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1
Narayana, Valérie. "Des Espèces de l’origine : le feuilleton scientifique de Louis Figuier dans La Presse de 1862." Études littéraires 40, no. 3 (February 15, 2010): 73–86. http://dx.doi.org/10.7202/039245ar.
Повний текст джерелаАнотація:
Dans la foulée de travaux ayant exploré la rhétoricité du feuilleton littéraire dans la presse du XIXe siècle, cette étude se penche sur la rhétorique du feuilleton scientifique de Louis Figuier, célèbre vulgarisateur sous le Second Empire et sous la Troisième République. Afin de voir comment Figuier traite une question très controversée à l’époque, soit l’origine des espèces, cette étude examine les livraisons de l’année 1862 de LaRevue scientifique de Figuier. Cette année est particulièrement riche en rebondissements scientifiques car L’origine des espèces paraît en traduction et d’importantes fouilles françaises sonnent le glas des théories fixistes de l’époque. Cette étude démontre tout ce que la plume de Figuier doit à certains dispositifs argumentatifs quand elle se trouve confrontée à la complexité de l’évolution.
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Mwabila, Moïse Lufuluabo, Alain Roddy Miteu Kalambayi, Roger Kizungu Vumilia, Justin Cishugi Murhula, Pierre Kalonji Kadima, Crispin Mofilinga Bindusa, Fortunat Kabemba Yamba Yamba, Aimée Mwanza Mbuyi, and César Zuka Kizika. "Typologie des Exploitations Agricoles Familiales et Technologie de Rouissage de Manioc: Cas des exploitations de la Commune de Maluku, en République Démocratique du Congo." European Scientific Journal, ESJ 19, no. 11 (April 29, 2023): 85. http://dx.doi.org/10.19044/esj.2023.v19n11p85.
Повний текст джерелаАнотація:
La consommation du manioc, sous forme des pâtes alimentaires (Foufou ou chikwangue) nécessite de passer par le rouissage qui réduit la toxicité due à la présence de l’acide cyanhydrique. Cependant, les caractéristiques des exploitations et les techniques de rouissages sont variées. Ainsi l’objectif de cette étude était de réaliser une typologie des exploitations agricoles familiales de la commune de Maluku, en rapport avec les techniques de rouissage du manioc. Une enquête portant sur 344 exploitations agricoles a permis de collecter les données y afférentes. Les caractéristiques sociodémographiques, les caractéristiques de l’exploitation, les contraintes auxquelles font face les exploitations ainsi que la localisation (villages) ont été prises en compte. La typologie a été réalisée sur base de l’Analyse en Composantes Multiples (ACM) et la Classification Hiérarchique Ascendante (CHA). Les résultats révèlent 3 types d’exploitations agricoles. Le premier axe principal est dominé par le village, le type de contraintes, la productivité en cosette, le type de la main-d’œuvre et le type de matériel végétal. Le second axe principal est dominé par les techniques de rouissage.
The objective of this study is to develop a typology of cassava-producing farms in the Maluku area, on the outskirts of Kinshasa in the Democratic Republic of Congo. The criteria chosen are: socio-economic characteristics (type of workforce, membership of a group of producers and type of production constraints); characteristics related to cassava production technology (exploited area, plowing equipment and type of plant material); the characteristics linked to the cassava processing technology (retting method, retting duration and chip yield) and the village. The data was collected by survey on 344 farms operating in 6 villages. The typology was made thanks to an ACM and finalized by a CAH. The results of the study made it possible to group cassava producers into three types on the basis of the variables retained. The results reveal 3 types of farms. With the village, the type of constraints, the productivity in cosette, the type of labor and the type of plant material as the dominant characteristics of the first axis of the typology and the mode and duration of retting as the dominant characteristics of the second axis.
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Liu, Delong, Yousif Matloub, Jaydip Mukhopadhyay, David Liu, and Stuart L. Goldberg. "Dasatinib Is Associated with Rapid and Durable Complete Hematologic Responses in Patients with Chronic-Phase Chronic Myeloid Leukemia (CPCML)." Blood 112, no. 11 (November 16, 2008): 2128. http://dx.doi.org/10.1182/blood.v112.11.2128.2128.
Повний текст джерелаАнотація:
Abstract Achieving a quick and durable complete hematologic response (CHR) is a near-term treatment goal in CP-CML. This is particularly relevant in patients with late CP-CML who are receiving second-line tyrosine kinase inhibitors (TKIs) after failing imatinib therapy. The rapidity of the CHR provides an early assessment of sensitivity or resistance to second-line TKIs and should be used to guide treatment decision in this patient population. In the CA180-013 trial (START-C), 387 subjects resistant to or intolerant of imatinib were treated with dasatinib. At 2 years of follow-up, CHR was achieved in 91% of all subjects (90% of 288 resistant subjects, and 94% of 99 intolerant subjects). Of the 233 patients with abnormal peripheral blood counts at baseline, 203 (87%) achieved CHR (86% imatinib-resistant and 92% imatinib-intolerant). The time to achieve CHR (defined as the duration between the first dose of dasatinib until the first day CHR criteria were met) was rapid, with a median time to CHR of 2.1 weeks (C.I: 2.1 to 2.4) across all cohorts. Furthermore, most subjects who achieved CHR did so within the first two months of treatment. In addition, CHRs achieved with dasatinib were durable; the 12- and 24-month CHR were 92% and 83%, respectively. Moreover, in an optimization trial (CA180-034) comparing efficacy between 100mg and 140mg total dasatinib administered in one or two doses, the rates of, time to, and duration of CHR were comparable to that observed in START-C (Table 1). No difference in time to or duration of CHR was observed between the two schedules. In summary, dasatinib is associated with a rapid and durable CHR in a majority of subjects with CP-CML resistant to or intolerant of imatinib therapy. Table 1: Percentage of Dasatinib-Treated Patients with CHR who are Imatinib Resistant (CA180-034 trial) Number (%) of Subjects by Treatment Group QD BID Best Hematologic Response 100 mg N = 124 140 mg N = 123 Total N = 247 50 mg N = 124 70 mg N = 126 Total N = 250 CHR 110 (89) 106 (86) 216 (87) 114 (92) 112 (89) 226 (90) no CHR 14 (11) 17 (14) 31 (13) 10 (8) 14 (11) 24 (10)
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Gicquel, Jean. "Le sens unique de la Constitution de la V e République." Titre VII N° 1, no. 1 (September 11, 2018): 3–10. http://dx.doi.org/10.3917/tvii.001.0003.
Повний текст джерелаАнотація:
4 octobre : jour de la Constitution ; 4 octobre 2018, fête du 60 e anniversaire de la Constitution de 1958. Une Constitution singulière, à tous égards, car finalisée et identifiée au pouvoir exécutif ; un pouvoir, désormais réhabilité et légitimé par le peuple souverain. Autrement dit, une Constitution copernicienne, transfigurée, en ce qu’elle s’inscrit à l’origine dans une perspective de rupture en mettant fin à la souveraineté parlementaire d’antan, puis instrumentalisée dans la posture du président de la République, devenu un authentique chef de l’État. Au total, une Constitution ordonnée, à la mesure de son efficacité, et régulée par la logique de l’alternance et celle de l’État de droit, incarnée, à titre essentiel par le Conseil constitutionnel. Ce faisant, une Constitution intériorisée par les citoyens, à preuve le surgissement du président MACRON au point d’être devenue la seconde nature , selon la formule anticipatrice de son fondateur, le général DE GAULLE.
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Hird, Emily, Paul Allen, Natasza Orlov, Gemma Modinos, Matthijs Bossong, Mathilde Antoniades, Carly Sampson, et al. "M163. GLUTAMATE METABOLITES ARE ASSOCIATED WITH ALTERED HIPPOCAMPAL ACTIVATION BUT NOT HIPPOCAMPAL-STRIATAL CONNECTIVITY IN SUBJECTS WITH A CLINICAL HIGH RISK FOR PSYCHOSIS." Schizophrenia Bulletin 46, Supplement_1 (April 2020): S198. http://dx.doi.org/10.1093/schbul/sbaa030.475.
Повний текст джерелаАнотація:
Abstract Background We recently used Magnetic Resonance Spectroscopy (MRS) to show that transition to psychosis is associated with higher baseline hippocampal glutamate levels (1). We also used functional Magnetic Resonance Imaging (fMRI) in the same CHR subjects and showed that compared to healthy controls (HC), subjects at a clinical high-risk of psychosis (CHR) show decreased hippocampal activation to novel stimuli and increased novelty-modulated hippocampal-striatal connectivity (2). The aim of the present analysis was to explore the relationship between hippocampal glutamatergic metabolites, hippocampal activity, and hippocampal-striatal connectivity in these CHR subjects. Methods 75 CHR and 31 HC subjects participated in a novelty salience task whilst undergoing fMRI to measure hippocampal and striatal activation, and MRS to measure hippocampal glutamatergic metabolite levels. First, we tested for a three-way interaction between the hippocampal response to novel versus neutral stimuli, hippocampal glutamatergic metabolite levels, and group, using a Region of Interest approach in the bilateral hippocampus. Second, we carried out a Psychophysiological Interaction (PPI) analysis on the extracted hippocampal coordinates from the first analysis and tested for an interaction with hippocampal glutamatergic metabolite levels and group. Results The CHR group had higher clinical scores and lower GAF scores at baseline than HC. CHR subjects were younger, more were taking antipsychotic medication and they smoked more cigarettes than HC. At follow-up, 12 CHR subjects (16%) developed a first episode of psychosis (CHR-TR) and 63 (86%) did not (CHR-NTR). The CHR-TR subjects smoked fewer cigarettes than the CHR-NTR subjects. The first analysis revealed a significant interaction between group, fMRI activity and MRS Glx (a combined measure of glutamate and glutamine) in the right hippocampus (pFWE= 0.03; x y z = 28 -32 -4; t=3.61, z=3.49). This was driven by the CHR-TR group: contrast estimates indicated a positive relationship between fMRI activity and MRS Glx in the HC and CHR-NTR subjects, but a negative relationship between fMRI activity and glutamate in the CHR-TR subjects. The second analysis revealed that CHR-TR individuals exhibited greater connectivity between the hippocampus and the striatum (pFWE= 0.03; x y z = -6 6 -8; t=3.35, z=3.17), but that this was not associated with Glx. Discussion Whilst hippocampal glutamate metabolite levels are associated with altered hippocampal activity in CHR individuals - especially in those who later transition to psychosis - hippocampal glutamate metabolite levels do not modulate connectivity between the hippocampus and striatum. These findings are broadly consistent with previous work indicating a role for glutamate in hippocampal dysfunction and risk for psychosis, and indicate a potential biomarker for psychosis risk. References
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Capolupo, Marco, Alessandro Girolamo Rombolà, Sadia Sharmin, Paola Valbonesi, Daniele Fabbri, and Elena Fabbri. "Assessing the Impact of Chrysene-Sorbed Polystyrene Microplastics on Different Life Stages of the Mediterranean Mussel Mytilus galloprovincialis." Applied Sciences 11, no. 19 (September 24, 2021): 8924. http://dx.doi.org/10.3390/app11198924.
