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Behiye Ozcan, Sebastian J C M M Neggers, Anne Reifel Miller, Hsiu-Chiung Yang, Virginia Lucaites, Thierry Abribat, Soraya Allas, Martin Huisman, Jenny A Visser, Axel P N Themmen, Eric J G Sijbrands, Patric J D Delhanty and Aart Jan van der Lely Department of Medicine, Erasmus University MC, 3000 CA, Rotterdam, The Netherlands, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA and Alize Pharma, 69 130 Ecully, France

Eli Lilly & Co. cut the ribbon last week on immuno-oncology labs for 40 researchers at the Alexandria Center for Life Science, a two-tower life sciences research facility on the East River in Manhattan. Lilly, the anchor tenant at the Alexandria Center, arrived in 2010 and added a second bank of labs in 2015 focused on immune-system oncology. Jan M. Lundberg, president of Lilly Research Laboratories, said the newest labs are intended to make the company’s research more “efficient and competitive” and to locate it “in an environment in which, just outside our center, are tremendous opportunities to collaborate with leading clinical centers.” The center’s neighbors include Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine.

Neuroscience Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA Departments of Neurology and Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, MO 63110, USA Scios, Inc., Sunnyvale, CA 94086, USA

For the past 25 years, I have devoted most of my research efforts to the application of molecular genetics to yield improvement and production of novel secondary metabolites in actinomycetes. My group at Lilly Research Laboratories worked with a variety of Streptomyces species and with strains of Amycolatopsis and Saccharopolyspora. We developed molecular genetic tools to manipulate actinomycete genes, and applied them to important secondary metabolites, including tylosin, daptomycin, vancomycin, chloroeremomycin, and spinosyns. In the early years, I helped establish recombinant DNA technology to manufacture mammalian proteins, and more recently, helped implement microbial genomics as a research tool for antibiotic discovery. In this paper, I review some highlights, primarily from the actinomycete work. Journal of Industrial Microbiology & Biotechnology (2000) 24, 79–88.

ADepartment of Energy report released in 1987 stated in a visionary prediction that “Knowledge of the human genome is as necessary to the continuing progress of medicine and other health sciences as knowledge of human anatomy has been for the present state of medicine” (Barnhart 1989). The pursuit of this knowledge has marked an era of rapid genomics-based discovery that continues to yield unique insights into connections between disease and molecular factors. One key method for transforming these initial insights into direct evidence of disease pathogenesis is molecular imaging. Imaging techniques that have been customized for laboratory animals provide scientists with the unprecedented ability to link detailed molecular understanding with the complexity of whole organism physiological responses and anatomical detail. The advancement of knowledge derived from the mammalian genome is likely to depend on the context provided by the unique blending of our knowledge of anatomy with the translational application of imaging technology. The primary objective of this ILAR Journal issue focused on laboratory animal imaging is to provide readers with a compendium of reviews that describe the methods, the limitations, and a few examples of the most common applications of small animal imaging to human disease. Because most disease processes are dynamic, there are inherent limitations to using static tissue-based techniques to study dynamic processes. Among these is that a large number of animals is needed for every experiment to enable the processing of tissue at given time points of interest, and histopathological examination of these tissues using standard microscopy is a daunting task. In addition, there is a degree of variability introduced when the control level of a factor is determined by comparing different animals instead of using each animal as its own control. Experimental designs of longitudinal studies pose particular limitations because a certain degree of understanding about the kinetics of a disease process is critical to the appropriate timing of tissue collections. The imaging modalities available for use with laboratory animals provide a means to explore the molecular mechanism of several diseases, minimize many of the limitations of static tissue-based techniques, and, most importantly, decrease the numbers of animals required. In fact, depending on the application, it is possible to reduce the number of animals required per study by as much as 80% to 90%. This feature is noteworthy because, perhaps unique to the ILAR Journal, there is an intentional effort to publish reviews that include considerations specifically relevant to animal care and use. The first article, by Brenda Klaunberg and Judith Davis, presents an overview of key considerations for laboratory animal imaging center design. This review not only is relevant to readers considering new facility design but also can provide a series of quick checks for existing centers as well as strategies for improvement. Contributing authors Isabel Hildebrandt, Helen Su, and Wolfgang Weber then discuss anesthesia for in vivo imaging of small animals in the context of how animal preparation differs among imaging modalities, and how the imaging procedures themselves can affect animal physiology. A general overview of practical considerations in rodent cardiac imaging is provided by Kennita Johnson as a segue to detailed reviews of specific imaging techniques. This article is a good source of baseline information about the particular challenges of cardiac imaging. The contributions of imaging technology to the biomedical sciences are incontrovertible. In fact, one has only to list the number of Nobel prizes awarded to scientists in nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) to appreciate the importance and recognition this field has received. These include the 2003 Nobel Prize for Physiology and Medicine awarded to Paul Lauterbur and Peter Mansfield for the development of MRI. Earlier NMRrelated Nobel Prizes were awarded for Chemistry (Kurt Wuthrich in 2002, Richard R. Ernst in 1991) and Physics (Felix Bloch and Edward M. Purcell in 1952 and Isidor I. Rabi in 1944; http://nobelprize.org). The first manuscript describing the MRI of a rat was published almost 25 years ago, and the technique continues to evolve and expand the scientific advances made possible Myrtle A. Davis, DVM, PhD, is a Research Advisor in Toxicology, Drug Disposition, and Pharmacokinetics at Lilly Research Laboratories in Greenfield, Indiana. Address correspondence and reprint requests to Dr. Myrtle Davis, Toxicology, Drug Disposition, and Pharmacokinetics, Lilly Research Laboratories, 2001 W. Main Street, Greenfield, IN 46140 or email davisma@lilly.com.

