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Articles 1 - 21 of 21
Full-Text Articles in Fluids and Secretions
Microfluidic Encapsulation Of Sorafenib-Loaded Zif-8 Nanoparticles In Ph-Responsive Alginate Microparticles For Oral Chemotherapy Of Hepatocellular Carcinoma, Mojdeh Mirshafiei, Zahra Mahmoudi, Mehdi Mehrpouya, Mahdi Mahmoudi, Masoud Rezaeian, Mona Navaei-Nigjeh, Zahra Katoli, Lobat Tayebi
Microfluidic Encapsulation Of Sorafenib-Loaded Zif-8 Nanoparticles In Ph-Responsive Alginate Microparticles For Oral Chemotherapy Of Hepatocellular Carcinoma, Mojdeh Mirshafiei, Zahra Mahmoudi, Mehdi Mehrpouya, Mahdi Mahmoudi, Masoud Rezaeian, Mona Navaei-Nigjeh, Zahra Katoli, Lobat Tayebi
Electrical & Computer Engineering Faculty Publications
Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality. Sorafenib is the current first-line oral therapy; however, its therapeutic efficacy is limited by poor aqueous solubility, low bioavailability, and gastrointestinal instability. This study aimed to develop a pH-responsive nano-in-microparticle delivery system using a single-step droplet-based microfluidic process to protect sorafenib in the gastric environment and achieve controlled release for enhanced oral chemotherapy. Sorafenib-loaded ZIF-8 nanoparticles (SZ NPs) were synthesized and characterized by scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, Energy-dispersive X-ray (EDX) spectroscopy, and X-ray diffraction (XRD), exhibiting a mean diameter of about 72 nm and …
In Situ-Generated Volumetric Dried Plasma Spots For The Analysis Of Edaravone And Metabolites In Animal Models, Michele Protti, Roberta Di Lecce, Jiri Adamec, Luca G. Regazzoni, Valeria Valsecchi, Claudia Volpi, Roberto Mandrioli, Laura Mercolini
In Situ-Generated Volumetric Dried Plasma Spots For The Analysis Of Edaravone And Metabolites In Animal Models, Michele Protti, Roberta Di Lecce, Jiri Adamec, Luca G. Regazzoni, Valeria Valsecchi, Claudia Volpi, Roberto Mandrioli, Laura Mercolini
School of Graduate Studies Faculty Publications
In this study, for the first time rat plasma microsampling was carried out by means of in situ-generated volumetric dried plasma spot (vDPS) technology and applied to the determination of the neuroprotective agent edaravone and its sulphate and glucuronide metabolites. Sampling was performed using Telimmune® plasma separation cards (vPSC), which allow the formation of volumetrically accurate dried plasma spots (3 µL) from blood drops deposited on them. After accelerated forced drying and solvent extraction in methanol, drying and redissolution, analytes were baseline separated and quantified through an original HPLC-MS/MS analytical method. Validation assays provided excellent results, with detection limits between …
Soft Tissue Envelope Compromise Following Low-Side Motorcycle Accident: A Case Study And Literature Review, Steven A. Bolton, Ali Ahmad, Jonathan Rodriguez, Hooman Mir
Soft Tissue Envelope Compromise Following Low-Side Motorcycle Accident: A Case Study And Literature Review, Steven A. Bolton, Ali Ahmad, Jonathan Rodriguez, Hooman Mir
School of Podiatric Medicine - Student Research
Purpose: This case report details a staged approach in managing a patient who presented to the ER with a displaced proximal second phalanx fracture, extensive soft tissue damage, and diffuse fracture blistering following a motorcycle crash. This case highlights that soft tissue damage may not always correlate with severe osseous injury.
Methodology: This case is a concurrent chart review of a 40-year-old who sustained a low side motorcycle injury resulting in a minimally displaced avulsion fracture of the medial 2nd toe proximal phalanx base with extensive soft tissue damage, fracture blisters, and lower extremity edema.
