Constrained Reinforcement Learning for Adaptive Controller Synchronization in Distributed SDN

In software-defined networking (SDN), the implementation of distributed SDN controllers, with each controller responsible for managing a specific sub-network or domain, plays a critical role in achieving a balance between centralized control, scalability, reliability, and network efficiency. These controllers must be synchronized to maintain a logically centralized view of the entire network. While there are various approaches for synchronizing distributed SDN controllers, most tend to prioritize goals such as optimization of communication latency or load balancing, often neglecting to address both the aspects simultaneously. This limitation becomes particularly significant when considering applications like Augmented and Virtual Reality (AR/VR), which demand constrained network latencies and substantial computational resources. Additionally, many existing studies in this field predominantly rely on value-based reinforcement learning (RL) methods, overlooking the potential advantages offered by state-of-the-art policy-based RL algorithms. To bridge this gap, our work focuses on examining deep reinforcement learning (DRL) techniques, encompassing both value-based and policy-based methods, to guarantee an upper latency threshold for AR/VR task offloading within SDN environments, while selecting the most cost-effective servers for AR/VR task offloading. Our evaluation results indicate that while value-based methods excel in optimizing individual network metrics such as latency or load balancing, policy-based approaches exhibit greater robustness in adapting to sudden network changes or reconfiguration

Direct Effects of Bundled Payments for Care Improvement Initiative: A County-Level Approach

Implementing a nonlinear, Difference-in-Differences estimation method, I quantify the positive impact bundled payment reforms have on vulnerable population groups living in U.S. counties where this cost reducing initiative was implemented. I find statistically significant effects of this health-care initiative on the elderly and the economically disadvantaged individuals

Δίκαιο του Ελεύθερου Ανταγωνισμού και Ιδιωτική Ασφάλιση

Η παρούσα διατριβή αναλύει τους κανόνες του ενωσιακού δικαίου του ελεύθερου ανταγωνισμού στον τομέα της ιδιωτικής ασφάλισης. Στην Ευρωπαϊκή Ένωση ήδη από τις αρχές της δεκαετίας του 1990 ίσχυε Κανονισμός Ομαδικής Απαλλαγής, που εξαιρούσε ορισμένες κατηγορίες συμφωνιών μεταξύ ασφαλιστικών επιχειρήσεων από την εφαρμογή του άρθρου 101 ΣΛΕΕ. Το 2017 έληξε η ισχύς του ΚΟΑ, καθώς η Επιτροπή έκρινε ότι παρόλο που ορισμένες συμφωνίες μεταξύ των ασφαλιστικών επιχειρήσεων διασφαλίζουν την ορθή λειτουργία του ασφαλιστικού τομέα και προωθούν τα συμφέροντα των καταναλωτών, δεν είναι αναγκαία η ύπαρξη ενός τόσο εξαιρετικού εργαλείου (KOA). Κατά συνέπεια ο KOA δεν ανανεώθηκε. Μετά το εισαγωγικό κεφάλαιο η διατριβή χωρίζεται σε δύο μέρη. Στο πρώτο μέρος αναλύεται η εφαρμογή των ενωσιακών κανόνων ανταγωνισμού (άρθρα 101-102 ΣΛΕΕ, έλεγχος συγκεντρώσεων) στον ασφαλιστικό τομέα. Στο δεύτερο μέρος της παρούσας διατριβής εξετάζονται ορισμένα επιχειρήματα που θα μπορούσαν να ληφθούν υπόψη υπέρ του ασφαλιστικού τομέα κατά την αξιολόγηση υπό το άρθρο 101 ΣΛΕΕ. Επίσης, αναλύεται η εφαρμογή των γενικών διατάξεων στις κατηγορίες συμφωνιών που έως το έτος 2017 απολάμβαναν της ομαδικής απαλλαγής. Η διατριβή ολοκληρώνεται με ενότητα τελικών συμπερασμάτων.The present thesis analyses the EU competition rules in the private insurance sector. In the European Union, since the early 1990s, a Block Exemption Regulation had been in force, which exempted certain categories of agreements between insurance undertakings from the application of article 101 TFEU. In 2017 the BER expired, as the Commission decided that although certain agreements between insurance undertakings ensure the proper functioning of the insurance sector and promote the interests of the consumers, the existence of such an exceptional legal instrument (BER) is not necessary. As a result, the BER was not renewed. Following the introductory chapter the thesis in divided in two parts. In the first part, the application of EU competition rules (Articles 101-102 TFEU, merger control) in the insurance sector is analyzed. In the second part of the present thesis, we examine certain arguments which could be taken into account in favor of the insurance sector during the assessment under article 101 TFEU. The application of the general principles of competition law on the categories of agreements which until 2017 were block exempted is also analyzed. The thesis is concluded with a final conclusions section

Acute Promyelocytic Leukemia: an Experience on 95 Greek Patients Treated in the All-Trans-Retinoic Acid Era

Acute promyelocytic leukemia (APL) is highly curable with the combination of all-transretinoic acid (ATRA) and anthracycline based chemotherapy, but the percentage of early deaths remains high. In the present study, we report the clinical, immunophenotypic, cytogenetic and molecular characteristics and outcome of APL patients diagnosed and treated in various Hospitals of Greece and Cyprus

Effect of splenectomy on type-1/type-2 cytokine gene expression in a patient with adult idiopathic thrombocytopenic purpura (ITP)

