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908 results on '"ELDER, G."'

1. Galois scaffolds for $p$-extensions in characteristic $p$

Author

Elder, G. Griffith and Keating, Kevin

Subjects
Mathematics - Number Theory, 11S15 (Primary) 11R33, 14L15, 16T05 (Secondary)
Abstract

Let $K$ be a local field of characteristic $p>0$ with perfect residue field and let $G$ be a finite $p$-group. In this paper we use Saltman's construction of a generic $G$-extension of rings of characteristic $p$ to construct totally ramified $G$-extensions $L/K$ that have Galois scaffolds. We specialize this construction to produce $G$-extensions $L/K$ such that the ring of integers $O_L$ is free of rank 1 over its associated order $A_0$, and extensions such that $A_0$ is a Hopf order in the group ring $K[G]$., Comment: 23 pages

Published
2023

2. Upper ramification sequences of nonabelian extensions of degree $p^3$ in characteristic $p$

Author

Elder, G. Griffith

Subjects
Mathematics - Number Theory, 11S15
Abstract

We classify the upper ramification breaks of totally ramified nonabelian extensions of degree $p^3$ over a local field of characteristic $p>0$. We find that nonintegral upper ramification breaks can occur for each nonabelian Galois group of order $p^3$, except the dihedral group of order $8$., Comment: 20 pages

Published
2023

3. A converse to the Hasse-Arf theorem

Author

Elder, G. Griffith and Keating, Kevin

Subjects
Mathematics - Number Theory, 11S15
Abstract

Let $L/K$ be a finite Galois extension of local fields. The Hasse-Arf theorem says that if Gal$(L/K)$ is abelian then the upper ramification breaks of $L/K$ must be integers. We prove the following converse to the Hasse-Arf theorem: Let $G$ be a nonabelian group which is isomorphic to the Galois group of some totally ramified extension $E/F$ of local fields with residue characteristic $p>2$. Then there is a totally ramified extension of local fields $L/K$ with residue characteristic $p$ such that Gal$(L/K)\cong G$ and $L/K$ has at least one nonintegral upper ramification break.

Published
2023

4. Galois scaffolds for cyclic $p^n$-extensions in characteristic $p$

Author

Elder, G. Griffith and Keating, Kevin

Subjects
Mathematics - Number Theory, 11S15
Abstract

Let $K$ be a local field of characteristic $p$ and let $L/K$ be a totally ramified Galois extension such that Gal$(L/K)\cong C_{p^n}$. In this paper we find sufficient conditions for $L/K$ to admit a Galois scaffold. This leads to sufficient conditions for the ring of integers $O_L$ to be free of rank 1 over its associated order $A_0$, and to stricter conditions which imply that $A_0$ is a Hopf order in the group ring $K[C_{p^n}]$.

Published
2022

5. Refined ramification breaks in characteristic $p$

Author

Elder, G. Griffith and Keating, Kevin

Subjects
Mathematics - Number Theory, 11S15
Abstract

Let $K$ be a local field of characteristic $p$ and let $L/K$ be a totally ramified elementary abelian $p$-extension with a single ramification break $b$. Byott and Elder defined the refined ramification breaks of $L/K$, an extension of the usual ramification data. In this paper we give an alternative definition for the refined ramification breaks, and we use Artin-Schreier theory to compute both versions of the breaks in some special cases., Comment: 26 pages

Published
2018

8. Ramified extensions of degree $p$ and their {H}opf-{G}alois module structure

Author

Elder, G. Griffith

Subjects
Mathematics - Number Theory, Primary 11S15, Secondary 11R33, 16T05
Abstract

Cyclic, ramified extensions $L/K$ of degree $p$ of local fields with residue characteristic $p$ are fairly well understood. Unless $\mbox{char}(K)=0$ and $L=K(\sqrt[p]{\pi_K})$ for some prime element $\pi_K\in K$, they are defined by an Artin-Schreier equation. Additionally, through the work of Ferton, Aiba, de Smit and Thomas, and others, much is known about their Galois module structure of ideals, the structure of each ideal $\mathfrak{P}_L^n$ as a module over its associated order $\mathfrak{A}_{K[G]}(n)=\{x\in K[G]:x\mathfrak{P}_L^n\subseteq \mathfrak{P}_L^n\}$ where $G=\mbox{Gal}(L/K)$. This paper extends these results to separable, ramified extensions of degree $p$ that are not Galois.

