tbuckley/cabot-search huggingface dataset:
Smart Start: Rituximab, Lenalidomide, and Ibrutinib Alone and in Combination with Standard Chemotherapy for Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma: Final Phase II Results
Authors: Jason R. Westin, Loretta J. Nastoupil, Luis Fayad, Fredrick B. Hagemeister, Yasuhiro Oki, Francesco Turturro, Sairah Ahmed, Maria Alma Rodriguez, Hun Ju Lee, Raphael Eric Steiner, Ranjit Nair, Simrit Parmar, Ken H. Young, Timothy J. McDonnell, Hubert Chuang, Michael R Green, Sattva S Neelapu, Eric Davis
Journal: Blood (2019)
PDTM-29. STRUCTURE FUNCTION AND CELL TYPE DETERMINANTS OF C11orf95-RELA DRIVEN TUMORS IN MICE
Authors: Jesse Dunnack, Ericka Randazzo, Jahmique Caines, Jame He, Joseph LoTurco
Journal: Neuro-Oncology (2019)

Abstract We used a new mouse model to better understand the cellular and molecular determinants of tumors driven by the C11orf95-RELA fusion. Our approach makes use of in utero electroporation and a binary transposase system to introduce human C11orf95-RELA sequence, wild type and mutant, into neural progenitors, and drive expression of the fusion in different glial and neuronal progenitor cell types. Our results indicate that truncations or point mutations in C11orf95 sequence which interfere with nuclear localization result in a complete loss of tumor-inducing activity. The mutations include truncations of the first 60 amino acids, internal truncations that delete possible mono and bipartite nuclear localization signals, and point mutations of two cysteines and histidines that make up a possible zinc finger domain in C11orf95. Interestingly, all of the mutations that block tumorigenesis also block signal independent nuclear localization of the wild type fusion, without blocking induction of NFKB response genes. We further found that over-expression of the NFKB1 subunit P50 which lacks a transcriptional activation domain significantly inhibits tumor formation by the fusion. In addition, we find that driving expression of the wild type fusion in glial progenitor types using promoters for either astrocytes or oligodendrocytes results in the formation of tumors with transcriptomes displaying significant similarities to human supratentorial ependymoma (ST-EPN), but with distinct patterns depending upon the glial progenitor promoter utilized. In contrast, promoters driving expression selectively in neuron restricted progenitors do not result in the formation of ST-EPN. Together our results reveal three new features of C11orf95-RELA driven tumorigenesis: i) multiple sequences within the C11orf95 domain are required for oncogenic driver activity of the fusion, ii) the P50 subunit of NFKB1 can inhibit fusion induced tumorigenesis, and iii) neuron-restricted precursors are less competent than glia-restricted precursors to form tumors induced by C11orf95-RELA.
High Avidity IgM-Based CD20xCD3 Bispecific Antibody (IGM-2323) for Enhanced T-Cell Dependent Killing with Minimal Cytokine Release
Authors: Ramesh Baliga, Keyu Li, Marigold Manlusoc, Paul Hinton, Dean Ng, Madeline Tran, Bing Shan, Hai Lu, Avneesh Saini, Sachi Rahman, Yuan Cao, Chitra Saraiya, Marvin Peterson, Steve Carroll, Daniel Chen, Bruce Keyt
Journal: Blood (2019)
ATIM-08. TRIAL IN PROGRESS: CA209-9Y8 PHASE 2 TRIAL OF TUMOR TREATING FIELDS (TTFS), NIVOLUMAB PLUS/MINUS IPILIMUMAB FOR BEVACIZUMAB-NAÏVE, RECURRENT GLIOBLASTOMA
Authors: Yazmin Odia, Fabio Iwamoto
Journal: Neuro-Oncology (2019)

