tbuckley/cabot-search huggingface dataset:
Abstract 15720: Transmembrane Stem Cell Factor Delivered in Nanocarriers Promotes Angiogenesis in Ischemia Without Mast Cell Activation
Authors: Eri Takematsu, Sanjana Srinath, Michael Sherman, Andrew K Dunn, Aaron Baker
Journal: Circulation (2020)

Introduction: The current standard cares for peripheral artery disease (PAD) include surgical revascularizations with bypass grafting or percutaneous interventions. However, these interventions cannot be performed in a significant portion of patients, and many do not respond to these surgical procedures. Protein therapy to stimulate the body to create new vasculature is another alternative, which is minimally invasive to patients. Stem cell factor (SCF) is a candidate protein for treating PAD, but clinical use of SCF has been limited due to toxicity related to mast cell activation. SCF also exists in a transmembrane form (tmSCF), possessing differential activities from soluble SCF and has not been explored as a therapeutic agent. Results: To develop tmSCF as a therapeutic we created tmSCF embedded in liposome or lipid nanodisc (Fig. A) . Hindlimb ischemia model on WT and ob/ob mice showed that tmSCF proteliposome (tmSCFPL) and nanodisc (tmSCFND) improved blood flow recovery significantly more than control (Fig. B, C) . Mouse model of anaphylaxis revealed that tmSCF-based therapies did not activate mast cells (Fig. D, E) . Colocalization assay of c-Kit and clathrin/caveolin revealed that mast cells preferentially use clathrin-mediated pathways to internalize SCF and caveolin-mediated pathways for tmSCF-based therapies (Fig. F, G) . Surface c-Kit internalization study on mast cells showed faster uptake of SCF in comparison to tmSCF-based therapies (Fig. H) . Previous study indicates that clathrin-mediated internalization causes increased activation of mast cells. Our studies together with the previous finding suggest that mast cell activation does not occur for tmSCF-based therapies because of the slower uptake, greater utilization of the caveolin internalization pathway and weaker activation of mast cells. Conclusions: TmSCF-based therapies can provide therapeutic benefits without off-target effects on mast cells by tuning activation with nanocarriers.
Abstract 16959: A Youthful Cardiomyocyte Phenotype Drives Enhanced Cardiac Recovery in Adult Spiny Mice
Authors: Hsuan Peng, Kazuhiro Shindo, Renee Donahue, Bryana Levitan, Jonathan Satin, Ashley W Seifert, Ahmed Abdel-latif
Journal: Circulation (2020)

Introduction: Adult mammals, including humans, experience limited recovery following myocardial infarction (MI). Recently, our group has uncovered a unique ability for enhanced cardiac recovery in adult spiny mice ( Acomys ). Methods and Results: Our preliminary studies have established appropriate similarities in heart structure and coronary anatomy between Acomys and Mus . Following the same permanent left artery descending (LAD) ligation surgery, Acomys and Mus showed a similar degree of early cardiac injury. Echocardiography and histological analyses showed more robust cardiac recovery and smaller scar area in Acomys . Moreover, Acomys exhibited a higher survival rate compared to Mus with no evidence of cardiac rupture or hypertrophy (measured by increasing heart/body weight) after MI. To investigate the mechanisms underlying this phenomenon, we isolated and quantified the size, nuclei number, and ploidy of adult cardiomyocytes (CMs) in both species (n=5 animals/group) using the Langendorff perfusion technique. Acomys CMs are significantly smaller in size compared to Mus and Acomys hearts have higher percentage of mononucleated cardiomyocytes. Using flow cytometry, we found that Acomys possess a higher percentage of diploid CMs compared to Mus . A closer examination of cardiomyocytes using electrophysiology revealed the presence of a T-type calcium current in adult Acomys CMs; a characteristic which is usually found in highly proliferative embryonic ventricular cardiomyocytes. Lastly, Acomys CMs demonstrated higher proliferative rates after injury compared to Mus . Conclusion: Taken together, our data provide strong evidence for enhanced cardiac repair in an adult mammalian model. Our results strongly suggest that Acomys maintain proliferative adult cardiomyocytes as adults and thus provide a cellular mechanism for their enhanced cardiac recovery after AMI.
Limited rejuvenation of aged hematopoietic stem cells in young bone marrow niche
Authors: Wakako Kuribayashi, Motohiko Oshima, Naoki Itokawa, Shuhei Koide, Yaeko Nakajima-Takagi, Masayuki Yamashita, Satoshi Yamazaki, Bahityar Rahmutulla, Fumihito Miura, Takashi Ito, Atsushi Kaneda, Atsushi Iwama
Journal: The Journal of Experimental Medicine (2020)

