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3. A high-throughput viral integration sequencing method reveals that mitochondrial DNA is frequently targeted by HBV integration

Author

Giosa, Domenico, primary, Lombardo, Daniele, additional, Musolino, Cristina, additional, Chines, Valeria, additional, Raffa, Giuseppina, additional, D’aliberti, Deborah, additional, di Tocco, Francesca Casuscelli, additional, Saitta, Carlo, additional, Cigliano, Riccardo Aiese, additional, Romeo, Orazio, additional, Alibrandi, Angela, additional, Navarra, Giuseppe, additional, Raimondo, Giovanni, additional, and Pollicino, Teresa, additional

Published
2022
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4. A new high-throughput HBV integration sequencing approach shows that mitochondrial DNA is frequently targeted by virus integration in liver cells with active HBV replication

Author

Giosa, D., primary, Lombardo, D., additional, Musolino, C., additional, Chines, V., additional, Raffa, G., additional, Casuscelli di Tocco, F., additional, D'Aliberti, D., additional, Saitta, C., additional, Alibrandi, A., additional, Aiese Cigliano, R., additional, Romeo, O., additional, Navarra, G., additional, Raimondo, G., additional, and Pollicino, T., additional

Published
2022
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8. Romosozumab improves lumbar spine BMD and bone strength greater than alendronate as assessed by quantitative computed tomography and finite element analysis in the ARCH trial

Author

Brown, Jacques P., primary, Chines, Arkadi, additional, Chapurlat, Roland, additional, Foldes, Joseph, additional, Nogues, Xavier, additional, Civitelli, Roberto, additional, De Villiers, Tobias, additional, Massari, Fabio, additional, Zerbini, Cristiano, additional, Yang, Wenjing, additional, Recknor, Chris, additional, and Libanati, Cesar, additional

Published
2020
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12. The role of glutamine in Pseudomonas mediterranea in biotechnological processes

Author

Rizzo, Maria Giovanna, Chines, Valeria, Franco, Domenico, Nicolò, Marco S., and Guglielmino, Salvatore

Subjects
0301 basic medicine, Pseudomonas mediterranea, Glutamine, Cell, Bioengineering, Polyhydroxyalkanoates, 03 medical and health sciences, chemistry.chemical_compound, Bioreactors, Pseudomonas, Glycerol, Bioreactor, medicine, MTT assay, Biotechnology, Molecular Biology, biology, Gene Expression Regulation, Bacterial, General Medicine, biology.organism_classification, Carbon, Kinetics, 030104 developmental biology, medicine.anatomical_structure, chemistry, Biochemistry, Batch Cell Culture Techniques, Genes, Bacterial
Abstract

In this work, in order to study the effect of glutamine as co-feeder on growth kinetics, biomass and PHA production in Pseudomonas mediterranea, different co-metabolic strategies were employed. Unrelated (glycerol and glucose) and related (sodium octanoate) carbon sources both in presence and absence of glutamine have been tested. For each cultural condition, we (i) evaluated growth kinetics and measured the cell metabolic activity by MTT assay, (ii) monitored PHA production and (iii) estimated the expression of phaC1 and phaC2 genes through RT-PCR. Our results show that the use of glutamine as co-feeder in P. mediterranea led to an improvement of the specific growth rate and cell metabolic activity and enhanced the uptake of all the carbon sources assayed. Moreover, the use of glutamine reduced significantly the time required for PHA production and increased biopolymer yield, as consequence of an early activation of phaC1 and phaC2.

Published
2017
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13. Frequency of TP53, CTNNB1, and TERT promoter mutations in patients with hepatocellular carcinoma

Author

Daniele Lombardo, Giuseppe Navarra, Giuseppe Caminiti, Domenico Giosa, C. Musolino, Carlo Saitta, G. Raimondo, Teresa Pollicino, F. Casuscelli di Tocco, Valeria Chines, and Maria Stella Franzè

Subjects
Hepatology, business.industry, Hepatocellular carcinoma, Gastroenterology, medicine, Cancer research, In patient, medicine.disease, business, Tert promoter
Published
2020
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14. Romosozumab improves lumbar spine BMD and bone strength greater than alendronate as assessed by quantitative computed tomography and finite element analysis in the ARCH trial

Author

Jacques P. Brown, Tobias De Villiers, Fabio E Massari, Roland Chapurlat, Cesar Libanati, Cristiano A. F. Zerbini, Xavier Nogués, Chris Recknor, Roberto Civitelli, Joseph Foldes, Arkadi Chines, and Wenjing Yang

Subjects
Orthodontics, lcsh:Diseases of the musculoskeletal system, medicine.diagnostic_test, business.industry, Endocrinology, Diabetes and Metabolism, Romosozumab, Finite element method, Bone strength, Medicine, Orthopedics and Sports Medicine, Lumbar spine, lcsh:RC925-935, Quantitative computed tomography, Arch, business
Published
2020
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15. Denosumab in postmenopausal women with osteoporosis and diabetes: Subgroup analysis of FREEDOM and FREEDOM extension

Author

Nicola Napoli, Ann V. Schwartz, Lorenz C. Hofbauer, Arkadi Chines, Steven R. Cummings, Richard Eastell, Nico Pannacciulli, Serge Ferrari, and Andrea Wang

Subjects
0301 basic medicine, medicine.medical_specialty, Histology, Physiology, Endocrinology, Diabetes and Metabolism, Osteoporosis, Population, 030209 endocrinology & metabolism, Subgroup analysis, Diseases and disorders of/related to bone, Placebo, 03 medical and health sciences, Clinical trials, 0302 clinical medicine, Bone Density, Diabetes mellitus, Internal medicine, Post-hoc analysis, Diabetes Mellitus, medicine, Humans, education, Osteoporosis, Postmenopausal, Aged, ddc:616, education.field_of_study, Bone Density Conservation Agents, business.industry, Incidence (epidemiology), Therapeutics antiresorptive, medicine.disease, 3. Good health, Postmenopause, 030104 developmental biology, Denosumab, Female, business, medicine.drug
Abstract

Purpose Diabetes and osteoporosis occur frequently in older adults and are both associated with increased fracture risk. Denosumab treatment reduced new vertebral, nonvertebral, and hip fractures over 3 years, with continued low fracture incidence for up to 10 years in postmenopausal women with osteoporosis. However, its effects in diabetic subjects with osteoporosis have not yet been investigated. Methods Post hoc analysis of the 3-year, placebo-controlled FREEDOM study and 7-year Extension included postmenopausal women with osteoporosis and diabetes. Effects on BMD, vertebral, and nonvertebral fracture incidence were evaluated. Results Of 7808 subjects in FREEDOM, 508 with diabetes received denosumab (n = 266) or placebo (n = 242). Among those, BMD increased significantly with denosumab versus placebo in FREEDOM, and continued to increase during the Extension in long-term (continuing denosumab) and crossover (placebo to denosumab) denosumab subjects. In FREEDOM, denosumab-treated subjects with diabetes had significantly lower new vertebral fracture rates (1.6%) versus placebo (8.0%) (RR: 0.20 [95% CI 0.07–0.61]; p = .001). Nonvertebral fracture incidence was higher with denosumab (11.7%) versus placebo (5.9%) (HR: 1.94 [95% CI 1.00–3.77]; p = .046), although there were fewer hip fractures with denosumab (World Health Organization, 2017 [ 1 ]) than placebo (4; nonsignificant). During the first 3 years in FREEDOM Extension, new vertebral and nonvertebral fracture incidences were low in long-term and crossover denosumab diabetic groups (≤6%), consistent with the overall Extension population; yearly nonvertebral fracture incidence was comparable to the FREEDOM placebo group. Conclusion Denosumab significantly increased BMD and decreased vertebral fracture risk in subjects with osteoporosis and diabetes. No reduction in nonvertebral fractures was observed.

Published
2020
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16. Reaction development for DNA-encoded library technology: From evolution to revolution?