Published
2015

9. Technical and Financial Impacts on Distribution Systems of Integrating Batteries Controlled by Uncoordinated Strategies

Author

Ronaldo S. Chacon Camargos, Priscilla A. Jua Stecanella, Daniel Vieira, Livia M. De R. Raggi, Fernando C. Melo, Elder G. Domingues, and Anesio De L. Ferreira Filho

Subjects
Battery energy storage systems, distribution systems, photovoltaic distributed generation, power quality, price arbitrage, self-consumption, Electrical engineering. Electronics. Nuclear engineering, TK1-9971
Abstract

This study assesses the technical and financial impacts on voltage levels, peak demand, and technical losses of distribution systems due to the integration of battery energy storage systems (BESSs) associated with photovoltaic distributed generation (PVDG). It assumes that the BESS features (location and storage capacity) are chosen by consumers individually, aiming to directly benefit themselves according to self-consumption and price arbitrage uncoordinated control strategies. Computational simulations of several PVDG/BESS penetration levels in residential feeders of a Brazilian utility were performed via OpenDSS, employing real data of the load (consumption and load profiles) and photovoltaic generation (irradiance and temperature). We address the PVDG/BESS locations and the selection of solar irradiance, temperature, and load profile based on the Monte Carlo method. As the impacts on voltage levels, peak demand, and technical losses are expressed in different units, they were stochastically converted into monetary amounts to identify the control strategy that enhances the technical benefits in the distribution system. The results show that BESS installation with location, size, and control strategy defined by consumers creates technical benefits for the distribution system. The risk analysis allows us to conclude that price arbitrage should be prioritized in deciding incentives for penetration levels of up to 60%. Above these levels, self-consumption should be prioritized as an incentive. However, it is worth mentioning that the two strategies could be encouraged regardless of the penetration levels, as both create technical benefits for the distribution networks. The proposed method can support policy proposals to encourage BESS integration in distribution systems.

Published
2021
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11. Sufficient Conditions for Large Galois Scaffolds

Author

Byott, Nigel P. and Elder, G. Griffith

Subjects
Mathematics - Number Theory, 11S15, 11R33, 16T05
Abstract

Let $L/K$ be a finite Galois, totally ramified $p$-extension of complete local fields with perfect residue fields of characteristic $p>0$. In this paper, we give conditions, valid for any Galois $p$-group $G={Gal}(L/K)$ (abelian or not) and for $K$ of either possible characteristic (0 or $p$), that are sufficient for the existence of a Galois scaffold. The existence of a Galois scaffold makes it possible to address questions of integral Galois module structure, which is done in a separate paper. But since our conditions can be difficult to check, we specialize to elementary abelian extensions and extend the main result of [G.G. Elder, Proc. A.M.S. 137 (2009), 1193-1203] from characteristic $p$ to characteristic 0. This result is then applied, using a result of Bondarko, to the construction of new Hopf orders over the valuation ring $\mathfrak{O}_K$ that lie in $K[G]$ for $G$ an elementary abelian $p$-group., Comment: Some minor changes to exposition, and references added/updated. To appear in Journal of Number Theory

Published
2013
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12. Scaffolds and Generalized Integral Galois Module Structure

Author

Byott, Nigel P., Childs, Lindsay N., and Elder, G. Griffith

Subjects
Mathematics - Number Theory, 11S15, 20C11, 16T05, 11R33
Abstract

Let $L/K$ be a finite, totally ramified $p$-extension of complete local fields with residue fields of characteristic $p > 0$, and let $A$ be a $K$-algebra acting on $L$. We define the concept of an $A$-scaffold on $L$, thereby extending and refining the notion of a Galois scaffold considered in several previous papers, where $L/K$ was Galois and $A=K[G]$ for $G=\mathrm{Gal}(L/K)$. When a suitable $A$-scaffold exists, we show how to answer questions generalizing those of classical integral Galois module theory. We give a necessary and sufficient condition, involving only numerical parameters, for a given fractional ideal to be free over its associated order in $A$. We also show how to determine the number of generators required when it is not free, along with the embedding dimension of the associated order. In the Galois case, the numerical parameters are the ramification breaks associated with $L/K$. We apply these results to biquadratic Galois extensions in characteristic 2, and to totally and weakly ramified Galois $p$-extensions in characteristic $p$. We also apply our results to the non-classical situation where $L/K$ is a finite primitive purely inseparable extension of arbitrary exponent that is acted on, via a higher derivation (but in many different ways), by the divided power $K$-Hopf algebra., Comment: Further minor corrections and improvements to exposition. Reference [BE] updated. To appear in Ann. Inst. Fourier, Grenoble

Published
2013

13. Galois scaffolds and Galois module structure in extensions of characteristic $p$ local fields of degree $p^2$

Author

Byott, Nigel P. and Elder, G. Griffith

Subjects
Mathematics - Number Theory, 11S15 (11R33)
Abstract

A Galois scaffold, in a Galois extension of local fields with perfect residue fields, is an adaptation of the normal basis to the valuation of the extension field, and thus can be applied to answer questions of Galois module structure. Here we give a sufficient condition for a Galois scaffold to exist in fully ramified Galois extensions of degree $p^2$ of characteristic $p$ local fields. This condition becomes necessary when we restrict to $p=3$. For extensions $L/K$ of degree $p^2$ that satisfy this condition, we determine the Galois module structure of the ring of integers by finding necessary and sufficient conditions for the ring of integers of $L$ to be free over its associated order in $K[Gal(L/K)]$.

