1,721,363 research outputs found
Immunotherapy in Chronic Myeloid Leukemia
No full textImatinib has become standard therapy for all phases of chronic myeloid leukemia (CML). However, data generated by monitoring several thousands of patients worldwide suggest that although imatinib is highly active against the differentiated mass of CML cells, it probably fails to eradicate all residual leukemia cells, even in the best responders. This is supported by several lines of evidence: (i) despite the fact that more than 80% of previously untreated patients achieve a complete cytogenetic remission (CCgR), only a minority of patients remain durably negative when tested by real-time quantitative polymerase chain reaction (RT-PCR) for BCR-ABL transcripts (1); (ii) even patients treated with imatinib who achieve a complete molecular response (CMolR) usually return to Philadelphia (Ph)-positivity if the drug is stopped (2); and (iii) studies performed in vitro suggest that primitive Ph-positive progenitors or stem cells are relatively insensitive to imatinib (3) and the persistence of BCR-ABL-positive precursors in complete cytogenetic response (CCyR) patients, despite continued imatinib therapy, has been recently documented (4). At least theoretically, any amount of residual disease under imatinib treatment could provide the basis for the emergence of Ph-positive sub-clones bearing mutations in the BCR-ABL kinase domain, which are associated with various degrees of resistance to this agent (5). For all these reasons recent CML guidelines recommend that alternative strategies should be considered in early chronic phase (CP) patients with suboptimal response or failure to adequate imatinib (6). Less straightforward is the management of residual “molecular” disease found in a great majority of patients. At present, these patients usually continue to receive standard doses of imatinib, and their response is monitored by RT-PCR and cytogenetics. Although we do not yet know the impact on survival of such minimal residual disease (MRD) (7), it appears prudent to develop specific additional therapies that could complete the excellent work of imatinib. The ultimate and ambitious aim of a supplementary treatment would be the attainment of a “true cure” of CML (eradication of all leukemia cells) instead of an “operational cure” (persistence of minimal amount of leukemia cells), which may be achieved with imatinib alone. One such strategy is to exploit the fact that CML is a disease known to be susceptible to immune attack. The most striking proof of this is the fact that until now, a “cure” (defined as continuous negativity for BCR-ABL by PCR) for CML patients is probably achieved only by the graft-versus-leukemia (GvL) effect following allogeneic stem cell transplantation or donor lymphocytes infusion (8), although it remains formally unproven that undetectability of BCR-ABL is equivalent to eradication of the malignant clone. Although the GvL effect is to a great extent due to major and minor HLA mismatches between donors and recipients, some experimental data suggest that CML-specific donor T lymphocytes could be the key to long-term control or even eradication of residual leukemia cells (9). Additionally, the activity of interferon-α (IFN-α), a biological modifier widely used for CML in the pre-imatinib era, could be partly due to an immune-mediated effect, and a possible role of this agent in the context of MRD surviving imatinib will be discussed. CML offers a unique opportunity to test the efficacy and feasibility of immunotherapeutic strategies, as currently most patients achieve very pronounced responses furnishing an ideal situation for immunotherapy in a disease known to be responsive in principle to immune attack. Immunotherapy approaches currently under evaluation include active specific immunotherapies (vaccines) and nonspecific immunotherapies [IFN-α, interleukin-2 (IL-2), granulocyte-macrophage colony stimulating factor (GM-CSF), and other immunostimulators]
Is there any role left for p210-derived peptide vaccines in chronic myeloid leukemia?
No full textDespite the fact that the idea of educating the immune system against tumor-specific antigens by using an active immunotherapy such as a vaccine has been pursued by many researchers, consistent clinical data on the effectiveness of anticancer vaccines have not yet been produced. Lack of tumor specific targets, low immunogenicity of the tumorassociated antigens, inappropriate vaccine formulation and large tumor burdens of the vaccinated patients are some of the most frequent reasons accounting for the current disappointing results
with anticancer vaccines
I perchè del sindacato. Mario Romani e la «Scuola del Wisconsin»
No full textLa biografia intellettuale di Mario Romani si caratterizza per un originale incontro tra il rigore intellettuale e metodologico dello storico economico e un’apertura alle analisi comparate e interdisciplinari che egli considerava indispensabili per accostare la complessa realtà contemporanea del lavoro e delle organizzazioni dei lavoratori. Un’impostazione che gli ha consentito di maturare una concezione del ruolo del sindacato dei lavoratori in un assetto istituzionale democratico di economia mista integrando le elaborazioni teoriche di matrice statunitense alla luce di apporti culturali propriamente europei declinati sul caso italian
Power system planning methods and experiences in the energy transition framework
Full text linkIn recent years, the unbundling of the electricity market together with the profound “energy landscape” transformation have made the transmission network development planning a very complex multi-objective problem. The climate and energy objectives defined at the European level aim for a deepening integration of the European power markets and the electricity sector is recognized as one of the main contributors to the energy transition from a thermal-based power system to a renewable-based one.
