Journal articles: 'CHR 2002'

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Kuhnert, Nikolai, Nicolai Burzlaff, Eberhard Dombrowski, and Wolfdieter A. Schenk. "Cationic Ruthenium-Sulfine Complexes: Synthesis and Dynamic Behaviour." Zeitschrift für Naturforschung B 57, no. 3 (March 1, 2002): 259–74. http://dx.doi.org/10.1515/znb-2002-0302.

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AbstractCationic ruthenium sulfine complexes [CpRu(PR´3)2(O=S=CHR)]PF6 have been obtained by a variety of methods. Oxidation of the thioaldehyde complexes [CpRu(PR´3)2(S=CHR)]PF6 with either 2-tosyl-3-phenyl-oxaziridine (PR´3 = PMe3 ) or magnesium-monoperoxyphthalate (PR´3 = 1/2 dppm) gave complexes of arylsulfines (R = Ph, 3-C6H4F, 4-C6H4Cl, 4- C6H4OMe) selectively in their thermodynamically less stable E form. Siloxane elimination from the sulfinato complexes [CpRu(PMe3)2(SO2CHRSiMe3)] yielded complexes of aliphatic sulfines, [CpRu(PMe3)2(O=S=CHR)]PF6 (R =H,Me). Treatment of [CpRu(dppm)(SO2CH2R)] with acetyl chloride led to an oxygen redistribution giving complexes of thioaldehydes [CpRu(dppm)(η2-S=CH2)]PF6 and [CpRu(dppm)(η1-S=CHR)]PF6 (R = Ph, 4-C6H4Cl). The structure of the latter was determined by X-ray crystallography. The loss of oxygen can be suppressed by performing the acylation-elimination sequence in the presence of poly-(4-vinylpyridine). This provided a selective access to complexes of Z-sulfines, [CpRu(PMe3)2(O=S=CHR)]PF6 (R = Ph, 4-C6H4Cl) and [CpRu(dppm)(O=S=CHR)]PF6 (R = Ph, 4-C6H4Cl, COOEt, Cl). Complexes of the parent sulfine O=S=CH2 were also obtained by SO transfer to the methylene complex [CpRu(PMe3)2(CH2)]PF6 and methylene transfer to the sulfur monoxide complex [Cp*Ru(PMe3)2 (SO)]PF6. Most of the new sulfine complexes exhibit dynamic behaviour in solution, i. e. ligand rotation, ligand inversion, and η2 /η1 hapticity change. O-Alkylation provided the dicationic complex [CpRu(PMe3)2 (EtO-S=CHMe)](PF6)2, and S-oxidation gave the sulfene complexes [(C5R5)Ru(PMe3)2 (O2S=CH2)]PF6 (R = H, Me).

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KITLV, Redactie. "Book Reviews." Bijdragen tot de taal-, land- en volkenkunde / Journal of the Humanities and Social Sciences of Southeast Asia 160, no. 1 (2004): 124–88. http://dx.doi.org/10.1163/22134379-90003737.

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-Barbara Watson Andaya, Susan Blackburn, Love, sex and power; Women in Southeast Asia. Clayton VIC: Monash Asia Institute, 2001, iv + 144 pp. [Monash papers on Southeast Asia 55.] -Kathryn Gay Anderson, Juliette Koning ,Women and households in Indonesia; Cultural notions and social practices. Richmond, Surrey: Curzon, 2000, xiii + 354 pp. [Nordic Institute of Asian studies, studies in Asian topics 27.], Marleen Nolten, Janet Rodenburg (eds) -Greg Bankoff, Takeshi Kawanaka, Power in a Philippine city. Chiba: Institute of developing economies, 2002, 118 pp. [IDE Occasional papers series 38.] -René van den Berg, John Lynch ,The Oceanic languages. Richmond, Surrey: Curzon, 2002, xvii + 924 pp., Malcolm Ross, Terry Crowley (eds) -H.J.M. Claessen, Douglas Oliver, Polynesia in early historic times. Honolulu: Bess Press, 2002, 305 pp. -Harold Crouch, Andrew Rosser, The politics of economic liberalisation in Indonesia; State, market and power. Richmond, Surrey: Curzon, 2002, xv + 232 pp. -Hans Hägerdal, Arend de Roever, De jacht op sandelhout; De VOC en de tweedeling van Timor in de zeventiende eeuw. Zutphen: Walburg Pers, 2002, 383 pp. -Fiona Harris, Lorraine V. Aragon ,Structuralism's transformations; Order and revision in Indonesian and Malaysian societies; Paper written in honor of Clark E. Cunningham. Tempe AZ: Arizona State University Press, 1999, lxii + 402 pp., Susan D. Russell (eds) -David Henley, Christiaan Heersink, Dependence on green gold: A socio-economic history of the Indonesian coconut island Selayar. Leiden: KITlV Press, 1999, xviii + 371 pp. [Verhandelingen 184.] -David Hicks, James T. Siegel ,Southeast Asia over three generations; Essays presented to Benedict R.O'G. Anderson 2003, 398 pp. Ithaca NY: Cornell University Southeast Asia program. [Studies on Southeast Asia 36.], Audrey R. Kahin (eds) -Janny de Jong, L. de Jong, The collapse of a colonial society; The Dutch in Indonesia during the second world war. With an introduction by Jeroen Kemperman. Leiden: KITLV Press, 2002, 570 pp. [Verhandelingen 206.] -Gerry van Klinken, Grayson Lloyd ,Indonesia today; Challenges of history. Singapore: Institute of Southeast Asian studies, 2001, 359 pp., Shannon Smith (eds) -Johanna van Reenen, Frédéric Durand, Timor Lorosa'e, pays au carrefour de l'Asie et du Pacifique; Un atlas géo-historique. Marne-la-Vallée: Presses Universitaires de Marne-la-Vallée, 2002, 208 pp. -William R. Roff, Mona Abaza, Debates on Islam and knowledge in Malaysia and Egypt; Shifting worlds. London: RoutledgeCurzon, 2002, xix + 304 pp. -Mariëtte van Selm, Chr. van Fraassen ,G.E. Rumphius, De Ambonse eilanden onder de VOC, zoals opgetekend in 'De Ambonse landbeschrijving'. Utrecht: Landelijk Steunpunt Educatie Molukkers, 2002, 254 pp., H. Straver (eds) -K. Thirumaran, Prema-Chandra Athukorala, Crisis and recovery in Malaysia; The role of capital controls. Cheltenham: Elgar, 2001, xii + 159 pp. -K. Thirumaran, John Hilley, Malaysia; Mahathirism, hegemony and the new opposition. London: Zed books, 2001, xiii + 305 pp. -Reina van der Wiel, Damien Kingsbury ,Foreign devils and other journalists. Clayton VIC: Monash Asia Institute, 2000, vi + 277 pp. [Monash papers on Southeast Asia 52.], Eric Loo, Patricia Payne (eds) -Jennifer Fraser, Philip Yampolsky, Music of Indonesia. Washington DC: Smithsonian Folkways recordings, 1991-2000, 20 compact discs plus a CD of selections from the series, Discover Indonesia. All with accompanying booklets. -Robert Wessing, Nicola Tannenbaum ,Founders' cults in Southeast Asia; Ancestors, polity, and identity. New Haven CT: Yale University Southeast Asian studies, 2003, xi + 373 pp. [Yale Southeast Asia studies Monograph 52.], Cornelia Ann Kammerer (eds) -Robert Wessing, Henri Chambert-Loir ,The potent dead; Ancestors, saints and heroes in contemporary Indonesia. Crows Nest, New South Wales: Allen and Unwin, Honolulu: University of Hawai'i Press, 2002, xxvi + 243 pp. [Southeast Asia publications series.], Anthony Reid (eds)

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Hasford, Joerg, Gianantonio Rosti, Doris Lindoerfer, Michele Baccarani, Joelle Guilhot, Lara Montrucchio, Francesca Rancati, et al. "Outcome and Prognosis of 1955 Patients with Chronic Myeloid Leukemia: First Results of the CML-Registry of the European Treatment and Outcome Study EUTOS." Blood 114, no. 22 (November 20, 2009): 1109. http://dx.doi.org/10.1182/blood.v114.22.1109.1109.

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Abstract Abstract 1109 Poster Board I-131 The main objective of the CML-Registry of the European Treatment and Outcome Study (EUTOS) is to collect diagnostic, treatment and outcome data of CML-patients in Europe in order to allow for the analysis of prognostic factors, the evaluation of the quality of care and the comparative assessment of outcomes. Methods Eligibility criteria were: diagnosis of chronic phase Ph+ or bcr/abl positive CML between 2002 and 2006, age ≥ 18 years, and start with any kind of imatinib-based treatment in a prospective study within six months after first diagnosis. For hematologic (HR), cytogenetic (CgR), and molecular (MR) remission the ELN criteria were used. Competing risk estimations and Landmark analyses were applied when indicated. Patients from the FI-LMC-group in France (n=526), Germany (n=644), Italy (n=513), The Netherlands (n=119), the Nordic Countries (Denmark, Finland, Norway, Sweden, n=140)) and Switzerland (n=13) were included (date: 07/11/2009), for an overall n of 1955 patients. Results Median age was 52.5 years and 45% were female. The Euro prognostic score profile was for 38% of the patients low, for 51% intermediate and for 11% high risk. Imatinib 400 mg was allocated to 41%, Imatinib 600 mg to 8%, Imatinib 800 mg to 17%, and Imatinib-based combinations with IFN or Ara C to 34% of the patients. Median observation time was 24 months (range: 1-81). Complete hematologic remission (CHR) was finally achieved by 97%, complete cytogenetic remission (CCgR) by 94%, and major molecular remission (MMR) after 18 months by 62%. Overall survival (OS) after 60 months was 92%. Euro score clearly separated high risk vs. non high risk patients with regard to CHR (p=.0002), CCgR (p=.0023), but not for MMR, whereas Sokal score did so for CCgR (p<.0001). Deletion 9q did not show any impact on CHR, CCgR or MMR. Using Landmark-analysis with those 1012 patients who provided complete data for CHR, CCgR and MMR, CHR within 6 months from day 1 of imatinib treatment showed an impact on the chance to achieve CCgR (96.1% vs. 87.5% p=.0003) and MMR at 18 month (56.1% vs. 48.5%, p=.087). CHR within 3 months did not show a relevant impact on CCgR and MMR. Partial CgR (Ph+ < 35%, n=725)) within 6 months was associated with a higher chance to achieve MMR at 18 month (62.8% vs. 51.4% p=.0003). Patients who did not achieve CCgR within 3 (93%), 6 (70%), 12 (29%) or 18 (18%) months experienced an increasing risk for disease progression of 6%, 7%, 11% and 14% respectively but still showed a chance to eventually achieve CCgR of 87%, 83%, 60%, and 36%. Conclusions: This combined analysis of multinational European data showed very good response data regarding CHR, CCgR, MMR, and OS. Current prognostic CML scores seem to not separate prognosis of CML-patients sufficiently well. Early response markers like CHR and CgR after 6 months allow to differentiate the prognosis with regard to MMR but their clinical relevance may be questioned. Patients without CCgR within 6 months have a higher risk for disease progression and thus a closer follow up is indicated. With accumulating observation time the European CML Registry will allow to answer many clinically relevant questions about the prognostic value of early response markers. Disclosures Hasford: Novartis Pharma: Research Funding. Rosti:Novartis Pharma, Bristol Myers Squibb: Consultancy, Speakers Bureau. Baccarani:Novartis Pharma, Bristol Myers Squibb, Merck Sharp & Dome, Pfizer: Consultancy, Speakers Bureau. Montrucchio:Novartis Pharma : Employment. Rancati:Novartis Pharma: Employment. Simonsson:Novartis, BMS, Schering-Plough: Consultancy, Honoraria, Research Funding. Ossenkoppele:Novartis Pharma, BMS: Consultancy. Hehlmann:Novartis Pharma: Research Funding.

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Pagnano, Katia BB, Marcia T. Delamain, Eliana C. M. Miranda, Vagner O. Duarte, Brunna Eulálio Alves, Carmino Antonio De Souza, and Irene Lorand-Metze. "Impact of Imatinib Dose Escalation in Chronic Myeloid Leukemia Patients in Chronic Phase with Sub-Optimal Response or Failure with Imatinib 400 Mg." Blood 114, no. 22 (November 20, 2009): 3289. http://dx.doi.org/10.1182/blood.v114.22.3289.3289.

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Abstract Abstract 3289 Poster Board III-1 Imatinib dose escalation has been used in sub-optimal response and therapeutic failure to imatinib in conventional doses. The aim of this study was to evaluate the efficacy of imatinib dose increase in CML patients in CP who did not achieve the best response to imatinib 400 mg QID. Patients and methods: All CML patients in CP treated in our institution with imatinib 400mg between March 2002 and December 2008 were evaluated. Imatinib was escalated to 600–800mg in cases with sub-optimal response or failure, according to Leukemia Net or IRIS Trial criteria. All survival curves were calculated from date of dose increase: overall survival (OS) until death or last follow-up, event free survival (EFS) until loss of complete hematological response (CHR) or major cytogenetic response (MCyR), progression to accelerated phase (AP) or blast crisis (BC) or death from any cause. Transformation free survival (TFS) was calculated from dose increase until progression to AP, BC or death. Results: 137 patients in CP were treated with imatinib 400 mg. Dose was escalated in 55 (40%) patients due to loss or failure to achieve CRH (13 = 24%); progression to BC (2 = 3.5%); no CCR (11 = 20%); loss of RCC (5 = 9%); CCR without major molecular response (MMR) after 18 months of imatinib (24 = 43.5%). Males: 37, females 18 cases. Median age: 44 (16–74) years. Twenty-eight patients (49%) were treated with imatinib as first line therapy and 51% had used IFN previously. Median time between diagnosis and imatinib start was 4.5 (0–94) months. Responses: 94% achieved CHR; 58% CCR and 34% MMR. After dose increase, 31 (56%) responded: 58% of the patients with previous sub-optimal molecular response achieved MMR. Among those who benefited from dose increase, only 3 cases lost the response: one with hematological resistance and two with cytogenetic resistance (2 lost CCR and one CHR). Seven out of 16 patients who increased dose due to cytogenetic failure (loss of response, failure and sub-optimal response) achieved response: one had partial cytogenetic response (PCyR) and 6 CCR. Five patients with hematological failure presented response: CHR (2), CCR (1), PCyR (1) and MMR (1). Patients with BC (2 cases) did not respond to dose escalation. TFS was 89% and 67% in 2 and 5 years, respectively. EFS was 71% and 64% in 2 and 5 years respectively. When stratified by the type of failure, EFS was 100%, 49% and 34% in the group with molecular sub-optimal response with median time of 22 (4–41) months, cytogenetic 17 (1.2–42) and hematological failure 7.7 (0.2–57), respectively (P<0.03). Conclusions: imatinib dose escalation was successful in molecular sub-optimal response. However, the patients who do not achieve MMR might be candidates to second line treatment. Patients who did not achieve cytogenetic or hematological response did worse with imatinib dose escalation. Disclosures: No relevant conflicts of interest to declare.

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Murugan, M., P. K. Shetty, Thomas George, R. Ravi, A. Subbiah, and K. Vijayakumar. "Pesticide Use in Indian Cardamom Hills." International Journal of Social Ecology and Sustainable Development 5, no. 3 (July 2014): 65–80. http://dx.doi.org/10.4018/ijsesd.2014070106.

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Surveys and analyses among cardamom and tea planters were carried out in and around cardamom hill reserves during 2009-2012 to quantify the annual pesticide consumption of cardamom and tea. The survey revealed that cardamom had consumed 26.59 kg a.i ha-1 in comparison with tea (8.70kg a.i ha-1). Pesticide intensity of cardamom (0.0322 kg kg-1) was higher than tea (0.0046 kg kg-1). Risk weighed active ingredients values were 3.326 and 0.029 kg ha-1 for cardamom and tea respectively. The pesticide use intensity in major cardamom growing areas of the CHR has experienced significant increase from 2002 and 2003. It was 7.10 kg a.i ha-1 in the year 2002 and decreased slightly to 5.42 kg a.i ha-1 for the year 2003. The number of pesticide sprays has been increased during the last two years (2011-2012). Pesticide residues in soils of all three cardamom growing hot spots were high. Hospital data of these cardamom hot spot regions showed higher levels of pesticide poisonings particularly for organophosphorous compounds. Therefore, the analysis and results reported here on pesticide consumption by cardamom and tea must be taken seriously to safeguard the degraded rainforest cardamom agroforestry system.

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Avitia, Miguel Angel Alvarez, Jose Luis Aguilar Ponce, Gisell Anaid Lara, Violeta Moreno Molina, Jaime G. De La Garza, Martin Granados-Garcia, Juan Cruz M, Andres Moran Mendoza, and Abraham Ruiz. "Induction chemotherapy (ICh) followed by concurrent chemoradiotherapy (ChR) in locally advanced squamous cell carcinoma of head and neck (SCCHN): Experience in a Mexican institute." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e17031-e17031. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e17031.