Published
2011

14. Integral Galois Module Structure for Elementary Abelian Extensions with a Galois Scaffold

Author

Byott, Nigel P. and Elder, G. Griffith

Subjects
Mathematics - Number Theory, 11S23
Abstract

This paper justifies an assertion in (Elder, Proc AMS 137 (2009), no 4, 1193--1203) that Galois scaffolds make the questions of Galois module structure tractable. Let $k$ be a perfect field of characteristic $p$ and let $K=k((T))$. For the class of characteristic $p$ elementary abelian $p$-extensions $L/K$ with Galois scaffolds described in mentioned paper, we give a necessary and sufficient condition for the valuation ring $\mathfrak{O}_L$ to be free over its associated order $\mathcal{A}_{L/K}$ in $K[\Gal(L/K)]$. Interestingly, this condition agrees with the condition found by Y. Miyata, concerning a class of cyclic Kummer extensions in characteristic zero.

Published
2009

15. Pre-Brachytherapy Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) Response as Predictor of Local Control in the Definitive Treatment of Cervical Cancer

Author

Moore, A., primary, Paudyal, R., additional, Elder, G., additional, Lakhman, Y., additional, White, C., additional, Zhang, Z., additional, Broach, V.A., additional, Liu, Y., additional, Damanto, A., additional, Cohen, G.N., additional, Nunez, D. Aramburu, additional, Dreyfuss, A., additional, Alektiar, K.M., additional, Dave, A., additional, and Kollmeier, M.A., additional

Published
2023
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16. A valuation criterion for normal basis generators in local fields of characteristic $p$

Author

Elder, G. Griffith

Subjects
Mathematics - Number Theory, Mathematics - Algebraic Geometry, 11S15
Abstract

Let $K$ be a complete local field of characteristic $p$ with perfect residue field. Let $L/K$ be a finite, fully ramified, Galois $p$-extension. If $\pi_L\in L$ is a prime element, and $p'(x)$ is the derivative of $\pi_L$'s minimal polynomial over $K$, then the relative different $\euD_{L/K}$ is generated by $p'(\pi_L)\in L$. Let $v_L$ be the normalized valuation normalized with $v_L(L)=\mathbb{Z}$. We show that any element $\rho\in L$ with $v_L(\rho)\equiv -v_L(p'(\pi_L))-1\bmod[L:K]$ generates a normal basis, $K[{Gal}(L/K)]\cdot\rho=L$. This criterion is tight: Given any integer $i$ such that $i\not\equiv -v_L(p'(\pi_L))-1\bmod[L:K]$, there is a $\rho_i\in L$ with $v_L(\rho_i)=i$ such that $K[{Gal}(L/K)]\cdot\rho_i\subsetneq L$.

Published
2008

18. On the necessity of new ramification breaks

Author

Byott, Nigel P. and Elder, G. Griffith

Subjects
Mathematics - Number Theory, 11S15
Abstract

Ramification invariants are necessary, but not in general sufficient, to determine the Galois module structure of ideals in local number field extensions. This insufficiency is associated with elementary abelian extensions, where one can define a refined ramification filtration -- one with more ramification breaks [JNTB 17 (2005)]. The first refined break number comes from the usual ramification filtration and is therefore necessary. Here we study the second refined break number.

Published
2007

19. A valuation criterion for normal bases in elementary abelian extensions

Author

Byott, Nigel P. and Elder, G. Griffith

Subjects
Mathematics - Number Theory, 11S15, 13B05
Abstract

Let $p$ be a prime number and let $K$ be a finite extension of the field $\mathbb{Q}_p$ of $p$-adic numbers. Let $N$ be a fully ramified, elementary abelian extension of $K$. Under a mild hypothesis on the extension $N/K$, we show that every element of $N$ with valuation congruent mod $[N:K]$ to the largest lower ramification number of $N/K$ generates a normal basis for $N$ over $K$., Comment: In addition to some small notational changes, the title "On the valuation of normal basis generators" was changed. The paper is accepted by the Bulletin of the LMS

Published
2006

20. The Galois structure of ambiguous ideals in cyclic extensions of degree 8

Author

Elder, G. Griffith

Subjects
Mathematics - Number Theory, 11S23, 20C10
Abstract

In cyclic, degree 8 extensions of algebraic number fields $N/K$, ambiguous ideals in N are canonical $\mathbb{Z}[C_8]$-modules. Their $\mathbb{Z}[C_8]$-structure is determined here. It is described in terms of indecomposable modules and determined by ramification invariants. Although infinitely many indecomposable $\mathbb{Z}[C_8]$-modules are available (classification by Yakovlev), only 23 appear., Comment: This article has appeared in the Lect. Notes Pure Appl. Math. without references. The article is being posted here, with permission, to remedy that problem