Procedures: Radiographic evaluation demonstrated no …
Optimization Of Spinal Cord Perfusion Pressure For Improvement Of Neurological Outcome In Traumatic Spinal Cord Injury: A Systematic Review And Meta-Analysis, Gabrielle E. Hovis, Brandon Sherrod, Nitin Agarwal, Berje H. Shammassian, Anthony M. Digiorgio, Ramesh Grandhi, Bryce Picton
Optimization Of Spinal Cord Perfusion Pressure For Improvement Of Neurological Outcome In Traumatic Spinal Cord Injury: A Systematic Review And Meta-Analysis, Gabrielle E. Hovis, Brandon Sherrod, Nitin Agarwal, Berje H. Shammassian, Anthony M. Digiorgio, Ramesh Grandhi, Bryce Picton
School of Medicine Faculty Publications
The optimal hemodynamic management of traumatic spinal cord injury (tSCI) is not well established. We performed a systematic review and meta-analysis of patients with acute tSCI to assess the role of lumbar cerebrospinal fluid drainage (CSFD) and to identify factors predictive of neurological improvement. Three studies involving 46 patients with acute tSCI, lumbar drain placement with CSFD, and available pre- and post-intervention American Spinal Injury Association (ASIA) Impairment Scale or International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) motor scores were identified. One study was analyzed separately (Cohort A) using ASIA grade because post-intervention ISNCSCI motor scores were …
Time Of Urine Sampling May Influence The Association Between Urine Specific Gravity And Body Composition, Patrick B. Wilson, Brian K. Ferguson, Ian P. Winter
Time Of Urine Sampling May Influence The Association Between Urine Specific Gravity And Body Composition, Patrick B. Wilson, Brian K. Ferguson, Ian P. Winter
Exercise Science Faculty Publications
Urine specific gravity (USG) is frequently utilized in sports practice and research to assess hydration status. Prior research suggests that individuals with large amounts of fat-free mass (FFM) and muscle have elevated USG, but little is known about whether the time of collection (first-morning vs. spot sampling) and various nutritional factors influence these relationships. This cross-sectional, observational study assessed fasted first-morning (n = 55) and non-fasted spot USG (n = 51) samples in adults and evaluated relationships of USG with body composition and nutrition intake. The InBody 770 was used to estimate FFM, skeletal muscle mass (SMM), and total body …
Optimization Of Serum And Salivary Cortisol Interpolation For Time-Dependent Modeling Frameworks In Healthy Adult Males, Nathaniel T. Berry, Travis Anderson, Christopher K. Rhea, Laurie Wideman
Optimization Of Serum And Salivary Cortisol Interpolation For Time-Dependent Modeling Frameworks In Healthy Adult Males, Nathaniel T. Berry, Travis Anderson, Christopher K. Rhea, Laurie Wideman
Rehabilitation Sciences Faculty Publications
Cortisol is an important marker of hypothalamic-pituitary-adrenal function and follows robust circadian and diurnal rhythms. However, biomarker sampling protocols can be labor-intensive and cost-prohibitive. Objectives: Explore analytical approaches that can handle differing biological sampling frequencies to maximize these data in more detailed and time-dependent analyses. Methods: Healthy adult males [N = 8; 26.1 (±3.1) years; 176.4 (±8.6) cm; 73.1 (±12.0) kg)] completed two 24 h admissions: one at rest and one including a high-intensity exercise session on the cycle ergometer. Serum and salivary cortisol were sampled every 60 and 120 min, respectively. Six alternative sampling profiles were defined by downsampling …
Advanced Nanocomposite-Based Electrochemical Sensor For Ultra-Sensitive Dopamine Detection In Physiological Fluids, Megha Shinde, Gymama Slaughter
Advanced Nanocomposite-Based Electrochemical Sensor For Ultra-Sensitive Dopamine Detection In Physiological Fluids, Megha Shinde, Gymama Slaughter
Center for Bioelectronics Publications
This study presents a novel point-of-care electrochemical sensor for dopamine (DA) detection, featuring a flexible laser-induced graphene (LIG) modified with a unique nanocomposite comprising Nb4C3Tx MXene, polypyrrole (PPy), and iron nanoparticles (FeNPs). The LIG-Nb4C3Tx MXene-PPy-FeNPs is characterized by scanning electron microscopy to confirm the successful surface modification. The electrochemical performance of the fabricated sensor via cyclic voltammetry showed significant electrochemical activity upon Nb4C3Tx MXene-PPy-FeNPs nanocomposite modification of the LIG surface with an increased peak anodic current (Ipa) from 43 μA to 104 μA. The sensor …
