Analyze Diet

Topic:Clinical Study

Clinical studies in equine research involve the systematic investigation of health and disease in horses through structured scientific methods. These studies aim to evaluate the safety and efficacy of treatments, understand disease mechanisms, and improve veterinary care practices. Clinical studies can include randomized controlled trials, observational studies, and case-control studies. They may focus on various aspects such as pharmacokinetics, therapeutic interventions, and diagnostic techniques. This page compiles peer-reviewed research studies and scholarly articles that explore the design, implementation, and findings of clinical studies in equine medicine, providing insights into their impact on horse health and veterinary practices.
Presumptive nonthyroidal illness syndrome in critically ill foals.
Equine veterinary journal. Supplement    May 19, 2012   Issue 41 43-47 doi: 10.1111/j.2042-3306.2011.00480.x
Himler M, Hurcombe SD, Griffin A, Barsnick RJ, Rathgeber RA, MacGillivray KC, Toribio RE.Hypothalamic-pituitary-thyroid (HPT) axis dysfunction is associated with morbidity and mortality in critically ill people. To date, investigations of HPT axis in critically ill foals are limited. Objective: To document the occurrence of low thyroid hormone concentrations (presumptive nonthyroidal illness syndrome; NTIS) in critically ill newborn foals and investigate whether NTIS is associated with severity of disease and outcome. Objective: NTIS occurs frequently in foals with sepsis and is associated with sepsis score and outcome. Reverse T3 (rT3) concentrations will be increased in septic f...
Prevalence of gastric and duodenal ulceration in 691 nonsurviving foals (1995-2006).
Equine veterinary journal. Supplement    May 19, 2012   Issue 41 76-79 doi: 10.1111/j.2042-3306.2011.00449.x
Elfenbein JR, Sanchez LC.Gastric ulcer disease is reported to be a significant cause of morbidity in foals, but the prevalence of ulcers in this population has not recently been evaluated. Objective: To determine the prevalence of gastric and duodenal ulceration in nonsurviving foals, and the association of ulceration with the body system of primary diagnosis. Secondary objectives were to evaluate a potential association between age and ulcer prevalence and to evaluate the use of antacid medication in the neonatal hospital population during the study years. Methods: Necropsy records were searched for all equine access...
Endocrine adaptations in the foal over the perinatal period.
Equine veterinary journal. Supplement    May 19, 2012   Issue 41 130-139 doi: 10.1111/j.2042-3306.2011.00505.x
Fowden AL, Forhead AJ, Ousey JC.In adapting to life ex utero, the foal encounters a number of physiological challenges. It has to assume the nutritional, respiratory and excretory functions of the placenta and activate full regulatory control over its own internal environment for the first time. To achieve this, there must be structural and functional changes to a wide range of tissues including several endocrine glands. In most species, including the horse, these maturational changes begin in late gestation and continue into the first few days of neonatal life. Consequently, during this perinatal period, there are major cha...
Hospital treatment as a foal does not adversely affect future sales performance in Thoroughbred horses.
Equine veterinary journal. Supplement    May 19, 2012   Issue 41 87-90 doi: 10.1111/j.2042-3306.2011.00477.x
Corley KT, Corley MM.Many Thoroughbred foals are intended to be sold at public auction. The impact of disease conditions necessitating hospital treatment as a foal on future sales performance is unknown. Objective: To determine whether Thoroughbred horses that were treated in a hospital before age 125 days and presented to public auction sell for a different mean price than controls. Methods: Foals aged < 125 days, treated at a hospital in Ireland in 2007 or 2008 and presented for sale to a public auction recorded on a publicly accessible database were selected for inclusion in the study. The sales outcome of thes...
Intraoperator, intraobserver and interoperator variability of echocardiographic measurements in healthy foals.
Equine veterinary journal. Supplement    May 19, 2012   Issue 41 69-75 doi: 10.1111/j.2042-3306.2011.00503.x
Slack J, Durandot MM, Belcher CN, Collins N, Palmer L, Ousey J, Birks EK, Marr CM.The repeatability of various echocardiographic measurements is unknown. Objective: To determine the intraoperator, intraobserver and interoperator variability of echocardiographic measures in healthy foals. Methods: Echocardiographic examinations were carried out on 6 healthy foals by 3 experienced echocardiographers. Intraoperator variability was determined by having a single echocardiographer obtain and measure images from 6 foals scanned on 3 consecutive days. Interoperator and intraobserver variability were determined by having 3 echocardiographers each obtain images from an additional 6 s...
