tbuckley/cabot-search huggingface dataset:
DNA methylation in serum as an independent marker of outcome and treatment response in TBCRC 005: A prospective study in metastatic breast cancer (MBC) patients.
Authors: Kala Visvanathan, Mary Jo Fackler, Zhe Zhang, Zoila Lopez-Bujanda, Stacie Jeter, Lori J. Sokoll, Leslie Cope, Christopher Umbricht, David Euhus, John T. Carpenter, Anna Maria Storniolo, Rita Nanda, Nancy U. Lin, Lisa A. Carey, James N. Ingle, Saraswati Sukumar, Antonio C. Wolff
Journal: Journal of Clinical Oncology (2015)

518 Background: Accurate markers are needed to assess the effect of therapies early in MBC. Emerging studies suggest that methylated tumor DNA in blood can predict poor prognosis. In the TBCRC 005 multi-site prospective biomarker study we tested whether serum DNA methylation assessed by the cMethDNA assay (PMID 2437128) is predictive of disease outcomes in MBC and compared our results to circulating tumor cells (CTC). Methods: Serum was collected from 2007-2009, and methylation of AKR1B1, HOXB4, RASFGR2, RASSF1A, HIST1H3C, TM6SF1 loci were determined in duplicate serum samples from 141 women with measurable MBC at baseline, week 3-4 and week 8-12. For each patient, the cumulative methylation index (CMI) was calculated, log-transformed, and modeled as a continuous or binary variable. The study specific cut-point was based on maximally selected logrank statistic and unbiased point estimates were obtained by cross-validation. Cox proportional hazard models were used to evaluate association between CMI at baseline and week 3-4, with PD at first re-staging, PFS, and OS. The added value of CMI to prognostic factors including CTC was assessed using the likelihood ratio test and concordance probability estimates. Results: Median age was 56 years; 89% white; 60% HR+/HER2-. Patients with high CMI at week 3-4 had a median OS of 12.8 months compared to 22.6 months among those with a low CMI. PFS results were similar. An increase in CMI units at 3-4 weeks was associated with PD (P = 0.003), PFS (P = 0.008), and OS (P < 0.001) in multivariate analyses. In joint models both CMI and CTC were predictive of PFS and OS. Furthermore, an increase in CMI from baseline to week 3-4 was significantly associated with PD (HR 1.58, CI 1.21-2.05, P < 0.001), worse PFS (HR 1.22, CI 1.10-1.35, P < 0.001) and OS (HR 1.10, CI 0.99-1.22, P = 0.077). Change in CTC between the same time points was not associated with disease outcomes. Conclusions: This is the most comprehensive study to date of DNA methylation in blood of MBC patients. The cMethDNA CMI of this gene marker set is an independent prognostic factor in MBC and is promising as useful marker for risk stratification and early assessment of treatment.
CENTRAL OBESITY PREDICTS CIRCULATING PROGENITOR CELL LEVELS
Authors: Jay Khambhati, Pratik Sandesara, Ayman Samman Tahhan, Matthew Topel, Frank Corrigan, Heval Mohamad Kelli, Eric Stahl, Marc Allard-Ratick, Ayman Alkhoder, Hiroshi Aida, Mohamad Mazen Gafeer, Iraj Hesaroieh, Ernestine Mahar, Edmund Waller, Viola Vaccarino, Thomas R. Ziegler, Laurence Sperling, Kenneth Brigham, Greg Martin, Arshed Quyyumi
Journal: Journal of the American College of Cardiology (2017)
IMPACT OF ADMISSION PLASMA GLUCOSE LEVEL ON MYOCARDIAL PERFUSION IN ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION (STEMI) PATIENTS
Authors: Martino Pepe, Domenico Zanna, Filippo Masi, Nicola Signore, Alessandro Santo Bortone, Annagrazia Cecere, Antonio Tito, Donato Quagliara, Stefano Favale
Journal: Journal of the American College of Cardiology (2017)
INSIGHTS ON DIASTOLIC DYSFUNCTION OF TREATED HYPERTENSIVE PATIENTS: FOCUSING ON HYPERTENSION CONTROL &amp; TREATMENT RESISTANCE
Authors: Dimitris Konstantinidis, Konstantinos Tsioufis, Alexandros Kasiakogias, Georgios Georgiopoulos, Nikolaos Vogiatzakis, Voula Pylarinou, Konstantinos Kyriazopoulos, Anastasios Milkas, Anastasios Frantzeskakis, Ioannis Kallikazaros
Journal: Journal of the American College of Cardiology (2017)
HIGH-SENSITIVITY CARDIAC TROPONIN I AND RISK OF CARDIOVASCULAR EVENTS IN PATIENTS WITH COPD AND HEIGHTENED CARDIOVASCULAR RISK: A BIOMARKER SUB-STUDY OF THE SUMMIT TRIAL
Authors: Nicholas L. Mills, Julie A. Anderson, Robert D. Brook, Peter M.A. Calverley, Bartolome R. Celli, Nicholas J. Cowans, Courtney Crim, Ian J. Dixon, Sally Kilbride, Fernando Martinez, Jørgen Vestbo, Julie Yates, David E. Newby
Journal: Journal of the American College of Cardiology (2017)
Failure of fertility therapy is associated with increased risk of cardiovascular events
Authors: Barbara Kermode-Scott
Journal: BMJ (2017)

Women who undergo fertility therapy but do not give birth have a higher risk of long term adverse cardiovascular events than those who undergo therapy and do give birth, a population based, longitudinal cohort analysis has found.