Published
2006

21. One-dimensional elementary abelian extensions have Galois scaffolding

Author

Elder, G. Griffith

Subjects
Mathematics - Number Theory, 11S15
Abstract

We define a variant of normal basis, called a {\em Galois scaffolding}, that allows for an easy determination of valuation, and has implications for Galois module structure. We identify fully ramified, elementary abelian extensions of local function fields of characteristic $p$, called {\em one-dimensional}, that, in a particular sense, are as simple as cyclic degree $p$ extensions, and prove the statement in the title above., Comment: 13 pages. This is a revision of "One-dimensional elementary-abelian extensions of local fields," which is being split into two papers. This paper restricts itself to local fields of characteristic $p$ and proves a stronger result than in the original

Published
2005

22. On wild ramification in quaternion extensions

Author

Elder, G. Griffith and Hooper, Jeffrey J.

Subjects
Mathematics - Number Theory, 11S15
Abstract

Quaternion extensions are often the smallest extensions to exhibit special properties. In the setting of the Hasse-Arf Theorem, for instance, quaternion extensions are used to illustrate the fact that upper ramification numbers need not be integers. These extensions play a similar role in Galois module structure. To better understand these examples, we catalog the ramification filtrations that are possible in totally ramified extensions of dyadic number fields. Interestingly, we find that the catalog depends, for sharp lower bounds, upon the refined ramification filtration, which is associated with the biquatratic subfield. Moreover these examples, as counter-examples to the conclusion of Hasse-Arf, occur only when the refined filtration is, in two different ways, extreme., Comment: 19 pages. This is an extensive revision of the earlier draft

Published
2005

28. Methodology for Measurement the Energy Efficiency Involving Solar Heating Systems Using Stochastic Modelling

Author

Bruno G. Menita, Girodani Pacífico Medeiros, Jose L. Domingos, Elder G. Domingues, Aylton J. Alves, Adriano F. Faria, Marcio L. S. Miguel, and Wesley P. Calixto

Subjects
energy efficiency, geometric brownian motion, monte carlo simulation, performance measurement and verification, solar water heating, Electrical engineering. Electronics. Nuclear engineering, TK1-9971, Environmental sciences, GE1-350
Abstract

The purpose of the present study is to evaluate gains through measurement and verification methodology adapted from the International Performance Measurement and Verification Protocol, from case studies involving Energy Efficiency Projects in the Goias State, Brazil. This paper also presents the stochastic modelling for the generation of future scenarios of electricity saving resulted by these Energy Efficiency Projects. The model is developed by using the Geometric Brownian Motion Stochastic Process with Mean Reversion associated with the Monte Carlo simulation technique. Results show that the electricity saved from the replacement of electric showers by solar water heating systems in homes of low-income families has great potential to bring financial benefits to such families, and that the reduction in peak demand obtained from this Energy Efficiency Action is advantageous to the Brazilian electrical system. Results contemplate also the future scenarios of electricity saving and a sensitivity analysis in order to verify how values of some parameters influence on the results, once there is no historical data available for obtaining these values.

Published
2017
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34. Dual endothelin antagonist aprocitentan for resistant hypertension (PRECISION): a multicentre, blinded, randomised, parallel-group, phase 3 trial