Comparing the pharmacokinetics of a fourth generation cephalosporin in three different age groups of New Forest ponies.
Equine veterinary journal. Supplement    May 19, 2012   Issue 41 52-56 doi: 10.1111/j.2042-3306.2011.00501.x
Smiet E, Haritova A, Heil BA, Fink-Gremmels J, Wijnberg ID.To compare the pharmacokinetics of the fourth generation cephalosporin, cefquinome, in neonatal foals, 6-week-old foals and mature New Forest ponies in order to recommend appropriate dosage regimens for use of this drug. Methods: Cefquinome was administered i.v. at 1 mg/kg bwt twice a day (q. 12 h), 1 mg/kg bwt 3 times a day (q. 8 h) or 4.5 mg/kg bwt q. 12 h to each age group (n = 6). Plasma cefquinome concentrations were analysed using high-performance liquid chromatography combined with electrospray tandem mass spectrometry. Results: Both foal age groups had comparable pharmacokinetic data e...
Parturition, dystocia and foal survival: a retrospective study of 1047 births.
Equine veterinary journal. Supplement    May 19, 2012   Issue 41 22-25 doi: 10.1111/j.2042-3306.2011.00476.x
McCue PM, Ferris RA.An understanding of the normal events of foaling, causes of dystocia and clinical outcomes is important for equine practitioners. Objective: The goals of the present study were to: 1) evaluate factors that influence gestation length; 2) report duration of Stage II labour; 3) determine the frequency of dystocia and premature placental separation; and 4) determine the relationship between problems at foaling and foal survival. Methods: Foaling records of 1047 mare births were evaluated. Results: The average gestation length was 342.7 days [corrected] +/- 0.4 days, with no effect of mare age or b...
Hypothalamic-pituitary-adrenal axis function in pony foals after neonatal ACTH-induced glucocorticoid overexposure.
Equine veterinary journal. Supplement    May 19, 2012   Issue 41 38-42 doi: 10.1111/j.2042-3306.2011.00448.x
Jellyman JK, Allen VL, Forhead AJ, Holdstock NB, Fowden AL.The effects of overexposure to glucocorticoids during early life of the foal on the subsequent HPA programming of the hypothalamic-pituitary-adrenal axis are unknown. Objective: To test the hypotheses that excess glucocorticoid exposure in early life subsequently increases both basal plasma concentrations of cortisol and the adrenocortical responsiveness to exogenous adrenocorticotropic hormone (ACTH). Methods: Foals received either saline (0.9% NaCl, n = 9) or long-acting ACTH (0.125 mg i.m. b.i.d., n = 6) for 5 days from Day 1 to increase endogenous cortisol concentrations. Long-term indwell...
Treatment with histamine-type 2 receptor antagonists and omeprazole increase the risk of diarrhoea in neonatal foals treated in intensive care units.
Equine veterinary journal. Supplement    May 19, 2012   Issue 41 80-86 doi: 10.1111/j.2042-3306.2011.00499.x
Furr M, Cohen ND, Axon JE, Sanchez LC, Pantaleon L, Haggett E, Campbell R, Tennent-Brown B.The use of anti-ulcer medication in the neonatal intensive care unit (ICU) is common due to the concern for development of catastrophic gastric ulcerdisease. In man, however, the use of acid-suppressive medication has been shown in some studies to be a substantial riskfactorfor the development of Clostridium difficile-associated diarrhoea (CDAD), bacteraemia and neonatal sepsis. Objective: The purpose of the study reported herein is to evaluate the influence of anti-ulcer medications on the development of diarrhoea in the neonatalfoal. Objective: The use of anti-ulcer medication does not alter...
The importance of ultrasonographic pneumatosis intestinalis in equine neonatal gastrointestinal disease.
