Academic literature on the topic 'LB 5.5 UL 2008'

Abstract Resistance to ibrutinib (PCI-32765) is uncommon and not well described. Here we describe a 78 year old Caucasian man with a long standing history of CLL originally diagnosed in 2004. He was treated at the James Cancer Hospital and Fellow Research Institute at the Ohio State University since that time and received multiple regimens including fludarabine and Rituxan based regimens under the care of John Byrd, MD. He progressed and more recently was on the clinical trial of ibrutinib for relapsed CLL, which he tolerated well and to which he had an excellent response for nearly 2 years. The patient developed resistance to ibrutinib and was taken off study. According to Dr. Byrd, DNA sequencing revealed a V600 mutation (personal communication). The patient was subsequently enrolled on a clinical trial of carfilzomib, to which he did not respond and developed increasing leukocytosis with increasing numbers of prolymphocytes and transformation to B-cell PLL. He was treated with single agent ofatumumab with transient responses and rapid regrowth. He was then referred to the clinic at the Penn State Hershey State College satellite facility for care closer to his home. Ibrutinib is a novel oral inhibitor of the bruton tyrosine kinase (BTK) which is a member of the Tec family of kinases and is downstream of the B-cell receptor. A Phase 1b-2 study of ibrutinib in patients with relapsed or refractory CLL or small lymphocytic lymphoma was recently conducted. Treatment with Ibrutinib was associated with durable remissions in this population including those with high-risk genetic mutations (Byrd et al NEJM 2013;369:32-42). We have previously shown that immunotherapy combined with epigenetic pharmacotherapy is a feasible strategy in non-Hodgkin's lymphoma (NHL) and CLL in a phase 2 study (NCT 00764517) initiated by Epner and colleagues (Spurgeon et al 2012 ASH abstract 3675, Hasanli et al 2013 AACR LB-140) in which a 100% response rate was observed in untreated mantle cell lymphoma using SAHA (Vorinostat), cladribine and Rituxin (SCR). Based on these results, we proposed a treatment strategy which would employ the same epigenetic pharmacotherapy of SAHA and cladribine in combination with the immunotherapy of ofatumumab. Dr. Byrd agreed with our treatment strategy. Therefore, the epigenetic drugs, SAHA and cladribine combined with ofatumumab were initiated to try to overcome resistance mediated by epigenetic mechanisms as a means to improve therapeutic efficacy.The patient received 5 days of SAHA (400mg PO daily) and cladribine (5mg/m2) and continuied to receive ofatumumab (2000mg IV), and had a dramatic decline in his white blood count from 230 K/uL to 25 K/uL over a period of 10 days. After 3 cycles of our epigenetic immunotherapy, he achieved a complete hematologic remission which is sustained for nearly 12 months. He receives ofatumumab maintenance therapy (2000mg IV every 60 days). Here, we have used ofatumumab in combination with epigenetic pharmacotherapy in a ofatumumab refractory patient with CLL who acquired a 17p deletion to overcome ibrutinib resistance. The mechanism of resistance to ibrutinib in this case and others has not been determined, but sequencing studies carried on in the lab of Dr. Byrd (personal communication) reveal the BRAF V600E mutation. We describe here a patient with CLL who progressed through multiple therapies including ibritunib who achieved a complete hematologic response with the combination of SAHA, cladrbine, and ofatumumab. In this case, epigenetic modulation with pharmacologic intervention consisting of a hypomethylating agent in combination with a histone deacetylase may have enhanced the activity of ofatumumab and overcame ibrutinib resistance. Furthermore, our data suggests that the combination of epigenetic agents with monoclonal antibodies should be studied and that epigenetic agents are potentially capable of activating multiple silenced genes in different pathways. The epigenetic approach and use of hypomethylation agents in CLL deserve further investigations. This particular case demonstrates that (by current standards) a most promising drug (Ibrutinib) has some failures and the epigenetic approach may provide a strategy to salvage these patients. Disclosures: Sharma: Celgene: Consultancy, Employment. Off Label Use: Cladribine: approved for Hairy Cell Lymphoma (HCL), used here to treat B-CLL Vorinostat: approved for Cutaneous T Cell Lymphoma (CTCL), used here to treat B-CLL.

The structure and dynamic organization of a mixed Langmuir film of glucose oxidase (GOx) and lipid at the air–water interface were studied. The film was transferred onto the Prussian Blue (PB)-modified Pt electrode for biosensor preparation. The PB modified electrode showed well defined redox peaks in 0.1 M PBS electrolyte. The Langmuir film was characterized at the air–water interface by π-A isotherms. The mixed monolayer was formed by spreading GOx on the LB trough covered with lipid. Time-pressure results show that at least 90 minutes are required to reach the equilibrium state of GOx-lipid film. The monolayer was transferred onto the PB-modified electrode when surface pressure was 40 mN/m. This sensor was characterized by a very low detection limit and a wide linear range. The optimal conditions for both fabricating and response of the sensor were investigated. The proposed biosensor showed a linear calibration range from 5 × 10−6 to 6 × 10−5 M. The detection limit was determined to be 1.5 × 10−6 M.

