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3. The soft path to water: A conservation-based approach to improved water access and sanitation for rural communities

Author

Josiah H. Heyman, Chilton L. Tippin, Nayeli Holguin, and William L. Hargrove

Subjects
Sanitation, business.industry, 0208 environmental biotechnology, 0211 other engineering and technologies, Soil Science, Water supply, Developing country, Distribution (economics), 021107 urban & regional planning, Context (language use), 02 engineering and technology, 020801 environmental engineering, Water demand, Geography, Water treatment, Rural area, business, Agronomy and Crop Science, Environmental planning, Nature and Landscape Conservation, Water Science and Technology
Abstract

The traditional approach to providing water in an urban or suburban context is a hard-engineered centralized system of water treatment and distribution from the point of treatment. For sanitation, the conventional system includes collection and delivery of waste to a centralized treatment system before discharge to a water body. Hard-engineered systems place most of their emphasis on managing/increasing water supply with much less attention to managing water demand. There are many small rural communities, particularly in the southwestern United States, but also in other regions of the United States, that are remote, isolated, and with relatively small populations who lack access to adequate water and sanitation. For these communities, hard-engineered systems are neither a reality today nor are likely to be in the near term. Many of these communities resemble rural areas in developing countries and share several of the following characteristics (Cardenas et al. 2010; Del Rio et al. 2017; Ford and Dzewaltowski 2008; Hargrove et al. 2015, 2018; Jepson 2014; Korc and Ford 2013; Lusk et al. 2012; Sullivan and Ward 2012; Van Derslice 2011; and Wutich et al. 2014)

Published
2020

5. An international study of intrachromosomal amplification of chromosome 21 (iAMP21): cytogenetic characterization and outcome

Author

Harrison, C J, Moorman, A V, Schwab, C, Carroll, A J, Raetz, E A, Devidas, M, Strehl, S, Nebral, K, Harbott, J, Teigler-Schlegel, A, Zimmerman, M, Dastuge, N, Baruchel, A, Soulier, J, Auclerc, M-F, Attarbaschi, A, Mann, G, Stark, B, Cazzaniga, G, Chilton, L, Vandenberghe, P, Forestier, E, Haltrich, I, Raimondi, S C, Parihar, M, Bourquin, J-P, Tchinda, J, Haferlach, C, Vora, A, Hunger, S P, Heerema, N A, and Haas, O A

Published
2014
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12. [K.sup.+] currents regulate the resting membrane potential, proliferation, and contractile responses in ventricular fibroblasts and myofibroblasts

Author

Chilton, L., Ohya, S., Freed, D., George, E., Drobic, V., Shibukawa, Y., MacCannell, K.A., Imaizumi, Y., Clark, R.B., Dixon, I.M.C., and Giles, W.R.

Subjects
Heart -- Research, Heart -- Physiological aspects, Fibroblasts -- Research, Fibroblasts -- Physiological aspects, Biological sciences
Abstract

Despite the important roles played by ventricular fibroblasts and myofibroblasts in the formation and maintenance of the extracellular matrix, neither the ionic basis for membrane potential nor the effect of modulating membrane potential on function has been analyzed in detail. In this study, whole cell patch-clamp experiments were done using ventricular fibroblasts and myofibroblasts. Time- and voltage-dependent outward [K.sup.+] currents were recorded at depolarized potentials, and an inwardly rectifying [K.sup.+] (Kir) current was recorded near the resting membrane potential (RMP) and at more hyperpolarized potentials. The apparent reversal potential of Kir currents shifted to more positive potentials as the external [K.sup.+] concentration ([[K.sup.+]]o) was raised, and this Kir current was blocked by 100-300 [micro]M B[a.sup.2+]. RT-PCR measurements showed that mRNA for Kir2.1 was expressed. Accordingly, we conclude that Kir current is a primary determinant of RMP in both fibroblasts and myofibroblasts. Changes in [[K.sup.+]]o influenced fibroblast membrane potential as well as proliferation and contractile functions. Recordings made with a voltage-sensitive dye, DiBA[C.sub.3](4), showed that 1.5 mM [[K.sup.+]]o resulted in a hyperpolarization, whereas 20 mM [[K.sup.+]]o produced a depolarization. Low [[K.sup.+]]o (1.5 mM) enhanced myofibroblast number relative to control (5.4 mM [[K.sup.+]]o). In contrast, 20 mM [[K.sup.+]]o resulted in a significant reduction in myofibroblast number. In separate assays, 20 mM [[K.sup.+]]o significantly enhanced contraction of collagen I gels seeded with myofibroblasts compared with control mechanical activity in 5.4 mM [[K.sup.+]]o. In combination, these results show that ventricular fibroblasts and myofibroblasts express a variety of [K.sup.+] channel [alpha]-subunits and demonstrate that Kir current can modulate RMP and alter essential physiological functions. rat ventricle; voltage clamp

Published
2005

16. Long‐term survival after childhood acute lymphoblastic leukaemia: population‐based trends in cure and relapse by clinical characteristics

Author

Smith, L, Glaser, AW, Kinsey, SE, Greenwood, DC, Chilton, L, Moorman, AV, and Feltbower, RG

Abstract

‘Cure models’ offer additional information to traditional approaches to assess survival for cancer patients by simultaneously estimating the proportion cured and the survival of those ‘uncured’. The proportion cured is a summary of long term survival while the median survival time of the uncured provides important information on those who are not long-term survivors. Population-based trends in the cure proportion and survival of the uncured for childhood acute lymphoblastic leukaemia (ALL) by clinical prognostic risk factors were estimated using flexible parametric cure models, based on overall survival and event-free survival. Children aged 1-17 years diagnosed from 1990-2011 in Yorkshire, UK, were included (n=492). The percentage cured increased from 77% (95%CI 70-84%) in 1990-1997 to 89% (84-93%) in 2003-2011, while the median survival time of the uncured decreased from 3.2 years (2.2-4.1 years) to 0.7 years (0-1.5 years). Models based on event-free survival showed a similar trend. The 5-year cumulative incidence of relapse substantially decreased from 35% in 1990-97 to 9% in 2003-2011. These results show selective improvement in survival between 1990 and 2011 with a significant reduction in the risk of relapse alongside a reduced absolute duration of survival for those destined to be uncured.