Hematopoietic stem cells (HSCs) exhibit functional alterations, such as reduced regenerative capacity and myeloid-biased differentiation, with age. The HSC niche, which is essential for the maintenance of HSCs, also undergoes marked changes with aging. However, it has been technically challenging to directly evaluate the contribution of niche aging to age-associated HSC alterations without niche-damaging myeloablation in HSC transplantation assays. We herein transplanted an excess of aged HSCs into young mice without preconditioning. Although aged HSCs successfully engrafted in the intact young bone marrow niche, they poorly regenerated downstream progenitors and exhibited persistent myeloid-biased differentiation, resulting in no significant functional rejuvenation. Transcriptome and methylome analyses revealed that the young niche largely restored the transcriptional profile of aged HSCs, but not their DNA methylation profiles. Therefore, the restoration of the young niche is insufficient for rejuvenating HSC functions, highlighting a key role for age-associated cell-intrinsic defects in HSC aging.
Abstract PR02: Integrated metabolic and epigenomic reprograming by H3K27M mutations in diffuse intrinsic pontine gliomas
Authors: Chan Chung, Stefan Sweha, Drew Pratt, Benita Tamrazi, Pooja Panwalkar, Adam Banda, Jill Bayliss, Debra Hawes, Fusheng Yang, Ho-Joon Lee, Mengrou Shan, Marcin Cieslik, Tingting Qin, Christian Werner, Daniel Wahl, Costas Lyssiotis, Viveka Nand Yadav, Carl Koschmann, Arul Chinnaiyan, Stefan Blüml, Alexander Judkins, Sriram Venneti
Journal: Cancer Research (2020)

Abstract H3K27M-midline gliomas are fatal tumors that mainly harbor H3.3K27M mutations resulting in global H3K27me3 reduction that impacts neuroglial-differentiation. However, the exact mechanisms by which H3.3K27M mutations promote cancer are poorly understood. Metabolic reprogramming is a hallmark of cancer and we hypothesized that H3.3K27M mutations can reprogram metabolism to support uncontrolled growth. We demonstrate that H3.3K27M-mutant cells show elevated levels of critical enzymes related to glycolysis and TCA cycle metabolism including hexokinase-2, isocitrate dehydrogenase (IDH)-1 and glutamate dehydrogenase. H3.3K27M cells also demonstrated enhanced glycolysis, glutamine and TCA-cycle metabolism accompanied by increased alpha-ketoglutarate (α-KG) production. Mutant IDH (mIDH)1/2 converts α-KG to D-2-hydroxyglutarate (D-2HG). D-2HG increases H3K27me3 by inhibiting α-KG’s function to drive H3K27-demethylases. We discovered that H3.3K27M cells use α-KG in an opposing manner to maintain low H3K27me3. Inhibiting enzymes related to α-KG generation including hexokinase-2, glutamate-dehydrogenase and wild type-IDH1 increased global H3K27me3, altered chromatin accessibility at neuroglial-differentiation factors, lowered tumor cell proliferation, and increased overall survival in vivo in two independent H3.3K27M animal models (p&amp;lt; 0.0001). H3K27M and mIDH1 were mutually exclusive in-patient tumor samples and D-2HG treatment or forced-mIDH1 expression in H3.3K27M cells increased global H3K27me3 and cell death. Finally, H3.3K27M and mIDH1 were synthetic lethal in vitro. Our data suggest that H3.3K27M and mIDH1 hijack a critical and conserved metabolic pathway in opposing manners to regulate global H3K27me3. These results have implications for understanding the pathogenesis of fatal H3K27M-gliomas and for developing therapeutic strategies by disruption of an integrated metabolic/epigenetic-axis. Citation Format: Chan Chung, Stefan Sweha, Drew Pratt, Benita Tamrazi, Pooja Panwalkar, Adam Banda, Jill Bayliss, Debra Hawes, Fusheng Yang, Ho-Joon Lee, Mengrou Shan, Marcin Cieslik, Tingting Qin, Christian Werner, Daniel Wahl, Costas Lyssiotis, Viveka Nand Yadav, Carl Koschmann, Arul Chinnaiyan, Stefan Blüml, Alexander Judkins, Sriram Venneti. Integrated metabolic and epigenomic reprograming by H3K27M mutations in diffuse intrinsic pontine gliomas [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PR02.
51P Real world outcomes in elderly women with HER2-positive advanced breast cancer
Authors: N. Evans, A. Anton, R. Wong, S.W. Lok, R. De Boer, L. Malik, S. Greenberg, B. Yeo, L. Nott, G. Richardson, I.M. Collins, J. Torres, F. Barnett, P. Gibbs, B. Devitt
Journal: Annals of Oncology (2020)
Abstract IA08: Metabolic compartmentalization in the regulation of chromatin modification
Authors: Kathryn Wellen
Journal: Cancer Research (2020)