Abstract Abstract 5067 Background: Hematologic neoplasms associated with the chromosomal translocation t(2;11)(p21;q23) form a distinct genetic entity with diverse manifestations, and have been strongly linked with up-regulation of the microRNA miR-125b-1 (Bousquet et al, J Exp Med, 2008). Of 41 patients with myeloid malignancies and t(2;11)(p21;23) reported in the world's literature, all but 2 were cases of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), the latter cases frequently high-grade MDS transforming to AML. In 20 of 41 cases deletion of 5q was detected as a secondary cytogenetic abnormality. Only two cases of chronic myeloproliferative disorders associated with t(2;11)(p21;23) have been reported: one of chronic myeloid leukemia with a secondary t(9;22) (Ph) translocation (Royer-Pokora et al, Leukemia, 2003) and one of polycythemia vera (Acar et al, Amer J Hematol, 2006). We encountered a patient with a mixed myelodysplastic/myeloproliferative neoplasm clinically resembling polycythemia vera that was associated with t(2;11)(p21;q23) who was found to have persistent elevation in the blood of the microRNA miR-125b-1. Case Report: A 52 year-old male presented with upper extremity pain and headache. A CBC revealed the white blood cell count was 12.5 ×103/uL (55% neutrophils, 12% lymphocytes, 8% monocytes, 5% eosinophils, 21% basophils), red blood cell count 6.62 × 106/uL, hemoglobin 22.4 g/dL, hematocrit 68.1%, MCV 103 fL, and platelets 112 × 103/uL. Bone marrow aspiration and biopsy revealed a markedly hypercellular marrow (100%) with 1+ reticulin fibrosis, mild trilineal dysplastic morphology, and a blast count of 0.8%. Cytogenetic studies disclosed 46, XY, t(2;11)(p21;q23) [4]/46, idem, del (5)(q15q31) [4]/46, XY, del (5) (q13q31) [2]/46, XY[10]. FISH studies were negative for BCR/ABL1 fusion and MLL rearrangement. Molecular analysis for the JAK2V617F allele was negative. A diagnosis of mixed myelodysplastic/myeloproliferative neoplasm, unclassified was made (WHO 2008). The patient was begun on hydroxyurea, 500 mg daily. Four months after diagnosis the blood counts were within normal range, at which time quantitative real-time PCR (qRT-PCR; Bousquet et al, J Exp Med, 2008) performed on a sample of whole blood revealed a twenty-fold elevation of the microRNA species miR-125b-1, compared to healthy donors (n=3), and JAK2V617F-negative (n=3) and JAK2V617F-positive (n=2) polycythemia vera controls. Repeat qRT-PCR performed on whole blood 15 months after diagnosis confirmed persistently elevated miR-125b-1, nearly 200-fold above healthy donor controls (n=3). 18 months after diagnosis the patient remains healthy, with normal blood counts on 500 mg of hydroxyurea daily (white blood cell count 5.54 ×103/uL, red cell count 5.35 × 106/uL, hemoglobin 13.7 g/dL, hematocrit 47.2%, MCV 88.2, platelets 132.0 × 103/uL). Conclusion: This case expands the clinical-pathologic spectrum of hematologic malignancies associated with t(2;11)(p21;23), and confirms the link between t(2;11)(p21;23) and up-regulation of miR-125b-1. Translocation t(2;11)(p21;23) with miR-125b-1 up-regulation should be considered as a rare possibility in the differential diagnosis of JAK2V617F-negative polycythemia vera. Disclosures: No relevant conflicts of interest to declare.

Gap junctions allow intercellular communication. Their structural subunits are four-transmembrane proteins named connexins (Cxs), which can be post-transcriptionally regulated by developmental and cellular signalling cues. Cx translation and mRNA stability is regulated by miRNAs and RNA-binding proteins (RBPs) such as human antigen R (HuR). In addition, several Cxs have also been suggested to contain 5′ internal ribosome entry site (IRES) elements that are thought to allow cap-independent translation in situations such as mitosis, stress and senescence. Furthermore, several recent reports have documented internal translation of Cx mRNAs that result in N-terminally truncated protein isoforms that may have unique gap junction-independent functions [Ul-Hussain et al. (2008) BMC Mol. Biol. 9, 52; Smyth and Shaw (2013) Cell Rep. 5, 611–618; Salat-Canela et al. (2014) Cell Commun. Signal. 12, 31; Ul-Hussain et al. (2014) J. Biol. Chem. 289, 20979–20990]. This review covers the emerging field of the post-transcriptional regulation of Cxs, with particular focus on the translational control of Cx 43 and its possible functional consequences.

