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6. Novel Association of the NOTCH Pathway Regulator MIB1 Gene With the Development of Bicuspid Aortic Valve.

Author

Tessler, I., Albuisson, J., Piñeiro-Sabarís, R., Verstraeten, A., Kamber Kaya, H.E., Siguero-Álvarez, M., Goudot, G., MacGrogan, D., Luyckx, I., Shpitzen, S., Levin, G., Kelman, G., Reshef, N., Mananet, H., Holdcraft, J., Muehlschlegel, J.D., Peloso, G.M., Oppenheim, O., Cheng, C., Mazzella, J.M., Andelfinger, G., Mital, S., Eriksson, P., Billon, C., Heydarpour, M., Dietz, H.C., Jeunemaitre, X., Leitersdorf, E., Sprinzak, D., Blacklow, S.C., Body, S.C., Carmi, S., Loeys, B.L., Pompa, J.L. de la, Gilon, D., Messas, E., Durst, R., Tessler, I., Albuisson, J., Piñeiro-Sabarís, R., Verstraeten, A., Kamber Kaya, H.E., Siguero-Álvarez, M., Goudot, G., MacGrogan, D., Luyckx, I., Shpitzen, S., Levin, G., Kelman, G., Reshef, N., Mananet, H., Holdcraft, J., Muehlschlegel, J.D., Peloso, G.M., Oppenheim, O., Cheng, C., Mazzella, J.M., Andelfinger, G., Mital, S., Eriksson, P., Billon, C., Heydarpour, M., Dietz, H.C., Jeunemaitre, X., Leitersdorf, E., Sprinzak, D., Blacklow, S.C., Body, S.C., Carmi, S., Loeys, B.L., Pompa, J.L. de la, Gilon, D., Messas, E., and Durst, R.

Abstract

Contains fulltext : 295944.pdf (Publisher’s version ) (Closed access), IMPORTANCE: Nonsyndromic bicuspid aortic valve (nsBAV) is the most common congenital heart valve malformation. BAV has a heritable component, yet only a few causative genes have been identified; understanding BAV genetics is a key point in developing personalized medicine. OBJECTIVE: To identify a new gene for nsBAV. DESIGN, SETTING, AND PARTICIPANTS: This was a comprehensive, multicenter, genetic association study based on candidate gene prioritization in a familial cohort followed by rare and common association studies in replication cohorts. Further validation was done using in vivo mice models. Study data were analyzed from October 2019 to October 2022. Three cohorts of patients with BAV were included in the study: (1) the discovery cohort was a large cohort of inherited cases from 29 pedigrees of French and Israeli origin; (2) the replication cohort 1 for rare variants included unrelated sporadic cases from various European ancestries; and (3) replication cohort 2 was a second validation cohort for common variants in unrelated sporadic cases from Europe and the US. MAIN OUTCOMES AND MEASURES: To identify a candidate gene for nsBAV through analysis of familial cases exome sequencing and gene prioritization tools. Replication cohort 1 was searched for rare and predicted deleterious variants and genetic association. Replication cohort 2 was used to investigate the association of common variants with BAV. RESULTS: A total of 938 patients with BAV were included in this study: 69 (7.4%) in the discovery cohort, 417 (44.5%) in replication cohort 1, and 452 (48.2%) in replication cohort 2. A novel human nsBAV gene, MINDBOMB1 homologue MIB1, was identified. MINDBOMB1 homologue (MIB1) is an E3-ubiquitin ligase essential for NOTCH-signal activation during heart development. In approximately 2% of nsBAV index cases from the discovery and replication 1 cohorts, rare MIB1 variants were detected, predicted to be damaging, and were significantly enriched compared with populati

Published
2023

7. Higher Fusion Power Gain with Current and Pressure Profile Control in Strongly Shaped DIII-D Tokamak Plasmas

Author

Lazarus, EA, Navratil, GA, Greenfield, CM, Strait, EJ, Austin, ME, Burrell, KH, Casper, TA, Baker, DR, DeBoo, JC, Doyle, EJ, Durst, R, Ferron, JR, Forest, CB, Gohil, P, Groebner, RJ, Heidbrink, WW, Hong, R-M, Houlberg, WA, Howald, AW, Hsieh, C-L, Hyatt, AW, Jackson, GL, Kim, J, Lao, LL, Lasnier, CJ, Leonard, AW, Lohr, J, La Haye, RJ, Maingi, R, Miller, RL, Murakami, M, Osborne, TH, Perkins, LJ, Petty, CC, Rettig, CL, Rhodes, TL, Rice, BW, Sabbagh, SA, Schissel, DP, Scoville, JT, Snider, RT, Staebler, GM, Stallard, BW, Stambaugh, RD, St. John, HE, Stockdale, RE, Taylor, PL, Thomas, DM, Turnbull, AD, Wade, MR, Wood, R, and Whyte, D

Subjects
Mathematical Sciences, Physical Sciences, Engineering, General Physics
Abstract

Fusion power has been increased by a factor of 3 in DIII-D by tailoring the pressure profile to avoid the kink instability in H-mode plasmas. The resulting plasmas are found to have neoclassical ion confinement. This reduction in transport losses in beam-heated plasmas with negative central shear is correlated with a dramatic reduction in density fluctuations. Improved magnetohydrodynamic stability is achieved by controlling the plasma pressure profile width. In deuterium plasmas the highest gain Q (the ratio of fusion power to input power), was 0.0015, corresponding to an equivalent Q of 0.32 in a deuterium-tritium plasma. © 1996 The American Physical Society.