Author

Schlaich, M, Bellet, M, Weber, M, Danaietash, P, Bakris, G, Flack, J, Dreier, R, Sassi-Sayadi, M, Haskell, L, Narkiewicz, K, Wang, J, Reid, C, Katz, I, Ajani, A, Biswas, S, Esler, M, Elder, G, Roger, S, Colquhoun, D, Mooney, J, De Backer, T, Persu, A, Chaumont, M, Krzesinski, J, Vanabsche, T, Girard, G, Pliamm, L, Schiffrin, E, Merali, F, Dresser, G, Vallee, M, Jolly, S, Chow, S, Mu, J, Yu, J, Yuan, H, Feng, Y, Zhang, X, Xie, J, Lin, L, Soucek, M, Widimsky, J, Cifkova, R, Vaclavik, J, Ullrych, M, Lukac, M, Rychlik, I, Guldager Lauridsen, T, Kantola, I, Taurio, J, Ukkola, O, Ormezzano, O, Gosse, P, Azizi, M, Courand, P, Delsart, P, Tartiere, J, Mahfoud, F, Schmieder, R, Stegbauer, J, Lurz, P, Koziolek, M, Ott, C, Toursarkissian, N, Tsioufis, K, Kyfnidis, K, Manolis, A, Patsilinakos, S, Zebekakis, P, Karavidas, A, Denes, P, Bezzegh, K, Zsom, M, Kovacs, L, Sharabi, Y, Elias, M, Sukholutsky, I, Yosefy, C, Kenis, I, Atar, S, Volpe, M, Lorenza, M, Taddei, S, Grassi, G, Veglio, F, Son, J, Kim, J, Park, J, Lee, C, Lee, H, Raugaliene, R, Marcinkeviciene, J, Kavaliauskiene, R, Deinum, J, Kroon, A, van den Born, B, Januszewicz, A, Tykarski, A, Walczewska, J, Gaciong, Z, Wiecek, A, Chrostowska, M, Kleinrok, A, Krekora, J, Kania, G, Podrazka-Szczepaniak, A, Golawski, C, Podziewski, M, Kaczmarek, B, Skoczylas, G, Wilkolaski, A, Wozniak, I, Janik-Palazzolo, M, Rewerska, B, Konradi, A, Shvarts, Y, Pecherina, T, Nikolaev, K, Liudmila, G, Orlikova, O, Mordovin, V, Petrochenkova, N, Kamalov, G, Kosmacheva, E, Tyrenko, V, Gorbunov, V, Obrezan, A, Supryadkina, T, Ler, I, Kotenko, O, Kuzin, A, Martinez, F, Redon, J, Oliveras, A, Beltran Romero, L, Shatylo, V, Rudenko, L, Bazylevych, A, Rudyk, Y, Karpenko, O, Stanislavchuk, M, Tseluyko, V, Kushnir, M, Asanov, E, Sirenko, Y, Yagensky, A, Collier, D, Gupta, P, Webb, D, Macleod, M, Mclay, J, Peace, A, Arora, S, Buchanan, P, Harris, R, Degarmo, R, Guillen, M, Karns, A, Neutel, J, Paliwal, Y, Pettis, K, Toth, P, Wayne, J, Butcher, B, Diller, P, Oparil, S, Calhoun, D, Brautigam, D, Goldman, J, Rashidi, A, Aslam, N, Haley, W, Andrawis, N, Lang, B, Miller, R, Powell, J, Dewhurst, R, Pritchard, J, Khanna, D, Tang, D, Gabra, N, Jones, C, Scott, C, Luna, B, Mussaji, M, Bhagwat, R, Bauer, M, Mcginty, J, Nambiar, R, Sangrigoli, R, Ross Davis, W, Eaves, W, Mcgrew, F, Awad, A, Bolster, E, Scott, D, Kalirao, P, Dabel, P, Calhoun, W, Gouge, S, Warren, M, Lawrence, M, Jamal, A, El-Shahawy, M, Mercado, C, Kumar, J, Velasquez-Mieyer, P, Busch, R, Lewis, T, Rich, L, Schlaich, Markus P, Bellet, Marc, Weber, Michael A, Danaietash, Parisa, Bakris, George L, Flack, John M, Dreier, Roland F, Sassi-Sayadi, Mouna, Haskell, Lloyd P, Narkiewicz, Krzysztof, Wang, Ji-Guang, Reid, Christopher, Schlaich, Markus, Katz, Ivor, Ajani, Andrew, Biswas, Sinjini, Esler, Murray, Elder, Grahame, Roger, Simon, Colquhoun, David, Mooney, John, De Backer, Tine, Persu, Alexandre, Chaumont, Martin, Krzesinski, Jean-Marie, Vanabsche, Thomas, Girard, Ginette, Pliamm, Lew, Schiffrin, Ernesto, Merali, Fatima, Dresser, George, Vallee, Michel, Jolly, Shivinder, Chow, Stephen, Wang, Jiguang, Mu, Jianjun, Yu, Jing, Yuan, Hong, Feng, Yingqing, Zhang, Xin, Xie, Jianhong, Lin, Ling, Soucek, Miroslav, Widimsky, Jiri, Cifkova, Renata, Vaclavik, Jan, Ullrych, Martin, Lukac, Martin, Rychlik, Ivan, Guldager Lauridsen, Thomas, Kantola, Ilkka, Taurio, Jyrki, Ukkola, Olavi, Ormezzano, Olivier, Gosse, Philippe, Azizi, Michel, Courand, Pierre-Yves, Delsart, Pascal, Tartiere, Jean Michel, Mahfoud, Felix, Schmieder, Roland, Stegbauer, Johannes, Lurz, Philipp, Koziolek, Michael, Ott, Christian, Toursarkissian, Nicole, Tsioufis, Konstantinos, Kyfnidis, Konstantinos, Manolis, Athanasios, Patsilinakos, Sotirios, Zebekakis, Pantelis, Karavidas, Apostolos, Denes, Pall, Bezzegh, Katalin, Zsom, Marianna, Kovacs, Laszlo, Sharabi, Yehonatan, Elias, Mazen, Sukholutsky, Ivetta, Yosefy, Chaim, Kenis, Irina, Atar, Shaul, Volpe, Massimo, Lorenza, Muiesan Maria, Taddei, Stefano, Grassi, Guido, Veglio, Franco, Son, Jung Woo, Kim, Jang-Young, Park, Joong-Il, Lee, Chang Hoon, Lee, Hae-Young, Raugaliene, Rasa, Marcinkeviciene, Jolanta