679 Background: 5-fluorouracil (5-FU), a synthetic fluoropyrimidine, is a critical component of chemotherapy in many cancers. Its metabolites inhibit Thymidylate Synthetase (TS) causing cessation of DNA synthesis and are misincorporated into DNA and RNA causing ineffective DNA repair and faulty mRNA splicing. The rate limiting step in the catabolism of 5-FU is by the Dihydropyrimidine Dehydrogenase enzyme (DPD) which catabolizes over 80% of 5-FU. Patients with near total DPD enzymatic deficiency develop life threatening toxicity after a single administration and those with less severe deficiency will have delayed elimination of 5-FU and slowly accumulate active metabolites leading to toxicities. Methods: We conducted a pilot retrospective cohort study of African American (AA) and Caucasian patients treated for colorectal cancer over a 9 year period, 2000 – 2008, in this IRB approved study. The primary outcome of interest was the rate of development of grade 3 or 4 neutropenia (Absolute Neutrophil Count <1000/uL = grade 3 and <500/uL = grade 4). Descriptive and univariate analysis were done. To test for differences between AA and Caucasians, we computed independent t-test for continuous and Fisher’s exact test for categorical variables. Relative Risk (RR) and p-values were computed. All statistics were done with SPSS v19 software. Results: There were 66 evaluable patients (40 men, 26 women), 40 AA, 24 Caucasians and 2 of other races. Thirty-eight patients (15 Caucasians and 23 AA) received 5-FU containing chemotherapy. The two groups were comparable in baseline characteristics. AA were more likely to develop grade 3-4 hematological toxicity. Nine of 23 AA (39.1%) and one of 15 Caucasians (6.7%) developed grade 3-4 hematological toxicity. RR 8.56, 95% confidence interval 0.95 – 421.06 (p-value of 0.0561) Conclusions: These results suggest that AA were more likely than Caucasians to have severe hematologic toxicity with the use of 5-FU containing chemotherapy. This difference did not meet statistical significance due to small sample size and few numbers of events in the Caucasian arm. A larger prospective study is needed to further evaluate the observed difference.

Abstract Abstract 2638 Poster Board II-614 Background: The importance of cytogenetics in prognosis of AML is now widely recognized and accepted in clinical practice. A recent study found that autosomal chromosomal monosomy predicted for an adverse outcome. The goal of this study is to characterize patients with monosomal karyotype by mutation status and clinical features. Methods: One-hundred forty consecutive AML patients diagnosed at Stanford University Hospital between 2005 and 2008 with adequate material for mutation analysis were studied. Cases were classified using the 2008 WHO criteria. Diagnostic cytogenetic findings were reviewed and patients were stratified into risk groups using Southwest Oncology Group criteria. An abnormality was considered clonal when at least two metaphases had the same aberration, except for clonal monosomy, which required at least three metaphases. The karyotype analysis was based on 20 or more metaphases. All samples were tested for NPM, FLT3 (ITD and D835) and CEBPA mutations. Clinical parameters including hemogram data at time of diagnosis were reviewed. Clinical follow-up including overall survival (OS), progression free survival (PFS) and complete remission (CR) rates were retrospectively determined. Kaplan-Meier methods and univariate Cox proportional hazards regression analysis were used to compare the clinical data. Results: The cases included 77 males and 63 females with a median age of 58 (range 17-83). Cytogenetic risk-group stratification resulted in 14 patients with favorable, 88 with intermediate and 28 with unfavorable risk status. Loss of one or more autosomal chromosomes was present in 18 /130 patients (13.8%) with available cytogenetic studies. A single autosomal monosomy was found in 5 patients while 13 patients had two or more autosomal monosomies. The most common chromosomes lost in these 18 patients included 7 (55% of 18 cases), 5 (50%), 17 (33%), 21 (22%), 20 (22%), 22 (17%) and 18 (11%). Using the 2008 WHO criteria, there were 66 AML with myelodysplasia-related changes (AML-MRC), 55 AML not otherwise specified (AML-NOS), 14 AML with either t(8;21), inv(16) or t(15;17) and 5 therapy related AMLs. Overall, 35 patients (25% of all patients) had a NPM1 mutation (19 of which were FLT3 mutated), 33 had FLT3-ITD mutation (24%), 11 had FLT3-D835 (8%) and 11 had a CEBPA mutation (8%) (4 of which were FLT3 mutated). Patients with monosomal karyotype were significantly older (83 vs. 59 years, p=0.0125) and presented with lower WBC (34 vs. 66 K/uL, p=0.0006), lower platelets (41 vs. 64 K/uL, p=0.0111), and lower blasts (38% vs. 65%, p=0.0030) as compared to the rest of AML patients. In addition, patients with monosomal karyotype were more frequently diagnosed with AML-MRC (16/18 vs. 48/107, p=0.0034) and exhibited a decreased frequency of NPM1 mutation (0/18 vs. 28/107, p=0.0138) and FLT3-ITD mutation (0/18 vs. 29/107, p=0.0117). Clinical outcome data showed that patients with monosomal karyotype had a significantly worse OS, PFS and CR compared to the rest of AML patients (OS p=0.001, PFS p=0.002 and CR p=0.0262). Dividing patients by number of monosomies showed that patients with 2 or more monosomies had a significantly worse OS (p=0.0001) and PFS (p=0.0045) than patients without any monosomies. However, no difference in OS or PFS was seen when comparing patients with 1 monosomy to those with 2 or more monosomies. Within the AML-MRC group, monosomal karyotype correlated with lower WBC (17 vs. 37 K/uL, p=0.0005), lower platelets (21 vs. 35 K/uL, p=0.0095), lower blasts (19% vs. 36%, p=0.0015) and shorter OS (p=0.0322) and PFS (p=0.0084). Conclusion: AML patients with monosomal karyotype exhibit a significantly worse OS, PFS and lower CR as compared to other AML patients. Most of patients fall within the newly defined AML-MRC group and are characterized by significant absence of NPM1 and FLT3-ITD mutations. Disclosures: No relevant conflicts of interest to declare.