Published
1996

8. Recent D-T results on TFTR

Author

Johnson, DW, Arunasalam, V, Barnes, CW, Batha, SH, Bateman, G, Beer, M, Bell, MG, Bell, R, Bitter, M, Bretz, NL, Budny, R, Bush, CE, Cauffman, S, Chang, CS, Chang, Z, Cheng, CZ, Darrow, DS, Dendy, R, Dorland, W, Duong, HH, Durst, R, Efthimion, PC, Ernst, D, Evenson, H, Fisch, N, Fisher, R, Fonck, RJ, Fredrickson, E, Fu, GY, Fujita, T, Furth, HP, Gorelenkov, N, Grek, B, Grisham, LR, Hammett, G, Hawryluk, RJ, Heidbrink, W, Herrmann, HW, Hill, KW, Hosea, J, Hsuan, H, Hughes, M, Janos, A, Jassby, DL, Jobes, FC, Johnson, LC, Kamperschroer, J, Kesner, J, Kotschenreuther, M, Kugel, H, Lamarche, PH, Leblanc, B, Levinton, FM, MacHuzak, J, Majeski, R, Mansfield, DK, Marmar, ES, Mazzucato, E, Mauel, M, McChesney, J, McGuire, KM, McKee, G, Meade, DM, Medley, SS, Mikkelsen, DR, Mirnov, SV, Mueller, D, Nazikian, R, Osakabe, M, Owens, DK, Park, H, Park, W, Parks, P, Paul, SF, Petrov, M, Phillips, CK, Phillips, M, Qualls, AL, Ramsey, A, Redi, MH, Rewoldt, G, Roberts, D, Rogers, J, Roquemore, AL, Ruskov, E, Sabbagh, SA, Sasao, M, Schilling, G, Schivell, J, Schmidt, GL, Scott, SD, Semenov, I, Sesnic, S, Skinner, CH, Spong, D, Stratton, BC, Strachan, JD, Stodiek, W, Synakowski, E, and Takahashi, H

Subjects
Fluids & Plasmas, Atomic, Molecular, Nuclear, Particle and Plasma Physics, Other Physical Sciences, Atomic, Molecular, Nuclear, Particle and Plasma Physics
Abstract

Routine tritium operation in TFTR has permitted investigations of alpha particle physics in parameter ranges resembling those of a reactor core. ICRF wave physics in a DT plasma and the influence of isotopic mass on supershot confinement have also been studied. Continued progress has been made in optimizing fusion power production in TFTR, using extended machine capability and Li wall conditioning. Performance is currently limited by MHD stability. A new reversed magnetic shear regime is being investigated with reduced core transport and a higher predicted stability limit.

Published
1995

9. Plasma-surface interactions in TFTR DT experiments

Author

Owens, DK, Adler, H, Alling, P, Ancher, C, Anderson, H, Anderson, JL, Ashcroft, D, Barnes, Cris W, Barnes, G, Batha, S, Bell, MG, Bell, R, Bitter, M, Blanchard, W, Bretz, NL, Budny, R, Bush, CE, Camp, R, Caorlin, M, Cauffman, S, Chang, Z, Cheng, CZ, Collins, J, Coward, G, Darrow, DS, DeLooper, J, Duong, H, Dudek, L, Durst, R, Efthimion, PC, Ernst, D, Fisher, R, Fonck, RJ, Fredrickson, E, Fromm, N, Fu, GY, Furth, HP, Gentile, C, Gorelenkov, N, Grek, B, Grisham, LR, Hammett, G, Hanson, GR, Hawryluk, RJ, Heidbrink, W, Hermann, HW, Hill, KW, Hosea, J, Hsuan, H, Janos, A, Jassby, DL, Jobes, FC, Johnson, DW, Johnson, LC, Kamperschroer, J, Kugel, H, Lam, NT, LaMarche, PH, Loughlin, MJ, LeBlanc, B, Leonard, M, Levinton, FM, Machuzak, J, Mansfield, DK, Martin, A, Mazzucato, E, Majeski, R, Marmar, E, McChesney, J, McCormack, B, McCune, DC, McGuire, KM, McKee, G, Meade, DM, Medley, SS, Mikkelsen, DR, Mueller, D, Murakami, M, Nagy, A, Nazikian, R, Newman, R, Nishitani, T, Norris, M, O'Connor, T, Oldaker, M, Osakabe, M, Park, H, Park, W, Paul, SF, Pearson, G, Perry, E, Petrov, M, Phillips, CK, Pitcher, S, Raftopoulos, S, Ramsey, A, Rasmussen, DA, Redi, MH, Roberts, D, and Rogers, J

Subjects
Materials Engineering, Energy
Abstract

TFTR has begun its campaign to study deuterium-tritium fusion under reactor-like conditions. Variable amounts of deuterium and tritium neutral beam power have been used to maximize fusion power, study alpha heating, investigate alpha particle confinement, and search for alpha driven plasma instabilities. Additional areas of study include energy and particle transport and confinement, ICRF heating schemes for DT plasmas, tritium retention, and fusion in high βp plasmas. The majority of this work is done in the TFTR supershot confinement regime. To obtain supershots, extensive limiter conditioning using helium fueled ohmic discharges and lithium pellet injection into ohmic and neutral beam heated plasmas is performed, resulting in a low recycling limiter. The relationship between recycling and core plasma confinement has been studied by using helium, deuterium and high-Z gas puffs to simulate high recycling limiter conditions. These studies show that confinement in TFTR supershots is very sensitive to the influx of neutral particles at the plasma edge. © 1995, All rights reserved.

