressure and flow. Additionally, the chapter compares viscoelastic and elastic models to evaluate how different vessel properties affect blood flow. Finally, the sixth chapter presents a discussion of the results, offering insights into the implications for clinical applications. The limitations of the current model will be addressed, and suggestions for future research will be provided. The chapter is concluded by a discussion how this research contributes to the understanding of retinal hemodynamics
Linear quadratic control of nonlinear systems with Koopman operator learning and the Nyström method
No full textIn this paper, we study how the Koopman operator framework can be combined with kernel methods to effectively control nonlinear dynamical systems. While kernel methods have typically large computational requirements, we show how random subspaces (Nystr & ouml;m approximation) can be used to achieve huge computational savings while preserving accuracy. Our main technical contribution is deriving theoretical guarantees on the effect of the Nystr & ouml;m approximation. More precisely, we study the linear quadratic regulator problem, showing that the approximated Riccati operator converges at the rate m-1/2, and the regulator objective, for the associated solution of the optimal control problem, converges at the rate m-1, where m is the random subspace size. Theoretical findings are complemented by numerical experiments corroborating our results. (c) 2025 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies
Practical handbook of pediatric orthopedic traumatology
No full textThe editorial format and title of the Practical Handbook of Pediatric Orthopedic Traumatology anticipate the essence of our work: to quickly and effectively give an idea of what pediatric traumatology can be, while trying to condense it all into a single, small, but equally effective volume. It is well known that some types of fractures in children are unique and peculiar: their diagnostic framework is crucial, as is the ability to determine the most appropriate treatment. Each fracture that can occur in children is examined in short chapters, rich in pictures and diagrams. Each topic is treated schematically, trying to give simple guidelines on clinical and instrumental examination, treatment and follow-up, as well as possible consequences depending on the type of fracture
Sources on the Sala Grande before Vasari
No full textThis essay is intended as a brief reflection on the resonance that Leonardo’s work
in the Sala Grande, commissioned by the Florentine Republic, enjoyed among
his contemporaries. I will comment on the evidence for Leonardo’s activity as it
appears in literary text—both printed and manuscript—from the first half of the
sixteenth century, and lead up to the Torrentiniana version of the Lives, the editio
princeps published by Vasari in 1550 in Florence
A New Typology for Classifying European Container Terminals, Considering Their Ability to Green Their Operations
No full textThe current container terminal market is facing challeng-ing and uncertain times. The growth in container vessel size and high competition are pushing terminals to increase their storage capacity and productivity. In addition, environmental regulations and local govern-ments are pushing terminals to reduce their environmental impact dur-ing terminal operations. Consequently, it is impossible for terminals to increase their productivity and terminal capacity without considering the environmental impact of container handling operations. This is the first paper of a two-part study that researches the readiness of certain clusters of container terminals to innovate their container handling operations. This paper identifies the variables that are essential for classifying Euro-pean container terminals. By conducting a literature review, nine char-acteristics have been identified: equipment, level of terminal automation, spatial dimensions (yard layout, terminal size, terminal capacity, quay length), geographical location, port and terminal governance structure, throughput, available energy sources, and labor and union organization. The terminal clusters that come out of the classification, depend on the research goal. For this reason, the actual clustering of terminals will be performed in the second part of this research, as the actual clustering of terminals depends on the goal of that research as some clusters are bet-ter suited for certain research goals. In the second paper of this research, terminals will be clustered according to their readiness to implement specific container terminal innovations