Academic literature on the topic 'G 60 UL 2009'

Abstract Aim Pegfilgrastim (Neulasta®) has proven efficacy as supportive therapy in a variety of chemotherapy regimens, but has not been studied in dose intensive, rapidly cycling regimens such as hyper-CVAD. We examined whether pegfilgrastim leads to similar kinetics of neutrophil recovery as daily G-CSF. Methods Using retrospective analysis, patients receiving pegfilgrastim were matched with controls (G-CSF) for cycle of chemotherapy, prior chemotherapy, dose of cytarabine received, age (<60 or >60), diagnosis (ALL or NHL) and bone marrow involvement. The primary endpoint was duration of grade IV neutropenia (ANC <500/ul). Secondary endpoints included time to neutrophil recovery, incidence of febrile neutropenia, positive blood cultures and delay in subsequent chemotherapy. Results Between 01/1999 – 06/2005 we identified 124 pegfilgrastim supported cycles in 43 patients. Cases were successfully matched to 124 G-CSF supported cycles from 38 controls. There were no significant differences between cases and controls with regards to prior chemotherapy, age, sex, cytarabine dose, diagnosis or bone marrow involvement. The median duration of grade IV neutropenia was 4 days in both groups (p =0.55). Pegfilgrastim (95% CI) G-CSF controls (95% CI) P value Grade IV neutropenia - All cycles 4 days (0–11) 4 days (0–10) 0.55 - A cycles 2 days (0–7) 2 days (0–6) 0.65 - B cycles 6 days (2–12) 6 days (0–10) 0.70 Time to ANC >500/ul 13 days (10–19) 14 days (8–18) 0.75 Time to ANC >2000/ul 14 days (11–29) 14.5 days (9–22) 0.27 Febrile Neutropenia 29% 38% 0.16 Positive Blood Cultures 11% 12% 0.85 Delay in next cycle 44% 47% 0.75 Conclusions A single dose of pegfilgrastim is as effective as daily G-CSF for supporting the hyper-CVAD chemotherapy regimen.

Abstract For the prevention of TA-GHVH in patients who received a allogeneic stem cell transplant is mandatory the gamma irradiation of the all cellular blood components. This irradiation is usually done with Cesium 137 and with a special blood bank irradiators. However these devices are expensive; because that, in developing countries, is frequent the utilization of Cobalt 60 and the same device that is used in the radiotherapy department, instead of blood bank irradiators. We present our experience with this technique. From Dec 2002 to Dec 2005 thirty patients received a allogeneic stem cell transplant and 28 were analysed. The stem cells source was: peripheral blood 25, unrelated cord blood 2, and bone marrow 1. The irradiation of the blood was performed with Cobalt 60–1.24 Mev- (theratron 780 C); the irradiation field was calculated for covering all of the bag surface and a dose of 3.5 Gy was administered to the mild plane of the bag. 158 blood concentrates were transfused, 68 red cell (X:2.5 per patient), and 90 platelets (3.2 per patient). The pre transfusion median hemoglobin and platelet levels were 7.63 g/dl and 12.000/ul; after transfusion was a median increase of 2.3 gm/dl (0.6–4.7) in hemoglobin and 18.000/ul (0–140.000) in platelets. There was no any case of TA-GVHD. Four patients developed pos transplant aGVHD, in all of the cases the disease began 50 days or more after the last transfusion, there were no pancytopenia and the aGVHD was resolved completely with the treatment. Conclusion In receptors of allogeneic stem cell transplant the gamma irradiation of blood components with Cobalt 60 and with the same device which is used for patients radiotherapy is 100% effective and safe in the prevention of TA-GVHD. This is a good alternative in centers without blood bank irradiator

Abstract BACKGROUND: Impact of Plerixafor (P) mobilized stem cells on immune reconstitution of autologous stem cell transplant (ASCT) patients has not been established. Early lymphocyte recovery (Absolute lymphocyte count of > 1 K/uL at day 30 after transplant) has been established to predict outcomes in multiple myeloma (MM) patients. The purpose of this study was to evaluate lymphocyte recovery in MM patients who underwent ASCT with stem cells mobilized with G-CSF vs G-CSF+P. Secondary objective was to evaluate the survival outcomes. METHODS: This is a retrospective analysis of MM patients who underwent first ASCT between 2008 and 2016 with either G-CSF or G-CSF+P mobilization at Karmanos Cancer Institute in Detroit, Michigan. Plerixafor was used per institutional guidelines when the peripheral CD-34+ve cell-count was < 20/ uL on day 5 of G-CSF mobilization. 610 total patients were identified. Mobilization agents used were G-CSF alone (n= 469) or G-CSF+P (n= 141). All patients underwent transplant after Melphalan (M) conditioning and dose of M was at treating physician's discretion (140 vs 200 mg/m2). The primary endpoint was the Absolute Lymphocyte Count at day 30 (ALC30). Secondary endpoints were PFS and OS Univariable and multivariable Cox proportional hazards regression models were fit to assess associations between ten pre chosen predictors( age, race, stage at diagnosis, doublet vs. triplet therapy, lines of treatment, disease status, mobilization agents, melphalan dose, ALC at day 30, post- transplant maintenance) and survival benefit (PFS and OS). RESULTS: Median age of patients was older in G-CSF+P group (62 vs 60 years, p=. 006) and they were more likely to receive triplet therapy (82 vs 72%, p=. 015) for induction compared to G-CSF group (Table 1). Patients in G-CSF group were more likely to receive greater than one line of treatment before transplant (p=. 006). Disease status at transplant was similar between the two groups. G-CSF patients received higher dose of M (at 200mg/ m2) more frequently (69 vs. 58%, p = 0.010) and median cell dose infused was higher in G-CSF group (3.19 vs 2.88 x106 CD 34+ve-cells/Kg, p= 0.001). Primary endpoint, ALC30, was 1.3 K/uL(.1-4.5) and 1.2 K/uL(.1-5.1) for G-CSF and G-CSF+P, respectively (p=. 608). Median day to neutrophil recovery were similar in both groups (ANC of 500 at Day 12). Post-transplant maintenance use was similar between the two groups. The median PFS was 2.46 years (95% CI, 2.14 to 3.15) and 2.77 years (95% CI, 1.99 to 3.27) for G-CSF and G-CSF+P, respectively (HR: 1.128; 95% CI, (.843-1.509); p=. 417) (Figure 1). The median OS was 6.09 years (95% CI, 4.55 to NR) and 3.73 years (95% CI, 3.20 to NR) for G-CSF and G-CSF+P, respectively (HR: 1.638; 95% CI, (1.118-2.399); p=. 011) (Figure 2) .In MVA, higher stage at diagnosis, less than PR before ASCT, and no post-transplant maintenance therapy were associated with worse PFS and OS. More lines of treatment adversely impacted PFS. Use of G-CSF+P for mobilization and Melphalan dose ≤ 200-mg/ m2 adversely impacted OS. ALC30 did not impact PFS or OS in MVA. There were no significant differences in causes of death among the 2 groups. CONCLUSIONS: In this large, retrospective analysis of MM patients mobilized with G-CSF vs G-CSF + P, there was no significant difference in lymphocyte recovery. Higher Melphalan dose resulted in improved OS in the MVA. There was an overall survival difference favoring the G-CSF group, however, differences in baseline characteristics not accounted for in the MVA may be responsible for this observation. A Prospective study comparing these mobilization regimens including patients with similar baseline characteristics is necessary to confirm this finding. Disclosures Deol: Kite Pharmaceuticals: Consultancy; Novartis: Consultancy.

