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KiDS+2dFLenS+GAMA: testing the cosmological model with the EG statistic
Amon, A,Blake, C,Heymans, C,Leonard, C D,Asgari, M,Bilicki, M,Choi, A,Erben, T,Glazebrook, K,Harnois-Dé,raps, J,Hildebrandt, H,Hoekstra, H,Joachimi, B,Joudaki, S,Kuijken, K,Lidman, C,Loveday, J Oxford University Press 2018 MONTHLY NOTICES- ROYAL ASTRONOMICAL SOCIETY Vol.479 No.3
Mü,ller, Martin C.,Cortes, Jorge E.,Kim, Dong-Wook,Druker, Brian J.,Erben, Philipp,Pasquini, Ricardo,Branford, Susan,Hughes, Timothy P.,Radich, Jerald P.,Ploughman, Lynn,Mukhopadhyay, Jaydip,Hochh American Society of Hematology 2009 Blood Vol.114 No.24
<B>Abstract</B><P>Dasatinib is a BCR-ABL inhibitor with 325-fold higher potency than imatinib against unmutated BCR-ABL in vitro. Imatinib failure is commonly caused by BCR-ABL mutations. Here, dasatinib efficacy was analyzed in patients recruited to phase 2/3 trials with chronic-phase chronic myeloid leukemia with or without BCR-ABL mutations after prior imatinib. Among 1043 patients, 39% had a preexisting BCR-ABL mutation, including 48% of 805 patients with imatinib resistance or suboptimal response. Sixty-threedifferent BCR-ABL mutations affecting 49 amino acids were detected at baseline, with G250, M351, M244, and F359 most frequently affected. After 2 years of follow-up, dasatinib treatment of imatinib-resistant patients with or without a mutation resulted in notable response rates (complete cytogenetic response: 43% vs 47%) and durable progression-free survival (70% vs 80%). High response rates were achieved with different mutations except T315I, including highly imatinib-resistant mutations in the P-loop region. Impaired responses were observed with some mutations with a dasatinib median inhibitory concentration (IC50) greater than 3nM; among patients with mutations with lower or unknown IC50, efficacy was comparable with those with no mutation. Overall, dasatinib has durable efficacy in patients with or without BCR-ABL mutations. All trials were registered at http://www.clinicaltrials.gov as NCT00123474, NCT00101660, and NCT00103844.</P>
Cortes, Jorge,Rousselot, Philippe,Kim, Dong-Wook,Ritchie, Ellen,Hamerschlak, Nelson,Coutre, Steven,Hochhaus, Andreas,Guilhot, Francois,Saglio, Giuseppe,Apperley, Jane,Ottmann, Oliver,Shah, Neil,Erben, American Society of Hematology 2007 Blood Vol.109 No.8
<B>Abstract</B><P>The prognosis for patients with chronic myeloid leukemia (CML) in myeloid blast crisis (MBC) or lymphoid blast crisis (LBC) remains poor. Although imatinib can induce responses in a subset of these patients, resistance to the drug develops rapidly. Dasatinib is a novel, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases. After promising phase 1 results, we report the results of phase 2 clinical trials of dasatinib in patients with imatinib-resistant or -intolerant blast crisis CML (MBC, n = 74; LBC, n = 42). At the 8-month follow-up, dasatinib induced major hematologic responses (MaHRs) in 34% and 31% of MBC- and LBC-CML patients and major cytogenetic responses (MCyRs) in 31% and 50% of these patients, respectively. Most (86%) of these MCyRs were complete cytogenetic responses (CCyRs). Responses were rapid and durable: 88% and 46%, respectively, of MBC- and LBC-CML patients achieving MaHR had not experienced disease progression at the 8-month follow-up. Response rates were similar in patients with and without BCR-ABL mutations known to confer resistance to imatinib. Dasatinib was well tolerated. Nonhematologic adverse events were mild to moderate. Cytopenias were common and could be managed by dose modification. Dasatinib is highly active and produces hematologic and cytogenetic responses in a significant number of patients with imatinib-resistant or -intolerant MBC- and LBC-CML. These trials were registered at www.clinicaltrials.gov as #CA180006 and #CA180015.</P>
Hughes, Timothy,Saglio, Giuseppe,Branford, Susan,Soverini, Simona,Kim, Dong-Wook,Mü,ller, Martin C,Martinelli, Giovanni,Cortes, Jorge,Beppu, Lan,Gottardi, Enrico,Kim, Dongho,Erben, Philipp,Shou, Y Grune Stratton ; American Society of Clinical Onco 2009 Journal of clinical oncology Vol.27 No.25