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e17031 Background: ICh has taken an important role in the treatment of locally advanced disease, but it has not been recognized in which patients (pts) may be the best option ICh followed by ChR or just ChR. We present our experience with ICh followed by ChR regimen in the National Cancer Institute of Mexico (INCan). Methods: We identified 69 patients (pts) diagnosed with locally and/or regionally advanced non-metastatic squamous cell cancer of head and neck, who were attended at the INCan from 2008-2012, in whom, the original treatment was ICh with two cycles of Paclitaxel (P), cisplatin (C) and 5Fluorouracil (5FU) scheme, followed by concurrent ChR with C. But only 35 pts of the original group accomplished the treatment. Results: 13 pts were women (37%) and 22 were men (63%).The median age at diagnosis was 59 years old. In stages III (28%), IVa (46%), and IVb (26%); AJCC, 2002. The subsites per pts. studied were: oral cavity 9 (25.7%), larynx 9 (25.7%), hypopharynx 7 (20%), paranasal sinuses 7 (20%) and oropharynx 3 (8.6%). The rate response was observed in 83%: complete objective rate response (CR) in13 pts (37%), partial response rate in 16 pts (46%) and progression rate in 6 pts. (17%). The mean survival was of 18.3 months (mth) (CI-95: 0.32-0.68).Median survival was not achieved in pts with CR with a median follow up of 2 yrs, pts with PR had a median survival of 15 mth (CI-95: 0.27-0.75) and the median progression was 11 mth (CI-95: 0.11-0.80). We have not got any CR with ICh only, but 13 patients obtained CR at the end of the ChR. Neither age, sex nor subsites were crucial to the clinical response. Conclusions: Our results cannot distinguish patients who might benefit from ICH. In the intention-to-treat population, more than a half of pts did not complete the proposed scheme. Recently, we reported a study using an alternative scheme: Cisplatin and gemcitabine concurrent with radiotherapy to treat pts with advanced SCCHN, and we found that this scheme of treatment is effective and well tolerated, with a 5 yr progression-free survival rate of 27.8 (CI-95: 0–61.5). Yet further studies are needed to compare ICh followed by RCh vs RCh to assess what the best treatment may be.

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Ferrari, Anna, Cristina Papayannidis, Carmen Baldazzi, Ilaria Iacobucci, Stefania Paolini, Antonella Padella, Viviana Guadagnuolo, et al. "Leukemia Associated TP53 Mutations in AML Patients ARE Strongly Associated with Complex Karyotype and Poor Outcome." Blood 124, no. 21 (December 6, 2014): 2379. http://dx.doi.org/10.1182/blood.v124.21.2379.2379.

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Abstract Background: AML is a heterogeneous disease with various chromosomal aberrations. The karyotype at diagnosis provides important prognostic information that influences therapy and outcome, and patients (pts) with complex karyotype (CK) have generally a poor outcome. TP53 is the most frequently mutated gene in human tumors. The reported TP53 mutation rate in AML is low (2.1%). In contrast, the incidence of TP53 mutations in AML with a complex aberrant karyotype is higher (69-78%). Aims: To investigate the frequency, the types of mutations, the associated cytogenetic abnormalities and the prognostic role of TP53 mutations in adult AML pts, we focused the screening on subgroups of AML with chromosome abnormalities. Patients and Methods: 886 AML patients were analysed at the Seràgnoli Institute of Bologna between 2002 and 2013 for morphology, immunophenotype, cytogenetic and for a panel of genetic alterations (FLT3, NPM, WT1, CBF fusion transcripts, DNMT3A, IDH1, IDH2, etc). Of these, 172 adult AML pts were also examined for TP53 mutations using several methods, including Sanger sequencing, Next-Generation deep-Sequencing (Roche) and HiSeq 2000 (Illumina) platform (35/172 pts). 40 samples were genotyped with Genome-Wide Human SNP 6.0 arrays or with CytoScan HD Array (Affymetrix) and analysed by Nexus Copy Number™ v7.5 (BioDiscovery). Results: Of the 886 AML patients beforehand analysed, 172 pts were screened for TP53 mutations and were correlated with cytogenetic analysis (excluding 15 pts where the karyotype was not available). 1. Fifty-two pts (30,2%) have 3 or more chromosome abnormalities, i.e. complex karyotype; 2. 71 (41,3%) presented one or two cytogenetic abnormalities (other-AML) and 3. 34 pts (19,8%) have normal karyotype. Sanger sequencing analysis detected TP53 mutations on 29 patients with 36 different types of mutations; seven pts (4%) have 2 mutations. Mostly (23/29) of the TP53 mutated pts (79.3%) had complex karyotype while only 6/29 mutated pts have “no CK” (21% and 3% of the entire screened population). Overall, between pts with complex karyotype, TP53 frequency is 44.2%. Regarding the types of the TP53 alterations, 32 were deleterious point mutations (http://p53.iarc.fr/TP53GeneVariations.aspx) and 4 deletions. Forty pts were also analysed for Copy Number Alterations (CNAs) by Affymetrix SNP arrays: several CNAs were found ranged from loss or gain of complete chromosome (chr) arms to focal deletions and gains targeting one or few genes involving macroscopic (>1.5 Mbps), submicroscopic genomic intervals (50 Kbps - 1.5 Mbps) and LOH (>5 Mbps) events. Of relevance, gains located on chr 8 were statistically associated with TP53 mutations (p = 0.001). Seven genes are included in these regions (RGS20, TCEA1, LINC01299, ARMC1, MTFR1, RAD54B, KIAA1429). In addition to the trisomy of the chr 8, others CNAs, located on other chromosomes are significantly associated (p = 0.05) with TP53 mutations: loss of chr 5q, chr 3 (p22.3), chr 12 (p12.3) and the gain of chr 17 (p11.2), chr 16 (p11.2-11.3) and chr 14 (q32.33). The zinc finger gene ZNF705B, implicated in the regulation of transcription was the most differentially associated gene (gain). WES analysis was done in 37 pts, 32 TP53 were wt while 5 pts were TP53 mutated: of importance, CDC27, PLIN4 and MUC4 were found also mutated in 3 out of 5 TP53 mutated (60%). Clinical outcome: as previously reported, alterations of TP53 were significantly associated with poor outcome in terms of both overall survival and disease free-survival (P < 0.0001). Conclusions: Our data demonstrated that TP53 mutations occur in 16.86% of AML with a higher frequency in the subgroup of complex karyotype AML (p< 0.0001–Fischer’s exact test). Since TP53 mutations have predicted to be deleterious and significantly correlated with prognosis, TP53 mutation screening should be recommended at least in complex karyotype AML pts. Furthermore, although further studies in larger numbers of patients are needed, the gain of chromosome 8 was observed to be significantly associated to TP53 mutations pts. Supported by: ELN, AIL, AIRC, PRIN, progetto Regione-Università 2010-12 (L. Bolondi), FP7 NGS-PTL project. Disclosures Martinelli: Novartis: Speakers Bureau; Bristol Mayers Squibb: Speakers Bureau; Pfizer: Speakers Bureau.

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Hehlmann, Ruediger, Susanne Saussele, Michael Lauseker, Ulrike Proetel, Elena Kovalevskaya, Armin Leitner, Claudia Haferlach, et al. "Randomized Comparison of Imatinib 400 Mg Vs. Imatinib + IFN Vs. Imatinib + AraC Vs. Imatinib after IFN Vs. Imatinib 800 Mg: Optimized Treatment and Survival. Designed First Interim Analysis of the German CML Study IV." Blood 112, no. 11 (November 16, 2008): 184. http://dx.doi.org/10.1182/blood.v112.11.184.184.

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Abstract In spite of favorable response and survival results for the majority of CML patients on imatinib therapy, in a substantial minority imatinib fails or shows suboptimal responses. A treatment optimization study was therefore designed to compare in a randomized fashion standard imatinib vs. imatinib + interferon alpha (IFN) vs. imatinib + low dose araC vs. imatinib after IFN (for low- and intermediate-risk patients) or vs. imatinib 800 mg (for high-risk patients). Inclusion criteria were newly diagnosed BCR/ABL positive CML in chronic phase. In July 2005, randomization to the arms imatinib + araC and imatinib after IFN was discontinued and recruitment for imatinib 800 mg was expanded to low- and intermediate-risk patients. Primary goals are: rates of hematologic, cytogenetic and molecular remissions, duration of chronic phase, overall survival, adverse events and analysis of subsequent allografting. Since its activation in 7/2002, 1203 patients have been randomized. The current evaluation represents the first of three designed, statistically adjusted interim analyses of 710 patients randomized by the end of 2005 with a followup of at least 2 years. Analysis was according to intention to treat. 666 patients (545 with primary imatinib, 121 with primary IFN) were evaluable for hematologic, 621 for cytogenetic, and 631 for molecular responses. Median age was 53 years, 60% were male, median values were for Hb 12.5 g/dl, WBC 71.2/nl and platelets 384/nl, 35% had low, 53% intermediate and 12% high risk (Euro score). Median observation time was 3.5 years. Median duration of IFN pretreatment was <4 months. At 1 year, the cumulative incidence of complete hematologic remission (CHR) was 82.3% and 74.4%, of major cytogenetic remission (MCR) 65.6% and 40.6%, of complete cytogenetic remission (CCR) 52% and 19.7%, and of major molecular remission (MMR) 33.2% and 4.7% for primary imatinib and IFN therapies, respectively. At 3 years, the cumulative incidence of CHR was 96.4% and 93.8%, of MCR 89.5% and 89.1%, of CCR 85.2% and 78.5%, and of MMR 79% and 63% for primary imatinib and IFN therapies, respectively. 5-year-survival probability of all patients currently exceeds 90% (94% for imatinib-, 91% for IFN-based therapy, Figure 1). Event free survival after two years (no progression, no death, CCR within the first 18 months, no loss of CHR or MCR) was 80.3%. 36 patients died, 51 patients were transplanted in first chronic phase, and 80 patients progressed, 43 of which were switched to alternative treatments (16 to new drugs, 18 to transplantation, 9 received both). Type and severity of adverse events (AE) did not significantly differ from those reported previously. Hematologic AEs (leukopenia, thrombocytopenia) were most frequent in the imatinib 800 mg arm. Nonhematologic AEs (gastrointestinal) were most frequent in the combination arms and with imatinib 800 mg. In no case recruitment had to be changed due to superiority or inferiority of any arm. This applies also to the high dose imatinib arm where earlier response might translate into better survival. In conclusion, this first interim analysis shows favorable survival and long term response rates. Imatinib in combination with, or after, IFN or with low dose araC are feasible and equally safe treatment alternatives. More definite information will be provided by the next interim evaluation after recruitment has been terminated. Figure Figure

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Ganesan, Prasanth, Tenali Gnana Sagar, Krishnarathnam Kannan, and Rejiv Rajendranath. "Upfront Imatinib in Pediatric Chronic Myeloid Leukemia Yields Results Comparable to Stem Cell Transplant,." Blood 118, no. 21 (November 18, 2011): 3763. http://dx.doi.org/10.1182/blood.v118.21.3763.3763.

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Abstract Abstract 3763 Background: Imatinib mesylate (IM) is the standard therapy in adult patients with chronic myeloid leukemia (CML). In children, the superiority of Imatinib over allogenic transplantation is not well established. Concerns exist about the long term effects of Imatinib in this population. Methods: Outcomes of children (≤18 years) diagnosed with chronic phase CML from 2002 to 2008 were retrospectively analysed. All received Imatinib at a dose of 260–300mg/m2/day. Progression free survival (PFS- time from starting treatment till loss of complete hematologic response (CHR), or disease acceleration), ad Overall survival (OS) were estimated by the Kaplan Meier method. Those who progressed received higher doses of Imatinb or were changed to hydroxyurea. No patient had access to second line tyrosine kinase inhibitors or to allogenic stem cell transplant. Results: 31 patients, median age 13 (6–18)years, Males-17 (48.6%), were treated. The presenting complaints over a median symptom duration of 1 month (10 days to 12 months) were abdominal distension and/or pain (68%), fever (38%), weight loss (13%), bone pains (10%), anemic symptoms (16%). Examination revealed splenomegaly (100%), heptomegaly (47%) and lymphadenopathy (6%). Laboratory: Hemoglobin (9.3g/dL;4.2–10.9), White cell count (228,000/mm3;10,000–800,000), Platelet count (412,000/mm3, 120,000–12,80,000), peripheral eosinophilia (2%;0–10), basophilia (2%; 0–7). CHR was seen in 30/31 (97%) at a median of 2 months (1.5–8). Sokal risk category was low in 13 (41%), intermediate in 15 (48.4%) and high in 3 (9.7%). The cumulative incidence of Major and Complete cytogenetic response (MCR and CCR) among those who had not progressed by 2 years (n=23) was 82% and 70% respectively. Molecular assessment done in 11 patients who had achieved CCR by 2 years showed MMR in 6/11 (55%). After a median follow up of 49.2 months (4.4 – 86.4) disease progression occurred in 8 patients (5-year PFS 68%-median not reached) which led to death in 6 patients (5-year OS 75.8%). Among those with cytogenetic data, the PFS for those with CCR vs those without was 93.8% and 53.6 % respectively at 5 years (p=0.048). The drug was well tolerated with no discontinuation because of toxicity. Conclusions: Imatinib is a reasonable option in the first line therapy of pediatric CML and gives 5 year PFS and OS rates comparable to the results of upfront allogenic transplant. It is to be considered as an alternative especially in resource constrained settings where options for transplant are limited. Disclosures: No relevant conflicts of interest to declare.

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Rea, Delphine, Gabriel Etienne, Franck Emmanuel Nicolini, Pascale Cony-Makhoul, Hyacinthe Johnson-Ansah, Laurence Legros, Francoise Huguet, et al. "Front-Line Imatinib Mesylate (IM) in Patients with Newly Diagnosed Accelerated Phase (AP)-Chronic Myeloid Leukemia (CML), a Study From the FILMC Group (France Intergroupe Leucemie Myeloide Chronique)." Blood 114, no. 22 (November 20, 2009): 3288. http://dx.doi.org/10.1182/blood.v114.22.3288.3288.

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Abstract Abstract 3288 Poster Board III-1 IM is approved for the treatment of AP-CML at 600mg daily. Clinical trials in which IM was evaluated in this setting have mainly enrolled patients (pts) who have failed prior therapies and the efficacy of the drug in newly diagnosed AP-CML has never been specifically studied. We collected data from 43 de novo pts with disease acceleration at diagnosis and treated with first-line IM. Thirty-three showed hematological acceleration (HEMAP) according to WHO 2002 or ELN 2006 criteria and 10 had cytogenetic acceleration only (CYAP), defined as the presence of chromosomal abnormalities additional (ACA) to the Philadelphia (Ph) chromosome. Ph variant translocations, loss of the Y chromosome and constitutional cytogenetic abnormalities were excluded from ACA definition. Ten out of 33 HEMAP pts (30%) had also ACA. ACA included Ph duplication (n=4), trisomy 8 (n=5), add(6) (n=3), monosomy 7 (n=1), del(5q) (n=1), t(3;21)(q26;q22) (n=1) and others (n=7). Median age at diagnosis was 51 years (19–67), 32 pts were males (75%) and 11 were females (25%). The median time from diagnosis to IM initiation was 15 days (0–140). The initial IM dose was 600mg/d (n=32) or 400mg/d (n=11). The median duration of IM therapy was 20 months (1–90). A sustained complete hematologic response (CHR) for at least 4 weeks was achieved in 38/43 pts (88.4%, 95% CI 78.4–99.3), including 29 HEMAP and 9 CYAP pts (87.9% versus 90%, not significant (ns)). The median time to achievement of CHR was 42 days (0–97). CHR was lost in 3 pts after 4, 6 and 10 months. Pts with lack or loss of CHR were initially classified as HEMAP (n=5) or CYAP (n=3), all except one harboured ACA at diagnosis. In addition, 4/7 screened pts had a BCR-ABL mutation (E255K n=3, E355G n=1) at the time of IM failure. A major cytogenetic response (MajCR) was observed in 31/43 patients (72.1%, 95% CI 58.1–86.1), and a complete cytogenetic response (CCR) was obtained by 27/43 pts (62.8 %, 95% CI 44.7–78.8), with 22 HEMAP pts and 5 CYAP pts (66.6% versus 50%, ns). The median time to reach CCR was 6 months (3–23). The rate of CCR in HEMAP pts with ACA was significantly lower than that in HEMAP pts without ACA (36.4% vs 80%, p=0.023). Eighteen pts with CCR (16 HEMAP pts and 2 CYAP pts) also gained a major molecular response (MMR: BCR-ABL/ABL ratio % IS ≤ 0.1%). The median time to MMR was 9 months (5–34). Seven pts subsequently lost their MajCR (CCR n=3, partial CR n=4) 3 to 31 months after first achieving it, 2 due to a poor compliance to IM and 5 due to acquired resistance. Of the latter, 4/5 had ACA at diagnosis and a BCR-ABL mutation emerged in 3/5 (E355G n=1, E255K n=1 and T315I n=1). Four pts (2 HEMAP and 2 CYAP) who failed to achieve CHR or CCR evolved toward blast crisis (BC) while on IM, after 1 to 11 months of treatment. The event-free survival (EFS) rate on IM was 57.1% (95% CI 41.4–72.7) at 24 months, events being defined as lack/loss of response, BC or death, whichever came first. The progression-free survival (PFS) rate on IM was 89.7% (95% CI 80–99.4) at 24 months, progression being defined as BC or death. EFS and PFS and did not significantly differ between HEMAP and CYAP pts but EFS at 24 months was significantly poorer in HEMAP pts with ACA at diagnosis than that in HEMAP pts without ACA (26% vs 74.7%, p=0.0055). Twenty-three out of 43 (53.5%) pts discontinued IM after a median duration of treatment of 11 months (1–90), because of treatment failure/progression (n=14), intolerance (n=8) or undetectable molecular residual disease (UMRD, n=1). For those on continuous IM therapy, the median observation time was 32 months (3–76). Following IM discontinuation, 15 pts were switched to second generation tyrosine kinase inhibitors (TKI) and 2 of them evolved toward BC and died, 3 pts underwent allogeneic hematopoietic stem cell transplantation, 4 pts received intensive chemotherapy with or without TKI and 1 was further transplanted, and the last pt with UMRD remained treatment-free. To conclude, although IM front-line induces substantial and durable responses in de novo AP-CML, our results suggest that there may be room for further improvement, especially in case of HEMAP together with ACA. The potential of other front-line therapies such as second generation TKI may be evaluated in this setting. Disclosures: No relevant conflicts of interest to declare.

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Simián, Rafael. "Chr. Jedan – N. Strobach, Modalities by perspective: Aristotle, the stoics and a modern reconstruction. Sankt Augustin 2002 (Academia Verlag, 144 págs.)." Méthexis 17, no. 1 (March 30, 2004): 143–46. http://dx.doi.org/10.1163/24680974-90000458.

