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Jan burger

Martijn H Hulsmans, Mark van Heijl, Roderick M Houwert, Bart J Burger, Egbert Jan M Verleisdonk, Dirk Jan Veeger, Olivier A van der Meijden
PURPOSE: Surgical treatment of displaced midshaft clavicle fractures requires a decision between plate fixation and intramedullary (IM) fixation. Numerous studies report on the biomechanical properties of various repair constructs. The goal of this systematic review was to provide an overview of studies describing the biomechanical properties of the most commonly used surgical fixations of midshaft clavicle fractures. Additionally, we aimed to translate these biomechanical results into clinically relevant conclusions...
February 21, 2018: Injury
Grazia Zulian, Erik Stange, Helen Woods, Laurence Carvalho, Jan Dick, Christopher Andrews, Francesc Baró, Pilar Vizcaino, David N Barton, Megan Nowel, Graciela M Rusch, Paula Autunes, João Fernandes, Diogo Ferraz, Rui Ferreira Dos Santos, Réka Aszalós, Ildikó Arany, Bálint Czúcz, Joerg A Priess, Christian Hoyer, Gleiciani Bürger-Patricio, David Lapola, Peter Mederly, Andrej Halabuk, Peter Bezak, Leena Kopperoinen, Arto Viinikka
Ecosystem service (ES) spatial modelling is a key component of the integrated assessments designed to support policies and management practices aiming at environmental sustainability. ESTIMAP ("Ecosystem Service Mapping Tool") is a collection of spatially explicit models, originally developed to support policies at a European scale. We based our analysis on 10 case studies, and 3 ES models. Each case study applied at least one model at a local scale. We analyzed the applications with respect to: the adaptation process; the "precision differential" which we define as the variation generated in the model between the degree of spatial variation within the spatial distribution of ES and what the model captures; the stakeholders' opinions on the usefulness of models...
February 2018: Ecosystem Services
Paolo Strati, Alessandra Ferrajoli, William G Wierda, Nitin Jain, Philip A Thompson, Susan M O'Brien, Katy Rezvani, Hagop M Kantarjian, Jan A Burger, Christina O Hinojosa, Michael J Keating, Zeev Estrov
No abstract text is available yet for this article.
February 20, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Uri Rozovski, David M Harris, Ping Li, Zhiming Liu, Preetesh Jain, Alessandra Ferrajoli, Jan Burger, Phillip Thompson, Nitin Jain, William Wierda, Michael J Keating, Zeev Estrov
Unlike normal B-cells, and similar to fat cells, chronic lymphocytic leukemia (CLL) cells aberrantly express lipoprotein lipase (LPL), which contributes to free fatty acids (FFAs) metabolism. Here we show that, in CLL cells, the B-cell receptor (BCR) inhibitor ibrutinib reduced LPL mRNA and protein levels and inhibited FFA metabolism in vitro. Likewise, in CLL cells from ibrutinib-treated patients, FFA metabolism was reduced and eventually stopped. Because ibrutinib disrupts CLL cells' ability to use FFAs for energy production, and because various BCR-dependent cellular functions rely on a continuous supply of chemical energy, ibrutinib interrupts several pathways imperative for cellular function in CLL cells...
February 21, 2018: Leukemia & Lymphoma
Susan O'Brien, Richard R Furman, Steven Coutre, Ian W Flinn, Jan A Burger, Kristie Blum, Jeff Sharman, William Wierda, Jeffrey Jones, Weiqiang Zhao, Nyla A Heerema, Amy J Johnson, Ying Luan, Danelle F James, Alvina D Chu, John C Byrd
We previously reported durable responses and manageable safety of ibrutinib from a 3-year follow-up of treatment-naive (TN) older patients (≥65 years) and relapsed/refractory (R/R) patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We now report on long-term efficacy and safety with median follow-up of 5 years in this patient population with TN (N=31) and R/R (N=101) CLL/SLL. With the current 5-year follow-up, ibrutinib continues to yield a high overall response rate of 89%, with complete response rates increasing over time to 29% in TN and 10% in R/R patients...
