No abstract

Lonafarnib is an orally bio-available farnesyltransferase inhibitor that prevents farnesylation of specific target proteins including Ras. In a multicenter study, 67 patients with advanced myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) were treated with a continuous oral dose of 200-300 mg of lonafarnib and were evaluated for hematologic, pathologic and pharmacodynamic response. The median age of patients was 70 years (range 44-86). There were 32 patients with MDS (RAEB-20 and RAEB-t-12) and 35 with CMML. Overall 16 (24%) of the patients responded with two patients achieving a complete remission and one a partial response. Responses were seen in 6/32 and 10/35 patients with MDS and CMML, respectively. Of the 19 patients who were platelet transfusiondependent prior to treatment, 5 (26%) became transfusion-free for a median duration of 185 days. A decrease in the farnesylation of the HDJ-2 protein measured in patient-derived cells was observed in the majority of patients during treatment with lonafarnib, but no clear correlation between changes in farnesylation and clinical effect could be made. Gastrointestinal toxicity was significant with 19% of patients discontinuing therapy due to diarrhea, nausea and/or anorexia. Lonafarnib has demonstrable activity in patients with advanced MDS and CMML.

Models of speech production typically assume that control over the timing of speech movements is governed by the selection of higher-level linguistic units, such as segments or syllables. This study used real-time magnetic resonance imaging of the vocal tract to investigate the anticipatory movements speakers make prior to producing a vocal response. Two factors were varied: preparation (whether or not speakers had foreknowledge of the target response) and pre-response constraint (whether or not speakers were required to maintain a specific vocal tract posture prior to the response). In prepared responses, many speakers were observed to produce pre-response anticipatory movements with a variety of articulators, showing that that speech movements can be readily dissociated from higher-level linguistic units. Substantial variation was observed across speakers with regard to the articulators used for anticipatory posturing and the contexts in which anticipatory movements occurred. The findings of this study have important consequences for models of speech production and for our understanding of the normal range of variation in anticipatory speech behaviors.

To evaluate the efficacy and tolerability of a high-dose mitoxanuniquely steep dose-response curve in clonogenic assays with trone-based induction regimen without consolidation therapy ovarian cancer and leukemic cells. 8,9 In a preliminary study had, for the most part, concluded that tolerance to dose-intenoccurred in 11 patients, three in the high-dose and eight in the sive induction therapy was poor in elderly patients, 11,12 our low-dose arm. Actuarial median survival was 6 months for the low-dose and 9 months for the high-dose group, and the experience suggested that the high-dose mitoxantrone inducrespective relapse-free survival is 3 and 5 months. The tion used in the study might be more acceptable to older indiobserved differences in outcome were not statistically signifividuals, while resulting in improved antileukemic activity. mg/m 2 ) mitoxantrone in combination with a fixed dose of

No abstract

A question may be asked not only to elicit information, but also to make a statement. Questions serving the latter purpose, called rhetorical questions, are often lexically and syntactically indistinguishable from other types of questions. Still, it is desirable to be able to identify rhetorical questions, as it is relevant for many NLP tasks, including information extraction and text summarization. In this paper, we explore the largely understudied problem of rhetorical question identification. Specifically, we present a simple n-gram based language model to classify rhetorical questions in the Switchboard Dialogue Act Corpus. We find that a special treatment of rhetorical questions which incorporates contextual information achieves the highest performance.

No abstract

Summary:ant to standard-dose chemotherapy, these patients often do not receive ABMT. 10 Refractoriness to standard-dose treatment, though, may not necessarily reflect total resistance to To evaluate a strategy of one cycle of dose-intensive chemotherapy for patients with Hodgkin's disease in high-dose therapy, as suggested by occasional successes with dose-intensive therapy in resistant patients. We theresensitive relapse and two cycles for those with refractory disease, 122 patients received dose-intensive fore decided to employ two sequential ABMTs to test in a polar fashion whether dose intensive treatment has a role chemotherapy followed by autotransplant in two consecutive studies. Patients with refractory disease were in the treatment of patients with ostensible resistance to conventional-dose chemotherapy, and to compare their outoffered a second transplant with different conditioning in the absence of progression or excessive toxicity. CR come to that of simultaneously referred patients with sensitive disease, treated with one autotransplant. In patients was present after treatment in 46% while 16% died in the peritransplant period. Of 41 patients with primary with refractory disease, we used two chemotherapeutically dissimilar regimens in order to exploit the theoretical benerefractory disease and 42 with refractory relapse, 24 and 21 respectively received a second cycle. Of these 45 fit of any non-cross resistance between successive treatments. [11][12][13] Two consecutive studies with different conrefractory patients, 12 were in CR and 11 in PR after the first cycle and 10 of these 11 in PR achieved a durditioning regimens were performed, while maintaining the general study design. able CR with the second transplant. The CR rate is 37% in patients with refractory relapse and 19% in those with primary refractory disease. At a median follow-up of 4 years, median survival is 45 months. Progressionfree survival of the refractory patients who couldPatients and methods receive a second cycle was similar to that of patients with sensitive disease. A sequential transplant strategy is feasible. A subgroup of patients with refractory disPatient selection ease can achieve long-term survival after sequential BMT. Keywords: Hodgkin's disease; double transplant; doseAll consecutive patients referred with histologically documented Hodgkin's disease that had not responded to or had intensive therapy; refractory disease relapsed after conventional-dose chemotherapy were eligible for dose-intensive treatment with autotransplantation according to protocols approved by the institutional review Dose-intensive chemotherapy with autologous bone marboard of New York Medical College. All patients signed row transplantation (ABMT) is considered appropriate an approved, informed consent. Patients with disease resisttreatment for patients with relapsing Hodgkin's disease. [1][2][3][4][5][6][7][8] ant to initial or subsequent conventional chemotherapy Relapsing disease, however, is prognostically different were eligible to recei...