The study, published in the Canadian Medical Association Journal , found that the annual rate of cardiovascular events was 19% higher among women who did not give birth after fertility therapy than among those who did (1.08 versus 0.91 per 100 patient years; relative rate ratio …
Maintenance Therapy after Autologous Haematopoietic Stem Cell Transplantation (auto-HSCT) in Multiple Myeloma Patients with and without Minimal Residual Disease (MRD)
Authors: Maxim V. Solovev, Larisa P. Mendeleeva, Olga S. Pokrovskaya, Eduard G. Gemdzhian, Larisa A. Kuzmina, Maya Firsova, Irina Galtseva, Julia Davydova, Valeri G. Savchenko
Journal: Blood (2016)
REAL-WORLD VERSUS RANDOMIZED TRIAL OUTCOMES IN SIMILAR POPULATIONS OF RIVAROXABAN-TREATED PATIENTS WITH NONVALVULAR ATRIAL FIBRILLATION IN ROCKET AF AND XANTUS
Authors: A. John Camm, Pierre Amarenco, Sylvia Haas, Susanne Hess, Paulus Kirchhof, Silvia Kuhls, Marc Lambelet, Martin van Eickels, Alexander Turpie, Bayer AG
Journal: Journal of the American College of Cardiology (2017)
Molecular Pathways: Oncologic Pathways and Their Role in T-cell Exclusion and Immune Evasion—A New Role for the AXL Receptor Tyrosine Kinase
Authors: Todd A. Aguilera, Amato J. Giaccia
Journal: Clinical Cancer Research (2017)

With the clinical impact of CTLA-4 and PD-1/PD-L1 immune checkpoint therapies, widespread interest in cancer immunotherapy has been ignited. However, the rate and extent of clinical responses to approved therapies are limited and often nonexistent in many solid tumors. This is partially because immune checkpoint therapies are most effective against T-cell-inflamed tumors, and non-T-cell-inflamed or T-cell-excluded tumors remain a significant barrier. New strategies are needed to overcome immune resistance mechanisms that arise during tumor development, which result in T-cell exclusion. Approaches may need to be combined with conventional therapies such as chemotherapy, radiotherapy, and molecularly targeted therapy, and many clinical trials are ongoing. This review discusses the challenge of T-cell exclusion and innate oncologic pathways that contribute to this problem, including β-catenin, STAT3, NF-κB, PTEN, and AXL tyrosine kinase. The GAS6/AXL pathway is of interest immunologically, as its targeting can lead to greater antitumor immune responses after radiotherapy. In addition, several targeted therapies that are selective and nonselective for AXL are in preclinical and clinical development in acute myelogenous leukemia and renal cell cancer. There remains much to learn, but the future is bright for anti-AXL therapies, though effective combinations and their impact may not be realized for years to come. Clin Cancer Res; 23(12); 2928-33. ©2017 AACR.