Published
1995

10. Deuterium and tritium experiments on TFTR

Author

Strachan, JD, Adler, H, Barnes, CW, Batha, S, Bell, MG, Bell, R, Bitter, M, Bretz, NL, Budny, R, Bush, CE, Caorlin, M, Chang, Z, Darrow, DS, Duong, H, Durst, R, Efthimion, PC, Fisher, R, Fonck, RJ, Fredrickson, E, Grek, B, Grisham, LR, Hammett, G, Hawryiuk, RJ, Heidbrink, W, Herrmann, HW, Hill, KW, Hosea, J, Hsuan, H, Janos, A, Jassby, DL, Jobes, FC, Johnson, DW, Johnson, LC, Kugel, H, Lam, NT, LeBlanc, B, Levington, FM, Machuzak, J, Mansfield, DK, Mazzucato, E, Majeski, R, Marmar, E, McChesney, J, McGuire, KM, McKee, G, Meade, DM, Medley, SS, Mikkelsen, DR, Mueller, D, Murakami, M, Nazikian, R, Osakabe, M, Owens, DK, Park, H, Paul, SF, Petrov, M, Phillips, CK, Ramsey, AT, Redi, MH, Roberts, D, Rogers, J, Roquemore, AL, Ruskov, E, Sabbagh, SA, Sasao, M, Schilling, G, Schivell, J, Schmidt, GL, Scott, SD, Skinner, CH, Snipes, JA, Stevens, J, Stevenson, T, Stratton, BC, Synakowski, E, Taylor, G, Terry, JL, von Halle, A, von Goeler, S, Wilgen, JB, Wilson, JR, Wong, KL, Wurden, GA, Yamada, M, Young, KM, Zarnstorff, MC, and Zweben, SJ

Subjects
Atomic, Molecular, Nuclear, Particle and Plasma Physics, Other Physical Sciences, Fluids & Plasmas
Abstract

Three campaigns, prior to July 1994, attempted to increase the fusion power in DT plasmas on the Tokamak Fusion Test Reactor (TFTR). The first campaign was dedicated to obtaining >5 MW of fusion power while avoiding MHD events similar to the JET X-event. The second was aimed at producing maximum fusion power irrespective of proximity to MHD limits, and achieved 9 MW limited by a disruption. The third campaign increased the energy confinement time using lithium pellet conditioning while raising the ratio of alpha heating to beam heating.

Published
1994

11. Confinement and heating of a deuterium-tritium plasma

Author

Hawryluk, RJ, Adler, H, Alling, P, Ancher, C, Anderson, H, Anderson, JL, Ashcroft, D, Barnes, Cris W, Barnes, G, Batha, S, Bell, MG, Bell, R, Bitter, M, Blanchard, W, Bretz, NL, Budny, R, Bush, CE, Camp, R, Caorlin, M, Cauffman, S, Chang, Z, Cheng, CZ, Collins, J, Coward, G, Darrow, DS, DeLooper, J, Duong, H, Dudek, L, Durst, R, Efthimion, PC, Ernst, D, Fisher, R, Fonck, RJ, Fredrickson, E, Fromm, N, Fu, GY, Furth, HP, Gentile, C, Gorelenkov, N, Grek, B, Grisham, LR, Hammett, G, Hanson, GR, Heidbrink, W, Herrmann, HW, Hill, KW, Hosea, J, Hsuan, H, Janos, A, Jassby, DL, Jobes, FC, Johnson, DW, Johnson, LC, Kamperschroer, J, Kugel, H, Lam, NT, LaMarche, PH, Loughlin, MJ, LeBlanc, B, Leonard, M, Levinton, FM, Machuzak, J, Mansfield, DK, Martin, A, Mazzucato, E, Majeski, R, Marmar, E, McChesney, J, McCormack, B, McCune, DC, McGuire, KM, McKee, G, Meade, DM, Medley, SS, Mikkelsen, DR, Mueller, D, Murakami, M, Nagy, A, Nazikian, R, Newman, R, Nishitani, T, Norris, M, O’Connor, T, Oldaker, M, Osakabe, M, Owens, DK, Park, H, Park, W, Paul, SF, Pearson, G, Perry, E, Petrov, M, Phillips, CK, Pitcher, S, Ramsey, A, Rasmussen, DA, Redi, MH, Roberts, D, Rogers, J, and Rossmassler, R

Subjects
Mathematical Sciences, Physical Sciences, Engineering, General Physics
Abstract

The Tomamak Fusion Test reactor has performed initial high-power experiments with the plasma fueled with nominally equal densities of deuterium and tritium. Compared to pure deuterium plasmas, the energy stored in the electron and ions increased by ∼20%. These increases indicate improvements in confinement associated with the use of tritium and possibly heating of electrons by α particles created by the D-T fusion reactions. © 1994 The American Physical Society.

Published
1994

12. Fusion power production from TFTR plasmas fueled with deuterium and tritium

Author

Strachan, JD, Adler, H, Alling, P, Ancher, C, Anderson, H, Anderson, JL, Ashcroft, D, Barnes, Cris W, Barnes, G, Batha, S, Bell, MG, Bell, R, Bitter, M, Blanchard, W, Bretz, NL, Budny, R, Bush, CE, Camp, R, Caorlin, M, Cauffman, S, Chang, Z, Cheng, CZ, Collins, J, Coward, G, Darrow, DS, DeLooper, J, Duong, H, Dudek, L, Durst, R, Efthimion, PC, Ernst, D, Fisher, R, Fonck, RJ, Fredrickson, E, Fromm, N, Fu, GY, Furth, HP, Gentile, C, Gorelenkov, N, Grek, B, Grisham, LR, Hammett, G, Hanson, GR, Hawryluk, RJ, Heidbrink, W, Herrmann, HW, Hill, KW, Hosea, J, Hsuan, H, Janos, A, Jassby, DL, Jobes, FC, Johnson, DW, Johnson, LC, Kamperschroer, J, Kugel, H, Lam, NT, LaMarche, PH, Loughlin, MJ, LeBlanc, B, Leonard, M, Levinton, FM, Machuzak, J, Mansfield, DK, Martin, A, Mazzucato, E, Majeski, R, Marmar, E, McChesney, J, McCormack, B, McCune, DC, McGuire, KM, McKee, G, Meade, DM, Medley, SS, Mikkelsen, DR, Mueller, D, Murakami, M, Nagy, A, Nazikian, R, Newman, R, Nishitani, T, Norris, M, O’Connor, T, Oldaker, M, Osakabe, M, Owens, DK, Park, H, Park, W, Paul, SF, Pearson, G, Perry, E, Petrov, M, Phillips, CK, Pitcher, S, Ramsey, AT, Rasmussen, DA, Redi, MH, Roberts, D, and Rogers, J

