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Search Results: 1 - 10 of 285986 matches for " Roger C. W. Wolfs "
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Cholesterol-Lowering Drugs and Incident Open-Angle Glaucoma: A Population-Based Cohort Study
Michael W. Marcus, Rogier P. H. M. Müskens, Wishal D. Ramdas, Roger C. W. Wolfs, Paulus T. V. M. De Jong, Johannes R. Vingerling, Albert Hofman, Bruno H. Stricker, Nomdo M. Jansonius
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0029724
Abstract: Background Open-angle glaucoma (OAG) is a progressive neurodegenerative disease that may lead to blindness. An elevated intraocular pressure (IOP) is its major risk factor. OAG treatment is currently exclusively directed towards the lowering of the IOP. IOP lowering does not prevent disease progression in all patients and thus other treatment modalities are needed. Earlier studies reported cholesterol-lowering drugs to have neuroprotective properties. The aim of this study was to determine the associations between the use of cholesterol-lowering drugs and incident OAG. Methodology/Principal Findings Participants in a prospective population-based cohort study underwent ophthalmic examinations, including IOP measurements and perimetry, at baseline and follow-up. The use of statins and non-statin cholesterol-lowering drugs was monitored continuously during the study. Associations between the use of cholesterol-lowering drugs and incident OAG were analyzed with Cox regression; associations between cholesterol-lowering drugs and IOP at follow-up were analyzed with multiple linear regression. During a mean follow-up of 9.8 years, 108 of 3939 eligible participants (2.7%) developed OAG. The hazard ratio for statin use was 0.54 (95% confidence interval 0.31–0.96; P = 0.034) and for non-statin cholesterol-lowering drugs 2.07 (0.81–5.33; P = 0.13). The effect of statins was more pronounced with prolonged use (hazard ratio 0.89 [0.41–1.94; P = 0.77] for use two years or less; 0.46 [0.23–0.94; P = 0.033] for use more than two years; P-value for trend 0.10). The analyzes were adjusted for age and gender, baseline IOP and IOP-lowering treatment, the family history of glaucoma, and myopia. There was no effect of statins on the IOP. Conclusions/Significance Long-term use of statins appears to be associated with a reduced risk of OAG. The observed effect was independent of the IOP. These findings are in line with the idea that statins have neuroprotective properties and may open a way to a new OAG treatment modality.
A Genome-Wide Association Study of Optic Disc Parameters
Wishal D. Ramdas equal contributor,Leonieke M. E. van Koolwijk equal contributor,M. Kamran Ikram equal contributor,Nomdo M. Jansonius,Paulus T. V. M. de Jong,Arthur A. B. Bergen,Aaron Isaacs,Najaf Amin,Yurii S. Aulchenko,Roger C. W. Wolfs,Albert Hofman,Fernando Rivadeneira,Ben A. Oostra,Andre G. Uitterlinden,Pirro Hysi,Christopher J. Hammond,Hans G. Lemij,Johannes R. Vingerling ,Caroline C. W. Klaver equal contributor,Cornelia M. van Duijn equal contributor
PLOS Genetics , 2010, DOI: 10.1371/journal.pgen.1000978
Abstract: The optic nerve head is involved in many ophthalmic disorders, including common diseases such as myopia and open-angle glaucoma. Two of the most important parameters are the size of the optic disc area and the vertical cup-disc ratio (VCDR). Both are highly heritable but genetically largely undetermined. We performed a meta-analysis of genome-wide association (GWA) data to identify genetic variants associated with optic disc area and VCDR. The gene discovery included 7,360 unrelated individuals from the population-based Rotterdam Study I and Rotterdam Study II cohorts. These cohorts revealed two genome-wide significant loci for optic disc area, rs1192415 on chromosome 1p22 (p = 6.72×10?19) within 117 kb of the CDC7 gene and rs1900004 on chromosome 10q21.3-q22.1 (p = 2.67×10?33) within 10 kb of the ATOH7 gene. They revealed two genome-wide significant loci for VCDR, rs1063192 on chromosome 9p21 (p = 6.15×10?11) in the CDKN2B gene and rs10483727 on chromosome 14q22.3-q23 (p = 2.93×10?10) within 40 kbp of the SIX1 gene. Findings were replicated in two independent Dutch cohorts (Rotterdam Study III and Erasmus Rucphen Family study; N = 3,612), and the TwinsUK cohort (N = 843). Meta-analysis with the replication cohorts confirmed the four loci and revealed a third locus at 16q12.1 associated with optic disc area, and four other loci at 11q13, 13q13, 17q23 (borderline significant), and 22q12.1 for VCDR. ATOH7 was also associated with VCDR independent of optic disc area. Three of the loci were marginally associated with open-angle glaucoma. The protein pathways in which the loci of optic disc area are involved overlap with those identified for VCDR, suggesting a common genetic origin.