Повний текст джерелаАнотація:
The sorption of organic pollutants to marine plastic litter may pose risks to marine organisms, notably for what concerns their intake and transfer through microplastic (MP) ingestion. This study investigated the effects of polystyrene MP loaded with chrysene (CHR) on early-stage and physiological endpoints measured in the Mediterranean mussel Mytilus galloprovincialis. The same concentrations of virgin microplastics (MP) and MP loaded with 10.8 µg CHR/mg (CHR-MP) were administered to mussel gametes/embryos (25 × 103 items/mL) and adults (5⋅× 103 items/L); further treatments included 0.1 mg/L of freely dissolved CHR and a second CHR concentration corresponding to that vehiculated by CHR-MP during exposure (3.78 µg/L and 0.73 ng/L for gamete/embryos and adults, respectively). None of the treatments affected gamete fertilization, while 0.1 mg/L CHR induced embryotoxicity. In adults, CHR-MP and MP similarly affected lysosomal membrane stability and neutral lipids and induced slight effects on oxidative stress endpoints. CHR affected tested endpoints only at 0.1 mg/L, with lysosomal, oxidative stress and neurotoxicity biomarkers generally showing greater alterations than those induced by CHR-MP and MP. This study shows that the CHR sorption on MP does not alter the impact of virgin MP on mussels and may pose limited risks compared to other routes of exposure.
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Matsumoto, Koji. "A new curvaturelike tensor field in an almost contact Riemannian manifold II." Publications de l'Institut Math?matique (Belgrade) 103, no. 117 (2018): 113–28. http://dx.doi.org/10.2298/pim1817113m.
Повний текст джерелаАнотація:
In the last paper, we introduced a new curvaturlike tensor field in an almost contact Riemannian manifold and we showed some geometrical properties of this tensor field in a Kenmotsu and a Sasakian manifold. In this paper, we define another new curvaturelike tensor field, named (CHR)3-curvature tensor in an almost contact Riemannian manifold which is called a contact holomorphic Riemannian curvature tensor of the second type. Then, using this tensor, we mainly research (CHR)3-curvature tensor in a Sasakian manifold. Then we define the notion of the flatness of a (CHR)3-curvature tensor and we show that a Sasakian manifold with a flat (CHR)3-curvature tensor is flat. Next, we introduce the notion of (CHR)3-?-Einstein in an almost contact Riemannian manifold. In particular, we show that Sasakian (CHR)3- ?-Einstein manifold is ?-Einstain. Moreover, we define the notion of (CHR)3- space form and consider this in a Sasakian manifold. Finally, we consider a conformal transformation of an almost contact Riemannian manifold and we get new invariant tensor fields (not the conformal curvature tensor) under this transformation. Finally, we prove that a conformally (CHR)3-flat Sasakian manifold does not exist.
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Fava, Carmen, Hagop M. Kantarjian, Elias Jabbour, Mary Beth Rios, Guillermo Garcia-Manero, Susan O’Brien, and Jorge Cortes. "Long-Term Significance of Achieving a Major Cytogenetic Response (MCyR) without a Complete Hematologic Response (CHR) among Patients (pts) with Chronic Myeloid Leukemia (CML) in Advanced Phase Treated with Second Generation Tyrosine Kinase Inhibitors (TKI)." Blood 110, no. 11 (November 16, 2007): 1944. http://dx.doi.org/10.1182/blood.v110.11.1944.1944.
Повний текст джерелаАнотація:
Abstract The BCR-ABL TKI, dasatinib (D) and nilotinib (N), are effective in Philadelphia chromosome-positive (Ph+) leukemias, including all stages of imatinib-resistant CML and Ph+ ALL. For both dasatinib and nilotinib, the reported rates of MCyR are higher than the rates of CHR; that is, some pts achieve MCyR but may have cytopenias that make their hematologic response less than a CHR; this has been attributed to myelosuppression induced by TKI. At present it is not known whether pts with MCyR who do not have CHR have a similar outcome as those with a CHR. We studied 135 pts with accelerated (AP; n=84) or blast phase (BP; n=47) CML or Ph+ ALL (n=4) treated with D (59) or N (76) for imatinib resistance, to see whether the presence of cytopenias at the time of best response affected the prognosis. The median age was 55 yrs (range, 15 to 98) and 62 were female. 56 (41%) had bcr/abl mutations at the start of therapy. Overall 36 pts (27%) achieved MCyR. All the 36 pts who achieved a MCyR after treatment with N or D had received imatinib for an average time of 34 mos (range 4–78) and 24/36 pts had obtained a MCyR under imatinib. They started the new TKI 66 mos after first diagnosis (12–336). 2-yr survival rates for pts that achieved MCyR was 72% compared to 35% for those without MCyR (p<0.001). There was a trend for an inferior survival for those not having a concomitant CHR at the time of MCyR compared to those with CHR (2-yr survival 58% vs 82%; p=0.11). The rates of CHR and MCyR were 68% and 29%, respectively in AP; 32% and 21% in BP, and 50% and 50% in Ph+ ALL. Among pts in AP, 17/24 (70%) who achieved a MCyR, had a CHR at the time of best cytogenetic response; 6 of these 17 (35%) pts eventually failed (lost response or transformed), compared to 3/7 (43%) of those with no CHR at the time of MCyR (p=0.28). The results are similar when analyzing separately pts treated with N or D. 2-yr survival was 88% and 66% for those with and without concomitant CHR (p=0.29). Among the 10 pts in BP that achieved a MCyR, 5 had a CHR at the time of best cytogenetic response. Three (60%) of these pts eventually failed (lost response), compared to 4 failures among the 5 pts with no CHR at the time of MCyR (p=1.0). Survival rates at 2 yrs were 60% and 40% for those with and without concomitant CHR (p=0.29). Among the 2 patients with ALL that achieved MCyR, one had comcomitant CHR (treated with N) and the other did not have CHR (D); both of them failed. Of the 18 pts who failed after having achieved an MCyR, 7 had a mutation before starting treatment with a 2nd TKI (A433T, G250E, E355G, E459K, M244V, M315T, F317L), and 6 developed a new mutation after treatment (F317L, F311I, Y253H, G476C, E255K, H359V). Five of them occurred in pts with a concomitant CHR and 1 without a CHR. These results suggest that achievement of MCyR with residual cytopenias (ie, without a concomitant CHR) may not have the same favorable outcome as that of MCyR with concomitant CHR. Whether this is related to pt- or disease-related characteristics remains to be determined.
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Fava, Carmen, Hagop M. Kantarjian, Elias Jabbour, Susan O'Brien, Nitin Jain, Mary Beth Rios, Guillermo Garcia-Manero, et al. "Failure to achieve a complete hematologic response at the time of a major cytogenetic response with second-generation tyrosine kinase inhibitors is associated with a poor prognosis among patients with chronic myeloid leukemia in accelerated or blast phase." Blood 113, no. 21 (May 21, 2009): 5058–63. http://dx.doi.org/10.1182/blood-2008-10-184960.
Повний текст джерелаАнотація:
Abstract Second-generation tyrosine kinase inhibitors are effective in Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML). Occasionally, patients with Ph+ ALL, or accelerated phase (AP) or blast phase (BP) CML achieve a major cytogenetic response (MCyR) but not a complete hematologic response (CHR). We analyzed 126 patients with CML in AP or BP, or with Ph+ ALL treated with dasatinib or nilotinib after imatinib failure. Twenty patients received sequential treatment with both dasatinib and nilotinib for a total of 146 instances. CHR and MCyR rates were 54% and 37%, respectively in AP, 17% and 39% in BP, and 33% and 50% in Ph+ ALL. Failure to achieve a CHR at the time of achievement of a MCyR was associated with an inferior outcome, similar to that of patients without a MCyR (2-year survival rate, 37% and 35%, respectively). In contrast, patients with MCyR and concomitant CHR had a 77% 2-year survival rate. Twelve of 29 patients with MCyR without concomitant CHR later achieved a CHR; the 2-year survival rate for these patients was 55% compared with 22% for those who never achieved a CHR. These results suggest that achievement of a MCyR without concomitant CHR is associated with poor outcome.
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Ibrahim Mamadou, AK. "Profil clinique, thérapeutique et évolutif de la tuberculose au centre hospitalier régional (CHR) de Tahoua, république du Niger." Bulletin de la société de pathologie exotique 113, no. 5 (December 28, 2020): 263–67. http://dx.doi.org/10.3166/bspe-2020-0153.
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Omelchenko, M. "Duration of therapy and treatment compliance of depressive patients at clinical high-risk for psychosis." European Psychiatry 65, S1 (June 2022): S680. http://dx.doi.org/10.1192/j.eurpsy.2022.1750.
Повний текст джерелаАнотація:
Introduction It is known that early withdrawal can lead to a worsening of mental health. This is particularly relevant for depressive patients with clinical high-risk for psychosis (CHR) for whom the recommended duration of treatment has not been established. Objectives Analyze the actual treatment duration of depressive patients at CHR after their discharge from hospital and compare it with the group of depressive patients without CHR. Methods A comparative study of 124 depressive patients with CHR and 27 depressive patients without CHR was conducted within a year after discharge from hospital to assess the therapy duration and treatment compliance. Results Within a year after discharge only 12.1% depressive patients with CHR and 29.6% ones without CHR continued to receive the therapy. The average duration of treatment after discharge was 7.4 months in the first group and 11.7 months in the second group. The majority of patients stopped treatment for the following reasons (in descending order of importance): lack of awareness of their mental condition (51.9% vs 40.3%), side effects (38.7% vs 11.1%), and negative attitudes towards the treatment on the part of patients’ immediate family members (8.9% vs 7.4%). Conclusions It has been found out that depressive patients with CHR are less likely to follow medical prescriptions than ones without CHR, they are more likely to have the lack of awareness of their mental condition, they are more likely to have side effects of the therapy. These findings require the development of a universal approach to the treatment of such patients after discharge from hospital. Disclosure No significant relationships.