February 2, 2018: Blood
Gerard M H Swaen, Miranda Langendam, Joost Weyler, Huibert Burger, Sabine Siesling, Willem Jan Atsma, Lex Bouter
OBJECTIVES: to develop a guideline on responsible epidemiologic research practice that will increase value and transparency, will increase the accountability of the epidemiologists and will reduce research waste. SETTING: A working group of the Netherland Epidemiological Society was given the task of developing a guideline that would meet these objectives. Several publications about the need to prevent Detrimental Research Practices triggered this work. Among these were a series in the Lancet on research waste and a subsequent series on transparency in the Journal of Clinical Epidemiology...
February 9, 2018: Journal of Clinical Epidemiology
Guillemette E Benoist, Eric van der Meulen, Inge M van Oort, Jan Hendrik Beumer, Diederik M Somford, Jack A Schalken, David M Burger, Nielka P van Erp
BACKGROUND: Enzalutamide is a potent androgen-signaling receptor inhibitor and is licensed for the treatment of metastatic castration-resistant prostate cancer. N-desmethylenzalutamide is the active metabolite of enzalutamide. A method to quantitate enzalutamide and its active metabolite was developed and validated according to the European Medicine Agency (EMA) guidelines. METHODS: Enzalutamide and N-desmethylenzalutamide were extracted by protein precipitation, separated on a C18 column with gradient elution and analyzed with tandem quadruple mass spectrometry in positive ion mode...
February 5, 2018: Therapeutic Drug Monitoring
Koichi Takahashi, Boyu Hu, Feng Wang, Yuanqing Yan, Ekaterina Kim, Candida Vitale, Keyur P Patel, Paolo Strati, Curtis Gumbs, Latasha Little, Samantha Tippen, Xingzhi Song, Jianhua Zhang, Nitin Jain, Philip Thompson, Guillermo Garcia-Manero, Hagop Kantarjian, Zeev Estrov, Kim-Anh Do, Michael Keating, Jan A Burger, Alessandra Ferrajoli, P Andrew Futreal, William G Wierda
Lenalidomide is clinically active in chronic lymphocytic leukemia (CLL), but its effectiveness in the context of the CLL mutational landscape is unknown. We performed targeted capture sequencing of 295 cancer genes in specimens from 102 CLL patients with treatment-naïve disease (TN patients) and 186 CLL patients with relapsed/refractory disease (R/R patients) who received lenalidomide-based therapy at our institution. The most frequently mutated gene was SF3B1 (15%), followed by NOTCH1 (14%) and TP53 (14%), with R/R patients having significantly more TP53 mutations than TN patients...
January 22, 2018: Blood
Hagop Kantarjian, Farhad Ravandi, Nicholas J Short, Xuelin Huang, Nitin Jain, Koji Sasaki, Naval Daver, Naveen Pemmaraju, Joseph D Khoury, Jeffrey Jorgensen, Yesid Alvarado, Marina Konopleva, Guillermo Garcia-Manero, Tapan Kadia, Musa Yilmaz, Gautam Bortakhur, Jan Burger, Steven Kornblau, William Wierda, Courtney DiNardo, Alessandra Ferrajoli, Jovitta Jacob, Rebecca Garris, Susan O'Brien, Elias Jabbour
BACKGROUND: Inotuzumab ozogamicin, an anti-CD22 monoclonal antibody bound to a toxin, calicheamicin, has shown single-agent activity in relapsed or refractory acute lymphoblastic leukaemia. We aimed to assess the activity and safety of inotuzumab ozogamicin in combination with low-intensity chemotherapy in older patients with acute lymphoblastic leukaemia. METHODS: We did a single-arm, phase 2 study at the MD Anderson Cancer Center (Houston, TX, USA). Eligible patients were aged 60 years or older and had newly diagnosed, Philadelphia chromosome-negative, acute lymphoblastic leukaemia, and an Eastern Cooperative Oncology Group performance status of 3 or lower...
January 15, 2018: Lancet Oncology
Jan A Burger, Adrian Wiestner
B cell receptor (BCR) signalling is crucial for normal B cell development and adaptive immunity. BCR signalling also supports the survival and growth of malignant B cells in patients with B cell leukaemias or lymphomas. The mechanism of BCR pathway activation in these diseases includes continuous BCR stimulation by microbial antigens or autoantigens present in the tissue microenvironment, activating mutations within the BCR complex or downstream signalling components and ligand-independent tonic BCR signalling...