EARLY DIASTOLIC MITRAL ANNULAR VELOCITY AT PEAK EXERCISE DETERMINES PEAK AEROBIC EXERCISE CAPACITY IN HEART FAILURE WITH PRESERVED EJECTION FRACTION
Authors: Cory Trankle, Justin Canada, Leo Buckley, Salvatore Carbone, Dave Dixon, Ross Arena, Benjamin Van Tassell, Antonio Abbate
Journal: Journal of the American College of Cardiology (2017)
Selection in Europeans on Fatty Acid Desaturases Associated with Dietary Changes
Authors: Matthew T. Buckley, Fernando Racimo, Morten E. Allentoft, Majken K. Jensen, Anna Jonsson, Hongyan Huang, Farhad Hormozdiari, Martin Sikora, Davide Marnetto, Eleazar Eskin, Marit E. Jørgensen, Niels Grarup, Oluf Pedersen, Torben Hansen, Peter Kraft, Eske Willerslev, Rasmus Nielsen
Journal: Molecular Biology and Evolution (2017)

FADS genes encode fatty acid desaturases that are important for the conversion of short chain polyunsaturated fatty acids (PUFAs) to long chain fatty acids. Prior studies indicate that the FADS genes have been subjected to strong positive selection in Africa, South Asia, Greenland, and Europe. By comparing FADS sequencing data from present-day and Bronze Age (5-3k years ago) Europeans, we identify possible targets of selection in the European population, which suggest that selection has targeted different alleles in the FADS genes in Europe than it has in South Asia or Greenland. The alleles showing the strongest changes in allele frequency since the Bronze Age show associations with expression changes and multiple lipid-related phenotypes. Furthermore, the selected alleles are associated with a decrease in linoleic acid and an increase in arachidonic and eicosapentaenoic acids among Europeans; this is an opposite effect of that observed for selected alleles in Inuit from Greenland. We show that multiple SNPs in the region affect expression levels and PUFA synthesis. Additionally, we find evidence for a gene-environment interaction influencing low-density lipoprotein (LDL) levels between alleles affecting PUFA synthesis and PUFA dietary intake: carriers of the derived allele display lower LDL cholesterol levels with a higher intake of PUFAs. We hypothesize that the selective patterns observed in Europeans were driven by a change in dietary composition of fatty acids following the transition to agriculture, resulting in a lower intake of arachidonic acid and eicosapentaenoic acid, but a higher intake of linoleic acid and α-linolenic acid.
Abstract 18833: Out of Hospital Cardiac Arrest Outcomes and Resource Utilization in the United States: Do Females Fare Worse?
Authors: Bolanle Akinyele, Shaker Eid, Lekshmi Raghavakurup, Nisha Chandra-Strobos, Aiham Albaeni
Journal: Circulation (2016)

Background: For many disease entities, women have been shown to have worse outcomes compared to men. Although, the association of gender and out of hospital cardiac arrest (OHCA) outcomes has been ...
Pmd-107: Marizomib, Pomalidomide and Low Dose-Dexamethasone Combination Study in Relapsed/Refractory Multiple Myeloma (NCT02103335): Full Enrollment Results from a Phase-1 Multicenter, Open Label Study
Authors: Andrew Spencer, Simon Harrison, Jacob P. Laubach, Jeffrey Zonder, Ashraf Z Badros, Krystal Bergin, Amit Khot, Todd Zimmerman, Kenneth C. Anderson, Ann MacLaren, Steven D Reich, Mohit Trikha, Paul G. Richardson
Journal: Blood (2016)
Corrigendum to: “European Consensus Conference on Diagnosis and Treatment of Germ Cell Cancer: A Report of the Second Meeting of the European Germ Cell Cancer Consensus group (EGCCCG): Part I” [Eur Urol 2008;53:478–96] and to: “European Consensus Conference on Diagnosis and Treatment of Germ Cell Cancer: A Report of the Second Meeting of the European Germ Cell Cancer Consensus group (EGCCCG): Part II” [Eur Urol 2008;53:497–513]
