Medicine and Health Sciences Commons^™

Identifying Priority And “Bright-Spot” Counties For Diabetes Preventive Care In Appalachia: An Exploratory Analysis, Peter J. Mallow, Michael Topmiller, Jennifer Rankin, Jene Grandmont, David Grolling, Jessica L. Mccann, Mark Carrozza

Journal of Appalachian Health

Introduction: Type 2 diabetes mellitus (T2DM) prevalence and mortality in Appalachian counties is substantially higher when compared to non-Appalachian counties, although there is significant variation within Appalachia.

Purpose: The objectives of this research were to identify low-performing (priority) and high-performing (bright spot) counties with respect to improving T2DM preventive care.

Methods: Using data from the Centers for Medicare and Medicaid (CMS), the Dartmouth Atlas of Health Care, and the Appalachia Regional Commission, conditional maps were created using county-level estimates for T2DM prevalence, mortality, and annual hemoglobin A1c (HbA1c) testing rates. Priority counties were identified using the following criteria: top 33rd …

Serum Cotinine Versus Parent Reported Measures Of Secondhand Smoke Exposure In Rural Appalachian Children, Samrat Yeramaneni, Kimberly Yolton, Kurunthachalam Kannan, Kim N. Dietrich, Erin N. Haynes

Journal of Appalachian Health

Background: Secondhand smoke (SHS) exposure in Appalachian children and associated adverse effects is understudied and not well documented. This study assessed the prevalence of SHS exposure in Appalachian children by parental self-report and internal biological measure.

Methods: SHS exposure was determined in children residing in rural Appalachian communities during their participation in the Communities Actively Researching Exposure Study between 2009 and 2013. Parents reported the number of smokers in the household and number of cigarettes smoked/day. Children ages 7-9 provided a serum sample for cotinine analysis. Parent reported measures and child serum cotinine measures of SHS exposure were compared with …

The Social Determinants Of Health And The Decline In U.S. Life Expectancy: Implications For Appalachia, Steven H. Woolf, Heidi Schoomaker, Latoya Hill, Christine M. Orndahl

Journal of Appalachian Health

For the past century, life expectancy in industrialized countries has increased, and the U.S. has shared in that progress. However, beginning in the 1980s, advances in U.S. life expectancy began to lose pace with peer countries. By 1998, U.S. life expectancy had fallen below the average for Organisation for Economic Cooperation and Development nations. U.S. life expectancy peaked in 2014 and has been decreasing for three consecutive years, a trend not been seen since the influenza pandemic a century ago. Put simply, U.S. health is in decline.

Delivering Health Knowledge And Wisdom From The Hills And Hollows Of Appalachia, F. Douglas Scutchfield Md, Erin N. Haynes, Robert M. Shapiro Ii, Charlotte S. Seidman

Journal of Appalachian Health

There is knowledge in the pages of Appalachia’s hills. This journal is positioned to find and publish those translations. It grows from a need to provide an outlet for scholarship about Appalachia’s health so that knowledge, and occasionally wisdom, is shared with those who care about and are committed to improving the region’s health.

Integrative Approaches To The Undergraduate Public Health Major Curriculum: Strengths, Challenges, And Examples, Marc T. Kiviniemi, Sarahmona M. Przybyla

Health, Behavior & Society Faculty Publications

Many “first generation” undergraduate public health degree programs were designed based on “siloed” course structures centered around subunits in the discipline (e.g., Introduction to Epidemiology, Introduction to Environmental Health) that may be meaningful primarily to experts in the field. An alternative to the siloed approach is an integrative curricular design, in which courses are designed around meaningful thematic units (e.g., explaining public health problems, asking and answering scientific questions in public health), with an emphasis on drawing connections between knowledge from different but complementary disciplinary areas as a means to improve student learning and retention. The integrative approach shifts the …

Systematic Review Of Gastrointestinal Nematodes Of Horses From Australia, Muhammad A. Saeed, Ian Beveridge, Ghazanfar Abbas, Anne Beasley, Jenni Bauquier, Edwina Wilkes, Caroline Jacobson, Kris J. Hughes, Charles El-Hage, Ryan O'Handley, John Hurley, Lucy Cudmore, Peter Carrigan, Lisa Walter, Brett Tennent-Brown, Martin K. Nielsen, Abdul Jabbar

Maxwell H. Gluck Equine Research Center Faculty Publications

Background: Equine gastrointestinal nematodes (GINs) have been the subject of intermittent studies in Australia over the past few decades. However, comprehensive information on the epidemiology of equine GINs, the efficacy of available anthelmintic drugs and the prevalence of anthelmintic resistance (AR) in Australasia is lacking. Herein, we have systematically reviewed existing knowledge on the horse GINs recorded in Australia, and main aspects of their pathogeneses, epidemiology, diagnoses, treatment and control.

