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  • 1
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  The introduction of the immunosuppressant cyclosporine has significantly improved renal transplant survival. It is an expensive drug and generic alternatives may offer cost advantages. However, generic alternatives must be shown to provide equivalent therapeutic efficacy and safety. This study reports our experience of a switch from the microemulsion formulation of cyclosporine, Neoral (Novartis), to the generic equivalent, Cysporin (Mayne Pharma).Method:  A two-period, single-sequence, cross-over study was done to compare cyclosporine blood levels and the area under the curve (AUC) of Neoral with Cysporin 2 weeks after a 1:1 dose switch. cyclosporine blood levels were measured at time points 0, 2, 4 and 8 h (C0, C2, C4, C8) after the switch. The cyclosporine AUC at 0–4 h and 0–12 h were calculated using the trapezoidal method. The two formulations were considered to result in equivalent blood levels if the 95% confidence interval (CI) of the ratio of the two levels was within 0.8–1.25.Results and Conclusion:  A total of 38 stable renal transplant patients aged 49.79 ± 11.38 years (mean ± SD), who were 7.84 ± 3.97 years postrenal transplantation, were studied. The Neoral dose at the time of the switch was 2.38 ± 1.21 mg per kg bodyweight. At all measured time points the 95% CI for the cyclosporine drug level ratio was between 0.9 and 1.15. There were no significant adverse events during the period of study. We conclude that the generic formulation of cylosporin, Cysporin, after a 1:1 switch from Neoral results in equivalent blood levels in stable renal transplant recipients. After switchover cyclosporine levels at C0 or C2 can continue to be monitored as per the institution's current monitoring practice.
    Type of Medium: Electronic Resource
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  • 2
    Publication Date: 2022-05-25
    Description: © The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Atmospheric Measurement Techniques 11 (2018): 1725-1739, doi:10.5194/amt-11-1725-2018.
    Description: An uncontrolled gas leak from 25 March to 16 May 2012 led to evacuation of the Total Elgin wellhead and neighbouring drilling and production platforms in the UK North Sea. Initially the atmospheric flow rate of leaking gas and condensate was very poorly known, hampering environmental assessment and well control efforts. Six flights by the UK FAAM chemically instrumented BAe-146 research aircraft were used to quantify the flow rate. The flow rate was calculated by assuming the plume may be modelled by a Gaussian distribution with two different solution methods: Gaussian fitting in the vertical and fitting with a fully mixed layer. When both solution methods were used they compared within 6 % of each other, which was within combined errors. Data from the first flight on 30 March 2012 showed the flow rate to be 1.3 ± 0.2 kg CH4 s−1, decreasing to less than half that by the second flight on 17 April 2012. δ13CCH4 in the gas was found to be −43 ‰, implying that the gas source was unlikely to be from the main high pressure, high temperature Elgin gas field at 5.5 km depth, but more probably from the overlying Hod Formation at 4.2 km depth. This was deemed to be smaller and more manageable than the high pressure Elgin field and hence the response strategy was considerably simpler. The first flight was conducted within 5 days of the blowout and allowed a flow rate estimate within 48 h of sampling, with δ13CCH4 characterization soon thereafter, demonstrating the potential for a rapid-response capability that is widely applicable to future atmospheric emissions of environmental concern. Knowledge of the Elgin flow rate helped inform subsequent decision making. This study shows that leak assessment using appropriately designed airborne plume sampling strategies is well suited for circumstances where direct access is difficult or potentially dangerous. Measurements such as this also permit unbiased regulatory assessment of potential impact, independent of the emitting party, on timescales that can inform industry decision makers and assist rapid-response planning by government.