Background: Hemophagocytic lymphohistiocytosis [HLH], is a rare life-threatening syndrome of excessive immune activation. It can be primary due to genetic predisposition or secondary due to infections, immune disorders or malignancies. With nonspecific clinical presentation, a high index of suspicion is required to make the diagnosis. Prompt treatment of underlying etiology and HLH specific therapy is warranted to prevent adverse clinical outcome. Methods: After IRB approval, we conducted a retrospective chart review of adult patients (pts) ≥ 18 years diagnosed with HLH between January 1st, 2010 and June 30th, 2019. We recorded age at diagnosis, gender, cause of HLH, symptoms, laboratory testing, bone marrow pathology, imaging, treatment and outcome. Results: We found a total of 15 patients in the time interval. Pt age ranged from 22 to 64 years with a median of 46 years. 60% were females and 40% were males. 14 pts had secondary HLH and one pt tested positive for HLH gene mutations. Etiology of HLH was malignancy in 6 (40%), infection in 5 (33%), rheumatological disease in 3 (20%) and cause was unclear in one pt but suspected to be an infection. One pt had prior allogenic stem cell transplant and one pt developed HLH even after completion of treatment for lymphoma. On presentation, 14 (93%) had fever, 6 (40%) had respiratory symptoms, 6 (40%) had neurological symptoms, 2 (13%) had a skin rash, 2 (13%) had bleeding manifestations and 3 (20%) required pressor support. Hemoglobin ranged from 5.5 to 13.3 g/dL on presentation, with median of 10.1 g/dL and 14 (93%) had Hb <9 g/dL. Absolute neutrophil count ranged from 0.3 to 16.94 x 103/uL with median of 2.87x103/uL and decreased to < 1000x103/uL in 11 (73%) and < 500x103/uL in 7 (46%). Platelet counts on presentation ranged from 18 to 244x103/uL with median of 82x103/uL and decreased to <100x103/uL in 14 (93%) and <20x103/uL in 8 (53%). 14 (93%) had bicytopenia. Initial ferritin levels ranged from 1,552 to 2,62,080 ng/ml with median of 5,515 ng/ml and increased to >10,000 ng/ml in 10 (66%) and highest level was 4,57,970 ng/ml. All 15 pts had some degree of hepatic dysfunction and one pt had acute kidney injury. Triglyceride levels were >265 mg/dL in 6 (40%). 10 (66%) had laboratory evidence of disseminated intravascular coagulation (DIC), one pt had clinical DIC. Blood cultures were negative in everyone, except 2 pts who developed infection during the hospital course, one with Candida krusei and the other with methicillin sensitive staphylococcus aureus. Bone marrow biopsy was performed in 14 (93%) and all of them demonstrated hemophagocytosis. 3 (20%) underwent lumbar puncture and 2 had elevated CSF protein. 11 (73%) had immunological testing and all of them had elevated soluble IL-2 receptor alpha (sCD25 or sIL-2R). Of the 3 pts who had HLH genetic testing, one had HLH associated mutations. Organomegaly was noted in 11 (73.3%) (4 had hepatosplenomegaly, 6 had splenomegaly, one had hepatomegaly). 6 (40%) had lung infiltrates. MRI brain was done in 5 (33%) and 2 had patchy hyperintensities. 11 (73.3%) were treated with HLH-94 protocol with etoposide and dexamethasone. One pt had matched unrelated donor Allogenic stem cell transplant. 13 (86.6%) had initial recovery. At the time of data cut off, 10 (66%) were alive. Of the 3 pts who initially recovered, one pt died of relapsed lymphoma, one died of HLH relapse and one developed Clostridium difficile infection with bowel perforation. [Refer to Table 1]. Conclusion: Even though literature suggests that malignancy associated HLH has a worse prognosis, our small series did not suggest that. We also noted that HLH associated with rheumatological diseases leads to a superior outcome if the underlying disease is adequately treated. The most significant finding in our series was a patient with diffuse large B cell lymphoma who was diagnosed to have primary HLH with HLH associated mutations. Typically, primary HLH presents in the first few years of life. This patient case points to the fact that patients with primary HLH can have a late presentation and can also be associated with immunological disorders with a predisposition to malignancy. This finding suggests that all patients diagnosed with HLH should have genetic testing done for HLH associated mutations, as this will impact treatment decisions and these patients will benefit from more intense treatment which may include an allogenic stem cell transplant. Disclosures No relevant conflicts of interest to declare.

Abstract Abstract 2839 Patients affected by low-risk essenthial thrombocythosis (ET) may develope thrombotic/haemorragic events at a lower rate compared to high-risk ET patients. So far, it has not be possible to identify useful markers to predict which of these patients are more likely to have an event. Previous authors [Carobbio A et al, Blood 2007] have shown that leukocytosis at diagnosis is associated with a high hazard risk (HR) of developing a thrombotic event, while high platelets count is not. Subsequently other authors [Gangant N et al, Cancer 2009] have contradicted this findings and instead shown that in low-risk ET, the increase in leukocyte count over time correlates with thrombotic events [Passamonti F et al ISTH 2009]. For these reasons we decided to evaluate risk parameters in a dynamic manner with the aim of identifying those patients who are more likely to have an event and might benefit from preventive treatment. We performed a large multicentre retrospective study that included several North Italian Haemathology centres and a large Austrian university hospital. Patient data was analysed using random effect linear regression model and a dedicated Cox model with dynamic proportional risk. We studied 136 patients with low risk ET. Out of those, 45 had a thrombotic/haemorragic event and 91 never had an event (events included: stroke, TIA, IMA, PE, PAD, epystaxis and gastrointestinal bleeding). Overall, the median age was 42 years (IQR 20; range 18–60), the median Hb was 14.0 g/dL (IQR 2.3; range 4.4–18), the median WBC was 8.1 ×103/Â μL (IQR 3.3; range 3.3–23.8), the median PLT was 701 ×103/ÂL (IQR 404; range 206–1806). Gender was M 33% (n=45), F 67% (n=91); smokers were 24% (n=18/N=74); hypercholesterolemia was 18% (n=17/N=92). The FBCs of both groups were recorded from the date of diagnosis (entry time) and up to 3 years of follow up or to the development of a thrombotic/haemorragic event (exit time). A total number of 1294 FBCs were provided by the group with event and compared to a total of 4487 FBCs from the group without event. The follow-up Hb values showed a decreasing linear pattern linear from baseline values. The PLT-count showed a trend similar to Hb over the period of follow-up in both the group without events and in the group with events. The WBC showed a decrease during follow-up in the group with events and an increase in the group without events. Surprisingly, the risk of developing an adverse event after 60 months of follow-up was reduced by 20% for each increase of 1 g/dL Hb (p =0.007), was increased by 8% for each WBC increase of 1 103/uL (p =0.026) and was decreased by 6% for each PLT increase of 100 × 103 /uL (p =0.434). No differences were seen between venous or arterious thrombotic events (Log rank test, p=0.842). In conclusion, this study confirms that baseline FBCs values are not predictive of events within the ET low risk group. The emerging new finding is that the risk of developing an event is higher when Hb is reduced. This strongly suggests a protective role of Hb in the low-risk ET group. Previous studies have shown that red cells might store and generate nitric oxide (NO), a key endothelial modulator [Kim-Shapiro DB et al 2006]. The presence of NO would keep PLT in resting state, would reduce endothelial cell adhesion and in turn reduce thrombosis rate. However this needs to be confirmed. Disclosures: Steurer: Amgen: Consultancy, Honoraria. Pizzolo:Hoffmann-La Roche: Consultancy, Honoraria.