Author

Silvia Chines, Katharina Götte, and Andreas Brunschweiger

Subjects
010405 organic chemistry, Chemistry, Emerging technologies, Synthesis methods, Organic Chemistry, Drug Discovery, Nanotechnology, 010402 general chemistry, 01 natural sciences, Biochemistry, Toolbox, First generation, 0104 chemical sciences
Abstract

DNA-encoded libraries of organic, synthesized molecules are an emerging technology for target-based compound screening. The design of first generation encoded libraries placed emphasis on ever increasing compound numbers that were synthesized from large sets of starting materials with a few well-established synthesis methods. In the last two years there has literally been an explosion of published research activities that have expanded the toolbox of reactions for designing DNA-encoded libraries. In this digest, we highlight latest developments that include modern photoredox chemistries as well as strategies to perform encoded compound synthesis in organic solvents or exploit nano-heterogeneous systems. The new chemistry developments carry the potential to revolutionize the technology as they enable access to unprecedented molecular diversity.

Published
2020
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17. Multiomic Profiling Identifies cis-Regulatory Networks Underlying Human Pancreatic β Cell Identity and Function

Author

Lawlor, Nathan, primary, Márquez, Eladio J., additional, Orchard, Peter, additional, Narisu, Narisu, additional, Shamim, Muhammad Saad, additional, Thibodeau, Asa, additional, Varshney, Arushi, additional, Kursawe, Romy, additional, Erdos, Michael R., additional, Kanke, Matt, additional, Gu, Huiya, additional, Pak, Evgenia, additional, Dutra, Amalia, additional, Russell, Sheikh, additional, Li, Xingwang, additional, Piecuch, Emaly, additional, Luo, Oscar, additional, Chines, Peter S., additional, Fuchbserger, Christian, additional, Sethupathy, Praveen, additional, Aiden, Aviva Presser, additional, Ruan, Yijun, additional, Aiden, Erez Lieberman, additional, Collins, Francis S., additional, Ucar, Duygu, additional, Parker, Stephen C.J., additional, and Stitzel, Michael L., additional

Published
2019
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18. The effects of bazedoxifene on bone structural strength evaluated by hip structure analysis

Author

Kenneth W. Gaither, Thomas Fuerst, Robert D. Williams, Thomas J. Beck, Santosh Sutradhar, Teresa Hines, Ching Ray Yu, Arkadi Chines, Sebastian Mirkin, and Amy B. Levine

Subjects
medicine.medical_specialty, Indoles, Histology, Physiology, Endocrinology, Diabetes and Metabolism, Osteoporosis, Urology, Subgroup analysis, Placebo, Bone and Bones, Bazedoxifene, Cohort Studies, Placebos, Absorptiometry, Photon, Bone Density, medicine, Humans, Osteoporosis, Postmenopausal, Dual-energy X-ray absorptiometry, Aged, Femoral neck, Bone Density Conservation Agents, medicine.diagnostic_test, business.industry, Section modulus, Middle Aged, medicine.disease, Surgery, medicine.anatomical_structure, Hip bone, Female, business, medicine.drug
Abstract

Bazedoxifene (BZA) is a selective estrogen receptor modulator that has been shown to prevent and treat postmenopausal osteoporosis. Hip structure analysis (HSA) can be used to extract bone structural properties related to strength from hip bone mineral density (BMD) scans. This exploratory analysis used HSA to evaluate changes in hip structural geometry in postmenopausal women enrolled in a phase 3 osteoporosis treatment study who were treated with BZA 20mg or placebo for 2 years. This analysis cohort included women at increased fracture risk based on known skeletal risk factors (n = 521); 1 or more moderate or severe fractures or 2 or more mild vertebral fractures and/or femoral neck BMD T-score ≤ -3.0 at baseline combined with additional women from the overall study population (n = 475); a subgroup analysis included just those women at increased fracture risk. HSA was applied to duplicate hip dual-energy X-ray absorptiometry (DXA) scans acquired at screening and 24 months. Percent change from baseline was evaluated using an analysis of covariance for BMD and geometric parameters including section modulus (SM), cross-sectional area (CSA), outer diameter (OD), and buckling ratio (BR). In all regions, BZA was associated with increased BMD and improvements in hip structural geometry. In the narrow neck, BZA 20mg significantly increased SM, CSA, OD, and BMD compared with placebo (P < 0.05 for all). In the intertrochanter region, BZA 20mg significantly increased CSA and BMD and decreased BR compared with placebo (P < 0.05 for all). Other than BMD (P < 0.05), effects of BZA 20mg at the shaft did not reach statistical significance. Similar trends toward improvement in structural geometry with BZA 20mg were observed in all three regions of the hip for the subgroup of women at increased fracture risk. Overall, BZA was associated with geometry-related improvements in bone strength with regard to resistance to bending and compressive forces and to local buckling. These improvements were evident at common fracture locations such as the femoral neck and intertrochanter regions, and are consistent with the significant treatment effect reported for BZA on nonvertebral fractures in higher-risk postmenopausal women with osteoporosis.

Published
2015
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19. Bazedoxifene versus Oral Bisphosphonates for the Prevention of Nonvertebral Fractures in Postmenopausal Women with Osteoporosis at Higher Risk of Fracture: A Network Meta-Analysis

Author

Arkadi Chines, Xuemei Luo, Santosh Sutradhar, Jeroen P. Jansen, Jean-Yves Reginster, Joseph C. Cappelleri, and Alexandra G Ellis

Subjects
medicine.medical_specialty, FRAX, Indoles, treatment comparisons, Osteoporosis, Postmenopausal osteoporosis, Article, Bazedoxifene, law.invention, Fractures, Bone, Randomized controlled trial, systematic review, law, Internal medicine, medicine, Humans, Osteoporosis, Postmenopausal, Postmenopausal women, Oral bisphosphonates, Bone Density Conservation Agents, Diphosphonates, business.industry, Health Policy, Public Health, Environmental and Occupational Health, medicine.disease, osteoporosis, meta-analysis, Meta-analysis, Physical therapy, Female, business, medicine.drug
Abstract

ObjectiveTo compare the efficacy of bazedoxifene and oral bisphosphonates for the prevention of nonvertebral fractures (NVFs) in women with higher risk of postmenopausal osteoporosis (i.e., the Fracture Risk Assessment Tool [FRAX] score ≥ 20%), based on currently available evidence from randomized controlled trials.MethodsRandomized controlled trials evaluating the NVF relative risk reduction (RRR) with oral bisphosphonates or bazedoxifene were identified by a systematic literature review and combined by means of a network meta-analysis. A subgroup of patients with a FRAX score of 20% or more in the bazedoxifene phase III osteoporosis study was selected as the population of interest on the basis of the bazedoxifene label. In one analysis (analysis 1), the placebo response of the subgroup with a FRAX score of 20% or more was the benchmark to select comparable bisphosphonate trials. Additional analyses incorporated the aggregate data from the bisphosphonate trials with all the FRAX subgroups (analysis 2) or with the individual patient data from the bazedoxifene trial (analysis 3).ResultsNine identified bisphosphonate trials (alendronate, ibandronate, risedronate; N = 23,440 patients) with a similar placebo response as observed for the subgroup of high risk patients in the bazedoxifene trial were included in analysis 1. The results of the network meta-analysis of this study set suggest that bazedoxifene is expected to have an RRR of 0.43 (95% credible interval [CrI] −0.19 to 0.72) versus alendronate, 0.58 (95% CrI 0.05–0.81) versus ibandronate, and 0.39 (95% CrI −0.29 to 0.70) versus risedronate. Analyses in which treatment effects with bisphosphonates were projected to a population with a FRAX score of 20% or more with meta-regression approaches (analysis 2 and analysis 3) provide similar findings.ConclusionBased on an indirect comparison of randomized trials, bazedoxifene is expected to have at least a comparable RRR of NVF as alendronate, ibandronate, and risedronate in women with higher risk of postmenopausal osteoporosis.