Equine veterinary journal. Supplement    May 19, 2012   Issue 41 64-68 doi: 10.1111/j.2042-3306.2011.00478.x
de Solis CN, Palmer JE, Boston RC, Reef VB.Recognising the presence of a necrotising component of the gastrointestinal disease may be clinically useful in ill equine neonates. Objective: To study the importance of abdominal sonograms in neonatal foals suffering from gastrointestinal conditions and to describe the clinical features of necrotising gastrointestinal disease. Objective: There is a subgroup of neonates with sonographically detectable pneumatosis intestinalis (PI), reflecting a necrotising disease. Methods: Records of foals aged < or = 7 days hospitalised from 2005 to 2009 with signs of gastrointestinal disease were evaluated...
Allopregnanolone infusion induced neurobehavioural alterations in a neonatal foal: is this a clue to the pathogenesis of neonatal maladjustment syndrome?
Equine veterinary journal. Supplement    May 19, 2012   Issue 41 109-112 doi: 10.1111/j.2042-3306.2011.00504.x
Madigan JE, Haggettt EF, Pickles KJ, Conley A, Stanley S, Moeller B, Toth B, Aleman M.Increased plasma progestagen concentrations have been reported in foals with neonatal maladjustment syndrome (NMS). These steroids may cross the blood-brain barrier and have dampening effects in the central nervous system. Objective: To evaluate if the infusion of a progesterone derivative (allopregnanolone) in a healthy neonatal foal would induce clinical signs compatible with NMS. Methods: A healthy neonatal foal from a healthy mare with a normal gestation (length, no complications), birth and placenta was infused with allopregnanolone to observe its neurobehavioural effects. Heparinised blo...
A racing start in life? The hurdles of equine feto-placental pathology.
Equine veterinary journal. Supplement    May 19, 2012   Issue 41 120-129 doi: 10.1111/j.2042-3306.2011.00507.x
Foote AK, Ricketts SW, Whitwell KE.Significant progress has been made in understanding and monitoring the causes of equine abortion over past decades. However, not all in utero pathology results in abortion. It has long been recognised that some in utero pathology, such as twinning or chronic placentitis, can result in the birth of live but growth-retarded foals and there is historical evidence that birth weight may influence future athletic performance. Clinical experience (e.g. from twins) and experimental studies (pony-Thoroughbred embryo transfer) have highlighted the importance of reduced functional placental area in limit...
Association of asinine herpesvirus-5 with pyogranulomatous pneumonia in a mare.
Journal of veterinary internal medicine    May 18, 2012   Volume 26, Issue 4 1064-1068 doi: 10.1111/j.1939-1676.2012.00943.x
De Witte FG, Frank N, Wilkes RP, Novak JM.No abstract available
Seasonal changes in the combined glucose-insulin tolerance test in normal aged horses.
Journal of veterinary internal medicine    May 18, 2012   Volume 26, Issue 4 1035-1041 doi: 10.1111/j.1939-1676.2012.00939.x
Funk RA, Wooldridge AA, Stewart AJ, Behrend EN, Kemppainen RJ, Zhong Q, Johnson AK.Equine metabolic syndrome (EMS) is an increasingly recognized problem in adult horses. Affected horses are often obese and predisposed to the development of laminitis, especially in the spring and summer months. In addition, in the summer and fall months, increases in endogenous insulin concentrations, a marker of EMS, have been reported. Objective: The purpose of this study was to evaluate seasonal changes in results of the combined glucose-insulin tolerance test (CGIT), a diagnostic test for EMS. Methods: Nine healthy, aged horses with no history of laminitis and no clinical signs of EMS. Me...
Evaluation of regional limb perfusion with amikacin using the saphenous, cephalic, and palmar digital veins in standing horses.
Journal of veterinary pharmacology and therapeutics    May 18, 2012   Volume 36, Issue 3 236-240 doi: 10.1111/j.1365-2885.2012.01414.x
Kelmer G, Bell GC, Martin-Jimenez T, Saxton AM, Catasus C, Elliot SB, Meibohm B.Previous studies have shown that regional limb perfusion (RLP) using the palmar digital (PD) vein delivers therapeutic concentration of amikacin to the distal limb. Our hypothesis was that using the cephalic and saphenous veins for RLP will enable delivery of therapeutic concentrations of amikacin to the distal limb. Nineteen healthy horses participated in the study. The cephalic, saphenous, or PD vein was used to perfuse the limb with amikacin. Two grams of amikacin was used for RLP using the saphenous and the cephalic veins, and one gram was used in the PD vein. Synovial samples were collect...