Published
2018

17. Intragenic amplification of PAX5: A novel subgroup in B-cell precursor acute lymphoblastic leukemia?

Author

Schwab, C, Nebral, K, Chilton, L, Leschi, C, Waanders, E, Boer, J, Žaliová, M, Sutton, R, Öfverholm, I, Ohki, K, Yamashita, Y, Groeneveld-Krentz, S, Froňková, E, Bakkus, M, Tchinda, J, Barbosa, T, Fazio, G, Mlynarski, W, Pastorczak, A, Cazzaniga, G, Pombo-de-Oliveira, M, Trka, J, Kirschner-Schwabe, R, Imamura, T, Barbany, G, Stanulla, M, Attarbaschi, A, Panzer-Grümayer, R, Kuiper, R, den Boer, M, Cavé, H, Moorman, A, Harrison, C, Strehl, S, Schwab, Claire, Nebral, Karin, Chilton, Lucy, Leschi, Cristina, Waanders, Esmé, Boer, Judith M., Žaliová, Markéta, Sutton, Rosemary, Öfverholm, Ingegerd Ivanov, Ohki, Kentaro, Yamashita, Yuka, Groeneveld-Krentz, Stefanie, Froňková, Eva, Bakkus, Marleen, Tchinda, Joelle, Barbosa, Thayana da Conceição, Fazio, Grazia, Mlynarski, Wojciech, Pastorczak, Agata, Cazzaniga, Giovanni, Pombo-de-Oliveira, Maria S., Trka, Jan, Kirschner-Schwabe, Renate, Imamura, Toshihiko, Barbany, Gisela, Stanulla, Martin, Attarbaschi, Andishe, Panzer-Grümayer, Renate, Kuiper, Roland P., den Boer, Monique L., Cavé, Hélène, Moorman, Anthony V., Harrison, Christine J., Strehl, Sabine, Schwab, C, Nebral, K, Chilton, L, Leschi, C, Waanders, E, Boer, J, Žaliová, M, Sutton, R, Öfverholm, I, Ohki, K, Yamashita, Y, Groeneveld-Krentz, S, Froňková, E, Bakkus, M, Tchinda, J, Barbosa, T, Fazio, G, Mlynarski, W, Pastorczak, A, Cazzaniga, G, Pombo-de-Oliveira, M, Trka, J, Kirschner-Schwabe, R, Imamura, T, Barbany, G, Stanulla, M, Attarbaschi, A, Panzer-Grümayer, R, Kuiper, R, den Boer, M, Cavé, H, Moorman, A, Harrison, C, Strehl, S, Schwab, Claire, Nebral, Karin, Chilton, Lucy, Leschi, Cristina, Waanders, Esmé, Boer, Judith M., Žaliová, Markéta, Sutton, Rosemary, Öfverholm, Ingegerd Ivanov, Ohki, Kentaro, Yamashita, Yuka, Groeneveld-Krentz, Stefanie, Froňková, Eva, Bakkus, Marleen, Tchinda, Joelle, Barbosa, Thayana da Conceição, Fazio, Grazia, Mlynarski, Wojciech, Pastorczak, Agata, Cazzaniga, Giovanni, Pombo-de-Oliveira, Maria S., Trka, Jan, Kirschner-Schwabe, Renate, Imamura, Toshihiko, Barbany, Gisela, Stanulla, Martin, Attarbaschi, Andishe, Panzer-Grümayer, Renate, Kuiper, Roland P., den Boer, Monique L., Cavé, Hélène, Moorman, Anthony V., Harrison, Christine J., and Strehl, Sabine

Abstract

Intragenic PAX5 amplification defines a novel, relapse-prone subtype of B-cell precursor acute lymphoblastic leukemia with a poor outcome