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Ibarrondo, Paloma, Andres Insunza, Sonia González de Villambrosia, María José Calasanz, Ana Belén Valencia, Valeria Santini, Francesca Torricelli, et al. "Prognostic Value of Chromosome 1 Abnormalities in Myelodysplastic Syndrome." Blood 124, no. 21 (December 6, 2014): 3240. http://dx.doi.org/10.1182/blood.v124.21.3240.3240.
Повний текст джерелаАнотація:
Abstract INTRODUCTION AND AIMS: Abnormalities of chromosome 1 (chr 1) are frequently found in hematopoietic stem cell disorders, but their impact and prognosis in Myelodysplastic Syndrome (MDS) remains unclear. For this reason, we retrospectively analyzed a large series of patients. MATERIALS AND METHODS: A series of 90 patients with MDS and abnormalities of chr 1 were retrospectively evaluated, coming from the Spanish Registry of MDS (68), Marqués de Valdecilla Universitary Hospital (16) and Azienda Careggi Universitary Hospital (Florence) (6). We compared this group to a control group of 992 patients with MDS and an abnormal karyotype, but without abnormalities of chr 1, included in the Spanish Registry of MDS. RESULTS: Abnormalities of chr 1 occurred in 8.3% of patients with MDS. Fifty seven percent belonged to the high/very high IPSS-R (Revised International Prognostic Scoring System) risk group. The median number of chromosomal abnormalities in the group with and without chr 1 involvement was 3.5 (1-15) and 1 (1-18), respectively (p<0.0001). A complex karyotype was found in 60% and in 16% of patients with and without abnormalities of chr 1, respectively (p<0.0001). The most frequent type of cytogenetic abnormality was translocation (30%). Long arm involvement was seen in 37.8% of patients whereas both arms were only affected in 14.4%. Forty three and thirty one percent of patients with abnormalities of chr 1 had also chr 5 and chr 7 affected, respectively. A low platelet count (<100 x 109/l) was more frequently found in patients with abnormalities of chr 1 (50% vs 32%; p=0.002). According to the number of cytogenetic abnormalities, translocation (43.2%) was the most frequent cytogenetic abnormality observed in the group of ≤2 abnormalities and chr 1 involvement (group 1), becoming chr 7 (16.2%) the most recurrently affected. However, deletion (24.5%) predominated in the group of ≥ 3 abnormalities and chr 1 involvement (group 2). In the first group, long arm was more frequently involved (48.6%) whilst both arms were involved in only 5.5% of cases, being this condition more common in the second group. Moreover, the short arm was mostly restricted to the second group (32.1%). In the first group, chr 5 and chr 7 were affected in 8.1% and 18.9% of cases, respectively, compared to group 2 (67% and 39.6%, respectively). A higher hemoglobin level was observed in the first group (10.6 vs. 9.6 g/dl; p=0.006). However, we observed no differences in terms of bone marrow blasts, platelet count and absolute neutrophil count between these two groups (table 1). The median survival was significantly lower in the group with chr 1 involvement (34.1 vs. 64.7 months; p<0.001). When patients were classified attending to the number of abnormalities, the prognostic impact of chromosome 1 was restricted to the group with ≤2 abnormalities (44.7 vs. 72.2 months; p=0.034) (figure 1). However, we observed no differences in terms of survival in the group with ≥ 3 abnormalities (24 vs. 19 months; p=0.283) (table 1). Transformation to acute myeloid leukemia (AML) was observed in 35.6% of patients with chr 1 involvement, in comparison to the 20.2% of the control group (p=0.001). CONCLUSIONS: Chr 1 involvement in patients with MDS is more frequently associated with complex karyotype, generally with chr 5 and 7 additionally involved and a low platelet count. In those patients carrying a complex karyotype, the presence of chromosome 1 does not provide additional prognostic information. However, in the group of patients with ≤ 2 abnormalities, chr 1 aberrations are associated with a significant reduced OS, suggesting that those should be included in the high risk cytogenetic group. Acknowledgments: Ministerio de Sanidad y Consumo, Spain (PI 11/02010); Red Temática de Investigación Cooperativa en Cáncer (RTICC, FEDER) (RD12/0036/0044); 2014 SGR225 (GRE) Generalitat de Catalunya,Fundació Internacional Josep Carreras, Obra Social “la Caixa” y de Celgene (España). Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.
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Sandu, Corinna. "La chute du Second Empire et la proclamation de la Troisième République vues par la presse Indochinoise." Outre-Mers N° 420-421, no. 2 (April 3, 2024): 63–72. http://dx.doi.org/10.3917/om.420.0063.
Повний текст джерелаАнотація:
Annoncée à 4 000 lieues de Paris et avec un retard de 43 jours, la proclamation de la III e République parvient en Cochinchine le 20 octobre 1870, avec les douloureuses nouvelles de la défaite dans la guerre franco-prussienne. Elle aura un impact définitoire sur l’orientation de presse francophone dans cette colonie. Nous proposons ici une analyse diachronique des périodiques parus en Indochine avant 1900, portant sur la chute du régime de Napoléon III et la proclamation de la III e République. Notre but est de montrer que le moment 1870 préside à la naissance d’une presse coloniale indochinoise placée sous le signe d’un discours médiatique démocratique, libre et ouvert à la parole publique.
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Wiśniewska, Dorota. "Être citoyenne dans la République nobiliaire de Pologne au temps des Lumières." Revue historique 708, no. 4 (November 29, 2023): 579–601. http://dx.doi.org/10.3917/rhis.234.0579.
Повний текст джерелаАнотація:
L’article caractérise la citoyenneté des femmes nobles dans la République nobiliaire de Pologne dans la seconde moitié du xviii e siècle. Il décrit les rapports des femmes des élites avec l’État, leurs sentiments d’appartenance à la nation et leur attachement aux lieux, où elles vivent. Il met en lumière la perception qu’ont les hommes de l’engagement des femmes dans la vie publique et de leur citoyenneté, ainsi que les similarités et les particularités du contexte polono-lituanien par rapport à l’Occident. Centré sur la correspondance féminine, l’article montre que les femmes nobles en Pologne-Lituanie non seulement se voient officiellement accorder le statut de citoyennes, mais aussi elles se sentent inclues à la nation politique et manifestent leur patriotisme. Elles agissent pour le bien commun qu’elles considèrent en accord avec les intérêts privés et familiaux. Le régime républicain, l’influence des Lumières et les circonstances particulières liées aux partages facilitent leur inclusion, mais elles ne contestent pas leur position sociale. Elles sont bien conscientes de leur subordination face aux hommes, mais vu que leurs familles et l’Église leur inculquent la vision patriarcale du monde dès le plus jeune âge, il ne vient pas à l’esprit des femmes de s’y opposer. Et car la « révolution polonaise » (1788-1792) est menée par la noblesse, la question de l’octroi de la citoyenneté à toutes les femmes ne se pose pas dans le débat public.
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Cavell, Janice. "The Second Frontier: The North in English-Canadian Historical Writing." Canadian Historical Review 83, no. 3 (September 2002): 364–89. http://dx.doi.org/10.3138/chr.83.3.364.
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Phillips, Ruth. "Re-placing Objects: Historical Practices for the Second Museum Age." Canadian Historical Review 86, no. 1 (March 2005): 83–110. http://dx.doi.org/10.3138/chr/86.1.83.
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Lee, Seok, Dong-Wook Kim, Yoo-Jin Kim, Nak-Gyun Chung, Yoo-Li Kim, Ji-Yeon Hwang, and Chun-Choo Kim. "Minimal residual disease–based role of imatinib as a first-line interim therapy prior to allogeneic stem cell transplantation in Philadelphia chromosome–positive acute lymphoblastic leukemia." Blood 102, no. 8 (October 15, 2003): 3068–70. http://dx.doi.org/10.1182/blood-2003-04-1180.
Повний текст джерелаАнотація:
Abstract Fourteen adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) were studied to evaluate the role of imatinib prior to allogeneic stem cell transplantation (SCT). Of these, 12 patients were in complete hematologic response (CHR), and 2 were refractory. Imatinib was administered as an interim schedule after each chemotherapy course. After the first imatinib cycle, 11 patients remained in sustained CHR with a decrease in the BCR-ABL/ABL ratios (0.89 logs), and one refractory patient achieved CHR. Meanwhile, 2 patients were resistant to imatinib. Ten patients receiving a second imatinib cycle following consolidation showed sustained CHR, including 2 molecular CR, with a further decrease in the BCR-ABL/ABL ratios (0.19 logs). Twelve patients underwent SCT in a favorable status, and of these, 11 are still alive in a leukemia-free status at 9 to 28+ months after SCT. First-line imatinib interim therapy appears to be a useful strategy to bridge the time to SCT for patients with Ph+ ALL.
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Gauzy-Krieger, Florence. "Remilitarisation et affirmation du processus démocratique : le cas du second réarmement allemand (1950-1955)." Revue d’Allemagne et des pays de langue allemande 30, no. 2 (1998): 155–74. http://dx.doi.org/10.3406/reval.1998.4061.
Повний текст джерелаАнотація:
Curieuse expérience que celle de ces hommes, militaires et civils, chargés par le chancelier Adenauer de réarmer le République fédérale moins de cinq ans après la capitulation sans conditions de l’Allemagne nazie, après la guerre et la défaite, la captivité et le dur apprentissage de la vie civile. Issus de l’ancien monde, celui de la Reichswehr et de la Wehrmacht, de la République de Weimar et du Troisième Reich, ils mettent sur pied la levée d’une armée nouvelle créée de toutes pièces qui, par une étonnante conversion des valeurs, non seulement n’a pas menacé la démocratie naissante mais au contraire, a fait le choix de s’en inspirer et de la servir. Comment ? Par une entreprise «légaliste» : en admettant dès la phase préparatoire la suprématie absolue du Politique en matière de défense et en refondant toute l’organisation interne de l’armée d’après les principes de la Loi fondamentale.