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Leclerc, Mathieu, Felipe Suarez, Marie-Pierre Noël, Anne Vekhoff, Xavier Troussard, Jean-François Claisse, Catherine Thieblemont, et al. "Rituximab For Hairy-Cell Leukemia (HCL): A Multicentric Retrospective Study Of 41 Cases." Blood 122, no. 21 (November 15, 2013): 5308. http://dx.doi.org/10.1182/blood.v122.21.5308.5308.

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Abstract Introduction the purine analogs (PA) cladribine (CDA) and pentostatin have dramatically improved the prognosis of HCL and are considered the standard of care both in front-line therapy and at relapse. However, some patients still fail to respond or will eventually relapse after treatment with PA. Chimeric anti-CD20 monoclonal antibody rituximab has shown significant activity in HCL and is an option for relapsed/refractory patients either alone or in combination with PA. Methods we retrospectively reviewed 49 treatments with rituximab for classical HCL, undertaken in 41 patients (pts) from 10 centers in France and Belgium between july 2002 and september 2012. Patients were included if they had received at least 3 infusions of rituximab. Eight pts were treated twice with rituximab. Complete hematologic response (CHR) was defined as recovery of normal blood counts (without circulating HCL cells) and absence of HCL-related symptoms. CHR was further divided into 3 groups: (i) stringent complete response (sCR), if bone marrow evaluation was normal; (ii) unconfirmed complete response (uCR), if bone marrow evaluation was not done and (iii) CHR with persistent medullar infiltration (iCHR). Partial response (PR) corresponded to a ≥ 50% improvement for every CHR-defining criterion or normalization of at least one blood count, without circulating HCL cells. Results characteristics of pts before treatment are summarized in table 1. Rituximab was given as front-line therapy in 8 cases (16.3%). When used at relapse/progression, the median number of previous lines was 3 (range 1-8) and all pts had already received PA (both CDA and pentostatin in one third of them). Rituximab was given alone in 55% of cases, while it was combined with a PA in the 45% remaining cases, mostly CDA (18 of 22 cases). The median number of infusions was 4 (3-12). After treatment, median absolute neutrophil count (ANC), hemoglobin (Hb) level and platelet count were 2.75 x 109/L, 135 g/L and 180 x 109/L respectively. Persistent significant neutropenia (ANC < 1 x 109/L) and anemia (Hb < 100g/L) were each found in only 2 cases and 10.6% of patients had platelets < 100 x 109/L. Overall response rate (ORR) was 89.6% with 70.8% CHR including 6 sCR (12.5%), 26 uCR (54.2%) and 2 iCHR (4.2%). PR was achieved in 9 cases (18.8%) and 5 pts were non responders (10.4%). All the 8 pts who received rituximab as front-line therapy (along with CDA in 5 of them) achieved CHR. In the relapsed pts, ORR was 87.5% (including 65% CHR) with a better outcome for those having received both rituximab and PA (100% ORR including 85.7% CHR versus 79.2% ORR and 54.2% CHR after rituximab alone). The 5 pts who failed to respond were relapsed pts treated with rituximab alone. Interestingly, all the 8 pts who were re-challenged with rituximab responded again to treatment (6 uCR, 1 iCHR and 1 PR). Multivariate analysis identified 3 independent prognostic factors for response to rituximab: absence of previous therapy (OR=0.027 [0,001-0,555], p=0,0192), combination therapy (OR=10,120 [1,227-83,485], p=0,0316) and ANC before treatment (OR=1,002 [1,001-1,004], p=0,006). The median follow-up is 36 months (4-117). Relapse or progression was observed in 15 cases (34.1%), with a median time to relapse of 19 months (2-39). Relapse rate was higher (54.5%) and time to relapse shorter (17.5 months) when rituximab was administered alone, as compared to combination therapy with a PA (10% and 38.5 months respectively). Overall, 3-year relapse-free survival is 68.3%. Six pts have died and 3-year overall survival is 90.3%. Conclusion this study confirms the efficacy of rituximab in HCL patients, mostly when combined to PA. Nevertheless, the relapse rate is high and time to relapse short when rituximab is used as monotherapy beyond front-line treatment. Further prospective studies are warranted to confirm the superiority of the combination PA + rituximab over PA alone. Disclosures: Off Label Use: Rituximab for the treatment of hairy-cell leukemia.

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Liu, Shuo, Shuangxi Fang, Peng Liu, Miao Liang, Minrui Guo, and Zhaozhong Feng. "Measurement report: Changing characteristics of atmospheric CH4 in the Tibetan Plateau: records from 1994 to 2019 at the Mount Waliguan station." Atmospheric Chemistry and Physics 21, no. 1 (January 14, 2021): 393–413. http://dx.doi.org/10.5194/acp-21-393-2021.

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Abstract. A 26-year, long-term record of atmospheric methane (CH4) measured in situ at the Mount Waliguan (WLG) station, the only World Meteorological Organization (WMO) and Global Atmosphere Watch (GAW) global station in inland Eurasia, is presented. Overall, a nearly continuous increase in atmospheric CH4 was observed at WLG, with a yearly growth rate of 5.1±0.1 parts per billion (ppb) per year during 1994–2019, except for some particular periods with near-zero or negative values, e.g., 1999–2000 and 2004–2006. The average CH4 mole fraction was only 1799.0±0.4 ppb in 1994 but increased to about 133 ppb and reached a historic level of 1932.0±0.1 ppb in 2019. The case study in the Tibetan Plateau showed that the atmospheric CH4 increased rapidly. During some special periods, it is even larger than that of city regions (e.g., 6.7±0.2 ppb yr−1 in 2003–2007). Generally, the characteristics of CH4 varied in different observing periods as follows: (i) the diurnal cycle has become apparent and the amplitudes of the diurnal or seasonal cycles increased over time; (ii) the wind sectors with elevated CH4 mole fractions switched from ENE-E-ESE-SE-SSE sectors (wind directions) in early periods to NNE-NE-ENE-E sectors in later years; (iii) the area of source regions increased as the years progressed, and strong sources shifted from northeast (city regions) to southwest (northern India); and (iv) the annual growth rates in recent years (e.g., 2008–2019) were significantly larger than those in the early periods (e.g., 1994–2007).

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Joshi, Durga Datt. "Study of Visceral Leishmaniasis (Kala-azar) in Children of Nepal." Journal of Nepal Paediatric Society 29, no. 2 (July 15, 2009): 67–73. http://dx.doi.org/10.3126/jnps.v29i2.2041.

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Introduction: Visceral leishmaniasis (VL) or Kala-azar is a potentially fatal vector-borne (sand fly phlebotomies spp) zoonotic disease caused by a protozoan parasite, Leishmania donovani. In Nepal, the disease is restricted to the Eastern Terai region which lies adjacent to the Bihar state of India. Although leishmaniasis is regarded as a significant health problem in Nepal by the Ministry of Health, there is no active case detection programme in the country. Objective: Objectives of this study were to determine the up-to-date morbidity and mortality trend for VL in children of Nepal. Method: The epidemiological surveillance team from the NZFHRC visited to eight zonal hospitals in Terai region during the month from September to December of each year 2003 to 2007. The morbidity and mortality data up to the year 2007 were collected every year. The team has also collected 66 blood serum samples of which 18 samples from children were collected for the diagnosis. Results: A total 25890 cases with 599 deaths were reported during the year 1980-2006. The case fatality rate (CFR) varied from 0.23% to 13.2%. Districtwise analysis showed that, during 2003, highest incidence was in Mahottari district (184/100,000), followed by Sarlahi (100/100,000) and Sunsari (96/100,000). The highest CFR was in Dhanusha (2.9%) followed by Bara (2.4%) and Saptari (2.0%). Majority (70.9%) of persons affected by VL were aged 15 years and above, followed by 10-14 years (13.9%), 5-9 years (11.9%) and 1-4 years (3.3%). VL cases recorded from different district of Nepal for the year 2004, 2005, 2006 and 2007 are recorded. CFR for the year 2004, 2005, 2006 and 2007 were 3.2%, 3.7%, 16.67% and 11.42% respectively. Conclusions: There should be regular surveillance research work to be carried out in endemic area. Mass public health education, to make the people aware about preventive aspects of the disease is important. The possibility of the existence of animal reservoirs as zoonotic disease should also be considered. This disease is very much serious in children below 15 years of age both in male and female, therefore it is essential to have paediatrician post at least in all VL six endemic districts. Key words: Epidemiology, Leishmaniasis, Kala-azar, Sandfly doi: 10.3126/jnps.v29i2.2041 J. Nepal Paediatr. Soc. Vol 29, No. 2, pp.67-73

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Reese, Zachary L., Danielle Tometich, Shiven B. Patel, Sunil Sharma, and Ignacio Garrido-Laguna. "Exceptional responses in patients with upper gastrointestinal malignancies enrolled in first-in-man studies: 2002-2012." Journal of Clinical Oncology 33, no. 3_suppl (January 20, 2015): 311. http://dx.doi.org/10.1200/jco.2015.33.3_suppl.311.

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311 Background: First-in-man (FIM) studies test the efficacy and safety of novel therapeutic agents with proven in vitro activity when used for the first time in humans. Patients with advanced upper gastrointestinal malignancies (UGIM) have limited systemic treatment options. We established a database of FIM studies published from 2002-2012 to identify exceptional responders in patients with UGIM. Methods: Using a Scopus search, we compiled a database of published FIM studies enrolling patients with UGIM between 2002 and 2012. We identified exceptional responders to therapy among these patients as a complete response or a partial response lasting at least 6 months. Results: We identified 84 FIM studies enrolling at least one patient with UGIM. In total 554 patients with UGIM were enrolled including 290 pancreatic adenocarcinomas (52.3%), 110 gastric adenocarcinomas (19.9%), 83 esophageal carcinomas (15.0%), 41 hepatocellular carcinomas (7.4%), and 30 cholangiocarcinomas/gallbladder carcinomas (5.4%). One patient with pancreatic cancer treated with bosutinib, a src kinase inhibitor, had a complete response with a progression-free survival (PFS) of 42 months. Four partial responses were reported including one pancreatic cancer patient treated with CHR-3996, a histone deacetylase inhibitor (PFS 12 mo); two pancreatic cancer patients treated with trametinib, a MEK inhibitor (10 and 11.75 mo); and one cholangiocarcinoma patient treated with SB-743921, a kinesin inhibitor (11 mo). Two additional partial responses were noted without available PFS data including one pancreatic cancer patient treated with KOS-1584, a second generation epothilone, and one gastric cancer patient treated with apatinib, a VEGFR-2 inhibitor. Conclusions: Exceptional responses are seen in patients with UGIM enrolled in FIM studies. Actionable genetic aberrations may be driving disease in these patients. Further studies are needed to understand these responses at the molecular level. These molecular studies could open new treatment opportunities for patients with advanced UGIM.

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Biswajit, D., R. Rejiv, N. Manjunath, G. Prasad, S. Lakshmi, P. Devika, K. Geetha, and T. G. Sagar. "Imatinib mesylate experience of young patients with chronic myeloid leukemia in chronic phase—Care to cure." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 7072. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.7072.

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7072 Background: Chronic myeloid leukemia (CML) with introduction of imatinib has been transformed into a chronic illness. The options of treatment in a patient less than 35 years include imatinib or allogenic stem cell transplantation. Hence we studied this unique subset to look at the response rates, adverse effects, progression free survival, and overall survival with imatinib mesylate. Methods: 477 patients with Philadelphia positive CML in chronic phase were retrospectively analyzed from January 2002 to December 2007 at Cancer Institute (WIA), Chennai, India. Standard criteria were used for response evaluation and adverse effects. Results: A total of 248 young CML patients with age less than 35 years (51.9%) were diagnosed in chronic phase. The median age of study population was 27 years (4–35). The male to female ratio was 1.9: 1. Risk stratification was done using Sokal index and were classified into low (32.3%), intermediate (50.4%), and high (17.3%). All patients received imatinib 400 mg as the initial dose. Complete hematological remission (CHR) was seen in 96.7%.Cytogenetic (FISH) and molecular (RTPCR) monitoring was possible in 53.2% and 17.3%, respectively. 72% of the patients had major cytogenetic response. Major molecular response was seen in 34.8% while complete molecular response occurred in 23.2% of the patients. Primary and secondary imatinib failure was seen in 3.1% and 16.9%, respectively. 6.7% had grade 3 and grade 4 hematological toxicities. The other common non hematological toxicities included pedal edema (13.7%), hypo or hyper pigmentation (60.0%), hyalgia (14.5%), diarrhea (1.6%), and liver dysfunction (1.6%). None of the patients discontinued imatinib due to toxicities. The 3-year DFS and OS was 86.2% and 89.5%, respectively. Patients with male sex (p = 0.04), spleen > 8 cm (p = 0.02), high sokal index (p = 0.02), and loss of CHR (p < 0.001) were associated with poor outcome. Conclusions: Imatinib in young patients have an excellent tolerance and response. A small subset does not respond to therapy or develop resistance during treatment. Hence it is essential to identify these poor responders and to offer stem cell transplantation at the earliest. No significant financial relationships to disclose.

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Kang, Matthew, Anargyros Xenocostas, Alejandro Lazo-Langner, Ian H. Chin-Yee, Kang Howson-Jan, Maisam Abouzeenni, Michael J. Kovacs, and Cyrus C. Hsia. "Impact of Transition to Generic Imatinib in the Molecular Response Among Patients with Chronic Myeloid Leukemia." Blood 124, no. 21 (December 6, 2014): 5527. http://dx.doi.org/10.1182/blood.v124.21.5527.5527.

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Abstract Background: The introduction of Imatinib Mesylate (Gleevec™), a tyrosine kinase inhibitor (TKI), has revolutionized the management of Chronic Myeloid Leukemia (CML). Recently, on April 2, 2013, Health Canada approved two generic versions of imatinib mesylate (Apotex and TEVA) for sale in Canada—both of which, have been shown to be bioequivalent to the brand name Gleevec™, with similar serum imatinib levels and area under the curve after oral ingestion. In one of the largest case series reported to date (N=126), it has been reported that complete hematologic response (CHR) was lost in 33% of CML patients who were switched from brand name to generic imatinib. In an effort to assess the generalizability of this claim, we conducted a retrospective review of all patients with CML treated with Gleevec™ at a single tertiary care centre to evaluate whether there was a change in CHR or major molecular responses (MMR) in all patients who were switched to generic imatinib. Method: We retrospectively evaluated adult CML patients who were treated from January 1, 2002 to December 2011 with brand name Imatinib (Gleevec™) and were switched to generic imatinib (Apotex or TEVA) during 2013. Patient-reported side effect profiles were also collected in a subset of patients before and after the change from Gleevec™ to generic. A follow-up period was defined as 12 months from the time of switch from brand name to generic. The primary outcome was a composite of rates of loss of CHR and/or MMR, based on the Canadian Consensus Group of the Management of Chronic Myelogneous Leukemia (CCGM-CML). Secondary outcome include side effect profiles, graded as per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), during the follow-up period. Results: During our study period, a total 71 adult CML patients were identified. Of these, only 30 patients were included in the analysis. Among the 41 patients who were excluded, data could not be retrieved in 23 (32.4%), 9 (12.7%) were on dasatinib, 3 (4.2%) were on nilotinib, 2 (2.8%) were transplanted and 4 (5.6%) had died at the time of the switch. Data was collected using electronic medical records from patient clinic visits. The median age of all included patients was 54 years and 16 (53.3%) were male. The primary endpoint was seen in 2 of 30 patients (6.7%; 95% CI 3.5-25.6). There was a loss of MMR in 1 (3.3%) where the BCR-ABL transcript declined from a 4.19 log reduction to a 2.78 log reduction after switching to TEVA-imatinib. There was a loss of CHR in 1 (3.3%) patient, where a 20 g/L drop in hemoglobin was seen after switching to APO-imatinib. In both patients in whom the primary endpoint was seen, their imatinib dose was 200 mg before and after switching. Further, in both patients, these losses of response were transient. The secondary outcomes will be presented at the meeting. Conclusion: The generic formulations of imatinib used in Canada do not seem to be associated with the same previously reported lack of clinical efficacy when compared to brand name Gleevec™ during a follow-up period of 12 months. Further, a loss of MMR and a loss of CHR were transient in the 2 of 30 patients identified. Despite these infrequent events, treating physicians should consider that a switch to a generic formulation may be a contributing factor for the patient’s loss of MMR or CHR. However, given the wide confidence intervals, larger studies and longer follow up are needed to address this issue. Disclosures No relevant conflicts of interest to declare.

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Cai, Yuli, Chao Liu, Ye Guo, Xiaojuan Chen, Li Zhang, Yumei Chen, Yao Zou, Wenyu Yang, and Xiaofan Zhu. "Analysis of 48 Cases Pediatric Chronic Myeloid Leukemia from China: Results from a Single Institute in China." Blood 134, Supplement_1 (November 13, 2019): 5911. http://dx.doi.org/10.1182/blood-2019-125565.