January 19, 2018: Nature Reviews. Cancer
Kristina M Wolf, Emma E Torbert, Dennis Bryant, Martin Burger, R Ford Denison, Israel Herrera, Jan Hopmans, Will Horwath, Stephen Kaffka, Angela Y Y Kong, R F Norris, Johan Six, Thomas P Tomich, Kate M Scow
The Century Experiment at the Russell Ranch Sustainable Agriculture Facility at the University of California, Davis provides long-term agroecological data from row crop systems in California's Central Valley starting in 1993. The Century Experiment was initially designed to study the effects of a gradient of water and nitrogen availability on soil properties and crop performance in ten different cropping systems to measure tradeoffs and synergies between agricultural productivity and sustainability. Currently systems include 11 different cropping systems-consisting of four different crops and a cover crop mixture-and one native grass system...
January 16, 2018: Ecology
Erika Tissino, Dania Benedetti, Sarah E M Herman, Elisa Ten Hacken, Inhye E Ahn, Kari G Chaffee, Francesca Maria Rossi, Michele Dal Bo, Pietro Bulian, Riccardo Bomben, Elisabeth Bayer, Andrea Härzschel, Julia Christine Gutjahr, Massimiliano Postorino, Enrico Santinelli, Ayed Ayed, Francesco Zaja, Annalisa Chiarenza, Gabriele Pozzato, Alexandre Chigaev, Larry A Sklar, Jan A Burger, Alessandra Ferrajoli, Tait D Shanafelt, Adrian Wiestner, Giovanni Del Poeta, Tanja Nicole Hartmann, Valter Gattei, Antonella Zucchetto
The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, which antagonizes B cell receptor (BCR) signals, demonstrates remarkable clinical activity in chronic lymphocytic leukemia (CLL). The lymphocytosis experienced by most patients under ibrutinib has previously been attributed to inhibition of BTK-dependent integrin and chemokine cues operating to retain the tumor cells in nodal compartments. Here, we show that the VLA-4 integrin, as expressed by CD49d-positive CLL, can be inside-out activated upon BCR triggering, thus reinforcing the adhesive capacities of CLL cells...
January 4, 2018: Journal of Experimental Medicine
Dan A Landau, Clare Sun, Daniel Rosebrock, Sarah E M Herman, Joshua Fein, Mariela Sivina, Chingiz Underbayev, Delong Liu, Julia Hoellenriegel, Sarangan Ravichandran, Mohammed Z H Farooqui, Wandi Zhang, Carrie Cibulskis, Asaf Zviran, Donna S Neuberg, Dimitri Livitz, Ivana Bozic, Ignaty Leshchiner, Gad Getz, Jan A Burger, Adrian Wiestner, Catherine J Wu
Treatment of chronic lymphocytic leukemia (CLL) has shifted from chemo-immunotherapy to targeted agents. To define the evolutionary dynamics induced by targeted therapy in CLL, we perform serial exome and transcriptome sequencing for 61 ibrutinib-treated CLLs. Here, we report clonal shifts (change >0.1 in clonal cancer cell fraction, Q < 0.1) in 31% of patients during the first year of therapy, associated with adverse outcome. We also observe transcriptional downregulation of pathways mediating energy metabolism, cell cycle, and B cell receptor signaling...
December 19, 2017: Nature Communications
Ian W Flinn, Susan O'Brien, Brad Kahl, Manish Patel, Yasuhiro Oki, Francine F Foss, Pierluigi Porcu, Jeffrey Jones, Jan A Burger, Nitin Jain, Virginia M Kelly, Kerstin Allen, Mark Douglas, Jennifer Sweeney, Patrick Kelly, Steven Horwitz
Duvelisib is an oral dual inhibitor of phosphoinositide 3-kinase-δ (PI3K-δ) and PI3K-γ in late-stage clinical development for hematologic malignancy treatment. This phase 1 study evaluated maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics (PD), efficacy, and safety of duvelisib in 210 patients with advanced hematologic malignancies. In the dose escalation phase (n = 31), duvelisib 8 to 100 mg twice daily was administered, with MTD determined as 75 mg twice daily. In the expansion phase (n = 179), patients with indolent non-Hodgkin lymphoma (iNHL), chronic lymphocytic leukemia (CLL), or T-cell lymphoma (TCL) were treated with 25 or 75 mg duvelisib twice daily continuously...
