Kinetics of Circulating Plasma Cell-Free DNA in Paediatric Classical Hodgkin Lymphoma

Levels of plasma cell-free DNA (cfDNA) of a large series of children with classical Hodgkin lymphoma (cHL) were evaluated and analyzed at diagnosis and during chemotherapy treatment in relation with clinical characteristics. CfDNA levels in cHL patients were significantly higher compared with controls (p=0.002). CfDNA at diagnosis was correlated with presence of B symptoms (p=0.027) and high erythrocyte sedimentation rate (p=0.049). We found that the increasing of plasma cfDNA after first chemotherapy cycle seems to be associated with a worse prognosis (p=0.049). Levels of plasma cfDNA might constitute an interesting non-invasive tool in cHL patients' management

Undoing the EU Security Architecture: Human Rights Violations in Poland (2015-2021)

openLe elezioni presidenziali e parlamentari che si tennero in Polonia nel 2015 videro la vittoria del partito di estrema destra Diritto e Giustizia. Da allora il partito ha portato avanti delle riforme volte a minare l’indipendenza del sistema giudiziario polacco, in particolare della Corte Costituzionale, della Corte Suprema e del Consiglio Nazionale della Magistratura. In seguito, queste istituzioni, ormai assoggettate al partito, hanno favorito l’adozione di leggi volte alla limitazione dei diritti delle donne, della comunità LGBTIQ+, nonché delle libertà di espressione, assemblea ed associazione delle organizzazioni attive nella protezione dei diritti umani; inoltre, le autorità pubbliche polacche sono da ritenersi responsabili, insieme a quelle bielorusse, per le violazioni dei diritti dei richiedenti asilo lungo il confine con la Bielorussia. Essendo la Polonia uno Stato membro dell’Unione Europea, è naturale chiedersi se questi eventi abbiano avuto e stiano avendo tuttora delle conseguenze a livello comunitario; infatti, l’UE ha vincolato il suo processo di integrazione e la sua legittimità al rispetto dei valori fondamentali sanciti nell’Articolo 2 del Trattato sull’Unione Europea, valori che le istituzioni polacche hanno mostrato di non riconoscere. Lo scopo di questo progetto è quello di determinare se le violazioni avvenute in Polonia in merito allo Stato di diritto e ai diritti fondamentali abbiano delle conseguenze sulla sicurezza dell’Unione. Per poter condurre questa ricerca, verrà in primo luogo fornito un quadro teorico volto a delineare l’approccio adottato dall’UE in termini di sicurezza ed a determinare l’importanza rivestita dai diritti fondamentali all’interno di quest’ultimo; successivamente verrà analizzato come il mancato rispetto dello Stato di diritto dei diritti fondamentali in Polonia, nonché la strategia adottata dall’Unione nei confronti di quest’ultima, abbiano avuto delle ripercussioni sulla sicurezza dell’UE; infine, verranno presi in esame dei “case-study” al fine di indagare gli effetti dell’approccio intrapreso dalla classe politica polacca nei riguardi dei valori fondamentali dell’UE sul funzionamento delle istituzioni dell'Unione Europea.In 2015 Polish presidential and parliamentary elections ended up with the victory of the right-wing party Law and Justice. Since then, the conservative party has put forward measures to undermine the independence of the Polish judicial system: main courts such as the Constitutional Tribunal, the Supreme Court and the National Council of the Judiciary were captured by the party. What is more, the captured institutions, in particular the Constitutional Tribunal, were used to adopt legal acts curtailing the rights of LGBTIQ+ people and also women access to sexual and reproductive health; additionally, human rights organizations, as well as media, were deprived of their freedom of expression, assembly and association; moreover, refugees that attempted to enter the Polish territory by crossing the Polish-Belarusian border were also subjected to severe human rights violations. Being Poland a EU member state the question arises on whether these violations result in negatively affecting the EU. Indeed, he European Union has bound its legitimacy and action, both within and beyond its borders, to the respect of core values that encompass the respect for the rule of law and human rights, as laid down in Article 2, Article 3 and Article 21 of the Consolidated Version of the Treaty on the European Union; moreover, observance, protection and promotion of these fundamental values are enshrined within the narrative adopted by the EU in approaching its security. The purpose of this research is indeed to determine whether violations that took place in Poland in regards to the rule of law and fundamental rights have consequences for EU security. To achieve this aim firstly a theoretical framework will be provided, which will investigate EU approach to security as connected to fundamental rights; secondly, EU core values’ violations within Polish jurisdiction and EU reaction to the latter will be analyzed in regards to their outcomes for the security of the EU; to conclude, two case studies related to the impact of Polish inconsistencies with EU core values on the functioning of EU institutions and their mechanisms will be provided