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Objective: Chronic myeloid leukemia (CML) is a rare disease among children. It comprises 3% of childhood leukemias. CML in children is different from CML in adult. Here we analyzed the clinical features and prognosis of pediatric CML in a single institute from China. Methods: A retrospective study was performed by reviewing clinical records of pediatric CML from 2002 to 2019. Results: A total of 48 pediatric CML cases were included in the study, with 35 males and 13 females (M: F=2.7:1). Four cases were diagnosed during 2002~2007, 12 cases during 2008~2013 and 32 cases during 2014~2019. Two (4.2%) patients were in accelerate phase (AP) and other 46 patients were in chronic phase (CP) at diagnosis. Median age of onset was 9y (range 1~17y). The most common symptoms were fever (21.6%), fatigue (14.9%) and cough (10.8%). Median size of spleen under left costal margin was 5cm (range 0~21cm). Median WBC count was 15.7/ul, hemoglobin 9.5g/dL, platelet count 58/ul, neutrophils percentage 56% (range 21~74%), basophils percentage 3% (range 1~16%) and median eosinophil percentage was 2% (range 0~19%). Thirty-five patients had done karyotype examination, and 28 cases (80%) with classical Philadelphia chromosome (Ph+). Other 13 patients without Ph chromosome but with BCR/ABL1 fusion gene. In our study, there were 4 patients treated by hydroxyurea and α-interferon, other 44 patients have been used imatinib (IM) 240-340mg/m2 per day. Median time from onset to diagnosis was 0.7 months (range 1 day~12 months). Median follow-up time was 52 months (range 1~200 months), while the 5-year overall survival (OS) and event-free survival (EFS) are 100% and 89.1%, respectively. Different gender, age at diagnosis, WBC count, platelet count, karyotype show no difference in OS and EFS. Four patients suffered from blast crisis (BC) (2 patients progressed after using hydroxyurea for 1 and 33 months, 2 patients progressed after using IM for 36 and 6 months, respectively). One patient's BCR/ABL1 transcript level was increased in 36 months after first administration of IM and recovered at 48 months by adding IM dosage from 200mg to 300mg per day. According to the European LeukemiaNet (ELN) criteria, 95.5% patients achieved complete hematologic response (CHR), 90.5% patients achieved complete cytogenetic response (CCyR) and 66.7% patients achieved major molecular response (MMR) at 3, 12, 18 months after IM administration, respectively. There was obvious correlation between WBC count at diagnosis and early molecular response (EMR). Median WBC count was 4.8/ul in patients with EMR and 38.1/ul in patients without EMR. Other clinical features, such as gender, age at diagnosis, hemoglobin count, platelet count and size of spleen, make no difference in EMR. Conclusion: This is a retrospective study on pediatric CML. The median age at diagnosis is 9 years old. Most of all patients are CML-CP. 5y OS and EFS are 100% and 89.1%. The CHR, CCyR, MMR at 3,12,18 months after IM therapy are 95.5%, 90.5% and 66.7% separately. Until now there is no sufficient data on efficiency and safety specific to pediatric CML patients. Further clinical investigations through international collaboration are need to help more and more patients to achieve treatment-free remission. Disclosures No relevant conflicts of interest to declare.

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Scheuring, Urban J., Heike Pfeifer, Barbara Wassmann, Patrick Brück, Johannes Atta, Eduard K. Petershofen, Brigitte Gehrke, Harald Gschaidmeier, Dieter Hoelzer, and Oliver G. Ottmann. "Early minimal residual disease (MRD) analysis during treatment of Philadelphia chromosome/Bcr-Abl–positive acute lymphoblastic leukemia with the Abl-tyrosine kinase inhibitor imatinib (STI571)." Blood 101, no. 1 (January 1, 2003): 85–90. http://dx.doi.org/10.1182/blood-2002-02-0360.

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Abstract The Abl kinase inhibitor imatinib mesylate (STI571) has significant and rapid antileukemic activity in Philadelphia chromosome/Bcr-Abl–positive acute lymphoblastic leukemia (Ph+ ALL) but such activity is usually of short duration except for a small proportion of patients. To determine the prognostic significance of early Bcr-Abl levels and changes in peripheral blood (PB) and bone marrow (BM), serial samples of 56 patients with relapsed or refractory Ph+ ALL treated in phase 2 trials of imatinib were analyzed by quantitative polymerase chain reaction (PCR). Imatinib induced a complete hematologic response (CHR) or complete marrow response (marrow-CR) in 40 patients (good responders) and a partial (n = 2) or no (n = 14) remission in the remaining patients (poor responders). Compared with baseline, the median Bcr-Abl/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) ratios decreased significantly in PB by 2.65, 2.64, and 3.11 log steps after 2 weeks, 4 weeks, and at the time of best response, respectively. In BM, the decline of median Bcr-Abl/GAPDH was 0.75, 1.37, and 2.78 logs, respectively. Thus, Bcr-Abl levels decreased more rapidly in PB than in BM (median time to best level 31 vs 39 days). Low Bcr-Abl/GAPDH ratios below 10−4 in PB and below 10−2 in BM after 2 weeks were significantly associated with good responses after 4 weeks. Moreover, Bcr-Abl levels (< 10−2) in BM of good responders after 4 weeks discriminated between 2 groups of patients with significantly different median time to progression (139 vs 22 days). The data show that Bcr-Abl levels in PB and BM after 2 weeks of imatinib treatment and in BM after 4 weeks have predictive relevance and may guide the application of additional therapies.

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Чорній, Анастасія. "Комунікативний аспект критерію "нейтральність" під час переговорів (на матеріалі сучасного англомовного конфліктного дискурсу)." East European Journal of Psycholinguistics 5, no. 1 (June 30, 2018): 16–24. http://dx.doi.org/10.29038/eejpl.2018.5.1.cho.

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У статті проаналізовано підходи до визначення і тлумачення поняття «нейтральність», а також практичні підходи його реалізації в межах процесу медіації. Психолінгвістика тлумачить медіативний дискурс як розгортання перемикань від внутрішнього коду до зовнішньої вербалізації у процесах породження мовлення та її інтерпретації з урахуванням соціально-психологічних типів мовних особистостей, рольових установок і приписів. За допомогою загальнонаукових методів вдалося спрямувати концептуальне значення слова «нейтральність» у комунікативну площину, а схеми комунікативних стратегій у реалізацію принципу «нейтральність». Принцип нейтральності є основоположним принципом процесу медіації, який закладений не лише у визначальних критеріях реалізації процесу, але є визначальним елементом статусу посередника. На прикладі англомовної художньої літератури виокремлено та проаналізовано низку комунікативних технік (техніки ігнорування, техніки нейтральних запитань, техніки однакових запитань), які виступають основними інструментами дотримання принципу нейтральності. Окремо звернено увагу і на мотиви введення тактик (оптимального контр реагування, рефлексії) у процес медіативного діалогу у форматі бесіди із залученням сторін та індивідуальних бесід із кожною із сторін окремо (у форматі кокус). Принцип нейтральності є плюралістичним і може розглядатись як синонімічна пара терміну «неупередженість» або ж терміну «справедливість». Ці поняття є близькими за значеннями, проте в межах лінгвістики тактики їх реалізації різняться. На прикладі англомовної художньої літератури, виокремлено не лише комунікативні техніки медіатора, вживання яких слугуватиме дотриманню принципу нейтральності, але й проаналізовано тенденції та умови їх застосування. Важливими аспектами в межах художньої літератури зокрема, є можливість передання ролі посередника іншому учаснику діалогу, а впродовж медіації загалом можна говорити про комбінаторний тип застосування технік. Література References Astor, H. (2000). Rethinking Neutrality: A Theory to Inform Practice. Australian Dispute Resolution Journal, 11(1), 73-83. Astor, H. (2000). Rethinking Neutrality: A Theory to Inform Practice. Australian Dispute Resolution Journal, 11(2), 145-154. Astor, H. (2002). Dispute Resolution in Australia. Sydney: LexisNexis Butterworths. Boulle, L. (2005). Mediation: Principles, Process, Practice. Chatswood: LexisNexis Butterworths. Cobb, S. (1991) Practice and Paradox: Deconstructing Neutrality in Mediation. Law and Social Inquiry, 16(1), 35-62. Cohen, O. (1999). The Limits of Mediator’s Neutrality. Mediation Quarterly, 16(4), 341-438. Douglas, S. (2008). Neutrality in Mediation: A Study of Mediator Perceptions. Retrieved from https://lr.law.qut.edu.au/article/view/88 European Code of Conduct for Mediators. Retrieved from: http://www.mediacia.com/documents.htm. Field, R. (2000). Neutrality and power: Myths and reality. The ADR Bulletin, 3(1), 16-19. Карасик В. И. Языковой круг: личность, концепты, дискурс: монография. [Электронный ресурс]. Волгоград: Перемена, 2002. Режим доступа: https://www.scribd.com/doc/52113602/ Lederach, J. (1995). Preparing for Peace: Conflict Transformation Across Culture. Syracuse University Press. Peterson N. (2007). The Mediation Dictionary. Retrieved from http://www.mediation dictionary.com/pdf/mediationdictionary.pdf Романишина І. М. Медіація як ефективний метод вирішення конфліктів у шкільній практиці / І. М. Романишина // Таврійський вісник освіти. 2014. № 3 (47). С. 248-255. The European Code of Conduct for Mediators. Retrieved from http://www.mediacia.com/ documents.htm. References (translated and transliterated) Astor, H. (2000). Rethinking Neutrality: A Theory to Inform Practice. Australian Dispute Resolution Journal, 11(1), 73-83. Astor, H. (2000). Rethinking Neutrality: A Theory to Inform Practice. Australian Dispute Resolution Journal, 11(2), 145-154. Astor, H. (2002). Dispute Resolution in Australia. Sydney: LexisNexis Butterworths. Boulle, L. (2005). Mediation: Principles, Process, Practice. Chatswood: LexisNexis Butterworths. Cobb, S. (1991) Practice and Paradox: Deconstructing Neutrality in Mediation. Law and Social Inquiry, 16(1), 35-62. Cohen, O. (1999). The Limits of Mediator’s Neutrality. Mediation Quarterly, 16(4), 341-438. Douglas, S. (2008). Neutrality in Mediation: A Study of Mediator Perceptions. Retrieved from https://lr.law.qut.edu.au/article/view/88 European Code of Conduct for Mediators. Retrieved from: http://www.mediacia.com/documents.htm. Field, R. (2000). Neutrality and Power: Myths and Reality. The ADR Bulletin, 3(1), 16-19. Karasik, V. (2002). Yazykovoi Krug: Lichnost, Kontsepty, Diskurs. [Language circle: Personality, Concepts, Discourse]. Retrieved from: https://www.scribd.com/doc/52113602/ Lederach, J. (1995). Preparing for Peace: Conflict Transformation Across Culture. Syracuse University Press. Peterson N. (2007). The Mediation Dictionary. Retrieved from http://www.mediation dictionary.com/pdf/mediationdictionary.pdf Romanyshyna, I. (2014). Mediatsiia yak Efectyvnyi Metod Vyrishennia Konfliktiv u Shkilnii Practytsi [Mediation as Effective Method in Conflict Resolution at School Practice]. Tavriiskyi Visnyk Osvity, 3 (47), 248-255. Sources Draper S. (1994). Teas of a Tiger. (Simon Pulse). Retrieved from: http://lgnavigators.weebly.com/uploads/5/8/5/2/58521739/tears_of_a_tiger__hazelwood_hig_-_sharon_m__draper.pdf Stockett K. (2009). The Help. (Penguin Group) Retrieved from: https://gelleresol.weebly.com/uploads/3/0/1/6/30164729/the_help_-_kathryn_stockett.pdf

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Lewis, Sarah A., Andrew T. Hudak, Peter R. Robichaud, Penelope Morgan, Kevin L. Satterberg, Eva K. Strand, Alistair M. S. Smith, Joseph A. Zamudio, and Leigh B. Lentile. "Indicators of burn severity at extended temporal scales: a decade of ecosystem response in mixed-conifer forests of western Montana." International Journal of Wildland Fire 26, no. 9 (2017): 755. http://dx.doi.org/10.1071/wf17019.

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We collected field and remotely sensed data spanning 10 years after three 2003 Montana wildfires to monitor ecological change across multiple temporal and spatial scales. Multiple endmember spectral mixture analysis was used to create post-fire maps of: char, soil, green (GV) and non-photosynthetic (NPV) vegetation from high-resolution 2003 hyperspectral (HS) and 2007 QuickBird (QB) imagery, and from Landsat 5 and 8 imagery collected on anniversary dates in 2002, 2003 (post fire), 2004, 2007 and 2013. Initial estimates of char and NPV from the HS images were significantly correlated with their ground-measured counterparts (ρ=0.60 (P=0.03) and 0.68 (P=0.01) respectively), whereas HS GV and Landsat GV were correlated with canopy GV (ρ=0.75 and 0.70 (P=0.003) respectively). HS imagery had stronger direct correlations with all classes of fine-scale ground data than Landsat and also had stronger predictive correlations with 10-year canopy data (ρ=0.65 (P=0.02) to 0.84 (P=0.0003)). There was less than 5% understorey GV cover on the sites initially, but by 2013, it had increased to nearly 60% regardless of initial condition. The data suggest it took twice as long for understorey GV and NPV to replace char and soil as primary ground cover components on the high-burn-severity sites compared with other sites.

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Brunke, E. G., R. Ebinghaus, H. H. Kock, C. Labuschagne, and F. Slemr. "Emissions of mercury in southern Africa derived from long-term observations at Cape Point, South Africa." Atmospheric Chemistry and Physics 12, no. 16 (August 17, 2012): 7465–74. http://dx.doi.org/10.5194/acp-12-7465-2012.

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Abstract. Mercury emissions in South Africa have so far been estimated only by a bottom-up approach from activities and emission factors for different processes. In this paper we derive GEM/CO (GEM being gaseous elemental mercury, Hg0), GEM/CO2, GEM/CH4, CO/CO2, CH4/CO2, and CH4/CO emission ratios from plumes observed during long-term monitoring of these species at Cape Point between March 2007 and December 2009. The average observed GEM/CO, GEM/CO2, GEM/CH4, CO/CO2, CH4/CO2, and CH4/CO emission ratios were 2.40 ± 2.65 pg m−3 ppb−1 (n = 47), 62.7 ± 80.2 pg m−3 ppm−1 (n = 44), 3.61 ± 4.66 pg m−3 ppb−1 (n = 46), 35.6 ± 25.4 ppb ppm−1 (n = 52), 20.2 ± 15.5 ppb ppm−1 (n = 48), and 0.876 ± 1.106 ppb ppb−1 (n = 42), respectively. The observed CO/CO2, CH4/CO2, and CH4/CO emission ratios agree within the combined uncertainties of the observations and emissions with the ratios calculated from EDGAR (version 4.2) CO2, CO, and CH4 inventories for South Africa and southern Africa (South Africa, Lesotho, Swaziland, Namibia, Botswana, Zimbabwe, and Mozambique) in 2007 and 2008 (inventories for 2009 are not available yet). Total elemental mercury emission of 13.1, 15.2, and 16.1 t Hg yr−1 are estimated independently using the GEM/CO, GEM/CO2, and GEM/CH4 emission ratios and the annual mean CO, CO2, and CH4 emissions, respectively, of South Africa in 2007 and 2008. The average of these independent estimates of 14.8 t GEM yr−1 is much less than the total emission of 257 t Hg yr−1 shown by older inventories which are now considered to be wrong. Considering the uncertainties of our emission estimate, of the emission inventories, and the fact that emission of GEM represents 50–78 % of all mercury emissions, our estimate is comparable to the currently cited GEM emissions in 2004 and somewhat smaller than emissions in 2006. A further increase of mercury emissions due to increasing electricity consumption will lead to a more pronounced difference. A quantitative assessment of the difference and its significance, however, will require emission inventories for the years of observations (2007–2009) as well as better data on the speciation of the total mercury emissions in South Africa.

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Tohjima, Y., M. Kubo, C. Minejima, H. Mukai, H. Tanimoto, A. Ganshin, S. Maksyutov, K. Katsumata, T. Machida, and K. Kita. "Temporal changes in the emissions of CH4 and CO from China estimated from CH4 / CO2 and CO / CO2 correlations observed at Hateruma Island." Atmospheric Chemistry and Physics Discussions 13, no. 8 (August 30, 2013): 22893–930. http://dx.doi.org/10.5194/acpd-13-22893-2013.

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Abstract. In-situ observation of the atmospheric CO2, CH4, and CO mixing ratios at Hateruma Island (HAT, 24.05° N, 123.80° E) often show synoptic-scale variations with correlative elevations during winter, associated with air transport from the East Asian countries. We examine winter (November–March) trends in ΔCH4 / ΔCO2, ΔCO / ΔCO2, and ΔCO / ΔCH4 observed at Hateruma over the period 1999 to 2010. Although the ratios ΔCH4 / ΔCO2 and ΔCO / ΔCO2 both show an overall gradual decrease over the study period due to a recent rapid increase in fossil fuel consumption in China, we note that ΔCH4 / ΔCO2 and ΔCO / ΔCO2 remains relatively flat (no trend) during 2005–2010 and 1999–2004, respectively. The CO/CH4 slope on the other hand shows an increasing trend during 1999–2004 but a decrease during 2005–2010. Calculation of the concentration footprint for the atmospheric observation at HAT by using the FLEXPART Lagrangian particle dispersion model indicates that most of the short-term variations are caused by emission variations from North and East China. Combined with a set of reported emission maps, we have estimated the temporal changes in the annual CH4 and CO emissions from China under the assumption that the estimate of the fossil fuel-derived CO2 emissions based on the energy statistics is accurate. The estimated annual CH4 emissions, corresponding to non-seasonal sources or anthropogenic sources without rice fields, show a nearly constant value of 39 ± 6 TgCH4 yr−1 during 1998–2002, and then gradually increases to 46 ± 7 TgCH4 yr−1 in 2009/2010. The estimated annual CO emissions increase from 134 ± 26 TgCO yr−1 in 1998/1999 to 182 ± 33 TgCO yr−1 in 2004/2005, level off after 2005, and then slightly decrease to less than 160 TgCO yr−1 in 2008–2010.

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Rosenberg, Aaron S., Ann M. Brunson, Theresa HM Keegan, Brian Jonas, Joseph Tuscano, and Ted Wun. "The Effect of Autologous Stem Cell Transplant (ASCT) on Survival in Californians with Multiple Myeloma (MM) in the Era of Modern Treatment." Blood 126, no. 23 (December 3, 2015): 1991. http://dx.doi.org/10.1182/blood.v126.23.1991.1991.