a Uni6ersity of California, San Diego, La Jolla, CA, USA b Emory Uni6ersity School of Medicine, 69 Butler Street, S.E., Atlanta, GA 30303, USA c Uni6ersity of California, San Francisco, San Francisco, CA, USA d Uni6ersity of Michigan, Ann Arbor, MI, USA e Royal Brompton Hospital and Imperial College, School of Medicine, London, UK f Uni6ersite Libre de Bruxelles, Brussels, Belgium g Lilly Research Laboratories, Indianapolis, IN, USA

Summary Background The discovery and clinical development of new drugs to treat cancer at Lilly Research Laboratories has undergone significant change during the past 15 years. During the early 1980s drug discovery relied heavily on a panel of syngeneic murine solid tumour models to identify new agents for clinical trial. New classes of oncolytic agents identified by this methodology include the difluoronucleoside antimetabolites, diarylsulfonylureas, and a series of folate-based enzyme inhibitors. Within the folate-based discovery programme at Lilly, a broad understanding of the structure activity relationships of folate antimetabolites and the biochemical basis of folate transport, processing, and enzyme inhibition has enabled a more rational approach for drug discovery. Current studies Folate receptor binding properties are being studied to predict tumour sensitivities and tissue toxicities. This information, together with knowledge of a compound's ability to undergo polyglutamation via the enzyme folylpolyglutamate syn-thase, assist in the more rational selection of agents with designed cellular selectivities. Ultimately, the complex metabolic pathways involving folate metabolism provide numerous targets for enzyme inhibition. Inhibitors of purine biosynthesis and thymidylate synthesis have demonstrated broad activity in preclinical models of disease including several human tumour xenografts, and are undergoing clinical testing. The folate-based drug discovery programme serves as a model for other biochemically based drug discovery programs including those based in drug resistance, signal transduction and cell cycle control.

Cellular in vitro assays have been both developed and employed by us to search for new, solid tumor specific anticancer agents. Parallel in vivo models are then used to assess the therapeutic efficacy of candidates selected by the in vitro assays. During the past 4 years, extracts as well as pure compounds from natural products have been obtained from collaborators at the University of Hawaii and Lilly Research Laboratories. The samples have been analyzed, the structures identified and a number of lead compounds proposed

Synchrotron X-ray sources provide the highest quality crystallographic data for structure-guided drug design. In general, industrial utilization of such sources has been intermittent and occasionally limited. The Lilly Research Laboratories Collaborative Access Team (LRL-CAT) beamline provides a unique alternative to traditional synchrotron use by pharmaceutical and biotechnology companies. Crystallographic experiments at LRL-CAT and the results therefrom are integrated directly into the drug discovery process, permitting structural data, including screening of fragment libraries, to be routinely and rapidly used on a daily basis as part of pharmaceutical lead discovery and optimization. Here we describe how LRL-CAT acquires and disseminates the results from protein crystallography to maximize their impact on the development of new potential medicines.

