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Relapses in acute myelogenous leukemia (AML) are a result of quiescent leukemic stem cells (LSCs) in marrow stromal niches, where they resist chemotherapy. LSCs employ CXCL12/CXCR4 to home toward protective marrow niches. Heparin disrupts CXCL12-mediated sequestration of cells in the marrow. CX-01 is a low-anticoagulant heparin derivative. In this pilot study, we combined CX-01 with chemotherapy for the treatment of AML. Induction consisted of cytarabine and idarubicin (7 + 3) with CX-01. Twelve patients were enrolled (median age, 56 years; 3 women). Three, 5, and 4 patients had good-, intermediate-, and poor-risk disease, respectively. Day 14 bone marrows were available on 11 patients and were aplastic in all without detectable leukemia. Eleven patients (92%) had morphologic complete remission after 1 induction (CR1). Eight patients were alive at a median follow-up of 24 months (4 patients in CR1). Three patients received an allogeneic stem cell transplant in CR1. Median disease-free survival was 14.8 months. Median overall survival was not attained at the maximum follow-up time of 29.4 months. No CX-01-associated serious adverse events occurred. Median day to an untransfused platelet count of at least 20?×?109/L was 21. CX-01 is well tolerated when combined with intensive therapy for AML and appears associated with enhanced count recovery and treatment efficacy.

This paper suggests that alternative dispute resolution is a process of compromise and settlement. As such, it should only be used in appropriate disputes. The paper discusses selection of appropriate cases for alternative dispute resolution by referencing certain general observations as well as characteristics of the process. It further suggests that understanding the goals and objectives of alternative dispute resolution also aids in the decision on whether to employ alternative dispute resolution. The paper then lists and discusses major alternative dispute resolution goals and objectives.

Purpose. To determine the prevalence of tobacco use among Centers for Disease Control and Prevention (CDC)/Agency for Toxic Substances and Disease Registry (ATSDR) employees and the effect of the smoke-free policy on smoking behavior and air quality at work.Design. A stratified telephone survey of 1181 CDC/ATSDR employees randomly selected from employee rosters.Setting. CDC/ATSDR work sites in Atlanta, Georgia, and other major CDC locations throughout the United States and Puerto Rico.Subjects. Randomly selected employees of CDC/ATSDR1, or about 22% of the total CDC/ATSDR population; 98% of eligible persons selected agreed to participate.Measures. Demographic and smoking history variables, attitudes toward and impact of the smoke-free policy on smoking behavior, and self-report changes in air quality were the measures used.Results. Overall cigarette smoking prevalence was only 11.1%. One percent reported using chewing tobacco, 1.1% reported smoking a pipe, and 1.4% reported smoking cigars. Average self-reported, daily cigarette comsumption significantly decreased after the smoking ban took effect. Overall, 90 % of the employees supported the smoke-free policy, and 80 % of the employees believed that smokers were complying with the smoke-free policy. Most employees believed that the air quality of work areas and nonwork areas (65% and 69%, respectively) had improved since the smoke-free policy was implemented.Conclusions. These findings are consistent with previous evaluations of smoke-free policies and suggest that most employees are generally supportive of workplace smoking restrictions. Such policies can also have a positive impact on smoking behavior and perceived air quality.

The structure and distribution of entries in the lexicon impose strong constraints on word recognition. A construct of value in operationalizing such constraints is that of uniqueness point Computed by reference to a phonetic dictionary, it is the earliest moment at which a word can be uniquely distinguished from all others in terms of a sequential phoneme by phoneme comparison. There is empirical evidence that the uniqueness point bears a close relationship to the recognition point, the moment at which a word can actually be recognized on the basis of incoming acoustic information. In reality, recognition depends upon noisy and unreliable acoustic information, making categorial phonetic decisions difficult, and the value of a uniqueness point, questionable. Minimal deviation is proposed as a new construct to represent the extent of mismatch between a given word and the closest non-identical word in the lexicon. A computer analysis of a large phonetic dictionary shows that on average minimal deviation increases almost constantly with stimulus input subsequent to the uniqueness point. This simulation suggests that the empirical success of the uniqueness point as an indicator of word recognition performance may be accounted for by this subsequent increase in deviation in addition to the single mismatch at the uniqueness point itself

A number of problems in speech recognition arise through the treatment of speech as a linear temporal sequence. These include word onset detection, temporal normalisation and variations in pronunciation. It is suggested, following Wickelgren (1969, 1972) that speech should instead be represented by a non-sequential associativeor context-sensitivecode.