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Abstract Background: The use and timing of ASCT on survival after MM in the era of modern therapy remain topics of debate. Using population based data, we evaluated factors associated with the receipt of ASCT and the effect of ASCT on overall survival (OS). Methods: Patients diagnosed with MM during 2000 - 2012 were identified in the California Cancer Registry (CCR) (n=12,714). CCR data were linked to the California Patient Discharge Database (PDD). Logistic regression estimated the odds ratio (OR) of having an early (< 1 year from diagnosis) or late (> 1 year) ASCT (vs. no ASCT). OS was calculated using the Kaplan-Meier (KM) method. To determine the effect of ASCT on OS from diagnosis date, Cox regression models estimated adjusted hazard ratios (aHR) of death treating ASCT as a time dependent covariate. OS time was compared after matching ASCT to no ASCT patients on age, sex, race/ethnicity, neighborhood socioeconomic status (SES), comorbidity at diagnosis, year of diagnosis, and accounting for time to transplant. Results: The majority of MM patients were male (54%) and of non-Hispanic white (58%) race/ethnicity; 19% Hispanic, 12% African American, and 9% Asian. Median age at diagnosis was 67 (range 18 - 104). African Americans and Hispanics were younger than non-Hispanic whites (median age 64 and 65 vs 69). Comorbidity data from the PDD was available in 59% of the patients in the 2 years prior to MM diagnosis: 7.5% had 0, 21% had 1-2, and 31% had ≥3 comorbidities. A total of 2136 (17%) patients underwent ASCT: 1347 < 1 year from and 789 ≥1 year after diagnosis. Time to ASCT did not change over time: among patients diagnosed 2000 - 2003 median time to transplant was 9.2 mo, 10 mo among those diagnosed 2004 - 2007 and 9.7 in those diagnosed 2008 - 2012. Patients who underwent ASCT were younger than those who did not (median age 56 vs 70 respectively). African Americans were less likely to undergo early ASCT (OR 0.7, P<0.001), but not late ASCT (OR 0.8, P=0.07). Patients with ≥3 comorbidities (vs. 0) at diagnosis were less likely to have ASCT (OR 0.42 P<0.001 and OR 0.28 P<0.001 for early and late, respectively), while patients with 1-2 comorbidities were less likely to have late ASCT (OR 0.59 P<0.001). The lowest 2 quintiles of SES was associated with less use of early ASCT (OR 0.62 p<0.001 and 0.65 p<0.001 respectively), but not late ASCT (OR 0.89 p=0.4 and 0.96 p=0.7 respectively). The likelihood of receiving ASCT increased over time: compared to 2000-2003, the ORs for patients diagnosed in 2004 - 2007 were 1.36 for early (P<0.001) and 1.64 (P<0.001) for late ASCT and were 2.64 (P<0.001) for early and 1.80 (P<0.001) for late for those diagnosed in 2008-2012. The median follow-up was 32 months. Median OS from diagnosis for the entire cohort, unadjusted for age, comorbidities, and SES was 37 months. Adjusting for sex, race/ethnicity, age at diagnosis, SES, comorbidities, insurance status and year of diagnosis, OS improved over time: compared to patients diagnosed in 2008 - 2012, aHR of death of those diagnosed 2000-2003 was 1.58 (P<0.001), and 1.35 (P<0.001) for those diagnosed 2004-2007. ASCT at any point was associated with a 23% reduction in the risk of death from all causes (aHR 0.77 P<0.001). Patients who received early ASCT had a 27% reduction (aHR 0.73 P<0.001), while those receiving late ASCT had an 11% decrease (aHR 0.89 P<0.001) in risk of all cause death. In the matched analysis, the median OS from date of transplant, or matched date in the no ASCT cohort, were: no ASCT = 49 mo, early ASCT = 83 mo, and late ASCT 65 mo (P<0.001 Figure 1). The effect of aSCT on OS differed by date of diagnosis (P for interaction <0.001). Improvements in OS due to ASCT were more pronounced in later time periods: aHR for early and late ASCT in 2000-2003 were 0.9 (P = 0.12) and 0.98 (P 0.86) compared with those in 2004-2007 (0.63 P<0.001 and 0.85 P = 0.06) and in 2008-2012 (0.55 P<0.001 and 0.74 P=0.08). Conclusions :ASCT was utilized in 17% of Californians with MM during 2000-2012, and its use increased over time. The use of ASCT, whether within a year of diagnosis or later in the disease course, is associated with improved OS and this effect may be more pronounced in the era of novel agents. Despite the inherent limitations of analyses of administrative databases, the large number of patients and established robust nature of CCR and PDD data makes accurate depiction of results in the community probable. These data support the continued role of ASCT in the management of patients with MM. Disclosures Jonas: Celgene: Honoraria; Incyte: Honoraria; Onyx: Honoraria; GlycoMimetics: Consultancy.

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Papayannidis, Cristina, Anna Ferrari, Stefania Paolini, Carmen Baldazzi, Chiara Sartor, Abbenante maria Chiara, Giovanni Marconi, et al. "Very Poor Outcome and Chemoresistance of Acute Myeloid Leukemia Patients with TP53 Mutations: Correlation with Complex Karyotype and Clinical Outcome." Blood 124, no. 21 (December 6, 2014): 484. http://dx.doi.org/10.1182/blood.v124.21.484.484.

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Abstract Background: AML is a heterogeneous disease. The karyotype provides important prognostic information that influences therapy and outcome. Identification of AML patients (pts) with poor prognosis such as those with complex karyotype (CK) has great interest and impact on therapeutic strategies. TP53 is the most frequently mutated gene in human tumours. TP53 mutation rate in AML was reported to be low (2.1%), but the incidence of TP53 mutations in AML with a complex aberrant karyotype is still debated. Aims: To investigate the frequency of TP53 mutations in adult AML pts, the types of mutations, the associations with recurrent cytogenetic abnormalities and their relationship with response to therapy, clinical outcome and finally their prognostic role. To this aim, we focused on a subgroup of TOT/886 AML pts treated at the Serˆgnoli Institute of Bologna between 2002 and 2013. Patients and Methods: 886 AML patients were analysed for morphology, immunophenotype, cytogenetic and for a panel of genetic alterations (FLT3, NPM1, DNMT3A, IDH1, IDH2 mutations, WT-1 expression, CBF fusion transcripts). Of these, 172 adult AML pts were also examined for TP53 mutations using several methods, including Sanger sequencing, Next-Generation Deep-Sequencing (Roche) and HiSeq 2000 (Illumina) platform. 40 samples were genotyped with Genome-Wide Human SNP 6.0 arrays or with CytoScan HD Array (Affymetrix) and analysed by Nexus Copy Numberª v7.5 (BioDiscovery). Results: Of the 886 AML patients, 172 pts were screened for TP53 mutations. Sanger sequencing analysis detected TP53 mutations in 29/172 AML patients with 36 different types of mutations; seven pts (4%) had 2 mutations. At diagnosis, the median age of TP53 mutated and wild type patients was 68 years (range 42-86), and 65 years (range 22-97) respectively. Median WBC count was 8955/mmc (range 580-74360/mmc) and 1240/mmc (range 400-238000/mmc). Conventional cytogenetics showed that: a) 52 pts (30,2%) had 3 or more chromosome abnormalities, i.e. complex karyotype; b) 71 (41,3%) presented with one or two cytogenetic abnormalities (other-AML); c) 34 pts (19,8%) had normal karyotype. Most of the TP53 mutated pts (23/29, 79.3%) had complex karyiotype, whereas only 6/29 mutated pts had “no complex Karyotype” (21% and 3% of the entire screened population, respectively). Overall, TP53 frequency was 44.2% in the complex karyotype group, suggesting a pathogenetic role of TP53 mutations in this subgroup of leukemias. As far as the types of TP53 alterations regards, the majority of mutations (32) were deleterious.. Copy Number Alterations (CNAs) analysis performed on 40 cases by Affymetrix SNP arrays showed the presence of several CNAs in all cases: they ranged from loss or gain of the full chromosome (chr) arm to focal deletions and gains targeting one or few genes involving macroscopic (>1.5 Mbps), submicroscopic genomic intervals (50 Kbps - 1.5 Mbps) and LOH (>5 Mbps) events. Of relevance, gains located on chr 8 were statistically associated with TP53 mutations (p = 0.001). In addition to the trisomy of the chr 8, others CNAs, located on chromosomes 5q, 3, 12, 17 are significantly associated (p = 0.05) with TP53 mutations. WES analysis was performed in 37 pts: 32 TP53 were wt while 5 pts were TP53 mutated. Interestingly, TP53 mutated patients had more incidence of complex karyotype, more aneuploidy state, more number of somatic mutations (median mutation rate 30/case vs 10/case, respectively). Regarding the clinical outcome, as previously reported (Grossmann V. et Al. Blood 2013), alterations of TP53 were significantly associated with poor outcome in terms of both overall survival (median survival: 4 and 31 months in TP53 mutated and wild type patients, respectively; p<0.0001) and relapse free-survival (RFS) (p < 0.0001). (Figure 1) Figure 1: Overall Survival curve of 172 AML patients with (red) or without (blue) TP53 mutations (p< 0.0001). Conclusions: Our data demonstrated that TP53 mutations are more frequent at diagnosis in the subgroup of complex karyotype AML (16.86%) (p< 0.0001–Fisher's exact test). They are mostly deleterious mutations and are significantly correlated with worst prognosis, fail to respond to therapy and rapidly progress. We recommend TP53 mutation screening at least in AML pts carrying either complex karyotype or chr. 8 gain. Supported by: ELN, AIL, AIRC, PRIN, progetto Regione-Universitˆ 2010-12 (L. Bolondi), FP7 NGS-PTL project. Disclosures No relevant conflicts of interest to declare.

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Turkina, Anna G., Sergey Kulikov, Kudrat Abdulkadirov, Sergey Kutsev, Anatoly Golenkov, Valentina Ivanova, Tatiana Pospelova, Tatiana Konstantinova, Olga Lazareva, and Nina Khoroshko. "Results of Tyrosine Kinase Inhibitors (TKI) Therapy of Patients (Pts) with Chronic Myeloid Leukemia (CML) In Clinical Practice Analysed In the Frame of International Research Project EUTOS In Russian Federation." Blood 118, no. 21 (November 18, 2011): 4447. http://dx.doi.org/10.1182/blood.v118.21.4447.4447.

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Abstract Abstract 4447 Background: High efficiency of imatinib (IM) in CML therapy has been proven in clinical trials. However, the outcomes of CML treatment by IM in clinical practice are not covered in the literature. Objectives: To evaluate the results of CML treatment by TKI in clinical practice in the Russian Federation. Patients and treatment: The data analysis from 28 administrative regions of theRussian Federation was performed. The selection of regions was based on the quality of the data from CML pts registry. 524 CML pts were included in this study. Inclusion criteria were: Ph/bcr-abl-positive CML diagnosed in 2002– 2006, age of pts ≥ 18 years (y), initiation of IM therapy ≤ 6 months (mo) from the date of diagnosis. Median (Me) age was 47(18 – 81) y, sex ratio (M/F (%)) 250/274 (48/52) pts, Me time from diagnosis to IM treatment was 2.4(0 – 6) mo. Pretreatment: Hydrea 398 (76%) pts; Mielosan 3 (0.5%) pts, chemotherapy 21(4%)pts, IFN-α 30 (5.7%) pts. Me follow-up since the beginning of CML treatment was 55.2 (1 – 108) mo (*6 pts have not data on the date of analysis). In Chronic Phase (CP) were 478 (91.2%) pts, in Accelerated Phase (AP) - 40 (7.6%) pts and in Blast Crisis (BC) - 6 (1.2%). Sokal risk stratification, %: 52 low (L)/22 intermediate (Int)/26 high(H) (78 pts with no baseline data. Statistical analysis was performed using a package SAS9.1.3. Result: 427 (89%) from 478 CP CML pts were alive on May2011, 51(11%) pts were died. In this cohort of CP CML pts 5-year Overall Survival (OS) and Progression Free Survival (PFS) to AP/BC were 89% and 95% respectively (Me 56.4 (1 – 108) mo). The slow achievement of complete hematologic response (CHR) and complete cytogenetic response (CCyR) should be noted. On the IM therapy, 48% pts have achieved CHR by 3 mo only and 86% pts have achieved CHR by 12 mo (Me 3.2 (0.1 – 85) mo); CCyR at any time was achieved in 77% of pts, but by 12 mo – in only 40% of pts (Me 15 mo (0.7 – 75). There was no clear evidence of the dependence of OS rate from % of Ph’-positive cells in bone marrow after 6, 12, 18 and 36 mo were not received (p>0.5 in all cases). Analysis of molecular response (MR) was performed in 338 (70%) pts (not standardized rtPCR method): major MR was achieved in 241 (71%) pts (Me 42 (6–86) mo), complete MR - in 172 (50%) pts (Me 53(6–100) mo). OS by Sokal in pts with L and Int risk groups was identical and better than in pts with H, consistent with 90 and 83%, respectively (p=0.04). The probability of CCyR by Sokal were 85, 80 and 70% for the L, Int and H risk of disease progression, respectively (p=0,0002). IM therapy is still ongoing in 362 (85%) pts in doses 400/600/800mg/day-54%/33%/13%, respectively. 41(10%) pts were switched to 2nd line TKI (25 pts to Nilotinib, 10 pts- Dasatinib, 6 pts-Bosutinib). In total, 51 (11%) pts died (21 pts with progression to AP/BC, 30pts with associated diseases). Conclusion: The research program EUTOS enabled Russian hematologists to cooperate with an international research group (ELN) and this cooperation allows to improve the quality of CML treatment, monitoring MRD and data collection in the Russian CML registry. The analysis of data shows high rates of OS and PFS in CP CML, despite the delay of CHR and CCyR achievement. In clinical practice the low significanse of Sokal risk criteria and the absence of the influence of cytogenetic response achievement on OS was established that differ from clinical trial data and that may be due to a non-standardized approach to treatment and retrospective data collection. Disclosures: Turkina: Novartis: Consultancy, Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau. Kulikov:Novartis: statistical tasks. Kutsev:Novartis: Research Funding, Speakers Bureau. Golenkov:Novartis: Speakers Bureau. Ivanova:Novartis: Honoraria, Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Pospelova:Novartis: Research Funding, Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Konstantinova:Novartis: Speakers Bureau. Lazareva:Novartis: Research Funding, Speakers Bureau, work with CML Registry. Khoroshko:Novartis: Speakers Bureau.

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Shan, LeeAnn, Zachary B. Millman, Joseph DeLuca, Mallory J. Klaunig, Pamela Rakhshan Rouhakhtar, Alicia Lucksted, and Deborah R. Medoff. "S27. EXAMINING DISCREPANCIES BETWEEN SELF-REPORT AND CLINICIAN-RATED ASSESSMENTS OF PSYCHOSIS RISK: DOES INTERNALIZED STIGMA MATTER?" Schizophrenia Bulletin 46, Supplement_1 (April 2020): S41. http://dx.doi.org/10.1093/schbul/sbaa031.093.

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Abstract Background Psychosis is one of the most highly stigmatized mental health conditions (Thornicroft et al., 2009). Compared to those with other mental health concerns, people diagnosed with schizophrenia spectrum disorders are more likely to be perceived by others as dangerous, violent, and unpredictable. As a result, they are often socially marginalized and discriminated against (Crisp et al., 2000; Martin et al., 2007). Individuals at clinical high risk (CHR) for psychosis may be at lower risk for experiencing public stigma, given that their symptoms are often less outwardly visible at this early stage of illness. However, evidence suggests that those at CHR experience high levels of self-stigma, as they may internalize negative stereotypes related to psychosis (Yang et al., 2010; Yang et al., 2015). Internalized stigma can negatively impact help-seeking behavior and has been associated with lower self-esteem and the underreporting of mental health symptoms (Corrigan, 2004; Corrigan, 2007; Saporito, Ryan, & Teachman, 2011; Rüsch, Angermeyer, & Corrigan, 2005). Despite these findings, no studies to-date have examined how internalized stigma may impact reporting of attenuated psychosis symptoms in the CHR population. The current study aims to examine whether discrepancies between self-report and clinician-rated measures of psychosis risk are associated with internalized stigma in a sample of help-seeking adolescents and young adults. We hypothesized that higher levels of self-stigma will predict inconsistencies between self-reported symptom severity and clinician-obtained diagnoses of psychosis risk. Methods Participants will include youth classified as either non-psychosis-related help-seeking controls or at clinical high risk (CHR) for psychosis, as determined by the Structured Interview for Psychosis-Risk Syndromes (SIPS; Miller et al., 2003). The SIPS is administered by trained raters and is currently considered the gold standard tool for diagnosing clinical high-risk syndromes (Thompson et al., 2018). In addition to SIPS diagnoses, psychosis risk will also be assessed using the Prime Screen – Revised (PS-R; Miller et al., 2004), a brief, 12-item self-report questionnaire designed to measure attenuated positive symptoms. Lastly, internalized stigma will be assessed using the Internalized Stigma of Mental Illness Inventory (ISMI; Ritsher, Otilingam, & Grajales, 2003), a 29-item self-report questionnaire designed to measure subjective experiences of stigma in adolescents (e.g., endorsement of negative stereotypes, social withdrawal and feelings of alienation due to mental health problems, etc.). Results Preliminary analyses demonstrate a significant interaction between Prime scores and internalized stigma in predicting SIPS diagnoses. Specifically, higher scores on the Prime were associated with increased odds of being diagnosed as CHR on the SIPS, but only for those participants who endorsed low and mean levels of stigma. For participants who endorsed high levels of stigma, there did not appear to be any relation between Prime scores and SIPS diagnoses. Discussion At the time of submission, participant recruitment is ongoing, and results and discussion will be presented on the final sample. Findings may inform efforts to improve detection and accurate diagnosis of psychosis risk syndromes in individuals at early stages of illness.

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Saunois, Marielle, Philippe Bousquet, Ben Poulter, Anna Peregon, Philippe Ciais, Josep G. Canadell, Edward J. Dlugokencky, et al. "Variability and quasi-decadal changes in the methane budget over the period 2000–2012." Atmospheric Chemistry and Physics 17, no. 18 (September 20, 2017): 11135–61. http://dx.doi.org/10.5194/acp-17-11135-2017.