Abstract Background: Low-risk myelodysplastic syndrome (LR-MDS) is a heterogeneous group of diseases characterized by dysplastic ineffective hematopoeisis and risk for acute myelogenous leukemia (AML). Despite improved risk classification, LR-MDS subgroups exhibit outcome heterogeneity. Non-hemopoeitic comorbidities highlight interaction of organ dysfunction and adverse outcomes. Previous studies have identified association between smoking and development of MDS (Du Y. Leuk Res. 2010). Among others, smoking induces DNA double strand breaks (Huang et al, 2012) and gene methylation modification leading to impaired environmental chemicals detoxification. In this study, we analyze the clinical impact of smoking and intensity of exposure on LR-MDS outcome. Methods: With prior IRB approval, 90 LR-MDS patients from the Michael E. DeBakey VA Medical Center cancer registry were analyzed between 2000-2012. Smoked pack-years (PY) was recorded according to accepted definition. PY estimate derived from Framingham heart study (Mannan H et al., Heart International. 2010) was used to evaluate smoking dose-dependent correlation with survival in: (1) non-smoker [NS], (2) <20, (3) >20-39, and (4) >40 PY. Univariate and multi-variable analysis evaluated the impact of potential confounding variables such as degree of cytopenia at disease initiation, blast count, karyotype, and R-IPSS score. Results: 69 (76%) and 22 (24%) pts were smokers and NS. Median age was 71 years (y) (range, 55-84) and 73 y (60-87), for smokers and NS, P=0.38. 22 (24%), 35 (38%) and 34 (37%) of pt were very low, low, and intermediate risk R-IPSS. Median hemoglobin, ANC, and platelet levels among smokers and NS were 9.4 g/dL vs 8.8 g/dL (P=0.18), 2.7 K/uL vs 3.2 K/uL (P=0.13) and 118 K/uL vs 158 K/uL (P=0.11). Median absolute R-IPSS score for smokers and NS were 0.5 (range, 0-1.5) and 0.25 (range, 0-2), P=0.40. OS in smokers vs NS was 728 vs 1877 days (d), P=0.04, 95% CI= 1.015 to 2.923 (Fig. 1). 65/71 (92%) pt contributed to analysis of cumulative effect of smoking on OS. Given the lack of significant survival difference among pt with >20-39 and >40 PY, 3 distinct subgroups were identified showing a median OS of 2117, 1020 and 717 d, for NS, <20 and >20 PY, respectively, P=0.01 (Fig. 2). Univariate and multivariate analysis revealed no impact of blast count, depth of cytopenias, karyotype, and R-IPSS on observed outcomes. Conclusions: Our study suggests a mechanistic link between smoking and adverse outcome in LR-MDS. Higher cumulative smoking exposure is potentially associated with worse OS. Larger studies involving LR-MDS pt with smoking history are necessary to confirm this association. Further research is needed to clarify underpinning mechanisms resulting in unfavorable smoking-induced LR-MDS phenotype. This could facilitate implementation of MDS directed therapy in subgroups with more aggressive outcome. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Abstract Autologous stem cell transplantation (SCT) is a potentially curative procedure for patients with relapsed lymphoma (NHL). Over 60% of the cases arise in adults over 60 years of age. We retrospectively analyzed the outcomes of patients &gt;60 years old who received high dose busulfan (Bu) and cyclophosphamide (Cy) and autologous SCT for NHL. Stem cells were mobilized with G-CSF with or without chemotherapy. Patients received a dose-adjusted regimen of Bu 0.8 mg/kg IV (n=17) or 1mg/kg po (n=9) q 6 hours x 14 doses starting on Day -7 and Cy 60 mg/kg IV q day on days -3 and -2. In overweight patients, IV Bu doses were calculated based on ideal body weight and oral Bu doses and Cy doses were calculated on an adjusted body weight. All patients were treated as inpatients and received our usual supportive care including transfusion support, pneumocystis prophylaxis, antiviral prophylaxis, growth factor support and broad-spectrum antibiotic coverage for febrile neutropenia. 26 consecutive patients &gt; 60 with relapsed NHL underwent autologous SCT at Massachusetts General Hospital between 1995 and February 2005. The median age of the population was 66 (range 60–78) years. 17 (65%) of the 26 patients were females. 15 patients had large cell lymphoma, 2 immunoblastic lymphoma, 3 follicular lymphoma, and 6 mixed small cleaved cell and large cell. All patients had recurrent disease; 7 patients were in a CR and 19 patients in a PR at the time of transplant. The median time from diagnosis to transplant was 32 months. All patients engrafted. The median time to absolute neutrophil count &gt; 500/uL was 10 days (range 9–11) days. The median time to platelet count &gt; 50,000/uL unsupported was 15 (range 12–39) days. The 100-day transplant related mortality was 0%. Patients experienced the following serious toxicities: interstitial lung disease (n=1), seizures in a patient with CNS lymphoma (n=1), venoocclusive disease which resolved (n=2), and transient atrial fibrillation (n=3). With a median follow-up of 22 months (range 4 months–9.5 years), the two year overall survival is 63% and two year progression-free survival is 42%. Six patients above the age of 70 years have been transplanted. 100-day transplant related mortality was 0%. With a median follow up of 25 months, all 6 patients are alive and 3 of 6 are progression free. In conclusion, 1) Bu/Cy is a well-tolerated conditioning regimen for patients with NHL above the age of 60 years, including selected patients over the age of 70; 2) Age alone should therefore not be used as an exclusion criterion for autologous SCT.

