Littérature scientifique sur le sujet « Reticoli e ideali »

Abstract Background: Anemia is a nearly universal complication of End Stage Renal Disease (ESRD). Erythropoiesis-stimulating agents (ESAs) have greatly decreased transfusion dependence in the anemia of ESRD. In some cases, ESAs are not effective, indicating ESA-resistance. ESA-resistant anemia is not well characterized and can be difficult to manage. Among the most frequent causes of ESA-resistant anemia is secondary hyperparathyroidism (SHP), which can induce bone marrow remodeling and fibrosis. Treatment protocols in SHP are centered on goal calcium, phosphorus and parathyroid hormone (PTH) levels and not the biologic consequences of high PTH. The hematologic insults secondary to SHP are rarely addressed. Instead, it is common to simply increase ESA dosing, rather than address the cause of ESA-resistance. In this retrospective review, we describe a cohort of patients with ESRD and SHP and highlight in detail one patient with reversible bone marrow changes and transfusion-dependent anemia, as well as descriptive and laboratory findings of bone marrow changes in patients with anemia and ESRD referred to our center. Methods: Using the EMR, the patient's data including demographics, progress notes, laboratory values, and bone marrow findings were extracted. Subsequently, the EMR was interrogated to reveal all patients with anemia and ESRD, who had undergone a bone marrow biopsy at out center over a ten year period from 2010 to 2020, revealing 64 patients. Data including demographics, laboratory values, bone marrow findings, and medications were extracted. Data was presented descriptively. Results: A 67-year-old male with ESRD secondary to hypertension and type 2 diabetes was referred to our Hematology clinic for anemia of ESRD. He was receiving Epoetin 20,000 IU three times weekly but was still transfusion-dependent to maintain a hemoglobin of 6.3 g/dL, with a concomitant PTH of 400.5 pg/mL. Calcium and phosphorus were normal and thus his SHP was not aggressively managed. Bone marrow biopsy revealed focal areas of bone marrow remodeling and reticulin fibrosis. Fluorescence in situ hybridization studies for myelodysplastic syndrome were negative, as were thyroid studies, serum protein electrophoresis, and free light chain ratio. In conjunction with his nephrologist, treatment of his SHP was optimized. His initial regimen was calcitriol 0.25 mcg once daily and calcium acetate 667 mg three times daily. Subsequently, cinacalcet 30 mg twice daily was added and calcium acetate was replaced with sevelamer 1600 mg three times daily. Following these changes, his hemoglobin remained stable in the range of 8-9 g/dL. He was no longer transfusion-dependent, despite only a modest reduction in PTH to 311.2 pg/mL. Repeat bone marrow biopsy revealed no bone marrow remodeling or reticulin fibrosis. Bone marrow findings for all patients referred to our clinic with ESRD and anemia are summarized in Table 1. The range of PTH for patients with bony remodeling was 183-16161.9 pg/mL versus 90.8-3283 pg/mL for those without bony remodeling. The range of PTH for patients with fibrotic changes was 183-2487 pg/mL versus 90.8-16161.9 pg/mL for those without fibrotic changes. ESA dosing varied among the patients. Conclusion: SHP is an increasingly identifiable cause of ESA-resistant anemia, as demonstrated by the reversal of transfusion dependence in our patient once SHP was more adequately treated. The degree of reversible ESA-resistant anemia and transfusion dependence in the setting of a PTH elevation to 400.5 in this case is surprising. The great variability in PTH levels of patients both with and without bone marrow changes presented here indicates the relationship between SHP and anemia is intricate. A single target level for the whole dialysis population is not appropriate; neither is targeting only and the same goal calcium, phosphorus, and PTH levels for the whole dialysis population either. Based on the findings of our institutional cohort, we suggest that it is justified to deviate from "on-size-fits-all" protocols and attempt a trial of aggressive management of SHP in patients with difficult to manage ESA-resistant anemia with what is considered only modest PTH elevation. Figure 1 Figure 1. Disclosures Moe: Allena Pharmaceutical: Consultancy; Janssen: Consultancy; Alnylum: Consultancy; DIcerna: Consultancy; Tricida: Consultancy.