On June 26, 2011, in San Diego, the Merrifield Award of the American Peptide Society was given to Richard DiMarchi of Indiana University. A day later, again in San Diego, the Outstanding Scientific Achievement Award of the American Diabetes Association was given to Matthias Tschop of the University of Cincinnati. Those attending both lectures might have witnessed many similarities; the Tschop and DiMarchi laboratories had been working as a single integrated unit across two universities for the last seven years, designing and optimizing new therapeutics for the treatment of diabetes and obesity (Figure ​(Figure1). 1). Figure 1 Richard DiMarchi (left) and Matthias Tschop. JCI: How did the two of you start collaborating? Tschop: We met at the Eli Lilly Research Laboratories, where Richard led drug discovery as a group vice president, while I was a postdoctoral fellow. Years later, when I had moved back to the US from Germany and Richard had left Lilly to be a chair of chemistry at Indiana University, we reconnected — our labs suddenly were just a two-hour drive apart. JCI: What avenue of research do you think has the greatest potential to improve the outlook for the obesity epidemic? Tschop: It seems increasingly clear that more than one neuroendocrine signal may have to be modulated at the same time in order to achieve beneficial metabolic effects with curative potential. Richard and I have been working on a series of approaches in which we are combining two or three gastrointestinal hormones into a single molecule. JCI: So are you both optimistic that we’ll find a drug-based cure for metabolic syndrome? DiMarchi: I am a perpetual optimist, supported by three decades of personal experiences. This kind of work requires steady progress made through contributions from many laboratories establishing a foundation for the discovery of transformative medicines. We believe that our work is contributing to the identification of a novel formula that might define a successful prescription for treatment. Tschop: More skeptical colleagues frequently point out to me that evolutionary pressures drove the development of redundant systems to efficiently ingest and store calories. My answer is always that reproduction is a pretty important requirement for the survival of the species too, but endocrinologists figured out how to interrupt it by tricking the brain into believing that there was already an ongoing pregnancy. We need to figure out how to trick the brain into believing that the stomach has been bypassed without actually cutting patients open. JCI: Your work at Lilly and now at Indiana University is largely based on macromolecules and, in particular, peptides — in spite of the limitation that peptide-based drugs almost always require injection. What are the advantages? DiMarchi: In many ways the peptides and proteins that have emerged as drugs are nature’s medicines. They have a high specificity of action with minimal off-target toxicity and natural routes of metabolic clearance. While injection is a limitation, the huge benefit is performance. However, it is important not to frame the question of drug discovery as an either/or option of conventional small molecules versus macromolecules. The combination of the two can deliver unprecedented efficacy with fewer adverse effects. JCI: Given that you moved from pharma to academe, you’re perhaps well positioned to answer the question of whether scientists will be successful in drug discovery outside of the pharmaceutical industry. DiMarchi: Large organizations may be required for cost-efficient drug development and production and marketing of drugs. However, it is individual scientists who deliver breakthrough discoveries. A laboratory composed of broadly trained chemists and pharmacologists can make a huge difference, if properly funded and appropriately nurtured. I am quite certain that Bruce Merrifield, the father of solid-phase chemical synthesis, could not have invented the concept if employed in a less supportive environment than an academic center like The Rockefeller University. JCI: You’re moving back to Germany this year. Will that be a challenge for your collaboration? Tschop: My wife and I are both from Munich, so when the Munich Hemholtz Centre together with the Technical University and the Ludwig Maximilians University Munich invited us to help build a new German Diabetes Center, it turned out to be an offer we couldn’t refuse. With our history of intense collaboration, Richard and I are both confident that the most fun is still ahead of us. And, Richard has a standing invitation for a sabbatical in the Bavarian Alps! JCI: How important have these collaborations been to shaping your science? Tschop: The most important lesson I have learned is that interdisciplinary and translational teamwork is — at least for us — key to every single breakthrough. It was painful at times, since we all speak different languages (literally and figuratively!) — but it always paid off.