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Twohig, Peter L. "The Second “Great Transformation”: Renegotiating Nursing Practice in Ontario, 1945–70." Canadian Historical Review 99, no. 2 (June 2018): 169–95. http://dx.doi.org/10.3138/chr.99.2.01.
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Jabbour, Elias, Hagop Kantarjian, Jenny Shan, Susan O’Brien, William Wierda, Farhad Ravandi, Gautam Borthakur, et al. "Prognostic Significance of Prior Best Response to Imatinib in Patients (pts) with Chronic Myeloid Leukemia (CML) in Chronic Phase (CP) Treated with Second Generation Tyrosine Kinase Inhibitors (TKIs)." Blood 110, no. 11 (November 16, 2007): 1942. http://dx.doi.org/10.1182/blood.v110.11.1942.1942.
Повний текст джерелаАнотація:
Abstract Backgound. Imatinib mesylate therapy has significantly improved the prognosis of CML. A minority of pts in CP-CML are primary resistant to imatinib or develop resistance during treatment. Second generation TKIs such as dasatinib and nilotinib demonstrated efficacy in overcoming imatinib resistance, with high rates of hematologic and cytogenetic responses in CML post imatinib failure. Study Aims and Study Group. We assessed the impact of prior best response to imatinib on outcome of 120 pts in CP treated with new TKIs at our institution after imatinib failure: 75 (62%) received dasatinib and 45 (38%) recived nilotinib. Median age was 57 years (range, 21–83). The median duration of the disease was 67 months (range, 4–241). Pts have been followed for a median of 22 months (range, 1–44) from the start of 2nd generation TKIs. Results. Best response to imatinib was hematologic in 47 pts (40%) and cytogenetic in 60 (50%) (complete in 28, partial in 16, minor in 16). Five pts (4%) were primary refractory and 8 (6%) were intolerant. At the start of 2nd generation TKIs, 87 pts (73%) were in active CP with no complete hematologic response (CHR). Eighty-five (71%) harbored more than 90% Philadelphia-positive metaphases, and clonal evolution was noted in 28 pts (23%). Patients that had achieved a cytogenetic response at any time during their imatinib therapy had a better outcome than those who had only a hematologic response: CHR rates 98% vs 68%, p <0.001; major cytogenetic response (MCyR) rates 75% vs 26%, p<0.001; and complete cytogenetic response (CCyR) rates 68% vs 23%, p<0.001. This translated into an improved 12-month event-free survival (EFS) of 92% vs 68% (p<0.001) and a trend for better 12-month survival of 92% vs 89% (p=0.06) (Table1). Pts with CHR at the start of therapy with 2nd generation TKIs had higher rates of cytogenetic response than those not already in CHR (88% vs 64%; p=0.01). Low disease burden defined by Philadelphia-positive metaphases <90% was associated with higher rates of hematologic response (p=0.006), MCyR (p<0.001) and CCyR (p=0.003), with no impact on EFS. There was no difference in activity between the two 2nd generation TKIs with CHR rates of 89% and 80% (p=0.18), MCyR rates of 57% and 51% (p=0.57) and CCyR rates of 52% and 47% (p=0.71) for dasatinib and nilotinib, respectively. Conclusion. The probability of response to 2nd generation TKIs is highly dependent on prior response to imatinib and disease burden at the start of therapy. Table 1. % CG response % 12-Month Best response to imatinib N % CHR Major Complete EFS Survival EFS=Event-free survival; CG=Cytogenetic; CHR=complete hematologic response No CHR 4 80 40 40 80 80 CHR 32 68 26 23 68 89 Any CG response 59 98 75 68 92 92 P-value <0.001 <0.001 <0.001 <0.001 0.06
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Morgan, Jennifer, Jean Bosco Bigirimana, Cam Nguyen, Rebecca Deboer, Cyprien Shyirambere, Alan Paciorek, Leslie E. Lehmann, and Lawrence N. Shulman. "Ten Years of Treating Chronic Myeloid Leukemia in Rural Rwanda: Feasible Approaches for Low-Resource Settings." Blood 134, Supplement_1 (November 13, 2019): 4788. http://dx.doi.org/10.1182/blood-2019-126152.
Повний текст джерелаАнотація:
Objective: To describe the characteristics and outcomes of chronic myeloid leukemia (CML) patients treated through the Glivec Patient Assistance Program (GIPAP) in Rwanda. Methods: We retrospectively reviewed all BCR-ABL positive CML patients treated with imatinib at two rural hospitals between 2009 and 2018. Clinical data were analyzed using descriptive statistics, Kaplan-Meier method, and proportional hazards regression. Results: One hundred twenty-four patients were included; median age 35 (range: 9-81), 60% male, 88% without comorbidities. All patients presented with symptomatic disease, median duration 11 months (IQR: 4-24) and median WBC count 225.5 x 109/L (IQR: 117.7-308.5). At diagnosis, 71% were in chronic phase. On imatinib, 91% achieved complete hematologic remission (CHR); 67% within 90 days. Of those who achieved CHR, 51 (45%) lost it at some point and, of which, 36 (71%) regained CHR. At four years, overall survival was 79% (95% CI:69%-86%) for the entire cohort; 93% (95% CI: 79%-98%) for 53 patients who remained in CHR, 89% (95% CI: 69%-96%) for 34 patients who lost but regained CHR, 19% (95% CI: 1%-54%) for 12 patients who lost and never regained CHR. Never achieving CHR was associated with increased mortality (HR: 40.89; 95% CI: 9.88-169.32; p<0.001) as was losing CHR without regaining it (HR 15.73; 95% CI: 4.14-59.81; p<0.001) compared to never losing CHR. Conclusions: Here we demonstrate the feasibility of coupling molecular diagnostics with chronic targeted therapy in a rural low-resource setting through health systems strengthening and international collaboration. Our CML patients are younger, slower to achieve CHR with imatinib, and have higher rates of primary and early hematologic resistance than historical cohorts, suggesting biological differences that warrant further investigation. It is uncertain what role non-adherence to medication influences these data. Without molecular response assessment, hematologic response is an accurate marker of disease control and survival. Our imatinib failure rates highlight the need for access to resistance testing and second generation tyrosine kinase inhibitors, as well as adherence rates. Disclosures No relevant conflicts of interest to declare.
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GABBRIELLI, MAURIZIO, JACOPO MAURO, MARIA CHIARA MEO, and JON SNEYERS. "Decidability properties for fragments of CHR." Theory and Practice of Logic Programming 10, no. 4-6 (July 2010): 611–26. http://dx.doi.org/10.1017/s1471068410000311.
Повний текст джерелаАнотація:
AbstractWe study the decidability of termination for two CHR dialects which, similarly to the Datalog like languages, are defined by using a signature which does not allow function symbols (of arity > 0). Both languages allow the use of the = built-in in the body of rules, thus are built on a host language that supports unification. However each imposes one further restriction. The first CHR dialect allows only range-restricted rules, that is, it does not allow the use of variables in the body or in the guard of a rule if they do not appear in the head. We show that the existence of an infinite computation is decidable for this dialect. The second dialect instead limits the number of atoms in the head of rules to one. We prove that in this case, the existence of a terminating computation is decidable. These results show that both dialects are strictly less expressive1 than Turing Machines. It is worth noting that the language (without function symbols) without these restrictions is as expressive as Turing Machines.
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Slongo, Paolo. "Sovranità e dominio nella République di Jean Bodin." Res Publica. Revista de Historia de las Ideas Políticas 24, no. 2 (June 21, 2021): 139–52. http://dx.doi.org/10.5209/rpub.70125.
Повний текст джерелаАнотація:
Abtract. This article aims to pose the problem of the relationship between State and Sovereignty in Jean Bodin. In the second half of the Sixteenth Century and then in the Seventeenth Century, Sovereignty was understood as an external principle, presupposed to the existence of political association. Classical terminology then remains. Only when Sovereignty appears as an internal, constitutive element of the Political Body, will the term State permanently take the place of the conceptuality inherited from tradition. Only in this specific phase of its historical conceptual development does the State appear as a reality that exists in itself. Consequently, political science will become the Theory of the State. Certainly not therefore in Bodin’s political thought.
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Cook, Tim. "Clio's Soldiers: Charles Stacey and the Army Historical Section in the Second World War." Canadian Historical Review 83, no. 1 (March 2002): 29–57. http://dx.doi.org/10.3138/chr.83.1.29.
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Sangster, Joan. "The Polish ‘Dionnes’: Gender, Ethnicity, and Immigrant Workers in Post–Second World War Canada." Canadian Historical Review 88, no. 3 (September 2007): 469–500. http://dx.doi.org/10.3138/chr.88.3.469.
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Cruz, Julio, Michael E. Miner, Steven J. Allen, Wayne M. Alves, and Thomas A. Gennarelli. "Continuous Monitoring of Cerebral Oxygenation in Acute Brain Injury: Assessment of Cerebral Hemodynamic Reserve." Neurosurgery 29, no. 5 (November 1, 1991): 743–49. http://dx.doi.org/10.1227/00006123-199111000-00017.
Повний текст джерелаАнотація:
Abstract A new index of cerebral hemodynamics, cerebral hemodynamic reserve (CHR), was evaluated in 12 comatose adults with severe, acute, traumatic, diffuse swelling of the brain, who underwent continuous monitoring with a fiberoptic catheter of the saturation difference in arteriojugular oxyhemoglobin. CHR was assessed as the ratio of changes in global cerebral oxygen extraction to changes in cerebral perfusion pressure (CPP) as a result of spontaneous increases in intracranial pressure (ICP). During the course of hyperventilation (Pco2 in the range of 20 mm Hg) for ICP control below 20 mm Hg. 34 observations were made over the initial 48 hours postinjury. Despite normal CPP. in 25 of the observations (73.5%). ICP elevations to the range of 20 mm Hg were associated with compromised CHR. as evidenced by decreases in jugular oxygenation directly attributed to the ICP increases. In the remaining nine observations (26.5%). CHR was preserved, as evidenced by no changes or increases in jugular oxygenation when ICP increased. The CHR improved on the second day. suggesting an improved tolerance of the cerebral hemodynamics to ICP increases. Before the ICP elevations, in most of the observations, the global cerebral blood flow was estimated as being optimally decreased (by hypocapnia). in relation to cerebral oxygen consumption. This was reflected by the occurrence of baseline normalized cerebral oxygen extraction. It is concluded that in this group of patients, under circumstances of profound hyperventilation. ICP elevations within the normal CPP range may result in decreased cerebral oxygenation, even when the normal CPP would imply otherwise. It is suggested that CHR assessment may provide information regarding the status of intracranial “tightness.” insofar as cerebral circulation and oxygenation are concerned.