Authors: Susanne Krege, Jörg Beyer, Rainer Souchon, Peter Albers, Walter Albrecht, Ferran Algaba, Michael Bamberg, István Bodrogi, Carsten Bokemeyer, Eva Cavallin-Ståhl, Johannes Classen, Christoph Clemm, Gabriella Cohn-Cedermark, Stéphane Culine, Gedske Daugaard, Pieter H.M. De Mulder, Maria De Santis, Maike de Wit, Ronald de Wit, Hans Günter Derigs, Klaus-Peter Dieckmann, Annette Dieing, Jean-Pierre Droz, Martin Fenner, Karim Fizazi, Aude Flechon, Sophie D. Fosså, Xavier Garcia del Muro, Thomas Gauler, Lajos Geczi, Arthur Gerl, Jose Ramon Germa-Lluch, Silke Gillessen, Jörg T. Hartmann, Michael Hartmann, Axel Heidenreich, Wolfgang Hoeltl, Alan Horwich, Robert Huddart, Michael Jewett, Johnathan Joffe, William G. Jones, László Kisbenedek, Olbjørn Klepp, Sabine Kliesch, Kai Uwe Koehrmann, Christian Kollmannsberger, Markus Kuczyk, Pilar Laguna, Oscar Leiva Galvis, Volker Loy, Malcolm D. Mason, Graham M. Mead, Rolf Mueller, Craig Nichols, Nicola Nicolai, Tim Oliver, Dalibor Ondrus, Gosse O.N. Oosterhof, Luis Paz Ares, Giorgio Pizzocaro, Jörg Pont, Tobias Pottek, Tom Powles, Oliver Rick, Giovanni Rosti, Roberto Salvioni, Jutta Scheiderbauer, Hans-Ulrich Schmelz, Heinz Schmidberger, Hans-Joachim Schmoll, Mark Schrader, Felix Sedlmayer, Niels E. Skakkebaek, Aslam Sohaib, Sergei Tjulandin, Padraig Warde, Stefan Weinknecht, Lothar Weissbach, Christian Wittekind, Eva Winter, Lori Wood, Hans von der Maase
Journal: European Urology (2008)
Myocardial Infarction and Oral Contraceptives
Journal: New England Journal of Medicine (1972)

10 cases of myocardial infarction in females (mean age 41 years 4 months) on estrogen/progestin compounds for oral contraception have shown up the determinant role of the associated atherogenic risk factors.  All patients had 1 other risk factor.  In 6 cases there was hyperlipidemia with a cholesterol of above 2.60 and hypertriglyceridemia in 1 case.  A family history of coronary artery disease was present in 5 cases.  There was heavy tobacco consumption in 8 of the 10 cases.  All of these factors especially in combination increase the risk of infarction in a female on estrogen/progestin tablets and constitute a contraindication to their use.  2 of the patients had hypertension 2 were obese and 1 was a mild diabetic.  There was no warning in 1 case in 2 and early dilatation in 4 of the 10 cases.  Coronary arteriography on 5 of 7 patients so examined revealed coronary lesions involving 1 trunk.  The histological appearances of the occluded segment of the left coronary trunk in the 27-year-old patient who died were those of an organized occluding thrombus perhaps having developed over a slight thickening of the intima.(AUTHORS MODIFIED)
ROLE OF ENDOMYOCARDIAL BIOPSY IN PATIENTS WITH STRUCTURAL HEART DISEASE AND NORMAL CORONARY ARTERIES PRESENTING WITH VENTRICULAR ARRHYTHMIAS
Authors: Giovanni Peretto, Simone Sala, Alida L.P. Caforio, Cristina Basso, Gaetano Thiene, Paolo Della Bella
Journal: Journal of the American College of Cardiology (2017)
The BC Cancer Agency experience with gefitinib in advanced non-small cell lung cancer (NSCLC)
Authors: C. Ho, N. Murray, B. Melosky, J. Laskin, H. Anderson, R. R. Karim, L. Hamata, G. Bebb
Journal: Journal of Clinical Oncology (2004)