Published
2017

22. Poster session 1Cell growth, differentiation and stem cells - Heart72Understanding the metabolism of cardiac progenitor cells: a first step towards controlling their proliferation and differentiation?73Expression of pw1/peg3 identifies a new cardiac adult stem cell population involved in post-myocardial infarction remodeling74Long-term stimulation of iPS-derived cardiomyocytes using optogenetic techniques to promote phenotypic changes in E-C coupling75Benefits of electrical stimulation on differentiation and maturation of cardiomyocytes from human induced pluripotent stem cells76Constitutive beta-adrenoceptor-mediated cAMP production controls spontaneous automaticity of human induced pluripotent stem cell-derived cardiomyocytes77Formation and stability of T-tubules in cardiomyocytes78Identification of miRNAs promoting human cardiomyocyte proliferation by regulating Hippo pathway79A direct comparison of foetal to adult epicardial cell activation reveals distinct differences relevant for the post-injury response80Role of neuropilins in zebrafish heart regeneration81Highly efficient immunomagnetic purification of cardiomyocytes derived from human pluripotent stem cells82Cardiac progenitor cells posses a molecular circadian clock and display large 24-hour oscillations in proliferation and stress tolerance83Influence of sirolimus and everolimus on bone marrow-derived mesenchymal stem cell biology84Endoglin is important for epicardial behaviour following cardiac injuryCell death and apoptosis - Heart87Ultrastructural alterations reflecting Ca2+ handling and cell-to-cell coupling disorders precede occurrence of severe arrhythmias in intact animal heart88Urocortin-1 promotes cardioprotection through ERK1/2 and EPAC pathways: role in apoptosis and necrosis89Expression p38 MAPK and Cas-3 in myocardium LV of rats with experimental heart failure at melatonin and enalapril introductionTranscriptional control and RNA species - Heart92Accumulation of beta-amyloid 1-40 in HF patients: the role of lncRNA BACE1-AS93Role of miR-182 in zebrafish and mouse models of Holt-Oram syndrome94Mir-27 distinctly regulates muscle-enriched transcription factors and growth factors in cardiac and skeletal muscle cells95AF risk factors impair PITX2 expression leading to Wnt-microRNA-ion channel remodelingCytokines and cellular inflammation - Heart98Post-infarct survival depends on the interplay of monocytes, neutrophils and interferon gamma in a mouse model of myocardial Infarction99Inflammatory cd11b/c cells play a protective role in compensated cardiac hypertrophy by promoting an orai3-related pro-survival signal100Anti-inflammatory effects of endothelin receptor blockade in the atrial tissue of spontaneously hypertensive rats101Mesenchymal stromal cells reduce NLRP3 inflammasome activity in Coxsackievirus B3-induced myocarditis102Mesenchymal stromal cells modulate monocytes trafficking in Coxsackievirus B3-induced myocarditis103The impact of regulatory T lymphocytes on long-term mortality in patients with chronic heart failure104Temporal dynamics of dendritic cells after ST-elevation myocardial infarction relate with improvement of myocardial functionGrowth factors and neurohormones - Heart107Preconditioning of hypertrophied heart: miR-1 and IGF-1 crosstalk108Modulation of catecholamine secretion from human adrenal chromaffin cells by manipulation of G protein-coupled receptor kinase-2 activity109Evaluation of cyclic adenosin-3,5- monophosphate and neurohormones in patients with chronic heart failureNitric oxide and reactive oxygen species - Heart112Hydrogen sulfide donor inhibits oxidative and nitrosative stress, cardiohemodynamics disturbances and restores cNOS coupling in old rats113Role and mechanisms of action of aldehydes produced by monoamine oxidase A in cardiomyocyte death and heart failure114Exercise training has contrasting effects in myocardial infarction and pressure-overload due to different endothelial nitric oxide synthase regulation115S-Nitroso Human Serum Albumin dose-dependently leads to vasodilation and alters reactive hyperaemia in coronary arteries of an isolated mouse heart model116Modulating endothelial nitric oxide synthase with folic acid attenuates doxorubicin-induced cardiomyopathy119Effects of long-term very high intensity exercise on aortic structure and function in an animal model120Electron paramagnetic resonance spectroscopy quantification of nitrosylated hemoglobin (HbNO) as an index of vascular nitric oxide bioavailability in vivo121Deletion of repressor activator protein 1 impairs acetylcholine-induced relaxation due to production of reactive oxygen speciesExtracellular matrix and fibrosis - Heart124MicroRNA-19b is associated with myocardial collagen cross-linking in patients with severe aortic stenosis. Potential usefulness as a circulating biomarker125A new ex vivo model to study cardiac fibrosis126Heterogeneity of fibrosis and fibroblast differentiation in the left ventricle after myocardial infarction127Effect of carbohydrate metabolism degree compensation to the level of galectin-3 changes in hypertensive patients with chronic heart failure and type 2 diabetes mellitus128Statin paradox in association with calcification of bicuspid aortic valve interstitial cells129Cardiac function remains impaired despite reversible cardiac fibrosis after healed experimental viral myocarditisIon channels, ion exchangers and cellular electrophysiology - Heart132Identifying a novel role for PMCA1 (Atp2b1) in heart rhythm instability133Mutations of the caveolin-3 gene as a predisposing factor for cardiac arrhythmias134The human sinoatrial node action potential: time for a computational model135iPSC-derived cardiomyocytes as a model to dissect ion current alterations of genetic atrial fibrillation136Postextrasystolic potentiation in healthy and diseased hearts: effects of the site of origin and coupling interval of the preceding extrasystole137Absence of Nav1.8-based (late) sodium current in rabbit cardiomyocytes and human iPSC-CMs138hiPSC-derived cardiomyocytes from Brugada Syndrome patients without identified mutations do not exhibit cellular electrophysiological abnormalitiesMicrocirculation141Atherogenic indices, collagen type IV turnover and the development of microvascular complications- study in diabetics with arterial hypertension142Changes in the microvasculature and blood viscosity in women with rheumatoid arthritis, hypercholesterolemia and hypertensionAtherosclerosis145Shear stress regulates endothelial autophagy: consequences on endothelial senescence and atherogenesis146Obstructive sleep apnea causes aortic remodeling in a chronic murine model147Aortic perivascular adipose tissue displays an aged phenotype in early and late atherosclerosis in ApoE-/- mice148A systematic evaluation of the cellular innate immune response during the process of human atherosclerosis149Inhibition of Coagulation factor Xa increases plaque stability and attenuates the onset and progression of atherosclerotic plaque in apolipoprotein e-deficient mice150Regulatory CD4+ T cells from patients with atherosclerosis display pro-inflammatory skewing and enhanced suppression function151Hypoxia-inducible factor (HIF)-1alpha regulates macrophage energy metabolism by mediating miRNAs152Extracellular S100A4 is a key player of smooth muscle cell phenotypic transition: implications in atherosclerosis153Microparticles of healthy origins improve atherosclerosis-associated endothelial progenitor cell dysfunction via microRNA transfer154Arterial remodeling and metabolism impairment in early atherosclerosis155Role of pannexin1 in atherosclerotic plaque formationCalcium fluxes and excitation-contraction coupling158Amphiphysin II induces tubule formation in cardiac cells159Interleukin 1 beta regulation of connexin 43 in cardiac fibroblasts and the effects of adult cardiac myocyte:fibroblast co-culture on myocyte contraction160T-tubular electrical defects contribute to blunted beta-adrenergic response in heart failure161Beat-to-beat variability of intracellular Ca2+ dynamics of Purkinje cells in the infarct border zone of the mouse heart revealed by rapid-scanning confocal microscopy162The efficacy of late sodium current blockers in hypertrophic cardiomyopathy is dependent on genotype: a study on transgenic mouse models with different mutations163Synthesis of cADPR and NAADP by intracellular CD38 in heart: role in inotropic and arrhythmogenic effects of beta-adrenoceptor signalingContractile apparatus166Towards an engineered heart tissue model of HCM using hiPSC expressing the ACTC E99K mutation167Diastolic mechanical load delays structural and functional deterioration of ultrathin adult heart slices in culture168Structural investigation of the cardiac troponin complex by molecular dynamics169Exercise training restores myocardial and oxidative skeletal muscle function from myocardial infarction heart failure ratsOxygen sensing, ischaemia and reperfusion172A novel antibody specific to full-length stromal derived factor-1 alpha reveals that remote conditioning induces its cleavage by endothelial dipeptidyl peptidase 4173Attenuation of myocardial and vascular arginase activity by vagal nerve stimulation via a mechanism involving alpha-7 nicotinic receptor during cardiac ischemia and reperfusion174Novel nanoparticle-mediated medicine for myocardial ischemia-reperfusion injury simultaneously targeting mitochondrial injury and myocardial inflammation175Acetylcholine plays a key role in myocardial ischaemic preconditioning via recruitment of intrinsic cardiac ganglia176The role of nitric oxide and VEGFR-2 signaling in post ischemic revascularization and muscle recovery in aged hypercholesterolemic mice177Efficacy of ischemic preconditioning to protect the human myocardium: the role of clinical conditions and treatmentsCardiomyopathies and fibrosis180Plakophilin-2 haploinsufficiency leads to impaired canonical Wnt signaling in ARVC patient181Improved technique for customized, easier, safer and more reliable transverse aortic arch banding and debanding in mice as a model of pressure overload hypertrophy182Late sodium current inhibitors for the treatment of inducible obstruction and diastolic dysfunction in hypertrophic cardiomyopathy: a study on human myocardium183Angiotensin II receptor antagonist fimasartan has protective role of left ventricular fibrosis and remodeling in the rat ischemic heart184Role of High-Mobility Group Box 1 (HMGB1) redox state on cardiac fibroblasts activities and heart function after myocardial infarction185Atrial remodeling in hypertrophic cardiomyopathy: insights from mouse models carrying different mutations in cTnT186Electrophysiological abnormalities in ventricular cardiomyocytes from a Maine Coon cat with hypertrophic cardiomyopathy: effects of ranolazine187ZBTB17 is a novel cardiomyopathy candidate gene and regulates autophagy in the heart188Inhibition of SRSF4 in cardiomyocytes induces left ventricular hypertrophy189Molecular characterization of a novel cardiomyopathy related desmin frame shift mutation190Autonomic characterisation of electro-mechanical remodeling in an in-vitro leporine model of heart failure191Modulation of Ca2+-regulatory function by three novel mutations in TNNI3 associated with severe infant restrictive cardiomyopathyAging194The aging impact on cardiac mesenchymal like stromal cells (S+P+)195Reversal of premature aging markers after bariatric surgery196Sex-associated differences in vascular remodeling during aging: role of renin-angiotensin system197Role of the receptor for advanced glycation end-products (RAGE) in age dependent left ventricle dysfunctionsGenetics and epigenetics200hsa-miR-21-5p as a key factor in aortic remodeling during aneurysm formation201Co-inheritance of mutations associated with arrhythmogenic and hypertrophic cardiomyopathy in two Italian families202Lamin a/c hot spot codon 190: form various amino acid substitutions to clinical effects203Treatment with aspirin and atorvastatin attenuate cardiac injury induced by rat chest irradiation: Implication of myocardial miR-1, miR-21, connexin-43 and PKCGenomics, proteomics, metabolomics, lipidomics and glycomics206Differential phosphorylation of desmin at serines 27 and 31 drives the accumulation of preamyloid oligomers in heart failure207Potential role of kinase Akt2 in the reduced recovery of type 2 diabetic hearts subjected to ischemia / reperfusion injury208A proteomics comparison of extracellular matrix remodelling in porcine coronary arteries upon stent implantationMetabolism, diabetes mellitus and obesity211Targeting grk2 as therapeutic strategy for cancer associated to diabetes212Effects of salbutamol on large arterial stiffness in patients with metabolic syndrome213Circulating microRNA-1 and microRNA-133a: potential biomarkers of myocardial steatosis in type 2 diabetes mellitus214Anti-inflammatory nutrigenomic effects of hydroxytyrosol in human adipocytes - protective mechanisms of mediterranean diets in obesity-related inflammation215Alterations in the metal content of different cardiac regions within a rat model of diabetic cardiomyopathyTissue engineering218A novel conductive patch for application in cardiac tissue engineering219Establishment of a simplified and improved workflow from neonatal heart dissociation to cardiomyocyte purification and characterization220Effects of flexible substrate on cardiomyocytes cell culture221Mechanical stretching on cardiac adipose progenitors upregulates sarcomere-related genes