Elena, Kavaliauskiene, Roma, Deinum, Jaap, Kroon, Abraham, van den Born, Bert-Jan, Januszewicz, Andrzej, Tykarski, Andrzej, Walczewska, Jolanta, Gaciong, Zbigniew, Wiecek, Andrzej, Chrostowska, Marzena, Kleinrok, Andrzej, Krekora, Jan, Kania, Grzegorz, Podrazka-Szczepaniak, Anna, Golawski, Cezary, Podziewski, Maciej, Kaczmarek, Barbara, Skoczylas, Grzegorz, Wilkolaski, Andrzej, Wozniak, Iwona, Janik-Palazzolo, Marzena, Rewerska, Barbara, Konradi, Alexandra, Shvarts, Yuriy, Pecherina, Tamara, Nikolaev, Konstantin, Liudmila, Gapon, Orlikova, Olga, Mordovin, Viktor, Petrochenkova, Natalia, Kamalov, Gadel, Kosmacheva, Elena, Tyrenko, Vadim, Gorbunov, Vladimir, Obrezan, Andrey, Supryadkina, Tatiana, Ler, Irina, Kotenko, Oleg, Kuzin, Anatoly, Martinez, Fernando, Redon, Josep, Oliveras, Anna, Beltran Romero, Luis, Shatylo, Valerii, Rudenko, Leonid, Bazylevych, Andriiy, Rudyk, Yurii, Karpenko, Oleksandr, Stanislavchuk, Mykola, Tseluyko, Vira, Kushnir, Mykola, Asanov, Ervin, Sirenko, Yuriy, Yagensky, Andriy, Collier, David, Gupta, Pankaj, Webb, David, MacLeod, Mary, McLay, James, Peace, Aaron, Arora, Samir, Buchanan, Patricia, Harris, Robert, Degarmo, Ronald, Guillen, Mario, Karns, Adam, Neutel, Joel, Paliwal, Yogesh, Pettis, Karlton, Toth, Phillip D., Wayne, Jeffrey M., Butcher, Bain, Diller, Phillip M., Oparil, Suzanne, Calhoun, David, Brautigam, Donald, Flack, John, Goldman, Jesse M., Rashidi, Arash, Aslam, Nabeel, Haley, William, Andrawis, Nabil, Lang, Brian, Miller, Randy, Powell, James, Dewhurst, Robert, Pritchard, James, Khanna, Dinesh, Tang, Dennis, Gabra, Nashwa, Park, Jean, Jones, Conigliaro, Scott, Cranford, Luna, Blanca, Mussaji, Murtaza, Bhagwat, Ravi, Bauer, Michael, McGinty, John, Nambiar, Rajesh, Sangrigoli, Renee, Ross Davis, William, Eaves, William, McGrew, Frank, Awad, Ahmed, Bolster, Eric, Scott, David, Kalirao, Paramjit, Dabel, Pascal, Calhoun, Wesley, Gouge, Steven, Warren, Mark, Lawrence, Mary Katherine, Jamal, Aamir, El-Shahawy, Mohamed, Mercado, Carlos, Kumar, Jayant, Velasquez-Mieyer, Pedro, Busch, Robert, Lewis, Todd, Rich, Lisa, Schlaich, M, Bellet, M, Weber, M, Danaietash, P, Bakris, G, Flack, J, Dreier, R, Sassi-Sayadi, M, Haskell, L, Narkiewicz, K, Wang, J, Reid, C, Katz, I, Ajani, A, Biswas, S, Esler, M, Elder, G, Roger, S, Colquhoun, D, Mooney, J, De Backer, T, Persu, A, Chaumont, M, Krzesinski, J, Vanabsche, T, Girard, G, Pliamm, L, Schiffrin, E, Merali, F, Dresser, G, Vallee, M, Jolly, S, Chow, S, Mu, J, Yu, J, Yuan, H, Feng, Y, Zhang, X, Xie, J, Lin, L, Soucek, M, Widimsky, J, Cifkova, R, Vaclavik, J, Ullrych, M, Lukac, M, Rychlik, I, Guldager Lauridsen, T, Kantola, I, Taurio, J, Ukkola, O, Ormezzano, O, Gosse, P, Azizi, M, Courand, P, Delsart, P, Tartiere, J, Mahfoud, F, Schmieder, R, Stegbauer, J, Lurz, P, Koziolek, M, Ott, C, Toursarkissian, N, Tsioufis, K, Kyfnidis, K, Manolis, A, Patsilinakos, S, Zebekakis, P, Karavidas, A, Denes, P, Bezzegh, K, Zsom, M, Kovacs, L, Sharabi, Y, Elias, M, Sukholutsky, I, Yosefy, C, Kenis, I, Atar, S, Volpe, M, Lorenza, M, Taddei, S, Grassi, G, Veglio, F, Son, J, Kim, J, Park, J, Lee, C, Lee, H, Raugaliene, R, Marcinkeviciene, J, Kavaliauskiene, R, Deinum, J, Kroon, A, van den Born, B, Januszewicz, A, Tykarski, A, Walczewska, J, Gaciong, Z, Wiecek, A, Chrostowska, M, Kleinrok, A, Krekora, J, Kania, G, Podrazka-Szczepaniak, A, Golawski, C, Podziewski, M, Kaczmarek, B, Skoczylas, G, Wilkolaski, A, Wozniak, I, Janik-Palazzolo, M, Rewerska, B, Konradi, A, Shvarts, Y, Pecherina, T, Nikolaev, K, Liudmila, G, Orlikova, O, Mordovin, V, Petrochenkova, N, Kamalov, G, Kosmacheva, E, Tyrenko, V, Gorbunov, V, Obrezan, A, Supryadkina, T, Ler, I, Kotenko, O, Kuzin, A, Martinez, F, Redon, J, Oliveras, A, Beltran Romero, L, Shatylo, V, Rudenko, L, Bazylevych, A, Rudyk, Y, Karpenko, O, Stanislavchuk, M, Tseluyko, V, Kushnir, M, Asanov, E, Sirenko, Y, Yagensky, A, Collier, D, Gupta, P, Webb, D, Macleod, M, Mclay, J, Peace, A, Arora, S, Buchanan, P, Harris, R, Degarmo, R, Guillen, M, Karns, A, Neutel, J, Paliwal, Y, Pettis, K, Toth, P, Wayne, J, Butcher, B, Diller, P, Oparil, S, Calhoun, D, Brautigam, D, Goldman, J, Rashidi, A, Aslam, N, Haley, W, Andrawis, N, Lang, B, Miller, R, Powell, J, Dewhurst, R, Pritchard, J, Khanna, D, Tang, D, Gabra, N, Jones, C, Scott, C, Luna, B, Mussaji, M, Bhagwat, R, Bauer, M, Mcginty, J, Nambiar, R, Sangrigoli, R, Ross