Effectiveness And Safety Of Intravenous Iron Therapy In Outpatient Obstetrical Clinic For Treatment Of Iron-Deficiency Anemia During Pregnancy, Ellen M. Murrin, Olivia S. Lebeau, Lillian Singer, Mark A. Kassab, Peyton Kalan, Julie Costanzo, Scott A. Sullivan, George L. Maxwell, George R. Saade, Antonio F. Saad
Effectiveness And Safety Of Intravenous Iron Therapy In Outpatient Obstetrical Clinic For Treatment Of Iron-Deficiency Anemia During Pregnancy, Ellen M. Murrin, Olivia S. Lebeau, Lillian Singer, Mark A. Kassab, Peyton Kalan, Julie Costanzo, Scott A. Sullivan, George L. Maxwell, George R. Saade, Antonio F. Saad
Department of Obstetrics & Gynecology Faculty Publications
Background
Iron-deficiency anemia (IDA) affects over one-third of pregnant patients globally, contributing to severe maternal morbidity and adverse neonatal outcomes. Oral iron supplementation, while cost-effective, is limited by poor absorption, significant gastrointestinal side effects, and poor adherence. The use of intravenous (IV) iron addresses many of these concerns, including eliminating GI side effects and the need for daily therapy. However, administration of IV iron in pregnant patients is typically restricted to specialized infusion centers or hospitals due to concerns about acute side effects, cost, resource utilization, the need for fetal heart rate monitoring, and extended infusion times.
Methods
This descriptive …
Stopping The Bleed At Uri, Emily Lefebre
Stopping The Bleed At Uri, Emily Lefebre
Senior Honors Projects
The number one cause of preventable death is uncontrolled bleeding from traumatic injury. From the unlikely scenario of a school shooting, to a campus car accident or an injury during a sports or club event, possessing skills to effectively stop a life-threatening bleed becomes a matter of life or death. The American College of Surgeons Committee on Trauma (ACS COT) STOP THE BLEED® program is a campaign to teach communities how to respond effectively and efficiently to life-threatening bleeding in emergencies. STOP THE BLEED® aims to empower individuals with the knowledge and skills to stop severe bleeding by tourniquet application, …
Differences In Urine Creatinine And Osmolality Between Black And White Americans After Accounting For Age, Moisture Intake, Urine Volume, And Socioeconomic Status, Patrick B. Wilson, Ian P. Winter, Josie Burdin
Differences In Urine Creatinine And Osmolality Between Black And White Americans After Accounting For Age, Moisture Intake, Urine Volume, And Socioeconomic Status, Patrick B. Wilson, Ian P. Winter, Josie Burdin
Exercise Science Faculty Publications
Urine osmolality is used throughout research to determine hydration levels. Prior studies have found black individuals to have elevated urine creatinine and osmolality, but it remains unclear which factors explain these findings. This cross-sectional, observational study sought to understand the relationship of self-reported race to urine creatinine and urine osmolality after accounting for age, socioeconomic status, and fluid intake. Data from 1,386 participants of the 2009–2012 National Health and Nutrition Examination Survey were utilized. Age, poverty-to-income ratio (PIR), urine flow rate (UFR), fluid intake, estimated lean body mass (LBM), urine creatinine, and urine osmolality were measured. In a sex-specific manner, …
Reliability And Minimal Detectable Change Of The Mx3 Hydration Testing System, Ian Winter, Josie Burdin, Patrick B. Wilson
Reliability And Minimal Detectable Change Of The Mx3 Hydration Testing System, Ian Winter, Josie Burdin, Patrick B. Wilson
Exercise Science Faculty Publications
Assessing hydration status outside of laboratories can be challenging given that most hydration measures are invasive, stationary, costly, or have questionable validity. This study investigated the within-day, test-retest reliability, and minimal detectable change (MDC) of the MX3 Hydration Testing System (MX3 Diagnostics), a relatively low cost, noninvasive, and portable method to measure saliva osmolality. Seventy-five adults (44 men, 31 women; 29.6±10.8 yr, 171.1±9.2 cm, 79.1±15.4 kg) presented two saliva samples approximately 3 to 5 minutes apart. Fluid intake was avoided for at least 5 minutes prior to sample collections. For each sample collection, a researcher used the MX3 to tap …