Author

Andre, E, primary, Yaniz-Galende, E, primary, Hamilton, C, primary, Dusting, G J, primary, Hellen, N, primary, Poulet, CE, primary, Diez Cunado, M, primary, Smits, AM, primary, Lowe, V, primary, Eckardt, D, primary, Du Pre, B, primary, Sanz Ruiz, R, primary, Moerkamp, A T, primary, Tribulova, N, primary, Smani, T, primary, Liskova, Y V, primary, Greco, S, primary, Guzzolino, E, primary, Franco, D, primary, Lozano-Velasco, E, primary, Knorr, M, primary, Pavoine, C, primary, Bukowska, A, primary, Van Linthout, S, primary, Miteva, K, primary, Sulzgruber, P, primary, Latet, S C, primary, Portnychenko, A, primary, Cannavo, A, primary, Kamilova, U, primary, Sagach, VF, primary, Santin, Y, primary, Octavia, Y, primary, Haller, PM, primary, Rubies, C, primary, Dei Zotti, F, primary, Wong, KHK, primary, Gonzalez Miqueo, A, primary, Kruithof, BPT, primary, Kadur Nagaraju, C, primary, Shaposhnikova, Y, primary, Songia, P, primary, Lindner, D, primary, Wilson, C, primary, Benzoni, P, primary, Fabbri, A, primary, Campostrini, G, primary, Jorge, E, primary, Casini, S, primary, Mengarelli, I, primary, Nikolov, A, primary, Bublikov, DS, primary, Kheloufi, M, primary, Walker, R E, primary, Van Dijk, RA, primary, Posthuma, JJ, primary, Dumitriu, I E, primary, Karshovska, E, primary, Sakic, A, primary, Alexandru, N, primary, Martin-Lorenzo, M, primary, Molica, F, primary, Taylor, RF, primary, Mcarthur, L, primary, Crocini, C, primary, Matsuyama, T-A, primary, Mazzoni, L, primary, Lin, W K, primary, Owen, TJ, primary, Scigliano, M, primary, Sheehan, A, primary, Bezerra Gurgel, A R, primary, Bromage, DI, primary, Kiss, A, primary, Ikeda, G, primary, Pickard, J M J, primary, Wirth, G, primary, Casos, K, primary, Khudiakov, A, primary, Nistal, JF, primary, Ferrantini, C, primary, Park, S-J, primary, Di Maggio, S, primary, Gentile, F, primary, Dini, L, primary, Buyandelger, B, primary, Larrasa-Alonso, J, primary, Schirmer, I, primary, Chin, SH, primary, Cimiotti, D, primary, Martini, H, primary, Hohensinner, P J, primary, Garabito, M, primary, Zeni, F, primary, Licholai, S, primary, De Bortoli, M, primary, Sivitskaya, L, primary, Viczenczova, C, primary, Rainer, PP, primary, Smith, LE, primary, Suna, G, primary, Gambardella, J, primary, Cozma, A, primary, De Gonzalo Calvo, D, primary, Scoditti, E, primary, Clark, B J, primary, Mansfield, C, primary, Gomez, L, primary, Llucia-Valldeperas, A, primary, De Pauw, A, additional, Porporato, P, additional, Bouzin, C, additional, Draoui, N, additional, Sonveaux, P, additional, Balligand, J-L, additional, Mougenot, N, additional, Formicola, L, additional, Nadaud, S, additional, Dierick, F, additional, Hajjar, RJ, additional, Marazzi, G, additional, Sassoon, D, additional, Hulot, J-S, additional, Zamora, VR, additional, Burton, FL, additional, Macquaide, N, additional, Smith, GL, additional, Hernandez, D, additional, Sivakumaran, P, additional, Millard, R, additional, Wong, RCB, additional, Pebay, A, additional, Shepherd, RK, additional, Lim, SY, additional, Owen, T, additional, Jabbour, RJ, additional, Kloc, M, additional, Kodagoda, T, additional, Denning, C, additional, Harding, SE, additional, Ramos, S, additional, Terracciano, C, additional, Gorelik, J, additional, Wei, K, additional, Bushway, P, additional, Ruiz-Lozano, P, additional, Mercola, M, additional, Moerkamp, AT, additional, Vegh, AMD, additional, Dronkers, E, additional, Lodder, K, additional, Van Herwaarden, T, additional, Goumans, MJ, additional, Pellet-Many, C, additional, Zachary, I, additional, Noack, K, additional, Bosio, A, additional, Feyen, DAM, additional, Demkes, EJ, additional, Dierickx, PJ, additional, Doevendans, PA, additional, Vos, MA, additional, Van Veen, AAB, additional, Van Laake, LW, additional, Fernandez Santos, ME, additional, Suarez Sancho, S, additional, Fuentes Arroyo, L, additional, Plasencia Martin, V, additional, Velasco Sevillano, P, additional, Casado Plasencia, A, additional, Climent, AM, additional, Guillem, M, additional, Atienza Fernandez, F, additional, Fernandez-Aviles, F, additional, Dingenouts, CKE, additional, Kruithof, BPT, additional, Smits, AM, additional, Knezl, V, additional, Szeiffova Bacova, B, additional, Egan Benova, T, additional, Viczenczova, C, additional, Goncalvesova, E, additional, Slezak, J, additional, Calderon-Sanchez, E, additional, Diaz, I, additional, Ordonez, A, additional, Salikova, S P, additional, Zaccagnini, G, additional, Voellenkle, C, additional, Sadeghi, I, additional, Maimone, B, additional, Castelvecchio, S, additional, Gaetano, C, additional, Menicanti, L, additional, Martelli, F, additional, Hatcher, C, additional, D'aurizio, R, additional, Groth, M, additional, Baugmart, M, additional, Mercatanti, A, additional, Russo, F, additional, Mariani, L, additional, Magliaro, C, additional, Pitto, L, additional, Lozano-Velasco, E, additional, Jodar-Garcia, A, additional, Galiano-Torres, J, additional, Lopez-Navarrete, I, additional, Aranega, A, additional, Wagensteen, R, additional, Quesada, A, additional, Franco, D, additional, Finger, S, additional, Karbach, S, additional, Kossmann, S, additional, Muenzel, T, additional, Wenzel, P, additional, Keck, M, additional, Favier, S, additional, Fuand, A, additional, Atassi, F, additional, Barbier, C, additional, Lompre, AM, additional, Hulot, JS, additional, Nikonova, Y, additional, Pluteanu, F, additional, Kockskaemper, J, additional, Chilukoti, RK, additional, Wolke, C, additional, Lendeckel, U, additional, Gardemann, A, additional, Goette, A, additional, Miteva, K, additional, Pappritz, K, additional, Mueller, I, additional, El-Shafeey, M, additional, Ringe, J, additional, Tschoepe, C, additional, Van Linthout, S, additional, Koller, L, additional, Richter, B, additional, Blum, S, additional, Koprak, M, additional, Huelsmann, M, additional, Pacher, R, additional, Goliasch, G, additional, Wojta, J, additional, Niessner, A, additional, Van Herck, P L, additional, Claeys, M J, additional, Haine, S E, additional, Lenders, G D, additional, Miljoen, H P, additional, Segers, V F, additional, Vandendriescche, T R, additional, Hoymans, V Y, additional, Vrints, C J, additional, Lapikova-Bryhinska, T, additional, Gurianova, V, additional, Portnichenko, H, additional, Vasylenko, M, additional, Zapara, Y, additional, Portnichenko, V, additional, Liccardo, D, additional, Lymperopoulos, A, additional, Santangelo, M, additional, Leosco, D, additional, Koch, WJ, additional, Ferrara, N, additional, Rengo, G, additional, Alieva, T, additional, Rasulova, Z, additional, Masharipova, D, additional, Dorofeyeva, N A, additional, Drachuk, KO, additional, Sicard, P, additional, Yucel, Y, additional, Dutaur, M, additional, Vindis, C, additional, Parini, A, additional, Mialet-Perez, J, additional, Van Deel, ED, additional, De Boer, M, additional, De Waard, MC, additional, Duncker, DJ, additional, Nagel, F, additional, Inci, M, additional, Santer, D, additional, Hallstroem, S, additional, Podesser, BK, additional, Kararigas, G, additional, Kietadisorn, R, additional, Swinnen, M, additional, Duimel, H, additional, Verheyen, F, additional, Chrifi, I, additional, Brandt, MM, additional, Cheng, C, additional, Janssens, S, additional, Moens, AL, additional, Batlle, M, additional, Dantas, AP, additional, Sanz, M, additional, Sitges, M, additional, Mont, L, additional, Guasch, E, additional, Lobysheva, I, additional, Beauloye, C, additional, Vanhoutte, PM, additional, Tang, EHC, additional, Beaumont, J, additional, Lopez, B, additional, Ravassa, S, additional, Hermida, N, additional, Valencia, F, additional, Gomez-Doblas, JJ, additional, San Jose, G, additional, De Teresa, E, additional, Diez, J, additional, Van De Merbel, AF, additional, Kruithof-De Julio, M, additional, Claus, P, additional, Dries, E, additional, Angelo