Abstract Autologous stem cell transplantation is curative for many patients with hematologic malignancies. Approximately 20% of patients do not have an adequate stem cell mobilization. Recently, work from our laboratories has shown that parathyroid hormone (PTH) increases osteoblast number and expansion of the stem cell compartment in mice. In murine models, the addition of PTH caused an increase in the absolute number of stem cells. Daily PTH injection caused an increase in the absolute number of murine stem cells and improved survival in transplant recipients of limiting numbers of stem cells. (Nature425: 841, 2003). This observation suggested that PTH might be able to increase stem cell numbers in humans. PTH is an FDA approved drug used for treatment of osteoporosis. In this Phase I study, patients who have collected less than 2 million CD34+ cells/kg after 1 or 2 stem cell mobilization attempts received 14 days of sc PTH, in escalating dose cohorts of 40 mcg, 60 mcg, 80 mcg, and 100 mcg per day, with G-CSF 10mcg/kg/day for the last four days. Patients with >5 CD34+/uL on Day +14 proceeded to stem cell apheresis and autologous stem cell transplant. 14 patients have enrolled on this study, now enrolling at the highest dose cohort, and 12 patients have completed treatment for this analysis with 3 patients per dose cohort. The median age was 57 years (range 24–71 years), and 9 (75%) patients are female. In 10 patients (83%) one attempt at stem cell mobilization failed with either growth factor alone or growth factor plus chemotherapy; in the other 2 patients (17%) two attempts at mobilization failed to attain adequate cells. The diagnoses were as follows: non Hodgkin’s lymphoma (7 patients, 58%), Hodgkin’s disease (5 patients, 42%). There were no dose limiting toxicities defined as calcium > 11.5, ionized calcium > 1.5, phosphate <1.0, or systolic blood pressure less than 80mm Hg. 3 patients had a self-limited fever, one patient had an unexplained eosinophilia, and 1 patient required an admission with fever, rigors, and headache. 6 of 12 patients (50%) achieved the target peripheral CD34 level of 5/uL, of whom 4 underwent stem cell apheresis. The median CD34 cells/uL on Day +14 was 4.3 (range 0–18.8). 2 patients who achieved the target peripheral CD34 level of 5/uL did not complete collections, 1 due to access problems, and 1 due to physician preference. The 4 patients who continued with the study collected a median CD34+ dose/kg of 2.2 x 106 (range 0.9–2.7) from stem cell apheresis with a median of 2 collections (range 1–4). These 4 patients proceeded to autologous stem cell transplant, with median days to neutrophil and platelet engraftments of 11 (range 10–12) and 14 (range 12–19), respectively. In conclusion, 1) PTH is well tolerated in this population, even at a dose of 100 mcg; 2) PTH plus G-CSF may be effective in patients that fail primary or secondary stem cell mobilization attempts; 3) PTH plus G-CSF should be tested in a larger Phase II study to improve donor stem cell yield. Future directions may also include the use of parathyroid hormone to improve engraftment efficiency in settings of low stem cell dose such as adult cord blood transplantation.

Background: Autologous stem cell transplantation (ASCT) performed early in the disease course or at first relapse leads to improved progression-free and overall survival in transplant-eligible patients with multiple myeloma (MM). Filgrastim, a recombinant granulocyte colony-stimulating factor (G-CSF), when used after ASCT has been shown to accelerate time to neutrophil engraftment (TNE), and in some studies, it has been associated with reduced length of hospitalization, infectious complications, and antibiotic use. Strategies that reserve G-CSF administration to when neutrophil recovery is delayed, have attempted to show that there is no difference in infectious complications, length of hospitalization or TNE when compared to early administration of G-CSF on the day after stem cell infusion (DOT). However, the optimal timing for administering G-CSF has not yet been determined in patients with MM undergoing ASCT. Methods: This is a retrospective, single-center analysis of patients with MM undergoing ASCT from mobilized peripheral blood stem cells. Patients enrolled in a clinical trial of high-dose lenalidomide and melphalan as conditioning therapy which mandated the administration of filgrastim from day +1 after DOT (Lenalidomide Plus Melphalan as a Preparative Regimen for Autologous Stem Cell Transplantation in Relapsed Multiple Myeloma, NCT01054196) were assigned to the early strategy group (ES). Patients receiving filgrastim as per our institutional guideline (starting on day +12 if ANC < 1000 cells/uL, or at the physician's discretion) were included in the delayed strategy group (DS). Patients were excluded from the analysis if their conditioning regimen included a different agent other than melphalan or lenalidomide. DOT was defined as the day of stem cell infusion. Date of neutrophil engraftment was defined as the first of three consecutive days with an ANC ≥ 500 cells/uL. TNE was calculated as the time from DOT to the date neutrophil engraftment. Total duration of neutropenia was defined as the time from onset of neutropenia (ANC < 500 cells/uL) to date of neutrophil engraftment. Length of hospitalization was defined as the time from DOT to the day of discharge. Results: We identified 59 patients in the ES group and 39 patients in the DS group from 08-16-2010 to 05-22-2019, for a total of 98 included in this analysis. Median age was 60 and 65 years in the ES and DS groups, respectively. Patients received a comparable dose of CD34+ cells, 5.05x106/kg in the ES group vs 4.66x106/kg in the DS group (p = 0.48). The ES group started filgrastim administration earlier (day +1 vs +9, p < 0.001) and received a greater median number of doses (10 vs 4, p < 0.001) as compared to patients in the DS group. Median time to neutrophil engraftment was shorter in the ES group compared to the DS group (10 vs 12 days, p < 0.001), as was the total duration of neutropenia (5 vs 6 days, p < 0.001). Documented infections were just as likely in both groups, 37% in the ES group and 39% in the DS group (p = 1). Length of hospitalization was shorter in the ES group as compared to the DS group (15 vs 17 days, p = 0.01). Discussion: Filgrastim use guided by an ES decreased the time to neutrophil engraftment, the duration of neutropenia and the length of hospitalization compared to a DS. Further analyses to identify predictive factors associated with a reduction in infectious complications and length of stay are underway, with the aim of developing a risk-adapted strategy for the use of filgrastim in patients with MM undergoing ASCT. Disclosures Van Besien: Miltenyi Biotec: Research Funding. Coleman:Kite Pharmaceuticals: Equity Ownership; Merck: Research Funding; Pharmacyclics: Speakers Bureau; Gilead, Bayer, Celgene: Consultancy, Research Funding, Speakers Bureau. Rosenbaum:Janssen: Research Funding; Honoraria Akcea: Other: Accordant Health. Rossi:Janssen, Celgene, Amgen: Consultancy; BMS: Research Funding. Niesvizky:Takeda, Amgen, BMS, Janssen, Celgene: Consultancy, Research Funding.