Abstract Recurrent glioblastoma has limited therapeutic options. The EF11 trial of TTFs vs. physician’s choice chemotherapy showed an objective response rate (ORR) of 14%, but no survival (OS) benefit. CheckMate 143 randomized phase 3, open-label trial of nivolumab vs. bevacizumab failed to show an OS benefit, though nivolumab led to ORR of 7.8% with more durable response than bevacizumab (11.1 vs. 5.3 months). Preclinical studies suggest synergism between TTFs and immunotherapy. TTFs expose calreticulin on cell surfaces, causing HMGB1 and ATP secretion—hallmarks of anticancer immunogenic cell death. Observed trends in a glioma cohort also suggest synergism: 77% of glioma patients treated with TTFs received concurrent temozolomide (16, 31%), nitrosourea (4,8%), bevacizumab (19,37%), or immunotherapy (28,54%). Only 2 (4%) experienced skin toxicity requiring TTFs hold. For TTFs plus immunotherapy vs. chemotherapy, there was a trend toward increased OS (8.3 vs. 6.5 months,p=0.32) and ORR (26% vs. 13%), with significant increase in PFS for glioblastomas (4.6 vs. 3.5 months,p=0.04). ORR was &gt;14% in EF11 or &lt; 5- 10% in meta-analyses of immunotherapy for recurrent glioblastoma. This open-label, phase 2 trial with 2 parallel arms uses a 2-stage Minimax design with stopping rules for futility. We will enroll 30 (15/Arm) to 60 (30/Arm) evaluable subjects. The primary endpoint is ORR by modified RANO. Secondary objectives are OS, PFS, safety, compliance, and biomarker correlations. Adults with glioblastoma at first or second recurrence and no prior CTLA inhibitor or bevacizumab are eligible. All receive TTFs with nivolumab for ≤24 months and ipilimumab for ≤4 doses. Arm A (no prior PD1/PDL1 inhibitor) receive nivolumab only and add ipiliumumab at progression. Arm B (prior PD1/PDL1 inhibitor) receive nivolumab and ipilumimab. Nivolumab is dosed IV q2weeks 240mg as monotherapy and 3mg/kg with ipilumimab IV 1mg/kg q6weeks. TTFs starts by 1 month and worn for ≥75% over ≤24 months.
Doctor who used sister’s disabled travel pass is suspended for eight months
Authors: Clare Dyer
Journal: BMJ (2019)

A junior doctor who used her sister’s disabled London travel pass 80 times before being caught by an inspector at King’s Cross station and fined £200 by a magistrate has been suspended from the UK medical register for eight months.

A medical practitioners tribunal found that Sharifa Scerif, 27, who qualified in 2017, had acted dishonestly in using the card and in the explanation she gave to the inspector and later in writing to Transport for London (TfL).

An inspector at King’s Cross station stopped Scerif on 1 February 2018 after noting that she had used a disabled pass at the automatic barrier. The photo was heavily rubbed on the Freedom Pass, which gives free travel to over 60s and disabled people on TfL services. It bore the name of Fatma Scerif.