Ultrasound confirmation of ovulation in mares: a normal corpus luteum or a haemorrhagic anovulatory follicle?
Reproduction in domestic animals = Zuchthygiene    May 18, 2012   Volume 48, Issue 1 105-111 doi: 10.1111/j.1439-0531.2012.02039.x
Cuervo-Arango J, Newcombe JR.The most common pathological anovulatory condition that occurs spontaneously during the breeding season in the mare is the haemorrhagic anovulatory follicle (HAF). A relatively high proportion of mares, soon after ovulation, develop a corpus haemorrhagicum (CH) with a central lacuna. This type of corpora lutea may resemble an HAF, which may complicate the accurate diagnosis of ovulation. The main objective of this study was to compare the ultrasound data of mares examined frequently with HAFs and CHs to elucidate whether it is possible to distinguish them from each other. A total of 135 ovulat...
Fell Pony syndrome: characterization of developmental hematopoiesis failure and associated gene expression profiles.
Clinical and vaccine immunology : CVI    May 16, 2012   Volume 19, Issue 7 1054-1064 doi: 10.1128/CVI.00237-12
Tallmadge RL, Stokol T, Gould-Earley MJ, Earley E, Secor EJ, Matychak MB, Felippe MJ.Fell Pony syndrome (FPS) is a fatal immunodeficiency that occurs in foals of the Fell Pony breed. Affected foals present with severe anemia, B cell lymphopenia, and opportunistic infections. Our objective was to conduct a prospective study of potential FPS-affected Fell Pony foals to establish clinical, immunological, and molecular parameters at birth and in the first few weeks of life. Complete blood counts, peripheral blood lymphocyte phenotyping, and serum immunoglobulin concentrations were determined for 3 FPS-affected foals, 49 unaffected foals, and 6 adult horses. In addition, cytology o...
Respiratory distress due to retropharyngeal and neck swelling in a horse with mediastinal lymphosarcoma.
Compendium (Yardley, PA)    May 15, 2012   Volume 34, Issue 5 E5 
Marqués FJ, Hehenberger E, Dickinson R, Wojnarowicz C, Lohmann K.A 9-year-old, 1494-lb (679-kg) Quarter horse gelding in good body condition was admitted to the Veterinary Teaching Hospital, Western College of Veterinary Medicine (WCVM), University of Saskatchewan, for evaluation and treatment of acute respiratory distress. On a trail ride 26 days before presentation, the gelding had been exposed to a horse with clinical signs of an upper respiratory tract infection. The gelding performed well on the trail ride but, 4 days later, developed a mild swelling in the retropharyngeal area and a slight bilateral mucoid nasal discharge. The gelding was examined at ...
Equine subepithelial keratomycosis.
Veterinary ophthalmology    May 14, 2012   Volume 16, Issue 2 93-96 doi: 10.1111/j.1463-5224.2012.01031.x
Brooks DE, Plummer CE, Mangan BG, Ben-Shlomo G.To describe clinical findings in equine subepithelial keratomycosis (SEK). Methods: Retrospective medical records study. Methods: Medical records of horses that had subepithelial keratomycosis (SEK) at the University of Florida Veterinary Medical Center from 2007 to 2011 were reviewed. Methods: Data collected from the medical records included signalment, clinical descriptions of ocular lesions, diagnostic techniques, and therapeutic outcomes. Results: Twenty-one horses, consisting of three Quarter horse geldings, two Morgan geldings, one Morgan mare, two Arabian mares, three Arabian geldings, ...
The impact of endophyte-infected fescue consumption on digital circulation and lameness in the distal thoracic limb of the horse.
Journal of animal science    May 14, 2012   Volume 90, Issue 9 3101-3111 doi: 10.2527/jas.2011-4371
Douthit TL, Bormann JM, Gradert KC, Lomas LW, DeWitt SF, Kouba JM.This experiment was conducted to evaluate if consumption of endophyte-infected fescue alters digital circulation in the distal thoracic limb of the horse and to assess if soundness of the hooves of horses is affected by consumption of endophyte-infected fescue. Twelve American Quarter Horses (mean initial BW 459 ± 31 kg), 6 mares and 6 geldings, were used in this 90-d study that comprised high-endophyte (E+) and low-endophyte (E-) treatment groups. Fescue seed was integrated into the E+ diet at a rate sufficient to bring total ergovaline to 200 μg/kg, and endophyte-free fescue seed was incor...