Published
2014
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20. Multiomic Profiling Identifies cis-Regulatory Networks Underlying Human Pancreatic β Cell Identity and Function

Author

Stephen C. J. Parker, Asa Thibodeau, Praveen Sethupathy, Evgenia Pak, Erez Lieberman Aiden, Oscar Junhong Luo, Emaly Piecuch, Muhammad S. Shamim, Michael R. Erdos, Eladio J. Márquez, Matt Kanke, Narisu Narisu, Christian Fuchbserger, Duygu Ucar, Yijun Ruan, Peter Orchard, Xingwang Li, Sheikh Russell, Amalia Dutra, Romy Kursawe, Aviva Presser Aiden, Peter S. Chines, Nathan Lawlor, Francis S. Collins, Michael L. Stitzel, Arushi Varshney, and Huiya Gu

Subjects
0301 basic medicine, Cell, Computational biology, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Cell Line, 3. Good health, Chromatin, Transcriptome, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Insulin-Secreting Cells, medicine, ISL1, Humans, PDX1, Gene Regulatory Networks, Allele, Genotyping, 030217 neurology & neurosurgery, Epigenomics
Abstract

SUMMARY EndoC-βH1 is emerging as a critical human β cell model to study the genetic and environmental etiologies of β cell (dys)function and diabetes. Comprehensive knowledge of its molecular landscape is lacking, yet required, for effective use of this model. Here, we report chromosomal (spectral karyotyping), genetic (genotyping), epigenomic (ChIP-seq and ATAC-seq), chromatin interaction (Hi-C and Pol2 ChIA-PET), and transcriptomic (RNA-seq and miRNA-seq) maps of EndoC-βH1. Analyses of these maps define known (e.g., PDX1 and ISL1) and putative (e.g., PCSK1 and mir-375) β cell-specific transcriptional cis-regulatory networks and identify allelic effects on cis-regulatory element use. Importantly, comparison with maps generated in primary human islets and/or β cells indicates preservation of chromatin looping but also highlights chromosomal aberrations and fetal genomic signatures in EndoC-βH1. Together, these maps, and a web application we created for their exploration, provide important tools for the design of experiments to probe and manipulate the genetic programs governing β cell identity and (dys)function in diabetes., In Brief EndoC-βH1 is becoming an important cellular model to study genes and pathways governing human β cell identity and function, but its (epi)genomic similarity to primary human islets is unknown. Lawlor et al. complete and compare extensive EndoC and primary human islet multiomic maps to identify shared and distinct genomic circuitry., Graphical Abstract

Published
2019
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21. Global Epigenomic Analysis of Primary Human Pancreatic Islets Provides Insights into Type 2 Diabetes Susceptibility Loci

Author

Terrence S. Furey, Stephen C. J. Parker, Praveen Sethupathy, Michael Boehnke, Ryan P. Welch, Daniel S. Pearson, Elliott H. Margulies, Francis S. Collins, Gregory E. Crawford, Peter S. Chines, Lingyun Song, Michael L. Stitzel, Alan P. Boyle, Laura J. Scott, and Michael R. Erdos

Subjects
Epigenomics, CCCTC-Binding Factor, endocrine system, endocrine system diseases, Physiology, Biology, Regulatory Sequences, Nucleic Acid, Methylation, Article, Histones, 03 medical and health sciences, Histone H3, Islets of Langerhans, 0302 clinical medicine, medicine, Deoxyribonuclease I, Humans, Enhancer, Promoter Regions, Genetic, Gene, Molecular Biology, 030304 developmental biology, Genetics, 0303 health sciences, Pancreatic islets, Lysine, Epigenome, Cell Biology, Repressor Proteins, medicine.anatomical_structure, Diabetes Mellitus, Type 2, CTCF, Regulatory sequence, Genetic Loci, 030217 neurology & neurosurgery, Genome-Wide Association Study, HeLa Cells
Abstract

SummaryIdentifying cis-regulatory elements is important to understanding how human pancreatic islets modulate gene expression in physiologic or pathophysiologic (e.g., diabetic) conditions. We conducted genome-wide analysis of DNase I hypersensitive sites, histone H3 lysine methylation modifications (K4me1, K4me3, K79me2), and CCCTC factor (CTCF) binding in human islets. This identified ∼18,000 putative promoters (several hundred unannotated and islet-active). Surprisingly, active promoter modifications were absent at genes encoding islet-specific hormones, suggesting a distinct regulatory mechanism. Of 34,039 distal (nonpromoter) regulatory elements, 47% are islet unique and 22% are CTCF bound. In the 18 type 2 diabetes (T2D)-associated loci, we identified 118 putative regulatory elements and confirmed enhancer activity for 12 of 33 tested. Among six regulatory elements harboring T2D-associated variants, two exhibit significant allele-specific differences in activity. These findings present a global snapshot of the human islet epigenome and should provide functional context for noncoding variants emerging from genetic studies of T2D and other islet disorders.

Published
2010
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22. Status and perspectives of the EXCYT facility at INFN-LNS

Author

M. Re, Alfio Pappalardo, Paolo Finocchiaro, F. Chines, Alberto Rovelli, Luigi Celona, Luciano Calabretta, Giacomo Cuttone, Danilo Rifuggiato, and Luigi Cosentino

Subjects
Nuclear physics, Radioactive ion beams, Nuclear and High Energy Physics, Superconducting cyclotron, Low energy, Tandem, law, Chemistry, Cyclotron, Instrumentation, Beam (structure), Ion, law.invention
Abstract

The aim of the EXCYT (EXotics with CYclotron and Tandem) facility is the production and acceleration of radioactive ion beams (RIBs). A primary beam provided by the K-800 superconducting cyclotron will produce, in a target-ion source complex (TIS), the required nuclear species which can be used for low energy experiments (up to 300 keV) or at higher energy by post-accelerating them with the 15 MV tandem. The nuclear experiments programme started in July 2006 with the experiments BIGBANG and RCS using the post-accelerated 8Li ions. Since then 8Li, 9Li and 21Na beams have been already produced and in the near future production of oxygen, fluorine and chlorine beams have been planned, according to the experimental proposals, with beam intensities ranging between 104 to 106 pps and at the typical energies of our tandem.

Published
2008
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23. Genetic Regulation of Adipose Gene Expression and Cardio-Metabolic Traits

Author

Civelek, Mete, primary, Wu, Ying, additional, Pan, Calvin, additional, Raulerson, Chelsea K., additional, Ko, Arthur, additional, He, Aiqing, additional, Tilford, Charles, additional, Saleem, Niyas K., additional, Stančáková, Alena, additional, Scott, Laura J., additional, Fuchsberger, Christian, additional, Stringham, Heather M., additional, Jackson, Anne U., additional, Narisu, Narisu, additional, Chines, Peter S., additional, Small, Kerrin S., additional, Kuusisto, Johanna, additional, Parks, Brian W., additional, Pajukanta, Päivi, additional, Kirchgessner, Todd, additional, Collins, Francis S., additional, Gargalovic, Peter S., additional, Boehnke, Michael, additional, Laakso, Markku, additional, Mohlke, Karen L., additional, and Lusis, Aldons J., additional

Published
2017
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24. EXCYT: The RIB project at INFN-LNS

Author

S. Passarello, Giacomo Cuttone, A. Amato, D. Rizzo, Danilo Rifuggiato, G. Cosentino, Alfio Pappalardo, Luciano Calabretta, Luigi Celona, G. De Luca, Valentina Scuderi, A. Rovelli, F. Chines, F. Tudisco, Marianna Lo Re, and E. Messina

Subjects
Nuclear and High Energy Physics, Tandem, Ion beam, chemistry.chemical_element, Tungsten, Ion, Nuclear physics, Ion beam deposition, chemistry, Isotopic shift, Ionization, Atomic physics, Instrumentation, Beam (structure)
Abstract

The EXCYT facility at the INFN-LNS is based on a K-800 superconducting cyclotron, as a driver for stable heavy ion beams (up to 80 MeV/amu, 1 pμA), and on a 15 MV tandem for post-accelerating the radioactive ion beams produced in a target-ion source (TIS) assembly. For some ion beam such as for Li, the higher extraction efficiency from the TIS is obtained by positive ionisation. Then the injection into the tandem is suitable only after a charge exchange (CEC) to obtain negative ions. The production of the radioactive ions were performed by injecting a 13C4+ primary beam of 45 MeV/amu on a graphite target up to a beam power of 150 W, while the ionisation was achieved by a tungsten positive surface ioniser. The Li+ has been produced at different energies to cross-check the transmission efficiency together with the charge exchange efficiency. The CEC consists of a cell containing Cs vapours which interact with the Li beam converting its charge from +1 to –1 by a two-step reaction; it was already characterized off-line and the results obtained at the EXCYT facility confirm our previous observations and expectations such as the efficiency at the extraction energies and the isotopic shift effect. Hereinafter the results of 8,9Li beams production are reported together with a brief presentation of the facility and with some future improvements and plan.