In this article, I analyze a concept central to the work of the Beninese philosopher Paulin Jidenu Hountondji: pluralism. Hountondji’s plu-ralism consists of both a theoretical pluralism, which emphasizes the importance of plurality and debate within philosophy and science, and a politico-economic pluralism, which arises in opposition to the dominative tendencies of cultural nationalism and the capitalist world-system. I contend that at the heart of both Hountondji’s theo-retical and politico-economic pluralism rests a concept of negative pluralism, a political principle derived from Hountondji’s immanent critique of his own historical conjuncture. I conclude that Hountondji’s negative pluralism offers a distinct and compelling ac-count of plurality as neither innately nor instrumentally ideal. In-stead, Hountondji’s negative pluralism allows us to identify, through a critique of existing political structures, forms of political compul-sion and economic exploitation which function as obstacles to uni-versal emancipation.

Abstract HV-MAPS are a novel type of CMOS depleted active pixel sensors for ionizing particles, implemented in standard CMOS processes, that have been proposed in several future particle physics experiments for particle tracking. In depleted monolithic sensors, the sensor element is the n-well/p-substrate diode. The sensor matrix and the readout are integrated in one single piece of silicon and the electronics is embedded in shallow wells inside deep n-wells, isolated from the substrate. High voltage biasing increases the depth of the depletion region, improving sensor properties as signal amplitude, charge collection speed and radiation tolerance. ATLASPix3 is the first full reticle size high voltage Monolithic Active Pixel CMOS sensor, designed to meet the specifications of the outer layers of the ATLAS inner tracker (ITk). Its thin design, the excellent position resolution, high readout rate and high radiation tolerance make ATLASPix3 an ideal candidate for large-area tracking detector R&D of future collider experiments such as the Circular Electron Positron Collider (CEPC) silicon tracker.

Abstract Abstract 3924 Targeted therapies in terms of monoclonal antibodies have become standard in the treatment of various lymphomas. Albeit being more specific than conventional therapy, the used antibodies target surface receptors both present on polyclonal and monoclonal hematopoietic cells. Due to its specificity for the malignant B-cell clone the B-cell receptor (BCR) is an ideal therapeutic target in lymphoma therapy. Moreover, using peptides has several advantages over whole antibodies: reduced immunogenicity, better epitope mimicry and tissue penetration, easier synthesis and more favourable pharmacokinetics (no uptake into the reticulo-endothelial system). Peptides mimicking the epitope recognized by lymphoma BCRs have therefore been praised as promising therapeutic tools for years (Lam, West J Med., 1993) but a proof-of-concept has only been published recently in mice bearing subcutaneous A20 lymphoma (Palmieri et al., Blood, 2010). In the current study, we have established a human cell line-derived disseminated Burkitt′s lymphoma model (SUP-B8) in NOD/SCID mice by intravenous injection. Our active principle was the tetramerized BCR binding peptide YSFEDLYRRGGK-biotin (termed T-peptide, Renschler et al., PNAS, 1994) which was applied intravenously on day (d) 12, 14, 16 and 19 after injection of the tumor cells, respectively. The therapeutic efficacy was evaluated in comparison to several control groups (tetramerized control peptide (termed C-peptide, RDYSYERLFGGK-biotin), vehicle (0.8% ACN in water, 200μl/d) and untreated animals). Tumor cell engraftment was monitored via daily surveillance of disease symptoms, FACS (anti-human lambda, CD19, anti-murine CD45) and fluorescence-based in vivo imaging system (FI, Kodak FX, Alexa750 labeled anti-human CD45) on days 12 and 21. SUP-B8 engrafted predominantly in the bone marrow (BM, take rate = 100%) and marrow infiltration increased in untreated mice between start and end of therapy from 1 ± 0.4% (d 12) to 39.8 ± 9.4% (d 21). Other sites of engraftment were subcutis (38%) and spleen (8%). The examined compounds were well tolerated in tumor-bearing mice, no acute toxicity could be observed and maximal body weight loss was below 15%. Treatment of xenograft mice with the tetramerized BCR-binding peptide significantly reduced bone marrow infiltration compared to controls (T-peptide 8.1 ± 4.6%, C-peptide: 32.8 ± 8%, p=0.037, vehicle: 30.5 ± 7.9%, p=0.029). Considering the short half-life of uncoupled peptides and the injection schedule every second day, this is a remarkable reduction. For further optimization of this promising therapeutic approach we plan to couple peptides to effector molecules via acid labile linkers; this is based on the evidence that confocal imaging of Burkitt lymphoma cell lines showed the processing of specific BCR binding peptides in acidic organelles of the cell. In summary, we conclude that BCR targeted peptide-based therapy is a feasible method with remarkable therapeutic results in vivo and future studies will focus on coupling specific peptides to appropriate effector molecules or combinational therapeutic approaches using conventional chemotherapeutics. Disclosures: No relevant conflicts of interest to declare.