    Repository Name: Woods Hole Open Access Server
    Type: Article
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  • 3
    Publication Date: 2022-05-27
    Description: © The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Stevens, B., Bony, S., Farrell, D., Ament, F., Blyth, A., Fairall, C., Karstensen, J., Quinn, P. K., Speich, S., Acquistapace, C., Aemisegger, F., Albright, A. L., Bellenger, H., Bodenschatz, E., Caesar, K.-A., Chewitt-Lucas, R., de Boer, G., Delanoë, J., Denby, L., Ewald, F., Fildier, B., Forde, M., George, G., Gross, S., Hagen, M., Hausold, A., Heywood, K. J., Hirsch, L., Jacob, M., Jansen, F., Kinne, S., Klocke, D., Kölling, T., Konow, H., Lothon, M., Mohr, W., Naumann, A. K., Nuijens, L., Olivier, L., Pincus, R., Pöhlker, M., Reverdin, G., Roberts, G., Schnitt, S., Schulz, H., Siebesma, A. P., Stephan, C. C., Sullivan, P., Touzé-Peiffer, L., Vial, J., Vogel, R., Zuidema, P., Alexander, N., Alves, L., Arixi, S., Asmath, H., Bagheri, G., Baier, K., Bailey, A., Baranowski, D., Baron, A., Barrau, S., Barrett, P. A., Batier, F., Behrendt, A., Bendinger, A., Beucher, F., Bigorre, S., Blades, E., Blossey, P., Bock, O., Böing, S., Bosser, P., Bourras, D., Bouruet-Aubertot, P., Bower, K., Branellec, P., Branger, H., Brennek, M., Brewer, A., Brilouet , P.-E., Brügmann, B., Buehler, S. A., Burke, E., Burton, R., Calmer, R., Canonici, J.-C., Carton, X., Cato Jr., G., Charles, J. A., Chazette, P., Chen, Y., Chilinski, M. T., Choularton, T., Chuang, P., Clarke, S., Coe, H., Cornet, C., Coutris, P., Couvreux, F., Crewell, S., Cronin, T., Cui, Z., Cuypers, Y., Daley, A., Damerell, G. M., Dauhut, T., Deneke, H., Desbios, J.-P., Dörner, S., Donner, S., Douet, V., Drushka, K., Dütsch, M., Ehrlich, A., Emanuel, K., Emmanouilidis, A., Etienne, J.-C., Etienne-Leblanc, S., Faure, G., Feingold, G., Ferrero, L., Fix, A., Flamant, C., Flatau, P. J., Foltz, G. R., Forster, L., Furtuna, I., Gadian, A., Galewsky, J., Gallagher, M., Gallimore, P., Gaston, C., Gentemann, C., Geyskens, N., Giez, A., Gollop, J., Gouirand, I., Gourbeyre, C., de Graaf, D., de Groot, G. E., Grosz, R., Güttler, J., Gutleben, M., Hall, K., Harris, G., Helfer, K. C., Henze, D., Herbert, C., Holanda, B., Ibanez-Landeta, A., Intrieri, J., Iyer, S., Julien, F., Kalesse, H., Kazil, J., Kellman, A., Kidane, A. T., Kirchner, U., Klingebiel, M., Körner, M., Kremper, L. A., Kretzschmar, J., Krüger, O., Kumala, W., Kurz, A., L'Hégaret, P., Labaste, M., Lachlan-Cope, T., Laing, A., Landschützer, P., Lang, T., Lange, D., Lange, I., Laplace, C., Lavik, G., Laxenaire, R., Le Bihan, C., Leandro, M., Lefevre, N., Lena, M., Lenschow, D., Li, Q., Lloyd, G., Los, S., Losi, N., Lovell, O., Luneau, C., Makuch, P., Malinowski, S., Manta, G., Marinou, E., Marsden, N., Masson, S., Maury, N., Mayer, B., Mayers-Als, M., Mazel, C., McGeary, W., McWilliams, J. C., Mech, M., Mehlmann, M., Meroni, A. N., Mieslinger, T., Minikin, A., Minnett, P., Möller, G., Morfa Avalos, Y., Muller, C., Musat, I., Napoli, A., Neuberger, A., Noisel, C., Noone, D., Nordsiek, F., Nowak, J. L., Oswald, L., Parker, D. J., Peck, C., Person, R., Philippi, M., Plueddemann, A., Pöhlker, C., Pörtge, V., Pöschl, U., Pologne, L., Posyniak, M., Prange, M., Quiñones Meléndez, E., Radtke, J., Ramage, K., Reimann, J., Renault, L., Reus, K., Reyes, A., Ribbe, J., Ringel, M., Ritschel, M., Rocha, C. B., Rochetin, N., Röttenbacher, J., Rollo, C., Royer, H., Sadoulet, P., Saffin, L., Sandiford, S., Sandu, I., Schäfer, M., Schemann, V., Schirmacher, I., Schlenczek, O., Schmidt, J., Schröder, M., Schwarzenboeck, A., Sealy, A., Senff, C. J., Serikov, I., Shohan, S., Siddle, E., Smirnov, A., Späth, F., Spooner, B., Stolla, M. K., Szkółka, W., de Szoeke, S. P., Tarot, S., Tetoni, E., Thompson, E., Thomson, J., Tomassini, L., Totems, J., Ubele, A. A., Villiger, L., von Arx, J., Wagner, T., Walther, A., Webber, B., Wendisch, M., Whitehall, S., Wiltshire, A., Wing, A. A., Wirth, M., Wiskandt, J., Wolf, K., Worbes, L., Wright, E., Wulfmeyer, V., Young, S., Zhang, C., Zhang, D., Ziemen, F., Zinner, T., and Zöger, M.: EUREC4A. Earth System Science Data, 13(8), (2021): 4067–4119, https://doi.org/10.5194/essd-13-4067-2021.