3104 Background: Institutional series suggest specific patient subgroups; female, Asian, non-smokers, respond preferentially to gefitinib. Vancouver, BC, has a large Asian population and therefore is an ideal location to study this differential effect. We performed a retrospective analysis of patients treated with single agent gefinitib to determine if our experience reflects this observation. Methods: Between April 2002 and August 2003, 31 patients were treated with gefitinib. Pathology, radiology, laboratory investigations and clinical records were reviewed. Partial radiologic response was defined as per SWOG response criteria. Symptom responses were subjectively evaluated from chart review. Tumor markers assessed included CEA, Ca 15.3, Ca 19–9 and Ca 125. Results: Baseline characteristics at diagnosis; 61% Caucasian, 39% Asian, male 45%, smokers 55%, non-smokers 39%, ECOG 0/1 87%. The tumor histology: 55% adenocarcinoma, 19% bronchoalveolar variant, 6.5% large cell, 3% squamous, 16.5% other. Median treatment length was 2 months. On radiologic review, 6 patients had a response, 13 had stable disease, 9 progressed, and 3 unknown. Fourteen patients reported improved symptoms, 6 had no change, and 9 had symptom progression. Tumor marker data was available in 18 patients: 7 had decrease in marker values, 4 had marker stabilization, and 7 had an increase. Toxicity was minimal; 1 patient had grade 3 hepatotoxicity that resolved with treatment cessation. There were 5 Asian female non-smokers; 2 had a response, 2 had stable disease and 1 progressed. Of the 6 radiological responders, 5 had ECOG 0/1, 4 were female, 5 non-smokers, 4 adenocarcinoma and 2 bronchoalveolar variant. A multivariate analysis of radiologic responders and those with stable disease is underway. Conclusions: At the BCCA, in a select number of patients with advanced NSCLC, gefitinib demonstrated clinical and radiologic anti-tumor benefit with minimal side effects. The molecular basis of the improved response rate observed in the subset of female, Asian, non-smokers with adenocarcinoma or bronchoalveolar variant warrants further exploration. No significant financial relationships to disclose.
Isocitrate dehydrogenase mutations suppress STAT1 and CD8+ T cell accumulation in gliomas
Authors: Gary Kohanbash, Diego A. Carrera, Shruti Shrivastav, Brian J. Ahn, Naznin Jahan, Tali Mazor, Zinal S. Chheda, Kira M. Downey, Payal B. Watchmaker, Casey Beppler, Rolf Warta, Nduka A. Amankulor, Christel Herold-Mende, Joseph F. Costello, Hideho Okada
Journal: Journal of Clinical Investigation (2017)

Mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 are among the first genetic alterations observed during the development of lower-grade glioma (LGG). LGG-associated IDH mutations confer gain-of-function activity by converting α-ketoglutarate to the oncometabolite R-2-hydroxyglutarate (2HG). Clinical samples and gene expression data from The Cancer Genome Atlas (TCGA) demonstrate reduced expression of cytotoxic T lymphocyte-associated genes and IFN-γ-inducible chemokines, including CXCL10, in IDH-mutated (IDH-MUT) tumors compared with IDH-WT tumors. Given these findings, we have investigated the impact of IDH mutations on the immunological milieu in LGG. In immortalized normal human astrocytes (NHAs) and syngeneic mouse glioma models, the introduction of mutant IDH1 or treatment with 2HG reduced levels of CXCL10, which was associated with decreased production of STAT1, a regulator of CXCL10. Expression of mutant IDH1 also suppressed the accumulation of T cells in tumor sites. Reductions in CXCL10 and T cell accumulation were reversed by IDH-C35, a specific inhibitor of mutant IDH1. Furthermore, IDH-C35 enhanced the efficacy of vaccine immunotherapy in mice bearing IDH-MUT gliomas. Our findings demonstrate a mechanism of immune evasion in IDH-MUT gliomas and suggest that specific inhibitors of mutant IDH may improve the efficacy of immunotherapy in patients with IDH-MUT gliomas.