Subjects
Neurodegenerative, Mathematical Sciences, Physical Sciences, Engineering, General Physics
Abstract

Peak fusion power production of 6.2±0.4 MW has been achieved in TFTR plasmas heated by deuterium and tritium neutral beams at a total power of 29.5 MW. These plasmas have an inferred central fusion alpha particle density of 1.2×1017 m-3 without the appearance of either disruptive magnetohydrodynamics events or detectable changes in Alfvén wave activity. The measured loss rate of energetic alpha particles agreed with the approximately 5% losses expected from alpha particles which are born on unconfined orbits. © 1994 The American Physical Society.

Published
1994

13. Preparations for deuterium–tritium experiments on the Tokamak Fusion Test Reactor*

Author

Hawryluk, RJ, Adler, H, Alling, P, Ancher, C, Anderson, H, Anderson, JL, Anderson, JW, Arunasalam, V, Ascione, G, Aschroft, D, Barnes, CW, Barnes, G, Batchelor, DB, Bateman, G, Batha, S, Baylor, LA, Beer, M, Bell, MG, Biglow, TS, Bitter, M, Blanchard, W, Bonoli, P, Bretz, NL, Brunkhorst, C, Budny, R, Burgess, T, Bush, H, Bush, CE, Camp, R, Caorlin, M, Carnevale, H, Chang, Z, Chen, L, Cheng, CZ, Chrzanowski, J, Collazo, I, Collins, J, Coward, G, Cowley, S, Cropper, M, Darrow, DS, Daugert, R, DeLooper, J, Duong, H, Dudek, L, Durst, R, Efthimion, PC, Ernst, D, Faunce, J, Fonck, RJ, Fredd, E, Fredrickson, E, Fromm, N, Fu, GY, Furth, HP, Garzotto, V, Gentile, C, Gettelfinger, G, Gilbert, J, Gioia, J, Goldfinger, RC, Golian, T, Gorelenkov, N, Gouge, MJ, Grek, B, Grisham, LR, Hammett, G, Hanson, GR, Heidbrink, W, Hermann, HW, Hill, KW, Hirshman, S, Hoffman, DJ, Hosea, J, Hulse, RA, Hsuan, H, Jaeger, EF, Janos, A, Jassby, DL, Jobes, FC, Johnson, DW, Johnson, LC, Kamperschroer, J, Kesner, J, Kugel, H, Kwon, S, Labik, G, Lam, NT, LaMarche, PH, Laughlin, MJ, Lawson, E, LeBlanc, B, Leonard, M, Levine, J, Levinton, FM, Loesser, D, Long, D, Machuzak, J, Mansfield, DE, and Marchlik, M

Subjects
Astronomical and Space Sciences, Atomic, Molecular, Nuclear, Particle and Plasma Physics, Classical Physics, Fluids & Plasmas
Abstract

The final hardware modifications for tritium operation have been completed for the Tokamak Fusion Test Reactor (TFTR) [Fusion Technol. 21, 1324 (1992)]. These activities include preparation of the tritium gas handling system, installation of additional neutron shielding, conversion of the toroidal field coil cooling system from water to a Fluorinert™ system, modification of the vacuum system to handle tritium, preparation, and testing of the neutral beam system for tritium operation and a final deuterium-deuterium (D-D) run to simulate expected deuterium-tritium (D-T) operation. Testing of the tritium system with low concentration tritium has successfully begun. Simulation of trace and high power D-T experiments using D-D have been performed. The physics objectives of D-T operation are production of ≈ 10 MW of fusion power, evaluation of confinement, and heating in deuteriumtritium plasmas, evaluation of α-particle heating of electrons, and collective effects driven by alpha particles and testing of diagnostics for confined a particles. Experimental results and theoretical modeling in support of the D-T experiments are reviewed. © 1994 American Institute of Physics.

Published
1994

19. The impact of type of dietary protein, animal versus vegetable, in modifying cardiometabolic risk factors: A position paper from the International Lipid Expert Panel (ILEP)