The authors studied the impact on clinical decision making of providing feedback of objective prognostic information describing the probability of survival for ICU patients with multiple organ system failure (OSF). The prognostic estimates, derived from a control period (1), were to be provided on a daily basis to physicians providing treatment in 25 French ICUs during a subsequent experimental period (2). The types of, frequencies of, and reasons for decisions to limit or stop treatment in the two periods were compared. In the experimental period 2, 17 ICUs participated in the feedback study. Within these 17 units, there was a small but significant (p <0.05) increase in decisions to stop active treatment and provide comfort care that was limited to patients with three or more OSFs. There was no change in decision making in the eight units that did not participate in the feedback study. Although these results suggest a direct causal relationship between the provision of objective prog nostic data and changes in physician decision making, the small increase in comfort care decisions (n = 14) between period 1 and period 2 and the fact that only 17 of the 25 original units participated in the feedback study make it difficult to eliminate other influences. There was no indication in this study, however, that explicit provision of prognostic data led to a sense of therapeutic futility. Key words:prediction; feedback; outcome; prognosis; organ system failure; treatment decisions. (Med Decis Making 1990;10:163-171)

This paper suggests that alternative dispute resolution is a process of compromise and settlement. As such, it should only be used in appropriate disputes. The paper discusses selection of appropriate cases for alternative dispute resolution by referencing certain general observations as well as characteristics of the process. It further suggests that understanding the goals and objectives of alternative dispute resolution also aids in the decision on whether to employ alternative dispute resolution. The paper then lists and discusses major alternative dispute resolution goals and objectives.

ABSTRACTPatients with recurrent malignant brain cancer, who were receiving gene therapy by intracerebral injection of murine retroviral vector producer cells (VPCs), were monitored for the presence of replication-competent retrovirus (RCR). RCR sequences were not detected by polymerase chain reaction (PCR) in any of the 608 peripheral blood leukocyte (PBL) samples analyzed. Vector DNA sequences were detected transiently in PBL samples from a subset of 34 patients. Humoral immune responses to a retroviral core protein p30 and murine VPC were detected in some patients, most frequently in patients receiving repeated administrations of VPC. RCR was not detected in biological assays of PBLs from 41 patients who had either anti-retroviral antibodies in sera and/or vector DNA in PBLs. Our data suggest that in situgeneration of RCR was not detected following intracerebral inoculation of VPCs in any of the 128 patients evaluated.

This paper discusses whether text on computer screens (Videotext) should be given a human “voice.” It focuses on computer-assisted writing instruction and suggests a framework for designing computer personalities to match user preferences.

Word processors with adjustable video screens are used to test students' writing facility with and without visual feedback. Lack of visual feedback seems to have a salutary effect in forcing concentration onto emerging thoughts rather than words and sentences. It also prevents interrupting the train of thought to edit and correct every few sentences. “Local editing” is regarded as counter-productive because it deals with individual words and lines instead of reconceptualization and reorganization. For some students, however, the lack of feedback per se was disturbing and thought-disrupting.

Nine patients with metastatic breast cancer received 30 × 106 I.U. of Interferon — Betaser (Betaseron) intravenously daily times five for two consecutive weeks followed by a two week rest period. Only one patient received more than one such cycle of Betaseron. The drug was well tolerated in eight of these patients. One patient, with liver metastases and liver dysfunction, developed hepatic decompensation during therapy. Toxicity consisted of anorexia, chills, fever, fatigue and nausea with an occasional patient having emesis. One patient developed severe thrombocytopenia, two, significant leukopenia and nine, mild elevations of serum transaminase. Two patients developed beta interferon binding antibodies but none developed neutralizing antibodies. No anti-tumor responses were seen and disease progression occurred rapidly during the four week cycle in eight of nine patients.

• We investigated the use of psychiatric consultations in short-term general hospitals using a national sample of 327 hospitals and examining the hospital experience of approximately 263 000 patients discharged from these hospitals. We found that the demographic characteristics of patients receiving psychiatric consultations in the national sample were roughly similar to those reported for patients receiving consultations in earlier, single-hospital studies. Rates of consultation were considerably lower, however: 0.9%, compared with a median rate of 3.3% reported in the literature. We also found that patients receiving psychiatric consultations used more hospital resources than other patients.