Senescence of human vocal fold fibroblasts in primary culture  [PDF]
George M. Adams, Chet C. Xu, Roger W. Chan
Journal of Biomedical Science and Engineering (JBiSE) , 2010, DOI: 10.4236/jbise.2010.32020
Abstract: This study examined the replicative senescence of primary-culture human vocal fold fibroblasts, in terms of changes in gross chromosomal structure with sub- culturing, and population doubling time (PDT). The mRNA expressions of 14 target genes were also examined. The objectives were to identify the onset of senescence for establishing the acceptable limit of sub-culturing, and to better understand the effect of cellular aging on matrix protein regulation in the vocal fold. Gross chromosomal changes in vocal fold fibroblasts from a 58-year-old woman were karyotyped with Giemsa stain. Proliferation of the fibroblasts was determined with cell recovery and PDT calculation. Transcript levels of the target genes were found by RT-PCR. Onset of significant chromosomal anomalies was seen with passage 5. For mRNA expressions, significant increases with passaging were observed in collagenase, macrophage elastase, lysyl oxidase and fibromodulin, whereas significant downregulation was detected in decorin, procollagen I, hyaluronic acid-synthase 2 and collagen III. This modulation pattern suggested that fibroblasts underwent in vitro aging, consistent with the significant increase in PDT. The inception of senescence did not occur until passage 5. These findings may facilitate the development of representative in vitro models for testing tissue engineering approaches involving primary-culture fibroblasts.
Financing Developing Country Debt: A Sovereign Borrowing Entity Proposal  [PDF]
David J. Moore, Roger W. Clark, George C. Philippatos
Journal of Financial Risk Management (JFRM) , 2014, DOI: 10.4236/jfrm.2014.33008

This paper proposes the creation of a Sovereign Borrowing Entity (SBE) under the auspices of the International Monetary Fund (IMF) and other International Financial Institutions (IFIs). The SBE guarantees bond issuances by developing nations, packages them in relatively small denominations, and auctions them to the public. Should a developing debtor country fail to pay its debt, the SBE would raise funds through a punitive tariff on all exports administered by the IMF member nations. We develop a theoretical model of the proposed Sovereign Borrowing Entity (SBE) and provide viability evidence using export and debt data from the World Bank. It is our hope that this paper will encourage further dialogue and research on financing developing country debt in a more effective manner.