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Abstract. Following the recent Global Carbon Project (GCP) synthesis of the decadal methane (CH4) budget over 2000–2012 (Saunois et al., 2016), we analyse here the same dataset with a focus on quasi-decadal and inter-annual variability in CH4 emissions. The GCP dataset integrates results from top-down studies (exploiting atmospheric observations within an atmospheric inverse-modelling framework) and bottom-up models (including process-based models for estimating land surface emissions and atmospheric chemistry), inventories of anthropogenic emissions, and data-driven approaches. The annual global methane emissions from top-down studies, which by construction match the observed methane growth rate within their uncertainties, all show an increase in total methane emissions over the period 2000–2012, but this increase is not linear over the 13 years. Despite differences between individual studies, the mean emission anomaly of the top-down ensemble shows no significant trend in total methane emissions over the period 2000–2006, during the plateau of atmospheric methane mole fractions, and also over the period 2008–2012, during the renewed atmospheric methane increase. However, the top-down ensemble mean produces an emission shift between 2006 and 2008, leading to 22 [16–32] Tg CH4 yr−1 higher methane emissions over the period 2008–2012 compared to 2002–2006. This emission increase mostly originated from the tropics, with a smaller contribution from mid-latitudes and no significant change from boreal regions. The regional contributions remain uncertain in top-down studies. Tropical South America and South and East Asia seem to contribute the most to the emission increase in the tropics. However, these two regions have only limited atmospheric measurements and remain therefore poorly constrained. The sectorial partitioning of this emission increase between the periods 2002–2006 and 2008–2012 differs from one atmospheric inversion study to another. However, all top-down studies suggest smaller changes in fossil fuel emissions (from oil, gas, and coal industries) compared to the mean of the bottom-up inventories included in this study. This difference is partly driven by a smaller emission change in China from the top-down studies compared to the estimate in the Emission Database for Global Atmospheric Research (EDGARv4.2) inventory, which should be revised to smaller values in a near future. We apply isotopic signatures to the emission changes estimated for individual studies based on five emission sectors and find that for six individual top-down studies (out of eight) the average isotopic signature of the emission changes is not consistent with the observed change in atmospheric 13CH4. However, the partitioning in emission change derived from the ensemble mean is consistent with this isotopic constraint. At the global scale, the top-down ensemble mean suggests that the dominant contribution to the resumed atmospheric CH4 growth after 2006 comes from microbial sources (more from agriculture and waste sectors than from natural wetlands), with an uncertain but smaller contribution from fossil CH4 emissions. In addition, a decrease in biomass burning emissions (in agreement with the biomass burning emission databases) makes the balance of sources consistent with atmospheric 13CH4 observations. In most of the top-down studies included here, OH concentrations are considered constant over the years (seasonal variations but without any inter-annual variability). As a result, the methane loss (in particular through OH oxidation) varies mainly through the change in methane concentrations and not its oxidants. For these reasons, changes in the methane loss could not be properly investigated in this study, although it may play a significant role in the recent atmospheric methane changes as briefly discussed at the end of the paper.

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Montero Herrero, Santiago. "La mujer romana y la expiación de los andróginos." Vínculos de Historia. Revista del Departamento de Historia de la Universidad de Castilla-La Mancha, no. 8 (June 20, 2019): 33. http://dx.doi.org/10.18239/vdh_2019.08.02.

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RESUMENEl nacimiento en la Antigua Roma de niños con rasgos sexuales masculinos y femeninos a la vez, los llamados andróginos o hermafroditas, eran considerados como un gravísimo prodigio. Su expiación, necesaria para el restablecimiento de las buenas relaciones entre los hombres y los dioses, quedó en manos exclusivamente de mujeres: ancianas, matronas y virgines.PALABRAS CLAVE: Antigua Roma, Matrona, prodigio, expiación, andróginoABSTRACTThe birth in ancient Rome of children with both male and female sexual features, so-called androgynes or hermaphrodites, was regarded as a an extraordinary phenomenon. Their expiation, necessary for the restoration of good relations between men and gods, remained exclusively in the hands of women: old women, midwives and virgines.KEY WORDS: Ancient Rome, midwife, prodigy, expiation, androgynus BIBLIOGRAFÍAAbaecherly Boyce, A. (1937), “The expiatory rites of 207 B. C.”, TAPhA, 68, 157-171.Allély, A. (2003), “Les enfants malformés et considerés comme prodigia à Rome et en Italie sous la République”, REA, 105, 1, 127-156.Allély, A. (2004), “Les enfants malformés et handicapés à Rome sous le Principat”, REA, 106, 1, 73-101.Androutsos, G. (2006), “Hermaphroditism in Greek and Roman antiquity”, Hormones, 5, 214-217.Berthelet, Y. (2010), “Expiation, par les autorités romaines, de prodiges survenus en terre alliée: Quelques réflexions sur le statut juridique des territoires et des communautés alliés, et sur le processus de romanisation”, Hypothèses, 13, 1, 169-178.Berthelet, Y. (2013), “Expiation, par Rome, de prodiges survenus dans les cités alliées du nomen latinum ou des cités alliées italiennes non latines”, L´Antiquité Classique 82, 91-109.Breglia Pulci Doria, L. (1983), Oracoli Sibillini tra rituali e propaganda (Studi su Flegonte di Tralles), Napoli, Liguori Editori.Brisson, L. (1986), “Neutrum utrumque. La bisexualité dans l´antiquité gréco-romaine”, en L´Androgyne, Paris, Albin Michel, 31-61.Brisson, L. (1997), Le sex incertain. Androgynie et hermaphroditisme dans l´Antiquité gréco-romaine, Paris, Les Belles Lettres.Caerols, J. J. (1991), Los Libros Sibilinos en la historiografía latina, Madrid, Editorial Complutense.Cantarella, E. (2002), Bisexuality in the Ancient World, New Haven CT, Yale University Press.Cantarella, E. (2005), “The Androgynous and Bisexuality in Ancient Legal Codes”, Diogenes, 52, 5, 5-14.Cid López, R. M. (2007), “Las matronas y los prodigios. Prácticas religiosas femeninas en los ‘márgenes’ de la religión romana”, Norba, 20, 11-29.Cousin, J. (1942-1943), “La crise religieuse de 207 av. J.-C.”, RHR, 126, 15-41.Crifò, G. (1999), Prodigium e diritto: il caso dell’ermafrodita, Index, 27, 113-120.Champeaux, J. (1996), “Pontifes, haruspices et décemvirs. L´expiation des prodiges de 207”, REL, 74, 67-91.Dasen, V. (2005), “Blessing or portents? Multiple births in ancient Rome”, en K. Mustakallio, J. Hanska, H.-L. Sainio, V. Vuolanto (éds.), Hoping for continuity.Childhood, education and death in Antiquity and the Middle Ages (Acta Instituti Romani Finlandiae XXXIII), Rome, 72-83.Delcourt, M. (1958), Hermaphrodite. Mythes et rites de la bisexualité dans l´antiquité classique, Paris, PUF.Delcourt, M. (1966), Hermaphroditea. Recherches sur l´être double promoteur de la fertilité dans le monde classique (Coll. Latomus 86), Bruxelles, Latomus.Doroszewska, J. (2013), “Between the monstrous and the Divine: Hermaphrodites in Phlegon of Tralles´Mirabilia”, Acta Ant. Hung, 53, 379–392.Freyburger, G. (1977), “La supplication d´actions de grâces dans la religion romaine archaïque”, Latomus, 36, 283-315.Freyburger, G. (1988), “Supplication grecque et supplication romaine”, Latomus, 47, 3, 501-525.Garland, R. (1995), The Eye of the Beholder. Deformity and Disability in the Graeco-Roman World, London, Duckworth.Graumann, L. A. (2013), “Monstrous Births and Retrospective diagnosis: the case of Hermafrodites in Antiquity”, en Chr. Laes, C.F. Goodey, M. Lynn Rose (eds.), Disabilities in Roman antiquity: disparate bodies, a capite ad calcem (Mnemosyne, supplements. History and archaeology of classical antiquity, 356), Leiden-Boston, Brill, 181-210.Guittard, Ch. (2004), “Les prodiges dans le livre XXVII de Tite-Live”, Vita Latina, 170, 56-81.Halkin, L. (1953), La supplication d´action de grâces chez les Romains, Paris, Les Belles Lettres.Lake, A. K. M. (1937), “The Supplicatio and Graecus Ritus”, en R.P. Casey, S. Lake- A.K. Lake (eds.), Quantulacumque: Studies Presented to Kirsopp Lake, London, Christophers, 243-251.Louis, P. (1975), Monstres et monstruosites dans la biologie d’Aristote, en J. Bingen, G. Cambier, G. Nachtergael (éd.), Le monde grec: pensée, litterature, histoire, documents. Hommages à Claire Préaux, Bruxelles, Éditions de l´Université de Bruxelles, 277-284.Mac Bain, B. (1982), Prodigy and expiation: a study in Religion and Politics in Republican Rome (Coll. Latomus 117), Bruxelles, Latomus.Maiuri, A. (2012), “Deformità e difformità nel mondo greco-romano”, en M. Passalacqua, M. De Nonno, A. M. Morelli (a cura di), Venuste noster. Scritti offerti a Leopoldo Gamberale (Spudasmata 147), Zurich, Georg Olms Verlag, 526-547.Maiuri, A. (2013), “Il lessico latino del mostruoso”, en I. Baglioni (a cura di), Monstra. Costruzione e Percezione delle Entità Ibride e Mostruose nel Mediterraneo Antico (Religio Collana di Studi del Museo delle Religioni “Rafaele Pettazzoni”), Roma, Quasar, Vol.II, 167-177.Mazurek, T. (2004), “The decemviri sacris faciundis: supplication and prediction”, en C.F. Konrad (ed.), Augusto augurio. Rerum humanarum et divinarum commentationes in honorem Jerzy Linderski, Stuttgart, Steiner Verlag, 151-168.Mineo, B. (2000), “L´anneé 207 dans le récit livien”, Latomus, 52, 512-540.Monaca, M. (2005), La Sibilla a Roma. I libri sibillini fra religione e politica, Cosenza, Giordano.Montero, S. (1993), “Los harúspices y la moralidad de la mujer romana”, Athenaeum. 81, 647-658.Montero, S. (1994), Diosas y adivinas. Mujer y adivinación en la Roma antigua, Madrid, Trotta.Montero, S. (2008), “La supplicatio expiatoria como factor de cohesión social”, en N. Spineto (a cura di), La religione come fattore di integrazione: modelli di convivenza e di scambio religioso nel mondo antico. Atti del IV Convegno Internazionale del Gruppo di Ricerca Italo-Spagnolo di Storia delle Religioni Università degli Studi di Torino (29-30 sept. 2006), Alessandria, Edizioni dell´Orso.Moussy, C. (1977), “Esquisse de l’histoire de monstrum”, RÉL, 55, 345-369.Péter, O. M. (2001), “Olim in prodigiis nunc in deliciis. Lo status giuridico dei monstra nel diritto romano”, en G. Hamza, F. Benedek (hrsg.), Iura antiqua-Iura moderna. Festschrift für Ferenc Benedek zum 75. Geburtstag, Pecs, Dialóg Campus Kiadó, 207-216.Sandoz, L. Ch. (2008), “La survie des monstres: ethnographie fantastique et handicap à Rome, la force de l´imagination”, Latomus, 68, 21-36.Scheid, J. (1988), “Les livres Sibyllins et les archives des quindecémvirs”, en C. Moatti (ed.), La mémoire perdue. Recherches sur l´administration romaine, Paris, École Française de Rome, 11-26.Schulz, C. E. (2006), Women´s Religious Activity in the Roman Republic, Chapel Hill, University of North Carolina Press.Segarra, D. (2005), “La arboricultura y el orden del mundo: de Vertumnus al ‘Dios’ que planta e injerta”, en R. Olmos, P. Cabrera, S. Montero (eds.), Paraíso cerrado, jardín abierto: el reino vegetal en el imaginario del Mediterráneo, Madrid, Polifemo, 207-232.Segarra, D. (2006), “‘Arboricoltori sacri’. L’operato degli aruspici nella sfera vegetale”, en M. Rocchi, P. Xella, J. A. Zamora (a cura di), Gli operatori cultuali, Atti del II Incontro di studio organizzato dal “Gruppo di contatto per lo studio delle religioni mediterranee” (Roma, 10 - 11 maggio 2005), Verona, Essedue.Trentin, L. (2011), “Deformity in the Roman Imperial Court”, G&R, II S., 58, 195-208.Vallar, S. (2013), “Les hermaphrodites l’approche de la Rome antique”, RIDA, 60, 201-217.

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Sacha, Tomasz. "IMATINIB IN CHRONIC MYELOID LEUKEMIA: AN OVERVIEW." Mediterranean Journal of Hematology and Infectious Diseases 6, no. 1 (December 31, 2013): e2014007. http://dx.doi.org/10.4084/mjhid.2014.007.

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Imatinib was the first signal transduction inhibitor (STI), used in a clinical setting. It prevents a BCR-ABL protein from exerting its role in the oncogenic pathway in chronic myeloid leukemia (CML). Imatinib directly inhibits the constitutive tyrosine kinase activity. Imatinib binds to BCR-ABL kinase domain by preventing the transfer of a phosphate group to tyrosine on the protein substrate and the subsequent activation of phosphorylated protein. As the result, the transmission of proliferative signals to the nucleus is blocked and leukemic cell apoptosis is induced. The FDA has approved imatinib as first-line treatment for newly diagnosed CML in December 2002 following an International Randomized Study (IRIS), initiated in June 2000, comparing imatinib at a single daily dose 400 mg to IFN alpha plus cytarabine in newly diagnosed patients with CML in CP. Results from this study show the outstanding effectiveness of imatinib and its superiority with respect to the rates of complete hematological response (CHR), major and complete cytogenetic response (MCyR, CCyR). Patients randomized to imatinib arm at 8 – year data cut off continue to have a durable hematologic and cytogenetic response, low progression rates to AP or BC, and remarkable survival outcomes. An overall survival (OS) rate is 85% for patients receiving imatinib (93% when only CML-related deaths and those prior to stem cell transplantation are considered). The results have been confirmed in the last years by several groups. According these cumulative results the rates of CCyR achieved after one year of therapy with imatinib at standard dose ranged from 49% to 77%, and the proportion of patients who achieved major molecular response (MMR) after one year ranged between 18% and 58%. Discontinuation of imatinib has been also tried in patients in MMR, a molecular relapse occurs in about one third of patients, generally within 6 months from imatinib cessation.

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Alemu, Aklilu, K. H. Ominski, and E. Kebreab. "Estimation of enteric methane emissions trends (1990–2008) from Manitoba beef cattle using empirical and mechanistic models." Canadian Journal of Animal Science 91, no. 2 (June 2011): 305–21. http://dx.doi.org/10.4141/cjas2010-009.

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Alemu, A. W., Ominski, K. H. and Kebreab, E. 2011. Estimation of enteric methane emissions trends (1990–2008) from Manitoba beef cattle using empirical and mechanistic models. Can. J. Anim. Sci. 91: 305–321. The objective of this study was to estimate and assess trends in enteric methane (CH4) emissions from the Manitoba beef cattle population from the base year of 1990 to 2008 using mathematical models. Two empirical (statistical) models: Intergovernmental Panel on Climate Change (IPCC) Tier 2 and a nonlinear equation (Ellis), and two dynamic mechanistic models: MOLLY (v3) and COWPOLL were used. Beef cattle in Manitoba were categorized in to 29 distinct subcategories based on management practice, physiological status, gender, age and production environment. Data on animal performance, feeding and management practices and feed composition were collected from the literature as well as from provincial and national sources. Estimates of total enteric CH4 production from the Manitoba beef cattle population varied between 0.9 and 2.4 Mt CO2 eq. from 1990 to 2008. Regardless of the type of models used, average CH4 emissions for 2008 were estimated to be 45.2% higher than 1990 levels. More specifically, CH4 emissions tended to increase between 1990 and 1996. Emissions were relatively stable between 1996 and 2002, increased between 2003 and 2005, but declined by 13.2% between 2005 and 2008, following the same trend as that observed in the beef cattle population. Models varied in their estimates of CH4 conversion rate (Ym, percent gross energy intake), emission factor (kg CH4 head−1 yr−1) and CH4 production. Total CH4 production estimates ranged from 1.2 to 2.0 Mt CO2 eq. for IPCC Tier 2, from 0.9 to 1.5 Mt CO2 eq. for Ellis, from 1.3 to 2.1 Mt CO2 eq. for COWPOLL and from 1.5 to 2.4 Mt CO2 eq. for MOLLY. The results indicate that enteric CH4 estimates and emission trends in Manitoba were influenced by the type of model and beef cattle population. As such, it is necessary to use appropriate models for reliable estimates for enteric CH4 inventory. A more robust approach may be to integrate different models by using mechanistic models to estimate regional Ym values, which may then be used as input for the IPCC Tier 2 model.

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Dilsky, Stefan, and Wolfdieter A. Schenk. "Diastereomeric Halfsandwich Rhenium Complexes Containing Thiolate and Thioaldehyde Ligands." Zeitschrift für Naturforschung B 59, no. 10 (October 1, 2004): 1093–102. http://dx.doi.org/10.1515/znb-2004-1003.

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Abstract The reaction of diastereomeric methyl rhenium complexes [CpRe(NO)(NMDPP)(CH3)] (NMDPP = neomenthyl-diphenylphosphine) and [CpRe(NO)(PAMP)(CH3)] (PAMP = phenyl-2- anisyl-methylphosphine) with thiols in the presence of HBF4 gave thiolate complexes [CpRe(NO)(NMDPP)(SCH2Ph)] and [CpRe(NO)(PAMP)(SCH2R)] (R = Ph, 4-C6H4Cl, 4-C6H4OMe, 2-C4H3O, CH3, CH=CH2). Treatment of [CpRe(NO)(PAMP)(THF)]BF4 with the thiols and Na2CO3 gave the same compounds under neutral conditions. Similarly, the reaction of the chelate complex {CpRe(NO)[κP(Ph)(Me)(CH2C4H3κS)]}BF4 with thiols and NaOEt yielded the ring-opened products {CpRe(NO)[P(Ph)(Me)(CH2C4H3S)](SCH2R)} (R = Ph, 4-C6H4Cl, 4-C6H4OMe). One of the benzylic hydrogen atoms can be abstracted with [Ph3C]BF4 to give the diastereomeric thiobenzaldehyde complexes [CpRe(NO)(PAMP)(S=CHR)]BF4 (R = Ph, 4-C6H4Cl, 4-C6H4OMe) and {CpRe(NO)[P(Ph)(Me)(CH2C4H3S)](S=CHPh)}BF4. In these products, the thioformyl group is predominantly η2(C,S) coordinated to rhenium, but in a few cases the corresponding η1(S) isomers were also detected by IR and NMR spectroscopy.