    Description: The science guiding the EUREC4A campaign and its measurements is presented. EUREC4A comprised roughly 5 weeks of measurements in the downstream winter trades of the North Atlantic – eastward and southeastward of Barbados. Through its ability to characterize processes operating across a wide range of scales, EUREC4A marked a turning point in our ability to observationally study factors influencing clouds in the trades, how they will respond to warming, and their link to other components of the earth system, such as upper-ocean processes or the life cycle of particulate matter. This characterization was made possible by thousands (2500) of sondes distributed to measure circulations on meso- (200 km) and larger (500 km) scales, roughly 400 h of flight time by four heavily instrumented research aircraft; four global-class research vessels; an advanced ground-based cloud observatory; scores of autonomous observing platforms operating in the upper ocean (nearly 10 000 profiles), lower atmosphere (continuous profiling), and along the air–sea interface; a network of water stable isotopologue measurements; targeted tasking of satellite remote sensing; and modeling with a new generation of weather and climate models. In addition to providing an outline of the novel measurements and their composition into a unified and coordinated campaign, the six distinct scientific facets that EUREC4A explored – from North Brazil Current rings to turbulence-induced clustering of cloud droplets and its influence on warm-rain formation – are presented along with an overview of EUREC4A's outreach activities, environmental impact, and guidelines for scientific practice. Track data for all platforms are standardized and accessible at https://doi.org/10.25326/165 (Stevens, 2021), and a film documenting the campaign is provided as a video supplement.
    Description: This research has been supported by the people and government of Barbados; the Max Planck Society and its supporting members; the German Research Foundation (DFG) and the German Federal Ministry of Education and Research (grant nos. GPF18-1_69 and GPF18-2_50); the European Research Council (ERC) advanced grant EUREC4A (grant agreement no. 694768) under the European Union’s Horizon 2020 research and innovation program (H2020), with additional support from CNES (the French National Centre for Space Studies) through the EECLAT proposal, Météo-France, the CONSTRAIN H2020 project (grant agreement no. 820829), and the French AERIS Research Infrastructure; the Natural Environment Research Council (NE/S015868/1, NE/S015752/1, and NE/S015779/1); ERC under the European Union’s H2020 program (COMPASS, advanced grant agreement no. 74110); the French national program LEFE INSU, by IFREMER, the French research fleet, CNES, the French research infrastructures AERIS and ODATIS, IPSL, the Chaire Chanel program of the Geosciences Department at ENS, and the European Union's Horizon 2020 research and innovation program under grant agreement no. 817578 TRIATLAS; NOAA’s Climate Variability and Prediction Program within the Climate Program Office (grant nos. GC19-305 and GC19-301); NOAA cooperative agreement NA15OAR4320063; NOAA's Climate Program Office and base funds to NOAA/AOML's Physical Oceanography Division; Swiss National Science Foundation grant no. 188731; the UAS Program Office, Climate Program Office, and Physical Sciences Laboratory and by the US National Science Foundation (NSF) through grant AGS-1938108; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy – EXC 2037 “CLICCS – Climate, Climatic Change, and Society” – project no. 390683824; and Poland’s National Science Centre grant no. UMO-2018/30/M/ST10/00674 and Foundation for Polish Science grant no. POIR.04.04.00-00-3FD6/17-02.
    Repository Name: Woods Hole Open Access Server
    Type: Article
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  • 4
    Publication Date: 2016-01-15
    Description: Two 21-year old dizygotic twin men of Iraqi descent were homozygous for HBB codon 8, deletion of two nucleotides (–AA) frame-shift β 0 -thalassaemia mutation (FSC8; HBB :c25_26delAA). Both were clinically well, had splenomegaly, and were never transfused. They had mild microcytic anaemia (Hb 120-130 g/l) and 98% of their haemoglobin was fetal haemoglobin (HbF). Both were carriers of Hph α-thalassaemia mutation. On the three major HbF quantitative trait loci (QTL), the twins were homozygous for G〉A HBG2 Xmn1 site at single nucleotide polymorphism (SNP) rs7482144, homozygous for 3-bp deletion HBS1L-MYB intergenic polymorphism (HMIP) at rs66650371, and heterozygous for the A〉C BCL11A intron 2 polymorphism at rs766432. These findings were compared with those found in 22 other FSC8 homozygote patients: four presented with thalassaemia intermedia phenotype, and 18 were transfusion dependent. The inheritance of homozygosity for HMIP 3-bp deletion at rs66650371 and heterozygosity for Hph α-thalassaemia mutation was found in the twins and not found in any of the other 22 patients. Further studies are needed to uncover likely additional genetic variants that could contribute to the exceptionally high HbF levels and mild phenotype in these twins.
    Print ISSN: 0007-1048
    Electronic ISSN: 1365-2141
    Topics: Medicine
    Published by Wiley-Blackwell
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