Scerif at first claimed that the …
Towards Non-Invasive Classification of DLBCL Genetic Subtypes By Ctdna Profiling
Authors: Mohammad Shahrokh Esfahani, Stefan Alig, David M. Kurtz, Joanne Soo, Michael C. Jin, Charles Macaulay, Alexander F. M. Craig, Andrea Garofalo, Chloe B. Steen, Florian Scherer, Brian Sworder, Maximilian Diehn, Ash A. Alizadeh
Journal: Blood (2019)
CPX-351 Induces Deep Response and Suppress the Impact of Poor Prognosis Mutations (TP53, ASXL1, RUNX1 and EVI1) Defined By ELN-2017 in t-AML and MRC AML: A Report from a Multicentric French Cohort
Authors: Edmond Chiche, Sarah Bertoli, Ramy Rahmé, Jean Baptiste Micol, Florence Pasquier, Pierre Peterlin, Patrice Chevallier, Xavier Thomas, Michael Loschi, Alexis Genthon, Olivier Legrand, Mohamad Mohty, Emmanuel Raffoux, Patrick Auberger, Alexis Caulier, Magalie Joris, Caroline Bonmati, Gabrielle Roth Guepin, Mathieu Sauvezie, Caroline Lejeune, Arnaud Pigneux, Christian Recher, Lionel Ades, Thomas Cluzeau
Journal: Blood (2019)
CMET-23. IMPACT OF SYSTEMIC THERAPY IN MELANOMA BRAIN METASTASIS
Authors: Soumya Sagar, Adam Lauko, Addison Barnett, Wei (Auston) Wei, Samuel Chao, David Peereboom, Glen Stevens, Lilyana Angelov, Jennifer Yu, Erin Murphy, Alireza Mohammadi, John Suh, Gene Barnett, Manmeet Ahluwalia
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Melanoma is the third most common malignancy that results in brain metastasis and is associated with a median overall survival (OS) of approximately 9 months. In recent years, management of melanoma brain metastases (MBM) by surgery and radiation [stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT)] has been bolstered by targeted therapy and immune checkpoint inhibitors (ICI). METHODS 351 patients, treated for MBM at our tertiary care center from 2000–2018, were grouped into: received chemotherapy, ICI, or targeted therapy. 34% of patients treated with ICI had received other systemic therapies as well as part of their management. OS was calculated from the date of diagnosis of the brain metastases. The Kaplan Meier analysis was utilized to determine median OS and difference in OS was determined by utilizing the Cox proportional hazard model. RESULTS The median survival after the diagnosis of brain metastasis was 10.4, 11.96, and 7.06 months in patients who received ICI, chemotherapy and targeted therapy respectively. A multivariate model was developed including the type of systemic therapy, presence of extracranial metastases, age, KPS and number of intracranial lesions. 114 patients underwent SRS alone, 56 underwent SRS and WBRT, 43 underwent SRS and surgical removal, 28 had surgical removal, SRS and WBRT, and 78 had no intracranial therapy. Compared to patients who received chemotherapy, patients who received immunotherapy had a hazard ratio, HR = 0.628 (confidence interval = 0.396 – 0.994, p-value = 0.047). Presence of EC metastases (HR= 1.25, p-value &lt; .001), lower KPS (HR = .97, p-value &lt; .0001) and multiple brain lesions (HR = 1.117, p-value &lt; .0001) were associated with significantly worse OS. CONCLUSIONS Addition of ICI significantly improves the OS in MBM compared to chemotherapy. Lower performance status, multiple brain metastases, and EC metastases are associated with poor OS.
Transfusion-Dependent Low Risk Myelodysplastic Syndrome (TD LR-MDS): Predictors Ofcardiovascular Events and Death
Authors: Marta Alonso Fernández de Gatta, Ana Martín García, Félix López Cadenas, Díaz Peláez Elena, Tamara Jimenez, Jesus Maria . Hernández-Rivas, Victor Vallejo García, Manuel Barreiro Pérez, Lucia Rodríguez Estévez, Juan Carlos Castro Garay, Diego Ávila, Adolfo Alejandro Cabanillas Cabral, Clara Sánchez Pablo, María Díez-Campelo, Pedro Luís Sánchez Fernández
Journal: Blood (2019)
Discovery of Novel IL3RA (CD123) Isoforms By Long Read Transcriptomics, Heterogeneous Expression Among AML Patient Cohorts and the Implications for Anti-CD123 Therapeutics
Authors: Jason G Underwood, Jenny L. Smith, Lindsey F. Call, Elizabeth Tseng, Tiffany A. Hylkema, Rhonda E. Ries, Amanda R. Leonti, Jason E. Farrar, Timothy Junius Triche, Soheil Meshinchi
Journal: Blood (2019)
Affordability of the EAT–Lancet reference diet: a global analysis
Authors: Kalle Hirvonen, Yan Bai, Derek Headey, William A Masters
Journal: The Lancet Global Health (2019)

The EAT-Lancet Commission drew on all available nutritional and environmental evidence to construct the first global benchmark diet capable of sustaining health and protecting the planet, but it did not assess dietary affordability. We used food price and household income data to estimate affordability of EAT-Lancet benchmark diets, as a first step to guiding interventions to improve diets around the world.
A Phase I Study of Nivolumab and Lenalidomide in Relapsed/ Refractory B Cell Lymphoma
Authors: David A. Bond, Vedat Yildiz, Lai Wei, Lapo Alinari, Basem M. William, Jonathan E. Brammer, Beth A. Christian, Kristie A. Blum, Kami J. Maddocks
Journal: Blood (2019)
ZNF802 (JAZF1), a Possible New Therapeutic Target for Treatment of β-Thalassemia
Authors: Chokdee Wongborisuth, Amornrat Tangprasittipap, Usanarat Anurathapan, Nuankanya Sathirapongsasuti, Orapan Sripichai, Duantida Songdej, Suradej Hongeng
Journal: Blood (2019)
Peripheral vascular disorders
Authors: N. D. Greyson
Journal: Clinical Nuclear Medicine (1991)