Non-Hodgkin Lymphoma in Children and Adolescents: Progress Through Effective Collaboration, Current Knowledge, and Challenges Ahead

Non-Hodgkin lymphoma is the fourth most common malignancy in children, has an even higher incidence in adolescents, and is primarily represented by only a few histologic subtypes. Dramatic progress has been achieved, with survival rates exceeding 80%, in large part because of a better understanding of the biology of the different subtypes and national and international collaborations. Most patients with Burkitt lymphoma and diffuse large B-cell lymphoma are cured with short intensive pulse chemotherapy containing cyclophosphamide, cytarabine, and high-dose methotrexate. The benefit of the addition of rituximab has not been established except in the case of primary mediastinal B-cell lymphoma. Lymphoblastic lymphoma is treated with intensive, semi-continuous, longer leukemia-derived protocols. Relapses in B-cell and lymphoblastic lymphomas are rare and infrequently curable, even with intensive approaches. Event-free survival rates of approximately 75% have been achieved in anaplastic large-cell lymphomas with various regimens that generally include a short intensive B-like regimen. Immunity seems to play an important role in prognosis and needs further exploration to determine its therapeutic application. ALK inhibitor therapeutic approaches are currently under investigation. For all pediatric lymphomas, the intensity of induction/consolidation therapy correlates with acute toxicities, but because of low cumulative doses of anthracyclines and alkylating agents, minimal or no long-term toxicity is expected. Challenges that remain include defining the value of prognostic factors, such as early response on positron emission tomography/computed tomography and minimal disseminated and residual disease, using new biologic technologies to improve risk stratification, and developing innovative therapies, both in the first-line setting and for relapse

Crizotinib in Advanced, Chemoresistant Anaplastic Lymphoma Kinase-Positive Lymphoma Patients

Anaplastic lymphoma kinase (ALK)-positive lymphomas respond to chemotherapy, but relapses, which bear a poor prognosis, occur. Crizotinib inhibits ALK in vitro and in vivo and was administered as monotherapy to 11 ALK+ lymphoma patients who were resistant/refractory to cytotoxic therapy. The overall response rate was 10 of 11 (90.9%; 95% confidence interval [CI] = 58.7% to 99.8%). Disease status at the latest follow-up is as follows: four patients are in complete response (CR) (months >21, >30, >35, >40) under continuous crizotinib administration; 4 patients had progression of disease (months 1, 2, 2, 2); 1 patient obtained CR on crizotinib, received an allogeneic bone marrow transplant, and is in CR; 2 patients (treated before and/or after allogeneic bone marrow transplant) obtained and are still in CR but they have stopped crizotinib. Overall and progression-free survival rates at 2 years are 72.7% (95% CI = 39.1% to 94.0%) and 63.7% (95% CI = 30.8% to 89.1%), respectively. ALK mutations conferring resistance to crizotinib in vitro could be identified in relapsed patients. Crizotinib exerted a potent antitumor activity with durable responses in advanced, heavily pretreated ALK+ lymphoma patients, with a benign safety profil

Anaplastic large cell lymphoma in paediatric and young adult patients.

Anaplastic large cell lymphoma (ALCL) is a heterogeneous disease of debateable origin that, in children, is largely anaplastic lymphoma kinase (ALK) positive with aberrant ALK activity induced following the formation of chromosomal translocations. Whilst the survival rates for this disease are relatively high, a significant proportion (20-40%) of patients suffer disease relapse, in some cases on multiple occasions and therefore suffer the toxic side-effects of combination chemotherapy. Traditionally, patients are treated with a combination of agents although recent data from relapse patients have suggested that low risk patients might benefit from single agent vinblastine and, going forward, the addition of ALK inhibitors to the therapeutic regimen may have beneficial consequences. There are also a plethora of other drugs that might be advantageous to patients with ALCL and many of these have been identified through laboratory research although the decision as to which drugs to implement in trials will not be trivial.Supported in part by the Pediatric Cancer Research Foundation and Fondazione Giacomo Ascoli. S.D.T. is supported with funding from BloodwiseThis is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1111/bjh.1395