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Lungambo, Alex Ngangolo, Dydo Nkongolo Katolo, and Charlot Mikobi Mikobi. "Effets des dates de semis et de cultivars de <i>Vigna unguiculata</i> (L. Walp.) sur le rendement dans les conditions éco-climatiques de Kananga, Kasaï Central en République Démocratique du Congo." Revue Africaine d’Environnement et d’Agriculture 7, no. 2 (July 24, 2024): 31–42. http://dx.doi.org/10.4314/rafea.v7i2.5.
Повний текст джерелаАнотація:
Description du sujet. Le niébé est une légumineuse à graines qui joue rôle important en Afrique subsaharienne, en particulier dans les zones de savane aride et semi-arides. Les moments de semis du niébé, son évolution végétative et les calendriers agricoles sont totalement perturbés par le changement climatique. C’est dans ce contexte que cette étude a été entreprise en vue de proposer l’itinéraire technique adaptée au milieu d’étude.Objectif. L’objectif de l’étude est d’analyser les effets des dates de semis et cultivars de Vigna unguiculata sur le rendement en graines sèches dans les conditions éco-climatiques de Kananga au Kasaï central en République Démocratique du Congo.Méthodes. Le dispositif expérimental en Split plot a été appliqué. La superficie du champ expérimental était de 432 m2 (12 m × 36) et deux variétés de niébé (V1 : variété H36, V2= variété Diamant) étaient semées en différentes dates (D1, D2, D3 et D4), respectivement pour le premier, le deuxième, le troisième et le quatrième semis, avec au total huit répétitions. Chaque unité d’échantillonnage (parcelle) avait une superficie de 9 m2 dans lequel le semis était fait aux écartements de 60 cm x 40 cm. Au niveau de chaque répétition, dans la parcelle principale (3 m x 3 m) étaient semées des variétés (traitement principal) de façon randomisée. Ainsi, au niveau de la parcelle élémentaire (3 m x 3 m), la date de semis était reprise (traitement élémentaire).Résultats. Les résultats obtenus indiquent que les différentes dates de semis n’ont pas influencé significativement la plupart des paramètres observés (nombre de plants à la floraison, nombre de gousses par plant, nombre de plants malades, le poids des gousses fraiches par plant et le nombre de plants avant la récolte). Les différences significatives ont été constatées pour les autres paramètres, tels que le poids de 1000 graines et le rendement. Le rendement en graines de niébé a été affecté par les différentes dates de semis et les variétés car l’analyse de la variance a montré qu’il existe des différences significatives entre les dates de semis. Les semis réalisés à la première et dernière date ont donné des faibles rendements de 278,1 kg/ha et 280,5 kg/ha par rapport au semis à la troisième date (388 kg/ha). Par ailleurs, le rendement le plus élevé a été obtenu avec la troisième date de semis et la variété diamant, soit 388 kg/ha et 373,3 kg/ha.Conclusion. Les résultats obtenus montrent que les semis précoce et tardif entraînent un ralentissement de croissance et une baisse de rendement. Cette étude apporte une contribution dans la diffusion et la détermination de la période optimale de semis en vue d’accroitre efficacement le rendement du niébé dans les conditions éco-climatiques de Kananga. Description of the subject. Cowpea is a grain legume that plays an important role in sub-Saharan Africa, particularly in arid and semi-arid savannah areas. Cowpea sowing times, its vegetative development and agricultural calendars are completely disrupted by climate change. It is in this context that this study was undertaken with a view to proposing the technical itinerary adapted to the study environment.Objective. The objective of the study is to analyze the effects of sowing dates and cultivars of Vigna unguiculata on the yield of dry seeds in the eco-climatic conditions of Kananga in central Kasai in the Democratic Republic of Congo.Methods. The Split plot experimental design was applied. The surface area of the experimental field was 432 m2 (12 m × 36) and two varieties of cowpea (V1: variety H36, V2= Diamant variety) were sown on different dates (D1, D2, D3 and D4), respectively for the first , the second, the third and the fourth sowing, with a total of eight repetitions. Each sampling unit (plot) had an area of 9 m2 in which sowing was done at spacings of 60 cm x 40 cm. At the level of each repetition, in the main plot (3 m x 3 m) varieties (main treatment) were sown in a randomized manner. Thus, at the level of the elementary plot (3 m x 3 m), the sowing date was repeated (elementary treatment).Results. The results obtained indicate that the different sowing dates did not significantly influence most of the parameters observed (number of plants at flowering, number of pods per plant, number of diseased plants, weight of fresh pods per plant and the number of plants before harvest). Significant differences were found for other parameters, such as 1000 seed weight and yield. Cowpea seed yield was affected by different sowing dates and varieties as analysis of variance showed that there are significant differences between sowing dates. Sowing carried out on the first and last dates gave low yields of 278.1 kg/ha and 280.5 kg/ha compared to sowing on the third date (388 kg/ha). Furthermore, the highest yield was obtained with the third sowing date and the diamond variety, i.e. 388 kg/ha and 373.3 kg/ha.Conclusion. The results obtained show that early and late sowing lead to a slowdown in growth and a reduction in yield. This study contributes to the dissemination and determination of the optimal sowing period with a view to effectively increasing cowpea yield in the eco-climatic conditions of Kananga.
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SUJATHA, K., P. NATARAJKUMAR, G. S. LAHA, B. MISHRA, K. SRINIVASA RAO, B. C. VIRAKTAMATH, P. B. KIRTI, et al. "Inheritance of bacterial blight resistance in the rice cultivar Ajaya and high-resolution mapping of a major QTL associated with resistance." Genetics Research 93, no. 6 (December 2011): 397–408. http://dx.doi.org/10.1017/s0016672311000577.
Повний текст джерелаАнотація:
SummaryThe cultivar Ajaya (IET 8585) exhibits durable broad-spectrum resistance to bacterial blight (BB) disease of rice and is widely used as a resistance donor. The present study was carried out to decipher the genetics of BB resistance in Ajaya and map the gene(s) conferring resistance. Genetic analysis in the F2 indicated a quantitative/additive nature of resistance governed by two loci with equal effects. Linked marker analysis and allelic tests revealed that one of the resistance genes is xa5. Sequence analysis of a 244 bp region of the second exon of the gene-encoding Transcription factor IIAγ (the candidate gene for xa5) confirmed the presence of xa5. Bulked-segregant analysis (BSA) revealed the putative location of the two quantitative trait loci (QTLs)/genes associated with resistance on chromosomes 5 and 8. Composite interval mapping located the first locus on Chr. 5S exactly in the genomic region spanned by xa5 and the second locus (qtl BBR 8.1) on Chr. 8L. Owing to its differential disease reaction with a set of seven hyper-virulent isolates of Xanthomonas oryzae, a map location on Chr. 8L, which was distinct from xa13 and data from allelism tests, the second resistance locus in Ajaya was determined to be novel and was designated as xaAj. A contig map spanning xaAj was constructed in silico and the genomic region was delimited to a 13·5 kb physical interval. In silico analysis of the genomic region spanning xaAj identified four putatively expressed candidate genes, one of which could be involved in imparting BB resistance in Ajaya along with xa5.
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Szabó, M., Z. Czajlik, K. Tankó, and L. Timár. "Polgár 1: L’habitat du second age du Fer (IIIesiecle av. J.-Chr.)." Acta Archaeologica Academiae Scientiarum Hungaricae 59, no. 2 (December 2008): 183–223. http://dx.doi.org/10.1556/aarch.59.2008.2.6.
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Nihan, Christophe. "Textual Fluidity and Rewriting in Parallel Traditions." Journal of Ancient Judaism 4, no. 2 (May 14, 2013): 186–209. http://dx.doi.org/10.30965/21967954-00402003.
Повний текст джерелаАнотація:
This article addresses some key aspects of the relation between textual fluidity and rewriting in the Second temple period on the basis of the comparison between the David traditions in Samuel and in Chronicles. While the discovery of Sam manuscripts in Cave 4 of Khirbet Qumran (especially 4QSama) has made likely that Chr used a source distinct from Sam MT, recent debates about the character of 4QSama and literary revisions in Sam MT and LXX suggest that the fluidity of the David traditions at the time of Chr’s composition may in fact have been even more significant than previously assumed. Building on this, the article compares the rewriting of these David traditions in Sam and Chr; in particular, it argues that although the scope of such rewriting is usually much more significant in Chr, there are several passages where Chr preserves an account of David which is less expansionist than Sam MT, and sometimes even than any other ancient version of Sam, as already observed by S. L. McKenzie and others. The implications of this finding for the characterization of Chr as rewritten composition are explored in the last part of the article. Chr’s relation to Sam emerges as a paradigmatic – albeit by no means unique – example of the complex dynamics that unite a rewritten composition to its source; this finding questions any simple, straightforward relation between the development of rewritten compositions and the textual stabilization of the source(s) on which these compositions are based. Furthermore, while it is possible to understand what features, precisely, would have led the ancient audience of Chr to see that work as a new composition, rather than as a variant edition of its source, it is dubious that such features may be used to define a literary genre proper.
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Vidlâkovâ, Olga. "La réforme des structures locales dans la République tchèque." Revue française d'administration publique 74, no. 1 (1995): 229–41. http://dx.doi.org/10.3406/rfap.1995.2954.
Повний текст джерелаАнотація:
The Reform of Local Structures in the Czech Republic. The reform of local structures in the Czech Republic consisted, in the first place, to guarantee the municipalities’ independence by fixing their powers and by enumerating their composing organs. Besides the prerogatives related to the management of local affairs, the municipalities were also given some atributions delegated by the State. The Constitutional Act of January lst, 1993, also provides for the creation of a second level of territorial divisions whith its own powers. Nevertheless, this reform has not been completed yet because of the difficulties to draw the territorial divisions and the necessity to define the State-local authorities relations.
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Evenden, Matthew. "Harold Innis, the Arctic Survey, and the Politics of Social Science during the Second World War." Canadian Historical Review 79, no. 1 (January 1998): 36–67. http://dx.doi.org/10.3138/chr.79.1.36.