We report the operation of an imaging Nd:YAG microchip-laser synthetic-aperture radar, with which we imaged two-dimensional (2-D) models of military targets. The images obtained showed spatial resolution significantly better than the diffraction limit of the real aperture in the along-track dimension. The signal processing is described, and the measurement sensitivity is both predicted and verified. In addition, 2-D images with high resolution in both dimensions were generated by using an asymmetric aperture to match the along-track synthetic-aperture resolution with the across-track diffraction-limited resolution.

Here we report the operation of an optical synthetic aperture radar employing, for the first time to our knowledge, a solid-state laser as the source. The experimental data-acquisition and digital processing techniques are described, by which spatial resolution superior to that limited by diffraction is demonstrated.

Studies were performed with a semisolid agar culture system to determine the in vitro sensitivity of human ovarian carcinoma to human leukocyte interferon (IFN-a) and standard chemotherapeutic agents (adriamycin, cis-platinum, hexamethylmelamine, melphalan, and velban). Growth in culture occurred in 67% of samples derived from ascitic fluid and 71% of these exhibited reduction in tumor colony number by =25% in response to 300 units interferon/ml. The responsiveness of the ascitic fluid samples to interferon ran parallel to the overall responsiveness to the other agents tested. Sensitivity to interferon was not related to the histology or grade of the tumor or to the stage of the disease.

The article presents a reprint of the article "Computers and English: Future Tense…Future Perfect?" by Stephen Marcus, which appeared in the Volume 12, Number 4 issue of "The Quarterly." It has been predicted that grading systems in schools will become more dependent on style checkers. The existence of instructional databases will allow for more home education. Handwriting will develop as part of fine or applied arts.

Kovacsovics: Seattle Genetics: Research Funding. Deininger:CTI BioPharma Corp.: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Ariad: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kennedy:Cantex Pharmaceuticals: Equity Ownership. Marcus:Cantex Pharmaceuticals: Employment, Equity Ownership. Shami:JSK Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Acute myeloid leukemia (AML) therapy is associated with pancytopenia and with a high failure rate due to resistant leukemia stem cells that home to marrow niches. We present here updated results of this study that combined the low anticoagulant heparin CX-01 with chemotherapy for the treatment of AML. Induction consisted of cytarabine and idarubicin (7+3) along with CX-01. Patients younger than 60 received consolidation therapy with high dose cytarabine along with CX-01. Twelve patients were enrolled (median age 56; range 22 - 74; 3 women). Three, 5, and 4 patients had good, intermediate, and poor risk disease, respectively. Two patients did not finish induction due to events unrelated to CX-01. Day 14 bone marrows were available on 11 patients and were aplastic in all without detectable leukemia. Eleven patients (92%) had a morphologic complete remission after one induction (CR1), including all patients with de novoAML (11/11). No patient required re-induction at Day 14. Eight patients are alive at a median follow-up of 24 months (range 13 - 29). Four patients remain in CR1. Four patients received an allogeneic stem cell transplant in CR1. All patients who received a full induction were evaluable for platelet recovery and had a median day to an untransfused platelet count ≥ 20,000/μl of 21. Five patients who received a full induction without myelopoietic growth factor support were evaluable for neutrophil recovery and had a median time to a neutrophil count ≥ 500/mL of 22 days (mean 22.6 ± 2.4, range 21 - 27). Median disease free survival was 14.8 months. Median overall survival was not attained at the maximum follow up time of 29.4 months. No CX-01-associated serious adverse events occurred. In a supplemental surface plasmon resonance study, CX-01 inhibited binding of CXCL12 to surface conjugated heparin with a 50% inhibitory concentration (IC50) of 4.7 nM, suggesting the possibility that CX-01 may enhance CR by disrupting the CXCL12-mediated leukemic stem cell marrow niche. We conclude that CX-01 is well tolerated when combined with intensive therapy for AML. It appears to be associated with enhanced count recovery and treatment efficacy. Thus, CX-01 warrants further study in this setting.