Abstract Telomeres, the terminal complex of hexameric repeats and shelterin protein of linear chromosomes, shorten with every mitosis. Telomere attrition is accelerated in patients with mutations in telomerase complex genes (Calado and Young, NEJM 2009) and with replicative stress, as in chronic bone marrow failure. Historically, male hormones were effective in some patients with aplastic anemia (AA), and case reports and retrospective observations have suggested hematologic improvement in patients with telomeropathies treated with male hormones. Exposure of normal lymphocytes and CD34+ cells to androgens increased telomerase activity in vitro, and in cells from individuals carrying loss-of-function TERT mutations to normal levels (Calado et al. Blood 2009). We have conducted a phase I/II single-center trial (www.clinicaltrials.gov NCT01441037) assessing the safety and the effect of male hormones on telomere attrition in patients with telomere disease. Entry criteria included age-adjusted mean telomere content ≤1%ile, ± identified mutations in telomerase complex genes, and low blood counts (hemoglobin <9.5g/dL, platelets <30,000/uL, or neutrophils <1,000/uL) and/or pulmonary fibrosis. Danazol, 800 mg/day, was administered for 2 years. Primary protocol objectives were safety and activity of danazol in slowing telomere attrition. Secondary endpoints were hematologic response at 3 and 6 months (increase in hemoglobin >1.5 g/dL or platelets >20,000/uL or neutrophils >500/uL). Twenty seven patients were enrolled, accrual commencing August 2011. Most patients had moderate (n=20) or severe (n=4) AA, one had myelodysplasia, and two pulmonary fibrosis. Median age was 41 years (range 17-66); 15 patients were females. There was only one severe adverse event possibly related to drug. Frequent reported symptoms were muscle cramping with dehydration and exacerbation of headaches. Changes in serum lipid profiles were observed in all patients, with increased serum LDL and decreased HDL. Severe elevation in liver enzymes was not observed. One death occurred on study, not treatment related (pneumonia in a pulmonary fibrosis case). Mean telomere content of leukocytes at enrollment was compared with mean telomere content at 6, 12, and 24 months on drug as well as available samples before starting danazol. Telomere attrition prior to protocol entry, determined by q-pcr, was estimated at loss of 227 bp/year (95% CI, 58-368bp; p=0.009). Androgen administration appeared to elongate telomeres: the average increase in telomere length at 6 months was 205 bp (95% CI, 82-329 bp; p=0.002), at 12 months 441 bp (95% CI, 263-620 bp; p=0.0001), and at 24 months 347 bp (95% CI, 87-607 bp; p=0.01). A similar trend of increase in mean telomere content with danazol was confirmed in flow-sorted lymphocytes. Hematologic response rate, as defined by protocol, was 67% at 3 months and 60% at 6 months. Nine of eleven patients who required RBCs became transfusion-independent; two of them also became platelet transfusion independent. Liver cirrhosis was present in 6 patients at enrollment; worsening of liver disease in one occurred with continued alcohol abuse. To date 8 patients have completed two years of danazol, all of them responders; 10 patients remain on danazol, and 9 patients stopped drug prior to 2 years. Blood counts in all patients have been stable with drug discontinuation, with median follow up of 258 days (range 31-335). In conclusion, male hormones are safe and efficacious in patients with inherited bone marrow failure associated with telomeropathies, producing clinically meaningful hematologic improvement. Increased mean telomere content in patients, suggests that in vitro demonstration of up-regulation by sex hormones of TERT and of telomerase enzymatic activity is the mechanism of action of androgens in vivo. To our knowledge, this is the first successful prospective effort to favorably modulate telomere length by pharmacologic intervention in humans. Sex hormones may be useful in other conditions of accelerated telomere attrition, as for example after chemotherapy, and other drugs and small molecules may be usefully screened for their effects on telomerase in vitro. Disclosures Off Label Use: we want to determine if treatment with male hormone danazol is safe and improves hematologic response as first-line treatment in patients with AA and telomere disease(www.clinicaltrials.gov NCT01441037)..

Dans les dernières années, un grand nombre d’inondations ont touché le Québec et ont eu des effets tant sur les populations que sur l’environnement bâti. Certaines populations sont d’ailleurs plus vulnérables aux impacts d’une inondation que d’autres. Pour évaluer cette vulnérabilité, deux dimensions peuvent être analysées, soit la sensibilité et la capacité à faire face. La capacité à faire face constitue souvent le maillon faible dans le processus d’évaluation de la vulnérabilité, en particulier lorsqu’on souhaite évaluer cette vulnérabilité sur un vaste territoire pour une échelle relativement fine. Parmi le nombre limité d’indicateurs disponibles de la capacité à faire face, la majorité concerne des indicateurs d’accessibilité et de proximité à des services. Ce manque de connaissances théoriques et pratiques sur la capacité à faire face rend l’analyse de la vulnérabilité incomplète étant donné qu’une population peut réduire sa vulnérabilité en améliorant sa capacité à faire face. Ainsi, ce mémoire vise à diversifier et proposer de possibles indicateurs de la capacité à faire face de la population québécoise aux inondations afin d’améliorer l’évaluation de la vulnérabilité de ces populations. Dans le but d’identifier ces indicateurs, une revue de littérature ainsi qu’un sondage auprès de professionnels du domaine de la sécurité incendie, des mesures d’urgence, de l’aménagement du territoire et autres s’appuyant sur la méthode de la cartographie conceptuelle ont été réalisés. À terme, les résultats du sondage ont permis d’identifier les indicateurs qui semblent déterminants pour la capacité à faire face aux inondations. Parmi ceux-ci, on retrouve la proportion d’espaces verts, le taux de possession automobile, la mise en place d’un plan de mesures d’urgence et d’un système d’alerte, la désignation d’un coordonnateur en mesures d’urgence, etc. Nos recherches ont toutefois démontré que certaines données nécessaires à l’élaboration de ces indicateurs sont indisponibles, inexistantes ou confidentielles. Ce mémoire met ainsi en évidence la pertinence d’approfondir la réflexion à ce sujet et de diversifier les indicateurs de la capacité à faire face aux inondations.
Dans les dernières années, un grand nombre d’inondations ont touché le Québec et ont eu des effets tant sur les populations que sur l’environnement bâti. Certaines populations sont d’ailleurs plus vulnérables aux impacts d’une inondation que d’autres. Pour évaluer cette vulnérabilité, deux dimensions peuvent être analysées, soit la sensibilité et la capacité à faire face. La capacité à faire face constitue souvent le maillon faible dans le processus d’évaluation de la vulnérabilité, en particulier lorsqu’on souhaite évaluer cette vulnérabilité sur un vaste territoire pour une échelle relativement fine. Parmi le nombre limité d’indicateurs disponibles de la capacité à faire face, la majorité concerne des indicateurs d’accessibilité et de proximité à des services. Ce manque de connaissances théoriques et pratiques sur la capacité à faire face rend l’analyse de la vulnérabilité incomplète étant donné qu’une population peut réduire sa vulnérabilité en améliorant sa capacité à faire face. Ainsi, ce mémoire vise à diversifier et proposer de possibles indicateurs de la capacité à faire face de la population québécoise aux inondations afin d’améliorer l’évaluation de la vulnérabilité de ces populations. Dans le but d’identifier ces indicateurs, une revue de littérature ainsi qu’un sondage auprès de professionnels du domaine de la sécurité incendie, des mesures d’urgence, de l’aménagement du territoire et autres s’appuyant sur la méthode de la cartographie conceptuelle ont été réalisés. À terme, les résultats du sondage ont permis d’identifier les indicateurs qui semblent déterminants pour la capacité à faire face aux inondations. Parmi ceux-ci, on retrouve la proportion d’espaces verts, le taux de possession automobile, la mise en place d’un plan de mesures d’urgence et d’un système d’alerte, la désignation d’un coordonnateur en mesures d’urgence, etc. Nos recherches ont toutefois démontré que certaines données nécessaires à l’élaboration de ces indicateurs sont indisponibles, inexistantes ou confidentielles. Ce mémoire met ainsi en évidence la pertinence d’approfondir la réflexion à ce sujet et de diversifier les indicateurs de la capacité à faire face aux inondations.