Author

Zhubi-Bakija, F., Bajraktari, G., Bytyci, I., Mikhailidis, D. P., Henein, M. Y., Latkovskis, G., Rexhaj, Z., Zhubi, E., Banach, M., Alnouri, F., Amar, F., Atanasov, A. G., Bartlomiejczyk, M. A., Bjelakovic, B., Bruckert, E., Cafferata, A., Ceska, R., Cicero, A. F. G., Collet, X., Descamps, O., Djuric, D., Durst, R., Ezhov, M. V., Fras, Z., Gaita, D., Hernandez, A. V., Jones, S. R., Jozwiak, J., Kakauridze, N., Katsiki, N., Khera, A., Kostner, K., Kubilius, R., Mancini, G. B. J., Marais, A. D., Martin, S. S., Martinez, J. A., Mazidi, M., Mirrakhimov, E., Miserez, A. R., Mitchenko, O., Moriarty, P. M., Nabavi, S. M., Nair, D., Panagiotakos, D. B., Paragh, G., Pella, D., Penson, P. E., Petrulioniene, Z., Pirro, M., Postadzhiyan, A., Puri, R., Reda, A., Reiner, Riadh, J., Richter, D., Rizzo, M., Ruscica, M., Sahebkar, A., Sattar, N., Serban, M. -C., Shehab, A. M. A., Shek, A. B., Sirtori, C. R., Stefanutti, C., Tomasik, T., Toth, P. P., Viigimaa, M., Vinereanu, D., Vohnout, B., von Haehling, S., Vrablik, M., Wong, N. D., Yeh, H. -I., Zhisheng, J., Zirlik, A., Zhubi-Bakija F, Bajraktari G, Bytyçi I, Mikhailidis DP, Henein MY, Latkovskis G, Rexhaj Z, Zhubi E, Banach M, International Lipid Expert Panel (ILEP), Cicero AFG, Zhubi-Bakija F., Bajraktari G., Bytyci I., Mikhailidis D.P., Henein M.Y., Latkovskis G., Rexhaj Z., Zhubi E., Banach M., Alnouri F., Amar F., Atanasov A.G., Bartlomiejczyk M.A., Bjelakovic B., Bruckert E., Cafferata A., Ceska R., Cicero A.F.G., Collet X., Descamps O., Djuric D., Durst R., Ezhov M.V., Fras Z., Gaita D., Hernandez A.V., Jones S.R., Jozwiak J., Kakauridze N., Katsiki N., Khera A., Kostner K., Kubilius R., Mancini G.B.J., Marais A.D., Martin S.S., Martinez J.A., Mazidi M., Mirrakhimov E., Miserez A.R., Mitchenko O., Moriarty P.M., Nabavi S.M., Nair D., Panagiotakos D.B., Paragh G., Pella D., Penson P.E., Petrulioniene Z., Pirro M., Postadzhiyan A., Puri R., Reda A., Reiner, Riadh J., Richter D., Rizzo M., Ruscica M., Sahebkar A., Sattar N., Serban M.-C., Shehab A.M.A., Shek A.B., Sirtori C.R., Stefanutti C., Tomasik T., Toth P.P., Viigimaa M., Vinereanu D., Vohnout B., von Haehling S., Vrablik M., Wong N.D., Yeh H.-I., Zhisheng J., Zirlik A., and UCL - (SLuc) Service de pathologie cardiovasculaire

Subjects
Adult, Male, Dietary protein, Weight loss, Cardiometabolic Risk Factors, food and beverages, Middle Aged, Recommended Dietary Allowances, Cardiovascular disease, Plant Proteins, Dietary, Cardiovascular disease, Cholesterol, Dietary protein, Metabolic syndrome, Weight loss, Adult, Aged, Animal Proteins, Dietary, Cardiometabolic Risk Factors, Cardiovascular Diseases, Diet, Healthy, Expert Testimony, Female, Humans, Male, Middle Aged, Plant Proteins, Dietary, Young Adult, Recommended Dietary Allowances, Metabolic syndrome, Young Adult, Cholesterol, Cardiovascular Diseases, Animal Proteins, Dietary, Humans, Female, Diet, Healthy, Expert Testimony, Aged
Abstract

Proteins play a crucial role in metabolism, in maintaining fluid and acid-base balance and antibody synthesis. Dietary proteins are important nutrients and are classified into: 1) animal proteins (meat, fish, poultry, eggs and dairy), and, 2) plant proteins (legumes, nuts and soy). Dietary modification is one of the most important lifestyle changes that has been shown to significantly decrease the risk of cardiovascular (CV) disease (CVD) by attenuating related risk factors. The CVD burden is reduced by optimum diet through replacement of unprocessed meat with low saturated fat, animal proteins and plant proteins. In view of the available evidence, it has become acceptable to emphasize the role of optimum nutrition to maintain arterial and CV health. Such healthy diets are thought to increase satiety, facilitate weight loss, and improve CV risk. Different studies have compared the benefits of omnivorous and vegetarian diets. Animal protein related risk has been suggested to be greater with red or processed meat over and above poultry, fish and nuts, which carry a lower risk for CVD. In contrast, others have shown no association of red meat intake with CVD. The aim of this expert opinion recommendation was to elucidate the different impact of animal vs vegetable protein on modifying cardiometabolic risk factors. Many observational and interventional studies confirmed that increasing protein intake, especially plant-based proteins and certain animal-based proteins (poultry, fish, unprocessed red meat low in saturated fats and low-fat dairy products) have a positive effect in modifying cardiometabolic risk factors. Red meat intake correlates with increased CVD risk, mainly because of its non-protein ingredients (saturated fats). However, the way red meat is cooked and preserved matters. Thus, it is recommended to substitute red meat with poultry or fish in order to lower CVD risk. Specific amino acids have favourable results in modifying major risk factors for CVD, such as hypertension. Apart from meat, other animal-source proteins, like those found in dairy products (especially whey protein) are inversely correlated to hypertension, obesity and insulin resistance.

Published
2021

20. Efficacy and safety of bempedoic acid for the treatment of hypercholesterolemia: A systematic review and meta-analysis