BACKGROUND: In view of clinical observations and laboratory results that support a central role of the spleen in idiopathic thrombocytopenic purpura (ITP) pathophysiology, we studied the effect of splenectomy on type-1 and type-2 cytokine gene expression in an adult ITP case, refractory to conservative treatment. CASE PRESENTATION: The patient was subjected to splenectomy 9 months after the diagnosis with complete response, attaining platelet counts over 150 × 10(6)/L within 10 days after the operation. Two consecutive blood samples were obtained from the patient, 3 and 7 months after the splenectomy for the purposes of this study. A control group consisted of 11 healthy adults. Peripheral blood mononuclear cells were prepared from each blood sample and cultured in vitro for 8 h with the addition of the mitogens phorbol myristate acetate and ionomycin. Total cellular RNA extracted from 10(6 )cells was submitted to semiquantitave reverse transcriptase-polymerase chain reaction (RT-PCR) for the amplification of IL-2, IFN-γ, IL-4, IL-5, and IL-10 metagraphs. The PCR products were run on ethidium-stained agarose gels, photographed and quantified by densitometry. A steep decrease of type-1 cytokine expression (IL-2, IFN-γ) and their calculated sum expressing Th1 activity was observed at 7 months post-splenectomy compared to 3 months post-splenectomy, in parallel with a rise of platelet count from 190 × 10(6)/L to 265 × 10(6)/L. The change of type-2 cytokine expression (IL-4, IL-5, IL-10) was slight and the Th2 activity (IL-4+IL-5) remained largely unchanged. The Th1/Th2 ratio, that reflects the pathogenic disease-specific T-cell immune deviation, was accordingly reduced 7 months post-splenectomy (Th1/Th2 = 1.3) compared to 3 months (Th1/Th2 = 3.5). CONCLUSIONS: The reduction of the Th1/Th2 cytokine ratio that was observed over time after splenectomy was accompanied by full clinical remission. Nevertheless, the persistence of a type-1 polarization, even after several months following spleen removal, is suggestive of a more basic abnormality of the immune function in these patients

Identification of novel biomarkers in chronic immune thrombocytopenia (ITP) by microarray-based serum protein profiling

The pathological mechanisms underlying the development of immune thrombocytopenia (ITP) are unclear and its diagnosis remains a process of exclusion. Currently, there are no known specific biomarkers for ITP to support differential diagnosis and treatment decisions. Profiling of serum proteins may be valuable for identifying such biomarkers. Sera from 46 patients with primary chronic ITP and 34 healthy blood donors were analysed using a microarray of 755 antibodies. We identified 161 differentially expressed proteins. In addition to oncoproteins and tumour-suppressor proteins, including apoptosis regulator BCL2, breast cancer type 1 susceptibility protein (BRCA1), Fanconi anaemia complementation group C (FANCC) and vascular endothelial growth factor A (VEGFA), we detected six anti-nuclear autoantibodies in a subset of ITP patients: anti-PCNA, anti-SmD, anti-Ro/SSA60, anti-Ro/SSA52, anti-La/SSB and anti-RNPC antibodies. This finding may provide a rational explanation for the association of ITP with malignancies and other autoimmune diseases. While RUNX1mRNA expression in the peripheral blood mononuclear cells (PBMC) of patients was significantly downregulated, an accumulation of RUNX1 protein was observed in the platelets of ITP patients. This may indicate dysregulation of RUNX1 expression in PBMC and megakaryocytes and may lead to an imbalanced immune response and impaired thrombopoiesis. In conclusion, we provide novel insights into the pathogenic mechanisms of ITP that warrant further exploration

Infections in relapsed myeloma patients treated with isatuximab plus pomalidomide and dexamethasone during the COVID-19 pandemic: Initial results of a UK-wide real-world study

© 2022 The Authors. Published by Taylor & Francis. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1080/16078454.2022.2082725Objectives There are no real-world data describing infection morbidity in relapsed/refractory myeloma (RRMM) patients treated with anti-CD38 isatuximab in combination with pomalidomide and dexamethasone (IsaPomDex). In this UK-wide retrospective study, we set out to evaluate infections experienced by routine care patients who received this novel therapy across 24 cancer centres during the COVID-19 pandemic. Methods The primary endpoint was infection morbidity (incidence, grading, hospitalization) as well as infection-related deaths. Secondary outcomes were clinical predictors of increased incidence of any grade (G2–5) and high grade (≥G3) infections. Results In a total cohort of 107 patients who received a median (IQR) of 4 cycles (2–8), 23.4% of patients experienced ≥1 any grade (G2–5) infections (total of 31 episodes) and 18.7% of patients experienced ≥1 high grade (≥G3) infections (total of 22 episodes). Median time (IQR) from start of therapy to first episode was 29 days (16–75). Six patients experienced COVID-19 infection, of whom 5 were not vaccinated and 1 was fully vaccinated. The cumulative duration of infection-related hospitalizations was 159 days. The multivariate (MVA) Poisson Regression analysis demonstrated that a higher co-morbidity burden with Charlson Co-morbidity Index (CCI) score ≥4 (incidence rate ratio (IRR) = 3, p = 0.012) and sub-optimal myeloma response less than a partial response (<PR) (p = 0.048) are independent predictors of ≥ G3 infections. Conclusion Our study described initial results of infection burden during IsaPomDex treatment. We recommend close monitoring particularly in elderly patients with co-morbidities, the effective use of an-infective prophylaxis, as well as optimal vaccination strategies, to limit infections