Abstract Hydroxyurea therapy is associated with reduced morbidity among patients with sickle cell disease (SCD). Avascular necrosis of the femoral head (AVN) is one potentially debilitating complication of SCD. In this study, we examined the relationship between hydroxyurea use and the prevalence of AVN among children with SCD. We performed a retrospective chart review of 202 children with SCD, aged 10–21 years, followed in the pediatric hematology program at the Children’s Hospital at Montefiore (Bronx, NY) between July 2007 and 2008. Abstracted data included age, ethnicity, SCD genotype, frequency of hospitalization, hip radiograph results, laboratory data and hydroxyurea use. Hip radiographs were performed prospectively as part of SCD health maintenance from 2005–2008. Forty-four patients were excluded because they did not have a screening hip radiograph. Descriptive statistics were calculated for independent variables. T-tests and chi-square tests were used to compare clinical and demographic characteristics of children with and without AVN. Multivariate logistic regressions were used to estimate the odds ratio of having AVN among SCD patients. Our final sample consisted of 158 patients whose demographic characteristics are listed in Table 1. The prevalence of AVN was 16.5% (n=26). Of the clinical variables analyzed, we identified significant associations between the presence of AVN and hydroxyurea use (p=.005), as well as older age (p=.013) (Table 1.) Children with AVN had significantly lower mean lactic dehydrogenase levels (LDH) (p=.04) and higher mean corpuscular volumes (MCV) (p=.012). (Table 2.) After controlling for gender, ethnicity, sickle cell genotype, and frequency of hospitalizations, age was also found to be associated with AVN (OR 1.15, 95% confidence interval (CI): 1.01,1.31, p=0.033). SCD patients on hydroxyurea had higher odds of having AVN compared to non-users (OR 3.51, 95% CI: 1.31, 9.38, p= 0.013). Laboratory values (MCV, Hemoglobin, LDH and Hematocrit) had a high degree of collinearity and were removed from the final model. In summary, the prevalence of AVN in our sample was 16.5%. This is substantially higher than the prevalence of approximately 6% reported by the Cooperative Study of Sickle Cell Disease for comparative age groups in a prospective study1. SCD patients exposed to hydroxyurea were three times more likely to have AVN than those not exposed to this drug. Vaso-occlusive pain crisis is a recognized risk factor for AVN, thus we could expect a higher rate of AVN among patients on hydroxyurea. However, the odds ratio of 3.5 is unexpectedly high and warrants further investigation into the role of hydroxyurea as a risk factor for AVN. Nonetheless, these preliminary results suggest that more stringent screening regimens for AVN may be indicated among this subset of patients. Table 1. Clinical characteristics of patients with and without avn *p&lt;0.05 **p&lt;0.01 No AVN (N =132) AVN (N = 26) Age * 15.7 years 17.4 years Sex Male 64 (49%) 17 (65%) Ethnicity Black 110 (83%) 23 (88%) Hispanic 22 (17%) 3 (12%) HgbSS 84 (64%) 20 (77%) HgbSC 38 (29%) 4 (15%) HgbSBthal0 5(3.8%) 2 (8%) Hgb SC HgbSBthal+ 5 (3.8%) 0 On Hydroxyurea** 38 (29%) 15 (58%) # Hospitalizations 0 60 (45%) 10 (38%) 1–5 64 (49%) 14 (54%) &gt;5 8 (6%) 2 (8%) Table 2. Mean Laboratory Values for Patients With And Without AVN No AVN AVN *p&lt;0.05 (N =132) (N = 26) WBC 10.7 k/uL 10.5 k/uL Hgb 9.4 gm/dL 9.6 gm/dL MCV* 83 fL 89 fL Platelets 381 k/uL 376 k/uL Reticulocyte 7.70% 8.10% Ferritin 369.8 ng/mL 438.7 ng/mL LDH* 471.6 U/L 389 U/L Creatinine 0.6 mg/dL 0.6 mg/dL Hgb F 9.80% 11.30%

Two keywords in implementing Quality Management System ISO 9001:2008 are customer satisfaction and continuous improvement. Both are important and always influence each other. In the practice of library service, user satisfaction becomes an essential aspect for the library to make a continuous improvement. This means when a library puts priority on user satisfaction, it will make continuous improvement. In other words, a continuous improvement will always be made when the library concentrates on achieving user satisfaction. This study is aimed at identifying the achievement level ofuser satisfaction reached at Sanata Dharma University Library (SD UL) in the period of 2008 to 2014 and to find out continuous improvement that has been made by SDUL, especially, the result analysis on monitoring and assessing user satisfaction. This study was a survey that used descriptive method. The result of the study showed the achievement level of monitoring and assessmentof user satisfaction at SDUL in the period of 2008 to 2014 reached maximum score, that is, 3.5 to 3.8 in the scale of I to 5. Observed from the user satisfaction analysis, continuous quality improvement conducted in SDUL covered three important fields, that is, information and information access facilities, library services, and infrastucture and work environment. Keywords: library user satisfaction, collection and information access, library services, infrastructure and work environment