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Gidney, Catherine. "Under the President's Gaze: Sexuality and Morality at a Canadian University during the Second World War." Canadian Historical Review 82, no. 1 (March 2001): 36–54. http://dx.doi.org/10.3138/chr.82.1.36.
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Mathes, Wendy Foulds, David L. Aylor, Darla R. Miller, Gary A. Churchill, Elissa J. Chesler, Fernando Pardo-Manuel de Villena, David W. Threadgill, and Daniel Pomp. "Architecture of energy balance traits in emerging lines of the Collaborative Cross." American Journal of Physiology-Endocrinology and Metabolism 300, no. 6 (June 2011): E1124—E1134. http://dx.doi.org/10.1152/ajpendo.00707.2010.
Повний текст джерелаАнотація:
The potential utility of the Collaborative Cross (CC) mouse resource was evaluated to better understand complex traits related to energy balance. A primary focus was to examine if genetic diversity in emerging CC lines (pre-CC) would translate into equivalent phenotypic diversity. Second, we mapped quantitative trait loci (QTL) for 15 metabolism- and exercise-related phenotypes in this population. We evaluated metabolic and voluntary exercise traits in 176 pre-CC lines, revealing phenotypic variation often exceeding that seen across the eight founder strains from which the pre-CC was derived. Many phenotypic correlations existing within the founder strains were no longer significant in the pre-CC population, potentially representing reduced linkage disequilibrium (LD) of regions harboring multiple genes with effects on energy balance or disruption of genetic structure of extant inbred strains with substantial shared ancestry. QTL mapping revealed five significant and eight suggestive QTL for body weight (Chr 4, 7.54 Mb; CI 3.32–10.34 Mb; Bwq14), body composition, wheel running (Chr 16, 33.2 Mb; CI 32.5–38.3 Mb), body weight change in response to exercise (1: Chr 6, 77.7Mb; CI 72.2–83.4 Mb and 2: Chr 6, 42.8 Mb; CI 39.4–48.1 Mb), and food intake during exercise (Chr 12, 85.1 Mb; CI 82.9–89.0 Mb). Some QTL overlapped with previously mapped QTL for similar traits, whereas other QTL appear to represent novel loci. These results suggest that the CC will be a powerful, high-precision tool for examining the genetic architecture of complex traits such as those involved in regulation of energy balance.
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Baudry, Robinson. "Les pratiques adoptives au dernier siècle de la République." Ktèma : civilisations de l'Orient, de la Grèce et de Rome antiques 46, no. 1 (2021): 343–56. http://dx.doi.org/10.3406/ktema.2021.3054.
Повний текст джерелаАнотація:
Even though adoption was one of the means used by aristocratic families to ensure social reproduction, such a practice remains difficult both to identify and measure. During the last century of the Republic, it is best-known for two borderline cases, which partly overlap, since one is a procedure, whereas the other means a specific aim – ‘testamentary adoptions’ and ‘political adoptions’. The first type implies successional and onomastic effects without leading to any change in family statuses. The second one has a political aim which entails a transformation of the family status. Both types of adoption can be accounted for by a growing competition among aristocrats, which required to resort to new family strategies.
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Koren-Michowitz, Maya, Philipp D. le Coutre, Justus Duyster, Christof Scheid, Panayiotis Panayiotidis, Witold Prejzner, Jacob M. Rowe, Michaela Schwarz, Neta Goldschmidt, and Arnon Nagler. "Prior Response to Imatinib Predicts Response to Second Line Treatment with Nilotinib in CML Patients Resistant or Intolerant to Imatinib." Blood 114, no. 22 (November 20, 2009): 3297. http://dx.doi.org/10.1182/blood.v114.22.3297.3297.
Повний текст джерелаАнотація:
Abstract Abstract 3297 Poster Board III-185 Nilotinib is active in imatinib resistant or intolerant CML patients and was recently FDA and EMEA approved for these indications in chronic and accelerated phases. We report the efficacy and safety of 400mg BID nilotinib treatment in 88 CML patients (CP=58, AP=11, BP=19) treated within 2 phase II expanded access clinical trials (CAMN107AIL01 and ENACT). Median age of included patients was 60 years (range 23-85) and the median disease duration 44 months (range 2-200). Imatinib resistance was the reason for inclusion in 66 (75%) and intolerance in 22 (25%). Thirty-five percent were previously treated with α interferon, 18% with another 2nd generation TKI and 7.5% have undergone SCT. Twenty-six percent harbored ABL KD mutations at study entry. Overall 90% of patients responded to nilotinib therapy with best responses of CHR in 23 (27%), PCyR in 10 (12%), CCyR in 12 (14%), MMolR in 16 (19%), stable disease in 15 (18%) and return to CP in 1 patient (1%). In CP, CHR was newly achieved in 25/35 (71%), PCyR in 14/32 (44%), CCyR in 14/37 (38%) and MMolR in 8/41 (20%) of patients not having those responses at study entry, while the respective responses in advanced phase (AP+BP) were 58% (CHR), 30% (PCyR), 33% (CCyR) and 7.7% (MMolR). In imatinib resistant and imatinib intolerant patients, response rates were, respectively, 61% and 75% for CHR, 36% and 50% for PCyR, 29% and 47% for CCyR and 16% and 33% for MMolR with group comparisons NS in all cases. The best response achieved on imatinib therapy was predictive of the best response to nilotinib while imatinib resistance as defined in the study inclusion criteria was predictive of progression or lack of response to nilotinib therapy. Sixty-one percent of patients whom best response to imatinib was a CHR achieved a CHR as their best response to nilotinib while 83% of patients with at least a MCyR to imatinib have achieved at least a MCyR to nilotinb therapy (p=0.0025). Moreover, at the time of analysis, 32% of imatinib resistant patients have discontinued therapy due to lack of efficacy or disease progression compared to none of the imatinib intolerant patients (p=0.0012). Responses were not statistically different in patients with ABL KD mutations compared to those without mutations, patients with and without additional cytogentic abnormalities at study entry and patients with prior treatment with another 2nd generation tyrosine kinase inhibitor compared to those without prior treatment. Adverse hematological events during nilotinib treatment included thrombocytopenia in 27% and leucopenia in 18%, being grade 3-4 in 13% and 10%, respectively. Common biochemical abnormalities included hyperbilirubinemia (17%, [grade 3-4 2%]), elevated liver enzymes (14%, [1%]) hyperglycemia (7%) and elevated amylase or lipase (6%). The majority of the non-hematological events were mild, the common being rash (14%, [1%]), infection (9%, [1%]), bone pain (6% [1%]), headache (5%) and nausea and vomiting (4%). In summary, nilotinib treatment is an efficient and safe therapy for imatinib resistant or intolerant patients. Prior response to imatinib therapy is a predictor for response to nilotinib. Disclosures le Coutre: Novartis: Honoraria. Nagler:Novartis: Consultancy, Honoraria, Research Funding, paprticipating in Leadsummite .
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Tomaselli, Carmen. "Use of nilotinib in the diabetic patient." Clinical Management Issues 4, no. 5S (October 13, 2015): 19–22. http://dx.doi.org/10.7175/cmi.v4i5s.1094.
Повний текст джерелаАнотація:
A 42-year-old man, diabetic patient, after CML Ph+ diagnosis started a treatment with imatinib reaching both CHR and CCyR within 6 months. Because of two episodes of vitreous haemorrhage the treatment was discontinued for four months with the lost of the CCyR and the maintenance of the CHR. The patient begun second line therapy with nilotinib, another TK inhibitor, recovering CCyR after 3 months and MMolR after 12 months, and keeping them up after 18 months of treatment. Nilotinib related side effects were transient rash and first degree arthromyalgia that occurred during the first month of therapy. In this case nilotinib therapy has shown to be safe and effective also for diabetic patients with intolerance to imatinib.
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Bourg, Wilson C., Theresa M. Launder, and Tariq I. Mughal. "Hematological Responses to Megesterol Acetate in Patients with Myelodysplastic Syndrome Involving an Abnormal Chromosome 6." Blood 106, no. 11 (November 16, 2005): 4922. http://dx.doi.org/10.1182/blood.v106.11.4922.4922.
Повний текст джерелаАнотація:
Abstract The presence of an abnormal chromosome (chr) 6 often confers a poor prognosis on patients with myelodysplastic syndrome (MDS), particularly therapy related-MDS (t-MDS). We report two patients with MDS and an abnormal chr 6 who achieved significant improvements in their hematological parameters after being subjected to megesterol actetate at 80mg/d; one patient achieved a complete cytogenetic remission, albeit based on a limited study. The first patient, a 73 y female presented with a monocytopenia (thrombocytopenia; 43K/dl), a bone marrow consistent with MDS, blasts 6% and an abnormal chr 6 (sole cytogenetic abnormality) in February 2003. In July 2005 she was asymptomatic with a platelet count of 353K/dl and is due to have cytogenetics shortly. The second patient, a 72 y female presented in December 2004 with trilineage cytopenias, a bone marrow consistent with MDS and a complex karyotype, including an abnormal chr 2, 5, 6, 7 & 16. She had had a history of primary (essential) thrombocythemia of 25 y duration and had received P 32 and intermittent courses of hydroxyurea and was on hydroxyurea at the penultimate presentation and probably had t-MDS. This therapy was promptly discontinued and megesteral acetate commenced at 80mg/d. In July 2005 her hematological parameters had improved significantly (W 3.3K/dl; Hb 11.3g/dl;Platelets 135K/dl); her bone marrow remained hypercellular with reticulin fibrosis and cytogenetic studies revealed a 46XX kayotype in a limited sample. At the time of this report, both patients remain well on megesterol acetate with normal or near normal hematological parameters. MDS is a heterogeneous stem cell disorder and hematological and possible cytogenetic responses are noteworthy. The patient with the sole abnormal chr 6 has remained in hematological remission for over 18 months; the second patient with the complex karyotype is also, remarkably, maintaining near normal hematological parameters. We speculate that megesterol acetate, a relatively inexpensive progestational agent with a defined palce in the management of malignancy-related anorexia may have a role in selected patients with MDS. Updated observations and suggested hypotheses will be presented.
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Bouthillon, Fabrice. "Un cas de sagesse orientale : le Second Ralliement de l’Église à la République." Commentaire Numéro159, no. 3 (2017): 593. http://dx.doi.org/10.3917/comm.159.0593.