Common Genetic Determinants of Intraocular Pressure and Primary Open-Angle Glaucoma
Leonieke M. E. van Koolwijk equal contributor,Wishal D. Ramdas equal contributor,M. Kamran Ikram,Nomdo M. Jansonius,Francesca Pasutto,Pirro G. Hysi,Stuart Macgregor,Sarah F. Janssen,Alex W. Hewitt,Ananth C. Viswanathan,Jacoline B. ten Brink,S. Mohsen Hosseini,Najaf Amin,Dominiek D. G. Despriet,Jacqueline J. M. Willemse-Assink,Rogier Kramer,Fernando Rivadeneira,Maksim Struchalin,Yurii S. Aulchenko,Nicole Weisschuh,Matthias Zenkel,Christian Y. Mardin,Eugen Gramer,Ulrich Welge-Lüssen,Grant W. Montgomery,Francis Carbonaro,Terri L. Young,The DCCT/EDIC Research Group,Céline Bellenguez,Peter McGuffin,Paul J. Foster,Fotis Topouzis,Paul Mitchell,Jie Jin Wang,Tien Y. Wong,Monika A. Czudowska,Albert Hofman,Andre G. Uitterlinden,Roger C. W. Wolfs,Paulus T. V. M. de Jong,Ben A. Oostra,Andrew D. Paterson,Wellcome Trust Case Control Consortium 2,David A. Mackey,Arthur A. B. Bergen,André Reis,Christopher J. Hammond,Johannes R. Vingerling,Hans G. Lemij,Caroline C. W. Klaver,Cornelia M. van Duijn
PLOS Genetics , 2012, DOI: 10.1371/journal.pgen.1002611
Abstract: Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consortium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p = 1.4×10?8), and with rs7555523, located in TMCO1 at 1q24.1 (p = 1.6×10?8). In a meta-analysis of 4 case-control studies (total N = 1,432 glaucoma cases), both variants also showed evidence for association with glaucoma (p = 2.4×10?2 for rs11656696 and p = 9.1×10?4 for rs7555523). GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina cribrosa, optic nerve, and retina. Both genes functionally interact with known glaucoma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation.
The PWN torus of PSR J0538+2817 and the Origin of Pulsar Velocities
Roger W. Romani,C. -Y. Ng
Physics , 2003, DOI: 10.1086/374259
Abstract: We find evidence for a faint wind nebula surrounding PSR J0538+2817 in CXO-ACIS imaging. This object is particularly interesting, as the pulsar spindown age is largest for any such X-ray PWN. If interpreted as an equatorial torus, the PWN supports the claimed association with the S147 supernova remnant and implies good alignment between the pulsar spin and space velocity. Comparison of the SNR age, X-ray cooling age and characteristic age suggests a birth spin period of >130ms. In turn, if we accept as causal the alignment of the linear and angular momenta, this places strong constraints on the origin of the `kick' at the neutron star birth.
Rationale and design of The Delphi Trial – I(RCT)2: international randomized clinical trial of rheumatoid craniocervical treatment, an intervention-prognostic trial comparing 'early' surgery with conservative treatment [ISRCTN65076841]
Jasper FC Wolfs, Wilco C Peul, Maarten Boers, Maurits W van Tulder, Ronald Brand, Hans JC van Houwelingen, Raph TWM Thomeer
BMC Musculoskeletal Disorders , 2006, DOI: 10.1186/1471-2474-7-14
Abstract: The authors have sent a Delphi Questionnaire about the current treatment strategies of craniocervical involvement by rheumatoid arthritis to an international forum of expert rheumatologists and surgeons. The timing of surgery in patients with radiographic instability without evidence of neurological deficit is an area of considerable controversy. If signs and symptoms of myelopathy are present there is little chance of recovery to normal levels after surgery.In this international multicenter randomized clinical trial, early surgical atlantoaxial fixation in patients with rheumatoid arthritis and radiological abnormalities without neurological deficits will be compared with prolonged conservative treatment. The main research question is whether early surgery can prevent radiological and neurological progression. A cost-effectivity analysis will be performed. 250 patients are needed to answer the research question.Early surgery could prevent serious neurological deficits, but may have peri-operative morbidity and loss of rotation of the head and neck. The objective of this study is to identify the best timing of surgery for patients at risk for the development of neurological signs and symptoms.Rheumatoid Arthritis (RA) is a chronic, systemic, inflammatory disease with an unknown etiology characterized by an erosive synovitis. Genetic and environmental factors play an important role. Both humoral and cellular immune responses are present. In caucasians the prevalence of RA is 0.8–1% [1] and the incidence is 27 per 100.000 of the general population [2]. The upper cervical spine shows signs of damage in 17–86% of patients with RA and is the most commonly involved structure after hands and feet [3]. The huge difference in the prevalence of cervical spine pathology is the result of absence of standardized international accepted definitions of subluxations of the atlantoaxial segment and inconsistent results in the literature. The use of better anti-inflammatory drugs in t