Author

Cicero A. F. G., Fogacci F., Hernandez A. V., Banach M., Alnouri F., Amar F., Atanasov A. G., Bajraktari G., Bartlomiejczyk M. A., Bjelakovic B., Bruckert E., Bielecka-Dabrowa A., Cafferata A., Ceska R., Collet X., Descamps O., Devaki N., Djuric D., Durst R., Ezhov M. V., Fras Z., Gaita D., von Haehling S., Jones S. R., Jozwiak J., Kakauridze N., Katsiki N., Khera A., Kostner K., Kubilius R., Latkovskis G., Mancini G. B. J., Marais A. D., Martin S. S., Martinez J. A., Mazidi M., Mikhailidis D. P., Mirrakhimov E., Miserez A. R., Mitchenko O., Moriarty P., Nabavi S. M., Panagiotakos D. B., Paragh G., Pella D., Penson P. E., Petrulioniene Z., Pirro M., Postadzhiyan A., Puri R., Reda A., Reiner Z., Riadh J., Richter D., Rizzo M., Ruscica M., Sahebkar A., Sattar N., Serban M. C., Shehab A. M. A., Shek A. B., Sirtori C. R., Stefanutti C., Tomasik T., Toth P. P., Viigimaa M., Vinereanu D., Vohnout B., Vrablik M., Wong N. D., Yeh H. I., Zhisheng J., Zirlik A., Cicero A.F.G., Fogacci F., Hernandez A.V., Banach M., Alnouri F., Amar F., Atanasov A.G., Bajraktari G., Bartlomiejczyk M.A., Bjelakovic B., Bruckert E., Bielecka-Dabrowa A., Cafferata A., Ceska R., Collet X., Descamps O., Devaki N., Djuric D., Durst R., Ezhov M.V., Fras Z., Gaita D., von Haehling S., Jones S.R., Jozwiak J., Kakauridze N., Katsiki N., Khera A., Kostner K., Kubilius R., Latkovskis G., Mancini G.B.J., Marais A.D., Martin S.S., Martinez J.A., Mazidi M., Mikhailidis D.P., Mirrakhimov E., Miserez A.R., Mitchenko O., Moriarty P., Nabavi S.M., Panagiotakos D.B., Paragh G., Pella D., Penson P.E., Petrulioniene Z., Pirro M., Postadzhiyan A., Puri R., Reda A., Reiner Z., Riadh J., Richter D., Rizzo M., Ruscica M., Sahebkar A., Sattar N., Serban M.C., Shehab A.M.A., Shek A.B., Sirtori C.R., Stefanutti C., Tomasik T., Toth P.P., Viigimaa M., Vinereanu D., Vohnout B., Vrablik M., Wong N.D., Yeh H.I., Zhisheng J., Zirlik A., Wierzbicki, Anthony, Penson, P, and Cicero AF, Fogacci F, Hernandez AV, Banach M

Subjects
Apolipoprotein B, Publication Ethics, 030204 cardiovascular system & hematology, Cardiovascular, Gastroenterology, Lipoprotein particle, Medical and Health Sciences, Biochemistry, chemistry.chemical_compound, Database and Informatics Methods, 0302 clinical medicine, Mathematical and Statistical Techniques, Anticholesteremic Agents, Apolipoproteins B, Cholesterol, Cholesterol, LDL, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic, Dicarboxylic Acids, Fatty Acids, Humans, Hypercholesterolemia, Peptide Fragments, Randomized Controlled Trials as Topic, Lipid and Blood Pressure Meta-Analysis Collaboration (LBPMC) Group and the International Lipid Expert Panel, Medicine and Health Sciences, Dicarboxylic Acids, 030212 general & internal medicine, Database Searching, Research Integrity, Randomized Controlled Trials as Topic, medicine.diagnostic_test, biology, Anticholesteremic Agents, Statistics, Fatty Acids, Drugs, General Medicine, Metaanalysis, Serious Mental Illness, Lipids, Phase III as Topic, Mental Health, Cholesterol, Physical Sciences, Medicine, Research Article, medicine.medical_specialty, RM, Science Policy, Lipoproteins, Hypercholesterolemia, Bempedoic acid, hypercholesterolemia, lipid profile, hsCRP, Research and Analysis Methods, LDL, 03 medical and health sciences, Clinical Trials, Phase II as Topic, Internal medicine, General & Internal Medicine, medicine, Humans, Clinical Trials, Statistical Methods, Apolipoproteins B, Pharmacology, Plasma Proteins, business.industry, Phase II as Topic, Statins, Biology and Life Sciences, Proteins, Odds ratio, Cholesterol, LDL, Confidence interval, Peptide Fragments, chemistry, Clinical Trials, Phase III as Topic, biology.protein, Uric acid, Creatine kinase, Lipid profile, business, Digestive Diseases, Mathematics
Abstract