Au Québec, l’implication féminine dans les accidents routiers avec blessés évolue et les raisons associées à ces changements doivent être mises en lumière afin de mieux cibler les interventions gouvernementales en matière de sécurité routière. Ce mémoire présente un portrait évolutif différencié selon le sexe de l’accidentologie québécoise pour deux périodes d’étude, 1990-1992 et 2007-2009. Les données proviennent du ministère des Transports (MTQ) et de la Société d’assurance automobile du Québec (SAAQ). Les résultats présentent, principalement par l’évolution du nombre de titulaires de permis de conduire, une augmentation de la présence féminine sur les routes du Québec et dans le bilan routier. On dénote également une diminution globale de l’implication des conducteurs québécois dans les accidents corporels, cette diminution étant plus faible chez les femmes. L’analyse des relations entre le sexe et les caractéristiques des accidents et les modèles de régression démontrent que le sexe demeure un déterminant en accidentologie. Mots-clés : Accidents; Conducteurs; Sexe; Femmes; Implication accidentelle; Sécurité routière; Victimes
The growing presence of women on the roads of Quebec is important and needs to be explored. Women's crash involvement is changing and the reasons associated must be highlighted in order to better target government road safety interventions. This analysis is an evolving portrait differentiated according to gender of the Quebec accidentology for two periods, 1990-1992 and 2007-2009. Data used in this study come from the Ministère des transports (MTQ) and the Société d'assurance automobile du Québec (SAAQ). The results present, mainly by the growth in the number of licence holders, an increase in the women’s presence in road safety records. Also, it reflects an overall decrease of the driver’s involvement in crash with injuries, this decrease being lower among women. Analysis of the relationship between sex and the accident characteristics and regression models demonstrate that sex remains a determinant in accidentology. Keywords : Crashes; Drivers; Sex; Women; Crash involvement; Road safety; Victims

Malgré d’abondantes recherches sur le pergélisol au Nunavik, les sols polygonaux et la fissuration thermique du sol, aucune étude n’a encore été réalisée concernant la distribution spatiale de la fissuration active du sol par le gel et sur les sols polygonaux. Cette étude évalue l’activité de fissuration par le gel des polygones à fissures de contraction thermique sous les conditions climatiques actuelles et l’impact des paléoclimats froids de l’Holocène sur la répartition des polygones à travers les différentes zones bioclimatiques du Nunavik. Des milliers de photographies aériennes géoréférencées (n= 80 737) ainsi que les images satellitaires disponibles et accessibles via le logiciel ArcMap d’Esri (264 504,14 km²) ont été analysés afin de dresser un inventaire des polygones de toundra du Nunavik. Au total, 4 567 réseaux polygonaux ont été inventoriés. Pour chaque site répertorié, l’arrangement géométrique (par exemple : réseaux ouverts, fermés ou sans structure organisée), les angles d’intersection, les ordres de fissuration, le type de bombement et de bourrelets (plats, à centre surélevé, etc.), la nature du dépôt de surface affecté et la nature de la végétation dominante ont été notés et enregistrés dans une base de données. Les résultats et la modélisation des conditions de fissuration indiquent que les réseaux polygonaux actuellement actifs sont localisés au-delà du 60e parallèle Nord dans les dépôts organiques ou sur les terrasses sablonneuses recouvertes par un dépôt organique. Les tests statistiques effectués sur notre échantillon (n= 4 567) ont démontré qu’il existe une forte relation de covariance entre la nature du dépôt et les différents angles formant les réseaux. Il existe une prépondérance des réseaux orthogonaux (90°) sur les terrains plats ouverts où les contraintes thermo-mécaniques sont spatialement réparties de façon homogène dans le sol. Lorsque la topographie locale irrégulière engendre des flux de chaleur inégaux et des contraintes thermo-mécaniques hétérogènes, forçant un patron de fissuration irrégulier, le réseau tend à former un patron hexagonal (120°).
Malgré d’abondantes recherches sur le pergélisol au Nunavik, les sols polygonaux et la fissuration thermique du sol, aucune étude n’a encore été réalisée concernant la distribution spatiale de la fissuration active du sol par le gel et sur les sols polygonaux. Cette étude évalue l’activité de fissuration par le gel des polygones à fissures de contraction thermique sous les conditions climatiques actuelles et l’impact des paléoclimats froids de l’Holocène sur la répartition des polygones à travers les différentes zones bioclimatiques du Nunavik. Des milliers de photographies aériennes géoréférencées (n= 80 737) ainsi que les images satellitaires disponibles et accessibles via le logiciel ArcMap d’Esri (264 504,14 km²) ont été analysés afin de dresser un inventaire des polygones de toundra du Nunavik. Au total, 4 567 réseaux polygonaux ont été inventoriés. Pour chaque site répertorié, l’arrangement géométrique (par exemple : réseaux ouverts, fermés ou sans structure organisée), les angles d’intersection, les ordres de fissuration, le type de bombement et de bourrelets (plats, à centre surélevé, etc.), la nature du dépôt de surface affecté et la nature de la végétation dominante ont été notés et enregistrés dans une base de données. Les résultats et la modélisation des conditions de fissuration indiquent que les réseaux polygonaux actuellement actifs sont localisés au-delà du 60e parallèle Nord dans les dépôts organiques ou sur les terrasses sablonneuses recouvertes par un dépôt organique. Les tests statistiques effectués sur notre échantillon (n= 4 567) ont démontré qu’il existe une forte relation de covariance entre la nature du dépôt et les différents angles formant les réseaux. Il existe une prépondérance des réseaux orthogonaux (90°) sur les terrains plats ouverts où les contraintes thermo-mécaniques sont spatialement réparties de façon homogène dans le sol. Lorsque la topographie locale irrégulière engendre des flux de chaleur inégaux et des contraintes thermo-mécaniques hétérogènes, forçant un patron de fissuration irrégulier, le réseau tend à former un patron hexagonal (120°).
Despite abundant research in Nunavik on permafrost, ice-wedge polygons and ground thermal cracking, no study has yet been addressing the spatial distribution of active frost cracking and of thermal contraction crack polygons. To fill that knowledge gap, this study evaluates the spatial distribution of actively cracking polygons under the current climate conditions across the different bioclimatic zones of Nunavik. The study also assesses the importance of cold Holocene climate episodes for the formation of polygonal networks over the territory. Thousands of geo-referenced aerial photographs (80 737) and Esri satellite images (264,504.14 km²) were analyzed to conduct an extensive inventory of Nunavik's tundra polygons. A total of 4,567 polygonal networks were inventoried. For each identified site, the arrangement (e. g. open, closed or unorganized networks), intersections (angles), cracking orders (primary, secondary and tertiary cracks), type of bulge and rims (flat, high-centred, low-centred), the affected surficial geological materials and the vegetation cover were noted and compiled in a database. Mapping of the results and modelling of cracking conditions indicate that currently active polygonal networks are only present beyond 60°N, in the herbaceous tundra principally in organic soils, on raised beaches and on sandy organic-covered fluvial terraces. In addition, the statistical tests carried out on our sampled population showed that there is a strong dependency between the types of surficial deposits and the different angles forming the polygonal networks. Orthogonal polygons (90° intersection angles) dominate on flat terrains where the thermo-mechanical stresses are spatially homogenous and hexagonal polygons (120° intersection angles) are observed more likely on uneven terrain where local topography generates non-homogenous heat flows and uneven thermo-mechanical stresses in the ground, thus forcing a less regular cracking pattern
Despite abundant research in Nunavik on permafrost, ice-wedge polygons and ground thermal cracking, no study has yet been addressing the spatial distribution of active frost cracking and of thermal contraction crack polygons. To fill that knowledge gap, this study evaluates the spatial distribution of actively cracking polygons under the current climate conditions across the different bioclimatic zones of Nunavik. The study also assesses the importance of cold Holocene climate episodes for the formation of polygonal networks over the territory. Thousands of geo-referenced aerial photographs (80 737) and Esri satellite images (264,504.14 km²) were analyzed to conduct an extensive inventory of Nunavik's tundra polygons. A total of 4,567 polygonal networks were inventoried. For each identified site, the arrangement (e. g. open, closed or unorganized networks), intersections (angles), cracking orders (primary, secondary and tertiary cracks), type of bulge and rims (flat, high-centred, low-centred), the affected surficial geological materials and the vegetation cover were noted and compiled in a database. Mapping of the results and modelling of cracking conditions indicate that currently active polygonal networks are only present beyond 60°N, in the herbaceous tundra principally in organic soils, on raised beaches and on sandy organic-covered fluvial terraces. In addition, the statistical tests carried out on our sampled population showed that there is a strong dependency between the types of surficial deposits and the different angles forming the polygonal networks. Orthogonal polygons (90° intersection angles) dominate on flat terrains where the thermo-mechanical stresses are spatially homogenous and hexagonal polygons (120° intersection angles) are observed more likely on uneven terrain where local topography generates non-homogenous heat flows and uneven thermo-mechanical stresses in the ground, thus forcing a less regular cracking pattern