Abstract One of the main problems of T cell mediated immunotherapy in delivering significant clinical impact and benefit to patients with malignant diseases and life threatening viral infections is the expansion of adequate numbers of functional antigen specific cytotoxic T cells. The current approaches for expanding T cells possess significant drawbacks in terms of timing, reproducibility and reliability. Many if not all these approaches rely on ex-vivo cell manipulation, which often leads to short T cell survival in-vivo after infusion. In-vivo artificial systems should be the ideal. There is no artificial APC system capable of both ex-vivo and, more importantly, in-vivo antigen specific T cell expansion. In order to address this we have developed a novel artificial nanotechnology system capable of priming and expanding antigen specific T cells in-vivo. As defined by the NIH, nanotechnology uses nanoscale injectable, targeted and traceable devices capable of important immunological/clinical functions. This nano-system was constructed using the latest generation of nanoscale immuno liposomes (100nm; 50 times smaller than average cells and same size as most human viruses), approved for in-vivo human use since they are non-toxic, biodegradable, avoid fast recognition by the reticulo-endothelial system, are safe in terms of size, have good stability and favourable pharmacokinetic behaviour for safe in-vivo trafficking. We have coated these liposomes with an optimised number of MHC Class I / peptide complexes and a specific and selected range of ligands for adhesion (ICAM-1), early activation (CD28, CD27), late activation (4-1BB) and survival receptors (CD40L). We have made these immuno liposomes traceable, either via a fluorescent lipid or iron oxide nano particles (13nm each), which make them traceable in vivo using Magnetic Resonance Imaging. Production of this system in a ready to use form is achievable in less than 48 hrs. We are currently working on an HLA-A2 transgenic mouse model to validate in-vivo behaviour of the system. After ex-vivo stimulation with this artificial system (using CMV pp65 as model antigen), we have measured successful expansions of high antigen specific T cell numbers (55 to 80 fold) in CMV positive individuals, which are superior when compared with other systems such as DCs (30 fold), beads (non antigen specific) and soluble tetramers and antibodies (30 fold). Expanded T cells are functional; they produce INF-γ and are predominantly of effector-memory and memory phenotype. We have demonstrated by double fluorescent staining that these liposomes are recognised directly on CD8+ T cells in an antigen specific fashion and also indirectly by being incorporated on the surface of the natural APCs as exosomes do. When tested in naive individuals, this system is also capable of priming naive T cells without additional adjuvants, as other APC systems use. In conclusion we have established the optimal conditions for an efficient artificial APC system, which embodies a powerful, controllable and superior approach with enormous potential for T cell immunotherapy in vivo. Figure Figure

Abstract Introduction Hemangioblastomas of the pineal region or pituitary stalk are extremely rare. Only two cases of hemangioblastomas involving the pineal region have been reported, and four involving the pituitary stalk. The purpose of the present manuscript is to describe an unusual case of supposed hemangioblastoma found concomitantly in the pineal region and pituitary stalk of a patient diagnosed with Von Hippel-Lindau (VHL) disease. Case Report A 35-year-old female patient with a previous diagnosis of VHL complaining of occipital headaches and balance disturbances for three weeks, who previously had a cerebellar hemangioblastoma resected. The visual characteristics of the tumor suggested a friable vascular lesion with a reddish-brown surface, and an incisional biopsy was performed. The tumor consisted of a dense vascular network surrounded by fibrous stroma abundant in reticulin and composed by both fusiform and dispersed xanthomatous cells; the immunohistochemistry was immunopositive for neuron-specific enolase and immunonegative for epithelial membranous antigen. The patient has been monitored closely for 2 years, and the supratentorial masses have not presented any volume alteration. Conclusion This rare association must be taken into account in patients with VHL disease, or at least be suspected in patients who present a thickening of the pituitary stalk and a pineal-region mass. We believe a biopsy of our asymptomatic patient could have been dangerous due to inherent complications like intraoperative bleeding. We recommend close observation of asymptomatic lesions with MRIs every six months or until the lesions become symptomatic. If the pineal-region tumor does become symptomatic, gross resection via a transcallosal approach would be ideal.