Abstract Metabolic processes are compartmentalized within cells. Many chromatin modifying enzymes utilize metabolites as substrates, and localized metabolite production may play important roles in the regulation of the epigenome. A number of metabolic enzymes have been detected and shown to be dynamically regulated within the nucleus. For example, nuclear localization and phosphorylation of the enzyme ATP-citrate lyase (ACLY) plays a key role in supplying acetyl-CoA for histone acetylation during DNA double strand break repair. A major barrier to understanding metabolic regulation of chromatin modification is the lack of methodology to reliably measure nuclear metabolite levels. In this talk, I will discuss efforts to quantify subcellular acyl-CoA levels, as well as insights into the regulation of nuclear metabolite pools emerging from this work. Citation Format: Kathryn Wellen. Metabolic compartmentalization in the regulation of chromatin modification [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr IA08.
Rapid Translation of COVID-19 Preprint Data into Critical Care Practice
Authors: Aidan J. C. Burrell, Ary Serpa Neto, Tony Trapani, Tessa Broadley, Craig French, Andrew A. Udy, Adam Visser, Adrian Mattke, Adrian Regli, Alan Rashid, Alexis Tabah, Alison Walker, Allen Cheng, Amanda Corley, Andrew Udy, Anil Ramnani, (Isabel) Anne Leditschke, Anthony Eidan, Bart DeKeulenaer, Baumik Mevavala, Ben Mulholland, Benjamin Reddi, Brent Richards, Cameron Knott, Cara Moore, Carmel Delzoppo, Catherine Boschert, Catherine Tacon, Claire Corrigan, Craig French, Danielle Austin, David Brewster, David Cooper, David Crosbie, David Hawkins, Edda Jessen, Eduardo Martinez, Edward Fysh, Edward Litton, Felix Oberender, Forbes McGain, Gavin Salt, Glenn Eastwood, Gopal Taori, Hannah Thompson, Hayden White, Hergen Buscher, Ian Seppelt, Ifrah Khan, Janelle Young, Jayshree Lavana, Jeremy Cohen, Jessica Lugsdin, Jill Garlick, Jim Buttery, John Botha, John Santamaria, Jonathan Barrett, Kasha Singh, Kevin Laupland, Khaled El-Khawas, Kristine Estensen, Kush Deshpande, Kyle White, Leigh Fitzpatrick, Lewis Campbell, Mahesh Ramanan, Manoj Saxena, Marie Draper, Marion Kainer, Mark Kol, Mark Page, Mark Plummer, Martin Sterba, Matthew Anstey, Matthew Brain, Matthew Maiden, Myrene Kilminster, Naomi Hammond, Neeraj Bhadange, Nicole Humphreys, Paras Jain, Paul Azzi, Paul Secombe, Paula Lister, Peter Chan, Peter McCanny, Phillip Britton, Pierre Janin, Rashmi Runiyar, Ravi Krishnamurthy, Ravikiran Sonawane, Ravindranath Tiruvoipati, Rebecca Jessup, Richard Totaro, Rinaldo Bellomo, Ritesh Sanghavi, Samantha Bates, Sandra Peake, Shailesh Bihari, Shane George, Sharon Waterson, Simon Erickson, Steve Webb, Subhash Arora, Subodh Ganu, Thomas Rozen, Toni McKenna, Umesh Kadam, Vineet Nayyar, Wei Han Choy, Wisam Albassam
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