Bortezomib As Salvage Treatment for Multiple Myeloma Relapsing after Allogeneic Haematopoietic Stem Cell Transplantation: Efficacy, Tolerance and Modulation of Graft Versus Host Disease: A Study of the French Society for Stem Cell Transplantation and Cell Therapies (SFGM-TC)
Authors: Tereza Coman, Richard Lemal, Laure Vincent, Reza Tabrizi, Patrice Chevallier, Mauricette Michallet, Didier Blaise, Nathalie Fegueux, Stephanie Nguyen, Jean-Henri Bourhis, Bruno Lioure, Caroline Regny, Pascal Lenain, Nicole Raus, Olivier Hermine, Gerard Socie, Mohamad Mohty, Ibrahim Yakoub-Agha, Regis Peffault de Latour, Marie T Rubio
Journal: Blood (2014)
EVALUATION OF LONG-TERM SUCCESS RATE OF OUTFLOW TRACT ABLATION IN PATIENTS WITH VENTRICULAR TACHYCARDIA
Authors: Pouria Alipour, Yaariv Khaykin, Zahra Azizi, Despina Michailidis, Amirhossein Sharifzad, Nikhil Nath, Evan Michaelov, Patrick Mallany, Sergio Conti, Alfredo Pantano, Atul Verma
Journal: Journal of the American College of Cardiology (2017)
Current Diagnosis Patterns for Acute Myeloid Leukemia (AML) in Clinical Practice Compared with World Health Organization (WHO) 2008 Recommendations: Outcomes from the CONNECT® Myelodysplastic Syndromes (MDS) and AML Disease Registry
Authors: Tracy I. George, Harry P. Erba, David P. Steensma, Daniel A Pollyea, Mehrdad Abedi, Rafael Bejar, Christopher R. Cogle, Guillermo Garcia-Manero, David L. Grinblatt, Rami S. Komrokji, Jaroslaw P Maciejewski, Dennis Revicki, Gail J. Roboz, Michael R. Savona, Bart L Scott, Mikkael A. Sekeres, Michael A Thompson, Albert Fliss, Arlene S. Swern, Melissa Nifenecker, Pavel Kiselev, Mary M. Sugrue, Kathryn Foucar
Journal: Blood (2016)
LAYER-SPECIFIC STRAIN ANALYSIS BY TWO-DIMENSIONAL SPECKLE TRACKING ECHOCARDIOGRAPHY: IMPROVEMENT OF CORONARY ARTERY DISEASE DIAGNOSTICS IN PATIENTS WITH STABLE ANGINA PECTORIS
Authors: Christoffer Hagemann, Søren Hoffmann, Rikke Andersen, Thomas Hansen, Flemming Javier Olsen, Peter Jørgensen, Jan Jensen, Tor Biering-Sørensen
Journal: Journal of the American College of Cardiology (2017)
Forty years of randomized trials in advanced/metastatic soft tissue sarcoma (STS): Endpoint selection, surrogacy and quality of reporting.
Authors: Alona Zer, Rebecca M. Prince, Eitan Amir, Albiruni R. A. Razak
Journal: Journal of Clinical Oncology (2015)

10513 Background: Randomized controlled trials (RCTs) in STS have utilized varying endpoints. Surrogacy of intermediate endpoints such as progression-free survival (PFS), response rate (RR), 3 month progression free survival (3moPFS) and 6 month progression free survival (6moPFS) with overall survival (OS) has not been established. The quality of reporting of efficacy and toxicity also remains uncertain. Methods: A systematic review of MEDLINE and EMBASE identified RCTs of systemic therapy in STS. Surrogacy between intermediate endpoints and OS was explored using meta-regression comprising a linear regression weighted by study sample size for the hazard ratio (HR) for OS with the HR for PFS or the odds ratio (OR) for RR, 3moPFS and 6moPFS. Quality of reporting of efficacy and toxicity were defined as described previously (Vera-Badillo et al, Ann Oncol 2013) and trends over time evaluated using simple linear regression. Results: Of 3329 articles initially identified; 52 RCTs published between 1974 and 2014 and comprising 9762 patients met the inclusion criteria. There was a moderate correlation between PFS and OS and between RR and OS (Table 1). The correlation between 3moPFS and 6moPFS with OS was however, weak. Only 44% of studies defined the primary endpoint clearly, but this deficiency improved over time (p for trend < 0.001). There has been a significant reduction in the use of RR as the primary endpoint over time, favouring time-based events (p for trend = 0.02). In 14% of RCTs, despite the primary endpoint not being met, the concluding statement suggested benefit from the experimental therapy. Toxicity was comprehensively reported in just 52% of RCTs while 17% reported toxicity poorly. Quality of toxicity reporting has not changed significantly over time (p = 0.70). Conclusions: In advanced STS RCTs PFS is a better surrogate for OS than RR. The correlation between 3moPFS/6moPFR and OS is weak and its use should be reconsidered. Although the quality of RCT reporting has improved over time, toxicity reporting and interpretation of results remain suboptimal. Surrogate endpoint Correlation coefficient with OS HR for PFS 0.61 OR for RR 0.51 OR for 3moPFS 0.27 OR for 6moPFR 0.31