Barbara E. Laughon, H. S. Allaudeen,* Jeffrey M. Becker, William L. Current, Judith Feinberg,* Jacob K. Frenkel, Richard Hafner, Walter T. Hughes, Catherine A. Laughlin, Joel D. Meyers, Lewis K. Schrager, and Lowell S. Young Developmental Therapeutics Branch of the Basic Research and Development Program, Medical Branch of the Treatment Research Program, Epidemiology Branch of the Division of AIDS, and Antiviral Research Branch of the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland; Department of Microbiology, University of Tennessee, Knoxville, and Department of Infectious Diseases, St. Jude Children s Research Hospital, Memphis, Tennessee; Lilly Research Laboratories, Indianapolis, Indiana; Department of Pathology, University of Kansas Medical Center, Kansas City; Department of Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, Washington; Kuzell Institute for Arthritis and Infectious Diseases, San Francisco, California

Background: Between 54%-85% of pediatric patients (pts) with ALL can be cured by definitive chemotherapy protocols. HSCT may be considered for high-risk pts after induction therapy or for refractory/relapsed pts. However, HSCT is recognized as a highly specialized, costly and resource intensive procedure requiring ongoing care over months to years. HSCT is associated with significant life-threatening complications with transplant related mortality of 20-30% and acute/chronic graft vs. host disease and infections. The objective of this study was to assess the economic burden up to 5 years of pediatric pts with ALL who received HSCT from the US commercial payers' perspective. Method: Pediatric pts ( Results: A total of 209 pediatric ALL pts were identified. Mean age was 10 years and 43.1% of pts were female. The median follow-up period after the index date was 1.3 years. During the 6 months prior to the index date, pts incurred average total healthcare costs of $287,001. The median duration of the initial hospitalization for the HSCT was 41 days (interquartile range 32-55). Over the five years following the index date, results showed substantial HRU and costs associated with the HSCT. The most intensive HRU and highest healthcare costs were observed within the first year following the index date; pts had an average of 49 days with outpatient (OP) visits, 29 days with OP laboratory services, and 68 inpatient (IP) days corresponding to 3.10 IP admissions (including the hospitalization for the first HSCT) and incurred mean total healthcare costs of $683,099 (median of $511,021) (Figure 1 and 2). Costs associated with the first HSCT hospitalization represented 62.4% of the total costs incurred during the first year. Although a decreasing trend was observed over time, HRU and costs remained high; 28.8% of pts had at least one IP admission at year 2, 19.6% at year 3, 20.0% at year 4, and 6.7% at year 5 (Figure 1). The number of days with OP visits and the number of days with laboratory services also remained high over time (Figure 1). The average total healthcare cost was $104,584 (median of $21,877) at year 2, $79,092 (median of $11,000) at year 3, $106,334 (median of $10,426) at year 4 and, and $38,291 (median of $10,082) at year 5 (Figure 2). Our results also showed high variation in healthcare costs across pediatric pts following the index date; 29.4% of the total costs (over the entire sample) in year 1 were incurred by the 10% pts with the highest costs. Starting from the second year, the 10% of pts with the highest costs accounted for 61.3 to 76.6% of the total costs for each year, suggesting that a small proportion of pts still incur very high costs several years after HSCT. Conclusions: Healthcare resource utilization and direct costs associated with allogeneic HSCT are substantial with the first year direct cost alone of $683,099 with substantial costs over the following years. Further studies are needed to understand the humanistic and financial burden of HSCT for pediatric pts and their caregivers. Figure 1. HRU after Index Date Figure 