Background Bempedoic acid is a first-in-class lipid-lowering drug recommended by guidelines for the treatment of hypercholesterolemia. Our objective was to estimate its average effect on plasma lipids in humans and its safety profile. Methods and findings We carried out a systematic review and meta-analysis of phase II and III randomized controlled trials on bempedoic acid (PROSPERO: CRD42019129687). PubMed (Medline), Scopus, Google Scholar, and Web of Science databases were searched, with no language restriction, from inception to 5 August 2019. We included 10 RCTs (n = 3,788) comprising 26 arms (active arm [n = 2,460]; control arm [n = 1,328]). Effect sizes for changes in lipids and high-sensitivity C-reactive protein (hsCRP) serum concentration were expressed as mean differences (MDs) and 95% confidence intervals (CIs). For safety analyses, odds ratios (ORs) and 95% CIs were calculated using the Mantel–Haenszel method. Bempedoic acid significantly reduced total cholesterol (MD −14.94%; 95% CI −17.31%, −12.57%; p < 0.001), non-high-density lipoprotein cholesterol (MD −18.17%; 95% CI −21.14%, −15.19%; p < 0.001), low-density lipoprotein cholesterol (MD −22.94%; 95% CI −26.63%, −19.25%; p < 0.001), low-density lipoprotein particle number (MD −20.67%; 95% CI −23.84%, −17.48%; p < 0.001), apolipoprotein B (MD −15.18%; 95% CI −17.41%, −12.95%; p < 0.001), high-density lipoprotein cholesterol (MD −5.83%; 95% CI −6.14%, −5.52%; p < 0.001), high-density lipoprotein particle number (MD −3.21%; 95% CI −6.40%, −0.02%; p = 0.049), and hsCRP (MD −27.03%; 95% CI −31.42%, −22.64%; p < 0.001). Bempedoic acid did not significantly modify triglyceride level (MD −1.51%; 95% CI −3.75%, 0.74%; p = 0.189), very-low-density lipoprotein particle number (MD 3.79%; 95% CI −9.81%, 17.39%; p = 0.585), and apolipoprotein A-1 (MD −1.83%; 95% CI −5.23%, 1.56%; p = 0.290). Treatment with bempedoic acid was positively associated with an increased risk of discontinuation of treatment (OR 1.37; 95% CI 1.06, 1.76; p = 0.015), elevated serum uric acid (OR 3.55; 95% CI 1.03, 12.27; p = 0.045), elevated liver enzymes (OR 4.28; 95% CI 1.34, 13.71; p = 0.014), and elevated creatine kinase (OR 3.79; 95% CI 1.06, 13.51; p = 0.04), though it was strongly associated with a decreased risk of new onset or worsening diabetes (OR 0.59; 95% CI 0.39, 0.90; p = 0.01). The main limitation of this meta-analysis is related to the relatively small number of individuals involved in the studies, which were often short or middle term in length. Conclusions Our results show that bempedoic acid has favorable effects on lipid profile and hsCRP levels and an acceptable safety profile. Further well-designed studies are needed to explore its longer-term safety., Maciej Banach and colleagues discuss the efficacy and safety of bempedoic acid, a drug that designed to lower LDL-C levels., Author summary Why was this study done? Lowering low-density lipoprotein cholesterol (LDL-C) is effective for reducing cardiovascular events over time. A number of phase II and phase III randomized controlled trials (RCTs) are already available showing encouraging results of bempedoic acid treatment on LDL-C. We aimed to perform a systematic review and meta-analysis on the clinical evidence available to date to better define the efficacy and tolerability profile of treatment with bempedoic acid. What did the researchers do and find? In this analysis of bempedoic acid that included 10 randomized clinical trials (n = 3,788 patients) comprising 26 arms (active arm [n = 2,460]; control arm [n = 1,328]), we confirmed that bempedoic acid significantly reduced total cholesterol (by 15%), non-high-density lipoprotein cholesterol (by 18.2%), LDL-C (by 22.9%), low-density lipoprotein particle number (by 20.7%), apolipoprotein B (by 15.2%), and high-sensitivity C-reactive protein (hsCRP) (by 27%), while negatively affecting serum levels of high-density lipoprotein cholesterol (−5.8%) and high-density lipoprotein particle number (−3.2%). Our results also confirmed that the therapy is overall safe and well tolerated, with no significant increase of serious adverse effects. What do these findings mean? The current meta-analysis demonstrates the multiple positive effects of bempedoic acid on lipid profile and hsCRP serum levels, as well as acceptable safety profile. This could be relevant in a setting where statin intolerance is very frequent and the LDL-C target suggested by international guidelines for dyslipidemia management is hard to achieve with standard therapies. An ongoing long-term cardiovascular outcomes trial will answer questions on the effect of bempedoic acid on cardiovascular events and mortality as well as on the drug’s safety issues.

Published
2020

32. Psychological distress among Ethiopian and Russian Jewish immigrants to Israel: a cross-cultural study

Author

Ponizovsky, A., Ginath, Y., Durst, R., Wondimeneh, B., Safro, S., Minuchin-Itzigson, S., and Ritsner, M.

Subjects
Jews -- Migrations, Russians in Israel -- Psychological aspects, Ethiopians in Israel -- Psychological aspects, Immigrants -- Psychological aspects, Psychology and mental health, Sociology and social work
Abstract

A community survey was conducted examining the differences in levels of psychological distress and its symptomatology, comparing 110 Ethiopian-Jewish and 400 Russian-Jewish immigrants to Israel. Psychological distress was measured by the Talbieh Brief Distress Inventory. Russian immigrants were found to be more distressed than their Ethiopian counterparts and this between-group difference can be attributed to the greater relative number of females, older immigrants and those with longer duration of stay in Israel in the Russian sample. The highest levels of distress were observed for paranoid ideation in the Ethiopian sample and anxiety and hostility in the Russian sample. These symptoms were independent of gender and time since immigration. Russians with longer duration of stay demonstrated higher scores signifying adjustment difficulties than their Ethiopian counterparts. These results suggest that the differences in levels and symptom expression of psychological distress are determined, to a considerable extent, by demographic factors (sex, age) and the differing cultural backgrounds of the two immigrant groups.

Published
1998

36. InterPlanetary internet

Author

Burleigh, S, Cerf, V, Durst, R, Fall, K, Scott, K, Torgerson, L, Weiss, H, and Hooke, A. J

Published
2003

44. Overview of the current status of familial hypercholesterolaemia care in over 60 countries - The EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