The widely prevalent problem of phlebitis, with its potentially fatal complication of pulmonary embolism, remains an important clinical problem both for the hospitalized and ambulatory patient. Peripheral vascular disease, resulting from atherosclerosis or other forms of vasculitis, with the complications of chronic cutaneous ulceration, pain, atrophy and gangrene, results in significant morbidity and incapacitation of the geriatric population.KeywordsDeep Vein ThrombosisDeep Venous ThrombosisPeripheral Vascular DiseaseBlood PoolRadionuclide AngiographyThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Identification of Optimized Peptide Nucleic Acid (PNA) Designs for Nuclease-Free Gene Editing in Sickle Cell Disease Hematopoietic Stem and Progenitor Cells (HSPCs)
Authors: Allen Ebens, Andrew Curd, Derek Sim, Elias Quijano, Florence Tam, James Coull, Lily Huang, Mark Hayes, Marshall Fordyce, Robert Pearson, Susan Whoriskey, Tumul Srivastava, Xiaojun Li, Zhen Zhang
Journal: Blood (2019)
RNA-Seq Can Help Identify IGH Disease Clones for MRD Monitoring in Childhood B-Lymphoblastic Leukemia
Authors: Zhenhua Li, Nan Jiang, Evelyn Huizi Lim, Winnie Hui Ni Chin, Shirley Kow Yin Kham, Wentao Yang, Thuan Chong Quah, Hai_peng Lin, Ah Moy Tan, Hany Ariffin, Jun J. Yang, Allen Eng Juh Yeoh
Journal: Blood (2019)
Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric Acute Myeloid Leukemia in the Contemporary Era
Authors: Erin E Doherty, Michele Redell, Ghadir Sasa, Khaled Yassine, Tami D John, John Craddock, Mengfen Wu, Tao Wang, Caridad A. Martinez, Robert A. Krance, Swati Naik
Journal: Blood (2019)
Deep Sequencing of Viral Cell-Free DNA for Noninvasive Detection of Immunosuppression-Related Lymphoid Malignancies
Authors: Andrea Garofalo, Joseph G Schroers-Martin, Joanne Soo, David M. Kurtz, Brian Sworder, Chih Long Liu, Benjamin A Pinsky, Helen Luikart, Ranjana H Advani, Yasodha Natkunam, Kiran Khush, Maximilian Diehn, Arash A. Alizadeh
Journal: Blood (2019)
NIMG-28. VALIDATION OF SINGLE-DOSE DSC-MRI PROTOCOLS FOR ROBUST PERFUSION ASSESSMENT IN BRAIN TUMORS
Authors: Chad Quarles, Laura Bell, Natenael Semmineh, Alberto Fuentes, Melissa Prah, Ashley Nespodzany, Lea Alhilai, John Karis, Scott Rand, Chris Dardis, Kelly Braun, Jennifer Connelly, Yuxiang Zhou, Kathleen Schmainda, Leland Hu, Jerry Boxerman, Ashley Stokes
Journal: Neuro-Oncology (2019)