Published
2007
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25. The Finland–United States Investigation of Non–Insulin-Dependent Diabetes Mellitus Genetics (FUSION) Study. I. An Autosomal Genome Scan for Genes That Predispose to Type 2 Diabetes

Author

Alyson Witt, Ethan M. Lange, David Rha, William Hagopian, Edna H. Ross, James E. Balow, Catherine Te, Richard M. Watanabe, Heather M. Stringham, Francis S. Collins, Richard C. McEachin, Zarir E. Karanjawala, Elizabeth R. Hauser, William L. Duren, Michael Boehnke, Thomas A. Buchanan, Timo T. Valle, Tasha E. Fingerlin, Richard N. Bergman, Jillian Blaschak-Harvan, Chun Li, Liisa Toivanen, Julie I. Knapp, Victoria L. Magnuson, Gabriele Vidgren, Leonid Segal, Delphine S. Ally, Anjene Musick, Jennie Chang, Stella J. Nylund, Arun M. Unni, Shane A. Shapiro, Peggy P. White, Karen L. Mohlke, Michael P. Epstein, Elza Demirchyan, Ben Shurtleff, Kristina Kudelko, Jaakko Tuomilehto, Joseph B. Rayman, Michael R. Erdos, Hong Shi Kaleta, Eva Tuomilehto-Wolf, Christian Welch, Carl D. Langefeld, Julie A. Douglas, Tiffany Musick, Joyce Tannenbaum, Carrie Pfahl, Ravi Sharaf, Kimmo Kohtamäki, Alistair So, Colin Martin, Jason Tovar, Soumitra Ghosh, Rachel Porter, Peter S. Chines, Edward H. Trager, Johan G. Eriksson, Ray Whiten, Kaisa Silander, Anabelle Morales-Mena, Gunther Birznieks, and William Eldridge

Subjects
Genetics, 0303 health sciences, Autosome, Genome Scan, Chromosome, chemical and pharmacologic phenomena, 030209 endocrinology & metabolism, Locus (genetics), Biology, Quantitative trait locus, Genome, 03 medical and health sciences, 0302 clinical medicine, Microsatellite, Genetics(clinical), Chromosome 20, Genetics (clinical), 030304 developmental biology
Abstract

We performed a genome scan at an average resolution of 8 cM in 719 Finnish sib pairs with type 2 diabetes. Our strongest results are for chromosome 20, where we observe a weighted maximum LOD score (MLS) of 2.15 at map position 69.5 cM from pter and secondary weighted LOD-score peaks of 2.04 at 56.5 cM and 1.99 at 17.5 cM. Our next largest MLS is for chromosome 11 (MLS = 1.75 at 84.0 cM), followed by chromosomes 2 (MLS = 0.87 at 5.5 cM), 10 (MLS = 0.77 at 75.0 cM), and 6 (MLS = 0.61 at 112.5 cM), all under an additive model. When we condition on chromosome 2 at 8.5 cM, the MLS for chromosome 20 increases to 5.50 at 69.0 cM (P=.0014). An ordered-subsets analysis based on families with high or low diabetes-related quantitative traits yielded results that support the possible existence of disease-predisposing genes on chromosomes 6 and 10. Genomewide linkage-disequilibrium analysis using microsatellite marker data revealed strong evidence of association for D22S423 (P=.00007). Further analyses are being carried out to confirm and to refine the location of these putative diabetes-predisposing genes.

Published
2000
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26. The Finland–United States Investigation of Non–Insulin-Dependent Diabetes Mellitus Genetics (FUSION) Study. II. An Autosomal Genome Scan for Diabetes-Related Quantitative-Trait Loci

Author

Richard C. McEachin, Gabriele Vidgren, William Hagopian, Tasha E. Fingerlin, Shane A. Shapiro, Christian Welch, Colin Martin, William L. Duren, Michael Boehnke, Johan G. Eriksson, Gunther Birznieks, William Eldridge, Ray Whiten, Liisa Toivanen, Julie A. Douglas, Zarir E. Karanjawala, Francis S. Collins, Thomas A. Buchanan, Soumitra Ghosh, Carl D. Langefeld, Anjene Musick, Jennie Chang, Stella J. Nylund, Timo T. Valle, Alistair So, Catherine Te, Chun Li, Leonid Segal, Karen L. Mohlke, Carrie Pfahl, Ravi Sharaf, Edna H. Ross, Rachel Porter, Richard M. Watanabe, Joseph B. Rayman, Eva Tuomilehto-Wolf, Elza Demirchyan, David Rha, Joyce Tannenbaum, Victoria L. Magnuson, Elizabeth R. Hauser, Michael P. Epstein, Kimmo Kohtamäki, Richard N. Bergman, Delphine S. Ally, Alyson Witt, Edward H. Trager, Ben Shurtleff, Kristina Kudelko, Jaakko Tuomilehto, Peggy P. White, Julie I. Knapp, Michael R. Erdos, Kaisa Silander, Peter S. Chines, Hong Shi Kaleta, James E. Balow, Christian Ehnholm, Heather M. Stringham, Arun M. Unni, Tiffany Musick, Jason Tovar, Jillian Blaschak-Harvan, Anabelle Morales-Mena, and Ethan M. Lange

Subjects
Blood Glucose, Male, Genetic Linkage, Matched-Pair Analysis, medicine.medical_treatment, chemical and pharmacologic phenomena, Locus (genetics), Type 2 diabetes, Quantitative trait locus, Biology, Body Mass Index, Nuclear Family, Quantitative Trait, Heritable, Sex Factors, Genetic linkage, Diabetes mellitus, Genetics, medicine, Chromosomes, Human, Humans, Insulin, Genetics(clinical), Genetic Predisposition to Disease, Genetic Testing, Finland, Genetics (clinical), Autosome, Genome, Human, Age Factors, Type 2 Diabetes Mellitus, Articles, Fasting, Middle Aged, medicine.disease, United States, Diabetes Mellitus, Type 2, Female
Abstract

Type 2 diabetes mellitus is a complex disorder encompassing multiple metabolic defects. We report results from an autosomal genome scan for type 2 diabetes-related quantitative traits in 580 Finnish families ascertained for an affected sibling pair and analyzed by the variance components-based quantitative-trait locus (QTL) linkage approach. We analyzed diabetic and nondiabetic subjects separately, because of the possible impact of disease on the traits of interest. In diabetic individuals, our strongest results were observed on chromosomes 3 (fasting C-peptide/glucose: maximum LOD score [MLS] = 3.13 at 53.0 cM) and 13 (body-mass index: MLS = 3.28 at 5.0 cM). In nondiabetic individuals, the strongest results were observed on chromosomes 10 (acute insulin response: MLS = 3.11 at 21.0 cM), 13 (2-h insulin: MLS = 2.86 at 65.5 cM), and 17 (fasting insulin/glucose ratio: MLS = 3.20 at 9.0 cM). In several cases, there was evidence for overlapping signals between diabetic and nondiabetic individuals; therefore we performed joint analyses. In these joint analyses, we observed strong signals for chromosomes 3 (body-mass index: MLS = 3.43 at 59.5 cM), 17 (empirical insulin-resistance index: MLS = 3.61 at 0.0 cM), and 19 (empirical insulin-resistance index: MLS = 2.80 at 74.5 cM). Integrating genome-scan results from the companion article by Ghosh et al., we identify several regions that may harbor susceptibility genes for type 2 diabetes in the Finnish population.