Partout en Côte d’Ivoire, la juxtaposition de la vulnérabilité sociale et des milieux naturels et artificiels favorisant la prolifération des moustiques, augmentec onsidérablement le risque de contracter le paludisme. Mais à l’échelle locale la transmission du paludisme peut significativement varier d’un espace à un autre. Ainsi, la mise en évidence d’un patron spatial qui permettra d’expliquer cette variation, s’avère nécessaire pour affiner la stratégie de lutte contre le paludisme à l’échelle locale. C’est dans cette logique que l’expertise géographique des questions de santé intervient au travers de cette étude pour identifier les caractéristiques biogéographiques, microclimatiques, topographiques, comportementales et socioéconomiques en lien avec la morbidité du paludisme à l’échelle des quartiers de M’Bahiakro, une petite ville située au centre de la Côte d’Ivoire en Afrique de l’Ouest. Pour ce faire, une image satellitaire Sentinel 2 à 10 m de résolution spatiale a été utilisée pour classifier l’occupation du sol. Des images Landsat 8 OLI/TIR (30 m) ont servi à estimer les paramètres microclimatiques en lien avec le développement des gîtes larvaires de moustiques dont la température de surface (TS) et l’indice TVDI (Temperature/Vegetation Dryness Index) de l’humidité de surface. La topographie de M’Bahiakro a pu être mise en évidence après le traitement d’un modèle numérique de terrain provenant de la base de données topographique GMTED 2010 (Global Multi Resolution ElevationData 2010). En plus, une régression logistique a permis d’estimer le poids du comportement des populations dans la transmission du paludisme à M’Bahiakro. L’analyse de l’occupation du sol et des paramètres microclimatiques et topographiques montre que tous les quartiers de M’Bahiakro sont soumis à un risque très élevé de prolifération de moustiques vecteurs du paludisme. Par ailleurs, une bonne corrélation positive a été observée entre la morbidité déclarée de paludisme et la proportion d’utilisation des moustiquaires imprégnées d’insecticides. Ces résultats tendent à indiquer que la variabilité spatiale du paludisme à M’Bahiakro est régie par le comportement des populations vis-à-vis du paludisme.

Ce projet de recherche, mené près d’Umiujaq (Nunavik), a été réalisé afin de documenter les processus gravitaires dominants qui se manifestent sur les versants escarpés de la vallée Tasiapik. Des relevés topographiques, granulométriques, morphométriques, pétrographiques et de végétation ont permis de caractériser 18 talus d’éboulis situés sur les versants sud-ouest et nord-est. Les résultats obtenus ont permis d’établir que l’éboulisation importante sur les versants de la vallée est un phénomène à la fois ancien, engendré par des processus paraglaciaires, et récent, résultat de processus périglaciaires toujours actifs aujourd’hui. Cela se traduit notamment par différents stades de développement des talus d’éboulis subactuels, illustrés par certains dépôts de versant frais et d’autres très anciens, mais aussi avec des topographies de pente très variables. Sur une échelle de temps plus courte, entre août 2017 et juillet 2018, les avalanches se sont avérées être un processus majeur, tel qu’observé sur les 14 000 photographies obtenues grâce à trois caméras à déclenchement automatique installées à l’été 2017. Ces avalanches, souvent déclenchées par des chutes de corniches à neige, ont été particulièrement fréquentes au printemps 2018, résultant de conditions météorologiques propices telles qu’une hausse rapide des températures journalières et des épisodes de pluie abondante. Des dépôts d’avalanches sales témoignent d’une grande capacité érosive, et incidemment de leur grand apport en débris vers les talus d’éboulis. Dans certains cas, les dépôts d’avalanche avoisinaient la route située en contrebas, démontrant ainsi un risque potentiel pour ses usagers.
This research project was conducted near Umiujaq (Nunavik) to document the main gravitational processes that occur on the slopes of Tasiapik Valley. 18 talus slopes on the southwest and northeast sides of the valley were characterized using topographic, granulometric, morphometric petrographic and vegetation surveys. Results show that talus formation in the valley is an ancient phenomena, due to paraglacial processes, and recent - and still ongoing – periglacial processes. This is evidenced by different development stages among the talus slopes, with fresh and very old debris covering the slopes, as well as contrasting slope topographies. On a shorter and more recent time scale, from August 2017 to July 2018, snow avalanches have proven to be a major process, as observed on the 14,000 photographs obtained using three automatic timelapse cameras installed in the summer of 2017. Snow avalanches were often triggered by a collapsing snow-cornice and were very frequent in the spring of 2018 due to favourable meteorological conditions such as a rapid increase in daily temperatures and abundant rainfall events. Dirty snow-avalanche deposits have shown the great erosive capacity of these snow avalanches, thus their important debris supply toward the talus slopes. In some cases, runout zones were located only a few meters from the road below, thus showing the potential risk for people travelling on the road

Cette recherche en géopolitique a pour ambition d’analyser la situation sociopolitique particulière de l’Arctique canadien par le biais des représentations qu’elle engendre à différentes échelles. L’engouement actuel pour la zone arctique, en lien avec le réchauffement climatique, amène à repenser certaines stratégies, notamment la réglementation des espaces maritimes. Un différend oppose déjà les États-Unis au Canada dans la manière de percevoir les eaux arctiques, dont le célèbre passage du Nord-Ouest. En effet, en matière de statut, les premiers considèrent le Passage du Nord-Ouest comme un détroit international, les seconds comme des eaux intérieures canadiennes. Dans ce contexte, le Canada -qui ces dernières années ne cesse de revendiquer sa souveraineté sur ces eaux arctiques - doit aussi y assurer une certaine sécurité de navigation, au risque de perdre toute crédibilité en cas de problème maritime. Ainsi, mon analyse se focalise sur la navigation dans les eaux arctiques. Je renseigne d’abord celle-ci de manière tangible pour réfléchir ensuite à ses enjeux et conséquences pour le territoire arctique et sa mise en valeur. En termes d’aménagement, les acteurs interagissent avec le territoire en fonction des perceptions et représentations qu’ils ont de celui-ci et, réciproquement, le territoire se construit par le biais de ces représentations engendrées. Or, la mise en valeur du territoire arctique sous l’effet de la navigation témoigne d’un développement plutôt exogène et empreint de représentations fort diversifiées. Il convient alors de s‘interroger sur le contexte de formation des représentations grâce à une approche historique avant de traiter des risques et vulnérabilités de la navigation en tant que tels.
The aim of this geopolitics research is to analyze the particular sociopolitical situation of the Canadian Arctic using the representations it generates at different scales. The increasing interest in the Arctic zone, associated with a warming climate, makes us think back certain strategies, especially the regulation of maritime spaces. There is already a conflict between the United States and Canada in how the Arctic water is perceived, including the Northwest Passage, in terms of statute: international strait versus Canadian inland waters. In this context, Canada – which, over the past years, is continually claiming sovereignty over those Arctic waters – must also guarantee a safe navigation; otherwise it will lose credibility if any maritime problem occurs. Thus, my analysis focuses on navigation in Arctic waters. First, I give information about this navigation in a tangible way. Second, I broaden the study to what are the stakes and the consequences on the Arctic territory and its development. From a management perspective, stakeholders interact with the territory according to the perceptions and the representations they have of it and, vice versa, the territory is built by the means of these generated representations. However, the enhancement of the Arctic territory under the influence of navigation expansion shows rather exogenous development and the mark of extremely diversified representations. Finally, we will enquire into the context of structuring formation by means of a historical approach before discussing risks and vulnerabilities of navigation.