Abstract Abstract 1608 Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous family of entities with a worse prognosis, stage by stage, than their B-cell counterparts. We have previously reported that an absolute lymphocyte count (ALC) <1000/uL is associated with a worse prognosis in Peruvian patients with PTCL (Castillo et al. 2010). The goal of this study is to investigate the prognostic value of absolute monocyte count (AMC) in the survival of patients with PTCL. Methods: A total of 251 cases of aggressive, non-primary cutaneous PTCL diagnosed at our institution between January 1997 and January 2012 were reviewed, reevaluated according to their morphological, immunological and clinical characteristics, and reclassified according to the 2008 WHO classification of lymphoid neoplasms. Characteristics will be presented descriptively. Kaplan-Meier method was used to estimate overall survival (OS) curves, which were compared using the log-rank test. The multivariate analysis was performed using the Cox proportional-hazard regression test. Results: According to the new WHO classification of lymphoid neoplasms, 104 cases (41%) were classified as adult T-cell leukemia/lymphoma (ATLL), 103 cases (41%) as PTCL, unspecified (PTCLU), 27 cases (11%) as analplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL), 11 cases (4%) as extranodal NK/T-cell lymphoma (NKTCL), nasal type, 4 cases (2%) as angioimmunoblastic lymphoma (AIL), and 2 cases (1%) were diagnosed with ALK+ ALCL. The median age at diagnosis was 57 years (range 14–92 years); 47% of patients were >60 years. The male-to-female ratio was 1:1. ECOG performance status >1 was seen in 51%, LDH was elevated in 67%, advanced stage was seen in 73%, and >1 extranodal sites were seen in 22% of the patients. Bone marrow involvement was reported in 30% and B symptoms in 64% of patients. An International Prognostic Index (IPI) score 3–5 was seen in 55%, and a Prognostic Index for PTCLU (PIT) score of 2–4 in 63%. The median overall survival (OS) for the whole group was 10 months. The IPI score, the PIT score, ALC <1000/uL and AMC >800/uL (Figure) showed statistical significance in the univariate survival analysis (p<0.001, p<0.001, p=0.001 and p=0.001, respectively). In the multivariate analysis, PIT score and AMC >800/uL showed statistical significance (p=0.006, p=0.046, respectively). Conclusions: Monocytosis, defined as AMC >800/uL, and the PIT score were independent prognostic factors for OS in patients with aggressive, non-primary cutaneous PTCL. Disclosures: No relevant conflicts of interest to declare.

590 Background: CMF (C 600 mg/m2, M 40 mg/m2, F 600 mg/m2) is an option for adjuvant therapy for patients with low risk early stage breast cancer. DD regimens as predicted by mathematical models of cancer growth and treatment response are superior. We previously demonstrated the safety of DD EC (epirubicin/cyclophosphamide) followed by paclitaxel at 10–11 day (d) intervals. We investigated the feasibility of administering DD adjuvant CMF every 14 d and then every 10–11 d in a 2-stage phase II trial. Methods: An initial cohort (A) was treated q 14 d with PEG-filgrastim (Neulasta) support. A second cohort (B) was treated every 10–11 d with filgrastim/Neupogen x 5 d and then, based on feasibility, modified (cohort C) to use 7 d filgrastim. The primary end point was feasibility defined as having ANC > 1.5 x 103/uL on day 1 of planned treatment for all 8 cycles with no grade 3 or higher non-hematologic toxicity. All three cohorts were tested using a Simon's two-stage optimal design with type I and type II errors set at 10%. This design would effectively discriminate between true tolerability (as protocol-defined) rates of< 60% and> 80%. Cohort A: 38 pts with early stage breast cancer were accrued from 3/2008 though 6/2008. Cohort B: 7 pts were accrued from June 2008 through August 2008. Cohort C: Is still open with 16 pts accrued from August 2008 through December 5, 2008. Results: Median age 51: range 38 to 78. Cohort A: 29/38 pts completed 8 cycles of CMF. The regimen was considered feasible. 2 other pts completed 7 cycles and were withdrawn for depression and grade 2 transaminitis. The 7 other pts completed between 1 and 6 cycles of CMF were withdrawn as follows: 3 personal, 1 (grade 3) bone pain, 2 allergy unrelated to CMF, and 1 seizure. Cohort B: 7 pts were accrued. 6 out of 7 pts could not complete 8 cycles of chemotherapy secondary to neutropenia and 1 secondary to grade 3 ALT elevation. Cohort C: Accrual has not been completed. 16 pts are currently enrolled. Conclusions: Dose dense adjuvant CMF is feasible at 14 d intervals with PEG-filgrastim support. Adjuvant CMF every 10–11 days with filgrastim given for 5 days beginning day 2 is not feasible. Accrual is ongoing for CMF at 10–11 days with filgrastim x 7 days. Updated results will be available for Cohort C. [Table: see text]