Published
2000
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27. Improvement of pagetic bone lesions with risedronate treatment: a radiologic study

Author

W.R Myers, Chines Arkadi Aaron, Jacques P. Brown, C.W Hayes, C Ritter-Hrncirik, and Rachelle Eusebio

Subjects
Male, musculoskeletal diseases, medicine.medical_specialty, Histology, Bone disease, Physiology, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Osteoporosis, Lesion, medicine, Humans, Femur, Tibia, Aged, business.industry, Etidronic Acid, Middle Aged, Bisphosphonate, Osteitis Deformans, medicine.disease, Surgery, Radiography, Paget's disease of bone, Risedronic acid, Female, medicine.symptom, business, Risedronic Acid, medicine.drug
Abstract

Risedronate is a potent pyridinyl bisphosphonate in clinical development for treatment and prevention of osteoporosis, and has been recently approved for treatment of Paget’s disease in the United States. An open-label study was conducted to determine the effect of risedronate treatment on pagetic bone lesions in patients with moderate to severe Paget’s disease (mean serum alkaline phosphatase levels [ALP] approximately seven times the upper limit of normal). Patients were treated with 30 mg/day oral risedronate for 84 days followed by a 112-day nontreatment period. This 196-day cycle was repeated once in patients whose ALP did not normalize or who experienced relapse, defined as a ≥25% increase in ALP from the lowest value measured. Radiographs of affected anatomical sites in 26 patients were collected at baseline, 6 months, and/or 12 months. Eleven patients received one course and 15 patients received two courses of treatment. Radiographs were examined by a skeletal radiologist who was blinded to their time sequence. Changes in pagetic lesions were categorized as “improved,” “deteriorated,” or “no change.” Between baseline and 6 months, 16 patients improved and 3 deteriorated; at 12 months, 11 patients improved and 2 deteriorated. Most lesions remained unchanged between 6 and 12 months. Improvements were noted in all skeletal sites (tibia, femur, humerus, forearm, pelvis, spine, and skull), but were most pronounced in weight-bearing long bones. In weight-bearing bones, nine lesions had osteolytic fronts. Of these, seven improved and two remained unchanged at 6 months; at 12 months, all but one lesion (which improved) remained unchanged. This radiographic assessment demonstrates that oral risedronate, 30 mg/day in one or two 3-month courses, is highly effective for improving bone lesions in patients with Paget’s disease. Risedronate treatment had no deleterious effect on osteolytic lesions in weight-bearing bones; indeed, the majority of lesions with osteolytic fronts were improved after 6 months of risedronate treatment.

Published
2000
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28. Methionine Synthase: High-Resolution Mapping of the Human Gene and Evaluation as a Candidate Locus for Neural Tube Defects

Author

Soumitra Ghosh, Anne M. Molloy, Peter S. Chines, Anjene Musick, James L. Mills, Lawrence C. Brody, Priscilla J. Baker, John M. Scott, Peadar N. Kirke, and Deborah A. Swanson

Subjects
Adult, Male, congenital, hereditary, and neonatal diseases and abnormalities, Candidate gene, Genotype, Homocysteine, Endocrinology, Diabetes and Metabolism, Locus (genetics), Hybrid Cells, Biology, 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase, Biochemistry, Linkage Disequilibrium, Contig Mapping, chemistry.chemical_compound, Endocrinology, Gene mapping, Genetics, Humans, Neural Tube Defects, Methionine synthase, Allele, Child, Molecular Biology, Alleles, Sequence Tagged Sites, Family Health, Genomic Library, Methionine, Chromosome Mapping, DNA, Molecular biology, Genes, chemistry, Chromosomes, Human, Pair 1, Genetic marker, Child, Preschool, biology.protein, Female, Lod Score, Microsatellite Repeats
Abstract

Periconceptual folate supplementation has been found to prevent the occurrence of many neural tube defects (NTDs). Consequently, genetic variation in folate metabolism genes is expected to contribute to the risk for neural tube defects. Methionine synthase catalyzes the vitamin B 12 -dependent conversion of homocysteine and 5-methyltetrahydrofolate to methionine and tetrahydrofolate. The observation that homocysteine and vitamin B 12 levels are independent predictors of NTD risk suggested that methionine synthase could be a candidate gene for NTDs. To assess the role of the MS gene in NTDs, we performed high-resolution physical mapping of the MS locus, isolated highly polymorphic markers linked to the MS gene, and tested for an association between specific MS alleles and NTDs. We mapped the MS gene to a position between 909 and 913 cR 10000 on chromosome 1 by radiation hybrid mapping. Polymorphic markers D1S1567 and D1S1568 map to locations no more than 900 and 194 kb from the MS gene, respectively. The segregation of these polymorphic markers was measured in 85 Irish NTD families. No allele of either marker showed a significant association with NTDs using the transmission disequilibrium test. A lack of association was also observed for the D1919G missense mutation within the gene. Our results suggest that inherited variation in the MS gene does not contribute to NTD risk in this population.

Published
1999
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29. Operational experience with the 450 kV injector for the superconducting cyclotron

Author

Santo Gammino, Luigi Celona, S. Marletta, G. Ciavola, M. Castro, and F. Chines

Subjects
Physics, Nuclear and High Energy Physics, Tandem, business.industry, Electrical engineering, Computer control system, Injector, law.invention, Superconducting cyclotron, Transmission (telecommunications), law, Magnet, Control system, Reduction (mathematics), business, Instrumentation
Abstract

In order to get a correct bunching of the tandem beams to be injected into the K-800 superconducting cyclotron at LNS and to improve further the transmission inside the tandem, the construction of a new injector providing 450 keV negative ions became necessary. The project, funded in 1990, is now complete. The commissioning of the 450 kV injector has been carried out paying particular attention to some technical problems: 1) the presence of two different sources, which permits to switch easily from one source to the other, has required to double all the hardware, except for the analyzing magnet and for the gas box, in order to be effective in reducing downtimes for maintenance: 2) the reduction of the electrical noise, which disturbs the computer control system; 3) the management of 79 analogic parameters and 110 digital parameters, which has been performed in an environment where the classical control system via insulated bars fails because of the high potential gradient (10 kV/in), one of the highest ever obtained in conditioned air environment for injectors. The main features of the 450 kV injector will be summarized. The main details of the commissioning with the platform performances will be presented and some details of ion optics will be given.

Published
1996
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30. Global Epigenomic Analysis of Primary Human Pancreatic Islets Provides Insights into Type 2 Diabetes Susceptibility Loci

Author

Lingyun Song, Praveen Sethupathy, Francis S. Collins, Terrence S. Furey, Michael R. Erdos, Nisc Comparative Sequencing Program, Michael L. Stitzel, Laura J. Scott, Michael Boehnke, Peter S. Chines, Alan P. Boyle, Stephen C. J. Parker, Ryan P. Welch, Daniel S. Pearson, Elliott H. Margulies, and Gregory E. Crawford

Subjects
Genetics, endocrine system, Primary (chemistry), endocrine system diseases, Physiology, Pancreatic islets, nutritional and metabolic diseases, Type 2 diabetes, Cell Biology, Biology, medicine.disease, Cell metabolism, medicine.anatomical_structure, Susceptibility locus, medicine, Molecular Biology, Epigenomics
Published
2010
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33. Simulation of Finnish Population History, Guided by Empirical Genetic Data, to Assess Power of Rare-Variant Tests in Finland

