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Search Results: 1 - 10 of 475040 matches for " Nicole T. M. Saksens "
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Analysis of Rare Variants in the C3 Gene in Patients with Age-Related Macular Degeneration
Maheswara R. Duvvari, Codrut C. Paun, Gabri?lle H. S. Buitendijk, Nicole T. M. Saksens, Elena B. Volokhina, Tina Ristau, Frederieke E. Schoenmaker-Koller, Johannes P. H. van de Ven, Joannes M. M. Groenewoud, Lambertus P. W. J. van den Heuvel, Albert Hofman, Sascha Fauser, André G. Uitterlinden, Caroline C. W. Klaver, Carel B. Hoyng, Eiko K. de Jong, Anneke I. den Hollander
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0094165
Abstract: Age-related macular degeneration (AMD) is a progressive retinal disorder affecting over 33 million people worldwide. Genome-wide association studies (GWASs) for AMD identified common variants at 19 loci accounting for 15–65% of the heritability and it has been hypothesized that the missing heritability may be attributed to rare variants with large effect sizes. Common variants in the complement component 3 (C3) gene have been associated with AMD and recently a rare C3 variant (Lys155Gln) was identified which exerts a large effect on AMD susceptibility independent of the common variants. To explore whether additional rare variants in the C3 gene are associated with AMD, we sequenced all coding exons in 84 unrelated AMD cases. Subsequently, we genotyped all identified variants in 1474 AMD cases and 2258 controls. Additionally, because of the known genetic overlap between AMD and atypical hemolytic uremic syndrome (aHUS), we genotyped two recurrent aHUS-associated C3 mutations in the entire cohort. Overall, we identified three rare variants (Lys65Gln (P = 0.04), Arg735Trp (OR = 17.4, 95% CI = 2.2–136; P = 0.0003), and Ser1619Arg (OR = 5.2, 95% CI = 1.0–25; P = 0.05) at the C3 locus that are associated with AMD in our EUGENDA cohort. However, the Arg735Trp and Ser1619Arg variants were not found to be associated with AMD in the Rotterdam Study. The Lys65Gln variant was only identified in patients from Nijmegen, the Netherlands, and thus may represent a region-specific AMD risk variant.
Modeling Biomarker Dynamics with Implications for the Treatment of Prostate Cancer
Erin B. Hedican,John T. Kemper,Nicole M. Lanie
Computational and Mathematical Methods in Medicine , 2007, DOI: 10.1080/17486700701349021
Abstract: The authors review existing models of biomarker dynamics and develop and investigate several new models which may better accommodate the underlying biology. While the general foundations of the models studied could be applied to a number of biomarker systems, the parameter values and specific applications to treatment regimens are focused on the role of prostate-specific antigen (PSA) as a biomarker for prostate cancer. Included are suggestions for possible clinical validation studies.
The Role of Zinc in Alzheimer's Disease
Nicole T. Watt,Isobel J. Whitehouse,Nigel M. Hooper
International Journal of Alzheimer's Disease , 2011, DOI: 10.4061/2011/971021
Abstract: Zinc, the most abundant trace metal in the brain, has numerous functions, both in health and in disease. Zinc is released into the synaptic cleft of glutamatergic neurons alongside glutamate from where it interacts and modulates NMDA and AMPA receptors. In addition, zinc has multifactorial functions in Alzheimer's disease (AD). Zinc is critical in the enzymatic nonamyloidogenic processing of the amyloid precursor protein (APP) and in the enzymatic degradation of the amyloid-β (Aβ) peptide. Zinc binds to Aβ promoting its aggregation into neurotoxic species, and disruption of zinc homeostasis in the brain results in synaptic and memory deficits. Thus, zinc dyshomeostasis may have a critical role to play in the pathogenesis of AD, and the chelation of zinc is a potential therapeutic approach.
Moving Cages Further Offshore: Effects on Southern Bluefin Tuna, T. maccoyii, Parasites, Health and Performance
Nicole T. Kirchhoff, Kirsty M. Rough, Barbara F. Nowak
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0023705
Abstract: The effects of offshore aquaculture on SBT health (particularly parasitic infections and haematology) and performance were the main aim of this study. Two cohorts of ranched Southern Bluefin tuna (SBT) (Thunnus maccoyii) were monitored throughout the commercial season, one maintained in the traditional near shore tuna farming zone and one maintained further offshore. SBT maintained offshore had reduced mortality, increased condition index at week 6 post transfer, reduced blood fluke and sealice loads, and haematological variables such as haemoglobin or lysozyme equal to or exceeding near shore maintained fish. The offshore cohort had no Cardicola forsteri and a 5% prevalence of Caligus spp., compared to a prevalence of 85% for Cardicola forsteri and 55% prevalence for Caligus spp. near shore at 6 weeks post transfer. This study is the first of its kind to examine the effects of commercial offshore sites on farmed fish parasites, health and performance.