Methods: Six electronic databases were searched for publications on GINs of Australian horses that met our inclusion criteria for the systematic review. Subsets of publications were subjected to review epidemiology, …

Local In Vivo Measures Of Muscle Lipid And Oxygen Consumption Change In Response To Combined Vitamin D Repletion And Aerobic Training In Older Adults, D. Travis Thomas, David M. Schnell, Maja Redzic, Mingjun Zhao, Hideat Abraha, Danielle Jones, Howard Brim, Guoqiang Yu

Health and Clinical Sciences Faculty Publications

Intramyocellular (IMCL), extramyocellular lipid (EMCL), and vitamin D deficiency are associated with muscle metabolic dysfunction. This study compared the change in [IMCL]:[EMCL] following the combined treatment of vitamin D and aerobic training (DAT) compared with vitamin D (D), aerobic training (AT), and control (CTL). Male and female subjects aged 60–80 years with a BMI ranging from 18.5–34.9 and vitamin D status of ≤ 32 ng/mL (25(OH)D) were recruited to randomized, prospective clinical trial double-blinded for supplement with a 2 × 2 factorial design. Cholecalciferol (Vitamin D₃) (10,000 IU × 5 days/week) or placebo was provided for 13 weeks …

Development And Evaluation Of A One-Step Multiplex Real-Time Taqman® Rt-Qpcr Assay For The Detection And Genotyping Of Equine G3 And G14 Rotaviruses In Fecal Samples, Mariano Carossino, Maria E. Barrandeguy, Erdal Erol, Yanqiu Li, Udeni B. R. Balasuriya

Veterinary Science Faculty Publications

Background: Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and has a negative impact on equine breeding enterprises worldwide. Among ERVA strains infecting foals, the genotypes G3P[12] and G14P[12] are the most prevalent, while infections by strains with other genomic arrangements are infrequent. The identification of circulating strains of ERVA is critical for diagnostic and surveillance purposes, as well as to understand their molecular epidemiology. Current genotyping methods available for ERVA and rotaviruses affecting other animal species rely on Sanger sequencing and are significantly time-consuming, costly and labor intensive. Here, we developed the first one-step …

Rediscovering The Axolotl As A Model For Thyroid Hormone Dependent Development, Anne Crowner, Shivam Khatri, Dana Blichmann, S. Randal Voss

Neuroscience Faculty Publications

The Mexican axolotl (Ambystoma mexicanum) is an important model organism in biomedical research. Much current attention is focused on the axolotl's amazing ability to regenerate tissues and whole organs after injury. However, not forgotten is the axolotl's equally amazing ability to thwart aspects of tissue maturation and retain juvenile morphology into the adult phase of life. Unlike close tiger salamander relatives that undergo a thyroid hormone regulated metamorphosis, the axolotl does not typically undergo a metamorphosis. Instead, the axolotl exhibits a paedomorphic mode of development that enables a completely aquatic life cycle. The evolution of paedomorphosis allowed axolotls …

The Promise Of Anti-Idiotype Revisited, Heinz Köhler, Anastas Pashov, Thomas Kieber-Emmons

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The promise of idiotype-based therapeutics has been disappointing forcing a new look at the concept and its potential to generate an effective approach for immunotherapy. Here, the idiotype network theory is revisited with regard to the development of efficacious anti-idiotype vaccines. The experience of polyclonal anti-Idiotype reagents in animal models as well as an understanding of the immune response in humans lends to the proposition that polyclonal anti-Idiotype vaccines will be more effective compared to monoclonal-based anti-Idiotype vaccines. This novel strategy can be adapted in Biotech-standard production of therapeutic antibodies.