Author

Wang, Sophie R., primary, Agarwala, Vineeta, additional, Flannick, Jason, additional, Chiang, Charleston W.K., additional, Altshuler, David, additional, Hirschhorn, Joel N., additional, Manning, Alisa, additional, Hartl, Christopher, additional, Fontanillas, Pierre, additional, Green, Todd, additional, Banks, Eric, additional, DePristo, Mark, additional, Poplin, Ryan, additional, Shakir, Khalid, additional, Fennell, Timothy, additional, Murphy, Jacquelyn, additional, Burtt, Noël, additional, Gabriel, Stacey, additional, Fuchsberger, Christian, additional, Kang, Hyun Min, additional, Sim, Xueling, additional, Ma, Clement, additional, Locke, Adam, additional, Blackwell, Thomas, additional, Jackson, Anne, additional, Teslovich, Tanya, additional, Stringham, Heather, additional, Chines, Peter, additional, Kwan, Phoenix, additional, Huyghe, Jeroen, additional, Tan, Adrian, additional, Jun, Goo, additional, Stitzel, Michael, additional, Bergman, Richard N., additional, Bonnycastle, Lori, additional, Tuomilehto, Jaakko, additional, Collins, Francis S., additional, Scott, Laura, additional, Mohlke, Karen, additional, Abecasis, Gonçalo, additional, Boehnke, Michael, additional, Strom, Tim, additional, Gieger, Christian, additional, Müller-Nurasyid, Martina, additional, Grallert, Harald, additional, Kriebel, Jennifer, additional, Ried, Janina, additional, Hrabé de Angelis, Martin, additional, Huth, Cornelia, additional, Meisinger, Christa, additional, Peters, Annette, additional, Rathmann, Wolfgang, additional, Strauch, Konstantin, additional, Meitinger, Thomas, additional, Kravic, Jasmina, additional, Ladenvall, Claes, additional, Toumi, Tiinamaija, additional, Isomaa, Bo, additional, Groop, Leif, additional, Gaulton, Kyle, additional, Moutsianas, Loukas, additional, Rivas, Manny, additional, Pearson, Richard, additional, Mahajan, Anubha, additional, Prokopenko, Inga, additional, Kumar, Ashish, additional, Perry, John, additional, Chen, Jeff, additional, Howie, Bryan, additional, van de Bunt, Martijn, additional, Small, Kerrin, additional, Lindgren, Cecilia, additional, Lunter, Gerton, additional, Robertson, Neil, additional, Rayner, Will, additional, Morris, Andrew, additional, Buck, David, additional, Hattersley, Andrew, additional, Spector, Tim, additional, McVean, Gil, additional, Frayling, Tim, additional, Donnelly, Peter, additional, and McCarthy, Mark, additional

Published
2014
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34. Leveraging Cross-Species Transcription Factor Binding Site Patterns: From Diabetes Risk Loci to Disease Mechanisms

Author

Claussnitzer, Melina, primary, Dankel, Simon N., additional, Klocke, Bernward, additional, Grallert, Harald, additional, Glunk, Viktoria, additional, Berulava, Tea, additional, Lee, Heekyoung, additional, Oskolkov, Nikolay, additional, Fadista, Joao, additional, Ehlers, Kerstin, additional, Wahl, Simone, additional, Hoffmann, Christoph, additional, Qian, Kun, additional, Rönn, Tina, additional, Riess, Helene, additional, Müller-Nurasyid, Martina, additional, Bretschneider, Nancy, additional, Schroeder, Timm, additional, Skurk, Thomas, additional, Horsthemke, Bernhard, additional, Spieler, Derek, additional, Klingenspor, Martin, additional, Seifert, Martin, additional, Kern, Michael J., additional, Mejhert, Niklas, additional, Dahlman, Ingrid, additional, Hansson, Ola, additional, Hauck, Stefanie M., additional, Blüher, Matthias, additional, Arner, Peter, additional, Groop, Leif, additional, Illig, Thomas, additional, Suhre, Karsten, additional, Hsu, Yi-Hsiang, additional, Mellgren, Gunnar, additional, Hauner, Hans, additional, Laumen, Helmut, additional, Voight, Benjamin F., additional, Scott, Laura J., additional, Steinthorsdottir, Valgerdur, additional, Morris, Andrew P., additional, Dina, Christian, additional, Welch, Ryan P., additional, Zeggini, Eleftheria, additional, Huth, Cornelia, additional, Aulchenko, Yurii S., additional, Thorleifsson, Gudmar, additional, McCulloch, Laura J., additional, Ferreira, Teresa, additional, Amin, Najaf, additional, Wu, Guanming, additional, Willer, Cristen J., additional, Raychaudhuri, Soumya, additional, McCarroll, Steve A., additional, Langenberg, Claudia, additional, Hofmann, Oliver M., additional, Dupuis, Josée, additional, Qi, Lu, additional, Segrè, Ayellet V., additional, van Hoek, Mandy, additional, Navarro, Pau, additional, Ardlie, Kristin, additional, Balkau, Beverley, additional, Benediktsson, Rafn, additional, Bennett, Amanda J., additional, Blagieva, Roza, additional, Boerwinkle, Eric, additional, Bonnycastle, Lori L., additional, Boström, Kristina Bengtsson, additional, Bravenboer, Bert, additional, Bumpstead, Suzannah, additional, Burtt, Noël P., additional, Charpentier, Guillaume, additional, Chines, Peter S., additional, Cornelis, Marilyn, additional, Couper, David J., additional, Crawford, Gabe, additional, Doney, Alex S.F., additional, Elliott, Katherine S., additional, Elliott, Amanda L., additional, Erdos, Michael R., additional, Fox, Caroline S., additional, Franklin, Christopher S., additional, Ganser, Martha, additional, Gieger, Christian, additional, Grarup, Niels, additional, Green, Todd, additional, Griffin, Simon, additional, Groves, Christopher J., additional, Guiducci, Candace, additional, Hadjadj, Samy, additional, Hassanali, Neelam, additional, Herder, Christian, additional, Isomaa, Bo, additional, Jackson, Anne U., additional, Johnson, Paul R.V., additional, Jørgensen, Torben, additional, Kao, Wen H.L., additional, Klopp, Norman, additional, Kong, Augustine, additional, Kraft, Peter, additional, Kuusisto, Johanna, additional, Lauritzen, Torsten, additional, Li, Man, additional, Lieverse, Aloysius, additional, Lindgren, Cecilia M., additional, Lyssenko, Valeriya, additional, Marre, Michel, additional, Meitinger, Thomas, additional, Midthjell, Kristian, additional, Morken, Mario A., additional, Narisu, Narisu, additional, Nilsson, Peter, additional, Owen, Katharine R., additional, Payne, Felicity, additional, Perry, John R.B., additional, Petersen, Ann-Kristin, additional, Platou, Carl, additional, Proença, Christine, additional, Prokopenko, Inga, additional, Rathmann, Wolfgang, additional, Rayner, N. William, additional, Robertson, Neil R., additional, Rocheleau, Ghislain, additional, Roden, Michael, additional, Sampson, Michael J., additional, Saxena, Richa, additional, Shields, Beverley M., additional, Shrader, Peter, additional, Sigurdsson, Gunnar, additional, Sparsø, Thomas, additional, Strassburger, Klaus, additional, Stringham, Heather M., additional, Sun, Qi, additional, Swift, Amy J., additional, Thorand, Barbara, additional, Tichet, Jean, additional, Tuomi, Tiinamaija, additional, van Dam, Rob M., additional, van Haeften, Timon W., additional, van Herpt, Thijs, additional, van Vliet-Ostaptchouk, Jana V., additional, Walters, G. Bragi, additional, Weedon, Michael N., additional, Wijmenga, Cisca, additional, Witteman, Jacqueline, additional, Bergman, Richard N., additional, Cauchi, Stephane, additional, Collins, Francis S., additional, Gloyn, Anna L., additional, Gyllensten, Ulf, additional, Hansen, Torben, additional, Hide, Winston A., additional, Hitman, Graham A., additional, Hofman, Albert, additional, Hunter, David J., additional, Hveem, Kristian, additional, Laakso, Markku, additional, Mohlke, Karen L., additional, Morris, Andrew D., additional, Palmer, Colin N.A., additional, Pramstaller, Peter P., additional, Rudan, Igor, additional, Sijbrands, Eric, additional, Stein, Lincoln D., additional, Tuomilehto, Jaakko, additional, Uitterlinden, Andre, additional, Walker, Mark, additional, Wareham, Nicholas J., additional, Watanabe, Richard M., additional, Abecasis, Goncalo R., additional, Boehm, Bernhard O., additional, Campbell, Harry, additional, Daly, Mark J., additional, Hattersley, Andrew T., additional, Hu, Frank B., additional, Meigs, James B., additional, Pankow, James S., additional, Pedersen, Oluf, additional, Wichmann, H.-Erich, additional, Barroso, Inês, additional, Florez, Jose C., additional, Frayling, Timothy M., additional, Sladek, Rob, additional, Thorsteinsdottir, Unnur, additional, Wilson, James F., additional, Froguel, Philippe, additional, van Duijn, Cornelia M., additional, Stefansson, Kari, additional, Altshuler, David, additional, Boehnke, Michael, additional, and McCarthy, Mark I., additional