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Varry, Dominique. "Imprimerie et librairie à Lyon sous la Seconde République et le Second Empire." Chrétiens et sociétés, no. 25 (October 10, 2018): 69–92. http://dx.doi.org/10.4000/chretienssocietes.4431.
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Pasolli, Lisa. "“I ask you, Mr. Mitchell, is the emergency over?”: Debating Day Nurseries in the Second World War." Canadian Historical Review 96, no. 1 (March 2015): 1–31. http://dx.doi.org/10.3138/chr.2642.
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Ueno, Takahiro, Johanne Tremblay, Jaroslav Kunes, Josef Zicha, Zdenka Dobesova, Zdenka Pausova, Alan Y. Deng, Yu-Lin Sun, Howard J. Jacob, and Pavel Hamet. "Rat model of familial combined hyperlipidemia as a result of comparative mapping." Physiological Genomics 17, no. 1 (March 12, 2004): 38–47. http://dx.doi.org/10.1152/physiolgenomics.00043.2003.
Повний текст джерелаАнотація:
Total genome scan was carried out in 266 F2 intercrosses from the Prague hypertriglyceridemic (HTG) rat that shares several clinical characteristics with human metabolic syndrome. Two loci for plasma triglycerides (TG) were localized on chromosome 2 (Chr 2) (LOD 4.4, 3.2). The first locus overlapped with the rat syntenic region of the human locus for the metabolic syndrome and for small, dense LDL, while the second overlapped with the syntenic region of another locus for small, dense LDL in humans by the comparative mapping approach. Loci for TG on rat Chr 13 (LOD 3.3) and Chr 1 (LOD 2.7) overlapped with the syntenic region of loci for human familial combined hyperlipidemia (FCHL) in Finnish and Dutch populations, respectively. The concordances of loci for TG localized in this study with previously reported loci for FCHL and its related phenotypes are underlying the generalized importance of these loci in dyslipidemia. These data suggest the close relationship between dyslipidemia in HTG rats and human FCHL, establishing a novel animal model for exploration of pathophysiology and therapy based on genomic determinants.
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Cano-Muñoz, Mario, Julie Lucas, Li-Yun Lin, Samuele Cesaro, Christiane Moog, and Francisco Conejero-Lara. "Conformational Stabilization of Gp41-Mimetic Miniproteins Opens Up New Ways of Inhibiting HIV-1 Fusion." International Journal of Molecular Sciences 23, no. 5 (March 3, 2022): 2794. http://dx.doi.org/10.3390/ijms23052794.
Повний текст джерелаАнотація:
Inhibition of the HIV-1 fusion process constitutes a promising strategy to neutralize the virus at an early stage before it enters the cell. In this process, the envelope glycoprotein (Env) plays a central role by promoting membrane fusion. We previously identified a vulnerability at the flexible C-terminal end of the gp41 C-terminal heptad repeat (CHR) region to inhibition by a single-chain miniprotein (named covNHR-N) that mimics the first half of the gp41 N-terminal heptad repeat (NHR). The miniprotein exhibited low stability, moderate binding to its complementary CHR region, both as an isolated peptide and in native trimeric Envs, and low inhibitory activity against a panel of pseudoviruses. The addition of a disulfide bond stabilizing the miniprotein increased its inhibitory activity, without altering the binding affinity. Here, to further study the effect of conformational stability on binding and inhibitory potency, we additionally stabilized these miniproteins by engineering a second disulfide bond stapling their N-terminal end, The new disulfide-bond strongly stabilizes the protein, increases binding affinity for the CHR target and strongly improves inhibitory activity against several HIV-1 strains. Moreover, high inhibitory activity could be achieved without targeting the preserved hydrophobic pocket motif of gp41. These results may have implications in the discovery of new strategies to inhibit HIV targeting the gp41 CHR region.
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Bellaloui, Nacer, Dounya Knizia, Jiazheng Yuan, Qijian Song, Frances Betts, Teresa Register, Earl Williams, et al. "Genetic Mapping for QTL Associated with Seed Nickel and Molybdenum Accumulation in the Soybean ‘Forrest’ by ‘Williams 82’ RIL Population." Plants 12, no. 21 (October 28, 2023): 3709. http://dx.doi.org/10.3390/plants12213709.
Повний текст джерелаАнотація:
Understanding the genetic basis of seed Ni and Mo is essential. Since soybean is a major crop in the world and a major source for nutrients, including Ni and Mo, the objective of the current research was to map genetic regions (quantitative trait loci, QTL) linked to Ni and Mo concentrations in soybean seed. A recombinant inbred line (RIL) population was derived from a cross between ‘Forrest’ and ‘Williams 82’ (F × W82). A total of 306 lines was used for genotyping using 5405 single nucleotides polymorphism (SNP) markers using Infinium SNP6K BeadChips. A two-year experiment was conducted and included the parents and the RIL population. One experiment was conducted in 2018 in North Carolina (NC), and the second experiment was conducted in Illinois in 2020 (IL). Logarithm of the odds (LOD) of ≥2.5 was set as a threshold to report identified QTL using the composite interval mapping (CIM) method. A wide range of Ni and Mo concentrations among RILs was observed. A total of four QTL (qNi-01, qNi-02, and qNi-03 on Chr 2, 8, and 9, respectively, in 2018, and qNi-01 on Chr 20 in 2020) was identified for seed Ni. All these QTL were significantly (LOD threshold > 2.5) associated with seed Ni, with LOD scores ranging between 2.71–3.44, and with phenotypic variance ranging from 4.48–6.97%. A total of three QTL for Mo (qMo-01, qMo-02, and qMo-03 on Chr 1, 3, 17, respectively) was identified in 2018, and four QTL (qMo-01, qMo-02, qMo-03, and qMo-04, on Chr 5, 11, 14, and 16, respectively) were identified in 2020. Some of the current QTL had high LOD and significantly contributed to the phenotypic variance for the trait. For example, in 2018, Mo QTL qMo-01 on Chr 1 had LOD of 7.8, explaining a phenotypic variance of 41.17%, and qMo-03 on Chr 17 had LOD of 5.33, with phenotypic variance explained of 41.49%. In addition, one Mo QTL (qMo-03 on Chr 14) had LOD of 9.77, explaining 51.57% of phenotypic variance related to the trait, and another Mo QTL (qMo-04 on Chr 16) had LOD of 7.62 and explained 49.95% of phenotypic variance. None of the QTL identified here were identified twice across locations/years. Based on a search of the available literature and of SoyBase, the four QTL for Ni, identified on Chr 2, 8, 9, and 20, and the five QTL associated with Mo, identified on Chr 1, 17, 11, 14, and 16, are novel and not previously reported. This research contributes new insights into the genetic mapping of Ni and Mo, and provides valuable QTL and molecular markers that can potentially assist in selecting Ni and Mo levels in soybean seeds.
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Msambya, Joseph Apolo. "De la République Démocratique du Congo voulue indépendante À la République Démocratique du Congo qui commémore ses fêtes d’indépendance." Studia Universitatis Babeș-Bolyai Studia Europaea 69, no. 1 (June 27, 2024): 89–112. http://dx.doi.org/10.24193/subbeuropaea.2024.1.05.
Повний текст джерелаАнотація:
From the Democratic Republic of Congo Seeking Independence to the Democratic Republic of Congo which Commemorates Its Independence Celebrations. On June 30, 1960, the independence of the Belgian Congo, once personal possession for 23 years of the Belgian King Leopold II, was proclaimed as the “Republic of the Congo”. Emery-Patrice Lumumba (1925-1961) played a capital role in this emancipation which resulted in the consecration of Joseph Kasavubu as first President of the Republic of Congo and himself, Emery Patrice Lumumba, as Prime Minister. Congo has proclaimed its independence, but the new country remains plagued by violence and infighting. Belgian troops and peacekeepers from the United Nations intervene in the territory as a standoff begins between Kasavubu and Lumumba. On September 14, 1960, Colonel Joseph Désiré Mobutu led a first coup d’état which was followed by the arrest and assassination of Lumumba. The following years would be punctuated by rebellions and fighting interspersed with ceasefires in protest against the dictatorship established by the Mobutu regime after its second coup d’état, five years later, during a new political crisis. After thirty-two years of unchallenged reign, Mobutu was ousted from power by Mzee Laurent Désiré Kabila in May 1997 and since then, it has been difficult to speak of the real independence of the country, which became the Democratic Republic of Congo. Keywords: formal independence, real independence, Independence Day, Zaïre, Democratic Republic of Congo, colonization, decolonization, political emancipation, sovereignty.
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Barkov, Andrei Y., Andrey A. Nikiforov, Vladimir N. Korolyuk, Larisa P. Barkova, and Robert F. Martin. "The chromian spinels of the Lyavaraka ultrabasic complex, Serpentinite Belt, Kola Peninsula, Russia: Patterns of zoning, hypermagnesian compositions, and early oxidation." Canadian Mineralogist 59, no. 6 (November 1, 2021): 1693–709. http://dx.doi.org/10.3749/canmin.2100019.
Повний текст джерелаАнотація:
ABSTRACT The maximum value of Mg# [= 100Mg/(Mg + Fe2+ + Mn)] in chromium-bearing spinel-group minerals (Chr) in the Ultrabasic Core Zone (UCZ) of the Lyavaraka orthopyroxenite – harzburgite – dunite complex of the Serpentinite Belt in the Kola Peninsula is 54.5–67.5. Such highly magnesian compositions of spinel are associated with notable enrichments of ferric iron (Fe3+# 58–63). There are two generations of accessory Chr in the UCZ unit. The first generation occurs as inclusions in olivine that is not unusually magnesian (Mg# 90.3), and the second is closely associated with serpentine. The compositional series of Chr at Lyavaraka attains more aluminous compositions than was observed in nearby intrusive bodies. The anomalously high level of Mg in Chr, also manifest in ilmenite, is mainly a result of the high intrinsic fugacity of oxygen attained locally in the melt. A progressive buildup in H2O and increase in fO2 likely resulted from efficient vesiculation and selective loss of H2 from the Al-undepleted komatiitic magma crystallizing in a shallow setting. The chromian spinel forming in such a modified magma is virtually unzoned in Mn, and a minor quantity of Mn is also present in olivine and orthopyroxene. In contrast, zinc is strongly partitioned in the core of Chr, as it is relatively incompatible in the coexisting olivine and orthopyroxene at that stage. Zinc efficiently partitioned into the H2O-enriched melt, which crystallized as the pegmatitic orthopyroxenite near the contacts at Lyavaraka. A high potential of oxidation appears to be characteristic of all orthopyroxenite – harzburgite – dunite suites of the Serpentinite Belt formed from a primitive melt of komatiitic composition.