In the deregulated framework, network planners have to satisfy multiple different objectives, including: facilitating competition between market participants, providing non-discriminatory access to all generation resources for all customers, including green resources, mitigating transmission congestions, efficiently allocating the network development actions, minimizing risks associated with investments, enhancing power system security and reliability and minimizing the transmission infrastructure environmental impact. Further complexities are related to the significant uncertainty about future energy scenarios and policy rules. In particular, the increasing distributed renewable energy source integration dictated by the European energy targets, raises several issues in terms of future power flow patterns, power system flexibility and inertia requirements, and cost-effective development strategies identification.
The thesis aims to investigate various aspects concerning the transmission network planning, with particular reference to the Italian power system and the experience gained working in the “Grid Planning and Interconnections Department” of Terna, the Italian Transmission System Operator.
One of the main topics of this work is the use of the series compensation to exploit operating limits of underused portions of the HV – EHV transmission network in parallel to critically loaded ones, in order to control and provide alternative paths for power flows. The purpose is to extend the allowable transmission capacity across internal market sections. To this aim, a specific application of series compensation (together with reconductoring) to exploit the transfer capacity of a 250 km long, 230 kV-50 Hz transmission backbone spanning the critical section Centre South – Centre North is illustrated. The results are validated by means of static assessment and similar applications could be hypothesized for grid portions in the South of Italy where the primary network is mainly unloaded whereas the sub-transmission network reaches high levels of loading because of the huge renewable generation capacity situated there.
A further characteristic of modern power systems is the need to integrate high levels of renewable energies while fulfilling reliability and security requirements. The offshore wind farms perspectives in the Italian transmission system are evaluated, considering policies, environmental and technical aspects. Furthermore, the adoption of the HVDC technology in parallel to the AC traditional system topic is addressed: planning static and dynamic studies involving a real HVDC Italian project are proposed. In particular, the impact of the planned HVDC link on the loadability and the dynamic performance of the system is investigated in medium and in long-term future planning scenarios.
The evaluation of the thermal performance of a specific grid portion in the South of Italy affected by significant increase of power generation by variable energy sources is proposed both in the current situation and in the future scenarios in order to highlight the benefits related to the presence of the planned network reinforcements. Finally, some issues of the prospective reduced inertia systems are illustrated and a possible methodology to evaluate the economic impact of inertia constraints in long-term market studies is proposed.
In the light of the emerging concept of power system flexibility, traditional planning evolved to assess the ability of the system to employ its resources when dealing with the changes in load demand and variable generation. Flexibility analyses of the Italian power system, carried out in terms of some market studies-based metrics and grid infrastructure-based indexes, are provided. The flexibility requirements assessment in planning scenarios are of interest to evaluate the impact of network development actions and have been included in the yearly National Development Plan.
The last research topic involves the cost-effective target capacity assessment methodology developed by Terna in compliance with the Regulator directives presented together with the results yielded by its application to each significant market section of the Italian power system. The methodology has been positively evaluated from academic independent expert reviewers, and its outputs are relevant for the policy makers, regulatory authority and market participant to assess and co-design the energy transition plan of a future European interconnected power system
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Towards the pharmacotherapy of hairy cell leukaemia
No full textHairy cell leukaemia (HCL) offers one of the few examples of rapid progress in the development of effective treatments for chronic lymphoproliferative disorders. After the first description of HCL as a separate disease in 1958, splenectomy was the treatment of choice, but rarely resulted in remission of disease and had scarce benefit on survival. In 1984, IFN-alpha became the first agent able to significantly modify the prognosis of HCL by inducing high response rates and long-term remissions. More recently, purine analogues have significantly further increased the percentages of remissions, with a reduced risk of relapse and are now generally used as first-line treatment. Monoclonal antibodies targeting CD20, CD22 and CD25 antigens, have also shown responses for resistant or relapsing disease. This article will review the current treatment strategies for HCL
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