Published
2014
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35. 67 SAFETY AND TOLERABILITY OF BAZEDOXIFENE/CONJUGATED ESTROGENS IN POSTMENOPAUSAL WOMEN: FINDINGS FROM A 1 -YEAR, RANDOMIZED, PLACEBO- AND ACTIVE-CONTROLLED, PHASE 3 TRIAL

Author

Sebastian Mirkin, Kaijie Pan, David F. Archer, Arkadi Chines, and Roger A. Lobo

Subjects
medicine.medical_specialty, Postmenopausal women, Tolerability, business.industry, Urology, medicine, Obstetrics and Gynecology, Placebo, Bazedoxifene/conjugated estrogens, business, General Biochemistry, Genetics and Molecular Biology
Published
2012
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36. 137 EFFECTS OF BAZEDOXIFENE/CONJUGATED ESTROGENS ON SLEEP PARAMETERS AND HEALTH-RELATED QUALITY OF LIFE IN POSTMENOPAUSAL WOMEN

Author

Jill Racketa, JoAnn V. Pinkerton, Lucy Abraham, Kaijie Pan, Arkadi Chines, and Sebastian Mirkin

Subjects
Health related quality of life, medicine.medical_specialty, Endocrinology, Postmenopausal women, business.industry, Internal medicine, Obstetrics and Gynecology, Medicine, Physiology, business, Bazedoxifene/conjugated estrogens, Sleep in non-human animals, General Biochemistry, Genetics and Molecular Biology
Published
2012
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39. Assessment of the safety of long-term bazedoxifene treatment on the reproductive tract in postmenopausal women with osteoporosis: Results of a 7-year, randomized, placebo-controlled, phase 3 study

Author

Palacios, Santiago, primary, de Villiers, Tobie J., additional, Nardone, Fiorenzo De Cicco, additional, Levine, Amy B., additional, Williams, Robert, additional, Hines, Teresa, additional, Mirkin, Sebastian, additional, and Chines, Arkadi A., additional

Published
2013
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40. Meta-analysis of Gene-Level Associations for Rare Variants Based on Single-Variant Statistics