To the Editor:
The global coronavirus disease (COVID-19) pandemic has seen a significant increase in the use of preprint services to enable the widespread dissemination of research findings (1). However, whether such facilities influence practice change is currently unknown. Here, we describe the impact of the preprint release and eventual publication of the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial (2) on corticosteroid use in clinical practice in Australian ICUs. The RECOVERY trial tested the efficacy of dexamethasone (6 mg by mouth or intravenously for up to 10 d) in hospitalized patients with clinically suspected or confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and demonstrated a reduction in 28-day mortality, particularly in those receiving either mechanical ventilation or oxygen. Before these results, the Australian and New Zealand Intensive Care Society COVID-19 guidelines recommended against the routine use of corticosteroids (3).
15144 Long-term safety of apremilast treatment in patients with psoriasis or psoriatic arthritis: Pooled analysis for 260 weeks and beyond in the ESTEEM 1 and 2 and PALACE 1-4 phase 3 trials
Authors: Kristina Callis-Duffin, Andreas Pinter, Philip Mease, Paolo Gisondi, Paul Steven Yamauchi, Maria Paris, Ling Yang, Eugenia Levi, Francisco A. Kerdel
Journal: Journal of the American Academy of Dermatology (2020)
日本人集団におけるGen-1 DESの5年間の臨床転帰:Cypherに対する日本人市販後調査研究からのデータ
Authors: Kotani Jun-ichi, Ikari Yuji, Kyo Eisho, Nakamura Masato, Yokoi Hiroyoshi, Kozuma Ken
Journal: Circulation (2012)
Treatment of Xanthoma Disseminatum With Narrowband UV-B Phototherapy
Authors: Marta García-Legaz Martínez, Álvaro Martínez-Doménech, Jorge Magdaleno-Tapial, Cristian Valenzuela-Oñate, Elena Iborra-Palau, Víctor Alegre de Miquel, Amparo Pérez-Ferriols
Journal: JAMA Dermatology (2020)

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Left Bundle Branch Block After Transcatheter Aortic Valve Implantation: Inconsequential or a Clinically Important Endpoint?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Antonio Colombo, Azeem Latib
Journal: Journal of the American College of Cardiology (2012)
Abstract 16283: Inhibition of Pannexin-1 Channels Attenuates Vascular Inflammation and Aortic Aneurysm Formation
Authors: Michael Spinosa, Gang Su, James H Mehaffey, Adishesh Narahari, Brant Isakson, Kodi S Ravichandran, Gilbert R Upchurch, Ashish K Sharma
Journal: Circulation (2018)

Introduction: Abdominal aortic aneurysm (AAA) formation involves vascular remodeling and inflammation. Recent reports indicate that Pannexin-1 (Panx1) channels are expressed on endothelial cells an...
15413 Dupilumab improves signs and symptoms in adult and adolescent patients with erythrodermic atopic dermatitis: A pooled subgroup analysis
Authors: Michael J. Cork, Benjamin Lockshin, Marie-Anne Morren, Takafumi Etoh, Zhen Chen, Ana Beatris Rossi, Yufang Lu, Ashish Bansal, Arsalan Shabbir
Journal: Journal of the American Academy of Dermatology (2020)
Abstract 17006: Reversing Membrane Clock Remodeling (MCR) Associated With Heart Failure With Preserved Ejection Fraction (HFpEF) in the Sinoatrial Node (SAN) Eliminates Chronotropic Incompetence (CI)
Authors: Jialiu A Liang, Kevin Sompel, Joseph K Yu, Thassio Mesquita, Eduardo Marban, Eugenio Cingolani, Natalia Trayanova
Journal: Circulation (2020)