Saliva As A Diagnostic Tool To Measure Polycyclic Aromatic Hydrocarbon Exposure In Dental Patients Exposed To Intimate Partner Violence (Ipv), Aramandla Ramesh, Leslie R. Halpern, Janet H. Southerland, Samuel E. Adunyah, Pandu R. Gangula
Saliva As A Diagnostic Tool To Measure Polycyclic Aromatic Hydrocarbon Exposure In Dental Patients Exposed To Intimate Partner Violence (Ipv), Aramandla Ramesh, Leslie R. Halpern, Janet H. Southerland, Samuel E. Adunyah, Pandu R. Gangula
School of Dentistry Faculty Publications
Background: Social habits such as tobacco use, alcohol consumption, and chemically contaminated diet contribute to poor oral health. Intimate Partner Violence (IPV) is a global public health epidemic which can exacerbate the prevalence of health conditions affecting a victim's lifespan. This study investigates using saliva as a biomarker for detecting levels of benzo(a)pyrene [B(a)P]; a toxicant present in cigarette smoke and barbecued meat in a population of IPV + female patients. Methods: A cross-sectional IRB-approved study utilized 63 female participants (37 African Americans [AA], and 26 non-African Americans [NAA]), who provided consent for the study. Participants submitted samples of saliva, …
Saliva Microrna Biomarkers Of Cumulative Concussion, Steven D. Hicks, Robert P. Olympia, Cayce Onks, Raymond Y. Kim, Kevin J. Zhen, Gregory Fedorchak, Samantha Devita, Aakanksha Rangnekar, Matthew Heller, Hallie Zwibel, Chuck Monteith, Zofia Gagnon, Callan D. Mcloughlin, Jason Randall, Miguel Madeira, Thomas R. Campbell, Elise Fengler, Michael N. Dretsch, Christopher Neville, Frank A. Middleton
Saliva Microrna Biomarkers Of Cumulative Concussion, Steven D. Hicks, Robert P. Olympia, Cayce Onks, Raymond Y. Kim, Kevin J. Zhen, Gregory Fedorchak, Samantha Devita, Aakanksha Rangnekar, Matthew Heller, Hallie Zwibel, Chuck Monteith, Zofia Gagnon, Callan D. Mcloughlin, Jason Randall, Miguel Madeira, Thomas R. Campbell, Elise Fengler, Michael N. Dretsch, Christopher Neville, Frank A. Middleton
Rehabilitation Sciences Faculty Publications
Recurrent concussions increase risk for persistent post-concussion symptoms, and may lead to chronic neurocognitive deficits. Little is known about the molecular pathways that contribute to persistent concussion symptoms. We hypothesized that salivary measurement of microribonucleic acids (miRNAs), a class of epitranscriptional molecules implicated in concussion pathophysiology, would provide insights about the molecular cascade resulting from recurrent concussions. This hypothesis was tested in a case-control study involving 13 former professional football athletes with a history of recurrent concussion, and 18 age/sex-matched peers. Molecules of interest were further validated in a cross-sectional study of 310 younger individuals with a history of no …
Visual Estimates Of Blood Loss By Medical Laypeople: Effects Of Blood Loss Volume, Victim Gender, And Perspective, Rachel Phillips, Marc Friberg, Mattias Lantz Cronqvist, Carl-Oscar Jonson, Erik Prytz
Visual Estimates Of Blood Loss By Medical Laypeople: Effects Of Blood Loss Volume, Victim Gender, And Perspective, Rachel Phillips, Marc Friberg, Mattias Lantz Cronqvist, Carl-Oscar Jonson, Erik Prytz
Psychology Faculty Publications
A severe hemorrhage can result in death within minutes, before professional first responders have time to arrive. Thus, intervention by bystanders, who may lack medical training, may be necessary to save a victim's life in situations with bleeding injuries. Proper intervention requires that bystanders accurately assess the severity of the injury and respond appropriately. As many bystanders lack tools and training, they are limited in terms of the information they can use in their evaluative process. In hemorrhage situations, visible blood loss may serve as a dominant cue to action. Therefore, understanding how medically untrained bystanders (i.e., laypeople) perceive hemorrhage …
Comparison Of Serum And Cervical Cytokine Levels Throughout Pregnancy Between Preterm And Term Births, Kristin Ashford, Niraj R. Chavan, Amanda T. Wiggins, Molly Malany Sayre, Andrea Mccubbin, Agatha S. Critchfield, John O'Brien
Comparison Of Serum And Cervical Cytokine Levels Throughout Pregnancy Between Preterm And Term Births, Kristin Ashford, Niraj R. Chavan, Amanda T. Wiggins, Molly Malany Sayre, Andrea Mccubbin, Agatha S. Critchfield, John O'Brien
Nursing Faculty Publications
Objective To assess differences in cytokine levels in cervicovaginal fluid (CVF) and serum across trimesters between women with preterm births (PTBs) and full-term births.