Eis Inhibitors, Sylvie Garneau-Tsodikova, Oleg V. Tsodikov

Pharmaceutical Sciences Faculty Patents

Compounds and compositions are disclosed, which are useful as inhibitors of acetyltransferase Eis, a mediator of kanamycin resistance in Mycobacterium tuberculosis.

A Novel Function Of Membrane-Associated Collagen In Cancer Metastasis, Hui Zhang, Ren Xu

Markey Cancer Center Faculty Publications

No abstract provided.

Surface-Controlled Dissolution Rates: A Case Study Of Nanoceria In Carboxylic Acid Solutions, Eric A. Grulke, Matthew J. Beck, Robert A. Yokel, Jason M. Unrine, Uschi M. Graham, Matthew L. Hancock

Chemical and Materials Engineering Faculty Publications

Nanoparticle dissolution in local milieu can affect their ecotoxicity and therapeutic applications. For example, carboxylic acid release from plant roots can solubilize nanoceria in the rhizosphere, affecting cerium uptake in plants. Nanoparticle dispersions were dialyzed against ten carboxylic acid solutions for up to 30 weeks; the membrane passed cerium-ligand complexes but not nanoceria. Dispersion and solution samples were analyzed for cerium by inductively coupled plasma mass spectrometry (ICP-MS). Particle size and shape distributions were measured by transmission electron microscopy (TEM). Nanoceria dissolved in all carboxylic acid solutions, leading to cascades of progressively smaller nanoparticles and producing soluble products. The dissolution …

Assessing The Criteria For Definition Of Perimembranous Ventricular Septal Defects In Light Of The Search For Consensus, Justin T. Tretter, Vi-Hue Tran, Seth Gray, Hieu Ta, Rohit S. Loomba, William O'Connor, Diane E. Spicer, Andrew C. Cook, Robert H. Anderson

Pathology and Laboratory Medicine Faculty Publications

Background: Discussions continue as to whether ventricular septal defects are best categorized according to their right ventricular geography or their borders. This is especially true when considering the perimembranous defect. Our aim, therefore, was to establish the phenotypic feature of the perimembranous defect, and to establish the ease of distinguishing its geographical variants.

Methods and results: We assessed unrepaired isolated perimembranous ventricular defects from six historic archives, subcategorizing them using the ICD-11 coding system. We identified 365 defects, of which 94 (26%) were deemed to open centrally, 168 (46%) to open to the outlet, and 84 (23%) to the inlet …

Incorporating Pathway Information Into Feature Selection Towards Better Performed Gene Signatures, Suyan Tian, Chi Wang, Bing Wang

Biostatistics Faculty Publications

To analyze gene expression data with sophisticated grouping structures and to extract hidden patterns from such data, feature selection is of critical importance. It is well known that genes do not function in isolation but rather work together within various metabolic, regulatory, and signaling pathways. If the biological knowledge contained within these pathways is taken into account, the resulting method is a pathway-based algorithm. Studies have demonstrated that a pathway-based method usually outperforms its gene-based counterpart in which no biological knowledge is considered. In this article, a pathway-based feature selection is firstly divided into three major categories, namely, pathway-level selection, …

Evaluation Of A Tennessee Statewide Initiative To Reduce Early Elective Deliveries Using Quasi-Experimental Methods, Michael P. Thompson, Ilana Graetz, Caitlin N. Mckillop, Peter H. Grubb, Teresa M. Waters

Health Management and Policy Faculty Publications

Background: Concerted quality improvement (QI) efforts have been taken to discourage the practice of early elective deliveries (EEDs), but few studies have robustly examined the impact of directed QI interventions in reducing EED practices. Using quasi-experimental methods, we sought to evaluate the impact of a statewide QI intervention to reduce the practice of EEDs.

Methods: Retrospective cohort study of vital records data (2007 to 2013) for all singleton births occurring ≥36 weeks in 66 Tennessee hospitals grouped into three QI cohorts. We used interrupted-time series to estimate the effect of the QI intervention on the likelihood of an EED birth …

Life-Long Reduction In Myomir Expression Does Not Adversely Affect Skeletal Muscle Morphology, Ivan J. Vechetti Jr., Yuan Wen, Thomas Chaillou, Kevin A. Murach, Alexander Alimov, Vandre C. Figueiredo, Maeli Dal-Pai-Silva, John J. Mccarthy