Singh, A, additional, Vermeulen, K, additional, Roderick, HL, additional, Sipido, KR, additional, Driesen, RB, additional, Ilchenko, I, additional, Bobronnikova, L, additional, Myasoedova, V, additional, Alamanni, F, additional, Tremoli, E, additional, Poggio, P, additional, Becher, PM, additional, Gotzhein, F, additional, Klingel, K, additional, Blankenberg, S, additional, Westermann, D, additional, Zi, M, additional, Cartwright, E, additional, Campostrini, G, additional, Bonzanni, M, additional, Milanesi, R, additional, Bucchi, A, additional, Baruscotti, M, additional, Difrancesco, D, additional, Barbuti, A, additional, Fantini, M, additional, Wilders, R, additional, Severi, S, additional, Benzoni, P, additional, Dell' Era, P, additional, Serzanti, M, additional, Olesen, MS, additional, Muneretto, C, additional, Bisleri, G, additional, Amoros-Figueras, G, additional, Raga, S, additional, Campos, B, additional, Alonso-Martin, C, additional, Rodriguez-Font, E, additional, Vinolas, X, additional, Cinca, J, additional, Guerra, JM, additional, Mengarelli, I, additional, Schumacher, CA, additional, Veldkamp, MW, additional, Verkerk, AO, additional, Remme, CA, additional, Veerman, C, additional, Guan, K, additional, Stauske, M, additional, Tan, H, additional, Barc, J, additional, Wilde, A, additional, Verkerk, A, additional, Bezzina, C, additional, Tsinlikov, I, additional, Tsinlikova, I, additional, Nicoloff, G, additional, Blazhev, A, additional, Garev, A, additional, Andrienko, AV, additional, Lychev, VG, additional, Vorobova, EN, additional, Anchugina, DA, additional, Vion, AC, additional, Hammoutene, A, additional, Poisson, J, additional, Dupont, N, additional, Souyri, M, additional, Tedgui, A, additional, Codogno, P, additional, Boulanger, CM, additional, Rautou, PE, additional, Torres, M, additional, Montserrat, JM, additional, Almendros, I, additional, Austin, C A, additional, Holt, C M, additional, Rijs, K, additional, Wezel, A, additional, Hamming, JF, additional, Kolodgie, FD, additional, Virmani, R, additional, Schaapherder, AF, additional, Lindeman, JHN, additional, Posma, JJN, additional, Van Oerle, R, additional, Spronk, HMH, additional, Ten Cate, H, additional, Dinkla, S, additional, Kaski, JC, additional, Schober, A, additional, Chaabane, C, additional, Ambartsumian, N, additional, Grigorian, M, additional, Bochaton-Piallat, ML, additional, Dragan, E, additional, Andrei, E, additional, Niculescu, L, additional, Georgescu, A, additional, Gonzalez-Calero, L, additional, Maroto, AS, additional, Martinez, PJ, additional, Heredero, A, additional, Aldamiz-Echevarria, G, additional, Vivanco, F, additional, Alvarez-Llamas, G, additional, Meens, MJ, additional, Pelli, G, additional, Foglia, B, additional, Scemes, E, additional, Kwak, BR, additional, Caldwell, JL, additional, Eisner, DA, additional, Dibb, KM, additional, Trafford, AW, additional, Chilton, L, additional, Smith, G L, additional, Nicklin, S A, additional, Coppini, R, additional, Ferrantini, C, additional, Yan, P, additional, Loew, LM, additional, Poggesi, C, additional, Cerbai, E, additional, Pavone, F S, additional, Sacconi, L, additional, Tanaka, H, additional, Ishibashi-Ueda, H, additional, Takamatsu, T, additional, Gentile, F, additional, Pioner, JM, additional, Santini, L, additional, Sartiani, L, additional, Bargelli, V, additional, Mugelli, A, additional, Maciejewska, M, additional, Bolton, E L, additional, Wang, Y, additional, O'brien, F, additional, Ruas, M, additional, Lei, M, additional, Sitsapesan, R, additional, Galione, A, additional, Terrar, D A, additional, Smith, JG, additional, Garcia, D, additional, Barriales-Villa, R, additional, Monserrat, L, additional, Marston, SB, additional, Watson, S, additional, Tkach, S, additional, Faggian, G, additional, Terracciano, C M, additional, Perbellini, F, additional, Eiros Zamora, J, additional, Papadaki, M, additional, Messer, A, additional, Marston, S, additional, Gould, I, additional, Johnston, A, additional, Dunne, M, additional, Smith, G, additional, Kemi, OJ, additional, Pillai, M, additional, Davidson, SM, additional, Yellon, DM, additional, Tratsiakovich, Y, additional, Jang, J, additional, Gonon, AT, additional, Pernow, J, additional, Matoba, T, additional, Koga, J, additional, Egashira, K, additional, Burke, N, additional, Korpisalo, P, additional, Hakkarainen, H, additional, Laidinen, S, additional, Yla-Herttuala, S, additional, Ferrer-Curriu, G, additional, Perez, M, additional, Permanyer, E, additional, Blasco-Lucas, A, additional, Gracia, JM, additional, Castro, MA, additional, Barquinero, J, additional, Galinanes, M, additional, Kostina, D, additional, Kostareva, A, additional, Malashicheva, A, additional, Merino, D, additional, Ruiz, L, additional, Gomez, J, additional, Juarez, C, additional, Gil, A, additional, Garcia, R, additional, Hurle, MA, additional, Mazzoni, L, additional, Rossi, A, additional, Tesi, C, additional, Belardinelli, L, additional, Olivotto, I, additional, Eun-Ji, EJ, additional, Lim, B-K, additional, Choi, D-J, additional, Milano, G, additional, Bertolotti, M, additional, De Marchis, F, additional, Zollo, F, additional, Sommariva, E, additional, Capogrossi, M C, additional, Pompilio, G, additional, Bianchi, M E, additional, Raucci, A, additional, Scellini, B, additional, Tardiff, J, additional, Diolaiuti, L, additional, Ferrari, P, additional, Mansfield, C, additional, Luther, P, additional, Knoell, R, additional, Villalba, M, additional, Sanchez-Cabo, F, additional, Lopez-Olaneta, MM, additional, Ortiz-Sanchez, P, additional, Garcia-Pavia, P, additional, Lara-Pezzi, E, additional, Klauke, B, additional, Gerdes, D, additional, Schulz, U, additional, Gummert, J, additional, Milting, H, additional, Wake, E, additional, Kocsis-Fodor, G, additional, Brack, KE, additional, Ng, GA, additional, Smolina, N, additional, Majchrzak, M, additional, Moehner, D, additional, Wies, A, additional, Stehle, R, additional, Pfitzer, G, additional, Muegge, A, additional, Jaquet, K, additional, Maggiorani, D, additional, Lefevre, L, additional, Cussac, D, additional, Douin-Echinard, V, additional, Ebenbauer, B, additional, Kaun, C, additional, Prager, M, additional, Rega-Kaun, G, additional, Costa, G, additional, Onetti, Y, additional, Jimenez-Altayo, F, additional, Vila, E, additional, Dantas, A P, additional, Scopece, A, additional, Piacentini, L, additional, Bianchi, ME, additional, Capogrossi, MC, additional, Colombo, G, additional, Blaz, M, additional, Kapelak, B, additional, Sanak, M, additional, Bauce, B, additional, Calore, C, additional, Lorenzon, A, additional, Calore, M, additional, Poloni, G, additional, Mazzotti, E, additional, Rigato, I, additional, Daliento, L, additional, Basso, C, additional, Thiene, G, additional, Melacini, P, additional, Corrado, D, additional, Rampazzo, A, additional, Danilenko, NG, additional, Vaikhanskaya, TG, additional, Davydenko, OG, additional, Kura, B, additional, Yin, CH, additional, Kukreja, R, additional, Tribulova, N, additional, Lee, DI, additional, Sorge, M, additional, Glabe, C, additional, Paolocci, N, additional, Guarnieri, C, additional, Tomaselli, GF, additional, Kass, DA, additional, Van Eyk, JE, additional, Agnetti, G, additional, Cordwell, SJ, additional, White, MY, additional, Wojakowski, W, additional, Lynch, M, additional, Barallobre-Barreiro, J, additional, Yin, X, additional, Mayr, U, additional, White, S, additional, Jahingiri, M, additional, Hill, J, additional, Mayr, M, additional, Sorriento, D, additional, Ciccarelli, M, additional, Fiordelisi, A, additional, Campiglia, P, additional, Trimarco, B, additional, Iaccarino, G, additional, Sitar Taut, AV, additional, Schiau, S, additional, Orasan, O, additional, Halloumi, W, additional, Negrean, V, additional, Zdrenghea, D, additional, Pop, D, additional, Van Der Meer, RW, additional, Rijzewijk, LJ, additional, Smit, JWA, additional, Revuelta-Lopez, E, additional, Nasarre, L, additional, Escola-Gil, JC, additional, Lamb, HJ, additional, Llorente-Cortes, V, additional, Pellegrino, M, additional, Massaro, M, additional, Carluccio, MA, additional, Calabriso, N, additional, Wabitsch, M, additional, Storelli, C, additional, De Caterina, R, additional, Church, S J, additional, Callagy, S, additional, Begley, P, additional, Kureishy, N, additional, Mcharg, S, additional, Bishop, P N, additional, Unwin, R D, additional, Cooper, G J S, additional, Mawad, D, additional, Tonkin, J, additional, Bello, S O, additional, Simonotto, J D, additional, Lyon, A R, additional, Stevens, M M, additional, Harding, S E, additional, Kernbach, M, additional, Czichowski, V, additional, Fuentes, L, additional, Hernandez-Redondo, I, additional, Guillem, MS, additional, Fernandez, ME, additional, Sanz, R, additional, Atienza, F, additional, Soler-Botija, C, additional, Prat-Vidal, C, additional, Galvez-Monton, C, additional, Roura, S, additional, Perea-Gil, I, additional, Bragos, R, additional, and Bayes-Genis, A, additional