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Wang, Di. "CHUS and CHR in 2003 and 2004: A personal memory." Chinese Historical Review 15, no. 1 (January 2008): 123–30. http://dx.doi.org/10.1179/tcr.2008.15.1.123.

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Ohnishi, Kazunori, Miki Nishimura, Jin Takeuchi, Shin Fujisawa, Tadashi Nagai, Koichi Miyamura, Yukihiko Kimura, et al. "Lower Dose of Imatinib Provides Outcomes Similar to the Standard Dose Imatinib in Japanese Patients with Early Chronic-Phase CML: The Interim Analyses of JALSG CML202 Study." Blood 110, no. 11 (November 16, 2007): 1044. http://dx.doi.org/10.1182/blood.v110.11.1044.1044.

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Abstract Background: The dose of imatinib 400 mg is considered to be standard for chronic-phase chronic myeloid leukemia (CML) based on the IRIS study. However, the optimal dose of imatinib is not yet settled and the response of lower dose imatinib has not been investigated. Lower dose of imatinib might be enough in Asian patients since the results of PK in IRIS study showed weak correlation between imatinib trough level and body weight. We showed the results of the interim analysis of JALSG CML202 study and analyzed the efficacy of imatinib according to the mean daily dose level. Methods: The objectives of CML202 study are to determine the efficacy of imatinib monotherapy in patients with newly diagnosed chronic-phase CML, and to test whether combining imatinib with IFN or cytarabine ocfosfate overcome the resistance of imatinib and to estimate the frequency and severity of toxicities. Primary end point of imatinib monotherapy was overall survival, and that of combination therapy was cytogenetic response after 9 months. Newly diagnosed patients with chronic phase CML will receive imatinib at a dose of 400mg daily. At 9 months, if patients don’t achieve major cytogenetic response (MCR), they were randomized to the combination therapies, imatinib plus conventional IFN or imatinib plus cytarabine ocfosfate. Results: From 2002 to 2006, 489 patients were enrolled to this study. On July 2007, 36 months median follow-up data were analyzed. Only 2 patients were enrolled to the combination therapy because a majority of patients achieved good response. 13 patients underwent HSCT. The estimated cumulative rates of complete hematologic response (CHR), MCR and complete cytogenetic response (CCR) were 97%, 97% and 91%, respectively. The estimated major molecular response (MMR) rate at 24 months was 55%. The estimated survival without AP/BC progression rate at 60 months was 94%. The overall estimated survival at 60 months was 94%. 95% of low risk patients achieved CCR significantly as compared with intermediate and high-risk patients according to Sokal risk. The mean daily dose of imatinib for the first 2 years was 400mg or more in 54% patients (400mg group), 300–399mg in 27% (300mg group), 200–299mg (200mg group) in 11%, and 100–199mg in 9% (100mg group), respectively. The cumulative rate of MCR and CCR at 60 months was 99% and 97% in 400mg group, 99% and 98% in 300mg group, 92% and 85% in 200mg group, and 81% and 48% in 100mg group, respectively (p=0.003 and p<0.0001). The cumulative rate of MMR at 18 months was 33% in 400mg group, 33% in 300mg group, 27% in 200mg group and 0% in 100mg group, respectively. The estimated rate of overall survival and progression-free survival at 60 months was 97% and 97% in 400mg group, 98% and 98% in 300mg group, 92% and 92% in 200mg group, and 87% and 87% in 100mg group, respectively (p=0.0002 and p=0.0009). Conclusion: The results of interim analyses of JALSG study were almost similar to those of IRIS study. However, the mean daily dose of imatinib was lower in our study than in IRIS study. The patients received imatinib 300mg showed outcomes similar to 400mg, suggesting that imatinib 300mg might be enough for Japanese patients. The comparative studies with PK measurement will ellucidate the optimal dose of imatinib.

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Bruhwiler, L., E. Dlugokencky, K. Masarie, M. Ishizawa, A. Andrews, J. Miller, C. Sweeney, P. Tans, and D. Worthy. "CarbonTracker-CH4: an assimilation system for estimating emissions of atmospheric methane." Atmospheric Chemistry and Physics 14, no. 16 (August 19, 2014): 8269–93. http://dx.doi.org/10.5194/acp-14-8269-2014.

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Abstract. We describe an assimilation system for atmospheric methane (CH4), CarbonTracker-CH4, and demonstrate the diagnostic value of global or zonally averaged CH4 abundances for evaluating the results. We show that CarbonTracker-CH4 is able to simulate the observed zonal average mole fractions and capture inter-annual variability in emissions quite well at high northern latitudes (53–90° N). In contrast, CarbonTracker-CH4 is less successful in the tropics where there are few observations and therefore misses significant variability and is more influenced by prior flux estimates. CarbonTracker-CH4 estimates of total fluxes at high northern latitudes are about 81 ± 7 Tg CH4 yr−1, about 12 Tg CH4 yr−1 (13%) lower than prior estimates, a result that is consistent with other atmospheric inversions. Emissions from European wetlands are decreased by 30%, a result consistent with previous work by Bergamaschi et al. (2005); however, unlike their results, emissions from wetlands in boreal Eurasia are increased relative to the prior estimate. Although CarbonTracker-CH4 does not estimate an increasing trend in emissions from high northern latitudes for 2000 through 2010, significant inter-annual variability in high northern latitude fluxes is recovered. Exceptionally warm growing season temperatures in the Arctic occurred in 2007, a year that was also anonymously wet. Estimated emissions from natural sources were greater than the decadal average by 4.4 ± 3.8 Tg CH4 yr−1 in 2007. CarbonTracker-CH4 estimates for temperate latitudes are only slightly increased over prior estimates, but about 10 Tg CH4 yr−1 is redistributed from Asia to North America. This difference exceeds the estimated uncertainty for North America (±3.5 Tg CH4 yr−1). We used time invariant prior flux estimates, so for the period from 2000 to 2006, when the growth rate of global atmospheric CH4 was very small, the assimilation does not produce increases in natural or anthropogenic emissions in contrast to bottom-up emission data sets. After 2006, when atmospheric CH4 began its recent increases, CarbonTracker-CH4 allocates some of the increases to anthropogenic emissions at temperate latitudes, and some to tropical wetland emissions. For temperate North America the prior flux increases by about 4 Tg CH4 yr−1 during winter when biogenic emissions are small. Examination of the residuals at some North American observation sites suggests that increased gas and oil exploration may play a role since sites near fossil fuel production are particularly hard for the inversion to fit and the prior flux estimates at these sites are apparently lower and lower over time than what the atmospheric measurements imply. The tropics are not currently well resolved by CarbonTracker-CH4 due to sparse observational coverage and a short assimilation window. However, there is a small uncertainty reduction and posterior emissions are about 18% higher than prior estimates. Most of this increase is allocated to tropical South America rather than being distributed among the global tropics. Our estimates for this source region are about 32 ± 4 Tg CH4 yr−1, in good agreement with the analysis of Melack et al. (2004) who obtained 29 Tg CH4 yr−1 for the most productive region, the Amazon Basin.

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Lemos Junior, Wilson. "O Canto Orfeônico na escola republicana brasileira e suas influências europeias (1890 – 1931)." Cadernos de História da Educação 19, no. 3 (August 21, 2020): 1069–79. http://dx.doi.org/10.14393/che-v19n3-2020-24.

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Este artigo tem por objetivo discorrer sobre o ensino do Canto Orfeônico na legislação brasileira entre 1890 e 1931 e sua relação com o ensino de Canto Orfeônico surgido na Europa ainda no século XVIII. Utiliza-se como fontes, as legislações escolares como as reformas de ensino de Benjamin Constant (1890) e de Francisco Campos (1931), assim como alguns artigos publicados por educadores como Veríssimo de Souza (1907; 1910) e Chasteau (1899). Somam-se às fontes, pesquisas de autores como Contier (1998), Souza (2000), Jardim (2003; 2006; 2009) e Gilioli (2008). O artigo está dividido em duas partes. A primeira parte investiga as relações entre a prática orfeônica brasileira e a europeia. A segunda aborda as características do Canto Orfeônico. A influência do orfeonismo praticado na Europa tornou-se definitiva para a realidade brasileira.

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Yow, Cheun Hoe. "China-ASEAN Relations, April 2002 to April 2003: Important Documents." China: An International Journal 1, no. 2 (2003): 363. http://dx.doi.org/10.1353/chn.2005.0041.

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Spahni, R., R. Wania, L. Neef, M. van Weele, I. Pison, P. Bousquet, C. Frankenberg, et al. "Constraining global methane emissions and uptake by ecosystems." Biogeosciences Discussions 8, no. 1 (January 11, 2011): 221–72. http://dx.doi.org/10.5194/bgd-8-221-2011.

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Abstract. Natural methane (CH4) emissions from wet ecosystems are an important part of today's global CH4 budget. Climate affects the exchange of CH4 between ecosystems and the atmosphere by influencing CH4 production, oxidation, and transport in the soil. The net CH4 exchange depends on ecosystem hydrology, soil and vegetation characteristics. Here, the LPJ-WHyMe global dynamical vegetation model is used to simulate global net CH4 emissions for different ecosystems: northern peatlands (45°–90° N), naturally inundated wetlands (60° S–45° N), rice agriculture and wet mineral soils. Mineral soils are a potential CH4 sink, but can also be a source with the direction of the net exchange depending on soil moisture content. The geographical and seasonal distributions are evaluated against multi-dimensional atmospheric inversions for 2003–2005, using two independent four-dimensional variational assimilation systems. The atmospheric inversions are constrained by the atmospheric CH4 observations of the SCIAMACHY satellite instrument and global surface networks. Compared to LPJ-WHyMe the inversions result in a significant reduction in the emissions from northern peatlands and suggest that LPJ-WHyMe maximum annual emissions peak about one month late. The inversions do not put strong constraints on the division of sources between inundated wetlands and wet mineral soils in the tropics. Based on the inversion results we adapt model parameters in LPJ-WHyMe and simulate the surface exchange of CH4 over the period 1990–2008. Over the whole period we infer an increase of global ecosystem CH4 emissions of +1.11 Tg CH4 yr−1, not considering potential additional changes in wetland extent. The increase in simulated CH4 emissions is attributed to enhanced soil respiration resulting from the observed rise in land temperature and in atmospheric carbon dioxide that were used as input. The long-term decline of the atmospheric CH4 growth rate from 1990 to 2006 cannot be fully explained with the simulated ecosystem emissions. However, these emissions show an increasing trend of +3.62 Tg CH4 yr−1 over 2005–2008 which can partly explain the renewed increase in atmospheric CH4 concentration during recent years.

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Spahni, R., R. Wania, L. Neef, M. van Weele, I. Pison, P. Bousquet, C. Frankenberg, et al. "Constraining global methane emissions and uptake by ecosystems." Biogeosciences 8, no. 6 (June 23, 2011): 1643–65. http://dx.doi.org/10.5194/bg-8-1643-2011.

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Abstract. Natural methane (CH4) emissions from wet ecosystems are an important part of today's global CH4 budget. Climate affects the exchange of CH4 between ecosystems and the atmosphere by influencing CH4 production, oxidation, and transport in the soil. The net CH4 exchange depends on ecosystem hydrology, soil and vegetation characteristics. Here, the LPJ-WHyMe global dynamical vegetation model is used to simulate global net CH4 emissions for different ecosystems: northern peatlands (45°–90° N), naturally inundated wetlands (60° S–45° N), rice agriculture and wet mineral soils. Mineral soils are a potential CH4 sink, but can also be a source with the direction of the net exchange depending on soil moisture content. The geographical and seasonal distributions are evaluated against multi-dimensional atmospheric inversions for 2003–2005, using two independent four-dimensional variational assimilation systems. The atmospheric inversions are constrained by the atmospheric CH4 observations of the SCIAMACHY satellite instrument and global surface networks. Compared to LPJ-WHyMe the inversions result in a~significant reduction in the emissions from northern peatlands and suggest that LPJ-WHyMe maximum annual emissions peak about one month late. The inversions do not put strong constraints on the division of sources between inundated wetlands and wet mineral soils in the tropics. Based on the inversion results we diagnose model parameters in LPJ-WHyMe and simulate the surface exchange of CH4 over the period 1990–2008. Over the whole period we infer an increase of global ecosystem CH4 emissions of +1.11 Tg CH4 yr−1, not considering potential additional changes in wetland extent. The increase in simulated CH4 emissions is attributed to enhanced soil respiration resulting from the observed rise in land temperature and in atmospheric carbon dioxide that were used as input. The long-term decline of the atmospheric CH4 growth rate from 1990 to 2006 cannot be fully explained with the simulated ecosystem emissions. However, these emissions show an increasing trend of +3.62 Tg CH4 yr−1 over 2005–2008 which can partly explain the renewed increase in atmospheric CH4 concentration during recent years.

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40

Standhartinger, Angela. "Luzia Sutter Rehmann, Konflikte zwischen ihm und ihr. Sozialgeschichtliche und exegetische Untersuchungen zur Nachfolgeproblematik von Ehepaaren, Gütersloh (Chr. Kaiser/Gütersloher Verlagshaus) 2002, 248 S., kart. EUR 24,95; ISBN 3-579-05380-9." Biblische Zeitschrift 48, no. 1 (April 5, 2004): 138–40. http://dx.doi.org/10.1163/25890468-04801015.

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41

Chevalier, A., F. Gheusi, J. L. Attié, R. Delmas, R. Zbinden, G. Athier, and J. M. Cousin. "Carbon monoxide observations from ground stations in France and Europe and long trends in the free troposphere." Atmospheric Chemistry and Physics Discussions 8, no. 1 (February 15, 2008): 3313–56. http://dx.doi.org/10.5194/acpd-8-3313-2008.

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Abstract. Continuous CO measurements performed at 3 high-altitude stations in France are analyzed for the first time. Data are provided by the new PAES (Pollution Atmospherique à l'Echelle Synoptique) network since 2002 for the Puy de Dôme and 2004 for the Pic du Midi and the Donon. CO measurements of 5 another European stations have been analysed to put the PAES stations in an European perspective. The January 2002–April 2005 CO mean levels of surface stations capture the stratification revealed by climatological CO profiles from the airborne observation system MOZAIC (Measurement of OZone and water vapour by Airbus In-service Aircraft). The deviation between the free tropospheric reference MOZAIC and surface data above 2000 m is less than 10% and this deviation can be explained in term of spatial variability, as evidenced by MOPITT CO retrievals at 700 hPa. This suggests that, averaged at a seasonal time scale (4 months), surface data at stations above 2000 m are representative of background CO concentration. This paper focuses then on trends since the 1980s–1990s. The comparison between old (1982–1983) and recent CO mixing ratio (2005) at the Pic du Midi leads to a 10% decrease, consistent with the continuous data series at Zugspitze (ZSP) from 1991 to 2004. This decrease was found to be mainly due to a negative trend of January–April mean levels. The decrease in CO sources over France and Europe appears to be responsible for that trend. The stable values of June–September mean levels suggest that the summertime oxidizing capacity of the atmosphere related to OH radicals is important enough to counterbalance any CO inputs into the troposphere. Our study shows a recent change in CO evolution since 2000 over Western Europe, with a slowed down decrease in CO concentration. Studying specifically the interactions between CO, CH4 and OH turns out to be needed, however, to find definitive explanations to those observations.

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Haug, Jeffrey S., Xi C. He, Justin C. Grindley, Joshua P. Wunderlich, Karin Gaudenz, Jason T. Ross, Ariel Paulson, et al. "N-cadherin Expression Level Distinguishes Reserved Versus Primed States of Hematopoietic Stem Cells." Blood 110, no. 11 (November 16, 2007): 1268. http://dx.doi.org/10.1182/blood.v110.11.1268.1268.

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Abstract Within the bone marrow, three hematopoietic stem cell niches have been identified; the osteoblastic niche (Arai et al., 2004; Calvi et al., 2003; Nilsson et al., 2001; Zhang et al., 2003), the vascular niche (Kiel et al., 2005), and the CAR cell niche (Sugiyama et al., 2006). The adhesion molecule N-cadherin has been found associated with the osteoblastic and CAR cell niches, implicating N-cadherin’s function for hematopoietic stem cell (HSC) anchoring and signaling (Arai et al., 2004; Muguruma et al., 2006; Zhang et al., 2003). However, as of yet, a HSC population expressing N-cadherin has not been fully characterized. Therefore, we examined how N-cadherin expression in HSCs relates to their function and lifecycle. Unexpectedly, we found that doses of 5000 bone marrow cells expressing the highest level of N-cadherin (N-cadherinhi) failed to reconstitute hematopoietic lineages in irradiated recipient mice. An explanation for this engraftment failure came with detailed cell surface phenotyping which revealed that these N-cadherinhi cells were primarily Lineage+ and devoid of the characteristic hematopoietic stem pool, Lineage-Sca+cKit+ (LSK) cells. Instead, we found that Flk2-LSK HSCs express a gradient of N-cadherin which could be described as low (N-cadherinlo) to intermediate (N-cadherinint) levels (Figure1). FACS applications were used to isolate pure populations of these N-cadherinlo and N-cadherinint Flk2-LSK HSCs. Real time RT-PCR (N-cadherin primers crossed the intron between Exon 2 and 3). (Figure 2), microarray studies, and competitive reconstitution transplantation assays revealed that this N-cadherin division of Flk2- LSK HSCs formed two populations with very distinct properties. In transplantation assays the N-cadherinlo population more robustly reconstituted the hematopoietic system. Principle Component Analysis and gene ontology analysis of microarray data revealed that the N-cadherinlo cells expressed genes that may prime them to respond to signals and to mobilize. This data was confirmed with mobilization studies which showed that HSCs mobilized from bone marrow to spleen were predominantly N-cadherinlo. In contrast, the expression profile of N-cadherinint cells suggests they are more ‘reserved’ and this population was also maintained with HSCs spared by 5-fluouracil (5FU) treatment. Our results suggest that differential N-cadherin expression reflects important functional distinctions between HSC subpopulations. N-cadherinlo HSCs, with their robust reconstitution efficiency and properties similar to mobilized HSCs, may have clinical relevance. Figure Figure Figure Figure

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43

Yow, Cheun Hoe. "China-ASEAN Relations, October 2002 to June 2003: Chronology of Events." China: An International Journal 1, no. 2 (2003): 354–62. http://dx.doi.org/10.1353/chn.2005.0040.