Multiple Benefits Derived from a Peer Teacher Program in Two Undergraduate Microbiology Lab Courses
Frances C. Sailer,Roger W. Melvold,Charles C. Hosford
Journal of Microbiology & Biology Education , 2010, DOI: 10.1128/jmbe.v11i2.190
Abstract: A peer teaching program was implemented to alleviate the problem of a limited number of lab instructors attempting to teach large numbers of students in two different undergraduate microbiology lab courses. The benefit of having peer teachers was immediately obvious to the lab instructors, faculty and staff who were responsible for conducting the labs, but it was soon evident that there were also benefits for everyone else involved in the program. The students enrolled in the labs reported that having peer teachers in the lab enhanced their learning, and they felt comfortable receiving help from a peer teacher who had recently completed the course. The peer teachers discovered that they gained valuable experience and confidence while teaching other students, and they appreciated the chance to gain hands-on experience. The lab instructors received the qualified help they needed in order to give more individual attention to the large numbers of students in the labs. The feedback from this program has been positive from everyone involved.
The Metabolism and Transplacental Transfer of Oseltamivir in the Ex Vivo Human Model
Kevin C. Worley,Scott W. Roberts,Roger E. Bawdon
Infectious Diseases in Obstetrics and Gynecology , 2008, DOI: 10.1155/2008/927574
Abstract: Oseltamivir phosphate is extensively metabolized in the ex vivo human placenta model, and the transplacental passage of the metabolite oseltamivir carboxylate is incomplete. Objective. To evaluate the metabolism and transplacental transfer of oseltamivir (Tamiflu) in the ex vivo human placental model. Study Design. Perfusion studies were performed in six placentas from term, uncomplicated deliveries. Concentrations of oseltamivir phosphate (OP) that were 5-6 fold, 20–30 fold, and 600–800 fold above the therapeutic peak were tested, as neither OP nor its active metabolite, oseltamivir carboxylate (OC), could be detected at near-therapeutic concentrations. The transplacental transfer and accumulation of OC were assessed using the 14C antipyrine reference method. Results. OP was extensively metabolized to OC. In the 4 placentas with the highest concentration of OP, OC had a mean clearance index of 0.13±0.08, suggesting that transplacental passage occurs at a relatively low rate. Measurable fetal accumulation occurred in the two placentas with the highest initial concentrations. Conclusions. Oseltamivir phosphate was extensively metabolized in the ex vivo model. Transplacental transfer of the metabolite was incomplete and accumulation was minimal.
CO2 Efflux from Cleared Mangrove Peat
Catherine E. Lovelock, Roger W. Ruess, Ilka C. Feller
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0021279
Abstract: Background CO2 emissions from cleared mangrove areas may be substantial, increasing the costs of continued losses of these ecosystems, particularly in mangroves that have highly organic soils. Methodology/Principal Findings We measured CO2 efflux from mangrove soils that had been cleared for up to 20 years on the islands of Twin Cays, Belize. We also disturbed these cleared peat soils to assess what disturbance of soils after clearing may have on CO2 efflux. CO2 efflux from soils declines from time of clearing from ~10 600 tonnes km?2 year?1 in the first year to 3000 tonnes km2 year?1 after 20 years since clearing. Disturbing peat leads to short term increases in CO2 efflux (27 umol m?2 s?1), but this had returned to baseline levels within 2 days. Conclusions/Significance Deforesting mangroves that grow on peat soils results in CO2 emissions that are comparable to rates estimated for peat collapse in other tropical ecosystems. Preventing deforestation presents an opportunity for countries to benefit from carbon payments for preservation of threatened carbon stocks.
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