Published
2016
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23. Targeted sequencing identifies associations between IL7R-JAK mutations and epigenetic modulators in T-cell acute lymphoblastic leukemia

Author

Vicente, C., primary, Schwab, C., additional, Broux, M., additional, Geerdens, E., additional, Degryse, S., additional, Demeyer, S., additional, Lahortiga, I., additional, Elliott, A., additional, Chilton, L., additional, La Starza, R., additional, Mecucci, C., additional, Vandenberghe, P., additional, Goulden, N., additional, Vora, A., additional, Moorman, A. V., additional, Soulier, J., additional, Harrison, C. J., additional, Clappier, E., additional, and Cools, J., additional

Published
2015
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24. Near term perspectives for fusion research and new contributions by the Ignitor program

Author

Coppi, Bruno, Airoldi, A., Albanese, R., Ambrosino, G., Berta, S., Bianchi, A., Bombarda, F., Cardinali, A., Cenacchi, G., Chilton, L., Clai, G., Detragiache, P., Faelli, G., Frattolillo, A., Frosi, P., Giunchi, G., Grasso, G., Mantovani, S., Migliori, S., Penco, R., Pierattini, S., Pironti, A., Pizzicaroli, G., Ramogida, G., Rebusco, P., Rubinacci, G., Sassi, M., Villone, F., Zhou, T. C., and Zucchetti, Massimo

Subjects
NUclear fusion, Ignitor, Tokamaks
Published
2010
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25. An international study of intrachromosomal amplification of chromosome 21 (iAMP21) : cytogenetic characterization and outcome

Author

Harrison, C. J., Moorman, A. V., Schwab, C., Carroll, A. J., Raetz, E. A., Devidas, M., Strehl, S., Nebral, K., Harbott, J., Teigler-Schlegel, A., Zimmerman, M., Dastuge, N., Baruchel, A., Soulier, J., Auclerc, M-F, Attarbaschi, A., Mann, G., Stark, B., Cazzaniga, G., Chilton, L., Vandenberghe, P., Forestier, Erik, Haltrich, I., Raimondi, S. C., Parihar, M., Bourquin, J-P, Tchinda, J., Haferlach, C., Vora, A., Hunger, S. P., Heerema, N. A., Haas, O. A., Harrison, C. J., Moorman, A. V., Schwab, C., Carroll, A. J., Raetz, E. A., Devidas, M., Strehl, S., Nebral, K., Harbott, J., Teigler-Schlegel, A., Zimmerman, M., Dastuge, N., Baruchel, A., Soulier, J., Auclerc, M-F, Attarbaschi, A., Mann, G., Stark, B., Cazzaniga, G., Chilton, L., Vandenberghe, P., Forestier, Erik, Haltrich, I., Raimondi, S. C., Parihar, M., Bourquin, J-P, Tchinda, J., Haferlach, C., Vora, A., Hunger, S. P., Heerema, N. A., and Haas, O. A.

Abstract

Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). To date, fluorescence in situ hybridisation (FISH), with probes specific for the RUNX1 gene, provides the only reliable detection method (five or more RUNX1 signals per cell). Patients with iAMP21 are older (median age 9 years) with a low white cell count. Previously, we demonstrated a high relapse risk when these patients were treated as standard risk. Recent studies have shown improved outcome on intensive therapy. In view of these treatment implications, accurate identification is essential. Here we have studied the cytogenetics and outcome of 530 iAMP21 patients that highlighted the association of specific secondary chromosomal and genetic changes with iAMP21 to assist in diagnosis, including the gain of chromosome X, loss or deletion of chromosome 7, ETV6 and RB1 deletions. These iAMP21 patients when treated as high risk showed the same improved outcome as those in trial-based studies regardless of the backbone chemotherapy regimen given. This study reinforces the importance of intensified treatment to reduce the risk of relapse in iAMP21 patients. This now well-defined patient subgroup should be recognised by World Health Organisation (WHO) as a distinct entity of BCP-ALL.