Davis, W, Eaves, W, Mcgrew, F, Awad, A, Bolster, E, Scott, D, Kalirao, P, Dabel, P, Calhoun, W, Gouge, S, Warren, M, Lawrence, M, Jamal, A, El-Shahawy, M, Mercado, C, Kumar, J, Velasquez-Mieyer, P, Busch, R, Lewis, T, Rich, L, Schlaich, Markus P, Bellet, Marc, Weber, Michael A, Danaietash, Parisa, Bakris, George L, Flack, John M, Dreier, Roland F, Sassi-Sayadi, Mouna, Haskell, Lloyd P, Narkiewicz, Krzysztof, Wang, Ji-Guang, Reid, Christopher, Schlaich, Markus, Katz, Ivor, Ajani, Andrew, Biswas, Sinjini, Esler, Murray, Elder, Grahame, Roger, Simon, Colquhoun, David, Mooney, John, De Backer, Tine, Persu, Alexandre, Chaumont, Martin, Krzesinski, Jean-Marie, Vanabsche, Thomas, Girard, Ginette, Pliamm, Lew, Schiffrin, Ernesto, Merali, Fatima, Dresser, George, Vallee, Michel, Jolly, Shivinder, Chow, Stephen, Wang, Jiguang, Mu, Jianjun, Yu, Jing, Yuan, Hong, Feng, Yingqing, Zhang, Xin, Xie, Jianhong, Lin, Ling, Soucek, Miroslav, Widimsky, Jiri, Cifkova, Renata, Vaclavik, Jan, Ullrych, Martin, Lukac, Martin, Rychlik, Ivan, Guldager Lauridsen, Thomas, Kantola, Ilkka, Taurio, Jyrki, Ukkola, Olavi, Ormezzano, Olivier, Gosse, Philippe, Azizi, Michel, Courand, Pierre-Yves, Delsart, Pascal, Tartiere, Jean Michel, Mahfoud, Felix, Schmieder, Roland, Stegbauer, Johannes, Lurz, Philipp, Koziolek, Michael, Ott, Christian, Toursarkissian, Nicole, Tsioufis, Konstantinos, Kyfnidis, Konstantinos, Manolis, Athanasios, Patsilinakos, Sotirios, Zebekakis, Pantelis, Karavidas, Apostolos, Denes, Pall, Bezzegh, Katalin, Zsom, Marianna, Kovacs, Laszlo, Sharabi, Yehonatan, Elias, Mazen, Sukholutsky, Ivetta, Yosefy, Chaim, Kenis, Irina, Atar, Shaul, Volpe, Massimo, Lorenza, Muiesan Maria, Taddei, Stefano, Grassi, Guido, Veglio, Franco, Son, Jung Woo, Kim, Jang-Young, Park, Joong-Il, Lee, Chang Hoon, Lee, Hae-Young, Raugaliene, Rasa, Marcinkeviciene, Jolanta Elena, Kavaliauskiene, Roma, Deinum, Jaap, Kroon, Abraham, van den Born, Bert-Jan, Januszewicz, Andrzej, Tykarski, Andrzej, Walczewska, Jolanta, Gaciong, Zbigniew, Wiecek, Andrzej, Chrostowska, Marzena, Kleinrok, Andrzej, Krekora, Jan, Kania, Grzegorz, Podrazka-Szczepaniak, Anna, Golawski, Cezary, Podziewski, Maciej, Kaczmarek, Barbara, Skoczylas, Grzegorz, Wilkolaski, Andrzej, Wozniak, Iwona, Janik-Palazzolo, Marzena, Rewerska, Barbara, Konradi, Alexandra, Shvarts, Yuriy, Pecherina, Tamara, Nikolaev, Konstantin, Liudmila, Gapon, Orlikova, Olga, Mordovin, Viktor, Petrochenkova, Natalia, Kamalov, Gadel, Kosmacheva, Elena, Tyrenko, Vadim, Gorbunov, Vladimir, Obrezan, Andrey, Supryadkina, Tatiana, Ler, Irina, Kotenko, Oleg, Kuzin, Anatoly, Martinez, Fernando, Redon, Josep, Oliveras, Anna, Beltran Romero, Luis, Shatylo, Valerii, Rudenko, Leonid, Bazylevych, Andriiy, Rudyk, Yurii, Karpenko, Oleksandr, Stanislavchuk, Mykola, Tseluyko, Vira, Kushnir, Mykola, Asanov, Ervin, Sirenko, Yuriy, Yagensky, Andriy, Collier, David, Gupta, Pankaj, Webb, David, MacLeod, Mary, McLay, James, Peace, Aaron, Arora, Samir, Buchanan, Patricia, Harris, Robert, Degarmo, Ronald, Guillen, Mario, Karns, Adam, Neutel, Joel, Paliwal, Yogesh, Pettis, Karlton, Toth, Phillip D., Wayne, Jeffrey M., Butcher, Bain, Diller, Phillip M., Oparil, Suzanne, Calhoun, David, Brautigam, Donald, Flack, John, Goldman, Jesse M., Rashidi, Arash, Aslam, Nabeel, Haley, William, Andrawis, Nabil, Lang, Brian, Miller, Randy, Powell, James, Dewhurst, Robert, Pritchard, James, Khanna, Dinesh, Tang, Dennis, Gabra, Nashwa, Park, Jean, Jones, Conigliaro, Scott, Cranford, Luna, Blanca, Mussaji, Murtaza, Bhagwat, Ravi, Bauer, Michael, McGinty, John, Nambiar, Rajesh, Sangrigoli, Renee, Ross Davis, William, Eaves, William, McGrew, Frank, Awad, Ahmed, Bolster, Eric, Scott, David, Kalirao, Paramjit, Dabel, Pascal, Calhoun, Wesley, Gouge, Steven, Warren, Mark, Lawrence, Mary Katherine, Jamal, Aamir, El-Shahawy, Mohamed, Mercado, Carlos, Kumar, Jayant, Velasquez-Mieyer, Pedro, Busch, Robert, Lewis, Todd, and Rich, Lisa