1. HRU after Index Date Figure 2. Total Healthcare Costs after Index Date Figure 2. Total Healthcare Costs after Index Date Disclosures Maziarz: Athersys: Consultancy, Patents & Royalties, Research Funding; Novartis: Consultancy. Guerin:GlaxoSmithKline, Janssen Scientific Affairs, Janssen-Ortho, Inc., Merck & Co., Inc., Merck Frosst Canada, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ogilvy Renault, Ortho-Clinical Diagnostics, Inc., Otsuka America Pharmaceutical, Inc.,: Consultancy, Other: Annie Guerin is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; Pfizer Canada, Inc., RX&D, Sanofi, Savient Pharmaceuticals, Inc., Shire Pharmaceuticals Inc., Sunovion Pharmaceuticals Inc., Takeda Global Research & Development Center, Inc., Takeda Pharmaceuticals U.S.A., Inc.: Consultancy, Other: Annie Guerin is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; AbbVie Inc., Alcon Laboratories, Bayer Healthcare Pharmaceuticals, LLC, Celgene Corporation, Cempra Inc., Centocor Ortho Biotech, Cooley LLP, Cyberonics, Inc., DLA Piper, Eli Lilly & Company,Forest Laboratories, Inc., Genentech, Inc.,: Consultancy, Other: Annie Guerin is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations. Gauthier:AbbVie Inc., Celgene Corporation, Eli Lilly & Company, Genentech, Inc. ,GlaxoSmithKline, Janssen Scientific Affairs, LLC, Novartis Pharmaceuticals Corporation, Pfizer Canada, Inc., Sanofi, Savient Pharmaceuticals, Inc., Shire Pharmaceuticals Inc.,: Consultancy, Other: Genevieve Gauthier is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; Sunovion Pharmaceuticals Inc.,Takeda Pharmaceuticals U.S.A., Inc.: Consultancy, Other: Genevieve Gauthier is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations. Heroux:AbbVie Inc., Alcon Laboratories, Celgene Corporation, Genentech, Inc., Merck Frosst Canada, Novartis Pharmaceuticals Corporation, Shire Pharmaceuticals Inc., Sunovion Pharmaceuticals Inc., Takeda Pharmaceuticals U.S.A., Inc.: Consultancy, Other: Julie Heroux is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations. Zhdanava:AbbVie Inc., Genentech, Inc., Merck Frosst Canada, Novartis Pharmaceuticals Corporation,Shire Pharmaceuticals Inc., Takeda Pharmaceuticals U.S.A., Inc.: Consultancy, Other: Maryia Zhdanava is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations. Wu:Molecular Insight Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Ortho McNeil Pharmaceuticals, Inc., Sanofi, Savient Pharmaceuticals, Inc., Shire Pharmaceuticals Inc.,: Consultancy, Other: Eric Q Wu is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; Takeda Global Research & Development Center, Inc., Takeda Pharmaceuticals U.S.A., Inc., TAP Pharmaceutical Products, Inc., Vertex Pharmaceuticals Incorporated: Consultancy, Other: Eric Q Wu is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; Janssen Pharmaceutica, Inc., Janssen Scientific Affairs, LLC, Lilly Research Laboratories, McNeil Consumer & Specialty Pharmaceuticals, MedImmune, LLC, Melinta Therapeutics, Inc., Millennium Pharmaceuticals, Inc.,: Consultancy, Other: Eric Q Wu is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; Celgene Corporation, Centocor Ortho Biotech, Cephalon, Inc., ConvaTec Inc., Corus Pharma, Inc., Eli Lilly & Company, Eli Lilly & Company, Ethicon, Inc., Forest Laboratories, Inc., Genentech, Inc., GlaxoSmithKline, Janssen Global Services, LLC,: Consultancy, Other: Eric Q Wu is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; AbbVie Inc., Alcon Laboratory, Astellas Pharma Inc., Astellas Pharma US, Inc., AstraZeneca, Barger & Wolen LLP, Bayer Healthcare Pharmaceuticals, LLC, Biosense Webster, Inc., Blue Cross Blue Shield Association, Boehringer Ingelheim, Bristol-Myers Squibb C: Consultancy, Other: Eric Q Wu is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations. Thomas:Novartis: Employment. Chen:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership, Other: Lei Chen is an employee of and owns stocks/options of Novartis Pharmaceuticals Corporation, the sponsor of this study.

