Successful Pregnancy and Delivery in a Patient with Chronic Myeloid Leukemia while on Dasatinib Therapy

Here we report the case of an 18-year-old woman with chronic myeloid leukemia (CML) who became pregnant while undergoing treatment with dasatinib. Before pregnancy, she received imatinib mesylate therapy but could not tolerate the treatment. The regimen was then changed to dasatinib at a dose of 70 mg b.i.d. While she was in hematological remission and on dasatinib therapy, she became pregnant. The unplanned pregnancy was identified after the patient had experienced four weeks of amenorrhea. Because the patient elected to continue the pregnancy to term, dasatinib was stopped immediately. Meanwhile, CML hematological relapse occurred and then she was treated with interferon-α (IFN-α) (9 million IU/day) throughout the pregnancy without a complete hematological response. She successfully gave birth to a male baby at 33 weeks by cesarean section delivery with no sequelae or malformations. Although this experience is limited to a single patient, it provides a useful contribution for counselling patients inadvertently exposed to dasatinib during pregnancy

Automated Reasoning and Presentation Support for Formalizing Mathematics in Mizar

This paper presents a combination of several automated reasoning and proof presentation tools with the Mizar system for formalization of mathematics. The combination forms an online service called MizAR, similar to the SystemOnTPTP service for first-order automated reasoning. The main differences to SystemOnTPTP are the use of the Mizar language that is oriented towards human mathematicians (rather than the pure first-order logic used in SystemOnTPTP), and setting the service in the context of the large Mizar Mathematical Library of previous theorems,definitions, and proofs (rather than the isolated problems that are solved in SystemOnTPTP). These differences poses new challenges and new opportunities for automated reasoning and for proof presentation tools. This paper describes the overall structure of MizAR, and presents the automated reasoning systems and proof presentation tools that are combined to make MizAR a useful mathematical service.Comment: To appear in 10th International Conference on. Artificial Intelligence and Symbolic Computation AISC 201

Applying SMT Solvers to the Test Template Framework

The Test Template Framework (TTF) is a model-based testing method for the Z notation. In the TTF, test cases are generated from test specifications, which are predicates written in Z. In turn, the Z notation is based on first-order logic with equality and Zermelo-Fraenkel set theory. In this way, a test case is a witness satisfying a formula in that theory. Satisfiability Modulo Theory (SMT) solvers are software tools that decide the satisfiability of arbitrary formulas in a large number of built-in logical theories and their combination. In this paper, we present the first results of applying two SMT solvers, Yices and CVC3, as the engines to find test cases from TTF's test specifications. In doing so, shallow embeddings of a significant portion of the Z notation into the input languages of Yices and CVC3 are provided, given that they do not directly support Zermelo-Fraenkel set theory as defined in Z. Finally, the results of applying these embeddings to a number of test specifications of eight cases studies are analysed.Comment: In Proceedings MBT 2012, arXiv:1202.582

New results on rewrite-based satisfiability procedures

Program analysis and verification require decision procedures to reason on theories of data structures. Many problems can be reduced to the satisfiability of sets of ground literals in theory T. If a sound and complete inference system for first-order logic is guaranteed to terminate on T-satisfiability problems, any theorem-proving strategy with that system and a fair search plan is a T-satisfiability procedure. We prove termination of a rewrite-based first-order engine on the theories of records, integer offsets, integer offsets modulo and lists. We give a modularity theorem stating sufficient conditions for termination on a combinations of theories, given termination on each. The above theories, as well as others, satisfy these conditions. We introduce several sets of benchmarks on these theories and their combinations, including both parametric synthetic benchmarks to test scalability, and real-world problems to test performances on huge sets of literals. We compare the rewrite-based theorem prover E with the validity checkers CVC and CVC Lite. Contrary to the folklore that a general-purpose prover cannot compete with reasoners with built-in theories, the experiments are overall favorable to the theorem prover, showing that not only the rewriting approach is elegant and conceptually simple, but has important practical implications.Comment: To appear in the ACM Transactions on Computational Logic, 49 page