Author

Hu, Yi-Juan, primary, Berndt, Sonja I., additional, Gustafsson, Stefan, additional, Ganna, Andrea, additional, Hirschhorn, Joel, additional, North, Kari E., additional, Ingelsson, Erik, additional, Lin, Dan-Yu, additional, Mägi, Reedik, additional, Wheeler, Eleanor, additional, Feitosa, Mary F., additional, Justice, Anne E., additional, Monda, Keri L., additional, Croteau-Chonka, Damien C., additional, Day, Felix R., additional, Esko, Tõnu, additional, Fall, Tove, additional, Ferreira, Teresa, additional, Gentilini, Davide, additional, Jackson, Anne U., additional, Luan, Jian’an, additional, Randall, Joshua C., additional, Vedantam, Sailaja, additional, Willer, Cristen J., additional, Winkler, Thomas W., additional, Wood, Andrew R., additional, Workalemahu, Tsegaselassie, additional, Hu, Yi-Juan, additional, Lee, Sang Hong, additional, Liang, Liming, additional, Min, Josine L., additional, Neale, Benjamin M., additional, Thorleifsson, Gudmar, additional, Yang, Jian, additional, Albrecht, Eva, additional, Amin, Najaf, additional, Bragg-Gresham, Jennifer L., additional, Cadby, Gemma, additional, den Heijer, Martin, additional, Eklund, Niina, additional, Fischer, Krista, additional, Goel, Anuj, additional, Hottenga, Jouke-Jan, additional, Huffman, Jennifer E., additional, Jarick, Ivonne, additional, Johansson, Åsa, additional, Johnson, Toby, additional, Kanoni, Stavroula, additional, Kleber, Marcus E., additional, König, Inke R., additional, Kristiansson, Kati, additional, Kutalik, Zoltán, additional, Lamina, Claudia, additional, Lecoeur, Cecile, additional, Li, Guo, additional, Mangino, Massimo, additional, McArdle, Wendy L., additional, Medina-Gomez, Carolina, additional, Müller-Nurasyid, Martina, additional, Ngwa, Julius S., additional, Nolte, Ilja M., additional, Paternoster, Lavinia, additional, Pechlivanis, Sonali, additional, Perola, Markus, additional, Peters, Marjolein J., additional, Preuss, Michael, additional, Rose, Lynda M., additional, Shi, Jianxin, additional, Shungin, Dmitry, additional, Smith, Albert Vernon, additional, Strawbridge, Rona J., additional, Surakka, Ida, additional, Teumer, Alexander, additional, Trip, Mieke D., additional, Tyrer, Jonathan, additional, Van Vliet-Ostaptchouk, Jana V., additional, Vandenput, Liesbeth, additional, Waite, Lindsay L., additional, Zhao, Jing Hua, additional, Absher, Devin, additional, Asselbergs, Folkert W., additional, Atalay, Mustafa, additional, Attwood, Antony P., additional, Balmforth, Anthony J., additional, Basart, Hanneke, additional, Beilby, John, additional, Bonnycastle, Lori L., additional, Brambilla, Paolo, additional, Bruinenberg, Marcel, additional, Campbell, Harry, additional, Chasman, Daniel I., additional, Chines, Peter S., additional, Collins, Francis S., additional, Connell, John M., additional, Cookson, William, additional, de Faire, Ulf, additional, de Vegt, Femmie, additional, Dei, Mariano, additional, Dimitriou, Maria, additional, Edkins, Sarah, additional, Estrada, Karol, additional, Evans, David M., additional, Farrall, Martin, additional, Ferrario, Marco M., additional, Ferrières, Jean, additional, Franke, Lude, additional, Frau, Francesca, additional, Gejman, Pablo V., additional, Grallert, Harald, additional, Grönberg, Henrik, additional, Gudnason, Vilmundur, additional, Hall, Alistair S., additional, Hall, Per, additional, Hartikainen, Anna-Liisa, additional, Hayward, Caroline, additional, Heard-Costa, Nancy L., additional, Heath, Andrew C., additional, Hebebrand, Johannes, additional, Homuth, Georg, additional, Hu, Frank B., additional, Hunt, Sarah E., additional, Hyppönen, Elina, additional, Iribarren, Carlos, additional, Jacobs, Kevin B., additional, Jansson, John-Olov, additional, Jula, Antti, additional, Kähönen, Mika, additional, Kathiresan, Sekar, additional, Kee, Frank, additional, Khaw, Kay-Tee, additional, Kivimaki, Mika, additional, Koenig, Wolfgang, additional, Kraja, Aldi T., additional, Kumari, Meena, additional, Kuulasmaa, Kari, additional, Kuusisto, Johanna, additional, Laitinen, Jaana H., additional, Lakka, Timo A., additional, Langenberg, Claudia, additional, Launer, Lenore J., additional, Lind, Lars, additional, Lindström, Jaana, additional, Liu, Jianjun, additional, Liuzzi, Antonio, additional, Lokki, Marja-Liisa, additional, Lorentzon, Mattias, additional, Madden, Pamela A., additional, Magnusson, Patrik K., additional, Manunta, Paolo, additional, Marek, Diana, additional, März, Winfried, additional, Leach, Irene Mateo, additional, McKnight, Barbara, additional, Medland, Sarah E., additional, Mihailov, Evelin, additional, Milani, Lili, additional, Montgomery, Grant W., additional, Mooser, Vincent, additional, Mühleisen, Thomas W., additional, Munroe, Patricia B., additional, Musk, Arthur W., additional, Narisu, Narisu, additional, Navis, Gerjan, additional, Nicholson, George, additional, Nohr, Ellen A., additional, Ong, Ken K., additional, Oostra, Ben A., additional, Palmer, Colin N.A., additional, Palotie, Aarno, additional, Peden, John F., additional, Pedersen, Nancy, additional, Peters, Annette, additional, Polasek, Ozren, additional, Pouta, Anneli, additional, Pramstaller, Peter P., additional, Prokopenko, Inga, additional, Pütter, Carolin, additional, Radhakrishnan, Aparna, additional, Raitakari, Olli, additional, Rendon, Augusto, additional, Rivadeneira, Fernando, additional, Rudan, Igor, additional, Saaristo, Timo E., additional, Sambrook, Jennifer G., additional, Sanders, Alan R., additional, Sanna, Serena, additional, Saramies, Jouko, additional, Schipf, Sabine, additional, Schreiber, Stefan, additional, Schunkert, Heribert, additional, Shin, So-Youn, additional, Signorini, Stefano, additional, Sinisalo, Juha, additional, Skrobek, Boris, additional, Soranzo, Nicole, additional, Stančáková, Alena, additional, Stark, Klaus, additional, Stephens, Jonathan C., additional, Stirrups, Kathleen, additional, Stolk, Ronald P., additional, Stumvoll, Michael, additional, Swift, Amy J., additional, Theodoraki, Eirini V., additional, Thorand, Barbara, additional, Tregouet, David-Alexandre, additional, Tremoli, Elena, additional, Van der Klauw, Melanie M., additional, van Meurs, Joyce B.J., additional, Vermeulen, Sita H., additional, Viikari, Jorma, additional, Virtamo, Jarmo, additional, Vitart, Veronique, additional, Waeber, Gérard, additional, Wang, Zhaoming, additional, Widén, Elisabeth, additional, Wild, Sarah H., additional, Willemsen, Gonneke, additional, Winkelmann, Bernhard R., additional, Witteman, Jacqueline C.M., additional, Wolffenbuttel, Bruce H.R., additional, Wong, Andrew, additional, Wright, Alan F., additional, Zillikens, M. Carola, additional, Amouyel, Philippe, additional, Boehm, Bernhard O., additional, Boerwinkle, Eric, additional, Boomsma, Dorret I., additional, Caulfield, Mark J., additional, Chanock, Stephen J., additional, Cupples, L. Adrienne, additional, Cusi, Daniele, additional, Dedoussis, George V., additional, Erdmann, Jeanette, additional, Eriksson, Johan G., additional, Franks, Paul W., additional, Froguel, Philippe, additional, Gieger, Christian, additional, Gyllensten, Ulf, additional, Hamsten, Anders, additional, Harris, Tamara B., additional, Hengstenberg, Christian, additional, Hicks, Andrew A., additional, Hingorani, Aroon, additional, Hinney, Anke, additional, Hofman, Albert, additional, Hovingh, Kees G., additional, Hveem, Kristian, additional, Illig, Thomas, additional, Jarvelin, Marjo-Riitta, additional, Jöckel, Karl-Heinz, additional, Keinanen-Kiukaanniemi, Sirkka M., additional, Kiemeney, Lambertus A., additional, Kuh, Diana, additional, Laakso, Markku, additional, Lehtimäki, Terho, additional, Levinson, Douglas F., additional, Martin, Nicholas G., additional, Metspalu, Andres, additional, Morris, Andrew D., additional, Nieminen, Markku S., additional, Njølstad, Inger, additional, Ohlsson, Claes, additional, Oldehinkel, Albertine J., additional, Ouwehand, Willem H., additional, Palmer, Lyle J., additional, Penninx, Brenda, additional, Power, Chris, additional, Province, Michael A., additional, Psaty, Bruce M., additional, Qi, Lu, additional, Rauramaa, Rainer, additional, Ridker, Paul M., additional, Ripatti, Samuli, additional, Salomaa, Veikko, additional, Samani, Nilesh J., additional, Snieder, Harold, additional, Sørensen, Thorkild I.A., additional, Spector, Timothy D., additional, Stefansson, Kari, additional, Tönjes, Anke, additional, Tuomilehto, Jaakko, additional, Uitterlinden, André G., additional, Uusitupa, Matti, additional, van der Harst, Pim, additional, Vollenweider, Peter, additional, Wallaschofski, Henri, additional, Wareham, Nicholas J., additional, Watkins, Hugh, additional, Wichmann, H.-Erich, additional, Wilson, James F., additional, Abecasis, Goncalo R., additional, Assimes, Themistocles L., additional, Barroso, Inês, additional, Boehnke, Michael, additional, Borecki, Ingrid B., additional, Deloukas, Panos, additional, Fox, Caroline S., additional, Frayling, Timothy, additional, Groop, Leif C., additional, Haritunian, Talin, additional, Heid, Iris M., additional, Hunter, David, additional, Kaplan, Robert C., additional, Karpe, Fredrik, additional, Moffatt, Miriam, additional, Mohlke, Karen L., additional, O’Connell, Jeffrey R., additional, Pawitan, Yudi, additional, Schadt, Eric E., additional, Schlessinger, David, additional, Steinthorsdottir, Valgerdur, additional, Strachan, David P., additional, Thorsteinsdottir, Unnur, additional, van Duijn, Cornelia M., additional, Visscher, Peter M., additional, Di Blasio, Anna Maria, additional, Hirschhorn, Joel N., additional, Lindgren, Cecilia M., additional, Morris, Andrew P., additional, Meyre, David, additional, Scherag, André, additional, McCarthy, Mark I., additional, Speliotes, Elizabeth K., additional, North, Kari E., additional, and Loos, Ruth J.F., additional

Published
2013
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46. 68 THE EFFECTS OF BAZEDOXIFENE/CONJUGATED ESTROGENS ON BREAST DENSITY IN POSTMENOPAUSAL WOMEN

Author

J.R. Thompson, Kaijie Pan, J.A. Harvey, Arkadi Chines, Sebastian Mirkin, and JoAnn V. Pinkerton

Subjects
medicine.medical_specialty, Postmenopausal women, Endocrinology, business.industry, Internal medicine, medicine, Obstetrics and Gynecology, Breast density, business, Bazedoxifene/conjugated estrogens, General Biochemistry, Genetics and Molecular Biology
Published
2012
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47. 99 REPRODUCTIVE SAFETY OF BAZEDOXIFENE IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS: RESULTS OF A 7-YEAR, RANDOMIZED, PLACEBO-CONTROLLED, PHASE 3 STUDY

Author

Robert D. Williams, Amy B. Levine, Santiago Palacios, Arkadi Chines, T. J. de Villiers, Teresa Hines, and F. De Cicco-Nardone

Subjects
medicine.medical_specialty, Postmenopausal women, business.industry, Osteoporosis, Obstetrics and Gynecology, Phases of clinical research, Placebo, medicine.disease, General Biochemistry, Genetics and Molecular Biology, Bazedoxifene, Internal medicine, medicine, business, medicine.drug
Published
2012
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48. Global Epigenomic Analysis of Primary Human Pancreatic Islets Provides Insights into Type 2 Diabetes Susceptibility Loci

Author

Stitzel, Michael L., primary, Sethupathy, Praveen, additional, Pearson, Daniel S., additional, Chines, Peter S., additional, Song, Lingyun, additional, Erdos, Michael R., additional, Welch, Ryan, additional, Parker, Stephen C.J., additional, Boyle, Alan P., additional, Scott, Laura J., additional, Sequencing Program, NISC Comparative, additional, Margulies, Elliott H., additional, Boehnke, Michael, additional, Furey, Terrence S., additional, Crawford, Gregory E., additional, and Collins, Francis S., additional

Published
2010
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