Anabolic steroid abuse causing recurrent hepatic adenomas and hemorrhage
Nicole M Martin, Barham K Abu Dayyeh, Raymond T Chung
World Journal of Gastroenterology , 2008,
Abstract: Anabolic steroid abuse is common among athletes and is associated with a number of medical complications. We describe a case of a 27-year-old male bodybuilder with multiple hepatic adenomas induced by anabolic steroids. He initially presented with tumor hemorrhage and was treated with left lateral hepatic segmentectomy. Regression of the remaining tumors was observed with cessation of steroid use. However, 3 years and a half after his initial hepatic segmentectomy, he presented with recurrent tumor enlargement and intraperitoneal hemorrhage in the setting of steroid abuse relapse. Given his limited hepatic reserve, he was conservatively managed with embolization of the right accessory hepatic artery. This is the first reported case of hepatic adenoma re-growth with recidivistic steroid abuse, complicated by life-threatening hemorrhage. While athletes and bodybuilders are often aware of the legal and social ramifications of steroid abuse, they should continue to be counseled about its serious medical risks.
In Vitro Anticancer Assessment of Annickia chlorantha (Oliv.) Setten & Maas Stem (Annonaceae) Bark from Democratic Republic of Congo  [PDF]
Damien S. Tshibangu, Selvaraj Divakar, Muthiah Ramanathan, Govindarajan Syamala, Koto-te-Nyiwa Ngbolua, Jean Chrysostome V. Mudogo, Dinangayi D. Tshilanda, Nicole M. Misengabu, Pius T. Mpiana
Journal of Biosciences and Medicines (JBM) , 2016, DOI: 10.4236/jbm.2016.44004
Abstract: In this study, we evaluated the anti-cancer property of five bark extracts and the isolates from chloroform and ethyl acetate of Annickia chlorantha by the tetrazolium salt method (MTT method). The anti-cancer activity was performed on human prostate cancer cell lines PC-3 and hormone-dependent breast cancer cell lines MCF-7. Results indicated that the two isolates displayed interesting cytotoxicity towards MCF-7 cell lines with CC50 of 3.84 CC50/mL and 4.87 CC50/mL for chloroform and ethyl acetate respectively; while the total bark extracts showed CC50 of 24.33 CC50/mL, 36.49 CC50/ mL and 73.52 CC50/mL for chloroform, ethyl acetate and methanol extracts respectively. By the other hand on PC-3, the CC50 of the isolates were higher than the one on MCF-7, more than 10 CC50/mL for both chloroform and ethyl acetate isolates and 49.14 CC50/mL, 77.33 CC50/mL, 89.38 CC50/mL and 92.37 CC50/mL, respectively for chloroform, ethyl acetate and methanol soluble extracts. From this study, we identified that the two isolates had anti-cancer properties against MCF-7 cell lines.
Anticipated Inversion and Visibility Conditions over Glacier Bay with a Changing Climate  [PDF]
Nicole M?lders, Scott Gende
Journal of Environmental Protection (JEP) , 2015, DOI: 10.4236/jep.2015.65048
Abstract: A RCP4.5 simulation from the Community Earth System Model was downscaled by the Weather Research and Forecasting Model, inline coupled with chemistry, to examine how climate change may affect inversions and visibility in Glacier Bay in the presence of cruise-ship visitations. Mean downscaled climate conditions for the tourist seasons for 2006-2012 were compared with downscaled conditions for 2026-2032 with identical cruise-ship entries and operating conditions thereby isolating pollutant retention and visibility differences caused by atmospheric climate change. Notable changes in future temperature, humidity, precipitation, and wind-speed occurred for large areas of Southeast Alaska and the Gulf of Alaska, although the anticipated differences were less pronounced in Glacier Bay due to the presence of the large glaciers and ice fields. While increased sensible heat and water vapor in the atmospheric boundary layer contributed to on average 4.5 h reduced inversion duration in Glacier Bay, the on average 0.23 m·s-1 reduced wind speeds increased inversion frequency by 4% on average. The future on average wetter conditions and altered precipitation patterns in Glacier Bay affected the removal of gases and particulate matter emitted by cruise ships locally or advected from areas outside the park. Season-spatial averaged visibility in Glacier Bay remained the same. However, visibility was degraded in the future scenario later in the season and slightly improved during spring. The warmer conditions contributed to decreased visibility indirectly by tieing up less NO2 in PAN and increasing biogenic NOx emissions. The wetter conditions contributed to reduced visibility in the last third of the tourist season.