Published
2014
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26. T(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: An international study of 62 patients

Author

Sandahl, J.D. (Julie Damgaard), Coenen, E.A. (Eva), Forestier, E. (Erik), Harbott, J. (Jochen), Johansson, B. (Bert), Kerndrup, G. (Gitte), Adachi, S. (Susumu), Auvrignon, A. (Anne), Beverloo, H.B. (Berna), Cayuela, J.-M. (Jean-Michel), Chilton, L. (Lucy), Fornerod, M.W.J. (Maarten), Haas, V. (Valerie) de, Harrison, C.J. (Christine), Inaba, H. (Hiroto), Kaspers, G.J.L. (Gertjan), Liang, D. (Der), Locatelli, F. (Franco), Masetti, R. (Riccardo), Perot, C. (Christine), Raimondi, S.C. (Susana), Reinhardt, K. (Katarina), Tomizawa, D. (Daisuke), Neuhoff, N. (Nils) von, Zecca, M. (Marco), Zwaan, C.M. (Michel), Heuvel-Eibrink, M.M. (Marry) van den, Hasle, H. (Henrik), Sandahl, J.D. (Julie Damgaard), Coenen, E.A. (Eva), Forestier, E. (Erik), Harbott, J. (Jochen), Johansson, B. (Bert), Kerndrup, G. (Gitte), Adachi, S. (Susumu), Auvrignon, A. (Anne), Beverloo, H.B. (Berna), Cayuela, J.-M. (Jean-Michel), Chilton, L. (Lucy), Fornerod, M.W.J. (Maarten), Haas, V. (Valerie) de, Harrison, C.J. (Christine), Inaba, H. (Hiroto), Kaspers, G.J.L. (Gertjan), Liang, D. (Der), Locatelli, F. (Franco), Masetti, R. (Riccardo), Perot, C. (Christine), Raimondi, S.C. (Susana), Reinhardt, K. (Katarina), Tomizawa, D. (Daisuke), Neuhoff, N. (Nils) von, Zecca, M. (Marco), Zwaan, C.M. (Michel), Heuvel-Eibrink, M.M. (Marry) van den, and Hasle, H. (Henrik)

Abstract

Acute myeloid leukemia with t(6;9)(p22;q34) is listed as a distinct entity in the 2008 World Health Organization classification, but little is known about the clinical implications of t(6;9)-positive myeloid leukemia in children. This international multicenter study presents the clinical and genetic characteristics of 62 pediatric patients with t(6;9)/DEK-NUP214-rearranged myeloid leukemia; 54 diagnosed as having acute myeloid leukemia, representing <1% of all childhood acute myeloid leukemia, and eight as having myelodysplastic syndrome. The t(6;9)/DEK-NUP214 was associated with relatively late onset (median age 10.4 years), male predominance (sex ratio 1.7), French-American-British M2 classification (54%), myelodysplasia (100%), and FLT3-ITD (42%). Outcome was substantially better than previously reported with a 5-year event-free survival of 32%, 5-year overall survival of 53%, and a 5-year cumulative incidence of relapse of 57%. Hematopoietic stem cell transplantation in first complete remission improved the 5-year event-free survival compared with chemotherapy alone (68% versus 18%; P<0.01) but not the overall survival (68% versus 54%; P=0.48). The presence of FLT3-ITD had a non-significant negative effect on 5-year overall survival compared with non-mutated cases (22% versus 62%; P=0.13). Gene expression profiling showed a unique signature characterized by significantly higher expression of EYA3, SESN1, PRDM2/RIZ, and HIST2H4 genes. In conclusion, t(6;9)/DEK-NUP214 represents a unique subtype of acute myeloid leukemia with a high risk of relapse, high frequency of FLT3-ITD, and a specific gene expression signature.

Published
2014
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27. An international study of intrachromosomal amplification of chromosome 21 (iAMP21): cytogenetic characterization and outcome

Author

Harrison, C, Moorman, A, Schwab, C, Carroll, A, Raetz, E, Devidas, M, Strehl, S, Nebral, K, Harbott, J, Teigler-Schlegel, A, Zimmerman, M, Dastuge, N, Baruchel, A, Soulier, J, Auclerc, M, Attarbaschi, A, Mann, G, Stark, B, Cazzaniga, G, Chilton, L, Vandenberghe, P, Forestier, E, Haltrich, I, Raimondi, S, Parihar, M, Bourquin, J, Tchinda, J, Haferlach, C, Vora, A, Hunger, S, Heerema, N, Haas, O, Harrison, C J, Moorman, A V, Carroll, A J, Raetz, E A, Auclerc, M-F, Raimondi, S C, Bourquin, J-P, Hunger, S P, Heerema, N A, Haas, O A, Harrison, C, Moorman, A, Schwab, C, Carroll, A, Raetz, E, Devidas, M, Strehl, S, Nebral, K, Harbott, J, Teigler-Schlegel, A, Zimmerman, M, Dastuge, N, Baruchel, A, Soulier, J, Auclerc, M, Attarbaschi, A, Mann, G, Stark, B, Cazzaniga, G, Chilton, L, Vandenberghe, P, Forestier, E, Haltrich, I, Raimondi, S, Parihar, M, Bourquin, J, Tchinda, J, Haferlach, C, Vora, A, Hunger, S, Heerema, N, Haas, O, Harrison, C J, Moorman, A V, Carroll, A J, Raetz, E A, Auclerc, M-F, Raimondi, S C, Bourquin, J-P, Hunger, S P, Heerema, N A, and Haas, O A

Abstract

Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). To date, fluorescence in situ hybridisation (FISH), with probes specific for the RUNX1 gene, provides the only reliable detection method (five or more RUNX1 signals per cell). Patients with iAMP21 are older (median age 9 years) with a low white cell count. Previously, we demonstrated a high relapse risk when these patients were treated as standard risk. Recent studies have shown improved outcome on intensive therapy. In view of these treatment implications, accurate identification is essential. Here we have studied the cytogenetics and outcome of 530 iAMP21 patients that highlighted the association of specific secondary chromosomal and genetic changes with iAMP21 to assist in diagnosis, including the gain of chromosome X, loss or deletion of chromosome 7, ETV6 and RB1 deletions. These iAMP21 patients when treated as high risk showed the same improved outcome as those in trial-based studies regardless of the backbone chemotherapy regimen given. This study reinforces the importance of intensified treatment to reduce the risk of relapse in iAMP21 patients. This now well-defined patient subgroup should be recognised by World Health Organisation (WHO) as a distinct entity of BCP-ALL.

Published
2014

28. t(6;9)(p22; q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients

Author

Sandahl, JD, Coenen, Eva, Forestier, E, Harbott, J, Johansson, B, Kerndrup, G, Adachi, S, Auvrignon, A, Beverloo, Berna, Cayuela, JM, Chilton, L, Fornerod, M, de Haas, V, Harrison, CJ, Inaba, H, Kaspers, GJL, Liang, DC, Locatelli, F (Franco), Masetti, R, Perot, C, Raimondi, SC, Reinhardt, K, Tomizawa, D, von Neuhoff, N, Zecca, M, Zwaan, CM, Eibrink, Marry, Hasle, H, Sandahl, JD, Coenen, Eva, Forestier, E, Harbott, J, Johansson, B, Kerndrup, G, Adachi, S, Auvrignon, A, Beverloo, Berna, Cayuela, JM, Chilton, L, Fornerod, M, de Haas, V, Harrison, CJ, Inaba, H, Kaspers, GJL, Liang, DC, Locatelli, F (Franco), Masetti, R, Perot, C, Raimondi, SC, Reinhardt, K, Tomizawa, D, von Neuhoff, N, Zecca, M, Zwaan, CM, Eibrink, Marry, and Hasle, H

Published
2014

29. Cobi: Community-Informed Conference Scheduling

Author

Kim, J., Zhang, H., Andre, P., Chilton, L. B., Bhardwaj, A., David Karger, Dow, S. P., and Miller, R. C.

Abstract

Creating a schedule for a large multi-track conference requires considering the preferences and constraints of organizers, authors, and attendees. Traditionally, a few dedicated organizers manage the size and complexity of the schedule with limited information and coverage. Cobi presents an alternative approach to conference scheduling by engaging the entire community to take active roles in the planning process. It consists of a collection of crowdsourcing applications that elicit preferences and constraints from the community, and software that enable organizers and other community members to take informed actions based on collected information.