Abstract

Background: Resistant hypertension is associated with increased cardiovascular risk. The endothelin pathway has been implicated in the pathogenesis of hypertension, but it is currently not targeted therapeutically, thereby leaving this relevant pathophysiological pathway unopposed with currently available drugs. The aim of the study was to assess the blood pressure lowering efficacy of the dual endothelin antagonist aprocitentan in patients with resistant hypertension. Methods: PRECISION was a multicentre, blinded, randomised, parallel-group, phase 3 study, which was done in hospitals or research centres in Europe, North America, Asia, and Australia. Patients were eligible for randomisation if their sitting systolic blood pressure was 140 mm Hg or higher despite taking standardised background therapy consisting of three antihypertensive drugs, including a diuretic. The study consisted of three sequential parts: part 1 was the 4-week double-blind, randomised, and placebo-controlled part, in which patients received aprocitentan 12·5 mg, aprocitentan 25 mg, or placebo in a 1:1:1 ratio; part 2 was a 32-week single (patient)-blind part, in which all patients received aprocitentan 25 mg; and part 3 was a 12-week double-blind, randomised, and placebo-controlled withdrawal part, in which patients were re-randomised to aprocitentan 25 mg or placebo in a 1:1 ratio. The primary and key secondary endpoints were changes in unattended office systolic blood pressure from baseline to week 4 and from withdrawal baseline to week 40, respectively. Secondary endpoints included 24-h ambulatory blood pressure changes. The study is registered on ClinicalTrials.gov, NCT03541174. Findings: The PRECISION study was done from June 18, 2018, to April 25, 2022. 1965 individuals were screened and 730 were randomly assigned. Of these 730 patients, 704 (96%) completed part 1 of the study; of these, 613 (87%) completed part 2 and, of these, 577 (94%) completed part 3 of the study. The least square m

Published
2022

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