Physiology Faculty Publications

We generated an inducible, skeletal muscle-specific Dicer knockout mouse to deplete microRNAs in adult skeletal muscle. Following tamoxifen treatment, Dicer mRNA expression was significantly decreased by 87%. Wild-type (WT) and Dicer knockout (KO) mice were subjected to either synergist ablation or hind limb suspension for two weeks. There was no difference in muscle weight with hypertrophy or atrophy between WT and KO groups; however, even with the significant loss of Dicer expression, myomiR (miR-1, -133a and -206) expression was only reduced by 38% on average. We next aged WT and KO mice for ~22 months following Dicer inactivation to determine …

Prevalence And Practice For Rare Diseases In Primary Care: A National Cross-Sectional Study In The Usa, Ara Jo, Samantha Larson, Peter Carek, Michael R. Peabody, Lars E. Peterson, Arch G. Mainous

Family and Community Medicine Faculty Publications

Objectives There are more than 7000 rare diseases in the USA, and they are prevalent in 8% of the population. Due to life-threatening risk and limited therapies, early detection and treatment are critical. The purpose of this study was to explore characteristics of visits for patients with rare diseases seen by primary care physicians (PCPs).

Design The study used a cross sectional study using a national representative dataset, the National Ambulatory Medical Care Survey for the years 2012–2014.

Setting Primary care setting.

Participants Visits to PCPs (n=22 306 representing 354 507 772 office visits to PCPs).

Primary outcome measures Prevalence …

Initial Results Of A Prospective Study Of Adjuvant Pancreatic Stereotactic Body Radiation Therapy For Close Or Positive Margins, Mark E. Bernard, Philip A. Sutera, Nicholas A. Iarrobino, Kimmen Quan, Steven A. Burton, Nathan Bahary, Melissa Hogg, Amer Zureikat, Dwight E. Heron

Radiation Medicine Faculty Publications

Purpose: Patients with close or positive margins after surgery for pancreatic carcinoma are at a high risk for recurrence. Stereotactic body radiation therapy (SBRT) allows for safe dose escalation with great conformity and short duration of treatment. Herein, we report the initial results of a prospective observational study that evaluated the efficacy and safety of this treatment option.

Methods and Materials: Patients eligible for the study had pathologically proven T1-4N0-1M0 pancreatic adenocarcinoma with a positive margin (≤ 1 mm) or a close margin defined as < 2.5 mm. Patients were treated with either neoadjuvant or adjuvant chemotherapy, if eligible for systemic therapy. All patients received 36 Gy in 3 fractions to the close or positive margin site.

Results: From February 2013 to January 2018, 50 patients were enrolled with 49 patients treated …

Rationale And Methods For A Multicenter Clinical Trial Assessing Exercise And Intensive Vascular Risk Reduction In Preventing Dementia (Rrad Study), Amanda N. Szabo-Reed, Eric Vidoni, Ellen F. Binder, Jeffrey Burns, C. Munro Cullum, William P. Gahan, Aditi Gupta, Linda S. Hynan, Diana R. Kerwin, Heidi Rossetti, Ann M. Stowe, Wanpen Vongpatanasin, David C. Zhu, Rong Zhang, Jeffrey N. Keller

Neurology Faculty Publications

Alzheimer's Disease (AD) is an age-related disease with modifiable risk factors such as hypertension, hypercholesterolemia, obesity, and physical inactivity influencing the onset and progression. There is however, no direct evidence that reducing these risk factors prevents or slows AD. The Risk Reduction for Alzheimer's Disease (rrAD) trial is designed to study the independent and combined effects of intensive pharmacological control of blood pressure and cholesterol and exercise training on neurocognitive function. Six hundred and forty cognitively normal older adults age 60 to 85 years with hypertension and increased risk for dementia will be enrolled. Participants are randomized into one of …

Beyond The Employment Dichotomy: An Examination Of Recidivism And Days Remaining In The Community By Post-Release Employment Status, Amanda Marie Bunting, Michele Staton, Erin Winston, Kevin Pangburn

Behavioral Science Faculty Publications

Criminological research has tended to consider employment in a dichotomy of employed versus unemployed. The current research examines a sample of individuals 1-year post-release to assess the extent to which four distinct employment categories (full-time, part-time, disabled, and unemployed) are associated with reincarceration and days remaining in the community. Findings indicate disabled individuals remain in the community longer and at a higher proportion compared with other employment categories. Furthermore, unique protective and risk factors are found to be associated with each employment category while some risk factors (e.g., homelessness) highlight the importance of addressing reentry barriers regardless as to employment …