<P>PURPOSE: Nilotinib is a second-generation tyrosine kinase inhibitor indicated for the treatment of patients with chronic myeloid leukemia (CML) in chronic phase (CP; CML-CP) and accelerated phase (AP; CML-AP) who are resistant to or intolerant of prior imatinib therapy. In this subanalysis of a phase II study of nilotinib in patients with imatinib-resistant or imatinib-intolerant CML-CP, the occurrence and impact of baseline and newly detectable BCR-ABL mutations were assessed. PATIENTS AND METHODS: Baseline mutation data were assessed in 281 (88%) of 321 patients with CML-CP in the phase II nilotinib registration trial. RESULTS: Among imatinib-resistant patients, the frequency of mutations at baseline was 55%. After 12 months of therapy, major cytogenetic response (MCyR) was achieved in 60%, complete cytogenetic response (CCyR) in 40%, and major molecular response (MMR) in 29% of patients without baseline mutations versus 49% (P = .145), 32% (P = .285), and 22% (P = .366), respectively, of patients with mutations. Responses in patients who harbored mutations with high in vitro sensitivity to nilotinib (50% inhibitory concentration [IC(50)] <or= 150 nM) or mutations with unknown nilotinib sensitivity were equivalent to those responses for patients without mutations (not significant). Patients with mutations that were less sensitive to nilotinib in vitro (IC(50) > 150 nM; Y253H, E255V/K, F359V/C) had less favorable responses, as 13%, 43%, and 9% of patients with each of these mutations, respectively, achieved MCyR; none achieved CCyR. CONCLUSION: For most patients with imatinib resistance and with mutations, nilotinib offers a substantial probability of response. However, mutational status at baseline may influence response. Less sensitive mutations that occurred at three residues defined in this study, as well as the T315I mutation, may be associated with less favorable responses to nilotinib.</P>
Bilicki, M.,Hoekstra, H.,Brown, M. J. I.,Amaro, V.,Blake, C.,Cavuoti, S.,de Jong, J. T. A.,Georgiou, C.,Hildebrandt, H.,Wolf, C.,Amon, A.,Brescia, M.,Brough, S.,Costa-Duarte, M. V.,Erben, T.,Glazebroo EDP Sciences 2018 Astronomy and astrophysics Vol.616 No.-
<P>We present a machine-learning photometric redshift (ML photo-<I>z</I>) analysis of the Kilo-Degree Survey Data Release 3 (KiDS DR3), using two neural-network based techniques: ANNz2 and MLPQNA. Despite limited coverage of spectroscopic training sets, these ML codes provide photo-<I>z</I>s of quality comparable to, if not better than, those from the Bayesian Photometric Redshift (BPZ) code, at least up to <I>z</I>phot ≲ 0.9 and <I>r</I> ≲ 23.5. At the bright end of <I>r</I> ≲ 20, where very complete spectroscopic data overlapping with KiDS are available, the performance of the ML photo-<I>z</I>s clearly surpasses that of BPZ, currently the primary photo-<I>z</I> method for KiDS. Using the Galaxy And Mass Assembly (GAMA) spectroscopic survey as calibration, we furthermore study how photo-<I>z</I>s improve for bright sources when photometric parameters additional to magnitudes are included in the photo-<I>z</I> derivation, as well as when VIKING and WISE infrared (IR) bands are added. While the fiducial four-band <I>ugri</I> setup gives a photo-<I>z</I> bias 〈<I>δz</I>/(1 + <I>z</I>)〉 = −2 × 10<SUP>−4</SUP> and scatter <I>σδz/(1+z)</I> < 0.022 at mean 〈<I>z</I>〉 = 0.23, combining magnitudes, colours, and galaxy sizes reduces the scatter by ~7% and the bias by an order of magnitude. Once the <I>ugri</I> and IR magnitudes are joined into 12-band photometry spanning up to 12 <I>μ</I>m, the scatter decreases by more than 10% over the fiducial case. Finally, using the 12 bands together with optical colours and linear sizes gives 〈<I>δz</I>/(1 + <I>z</I>)〉 < 4 × 10<SUP>−5</SUP> and <I>σ</I><I>δz</I>/(1+<I>z</I>) < 0.019. This paper also serves as a reference for two public photo-<I>z</I> catalogues accompanying KiDS DR3, both obtained using the ANNz2 code. The first one, of general purpose, includes all the 39 million KiDS sources with four-band <I>ugri</I> measurements in DR3. The second dataset, optimised for low-redshift studies such as galaxy-galaxy lensing, is limited to <I>r</I> ≲ 20, and provides photo-<I>z</I>s of much better quality than in the full-depth case thanks to incorporating optical magnitudes, colours, and sizes in the GAMA-calibrated photo-<I>z</I> derivation.</P>