Published
2013

30. t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients

Author

Sandahl, J. D., primary, Coenen, E. A., additional, Forestier, E., additional, Harbott, J., additional, Johansson, B., additional, Kerndrup, G., additional, Adachi, S., additional, Auvrignon, A., additional, Beverloo, H. B., additional, Cayuela, J.-M., additional, Chilton, L., additional, Fornerod, M., additional, de Haas, V., additional, Harrison, C. J., additional, Inaba, H., additional, Kaspers, G. J. L., additional, Liang, D.-C., additional, Locatelli, F., additional, Masetti, R., additional, Perot, C., additional, Raimondi, S. C., additional, Reinhardt, K., additional, Tomizawa, D., additional, von Neuhoff, N., additional, Zecca, M., additional, Zwaan, C. M., additional, van den Heuvel-Eibrink, M. M., additional, and Hasle, H., additional

Published
2014
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31. The Rough Guide to the Greek Islands

Author

Chilton, L., Dubin, Marc, Rough Guides (Firm), Edwards, Nick, Ellingham, Mark, Chilton, L., Dubin, Marc, Rough Guides (Firm), Edwards, Nick, and Ellingham, Mark

Subjects
Islands--Greece--Guidebooks
Abstract

Description based on print version record.

Published
2009

35. The clinical characteristics, therapy and outcome of 85 adults with acute lymphoblastic leukemia and t(4;11)(q21;q23)/MLL-AFF1 prospectively treated in the UKALLXII/ECOG2993 trial

Author

Marks, D. I., primary, Moorman, A. V., additional, Chilton, L., additional, Paietta, E., additional, Enshaie, A., additional, DeWald, G., additional, Harrison, C. J., additional, Fielding, A. K., additional, Foroni, L., additional, Goldstone, A. H., additional, Litzow, M. R., additional, Luger, S. M., additional, McMillan, A. K., additional, Racevskis, J., additional, Rowe, J. M., additional, Tallman, M. S., additional, Wiernik, P., additional, and Lazarus, H. M., additional

Published
2013
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37. Treating childhood acute lymphoblastic leukemia in Malawi

Author

Chagaluka, G., primary, Carey, P., additional, Banda, K., additional, Schwab, C., additional, Chilton, L., additional, Schwalbe, E., additional, Skinner, R., additional, Israels, T., additional, Moorman, A., additional, Molyneux, E., additional, and Bailey, S., additional

Published
2012
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44. K+ currents regulate the resting membrane potential, proliferation, and contractile responses in ventricular fibroblasts and myofibroblasts.

Author

Chilton, L., Ohya, S., Freed, D., George, E., Drobic, V., Shibukawa, Y., MacCannell, K. A., Imaizumi, Y., Clark, R. B., Dixon, I. M. C., and Giles, W. R.

Subjects
*CARDIAC contraction, *MYOFIBROBLASTS, *FIBROBLASTS, *POTASSIUM channels, *VOLTAGE-clamp techniques (Electrophysiology), *ELECTROPHYSIOLOGY techniques
Abstract

Despite the important roles played by ventricular fibroblasts and myofibroblasts in the formation and maintenance of the extracellular matrix, neither the ionic basis for membrane potential nor the effect of modulating membrane potential on function has been analyzed in detail. In this study, whole cell patch-clamp experiments were done using ventricular fibroblasts and myofibroblasts. Time- and voltage-dependent outward K+ currents were recorded at depolarized potentials, and an inwardly rectifying K+ (Kir) current was recorded near the resting membrane potential (RMP) and at more hyperpolarized potentials. The apparent reversal potential of Kir currents shifted to more positive potentials as the external K+ concentration ([K+]o) was raised, and this Kir current was blocked by 100–300 μM Ba2+. RT-PCR measurements showed that mRNA for Kir2.1 was expressed. Accordingly, we conclude that Kir current is a primary determinant of RMP in both fibroblasts and myofibroblasts. Changes in [K+]o influenced fibroblast membrane potential as well as proliferation and contractile functions. Recordings made with a voltage-sensitive dye, DiBAC3(4), showed that 1.5 mM [K+]o resulted in a hyperpolarization, whereas 20 mM [K+]o produced a depolarization. Low [K+]o (1.5 mM) enhanced myofibroblast number relative to control (5.4 mM [K+]o). In contrast, 20 mM [K+]o resulted in a significant reduction in myofibroblast number. In separate assays, 20 mM [K+]o significantly enhanced contraction of collagen I gels seeded with myofibroblasts compared with control mechanical activity in 5.4 mM [K+]o. In combination, these results show that ventricular fibroblasts and myofibroblasts express a variety of K+ channel α-subunits and demonstrate that Kir current can modulate RMP and alter essential physiological functions. [ABSTRACT FROM AUTHOR]

Published
2005
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48. Blockade of KATP Channels Reduces Endothelial Hyperpolarization and Leukocyte Recruitment upon Reperfusion After Hypoxia

Author

Figura, M., Chilton, L., Liacini, A., Viskovic, M. Maric, Phan, V., Knight, D., Millar, T. M., Patel, K., Kubes, P., Giles, W. R., and Tibbles, L. A.

Abstract

Ischemiareperfusion injury in renal transplantation leads to slow or initial nonfunction, and predisposes to acute and chronic rejection. In fact, severe ischemia reperfusion injury can significantly reduce graft survival, even with modern immunosuppressive agents. One of the mechanisms by which ischemiareperfusion causes injury is activation of endothelial cells resulting in inflammation. Although several therapies can be used to prevent leukocyte recruitment to ischemic vessels (e.g. antiadhesion molecule antibodies), there have been no clinical treatments reported that can prevent initial immediate neutrophil recruitment upon reperfusion. Using intravital microscopy, we describe abrogation of immediate neutrophil recruitment to ischemic microvessels by the KATPantagonist glibenclamide (GlyburideT). Further, we show that glibenclamide can reduce leukocyte recruitment in vitrounder physiologic flow conditions. ATP-regulated potassium channels (KATP) are important in the control of cell membrane polarization. Here we describe profound hyperpolarization of endothelial cells during hypoxia, and the reduction of this hyperpolarization using glibenclamide. These findings suggest that control of endothelial membrane potential during ischemia may be an important therapeutic tool in avoiding ischemiareperfusion injury, and therefore, enhancing transplant long-term function.

Published
2009
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49. Blockade of KATPChannels Reduces Endothelial Hyperpolarization and Leukocyte Recruitment upon Reperfusion After Hypoxia

Author

Figura, M., Chilton, L., Liacini, A., Viskovic, M. Maric, Phan, V., Knight, D., Millar, T.M., Patel, K., Kubes, P., Giles, W.R., and Tibbles, L.A.

Abstract

Ischemia/reperfusion injury in renal transplantation leads to slow or initial nonfunction, and predisposes to acute and chronic rejection. In fact, severe ischemia reperfusion injury can significantly reduce graft survival, even with modern immunosuppressive agents. One of the mechanisms by which ischemia/reperfusion causes injury is activation of endothelial cells resulting in inflammation. Although several therapies can be used to prevent leukocyte recruitment to ischemic vessels (e.g. antiadhesion molecule antibodies), there have been no clinical treatments reported that can prevent initial immediate neutrophil recruitment upon reperfusion. Using intravital microscopy, we describe abrogation of immediate neutrophil recruitment to ischemic microvessels by the KATPantagonist glibenclamide (Glyburide™). Further, we show that glibenclamide can reduce leukocyte recruitment in vitrounder physiologic flow conditions. ATP-regulated potassium channels (KATP) are important in the control of cell membrane polarization. Here we describe profound hyperpolarization of endothelial cells during hypoxia, and the reduction of this hyperpolarization using glibenclamide. These findings suggest that control of endothelial membrane potential during ischemia may be an important therapeutic tool in avoiding ischemia/reperfusion injury, and therefore, enhancing transplant long-term function.

Published
2009
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