Venoarterial Extracorporeal Membrane Oxygenation And Implantable Cardioverter-Defibrillator Implantation In A Hemodynamically Unstable Infant With Ventricular Tachycardia From Multiple Cardiac Rhabdomyomas, Victor Kieu, Richard J. Czosek, Timothy K. Knilans, James A. Quintessenza, Roosevelt Bryant Iii, Shaun Mohan

Pediatrics Faculty Publications

Tuberous sclerosis complex (TSC) is a neurocutaneous disorder characterized by benign tissue hamartomas in multiple organ systems, including cardiac rhabdomyomas. Though prevalent in TSC, cardiac tumors are rare in children, occurring in about 0.03%–0.17%. Rhabdomyomas are the most common, accounting for 45%. When present, they are multiple and in the ventricular myocardium. Frequently, they regress and surveillance is all that is required until spontaneous regression. Intervention is necessary when life-threatening obstruction or hemodynamically significant refractory arrhythmias occur. This case highlights the course of a 6-month-old infant with TSC and cardiac rhabdomyomas who presented in refractory ventricular tachycardia (VT) with decompensation …

Neuroprotective Activity Of Leukemia Inhibitory Factor Is Relayed Through Myeloid Zinc Finger-1 In A Rat Model Of Stroke, Stephanie M. Davis, Lisa A. Collier, Elspeth A. Foran, Christopher C. Leonardo, Craig T. Ajmo Jr., Keith R. Pennypacker

Neurology Faculty Publications

The aim of this study was to determine whether leukemia inhibitory factor (LIF) exerts its neuroprotective effects through signal transduction of the transcription factor myeloid zinc finger-1 (MZF-1). According to the hypothesis of this study, MZF-1 mediates LIF-induced neuroprotective signaling during ELVO through increased expression and transcriptional activity. To determine the in vivo role of MZF-1 in LIF-induced neuroprotection, we used Genomatix software was used to MZF-1 sites in the promoter region of the rat superoxide dismutase 3 (SOD3) gene. Stroke was induced via middle cerebral artery occlusion, and animals were administered PBS or 125 μg/kg LIF at …

Elastic Resistance Effectiveness On Increasing Strength Of Shoulders And Hips, Kelsey J. Picha, Muataz R. Almaddah, Jordan Barker, Tavis Ciochetty, W. Scott Black, Timothy L. Uhl

Physical Therapy Faculty Publications

Elastic resistance is a common training method used to gain strength. Currently, progression with elastic resistance is based on the perceived exertion of the exercise or completion of targeted repetitions; exact resistance is typically unknown. This study's objective is to determine if knowledge of load during elastic resistance exercise will increase strength gains during exercises. Participants were randomized into two strength training groups, elastic resistance only and elastic resistance using a load cell (LC) that displays force during exercise. The LC group used a Smart Handle (Patterson Medical Supply, Chicago, IL) to complete all exercises. Each participant completed the same …

Nutrition And Environmental Pollution Extension Curriculum Improved Diet-Related Behaviors And Environmental Health Literacy, Dawn Brewer, Hannah Bellamy, Anna Hoover, Annie Koempel, Lisa Gaetke

Dietetics and Human Nutrition Faculty Publications

Kentucky experiences some of the nation’s worst health outcomes related to obesity, diabetes, high blood pressure, and other age-related chronic diseases linked with oxidative stress and inflammation, which in turn are associated with poor diet, lack of physical activity, and exposure to certain environmental pollutants. In the Commonwealth, deteriorating infrastructure, inappropriate waste disposal, and potential occupational injury related to mining, agriculture, and other regionally important industries exacerbate the need for residents to have basic knowledge of potential environmental health threats. Unfortunately, community-level understanding of the complex connections between environmental exposures and health is limited, with many Kentuckians unaware that the …

Tobacco Smoking And Dementia In A Kentucky Cohort: A Competing Risk Analysis, Erin L. Abner, Peter T. Nelson, Gregory A. Jicha, Gregory E. Cooper, David W. Fardo, Frederick A. Schmitt, Richard J. Kryscio