Introduction: While CI, or the inability of heart rate (HR) to adequately respond to exercise, is a strong indicator of mortality in HFpEF, treatment options remain limited as its mechanisms remain underexplored. Ionic remodeling of the SAN, both of the membrane (MC) and calcium clocks (CC), is associated with HFpEF and CI. Aim: Using an in silico approach, we investigated whether SAN ionic remodeling can contribute to 3 different CI presentations (Fig A) and explored the effectiveness of targeting the remodeling of the MC or CC (MCR and CCR, resp.) in eliminating CI. Methods: A human SAN model (control) was used, in which ionic remodeling was integrated using experimental data from HFpEF rat model with CI (Fig B top). A family of HFpEF SAN models (n = 147) was generated because the uniqueness of Ca 2+ handling parameters constrained to experimentally-based Ca 2+ transients could not be guaranteed (Fig B middle). To assess the level of CI, max beat rate (BR), BR response (τ on ), and BR recovery (τ off ) were quantified for each model in response to a transient 40s pulse of 1 μM isoproterenol (ISO) (Fig B bottom). Lastly, the effect of reversing either CCR or MCR on CI was determined. Results: Without ISO, BR of HFpEF SAN models was similar to that of control; when ISO was applied (Fig C), HFpEF models exhibited all aspects of CI: submaximal BR (Fig D), and elevated τ on and τ off (Fig E). In CCR reversed models, BR without ISO was similar to that of control; with ISO, they exhibited submaximal BR (Fig F). In MCR reversed models, BR without ISO was slightly lower compared to control; with ISO, while they exhibited submaximal BR, the increase in BR with ISO was similar to that of control (Fig F). τ on and τ off were elevated in CCR reversed models, but they were not in MCR reversed models (Fig G). In summary, CCR reversed models exhibited all aspects of CI, but MCR reversed models did not. Conclusion: Ionic remodeling of the SAN contributes to CI in HFpEF, and targeting MCR could be a promising strategy for eliminating CI.
90Y Radiosynovectomy in Persistent Synovitis Caused by Knee Replacement
Authors: Knut Liepe, Marcel Baehr
Journal: Clinical Nuclear Medicine (2020)