Kennedy: Cantex Pharmaceuticals: Equity Ownership. Bavisotto:Cantex Pharmaceuticals: Consultancy. Marcus:Cantex Pharmaceuticals: Employment, Equity Ownership. Shami:JSK Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Lone Star Thiotherapies: Equity Ownership; Cantex Pharmaceuticals: Research Funding.

Introduction

Marcus: Paringenix: Employment, Equity Ownership.

Combination G/A has been shown to be apromising investigational therapy for patients with metastatic pancreatic cancer. A randomized phase II trial was initiated to determine if ODSH, a low anticoagulant heparin derivative that blocks several pancreatic cancer cell survival pathways, would enhance the efficacy of G/A. Preliminary data from the first 10 patients administered ODSH demonstrated an unexpected and profound preservation of peripheral blood counts, despite the highly myelosuppressive G/A regimen they also received.Patients with previously untreated, metastatic pancreatic cancer were treated with G (1000 mg/m2) and A (125 mg/m2) on days 1, 8, and 15 every 28 days until either disease progression or unacceptable toxicities ensued. ODSH (4 mg/kg bolus followed by a 48 hr. continuous IV infusion at a dose of 0.375 mg/kg/hr for 48 hrs) was administered with each treatment. The first 10 patients received A/G plusODSH with plans for a randomized comparison between A/G with and without ODSH involving 50 patients. Patients were required to have ECOG 0–1 as well as adequate hematological and bilirubin level <1.5 ULN. G-CSF administration was permitted per investigator discretion. Here we present hematological data on the 10 patients treated with A/G plus ODSH.10 patients were administered up to 5 cycles of G/A plus ODSH. The patients had a median age of 66 years (range, 59 to 75 years) and 50% were male. The median platelet and neutrophil counts prior to each cycle are listed in Table 1. No patients had grade 3/4 thrombocytopenia during any of the cycles. Forty percent of patients had grade 3 neutropenia, but none had grade 4 during any of the cycles. Only 1 patient received 1 dose of G-CSF after day 15 in cycle #1.A previous trial of G/A in patients with previously untreated, metastatic pancreatic cancer reported grade 3/4 thrombocytopenia and neutropenia in 28% (19% grade 3 and 9% grade 4) and 75% (26% grade 3 and 49% grade 4) of patients, respectively (Von Hoff, J Clin Oncol, 2011). With the addition of ODSH to an equivalent chemotherapy regimen in a similar patient cohort, the current trial reported grade 3 thrombocytopenia and neutropenia in 0% and 40% of patients, respectively, with no patients having grade 4 thrombocytopenia or neutropenia. With successive cycles, median platelet counts were stable to improved and a trend existed for reduced neutropenia with ODSH treatment. An explanation for the apparent salutary effects of ODSH on marrow function may involve its interaction with platelet factor 4 (PF4). PF4 is released from the alpha-granules of injured megakaryocytes after chemotherapy delivery. Increased PF4 levels promote thrombocytopenia by inhibiting thrombopoietin production and megakaryopoiesis (Lambert, Blood, 2007; Lambert, Int J Radiation Oncology Biol Phys, 2011). The high molecular weight and strong negative charge of ODSH may result in avid binding to platelet factor 4 (PF4), possibly leading to decreased PF4 levels and more rapid post-chemotherapy platelet recovery (Joglekar, Thromb Haemost, 2012). PF4 may also facilitate neutrophil adhesion to endothelial cells, and reduced PF4 levels from ODSH binding may demarginate and preserve neutrophil values (Kasper, Blood, 2006). Further study of ODSH as a marrow protective agent in myelosuppressivechemotherapy regimens is warranted.Off Label Use: The use of nab-paclitaxel and ODSH in pancreatic cancer. Marcus:Paringenix: Employment, Equity Ownership. Quintana Diez:Paringenix, Inc.: Employment.

Abstract 4723

Abstract 386

No relevant conflicts of interest to declare.

Abstract 723

Opinion. Comments about the need to create an attitude of regional cooperation to develop communities in Wisconsin's metropolitan areas. Example of the debate on transportation and the East-West Corridor; Support for arts funding.

Opinion. Comments on the role played by the Performing Arts Center (PAC) in Milwaukee, Wisconsin's performing arts community. PAC as cultural hub; Formation of the Silver Renaissance Campaign for the renovation of the center; Call for corporate, foundation, and individual donations for the center's renovation project.