Epidemiology and Environmental Health Faculty Publications

Tobacco smoking was examined as a risk for dementia and neuropathological burden in 531 initially cognitively normal older adults followed longitudinally at the University of Kentucky’s Alzheimer’s Disease Center. The cohort was followed for an average of 11.5 years; 111 (20.9%) participants were diagnosed with dementia, while 242 (45.6%) died without dementia. At baseline, 49 (9.2%) participants reported current smoking (median pack-years = 47.3) and 231 (43.5%) former smoking (median pack-years = 24.5). The hazard ratio (HR) for dementia for former smokers versus never smokers based on the Cox model was 1.64 (95% CI: 1.09, 2.46), while the HR for …

Eeg Findings In Infants With Neonatal Abstinence Syndrome Presenting With Clinical Seizures, Murali Reddy Palla, Gulam Q. Khan, Zahra M. Haghighat, Henrietta S. Bada

Pediatrics Faculty Publications

Neonatal abstinence syndrome (NAS) refers to a constellation of signs occurring in newborn infants who were exposed to opioids or opiates in utero. These manifestations include poor feeding, gastrointestinal disorders, abnormal sleep patterns, and neurological signs such as jitteriness, tremors, and seizures (1, 2). Myoclonus, jitteriness, and tremors often may be interpreted as seizures and therefore treated as epileptic seizures.

Objective: To determine whether seizure like activity observed in infants with NAS correlate with electroencephalogram (EEG) findings.

Design/ Method: We reviewed the standard EEG or video electroencephalogram (VEEG) of infants with NAS who were admitted because of seizure-like clinical …

The Effects Of Bacterial Endotoxin Lps On Synaptic Transmission At The Neuromuscular Junction, Robin L. Cooper, Micaiah Mcnabb, Jeremy Nadolski

Biology Faculty Publications

The direct action of bacterial lipopolysaccharides (LPS) endotoxin was shown to enhance synaptic transmission and hyperpolarize the membrane potential at low doses, but block glutamatergic receptors and decrease observable spontaneous events at a high dosage. The dosage effects are LPS type specific. The hyperpolarization is not due to voltage-gated potassium channels or to activation of nitric oxide synthase (NOS). The effects are induced directly by LPS, independent of an immune response.

Proteomic Alterations Of Hdl In Youth With Type 1 Diabetes And Their Associations With Glycemic Control: A Case-Control Study, Evgenia Gourgari, Junfeng Ma, Martin P. Playford, Nehal N. Mehta, Radoslav Goldman, Alan T. Remaley, Scott M. Gordon

Saha Cardiovascular Research Center Faculty Publications

Background: Patients with type 1 diabetes (T1DM) typically have normal or even elevated plasma high density lipoprotein (HDL) cholesterol concentrations; however, HDL protein composition can be altered without a change in cholesterol content. Alteration of the HDL proteome can result in dysfunctional HDL particles with reduced ability to protect against cardiovascular disease (CVD). The objective of this study was to compare the HDL proteomes of youth with T1DM and healthy controls (HC) and to evaluate the influence of glycemic control on HDL protein composition.

Methods: This was a cross-sectional case–control study. Blood samples were obtained from patients with T1DM and …

Kinase Suppressor Of Ras 1 And Exo70 Promote Fatty Acid-Stimulated Neurotensin Secretion Through Erk1/2 Signaling, Stephanie Rock, Xian Li, Jun Song, Courtney M. Townsend, Heidi L. Weiss, Piotr G. Rychahou, Tianyan Gao, Jing Li, B. Mark Evers

Markey Cancer Center Faculty Publications

Neurotensin is a peptide hormone released from enteroendocrine cells in the small intestine in response to fat ingestion. Although the mechanisms regulating neurotensin secretion are still incompletely understood, our recent findings implicate a role for extracellular signal–regulated kinase 1 and 2 as positive regulators of free fatty acid-stimulated neurotensin secretion. Previous studies have shown that kinase suppressor of Ras 1 acts as a molecular scaffold of the Raf/MEK/extracellular signal–regulated kinase 1 and 2 kinase cascade and regulates intensity and duration of extracellular signal–regulated kinase 1 and 2 signaling. Here, we demonstrate that inhibition of kinase suppressor of Ras 1 attenuates …