L’évolution de l’espace francophone du Grand Moncton au Nouveau-Brunswick, est, depuis 1960, le fruit de nombreuses luttes menées par les francophones aux niveaux culturel, politique, économique, social et linguistique. Ces luttes ont notamment permis l’ajout de postulats fondamentaux nécessaires au développement de la communauté de langue française et ont contribué à la diversification et l’enrichissement des espaces vécu et institutionnel ainsi que des liens supra régionaux de la communauté. Ces différents éléments ont directement influencé la zone d’influence francophone en milieu urbain qui, durant cette période, a pris de l’expansion. Malgré son développement constant depuis 1960, de nombreux défis attendent la communauté francophone du Grand Moncton toujours aux prises avec des taux d’assimilation élevés et l’absence de loi protégeant la langue d’affichage et de travail. La récente ouverture d’esprit de la communauté anglophone permettra néanmoins de relever ces défis dans un environnement plus favorable que celui des années 1960.

Mitsubishi Heavy Industries (MHI) G series gas turbine is the industry pioneer in introducing steam cooling technology for gas turbines. The first M501G unit started commercial operation in 1997 and to date, with 62 G units sold, MHI G fleet is the largest steam cooled fleet in the market. The existing commercial fleet includes 35 commercial units with more than 734,000 accumulated actual operating hours, and over 9,400 starts. Upgraded versions have been introduced in the 60 and 50Hz markets (M501G1 and M701G2 respectively). On a different arena, MHI is engaged since 2004 in a Japanese National Project for the development of 1,700°C (3092°F) class gas turbine. Several enhanced technologies developed through this Japanese National Project, including lower thermal conductivity TBC, are being retrofitted to the existing F and G series gas turbines. Retrofitting some of these technologies to the existing M501G1 together with the application of an F class air cooled combustion system will result in an upgraded air-cooled G class engine with increased power output and enhanced efficiency, while maintaining the same 1500°C (2732°F) Turbine Inlet Temperature (TIT). By using an open air cooling scheme, this upgraded machine represents a better match for highly cyclic applications with G class efficiency, while the highly reliable and durable steam cooled counterpart is still offered for more base-loaded applications. After performing various R&D tests, the verification process of the air cooled 60 Hz G gas turbine has moved to component testing in the in-house verification engine. The final verification test prior to commercial operation is scheduled for 2009. This article describes the design features and verification plan of the upgraded M501G gas turbine.

Gas bearings in microturbomachinery (MTM) offer significant system level benefits, such as improved fuel efficiency, reduction in weight and number of components, extending life cycle and maintenance intervals, and reducing NOX emissions with a lower CO2 footprint. Emerging opportunities for gas bearings applications range from automotive turbochargers to engines for business jet aircraft, for example. Gas bearings, because of the inherently low gas viscosity, have low damping relative to oil-lubricated bearings and are prone to wear during rotor start-up and shut down procedures. The lack of damping brings concerns about rotor-gas bearing system robustness and endurance to tolerate shock induced loads, sudden while landing in jet engines, or intermittent in vehicles while moving across a rough terrain, for example. The paper demonstrates the reliability of a hybrid gas bearing system from rotor vibration measurements induced by sporadic shock loads acting on the base of a test rig and while the rotor is coasting down from a top speed of 60 krpm (1000 Hz). In the tests, (1) an electromagnetic pusher delivers impacts to the rig base, or (2) the whole rig is manually tilted and dropped. The test rig consists of a rigid rotor, 0.825 kg and 28.6 mm in diameter, supported on two flexure pivot tilting pad type, hybrid gas bearings, each with four pads and 60% pivot offset and 0.6 mm feeding holes. The bearings are supplied with feed pressures of 2.36, 3.72, and 5.08 bar (ab). Intermittent shocks, up to 30 g pk-pk and exciting a broad frequency range to 400 Hz, produce a remarkable momentary increase of the overall rotor response amplitude, up to 50 μm (pk-pk). The shocks readily excite the fundamental natural frequency of the rotor-bearing system (150–200 Hz), and on occasion the natural frequency (40 Hz) of the whole test rig. For operation at rotor speeds above the system critical speed, the rotor synchronous response is isolated; with transient motions induced by a shock, subsynchronous in whirl frequency, quickly disappearing. Full recovery takes place in ∼0.10 second. The measurements demonstrate that the hybrid gas bearings have enough damping to rapidly attenuate rotor transient motions and to dissipate the energy induced from intermittent shocks. Note that the shocks acted while the rotor traversed its critical speeds. The reliability of engineered gas bearings to forced transient events is no longer in question.

A comparative study on engine performance and emissions (NOx, soot) formation has been carried out for the Volvo D12C diesel engine fueled by Rapeseed Methyl Ester, RME and conventional diesel oil. The combustion models, used in this paper, are the modifications of those described in [1–2]. After the compilation of liquid properties of RME specified as methyl oleate, C19H36O2, making up 60% of RME. The oxidation mechanism has been compiled based on methyl butanoate ester, mb, C5H10O2 oxidation model [3] supplemented by the sub-mechanisms for two proposed fuel constituent components, methyl decanoate, md, C11H22O2, n-heptane, C7H16, and soot and NOx formations reduced and “tuned” by using the sensitivity analysis. A special global reaction was introduced to “crack” the main fuel into constituent components, md, mb and propyne, C3H4, to reproduce accurately the proposed RME chemical formula. The sub-mechanisms were collected in the general one consisting of 99 species participating in 411 reactions. The combustion mechanism was validated using shock-tube ignition-delay data at diesel engine conditions and flame propagation speeds at atmospheric conditions. The engine simulations were carried out for Volvo D12C engine fueled both RME and conventional diesel oil. The numerical results illustrate that in the case of RME, nearly 100% combustion efficiency was predicted when the cumulative heat release, was compared with the RME LHV, 37.2 kJ/g.. To minimize NOx emissions, the effects of 20–30% EGR levels depending on the engine loads and different injection strategies were analyses. To confirm the optimal engine operation conditions, a special technique based on the time-transient parametric φ-T maps [4] has been used.