Depuis quelques années, de nombreuses études se sont intéressées à la musique, particulièrement à l’influence que celle-ci peut apporter dans certains domaines. Ainsi, de récents travaux scientifiques menés en éducation et en psychologie démontrent l’importance de l’apprentissage de la musique pour le développement des jeunes enfants (McPherson, 2005; Hallam, Cross et Haut, 2008). La musique engage l’ensemble du cerveau à travers un nombre diversifié d’opérations perceptives et cognitives (Altenmuller, 2003). En outre, quelques études empiriques relèvent que de nombreuses habiletés musicales émergent et se consolident au cours des premières années de vie, particulièrement entre l’âge de quatre et six ans (Gordon, 2003 ; Ilari, 2002 ; Radocy et Boyle, 2003). L’écoute musicale semble faciliter le développement cognitif et plus particulièrement langagier (Kraus et al., 2014). Cette étude qualitative tisse les liens entre la musique et le langage. Elle a pour but d’explorer dans quelle mesure l’écoute de la musique chez des enfants d’âge préscolaire peut aider leur expression orale. Elle porte sur l’analyse de l’écoute de la musique classique pendant des moments de jeux de dix enfants de quatre et cinq ans et plus particulièrement pendant des causeries, afin d’examiner si la musique influence l’expression orale chez ces enfants. L’analyse des résultats soulignent que la majorité des participants sont devenus plus sensibles à l’écoute de la musique et que certains de leurs comportements et gestes suivaient le rythme des chansons. Par ailleurs, les résultats relèvent également que plusieurs participants du groupe ont amélioré leur expression orale et que celle-ci semblait influencée par l’écoute musicale.
In recent years, many studies have focused on music, especially the influence that it can bring in some areas. Thus, recent scientific work in education and psychology show the importance of learning music in the development of young children (McPherson, 2005; Hallam, Cross and Thaut, 2008). Music engages the whole brain across a variety of perceptual and cognitive operations. (Altenmuller, 2003). Moreover, according to the latest research, studies indicate that many musical skills emerge and consolidate during the first years of life, particularly between the ages of four to six (Gordon, 2003; Ilari, 2002; Radocy et Boyle, 2003). Musical listening seems to favor cognitive and more specifically language development (Kraus et al., 2014). This qualitative study forges the links between music and language. It aims to explore the extent to which listening to music in preschool children can promote their oral expression. It focuses on the analysis of listening to classical music during playful moments of ten children aged four and five, and more particularly on talks, to examine whether music influences oral expression in these children. The analysis of the results highlights that most participants became more sensitive to listening to music and that some of their behaviors and gestures followed the rhythm of the songs. In addition, the results also indicate that several of the group's participants improved their speaking skills and that this seemed to be influenced by musical listening.

Le présent mémoire porte sur les habiletés pragmatiques des enfants âgés de 5-6 ans et la qualité des interactions enseignante-enfants en maternelle 5 ans. De manière plus précise, il vise à étudier les habiletés pragmatiques des enfants selon trois sources et méthodes d’évaluation : 1) la pragmatique perçue par l’enseignante [CELF CDN-F] (Semel, Wiig et Secord, 2009a); 2) la pragmatique manifestée par l’enfant dans le cadre d’une situation de jeu symbolique semi-dirigée [Protocole du pique-nique] (Bouchard, Blain-Brière et Leboeuf, 2014); et 3) la pragmatique observée en situation naturelle de classe [Individualized Classroom Assessment Scoring System] (Downer et al., 2012; Downer, Booren, Lima, Luckner et Pianta, 2010), à partir des dimensions « Communication avec l’enseignante » et « Communication avec les pairs ». La qualité des interactions est par ailleurs étudiée à partir du Classroom Assessment Scoring System (CLASS; Pianta, La Paro, et Hamre, 2008), composé de trois domaines : le soutien émotionnel, l’organisation de la classe et le soutien à l’apprentissage. Les participants sont, d’une part, 1131 enfants (66 filles et 46 garçons) âgés de 73,41 mois (ET = 4,08) qui fréquentent des classes maternelles 5 ans de la région de Québec, et d’autre part, 12 enseignantes ayant en moyenne 11,99 années d’expérience dans le domaine de l’enseignement (ET = 7,14), dont en moyenne 8,44 années en maternelle (ET = 5,45). Les résultats révèlent notamment que, selon les enseignantes, 80 % des enfants ont démontré, souvent ou toujours, une majorité d’habiletés pragmatiques (pragmatique perçue). Toutefois, seulement le quart des intentions de communication et règles conversationnelles sollicitées sont manifestées par 90 % des enfants et plus, dans le contexte d’un jeu semi-dirigé [Protocole du pique-nique] (pragmatique manifestée). De plus, les enfants de cet échantillon démontrent un faible niveau d’initiation et de maintien de la conversation avec leur enseignante et avec leurs pairs (pragmatique observée). En ce qui concerne les relations entre les variables de la pragmatique, les analyses corrélationnelles indiquent des liens significatifs et positifs entre les variables de la pragmatique perçue. En revanche, la pragmatique perçue n’est ni associée à la pragmatique manifestée ni à la pragmatique observée avec l’adulte ainsi qu’avec les pairs. La pragmatique manifestée et la pragmatique observée avec l’adulte sont significativement et négativement reliées entre elles, mais la taille de l’effet est faible. En ce qui a trait à la qualité des interactions en classe de maternelle 5 ans, l’organisation de la classe constitue le domaine pour lequel le score est le plus élevé, vient en second le soutien émotionnel, tandis que le domaine du soutien à l’apprentissage affiche le score moyen le plus faible. Quant aux liens entre les habiletés pragmatiques et la qualité des interactions en classe, les analyses corrélationnelles indiquent que la pragmatique perçue n’est pas associée aux domaines de la qualité des interactions. En outre, la pragmatique manifestée et le domaine du soutien à l’apprentissage entretiennent des liens significatifs, bien que faibles. La pragmatique observée avec les pairs est associée au soutien émotionnel et à l’organisation de la classe. Cependant, la pragmatique observée avec l’adulte n’est pas associée aux domaines de la qualité des interactions en classe. Ces résultats sont discutés en regard de leur implication pour la recherche et la pratique enseignante à l’éducation préscolaire. Mots-clés : Habiletés pragmatiques perçues, manifestées, observées, maternelle 5 ans, qualité des interactions enseignante-enfants, CELF CDN-F, Protocole du pique-nique, inCLASS, CLASS.