Two successful pregnancies in a woman with chronic myeloid leukemia exposed to nilotinib during the first trimester of her second pregnancy: case study

The occurrence of chronic myeloid leukemia in pregnancy is rare and its management poses a clinical challenge for physicians treating these patients. We report a 30-year-old woman with chronic myeloid leukemia who became pregnant twice successfully. Philadelphia-positive CML in its chronic phase was diagnosed at 16 weeks of her first gestation. At that time, she received no treatment throughout her pregnancy. At 38 weeks of gestation, a normal infant was delivered by cesarean section. At six weeks postpartum, the patient underwent imatinib mesylate therapy but she could not tolerate the treatment. The treatment was then changed to nilotinib at 400 mg orally b.i.d. Two years later, she became pregnant again while she was on nilotinib 200 mg b.i.d. The unplanned pregnancy was identified during her 7.4 weeks of gestation. Because the patient elected to continue her pregnancy, nilotinib was stopped immediately, and no further treatment was given until delivery. Neither obstetrical complications nor structural malformations in neonates in both pregnancies were observed. Both babies' growth and development have been normal. Although this experience is limited to a single patient, the success of this patient demonstrates that the management of chronic myeloid leukemia in pregnant women may be individualized based on the relative risks and benefits of the patient and fetus

Building Better Bit-Blasting for Floating-Point Problems

An effective approach to handling the theory of floating-point is to reduce it to the theory of bit-vectors. Implementing the required encodings is complex, error prone and requires a deep understanding of floating-point hardware. This paper presents SymFPU, a library of encodings that can be included in solvers. It also includes a verification argument for its correctness, and experimental results showing that its use in CVC4 out-performs all previous tools. As well as a significantly improved performance and correctness, it is hoped this will give a simple route to add support for the theory of floating-point

Perioperative thirst: an analysis from the perspective of the Symptom Management Theory

A theoretical study aimed to analyze the existing knowledge in the literature on the perioperative thirst symptom from the perspective of Symptom Management Theory, and supplemented with the experience of the study group and thirst research. Thirst is described as a very intense symptom occurring in the perioperative period, and for this reason it cannot be ignored. The Symptom Management Theory is adequate for understanding the thirst symptom and is a deductive theory, focused on the domains of the Person, Environment and Health / Illness Status, as well as on the dimensions of Experience, Management Strategies and Symptom Outcomes. Using the theory leads us to consider perioperative thirst in its multifactorial aspects, analyzing the interrelation of its domains and dimensions in order to draw attention to this symptom that has been insufficiently valued, recorded and treated in clinical practice

Quaternary glacial history of the Mediterranean mountains

Glacial and periglacial landforms are widespread in the mountains of the Mediterranean region. The evidence for glacial and periglacial activity has been studied for over 120 years and it is possible to identify three phases of development in this area of research. First, a pioneer phase characterized by initial descriptive observations of glacial landforms; second, a mapping phase whereby the detailed distribution of glacial landforms and sediments have been depicted on geomorphological maps; and, third, an advanced phase characterized by detailed understanding of the geochronology of glacial sequences using radiometric dating alongside detailed sedimentological and stratigraphical analyses. It is only relatively recently that studies of glaciated mountain terrains in the Mediterranean region have reached an advanced phase and it is now clear from radiometric dating programmes that the Mediterranean mountains have been glaciated during multiple glacial cycles. The most extensive phases of glaciation appear to have occurred during the Middle Pleistocene. This represents a major shift from earlier work whereby many glacial sequences were assumed to have formed during the last cold stage. Glacial and periglacial deposits from multiple Quaternary cold stages constitute a valuable palaeoclimatic record. This is especially so in the Mediterranean mountains, since mountain glaciers in this latitudinal zone would have been particularly sensitive to changes in the global climate system. © 2006 Edward Arnold (Publishers) Ltd