Study Design This multicenter study enrolled 302 women with a singleton gestation. CVF and serum cytokines, interleukin 1α (IL-1α), IL-1β, IL-6, IL-8, IL-10, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and matrix metalloproteinase (MMP)-8, were measured. Women with at least one cytokine assessment and noted PTB status in their medical record were retained in the study (N = 272). Data were analyzed using mixed modeling (main effects of PTBs and time/trimester).
Results For the CVF …
Better Cognitive Control Of Emotional Information Is Associated With Reduced Pro-Inflammatory Cytokine Reactivity To Emotional Stress, Grant S. Shields, Shari Young Kuchenbecker, Sarah D. Pressman, Ken D. Sumida, George M. Slavich
Better Cognitive Control Of Emotional Information Is Associated With Reduced Pro-Inflammatory Cytokine Reactivity To Emotional Stress, Grant S. Shields, Shari Young Kuchenbecker, Sarah D. Pressman, Ken D. Sumida, George M. Slavich
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Stress is strongly associated with several mental and physical health problems that involve inflammation, including asthma, cardiovascular disease, certain types of cancer, and depression. It has been hypothesized that better cognitive control of emotional information may lead to reduced inflammatory reactivity to stress and thus better health, but to date no studies have examined whether differences in cognitive control predict pro-inflammatory cytokine responses to stress. To address this issue, we conducted a laboratory-based experimental study in which we randomly assigned healthy young-adult females to either an acute emotional stress (emotionally evocative video) or no-stress (control video) condition. Salivary levels of …
Disposable Platform Provides Visual And Color-Based Point-Of-Care Anemia Self-Testing, Erika A. Tyburski, Scott E. Gillespie, William A. Stoy, Robert G. Mannino, Alexander J. Weiss, Alexa F. Siu, Rayford H. Bulloch, Karthik Thota, Anyela Cardenas, Wilena Session, Hanna J. Khoury, Siobhán O'Connor, Silvia T. Bunting, Jeanne Boudreaux, Craig R. Forest, Manila Gaddh, Traci Leong, L. Andrew Lyon, Wilbur A. Lam
Disposable Platform Provides Visual And Color-Based Point-Of-Care Anemia Self-Testing, Erika A. Tyburski, Scott E. Gillespie, William A. Stoy, Robert G. Mannino, Alexander J. Weiss, Alexa F. Siu, Rayford H. Bulloch, Karthik Thota, Anyela Cardenas, Wilena Session, Hanna J. Khoury, Siobhán O'Connor, Silvia T. Bunting, Jeanne Boudreaux, Craig R. Forest, Manila Gaddh, Traci Leong, L. Andrew Lyon, Wilbur A. Lam
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Anemia, or low blood hemoglobin (Hgb) levels, afflicts 2 billion people worldwide. Currently, Hgb levels are typically measured from blood samples using hematology analyzers, which are housed in hospitals, clinics, or commercial laboratories and require skilled technicians to operate. A reliable, inexpensive point-of-care (POC) Hgb test would enable cost-effective anemia screening and chronically anemic patients to self-monitor their disease. We present a rapid, standalone, and disposable POC anemia test that, via a single drop of blood, outputs color-based visual results that correlate with Hgb levels.