Tableau d’honneur de la Faculté des études supérieures et postdoctorales, 2007-2008
x200811\u Esta investigación trata de la implementación del Convenio sobre la Diversidad Biológica. Puesto que la biodiversidad se ve afectada por una variada gama de actividades humanas, de las cuales varias no dependen de los gobiernos nacionales, en el contexto del presente trabajo la implementación es evaluada al nivel infra-nacional. Un estudio de diversos casos fue llevado a cabo en el sur del Ecuador con el objetivo de determinar cuales de los seis factores evaluados (recursos financieros y humanos, estabilidad y voluntad política, capacidades de la sociedad civil, implicación de actores externos) se encuentran más íntimamente relacionados con las diferencias observadas en la implementación del convenio entre los niveles gubernamentales y entre las unidades políticas. Los datos acumulados no permiten identificar ni un factor, ni varios factores pudiendo ser citados como más determinantes con respecto a un nivel dado. Sin embargo, otras observaciones de terreno parecen indicar la importancia de la implicación de actores externos. Por otro lado, según la opinión de varias de las personas entrevistadas, los recursos disponibles son determinantes, pero su importancia sería condicional a la sensibilización de la población y de l@s polític@s.
x200812\u This research looks at the level of implementation of the Convention on biological diversity. Since biodiversity is affected by myriads of human activities, many of which do not depend on national governments, implementation is measured in subnational governments. A multiple case study was conducted in southern Ecuador in order to study which of six factors (financial and human resources, political stability and will, civil society capacities, external actors’ implication) are more closely linked to observed differences in the implementation between governmental levels and political units. The data collected in the field does not enable us to identify one or more factors as more determining. Nevertheless, other field observations seem to indicate the importance of external actors’ implication. Furthermore, according to some thirty interviews carried on, resources are crucial, but, as mentioned by several, depend on the sensitisation of the population and political figures.

La présente recherche a pour but d’étudier la relation entre les comportements extériorisés et la stabilité de l’expérience de garde chez les enfants âgés de 4 à 5 ans qui fréquentent un centre de la petite enfance. L’échantillon est composé de 107 enfants (53 filles et 54 garçons), dont l’âge moyen se situe à 59,9 mois (É.T. = 4,8). Parallèlement, l’échantillon est constitué de 15 éducatrices provenant de cinq centres de la petite enfance de la région de Québec, ayant en moyenne 23,5 ans (É.T. = 7,8) d’expérience dans le domaine. Une analyse de covariance univariée (ANCOVA) a été réalisée entre les comportements extériorisés et la stabilité de l’expérience de garde, en tenant compte du genre. Les résultats ne montrent aucune différence significative entre les comportements extériorisés et la stabilité de l’expérience de garde des enfants, si l’on tient compte du genre. Ces résultats sont discutés en fonction des éléments susceptibles d’influencer les différences de genre dans les comportements extériorisés des enfants et ceux relatifs à la stabilité de l’expérience de garde.

