Hypomethylating Agents in Treatment of Myelodysplastic Syndrome

Thelkey to the successful treatment of myelodysplastic syndrome is the careful characterization and diagnosis of the disease, which includes clinical, cytogenetic, biological and molecular investigation of individual patients. Today therapeutic approaches to the treatment of such patients are differentiated and depend, first of all, on the subtype of the disease, age, general condition of the patients and the possibility of allogeneic hematopoietic cell transplantation. For young patients, the best option is transplantation, whereas in older patients, the standard of therapy is the use of hypomethylating agents (azacitidine, decitabine). These drugs promote hematologic improvement, elimination of transfusion dependence and prolongation of the duration of both general and leukemia free survival in elderly patients with concomitant pathology.Despite the fact that therapy with hypomethylating drugs is widely used and has good results, many respondents are losing their response within 1–2 years. Reasons for the development of resistance to this type of treatment are still unclear, and the insensitivity to drugs is associated with very poor prognosis in patients with all subtypes of myelodysplastic syndrome. Such data and the presence of numerous genetic and epigenetic mechanisms for the development of this pathology have prompted the use of combinations of drugs with different application points and are relevant in terms of research. In the literature review, the results of clinical studies on the use of hypomethylating agents in patients with MDS of low and high risk, as in monotherapy and combined schemes are presented.The nearest prospect of treatment of myelodysplastic syndrome is the creation of new treatment regimens based on a combination of drugs of different pathogenetic direction for the elimination of the dysplastic clone in order to achieve not only long-term remissions, but also lengthening the duration of overall survival, especially for patients with high risk myelodysplastic syndrome

ALFRED-DONAT AGACHE URBAN PROPOSAL FOR COSTA DO SOL. FROM THE TERRITORY TO THE CITY.

This paper reviews the development of Costa do Sol, as planned by architect urbanist Alfred-Donat Agache, for Lisbon Region in Portugal. The Plano Expansão Região Oeste de Lisboa (1934-1936) prepared by Agache and requested by Portuguese Minister of Public Works, Duarte Pacheco will be analyzed. This paper aims also to identify the principles and the theoretical foundations that have determined Agache urban vision for Lisbon City and its Territory. Finally, this paper aims to demonstrate that Alfred-Donat Agache methodological framework has applied Frederick Le Play socio-economic scientific approach. Such approach has informed the construction of a ‘civic’ urbanism that will be identified and analyzed. Two main goals seem to have guided Agache work at Costa do Sol: (i) the fully urban analysis of the city, throughout its social, economic, geographic and urban conditions (past and present) and (ii) the need to expose such analysis to the city’s inhabitants. Finally, this paper demonstrates Costa do Sol proposal to testify a comprehensive understanding of three distinct scales: (i) the territory; (ii) the city; (iii) but also the urban form. The acknowledgment of Agache ‘civic’ urban vision requests a public divulgation to allow the building of Good Practice Lessons for contemporary urban planning theory and practice

Bill of lading from Smith & Lamar, Agents

Bill of lading from Smith & Lamar, Agents, to Emma P. Larimore. The bill of lading appears to be for transportation of books. The one-page form is dated 12 December 1912

Software Agents

being used, and touted, for applications as diverse as personalised information management, electronic commerce, interface design, computer games, and management of complex commercial and industrial processes. Despite this proliferation, there is, as yet, no commonly agreed upon definition of exactly what an agent is — Smith et al. (1994) define it as “a persistent software entity dedicated to a specific purpose”; Selker (1994) takes agents to be “computer programs that simulate a human relationship by doing something that another person could do for you”; and Janca (1995) defines an agent as “a software entity to which tasks can be delegated”. To capture this variety, a relatively loose notion of an agent as a self-contained program capable of controlling its own decision making and acting, based on its perception of its environment, in pursuit of one or more objectives will be used here. Within the extant applications, three distinct classes of agent can be identified. At the simplest level, there are “gopher ” agents, which execute straightforward tasks based on pre-specified rules and assumptions (eg inform me when the share price deviates by 10 % from its mean position or tell me when I need to reorder stock items). The next level of sophistication involves “service performing” agents, which execute a well defined task at the request of a user (eg find me the cheapest flight to Paris or arrange a meeting with the managing director some day next week). Finally, there are “predictive ” agents, which volunteer information or services to a user, without being explicitly asked, whenever it is deemed appropriate (eg an agent may monitor newsgroups on the INTERNET and return discussions that it believes to be of interest to the user or a holiday agent may inform its user that a travel firm is offering large discounts on holidays to South Africa knowing that the user is interested in safaris). Common to all these classes are the following key hallmarks of agenthoo

Programmable Agents

We build deep RL agents that execute declarative programs expressed in formal language. The agents learn to ground the terms in this language in their environment, and can generalize their behavior at test time to execute new programs that refer to objects that were not referenced during training. The agents develop disentangled interpretable representations that allow them to generalize to a wide variety of zero-shot semantic tasks

Disloyal Agents

This paper examines the consequences of an agent\u27s breach of the fiduciary duty of loyalty. These consequences are underexplored in academic literature, in contrast to rationales for fiduciary duties more generally. The consequences of an agent\u27s disloyalty are, moreover, not uniform across jurisdictions. The paper begins by differentiating between the meaning and consequences that the law ascribes to agency and its meaning in other academic disciplines, including economics and philosophy. It then considers the extent to which principles derived from contract and tort law can account for the consequences that courts assign to agents\u27 disloyal conduct and concludes that a more complex doctrinal and normative vocabulary is required. The paper focuses more specifically on remedies available to a principal when an agent acts disloyally, then turns to an agent\u27s duty to disclose prior misconduct to the principal and then to the impact of disloyalty on contractual provisions and to the consequence for organizations that carry out agency functions when employees of the organization indulge in self-interested fiduciary transgressions. These specific topics are addressed (often with divergent outcomes) by recent or well-known cases and provide good vehicles for analysis of the implications and limitations of more general questions about the nature and function of the fiduciary of loyalty. In general, the remedies available to a principal when an agent is disloyal are varied, distinctive, and in some respects ferocious, all qualities the paper argues are helpful in understanding the theoretical and functional position of fiduciary duties of loyalty

Asimovian Adaptive Agents

The goal of this research is to develop agents that are adaptive and predictable and timely. At first blush, these three requirements seem contradictory. For example, adaptation risks introducing undesirable side effects, thereby making agents' behavior less predictable. Furthermore, although formal verification can assist in ensuring behavioral predictability, it is known to be time-consuming. Our solution to the challenge of satisfying all three requirements is the following. Agents have finite-state automaton plans, which are adapted online via evolutionary learning (perturbation) operators. To ensure that critical behavioral constraints are always satisfied, agents' plans are first formally verified. They are then reverified after every adaptation. If reverification concludes that constraints are violated, the plans are repaired. The main objective of this paper is to improve the efficiency of reverification after learning, so that agents have a sufficiently rapid response time. We present two solutions: positive results that certain learning operators are a priori guaranteed to preserve useful classes of behavioral assurance constraints (which implies that no reverification is needed for these operators), and efficient incremental reverification algorithms for those learning operators that have negative a priori results

Agents of Hope

This paper considers the Christian teacher’s “place” in today’s increasingly diverse public school classrooms. Specifically, the paper explores the complexities of working as a Christian within educational systems which promote tolerance of all cultures and religious views. Is it possible for a Christian teacher to remain committed to The Way while employed in a system which encourages pluralism, equity, and diversity? Using insights and responses of participants in a Christian university education course on teaching in multicultural classrooms, a framework is provided to consider what it means to teach as a Christian in multicultural school settings