Because the increased prescriptions of antidepressants are correlated to increased medical visits, it is tempting to conclude, as Hockey did [1], that decreased suicides are a function of greater recognition of depression. It should be noted that the biggest cause of suicide is clinical major depression and increased visits do not treat that; antidepressants do. In a comprehensive review of the literature on the role of long-term antidepressant use to prevent relapse of major depression, Geddes et al. [2] reported that “data were pooled from 31 randomised trials (4410 participants). Continuing treatment with antidepressants reduced the odds of relapse by 70% (95% CI 62–78; 2p

LY333328 is a novel glycopeptide from Lilly Research Laboratories which is claimed to have activity both in vitro and in vivo against vancomycin-resistant enterococci. Information on this compound has been published at three recent meetings, the 7th European Congress of Clinical Microbiology and Infectious Diseases (March 26 - 30, Vienna, Austria); On the Frontier of Antibacterial Drug Discovery (April 27 - 28, Princeton, USA); and the 19th International Chemotherapy Congress (July 16 - 21, Montreal, Canada). This update draws together the published data and attempts to assess the potential therapeutic use of this interesting new compound.

With the intention of bringing together leading academic researchers, industry scientists, business development experts and scientific policy makers, the Society for Medicines Research (SMR) hosted a highly engaging and thought-provoking meeting entitled "Partnerships: Future Models for Drug Discovery" at the Lilly Research Centre in Windlesham, Surrey. With the challenges to discover and develop innovative and differentiated new medicines having never been greater and with many questions arising around the viability of current pharmaceutical business models, this meeting offered the opportunity to explore potential new ways to bring innovation and productivity to the drug discovery sector. Through a series of presentations from leading figures from across the public and private sector, the conference aimed to explore novel business models for research and development and to discuss on the changing dynamics around the interactions between traditional models for academia, industry and funders. Copyright © 2013 Prous Science, S.A.U. or its licensors. All rights reserved.

Jean Ferrieres [Orateur] (1), Guy Berkenboom (2), Zdenek Coufal (3), Stefan James (4), Attila MohaCsi (5), Gregory Pavlides (6), Kirsi Norrbacka (7), Magali Sartral (8), Marie-Ange Paget (8), Molly Tomlin (9), Uwe Zeymer (10) (1) CHU Rangueil, Cardiologie B, Toulouse, France – (2) ULB Erasme University Hospital, Department of Cardiology, Brussels, Belgium – (3) Batova Krajska Nemocnice Zlin, Department of Cardiology, Zlin, Republique Tcheque – (4) Uppsala University Hospital, Dept. of Cardiology and Uppsala Clinical Research Center, Uppsala, Suede – (5) Gottsegen Institute of Hungarian Cardiology, Budapest, Hungaria – (6) Onassis Cardiac Surgery Center, Kallithea, Grece – (7) Lilly Research Laboratories, Eli Lilly and Company, Vantaa, Finlande – (8) Lilly Research Laboratories, Eli Lilly and Company, Paris, France – (9) Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, United-States – (10) Klinikum Ludwigshafen, Ludwigshafen, Allemagne

Atomoxetine (originally named tomoxetine), a new therapy for attention deficit hyperactivity disorder (ADHD) marketed by Eli Lilly, was compared to methylphenidate in a prospective, randomized, open-label study for 10 weeks duration, at the University of Nebraska Medical Center, Massachusetts General Hospital, Mount Sinai Medical Center, Carolinas Medical Center, and Lilly Research Laboratories.

G. Umpierrez, T. Blevins, J. Rosenstock, C. Cheng, E. Bastyr, J. Anderson 1 Emory University School of Medicine, Division of Endocrinology, Atlanta, USA 2 Texas Diabetes and Endocrinology, , Austin, USA 3 Dallas Diabetes and Endocrinology Center, , Dallas, USA 4 Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, USA 5 Eli lilly and Company, Lilly Research Laboratories, Indianapolis, USA

Hyung Ki Choi, Je Jong Kim, Sae-Chul Kim, JunKyu Suh, Yoon Kyu Park, Seong Choi, Woong Hee Lee, Ki Hak Moon, Hae Young Park, Jong Kwan Park, Wei Christine Wang, Vladimir Kopernicky From the Department of Urology, Yongdong Severance Hospital, Seoul, Korea University Ansan Hospital, Ansan, Chungang University Hospital, Seoul, Inha University Hospital, Incheon, Kyungpook University Hospital, Daegu, Kosin University Hospital, Busan, Dong Seoul Hospital, Seoul, Yeungnam University Hospital, Daegu, Hanyang University Hospital, Seoul, Chonbuk National University Hospital, Jeonju, Korea, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA, Lilly Area Medical Center, Vienna, Austria