After knee replacement, therapy resistant, persistent synovitis is a common issue, which causes effusion and pain, and leads to loosing. It has been hypothesized that radiosynovectomy (RSO) is useful in these patients.A cohort of 55 patients with 57 knee replacements and persistent synovitis underwent RSO using 4.9 ± 0.24 mCi (182 ± 9 MBq) of Y-citrate. The number of RSOs ranged from 1 to 4. Bone scans before and 3 months after every RSO were performed. Long-term follow-up ranged from 0.8 to 7.6 years with a mean of 23.2 months. For qualitative analysis, an established 4 steps scoring was used. For quantification, the uptake was determined within the Tc-MDP scintigraphy blood pool phase before and after therapy.Long-term response was in 27% with excellent, 24% good, 30% weak, and 20% no response. The duration of response was 12.0 ± 12.0 months (maximum, 54 months). In patients with repeated treatment, the effect after the first therapy was lesser than in patients who received a single treatment in total. However, 3 months after the last RSO, patients with repeated treatment showed a similar effectiveness than single treated patients. At the end of long-term follow-up, patients with repeated RSOs had a higher effectiveness at similar duration response. In bone scan, 65% of patients showed a reduction of uptake. When comparing subjective and objective response, 78% of patients showed a concordance in both symptoms and scintigraphy. Pilot histological analysis revealed that the synovitis is triggered by small plastic particles.We concluded that RSO is an effective therapy in patients with knee replacement and persistent synovitis with high long-term response. Repeated treatment leads to a stronger long-time response.
A Large Cohort Comparison of 2005 National Institutes of Health Chronic Graft-Versus-Host Disease Staging Criteria to 2014 National Institutes of Health Chronic Graft-Versus-Host Disease Staging Criteria
Authors: Ana Z Kerep, Jacob Broome, Filip Pirsl, Seth M. Steinberg, Sandra A Mitchell, Edward W Cowen, Dominique C. Pichard, Galen O Joe, Leora E Comis, Jacqueline W Mays, Manuel B Datiles, Pamela Stratton, Jesica Zolton, Ann Berger, Jennifer Hendricks, Megan Kenyon, Judy Baruffaldi, Marina Denisova, Lauren M. Curtis, Drazen Pulanic, Kristin Baird, Daniel H. Fowler, Ronald E. Gress, Steven Z. Pavletic
Journal: Blood (2017)
Iron Oxide Magnetic Resonance Imaging for Atherosclerosis Therapeutic Evaluation: Still “Rusty?”⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Zahi A. Fayad, Louai Razzouk, Karen C. Briley-Saebo, Venkatesh Mani
Journal: Journal of the American College of Cardiology (2009)
410P Frequency and spectrum of primary resistance mechanism in Chinese ALK+ non-small cell lung cancer patients progressing on crizotinib: A multicenter study
Authors: W-X. Wang, C. Xu, Q-X. Zhang, W. Zhuang, Z-B. Song, Y-C. Zhu, G. Chen, M-Y. Fang, T-F. Lv, Y. Song
Journal: Annals of Oncology (2020)
Multicentric evaluation of BioFire FilmArray Pneumonia Panel for rapid bacteriological documentation of pneumonia
Authors: Nabil Gastli, Julien Loubinoux, Matthieu Daragon, Jean-Philippe Lavigne, Pierre Saint-Sardos, Hélène Pailhoriès, Carole Lemarié, Hanaa Benmansour, Camille d’Humières, Lauranne Broutin, Olivier Dauwalder, Michael Levy, Gabriel Auger, Solen Kernéis, Vincent Cattoir, Sophie Alviset, Laurence Armand-Lefèvre, Marion Baldeyrou, Agathe Becker, André Boibieux, Stéphane Bonacorsi, Christophe Burucoa, Emmanuelle Cambau, Jean-Sébastien Casalegno, Aurélie Cointe, Julie Cremniter, Grégory Destras, Paul Duquaire, Guillaume Geslain, Claude-Alexandre Gustave, Hervé Jacquier, Achille Kouatchet, Emmanuel Lecorche, Manon Lejeune, Bruno Lina, Rafaël Mahieu, Adel Maamar, Anthony Michaud, Céline Monnard, Philippe Montravers, Catherine Neuwirth, Gauthier Péan de Ponfilly, Maxime Pichon, Chloé Plouzeau, Claire Poyart, Jean-Pierre Quenot, Vincent Rzepecki, Robin Stéphan, Jean-François Timsit, Alexy Tran-Dinh, François Vandenesch, Emmanuelle Vigier
Journal: Clinical Microbiology and Infection (2020)
16785 Relationship between acne and use of cosmetics: Results of a questionnaire study in 216 Korean individuals
Authors: Dong-Hye Suh, Haneul Oh, Jae Yeong Jeong, Sook In Ryu, Sang Jun Lee, Hyun Joo Kim, Ka Yeun Chang, Hyung Sub Kim, Hwa Jung Ryu
Journal: Journal of the American Academy of Dermatology (2020)
Right Ventricular Adaptation Assessed Using Cardiac Magnetic Resonance Predicts Survival in Pulmonary Arterial Hypertension
Authors: Ze Ming Goh, Samer Alabed, Yousef Shahin, Alexander M.K. Rothman, Pankaj Garg, Allan Lawrie, David Capener, A.A. Roger Thompson, Faisal A.A. Alandejani, Christopher S. Johns, Robert A. Lewis, Krit Dwivedi, James M. Wild, Robin Condliffe, David G. Kiely, Andrew J. Swift
Journal: JACC. Cardiovascular imaging (2020)

Pulmonary arterial hypertension (PAH) is a rare but life-limiting condition.Assessments of disease severity and prognosis are essential in the selection of treatment options and the timing of lung transplantation (1).Right ventricular (RV) volume and mass parameters measured using cardiac magnetic resonance have been suggested to be prognostic in PAH (1-3).This study aimed to determine the prognosis of patients with PAH based on patterns of RV adaption in PAH using RV volume and mass.Ethical approval by the North Sheffield ethics committee and