Impacts of Cruise-Ship Entry Quotas on Visibility and Air Quality in Glacier Bay  [PDF]
Nicole M?lders, Scott Gende
Journal of Environmental Protection (JEP) , 2015, DOI: 10.4236/jep.2015.611109
Abstract: Managers at Glacier Bay National Park must annually determine the allowable number of cruise-ship entries into the park. This decision considers how differences in visitor volume may affect park resources. This study quantified the impacts to air quality and visibility under different ship quotas using simulations with the Weather Research and Forecasting model inline coupled with chemistry. Results of the simulation assuming two entries per day for May 15 to September 15, 2008 (QTA; 248 ship entries representing a 35% increase) were compared to those of the 2008 cruise-ship activity (REF; 184) during that timeframe. A simulation without anthropogenic emissions (CLN) served to assess the overall impacts of cruise-ship emissions on visibility and air quality in Glacier Bay. Compared to REF, the increased entry quotas shifted chemical regimes and aerosol composition, depending upon thermodynamical conditions, and ambient concentrations. On days with notable regime shifts, sulfur-dioxide concentrations deceased while ammonium-sulfate aerosol concentrations increased. The increased quotas also altered the fine-to-coarse aerosol ratios in both directions despite constant ratio of fine-to-coarse aerosol emissions. In Glacier Bay, the days with worst visibility coincided with high relative humidity, although this relationship varied by scenario. On the 20% worst days, mean visibility was slightly better in CLN (mean haze index over Glacier Bay waters = 2.9 dv) than in REF ( = 3.1 dv). While increased emissions in QTA reduced mean visibility by 0.1 dv, the 10th, 50th and 90th percentile of haze indices remained identical to those in REF. Best (worst) visibility occurred on the same days in REF and QTA due to emission impacts, but on different days than in CLN because relative humidity solely governed visibility in CLN. While calm wind played no role for visibility in CLN, wind speed gained similar importance for visibility as relative humidity in REF and QTA. Overall, increasing ship quotas would only marginally affect air quality and visibility as compared to REF, although even small changes in these parameters need careful consideration in the context of conserving the values of Glacier Bay.
On the Limits to Manage Air-Quality in Glacier Bay  [PDF]
Nicole M?lders, Scott Gende
Journal of Environmental Protection (JEP) , 2016, DOI: 10.4236/jep.2016.712151
Abstract: In Glacier Bay National Park, about 95% of the visitors come on board of cruise ships. The National Park Service has the mandate to manage park resources like air quality and visibility, while ensuring visitation. To understand the impact of cruise-ship emissions on the overall concentrations in Glacier Bay, emission-source contribution ratios (ESCR) and the interaction of pollutant from local and/or distant sources were determined using results from four WRF/Chem simulations of the 2008 tourist season (May 15 to September 15). These simulations only differed by the emissions considered: Biogenic emissions only (CLN), biogenic plus activity-based cruise-ship emissions (REF), biogenic plus all anthropogenic emissions except cruise-ship emissions (RETRO), and all aforementioned emissions (ALL). In general, ESCRs differed among pollutants. Interaction between pollutants from cruise-ship emissions and species from other sources including those advected into the bay decreased towards the top of the atmospheric boundary layer. Pollutants from different sources interacted strongest (lowest) in the west arm of the fjord where ships berthed for glacier viewing (in areas of the bay without cruise-ship travel). Pollutant interaction both enhanced/reduced NO2 concentrations by 10% (4 - 8 ppt absolute). Except for ozone, cruise-ship emissions on average governed air quality in the bay. On days with cruise-ship visits, they contributed between 60% and 80% of the bay-wide daily mean SO2 and NO2 concentrations below 1 km height. On days without visits, cruise-ship contributions still reached 40% due to previous visits. Highest cruise-ship ESCRs occurred during stagnant weather conditions. Despite the fact that all coarse particulate matter was due to anthropogenic sources, worst visibility conditions were due to meteorology. The results suggest limits as well as windows for managing air quality and visibility in Glacier Bay.
Climatology of Air Quality in Arctic Cities—Inventory and Assessment  [PDF]
Nicole M?lders, Gerhard Kramm
Open Journal of Air Pollution (OJAP) , 2018, DOI: 10.4236/ojap.2018.71004
Abstract: Freely available data of sulfur dioxide (SO2), ammonia (NH3), nitrogen dioxide (NO2), ozone (O3), and particulate matter (PM) observed in Arctic cities (north of 59.99 N) between 1972 and 2016 were compiled into an air-quality inventory of samples taken for limited periods. For cities with multiple years of data, air-quality climatology was determined in terms of daily means in the annual course. Mean urban air-quality climatology was calculated for regions of similar insolation, emission standards, topography, Köppen-Geiger classification, and city size. Urban concentrations of PM precursors (SO2, NH3, NO2), PM2.5 and PM10 (PM with diameter less than 2.5 and 10 μm) were assessed in the sense of climatology with evidence from current knowledge. Typically, annual SO2 and NO2 means were lower for small than large Arctic cities, but can vary more than an order of magnitude over short distance. Cities seeing seasonal sea-ice had W-shaped mean annual courses of daily O3, while other cities had a spring maximum. Typically, annual means of urban pollutants in North America exceeded those in Scandinavia except for O3, where the opposite was true. Annual mean urban PM2.5 and PM10 concentrations varied from 1.6 to 21.2 μg·m-3 and 2 to 18.2 μg·m-3, respectively. Since PM10 encompasses PM2.5, annual PM10 means must be at least 21.2 μg·m-3. According to rural-to-urban ratios of species, seasonal transport of pollutants from
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