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44

Lewis, Delyth, Glynis Tranter, and Alan T. Axford. "Use of videoconferencing in Wales to reduce carbon dioxide emissions, travel costs and time." Journal of Telemedicine and Telecare 15, no. 3 (April 2009): 137–38. http://dx.doi.org/10.1258/jtt.2009.003010.

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In September 2005 a telemedicine service was started to assist multidisciplinary teams in Wales to improve cancer services. In October 2006 and October 2007 users of videoconferencing equipment at one site completed questionnaires. During October 2006 a total of 18,000 km of car travel were avoided, equivalent to 1696 kg of CO2 emission. During October 2007 a total of 20,800 km of car travel were avoided, equivalent to 2590 kg of CO2 emission. We estimate that 48 trees would take a year to absorb that quantity of CO2. The results of the surveys show that exploiting telemedicine makes better use of staff time, reduces the time spent travelling and assists in reducing climate change by limiting the emissions of CO2.

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45

Tohjima, Y., M. Kubo, C. Minejima, H. Mukai, H. Tanimoto, A. Ganshin, S. Maksyutov, K. Katsumata, T. Machida, and K. Kita. "Temporal changes in the emissions of CH4 and CO from China estimated from CH4 / CO2 and CO / CO2 correlations observed at Hateruma Island." Atmospheric Chemistry and Physics 14, no. 3 (February 13, 2014): 1663–77. http://dx.doi.org/10.5194/acp-14-1663-2014.

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Abstract. In situ observation of the atmospheric CO2, CH4, and CO mixing ratios at Hateruma Island (HAT, 24.05° N, 123.80° E) often show synoptic-scale variations with correlative elevations during winter, associated with air transport from the East Asian countries. We examine winter (November– March) trends in ΔCH4 / ΔCO2, ΔCO / ΔCO2, and ΔCO / ΔCH4 observed at Hateruma over the period 1999 to 2010. To investigate the relationship between the East Asian emissions and the short-term variations in the atmospheric mixing ratios, we use the FLEXPART Lagrangian particle dispersion model (LPDM). The observed ratios ΔCH4 / ΔCO2 and ΔCO / ΔCO2 both show an overall gradual decrease over the study period due to a recent rapid increase in fossil fuel consumption in China. We note, however, that the decreasing rates of ΔCH4 / ΔCO2 and ΔCO / ΔCO2 show gradual decrease and increase, respectively, during the entire observation periods used in this study. The ΔCO / ΔCH4 slope, on the other hand, shows an increasing trend during 1999–2004 but a decrease during 2005–2010. Calculation of the concentration footprint for the atmospheric observation at HAT by using the FLEXPART LPDM indicates that most of the short-term variations are caused by emission variations from northern and eastern China. Combined with a set of reported emission maps, we have estimated the temporal changes in the annual CH4 and CO emissions from China under the assumption that the estimate of the fossil-fuel-derived CO2 emissions based on the energy statistics are accurate. The estimated annual CH4 emissions, corresponding to nonseasonal sources or anthropogenic sources without rice fields, show a nearly constant value of 39 ± 7 TgCH4 yr−1 during 1998–2002, and then gradually increase to 46 ± 8 TgCH4 yr−1 in 2009/2010. The estimated annual CO emissions increase from 134 ± 32 TgCO yr−1 in 1998/1999 to 182 ± 42 TgCO yr−1 in 2004/2005, level off after 2005, and then slightly decrease to less than 160 TgCO yr−1 in 2008–2010.

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46

van der Werf, G. R., J. T. Randerson, L. Giglio, G. J. Collatz, M. Mu, P. S. Kasibhatla, D. C. Morton, R. S. DeFries, Y. Jin, and T. T. van Leeuwen. "Global fire emissions and the contribution of deforestation, savanna, forest, agricultural, and peat fires (1997–2009)." Atmospheric Chemistry and Physics Discussions 10, no. 6 (June 30, 2010): 16153–230. http://dx.doi.org/10.5194/acpd-10-16153-2010.

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Abstract. New burned area datasets and top-down constraints from atmospheric concentration measurements of pyrogenic gases have decreased the large uncertainty in fire emissions estimates. However, significant gaps remain in our understanding of the contribution of deforestation, savanna, forest, agricultural waste, and peat fires to total global fire emissions. Here we used a revised version of the Carnegie-Ames-Stanford-Approach (CASA) biogeochemical model and improved satellite-derived estimates of area burned, fire activity, and plant productivity to calculate fire emissions for the 1997–2009 period on a 0.5° spatial resolution with a monthly time step. For November 2000 onwards, estimates were based on burned area, active fire detections, and plant productivity from the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor. For the partitioning we focused on the MODIS era. We used burned area estimates based on Tropical Rainfall Measuring Mission (TRMM) Visible and Infrared Scanner (VIRS) and Along-Track Scanning Radiometer (ATSR) active fire data prior to MODIS (1997–2000) and Advanced Very High Resolution Radiometer (AVHRR) derived estimates of plant productivity during the same period. Average global fire carbon emissions were 2.0 Pg yr−1 with significant interannual variability during 1997–2001 (2.8 Pg yr−1 in 1998 and 1.6 Pg yr−1 in 2001). Emissions during 2002–2007 were relatively constant (around 2.1 Pg yr−1) before declining in 2008 (1.7 Pg yr−1) and 2009 (1.5 Pg yr−1) partly due to lower deforestation fire emissions in South America and tropical Asia. During 2002–2007, emissions were highly variable from year-to-year in many regions, including in boreal Asia, South America, and Indonesia, but these regional differences cancelled out at a global level. During the MODIS era (2001–2009), most fire carbon emissions were from fires in grasslands and savannas (44%) with smaller contributions from tropical deforestation and degradation fires (20%), woodland fires (mostly confined to the tropics, 16%), forest fires (mostly in the extratropics, 15%), agricultural waste burning (3%), and tropical peat fires (3%). The contribution from agricultural waste fires was likely a lower bound because our approach for measuring burned area could not detect all of these relatively small fires. For reduced trace gases such as CO and CH4, deforestation, degradation, and peat fires were more important contributors because of higher emissions of reduced trace gases per unit carbon combusted compared to savanna fires. Carbon emissions from tropical deforestation, degradation, and peatland fires were on average 0.5 Pg C yr−1. The carbon emissions from these fires may not be balanced by regrowth following fire. Our results provide the first global assessment of the contribution of different sources to total global fire emissions for the past decade, and supply the community with an improved 13-year fire emissions time series.

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Sassim, Paulo Vitor de Souza, Tereza Cristina dos Reis Ferreira, Júlio César Veiga Pena, Paula Thayna Soares Lima, Carlos Augusto da Silva Costa Neto, Danilo Gouveia Gabriel, Anne Beatriz Duarte Conceição, Lee Bezerra Falcão, and Késsya Alves da Costa. "PERFIL DOS PACIENTES INTERNADOS POR ACIDENTES AUTOMOBILÍSTICOS NO HOSPITAL METROPOLITANO DE URGÊNCIA E EMERGÊNCIA DE ANANINDEUA NO PERÍODO DE 2006 À 2012." Centro de Pesquisas Avançadas em Qualidade de Vida, v12n3 (July 13, 2020): 1–12. http://dx.doi.org/10.36692/v12n3-4.

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Methods: A retrospective observational descriptive obtained through secondary data, carried out at the statistics of the Metropolitan Hospital Emergency and Emergency. We recorded 10,476 admissions due to traffic accidents from March 2006 to September 2012. Objective: To evaluate the profile of patients hospitalized for traffic accidents at the Metropolitan Hospital for Urgency and Emergency in Belém from 2006 to 2012. Results: Of 10,476 patients, 7179 were men, 1839 are women, mean age 30 years, coming from interior of the state 8034 cases, and motorcycle accidents over the incidents with 3514 of admissions, followed roadkill with 2395 cases, car accidents with 2050 and bicycle accidents with 173 cases. The CID was prevalent S06 with 2238 cases. The incident was over Belém municipality with 2102 cases and the months were more incidents in August in 2007 (10.02%) and 2009 (9.68%), September in the years 2010 (10.28%) and 2012 (14.03%) and October 2006 (13.44%) and 2008 (10.20%). Conclusion: We observed that victims of car accidents in HMUE hospitalized between 2006 to 2012 are men aged 30 years from the interior, and the motorcycle accidents the leading cause of hospitalization highlighting the CID S06 as most incident. The municipality with the highest accident record was Belém and months were more incidents in August in 2007 and 2009, the years 2010 and September 2012 and October 2006 and 2008.

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M.K.D. "Acknowledgment: The Journal Thanks Our 2006-2007* Reviewers." Journal of the American Academy of Child & Adolescent Psychiatry 46, no. 12 (December 2007): 1686–88. http://dx.doi.org/10.1097/chi.0b013e31815b6660.

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49

Latagliata, Roberto, Massimo Breccia, Dario Ferrero, Francesco Cavazzini, Malgorzata Monika Trawinska, Fausto Castagnetti, Mario Annunziata, et al. "Long-Term Follow-up in Very Elderly Patients with Chronic Myeloid Leukemia Treated with Imatinib Frontline." Blood 126, no. 23 (December 3, 2015): 1598. http://dx.doi.org/10.1182/blood.v126.23.1598.1598.

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Abstract In the current clinical practice, imatinib is widely used also in very elderly patients with chronic myeloid leukemia (CML) at different doses based on concomitant diseases and physician' judgment. However, data on long-term follow-up of these patients are still lacking. To address this issue, we revised in our retrospective database 233 CML patients aged ≥ 75 years and treated with imatinib frontline in 34 italian hematological centers from 2/2002 to 7/2014. Median age at diagnosis was 78.4 years [interquartile range (IQR) 76.3 - 81.3], there were 113 males (48.5%) and 120 females (51.5%), median WBC, Hb and PLT counts were 45.0 x 109/l (IQR 29.4 - 83.4), 12,4 g/dl (IQR 11.0 - 13.6) and 375 x 109/l (IQR 238 - 680), respectively. Sokal Risk at diagnosis was low in 1 patient (0.4%), intermediate in 149 (67.4%), high in 71 (32.2%) and not evaluable in 12. One or more concomitant diseases requiring specific treatments were present in 225/233 patients (96.5%). Median interval from diagnosis to imatinib start was 0.7 month (IQR 0.2 - 1.4): the initial imatinib dose was 400 mg/day in 161 patients (69.1%), 300 mg/day in 57 (24.5%) and < 300 mg/day in 15 (6.4%). According to WHO, a grade 3 - 4 hematological and extra-hematological toxicity was reported in 44 (18.8%) and 41 (17.6%) patients, respectively. As to cumulative response, 13 patients (5.6%) discontinued IM due to early toxicity, 4 (1.7%) were resistant and 2 (0.8%) died from unrelated cause early after IM initiation: the remaining 214 patients (91.9%) achieved a complete haematological response (CHR). Among these 214 patients in CHR, 13 refused any other karyotipic or molecular evaluation, 23 achieved CHR only and 178 (76.4% of all 233 patients) achieved a cytogenetic response (CyR), which was partial in 16 patients and complete (CCyR) in 162 (69.5% of all 233 patients). In addition, among the 162 patients in CCyR, 125 (53.6% of all 233 patients) achieved a molecular response (MolR) (ratio < 0.1). A blastic phase occurred in 11 patients (4.7%). After a median follow-up from imatinib start of 45.0 months (IQR 22.3 - 72.0), 70 patients have died (9 from disease progression and 61 from unrelated causes), 16 patients were lost to follow-up and 147 are still alive (115 of them still in treatment with imatinib): 5-year event-free survival (EFS) and overall survival (OS) were 51.4% (CI95% 43.9 - 58.9) and 68.5% (CI95% 61.2 - 75.8), respectively. At univariate analysis, only the initial dose of imatinib (400 vs ≤ 300, p=0.03) was a significant predictive factor for CCyR achievement while only PLT count ≤ 500 x 109/l (p=0.031) was a significant predictive factor for MolR achievement. At multivariate analysis for EFS, achievement of a MolR (OR 0.25, 95%CI 0.14 - 0.43, p<0.001), achievement of a CCyR (OR 0.40, 95%CI 0.23 - 0.67, p=0.001) and spleen enlargement (OR 1.56, 95%CI 1.01 - 2.41, p=0.042) were independent prognostic factors; at multivariate analysis for OS, achievement of a MolR (OR 0.30, 95%CI 0.18 - 0.49, p<0.001), age < 80 yrs (OR 0.53, 95%CI 0.33 - 0.86, p=0.011) and male gender (OR 1.80, 95%CI 1.11 - 2.91, p=0.016) were independent prognostic factors. In conclusion, the long term follow-up of very elderly CML patients who started imatinib is very good and justify any effort to treat these patients with standard doses, in order to achieve cytogenetic and molecular responses as in younger subjects. Disclosures Castagnetti: BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; ARIAD: Consultancy, Honoraria. Tiribelli:Ariad Pharmaceuticals: Consultancy, Speakers Bureau; Novartis Farma: Consultancy, Speakers Bureau; Bristol Myers Squibb: Consultancy, Speakers Bureau. Gugliotta:BMS: Honoraria; Novartis: Honoraria. Abruzzese:BMS, Novartis, Pfizer, Ariad: Consultancy.

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50

Gorucu, Fatma Burcu, Sinisha A. Jikich, Grant S. Bromhal, W. Neal Sams, Turgay Ertekin, and Duane H. Smith. "Effects of Matrix Shrinkage and Swelling on the Economics of Enhanced-Coalbed-Methane Production and CO2 Sequestration in Coal." SPE Reservoir Evaluation & Engineering 10, no. 04 (August 1, 2007): 382–92. http://dx.doi.org/10.2118/97963-pa.

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Summary Increases in carbon dioxide (CO2) levels in the atmosphere and their contributions to global climate change are a major concern. CO2 sequestration in unmineable coals may be a very attractive option, for economic as well as environmental reasons, if a combination of enhanced-coalbed-methane (ECBM) production and tax incentives becomes sufficiently favorable compared to the costs of capture, transport, and injection of CO2. Darcy flow through cleats is an important transport mechanism in coal. Cleat compression and permeability changes caused by gas sorption/desorption, changes of effective stress, and matrix swelling and shrinkage introduce a high level of complexity into the feasibility of a coal sequestration project. The economic effects of CO2-induced swelling on permeabilities and injectivities has received little (if any) detailed attention. CO2 and methane (CH4) have different swelling effects on coal. In this work, the Palmer-Mansoori model for coal shrinkage and permeability increases during primary methane production was rewritten to also account for coal swelling caused by CO2 sorption. The generalized model was added to a compositional, dual-porosity coalbed-methane reservoir simulator for primary (CBM) and ECBM production. A standard five-spot of vertical wells and representative coal properties for Appalachian coals was used (Rogers 1994). Simulations and sensitivity analyses were performed with the modified simulator for nine different parameters, including coal seam and operational parameters and economic criteria. The coal properties and operating parameters that were varied included Young's modulus, Poisson's ratio, cleat porosity, and injection pressure. The economic variables included CH4 price, CO2 cost, CO2 credit, water disposal cost, and interest rate. Net-present-value (NPV) analyses of the simulation results included profits resulting from CH4 production and potential incentives for sequestered CO2. This work shows that for some coal seams, the combination of compressibility, cleat porosity, and shrinkage/swelling of the coal may have a significant impact on project economics. Introduction In recent years, primary production of natural gas from coal seams has become an important source of energy in the United States. Proven CBM reserves have been estimated at 18.5 Tscf, representing 10% of the total natural-gas reserves in the United States. CBM production started in the early 1980s as a small, high-cost operation but reached 1.6 Tscf in 2002. This was more than 8% of the total US natural-gas production that year (Kuuskraa 2003). The production of CBM reservoirs begins with the pumping of significant volumes of water to lower reservoir pressure and to allow CH4desorption and flow (Stevens et al. 1998). The fraction of the original gas in place typically produced by primary depletion seems to be somewhat controversial. However, according to recent publications, recoveries are often between 20 and 60% of the original gas in place, so that considerable amounts of gas are left behind (Gale and Freund 2001; Stevens et al. 1999; Van Bergen et al. 2001).Because of this, and because of concerns about global warming caused by accumulations of CO2 in the atmosphere (National Energy Technology Laboratory 2003, 2004), new technologies for ECBM production based on the injection of carbon are being investigated in the US, Europe, China, and Japan (Coal-Seq Forum 2004, 2006). In the CO2-ECBM/sequestration process, injected CO2 flows through the cleats in the coal by Darcy flow, diffuses into the coal matrix, and is sorbed by it; CH4 diffuses from the matrix into the cleats, through which it flows to production wells (Sams et al. 2005). The injection of CO2 into coalbeds has many potential advantages: It sequesters CO2, it reduces the production time for CBM, and it increases reserves by improving the recovery of CBM. However, the improved CH4 recovery is accompanied by an increase in costs for CO2 supply, additional drilling, and well and surface equipment. Thus, CO2-ECBM and sequestration are accompanied not only by promised benefits but also by new technical challenges and financial risks.

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Journal articles on the topic 'CHR 2002'

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