METHODS. We tested blood from 238 pediatric and adult patients with anemia of varying …
Digital And Clinical Refractometers Are Valid Instruments For The Measure Of Hydration Status, A. J. Niemann, S. W. Yeargin, L. E. Eberman, H. M. Mata, H. A. Adams, D. J. Dziedzicki
Digital And Clinical Refractometers Are Valid Instruments For The Measure Of Hydration Status, A. J. Niemann, S. W. Yeargin, L. E. Eberman, H. M. Mata, H. A. Adams, D. J. Dziedzicki
Symposium 2012
Although some instruments have been validated for clinical measure of hydration status, new and currently invalid instruments are available for purchase and clinical use. Athletic trainers commonly use these instruments to assess hydration status for weight checks and body mass loss charts due to their ease of use. However, the validity of these popular instruments has not yet been established.
Liquid Chromatography-Tandem Mass Spectrometry For The Determination Of Methylprednisolone In Rat Plasma And Liver After Intravenous Administration Of Its Liver-Targeted Dextran Prodrug, Shuang-Qing Zhang, Helen R. Thorsheim, Suman Penugonda, Venkateswaran C. Pillai, Quentin R. Smith, Reza Mehvar
Liquid Chromatography-Tandem Mass Spectrometry For The Determination Of Methylprednisolone In Rat Plasma And Liver After Intravenous Administration Of Its Liver-Targeted Dextran Prodrug, Shuang-Qing Zhang, Helen R. Thorsheim, Suman Penugonda, Venkateswaran C. Pillai, Quentin R. Smith, Reza Mehvar
Pharmacy Faculty Articles and Research
A specific and sensitive liquid chromatography (LC)-tandem mass spectrometric method for quantitative determination of methylprednisolone (MP) in rat plasma and liver was developed and validated using triamcinolone acetonide as an internal standard. Liquid-liquid extraction using tert-butyl methyl ether was used to extract the drug and the internal standard from plasma and liver. The separation of MP was performed on a C(18) column with a mobile phase of acetonitrile:0.5% formic acid aqueous solution (85:15, v/v) over 4 min. The assay was based on the selected reaction monitoring transitions at m/z 375 -> 161 for MP in plasma, 375 -> 357 for …
Individual, Temporal, And Seasonal Variation In Sperm Concentration In Tree Swallows, Michael P. Lombardo, Armetris N. Forman, Matthew R. Czarnowski, Patrick A. Thorpe
Individual, Temporal, And Seasonal Variation In Sperm Concentration In Tree Swallows, Michael P. Lombardo, Armetris N. Forman, Matthew R. Czarnowski, Patrick A. Thorpe
Peer Reviewed Publications
We determined sperm concentrations in Tree Swallows (Tachycineta bicolor) by manually expressing semen samples from males during prelaying, egg-laying, incubation, and nestling periods. Sperm concentrations varied by orders of magnitude (0-109 sperm mL-1) among males. Sperm concentrations were highest during the incubation period and lowest during the prelaying period. None of the samples collected during the prelaying, egg-laying, and incubation periods were devoid of sperm. In contrast, 45% of samples collected during the nestling period lacked sperm. Sperm concentrations (1) did not vary over the course of the morning during prelaying, egg-laying, and incubation periods …
Effects Of Sodium Intake, Furosemide, And Infusion Of Atrial Natriuretic Peptide On The Urinary And Metabolic Clearances Of Arginine Vasopressin In Normal Subjects, Arnold M. Moses, Carol Jones, Carolyn B. Yucha
Effects Of Sodium Intake, Furosemide, And Infusion Of Atrial Natriuretic Peptide On The Urinary And Metabolic Clearances Of Arginine Vasopressin In Normal Subjects, Arnold M. Moses, Carol Jones, Carolyn B. Yucha
Nursing Faculty Research
Arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) have important influences on water and electrolyte metabolism, and studies on the interactions between these hormones may have important implications. We have investigated the effects of sodium intake, furosemide, and infusion of ANP on the urinary and metabolic (nonurinary) clearances of AVP in hydrated normal subjects. On a high sodium diet there was an increase in urine volume, sodium excretion, osmolal clearance, plasma ANP concentration, and urinary clearance and fractional excretion of AVP, with a decrease in PRA. The infusion of furosemide increased urine volume, sodium excretion, osmolal clearance, and PRA, but …