In questa tesi si presentano principalmente tre classi di reticoli: quelli distributivi, quelli modulari e quelli geometrici. Siccome i reticoli sono degli insiemi parzialmente ordinati che soddisfano certe proprietà, nel primo capitolo si richiamo alcuni concetti fondamentali della teoria dell'ordine. Il secondo capitolo si apre con la definizione classica di reticolo distributivo. Successivamente ci si è soffermati sulla decomposizione degli elementi in sup-irriducibili, che nei reticoli distributivi risulta essere ben definita ed unica per ogni elemento. Alla luce di ciò si caratterizzano tali reticoli in tre modi differenti: come reticolo degli ideali d'ordine, come prodotto di catene e attraverso identità soddisfatte dalla funzione rango. Il terzo capitolo riguarda i reticoli modulari e semimodulari. Grazie al teorema di isomorfismo canonico vengono caratterizzati i reticoli modulari per mezzo di due morfismi di reticoli. In questi reticoli viene meno l'unicità della decomposizione in sup-irriducibili ma risulta comunque soddisfatta la proprietà di scambio. Vengono poi definiti i reticoli semimodulari. Il capitolo si conclude dando una caratterizzazione dei reticoli modulari e semimodulari per mezzo di identità soddisfatte dalla funzione rango, che si dimostra essere ben definita in entrambi i casi. Il quarto capitolo riguarda la classe più generica, quella dei reticoli geometrici. Vengono definiti alcuni oggetti (matroidi, reticoli complementati e relativamente complementati) grazie ai quali si riescono a dedurre proprietà e dare nuove caratterizzazioni di tali reticoli. Nel quinto capitolo vengono approfonditi alcuni esempi precedentemente citati: le catene, il reticolo dei divisori, l'algebra di Boole, il reticolo dei sottospazi di uno spazio vettoriale e il reticolo delle partizioni; in particolare gli elementi di ogni reticolo vengono classificati in base al loro rango.

La funzione di Möbius definita per insiemi parzialmente ordinati localmente finiti è un classico strumento di analisi combinatoria. Si tratta di una generalizzazione della funzione di Möbius nota in teoria dei numeri e ha varie applicazioni pure in teoria dei gruppi, dalla caratteristica di Eulero di complessi di sottogruppi fino allo studio di aspetti algebrici in automi cellulari. Nella prima parte della tesi richiamiamo alcune informazioni elementari per strutture d'ordine che sono legate alla funzione di Möbius, e ne presentiamo le principali proprietà, quali ad esempio la formula di inversione di Möbius e i teoremi di Crapo. Inoltre analizziamo alcuni legami importanti con argomenti di teoria dei gruppi, al fine di motivare il nostro interesse nei confronti della funzione di Möbius di gruppi lineari finiti. Nella seconda parte, lavoriamo su questi gruppi per studiarne la funzione di Möbius e otteniamo risultati originali che si rivelano utili per calcolarla, nota la struttura di alcuni particolari reticoli di sottospazi associati ai sottogruppi. Vediamo in dettaglio il caso in cui abbiamo un reticolo di sottospazi distributivo. In seguito mostriamo un esempio di sottogruppo del gruppo lineare generale, tale che il reticolo di sottospazi associato al sottogruppo non è distributivo. In questo modo osserviamo che i nostri ragionamenti hanno una validità più ampia e possono essere applicati a situazioni differenti, sotto determinate condizioni. Nell'ultima parte della tesi, colleghiamo i risultati ottenuti in precedenza ad alcune questioni aperte che riguardano gruppi profiniti finitamente generati e gruppi finiti almost-simple, presentando un approccio originale al problema. Benché poi questo problema non venga completamente risolto, otteniamo degli utili risultati parziali che possono essere sviluppati in futuro.
The Möbius function of locally finite partially ordered sets is a classical tool in enumerative combinatorics. It is a generalization of the number-theoretic Möbius function and it has several applications in group theory, from the Euler characteristic of subgroup complexes to algebraic aspects of cellular automata. In the first part of the thesis, we recall some basic notions about the order structures which are related to the Möbius function, and we present its main properties, such as the Möbius inversion formula and Crapo's theorems. Moreover, we investigate some relevant connections with group-theoretical topics to motivate our interest in the Möbius function of finite linear groups. In the second part, we work on these groups to obtain information about their Möbius function, and our original results are useful to compute it if we know the structure of some special subspace lattices related to subgroups. We study in detail the case of distributive subspace lattices. Then we show an example of a subgroup in the general linear group, such that the subspace lattice associated to the subgroup is non-distributive. In this way, we see that our arguments can also be applied to different situations, under certain conditions. In the last part of the thesis, we connect the previously obtained results to an open question about finitely generated profinite groups and finite almost-simple groups, introducing an original approach to the problem. Although we do not completely answer to this last question, we get some useful partial results.