Pesquisa e teoria da agência comportamental: uma revisão e agenda de pesquisa

The behavioral agency theory verifies the relationship between company executives, CEOs, and managers, and their decision-making within the firm. The mechanisms of governance and the forms of remuneration are instruments that monitor internal members avoiding risks that potentially harm the organization’s valuation. This article highlights the importance of the behavioral agency theory both for firms that trust their decision-making process to an agent and for the behavior of this agent. Both aspects are subject to concerns that usually lead to recommendations to establish or improve the executives’ compensation plans. Through bibliometric research analyzing 107 articles, it was possible to verify that executives’ performance compensation, according to agency theory, is the most used mechanism to stimulate executives to make decisions toward the company’s growth and best performance. This study’s theoretical and empirical contribution point to the need for future research on this topic since understanding the agent’s behavior is strategic for companies to help the agent to act on its benefit while reducing the possibilities of inadequate and harmful behavior.La teoría de la agencia comportamental verifica la relación entre los ejecutivos de la empresa, los directores ejecutivos y los gerentes, y su toma de decisiones dentro de la empresa. Los mecanismos de gobierno y las formas de remuneración se convierten en monitores de los miembros internos con respecto a la experiencia de la junta directiva para evitar la subvaloración. Este artículo destaca la importancia de la teoría de la agencia de comportamiento tanto para las empresas que confían su proceso de toma de decisiones a un agente como para el comportamiento de este agente. Ambos aspectos están sujetos a preocupaciones que generalmente llevan a recomendaciones para establecer o mejorar los planes de remuneración de los ejecutivos. A través de una investigación bibliométrica que analiza 107 artículos, fue posible verificar que la remuneración de desempeño de los ejecutivos, según la teoría de la agencia, es el mecanismo más utilizado para estimular a los ejecutivos a tomar decisiones sobre el crecimiento y el mejor desempeño de la compañía. La contribución teórica y empírica de este estudio apunta a la necesidad de futuras investigaciones sobre este tema, ya que entender el comportamiento del agente es estratégico para que las empresas ayuden al agente a actuar en su beneficio, al tiempo que reducen las posibilidades de comportamiento inadecuado y perjudicial.A teoria da agência comportamental verifica a relação entre os executivos, CEOs e gerentes da empresa e suas decisões dentro da empresa. Os mecanismos de governança e as formas de remuneração passam a ser monitores dos membros internos quanto à experiência do conselho de administração para evitar desvalorizações. Este artigo destaca a importância da teoria da agência comportamental tanto para empresas que confiam em seu processo de tomada de decisão a um agente quanto para o comportamento desse agente. Ambos os aspectos estão sujeitos a preocupações que geralmente levam a recomendações para estabelecer ou melhorar os planos de remuneração dos executivos. Por meio de uma pesquisa bibliométrica que analisou 107 artigos, foi possível verificar que a remuneração por desempenho dos executivos, segundo a teoria da agência, é o mecanismo mais utilizado para estimular os executivos a tomar decisões sobre o crescimento e o melhor desempenho da empresa. A contribuição teórica e empírica deste estudo aponta para a necessidade de pesquisas futuras sobre esse tema, uma vez que a compreensão do comportamento do agente é estratégica para que as empresas ajudem o agente a atuar em benefício dela enquanto reduzem as possibilidades de comportamentos inadequados e prejudiciais

Aplicação de machine learning na gestão de riscos da supply chain de uma empresa de alta tecnologia

Orientador: Prof. Luiz Eduardo Soares de OliveiraMonografia (especialização) - Universidade Federal do Paraná, Setor de Ciências Exatas, Curso de Especialização em Data Science & Big DataInclui referênciasResumo: A gestão das cadeias de suprimento global dentro do escopo de manufatura tem se tornado cada vez mais complexa e vunerável a paradas de entregas. Em tal ambiente, empresas devem mapear riscos em suas cadeias de suprimento para que possam agir a tempo de impedir ou remediar essas interrupções. Essa vulnerabilidade aumentou o interesse na Gestão de Riscos de Cadeias de Suprimento (GRCS) nos ambientes corporativo e acadêmico. A GRCS visa entender as causas das interrupções, monitorá-las e tratá-las quando necessário. A ferramenta de Aprendizagem de Máquina (AM) está se apresentando como um ótimo meio de facilitar as interações com os novos dados das cadeias de suprimento. Esse artigo documenta a aplicação de Aprendizagem de Máquina em conujnto com a biblioteca SHAP do Python como uma ferramenta de suporte para diversas etapas do GRCS dentro de uma empresa de manufatura de alta tecnologia. Essa aplicação irá focar em prever atrasos de entregas e desenvolver informação dos riscos relacionadosAbstract: Supply Chain Management in global manufacturing has become more complex and vulnerable to interruptions. In such environment, companies must be able to identify related risks before it is too late to address or mitigate these interruptions. Because of such vunerability, the interest in Supply Chain Risk Management (SCRM) has increased both in the academic and cooperative scenes. SCRM seeks to understand, track and treat the cause of interruptions. Machine Learning has been presented as a great tool to facilitate interactions with the new data in supply chains. This article documents the implementation of ML in junction with SHAP python library as a tool to support various steps in SCRM inside a high techonology manufacturing company. This implementation will predict delivery delays and develop information about the various risks related to these delay