During the past several years, we have initiated studies to determine the role of plasma factors and platelets, and the properties of the blood vessel, which influence the activation of the coagulation mechanism on the subendothelium. Studies were performed by exposing everted segments of de-endothelialized rabbit aorta, mounted in a perfusion chamber, to non-anticoagulated human blood for 5 to 10 minutes under a range of flow conditions, and measuring fibrin and platelet deposition on the subendothelium, and fibrinopepstide A (FPA) levels in post-chamber blood. In normal subjects, platelet deposition increased progressively with increasing shear rates (50-2600 sec-1 ), whereas fibrin deposition and FPA levels decreased sharply at shear rates greater than 650 sec-1 . To examine the role of plasma coagulation factors, we utilized a shear rate of 650 sec-1 to study patients with severe deficiencies of factors XII, XI, IX or VIII. In contrast to the partial thromboplastin time (PTT), which was most strikingly abnormal in patients with factor XII or XI deficiency, fibrin deposition and FPA levels were greater in patients deficient in factor XII or XI than in those with factor VIII or IX deficiency. In addition, we observed smaller platelet thrombi in hemophilia (but not afibrinogenemia), suggesting that thrombin influenced the formation of platelet thrombi under these shear conditions. The findings suggested that tissue factor-Vila activation of factor IX could be important in mediating fibrin deposition on subendothelium and might explain why patients with factor XII deficiency (and some with factor XI deficiency) do not bleed. Initial studies to demonstrate tissue factor activity in subendothelium were inconclusive. More recently, utilizing shorter (1.5, 2 and 3 min) perfusion periods, we have observed decreased fibrin deposition and FPA levels in patients with factor VII deficiency and we have obtained further support for the presence of tissue factor in subendothelium in experiments utilizing a monoclonal antibody to tissue factor. Our studies suggest that activation of factor IX by tissue factor-Vila could account for the results obtained in patients with plasma coagulation defects. Direct experimental verification of this hypothesis will require more extensive studies on the kinetics governing the activation of coagulatjon factors on the subendothelium. In subsequent studies, we examined the role of platelets in mediating fibrin deposition. At a shear rate of 650 sec-1 we found (utilizing patients with thrombocytopenia) that platelets were required for fibrin deposition ; little or no fibrin was deposited on the subendothelium when platelet adhesion was less than 4%, corresponding to blood platelet counts less than 5000/ul. Studies performed in patients with functional platelet disorders provided additional information on the specific platelet properties that contribute to fibrin deposition at this shear rate. Decreased fibrin deposition was observed in a patient with Scott Syndrome, a disorder characterized by an impaired capacity of the platelets to catalyze the conversion of factor X to factor Xa (in the presence of factor IXa and VIII) and prothrombin to thrombin (in the presence of factor Va), the latter defect owing to a decreased factor Xa-binding capacity of the platelets. In contrast to the findings in Scott Syndrome, both fibrin deposition and FPA values were completely normal (and possibly increased) in patients with glycoprotein Ilb/IIIa deficiency. In patients with glycoprotein lb deficiency, the major defect was an impaired association of fibrin with platelets, but not subendothelium. The findings in patients with functional platelet disorders indicate that a monolayer of platelets (including those deficient in glycoprotein Ilb/IIIa) is completely active in promoting fibrin deposition on subendothelium. In addition, they suggest that an agent capable of inducing a platelet defect similar to that observed in Scott Syndrome might prevent platelet-fibrin thrombi at shear rates (200-800 sec-1 ) comparable to those in the coronary circulation. Studies performed at a variety of shear rates in both normal subject^ and patients with platelet disorders suggested that, under the conditions used, platelets were essential for fibrin formation at intermediate (650 sec-1 ), but not low (50 sec-1 ) shear rates. Since platelets have been shown to bind activated coagulation proteins (such as factor Xa, Va, and IXa) to their surface, the presence of adherent platelets on the subendothelium could, with increasing shear rates, serve to maintain activated coagulation proteins in the .boundary layer at a concentration that would otherwise be reduced through convective diffusion in their absence. Thus, at low shear rates (50 sec-1 ), the concentration of activated coagulation factors in the boundary layer might be sufficient to support fibrin deposition despite the absence of platelets, whereas at very high shear rates (2,600 sec-1 and above), even the presence of platelets is insufficient to maintain the required concentration. The shear-dependent defect of fibrin formation that we observed in Scott Syndrome is consistent with such a theory. The results of our various studies demonstrate the complex role of blood flow, plasma coagulation factors, specific platelet properties, and the procoagulant properties (tissue factor) of the vessel in mediating subendothelium-induced coagulation and suggest further experiments for studying the mechanisms involved.

The frictional pressure drops of gas-liquid two-phase flow in mini-micro pipes and at vena contract and expansion were investigated experimentally and analytically. Pressure drops of straight pipe, sudden enlargement and sudden contraction of gas-liquid two-phase flow in mini-pipes were measured. Test liquid was water at room temperature; test gas was argon. The diameter of the test mini-pipe was 1.0 and 0.5 mm, respectively. Each test tube was connected at both ends to small tanks. The diameter of the small tank was 15 mm for 1.0 mm diameter of test tube and 5 mm for 0.5 mm diameter of test tube, respectively. Thus, the cross-sectional ratio of the contraction was about 1000; the ratio of the enlargement was about 0.001. The pressure drop data were collected over 3.0 < UG < 130 m/s for the superficial gas velocity and 0.02 < UL < 6.0 m/s for the superficial liquid velocity. The present experimental results of sudden contraction pressure loss factor Kc and sudden enlargement pressure loss factor Ke of single-phase liquid flow in mini-pipes differed from the conventional values, Kc = 0.5 and Ke = 1.0. The calculated results by using a commercial code, STAR-CD, agreed with the present experimental results for mini-pipes. Assuming to homogenous flow and incompressible flow, sudden contraction pressure loss, sudden enlargement pressure loss and their factors Kc, Ke for gas-liquid two-phase flow were estimated by using momentum equation and energy equation. The contraction pressure losses by Hewitt’s correlation for conventional pipes were similar to the present experimental results of the contraction for mini-circular pipe. Collier’s correlation of the enlargement pressure loss for conventional pipes underpredicted the present experimental results of the enlargement for mini-tube. Based on the present experimental results, new correlations were obtained for the enlargement and the contraction pressure losses in mini-channel.