Author

Vallejo-Vaz, A.J. Marco, M.D. Stevens, C.A.T. Akram, A. Freiberger, T. Hovingh, G.K. Kastelein, J.J.P. Mata, P. Raal, F.J. Santos, R.D. Soran, H. Watts, G.F. Abifadel, M. Aguilar-Salinas, C.A. Al-Khnifsawi, M. Alkindi, F.A. Alnouri, F. Alonso, R. Al-Rasadi, K. Al-Sarraf, A. Ashavaid, T.F. Binder, C.J. Bogsrud, M.P. Bourbon, M. Bruckert, E. Chlebus, K. Corral, P. Descamps, O. Durst, R. Ezhov, M. Fras, Z. Genest, J. Groselj, U. Harada-Shiba, M. Kayikcioglu, M. Lalic, K. Lam, C.S.P. Latkovskis, G. Laufs, U. Liberopoulos, E. Lin, J. Maher, V. Majano, N. Marais, A.D. März, W. Mirrakhimov, E. Miserez, A.R. Mitchenko, O. Nawawi, H.M. Nordestgaard, B.G. Paragh, G. Petrulioniene, Z. Pojskic, B. Postadzhiyan, A. Reda, A. Reiner, Ž. Sadoh, W.E. Sahebkar, A. Shehab, A. Shek, A.B. Stoll, M. Su, T.-C. Subramaniam, T. Susekov, A.V. Symeonides, P. Tilney, M. Tomlinson, B. Truong, T.-H. Tselepis, A.D. Tybjærg-Hansen, A. Vázquez-Cárdenas, A. Viigimaa, M. Vohnout, B. Widén, E. Yamashita, S. Banach, M. Gaita, D. Jiang, L. Nilsson, L. Santos, L.E. Schunkert, H. Tokgözoğlu, L. Car, J. Catapano, A.L. Ray, K.K. Schreier, L. Pang, J. Dieplinger, H. Hanauer-Mader, G. Desutter, J. Langlois, M. Mertens, A. Rietzschel, E. Wallemacq, C. Isakovic, D. Dzankovic, A.M. Obralija, J. Pojskic, L. Sisic, I. Stimjanin, E. Torlak, V.A. Jannes, C.E. Krieger, J.E. Pereira, A.C. Ruel, I. Asenjo, S. Cuevas, A. Pećin, I. Miltiadous, G. Panayiotou, A.G. Vrablik, M. Benn, M. Heinsar, S. Béliard, S. Gouni-Berthold, I. Hengstenberg, W. Julius, U. Kassner, U. Klose, G. König, C. König, W. Otte, B. Parhofer, K. Schatz, U. Schmidt, N. Steinhagen-Thiessen, E. Vogt, A. Antza, C. Athyros, V. Bilianou, E. Boufidou, A. Chrousos, G. Elisaf, M. Garoufi, A. Katsiki, N. Kolovou, G. Kotsis, V. Rallidis, L. Rizos, C. Skalidis, E. Skoumas, I. Tziomalos, K. Shawney, J.P.S. Abbaszadegan, M.R. Aminzadeh, M. Hosseini, S. Mobini, M. Vakili, R. Zaeri, H. Agar, R. Boran, G. Colwell, N. Crowley, V. Durkin, M. Griffin, D. Kelly, M. Rakovac-Tisdall, A. Bitzur, R. Cohen, H. Eliav, O. Ellis, A. Gavish, D. Harats, D. Henkin, Y. Knobler, H. Leavit, L. Leitersdorf, E. Schurr, D. Shpitzen, S. Szalat, A. Arca, M. Averna, M. Bertolini, S. Calandra, S. Tarugi, P. Erglis, A. Gilis, D. Nesterovics, G. Saripo, V. Upena-Roze, A. Elbitar, S. Jambart, S. Khoury, P.E. Gargalskaite, U. Kutkiene, S. Al-Khateeb, A. An, C.Y. Ismail, Z. Kasim, S. Ibrahim, K.S. Radzi, A.B.M. Kasim, N.A. Nor, N.S.M. Ramli, A.S. Razak, S.A. Muid, S. Rosman, A. Sanusi, A.R. Razman, A.Z. Nazli, S.A. Kek, T.L. Azzopardi, C. Aguilar Salinas, C.A. Galán, G. Rubinstein, A. Magaña-Torres, M.T. Martagon, A. Mehta, R. Wittekoek, M.E. Isara, A.R. Obaseki, D.E. Ohenhen, O.A. Holven, K.B. Gruchała, M. Baranowska, M. Borowiec-Wolny, J. Gilis-Malinowska, N. Michalska-Grzonkowska, A. Pajkowski, M. Parczewska, A. Romanowska-Kocejko, M. Stróżyk, A. Żarczyńska-Buchowiecka, M. Kleinschmidt, M. Alves, A.C. Medeiros, A.M. Ershova, A. Korneva, V. Kuznetsova, T. Malyshev, P. Meshkov, A. Rozhkova, T. Popovic, L. Lukac, S.S. Stosic, L. Rasulic, I. Lalic, N.M. Chua, T.S.J. Ting, S.P.L. Raslova, K. Battelino, T. Cevc, M. Jug, B. Kovac, J. Podkrajsek, K.T. Sustar, U. Trontelj, K.J. Marais, D. Isla, L.P. Martin, F.J. Charng, M.-J. Chen, P.-L. Kayikçioglu, M. Dell’oca, N. Fernández, G. Ressia, A. Reyes, X. Zelarayan, M. Alieva, R.B. Hoshimov, S.U. Nizamov, U.I. Kurbanov, R.D. Lima-Martínez, M.M. Nguyen, M.-N.T. Do, D.-L. Kim, N.-T. Le, T.-T. Le, H.-A.

Abstract

Background and aims: Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries. Methods: Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management. Results: 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in ∼2/3 countries. Lipoprotein-apheresis is offered in ∼60% countries, although access is limited. Conclusions: FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed. © 2018 Elsevier B.V.

Published
2018

50. A space demonstration of the next generation TT and C standards

Author

Shave, N. P, Wells, N. S, Hooke, A, and Durst, R

Subjects
Space Communications, Spacecraft Communications, Command And Tracking
Abstract

An initiative to develop an integrated set of space data communication protocols, which will complement and expand upon the current Consultative Committee for Space Data Systems (CCSDS) telemetry and telecommand standards, is reported on. The aim is to provide a comprehensive set of spacecraft control and monitoring data handling services. The space communications protocol standards (SCPS) initiative will provide a set of spacecraft telemetry, telecommand and control (TT and C) standards that will serve a wide range of civilian and military space missions. A software flight test and demonstration of the capabilities of the SCPS protocols was performed using the in orbit space technology research vehicle and compared to laboratory simulations. The results from this test will contribute to the continued SCPS protocol development program.

Published
1996

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