Abstract Dynamic susceptibility contrast (DSC) MRI measures of brain tumor cerebral blood volume (CBV) are able to predict grade, overall survival and response to treatment. Wide-spread acceptance of DSC-MRI has been challenged by the need to balance contrast agent dose and CBV accuracy. The goal of this study was to identify and validate single-dose, BTIP compliant, DSC-MRI protocols. Using a validated, patient-based DRO, we evaluated CBV accuracy across a range of acquisition parameters (field strength, TR, TE, flip angle, multi-echo acquisitions, dosing protocols) and post-processing steps. To validate the optimal protocols, we next collected DSC-MRI data following ASFNR’s recommended “double – dose” approach, where a single-dose preload (to minimize T1 effects) is given prior to a second bolus injection (for DSC-MRI data acquisition). The single-dose DSC-MRI data was collected during the preload bolus injection. Consistency of the derived CBV data, visual agreement and data characteristics (e.g. CNR) was statistically evaluated. When using a single-dose and routine single-echo pulse sequence, the DRO analysis found that a low flip angle (LFA = 30o) and 30ms TE provided the highest CBV accuracy (concordance correlation coefficient (CCC) = 0.92) and precision (coefficient of variation (CV) = 8.2%)). For comparison, the maximum accuracy found with the DRO utilizes a double-dose injection protocol and yielded a CCC of 0.98 and CV of 6.8%. Single-dose, multi-echo acquisitions provided higher accuracy than the LFA data and matched that found with the double-dose approach. In patients (data collection ongoing), the agreement between single-dose LFA (n &gt; 40) or multi-echo (n &gt; 40) based CBV values and the reference double-dose approach was very high (CCC &gt; 0.94) and were statistically equivalent. Optimized single-dose DSC-MRI protocols provide highly accurate CBV data, use lower doses of contrast agent, and simplify scan procedures, indicating their potential for robust use in clinical practice and trials.
Successful and Safe Treatment of Intestinal Graft-Versus-Host Disease (GvHD) with Pooled-Donor Full Ecosystem Microbiota Biotherapeutics
Authors: Florent Malard, Faezeh Legrand, Jérôme Cornillon, Amandine Le Bourgeois, Jean-Baptiste Mear, Deborah Desmier, Emilie Plantamura, Ronald Carter, Thierry Lamy De La Chapelle, Patrice Chevallier, Denis Guyotat, Didier Blaise, Mohamad Mohty
Journal: Blood (2019)
Analysis of JAK2 Mutation in Essential Thrombocythemia (ET) Patients with Monoclonal and Polyclonal X-Chromosome Inactivation Patterns (XCIPs).
Authors: Jean-Jacques Kiladjian, Nahed Elkassar, Gilles Hetet, Nicole Balitrand, Carole Conejero, Stephane Giraudier, Bruno Cassinat, Claude Gardin, Pierre Fenaux, Christine Chomienne, Bernard Grandchamp
Journal: Blood (2005)
Strategies for Analysis of Novel Molecular Variants in the RUNX1 Gene As a Cause of Familial Platelet Disorder with Predisposition to Acute Myeloid Leukemia (FPD/AML)
Authors: Veronica Palma-Barqueros, Jf Ruiz-Pividal, Jose Maria Bastida, Natalia Bohdan, MJ Lopez-Andreu, Raul Teruel-Montoya, Ana Isabel Antón, Francisca Ferrer Marin, Jose Padilla, Rosa Cifuentes-Riquelme, A Marín-Quilez, Marta Martín Izquierdo, Rocio Benito, Vicente Vicente, Jesus Maria . Hernández-Rivas, José Ramón González-Porras, Jose Rivera, Maria Luisa Lozano
Journal: Blood (2019)
Environmental hazards kill fivemillion children ayear.
Authors: Owen Dyer
Journal: BMJ (2003)

The World Health Organization has called for concerted action to reduce environmental hazards to children, which, the agency says, claim more than five million lives a year among the under 14s, mainly in the developing world.

WHO's director general, Dr Gro Harlem Brundtland, speaking at the World Health Day launch on Monday in New Delhi, India, identified acute respiratory infections as the number one killer of children, cutting short two million lives each year. She said indoor air pollution from cooking and heating with dirty household fuels was a major factor in respiratory infections, as was second hand tobacco smoke.

Diarrhoeal diseases caused by inadequate sanitation and poor quality water killed 1.3 million children annually, and malaria, the third biggest killer among children, took one million lives a year, mostly in sub-Saharan Africa. Many accidental deaths such as drowning, poisoning, and pedestrian traffic deaths could also be linked to the environments that children grow up in, said Dr Brundtland.
Hyperoxemia: The Poison Is in the Dose
Authors: François Lellouche, Erwan L’Her
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

The Poison Is in the DoseTo the Editor:The counterintuitive question of the link between hyperoxemia and increased mortality has frequently been raised in the last 10 years.The Austin and colleagues' randomized controlled trial in 2010 was the first study to demonstrate an excess of mortality with a short exposure to liberal use of oxygen in patients with acute respiratory failure (1).The results of the recently published meta-analysis by Chu and colleagues, which included 16,037 patients from 25 randomized controlled studies, were compelling.
Preemptive Administration of Ruxolitinib Rapidly Ameliorate Gvhd after Allo-Hematopoietic Stem Cell Transplantation: A Single-Center Retrospective Study
Authors: Kangni Lin, Minmin Chen, Qian Li, Jinhua Ren, Haojie Zhu, Jingjing Xu, Rong Zheng, Zhizhe Chen, Jianda Hu, Ting Yang
Journal: Blood (2019)
Pelvic Inflammatory Disease
Authors: Nancy F Crum-Cianflone
Journal: New England Journal of Medicine (2015)