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Gernone, A., S. Trabucco, G. Troccoli, V. Pagliarulo, and A. Pagliarulo. "Prognostic role of chromogranin A expression for docetaxel response in hormone-refractory metastatic prostate cancer." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 15528. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.15528.
Повний текст джерелаАнотація:
15528 Background: The neuroendocrine (NE) cells in prostate cancer are indistinguishable from non-NE cancer cells morphologically and are usually detected by immunohistochemical study for NE markers. We analyzed the expression of Chromogranin A (Chr A) in malignant prostate tissue as prognostic factor for docetaxel response in metastatic HRPC. Methods: From January 2003 to December 2006, 40 patients with metastatic HRPC received a median of 12 cycles (range 2–18) of Docetaxel 75 mg/mq every 21 days and 5 mg of prednisone twice daily as initial therapy. Tissue blocks from primary prostate cancer tissues were obtained and immunostaining for Chr A was performed. The median age was 70 years (range 46–82); median baseline PSA: 310 ng/ml (range 0.15–700); median ECOG Performance Status: 1 (range 0- 2). PSA level was measured every 4 weeks and the treatment was considered effective if a rate of PSA-decline > 50% from baseline was found. TTP was the preliminary end point. Results: Response to Docetaxel was assessed at every 3 cycles of treatment. The Chr A expression was found in 19/40 patients with Gleason = 7, PSA < 20, bone and soft tissue metastasis; 10 of them showed PR (decrease in PSA < 50%), 4 SD and TTP was 9.2 months. Moreover they received second line chemotherapy without significant efficacy. 5/19 patients with Chr A expression showed PD, the PSA level was not correlated with clinical outcome, TTP was 5 months and were chemoresistant to different line treatment. Besides, Chr A was not detected in 21/40 patients with Gleason = 7, PSA > 20 and bone metastasis; 10 of them showed CR (PSA normalized) and 11 PR, TTP was 20 months. Conclusions: NE differentiation do not constituite a different histopathological category of prostate cancer but the NE phenotype can be correlated with poorly differentiated adenocarcinoma. NE differentiation can be considered a factor that influences prognosis and treatment in advanced prostate cancer; cases with Chr A expression did not benefit from Docetaxel and had poor prognosis. These preliminary data indicate that initial therapeutic approach should be different according to Chr A expression. No significant financial relationships to disclose.
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Dawson, Michael. "From ‘Business as Usual’ to ‘Salesmanship in Reverse’: Tourism Promotion in British Columbia during the Second World War." Canadian Historical Review 83, no. 2 (June 2002): 230–54. http://dx.doi.org/10.3138/chr.83.2.230.
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Chansung, Kanchana, Chittima Sirijerachai, Arnuparp Lekhakula, Pongtep Viboonjuntra, Pimjai Niparuck, Teeraya Pauvilai, Tontanai Numbenjapon, et al. "Nilotinib As Second-Line Therapy in Patients with Chronic Myeloid Leukemia in Chronic Phase: Thailand Experience." Blood 128, no. 22 (December 2, 2016): 5448. http://dx.doi.org/10.1182/blood.v128.22.5448.5448.
Повний текст джерелаАнотація:
Abstract Background: Nilotinib, a second generation tyrosine kinase inhibitor, was proved to have high efficacy on treatment of Philadelphia chromosome positive CML patients who failed or were intolerant to imatinib. Limited data was available on its efficacy and safety in Asian population. Methods: Chronic phase CML patients who have failure, suboptimal response or intolerance to imatinib according to ELN 2009 guideline were treated with nilotinib 400 mg twice daily on 7 centers in Thailand. Prospective data collection for 24 months was performed. Results: There were 106 cases participated in this study, 2 cases with initial T315I mutation were excluded from the study, total 104 cases were analysed. The median age was 46 (16-79) years with a slight male predominance over female at the ratio of 1.4:1 respectively. Twenty five percent received imatinib less than 12 months whilst 20% received imatinib longer than 60 months. The median duration of the prior imatinib treatment was 18 months (2-142 months). Best response to imatinib treatment were major molecular response (MMR) 5.8%, complete cytogenetic response (CCyR) 26%, major cytogenetic response (MCyR) 12.5%, complete hematologic response (CHR) 47%, and no CHR 8.7%. The reasons for nilotinib switching were imatinib failure 65%, imatinib intolerance 28%, imatinib suboptimal response 7%. Sixty-eight percent were completed 24 months follow up. Of those, 32% early discontinued treatment mostly because of unsatisfactory results or adverse events. Two patients died of infection and CNS bleeding during the study period. Evaluation were made every 3 months based on ELN 2009 criteria . Best response to nilotinib treatment included MMR 57%, CCyR 16%, MCyR 6%, CHR 16%, and no CHR 5%. At 3 months, 91%, 35%, and 14% of the patients CHR,CCyR, and MMR, respectively. Achieving CCyR or MMR at 3 months predicted a chance of achieving MMR (P= 0.00001) Those who did not achieve at least CHR at 3 months never achieved MMR, while 86 % of those who achieved CCyR at 3 months achieved MMR and 100% of those achieving MMR at 3 months had sustained MMR throughout the study period (24 months). Imatinib suboptimal response had significantly better outcome as compared to imatinib failure and imatinib intolerance group (P = 0.017). All of suboptimal response cases achieved CCyR , 86% achieved MMR, no early discontinue treatment in this group. While 75% of failure group achieved CCyR, 62% achieved MMR and 62% of intolerance group achieved CCyR, 38% achieved MMR. The reason for poorer response of intolerance group was high rate of early discontinue due to side effects, 17% vs 5% in the imatinib failure group. Initial BCR-ABL mutation analysis was performed on 90 cases, mutations were found on 16 cases, 2 of them were T315I which were excluded from the study. The cases with mutation significantly had poorer response to treatment than those without mutation (P = 0.001). There was one case with initial G250E mutation, who developed T315I mutation after treatment with nilotinib. At 24 months, 1 case progressed to accelerated phase and 3 cases progressed to blastic transformation. The 2-year progression-free survival and 2-year overall survival was 96% and 98%, respectively. Skin rash, musculoskeletal pain, and infection were the three most common non-hematologic adverse events found in 18%, 13%, and 6% of the patients, respectively; however, most of them were grade 1-2, except for 4 cases with grade 3-4 infections .Grade 3-4 hematologic adverse events included thrombocytopenia (12%), neutropenia (11%), anemia (5%), and leucopenia (4%); and most of them were manageable. Although biochemical abnormalities were commonly found, most of them were mild. Grade 3-4 events found were hypophosphatemia (6%), hyperglycemia (4%), and elevated serum lipase (4%). Only 10 cases (9%) permanently discontinued nilotinib due to its adverse effects. Conclusions: Nilotinib, as a second line treatment for Thai patients with chronic phase CML showed excellent efficacy and tolerability. Indication for nilotinib treatment, initial mutation status and depth of response at 3 months after treatment can predict outcomes of the patients. Author contact: KanchanaChansung M.D. Division of Hematology, Department of Medicine, Faculty of Medicine, Khonkaen University, Khonkaen, Thailand e-mail: kchansung@gmail.com Disclosures No relevant conflicts of interest to declare.
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Abdulkadirov, Kudrat, Elza Lomaia, Alla Abdulkadirova, Vasiliy Shuvaev, Vera Udalieva, Elena Usacheva, Elena Machulaitene, et al. "Experience in Second Line TKI Treatment in 6 Million Region of Russia (St-Petersburg and Leningrad region)." Blood 114, no. 22 (November 20, 2009): 4288. http://dx.doi.org/10.1182/blood.v114.22.4288.4288.
Повний текст джерелаАнотація:
Abstract Abstract 4288 Resistance to imatinib could be overcome by new generations of TKIs. Data about the efficacy of second line TKI treatment may help to create a system for prognosing the duration of 2nd line TKI treatment and time of switching from second line TKI treatment to hematopoietic stem cell transplantation. The aim of the study was to evaluate the results of 2nd line TKI treatment in patients resistant or intolerant to imatinib. Patients and methods 44 resistant and 3 intolerant to imatinib pts were included. Cytogenetics with G-banding and PCR with sequencing were performed for evaluation the response and mutations. There were 39, 7 and 1 pts in CP, AP and BP respectively, Patients were treated by three different ATP-pocket inhibitors. The follow-up on 2nd line TKIs was 0.9-48mons (Median - 15.9 mons), median follow-up from diagnosis was 73,9 mons. In prognosis analysis (CHR, cytogenetics, Sokal) intolerant patients were not included. Results Probability of overall survival from diagnosis by 10 years was 85%. Probability of survival from the start of TKI2 by 4 y -90%. There were no differences in survival in pts with primary and secondary resistance, in CP and AP. Patients with low and intermediate Sokal risk did better than patients with high risk (p=0.014, Fig. 1.). 8 pts had T315I mutation when studied on second line TKI therapy. Achievement of CCyR was 50% (58% when T3151 patients were excluded), it was higher in low+intermediate in comparison with high risk pts (60% vs 30%, p=0.091), in CP than in AP (56% vs 20%,p=0.07), in patients with CHR at switching than in those without CHR (72% vs 18%, p=0.014). We failed to find any differences in CCyR achievement in pts with different best cytogenetic response on imatinib (complete, major, minor, minimal responses, absence of cytogenetic response). MCyR depended on the type of resistance - it was higher in secondary, than in primary resistant pts (80% vs 45%,p=0.06, Fig2). Probability of MCCyR loss was 20%, all of them appear during the first year of treatment. It was higher in AP than in CP (40% vs 12%,P=0.04). Probability of 4 years PFS was high - 75%, also without differences in primary vs secondary resistance and even in AP vs CP. Conclusion Second line TKI treatment is very efficacious in imatinib resistant pts. The effect depended on the type of resistance and phase of the disease, CHR at the moment of switching to 2nd line treatment. Disclosures: No relevant conflicts of interest to declare.