February 22, 2018: Blood
Wolfram Eichler, Helena Savković-Cvijić, Susanne Bürger, Mike Beck, Manuela Schmidt, Peter Wiedemann, Andreas Reichenbach, Jan Darius Unterlauft
Background/ Aims: This study was performed to reveal signaling pathways exploited by pigment epithelium-derived factor (PEDF) derived from retinal (glial) Müller cells to protect retinal ganglion cells (RGCs) from cell death. METHODS: The survival of RGCs was determined in the presence of conditioned culture media (MCM) from or in co-cultures with Müller cells. The significance of PEDF-induced STAT3 activation was evaluated in viability assays and using Western blotting analyses and siRNA-transfected cells...
2017: Cellular Physiology and Biochemistry
Steven Coutre, Alessandra Tedeschi, Tadeusz Robak, Paul M Barr, Carolyn Owen, Osnat Bairey, Jan Burger, Cathy Zhou, Lori Styles, Danelle F James, Thomas J Kipps
No abstract text is available yet for this article.
November 23, 2017: Haematologica
Preetesh Jain, Graciela M Nogueras González, Rashmi Kanagal-Shamanna, Uri Rozovski, Nawid Sarwari, Constantine Tam, William G Wierda, Philip A Thompson, Nitin Jain, Rajyalakshmi Luthra, Andres Quesada, Gabriela Sanchez-Petitto, Alessandra Ferrajoli, Jan Burger, Hagop Kantarjian, Jorge Cortes, Susan O'Brien, Michael J Keating, Zeev Estrov
The degree of somatic hypermutation, determined as percent deviation of immunoglobulin heavy chain gene variable region sequence from the germline (IGHV%), is an important prognostic factor in chronic lymphocytic leukaemia (CLL). Currently, a cut-off of 2% deviation or 98% sequence identity to germline in IGHV sequence is routinely used to dichotomize CLL patients into mutated and unmutated groups. Because dissimilar IGHV% cut-offs of 1-5% were identified in different studies, we wondered whether no cut-off should be applied and IGHV% treated as a continuous variable...
January 2018: British Journal of Haematology
Philip A Thompson, Jan A Burger
The BTK inhibitor ibrutinib is effective in both low- and high-risk CLL patients, achieving durable remissions with continuous therapy in the majority of patients. Ibrutinib lacks myelotoxicity and is generally well tolerated by older and unfit patients; however, side effects, such as atrial fibrillation or hemorrhage, can result in treatment interruption or discontinuation. Given the high efficacy and overall safety, ibrutinib is increasingly used in untreated and previously treated CLL patients. Second-generation BTK inhibitors are being developed, with different and generally more BTK-selective kinase inhibition profiles, which may increase the safety and/or efficacy...
November 10, 2017: Expert Opinion on Investigational Drugs
Maciej Jan Dańko, Oskar Burger, Jan Kozłowski
The role of extrinsic mortality in shaping life histories is poorly understood. However, substantial evidence suggests that extrinsic mortality interacts with density-dependence in crucial ways. We develop a model combining Evolutionarily Stable Strategies with a projection matrix that allows resource allocation to growth, tissue repairs, and reproduction. Our model examines three cases, with density-dependence acting on: (i) mortality, (ii) fecundity, and (iii) production rate. We demonstrate that density-independent extrinsic mortality influences the rate of aging, age at maturity, growth rate, and adult size provided that density-dependence acts on fertility or juvenile mortality...
2017: PloS One
Karin Burger, Katarina Ilicic, Martin Dierolf, Benedikt Günther, Dietrich W M Walsh, Ernst Schmid, Elena Eggl, Klaus Achterhold, Bernhard Gleich, Stephanie E Combs, Michael Molls, Thomas E Schmid, Franz Pfeiffer, Jan J Wilkens
X-ray microbeam radiotherapy can potentially widen the therapeutic window due to a geometrical redistribution of the dose. However, high requirements on photon flux, beam collimation, and system stability restrict its application mainly to large-scale, cost-intensive synchrotron facilities. With a unique laser-based Compact Light Source using inverse Compton scattering, we investigated the translation of this promising radiotherapy technique to a machine of future clinical relevance. We performed in vitro colony-forming assays and chromosome aberration tests in normal tissue cells after microbeam irradiation compared to homogeneous irradiation at the same mean dose using 25 keV X-rays...
2017: PloS One
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