To the Editor: In the review by Brunham et al. (May 21 issue),1 Mycoplasma genitalium is included as an etiologic agent of pelvic inflammatory disease. Studies have shown that this pathogen may be as prevalent as Chlamydia trachomatis in genital infections2; hence, guidance on treatment for infection with this organism is critically important. As such, it is surprising that Brunham states, “Substitution of azithromycin for doxycycline covers M. genitalium and simplifies dosing.” Such a statement ignores the widespread macrolide resistance (approximately 40%) among M. genitalium isolates.3,4 Furthermore, a recent randomized trial showed that clinical cure rates were low . . .
Impact of Hematopoeitic Cell Transplantation-Co-Morbidity Index (HCT-CI) and Its Individual Components on Allogeneic Transplant Outcomes
Authors: Sunu Cyriac, Auro Viswabandya, Jeffrey H. Lipton, Dennis Dong Hwan Kim, Rajat Kumar, Wilson Lam, Arjun Law, Zeyad Al-Shaibani, Jonas Mattsson, Fotios V. Michelis
Journal: Blood (2019)
Morphologic Assessment of Terminal Erythroid Differentiation Predicts Outcomes in Myelodysplastic Syndromes
Authors: Maria Julia Montoro, Ana Perez, Silvia Saumell, Maida Navarrete, Gael Roue, Moraima Jimenez, Margarita Ortega, Bárbara Tazón, Antonieta Molero, Olga Salamero, Francesc Bosch, David Valcarcel
Journal: Blood (2019)
PDTM-45. MECHANISM OF NEURAL STEM CELL TRANSFORMATION BY C11ORF95-RELA TRANSLOCATIONS
Authors: Robert Kupp, Richard J Gilbertson
Journal: Neuro-Oncology (2019)

Abstract Highly recurrent chromosome translocations that produce oncogenic fusions are a prime example of practical therapeutic targets translating into clinical successes. We have previously described the genetic driver of supratentorial ependymomas as translocation fusions of the C11orf95 gene of unknown function and RELA, the canonical nuclear transducer of NF-κB signaling5. Subsequent studies have reinforced our original findings on the frequency (&gt;70%) of these C11orf95-RELA (CR) fusions in human disease, as well as their transformative potential in murine models. However, the mechanisms by which CR fusions transform neural stem cells into ependymomas remain elusive. Using a multi-OMICS approach, we show that oncogenic C11orf95 fusions co-opt spatio-temporally regulated transcriptional activators in ependymoma. We henceforth demonstrate that supratentorial ependymomas, which have been previously described as a RELA fusion disease6, are truly a C11orf95 fusion disease, with C2H2-ZFs serving as a scaffold for transcriptional dysregulation. Our studies lay the architectural framework for a molecular roadmap into the heart of C11orf95 fusion ependymomas, elucidating the biochemical mechanisms which furnish the capacity of these fusions to operate as single gene oncogenes, and henceforth providing potential avenues for therapeutic intervention in ependymoma.
SF3B1 Clone Size Is an Independent Determinant for Overall Survival and Response to Treatment in Patients with Myelodysplastic Syndrome
Authors: Rami S. Komrokji, David A Sallman, Najla Al Ali, Andrew T Kuykendall, Chetasi Talati, Kendra L. Sweet, Jeffrey E. Lancet, Eric Padron, Alan F. List
Journal: Blood (2019)
Invincible arrogance--and patients suffer
Authors: P. Oppenheimer
Journal: BMJ (1981)

sprinters lack stamina, but I imagine that no one would question their cardiopulmonary fitness-while in training.I am also worried by the modified physical fitness index, as this fails to take account of the resting pulse rate.Surely a formula based on percentage increase over resting rate at two, five, and 10 minutes would seem more reasonable, since the normal resting pulse rate can vary from the 40s to the 90s at least-or does a naturally slow pulse rate confer a fitness advantage ?Interestingly, Lieutenant-ColonelPearn referred to Zatopek's fitness index of 172; he was a distance runner with a resting pulse rate of about 40 per minute.But I wonder how Zatopek would have fared on the squash court, where explosive bursts of energy are required, or in gymnastics, in which a completely different sort of fitness and body control is demanded, or in the swimming pool.He certainly would have been