Temperatures from 4 to 15 °C are suitable for preserving the fertilizing capacity of stallion semen stored for 22 h or more in INRA96 extender.
Theriogenology    May 11, 2012   Volume 78, Issue 2 297-307 doi: 10.1016/j.theriogenology.2012.01.018
Vidament M, Magistrini M, Le Foll Y, Levillain N, Yvon JM, Duchamp G, Blesbois E.This study tested whether variable temperatures (from -0.5 to 15 °C) and air exposure could be used under laboratory and under field conditions to store stallion sperm diluted in extender INRA96 without loss of fertility. Experiment 1 (laboratory conditions) measured the effects of two 72 h storage conditions (5 °C with air vs. 15 °C without air). Experiment 2 (fixed field conditions) measured the effects of 22 h of storage without air in disposable containers maintained at four ambient temperatures (7 °C, 17 °C, 27 °C, 39 °C with semen at -0.5 °C to 3 °C, 4 °C to 7 °C, 8 °C to 10 ...
A comparative study of xylazine-induced mechanical hypoalgesia in donkeys and horses.
Veterinary anaesthesia and analgesia    May 11, 2012   Volume 39, Issue 5 533-538 doi: 10.1111/j.1467-2995.2012.00725.x
Lizarraga I, Beths T.To compare the effects of xylazine on mechanical nociceptive thresholds in donkeys and horses. Methods: Randomized, controlled, crossover, Latin-square, operator-blinded design. Methods: Six 3.1 ± 0.89 year old standard donkeys weighing 145.0 ± 30.5 kg and six 9.6 ± 4.4 year old Thoroughbred horses weighing 456.0 ± 69.0 kg. Methods: Each animal received one of four doses of xylazine (0.5, 0.7, 0.9, and 1.1 mg kg(-1) ), or acepromazine (0.05 mg kg(-1) ) or saline solution (0.9%) intravenously and mechanical nociceptive thresholds were assessed over 90 minutes. The areas under the threshold ...
mRNA transcription of prostaglandin synthases and their products in the equine endometrium in the course of fibrosis.
Theriogenology    May 11, 2012   Volume 78, Issue 4 768-776 doi: 10.1016/j.theriogenology.2012.03.024
Szóstek AZ, Siemieniuch MJ, Lukasik K, Galvão AM, Ferreira-Dias GM, Skarzynski DJ.Accurate regulation of the reproductive cycle and successful implantation depend on proper functioning of the endometrium. The aim of this study was to determine whether mRNA transcription of specific enzymes responsible for prostaglandin (PG) synthesis (prostaglandin-endoperoxide synthase, PTGS-2; prostaglandin F(2α) synthase, PGFS; and prostaglandin E(2) synthases, PGES) and PG concentrations in endometrial extracts would change in moderate (Kenney's Category II) and severe phases of fibrosis (Kenney's Category III; endometrosis), compared with healthy endometrium (Kenney's Category I), dur...
Osmotic shock induces structural damage on equine spermatozoa plasmalemma and mitochondria.
Theriogenology    May 11, 2012   Volume 78, Issue 2 415-422 doi: 10.1016/j.theriogenology.2012.02.021
González-Fernández L, Morrell JM, Peña FJ, Macías-García B.The present study aimed to elucidate the effects that osmotic shock exerts on equine spermatozoa. To achieve this goal, a retrospective study of the cellular volume of 40 equine ejaculates subjected to osmolarities ranging from 75 to 900 mOsm in Biggers-Whitten-Whittingham (BWW) media was performed using a Multisizer3 Coulter Counter®. The 300 mOsm BWW solution was used as control. The sperm volume ranged between 37.93±0.6 (mean±Standard Error of the Mean (SEM)) in 75 mOsm BWW to 21.61±0.27 (mean±SEM) for 900 mOsm BWW. Thus the spermatozoa behaved as linear osmometers when adjusted to the...
Effects of hypercapnic hyperpnea on recovery from isoflurane or sevoflurane anesthesia in horses.
Veterinary anaesthesia and analgesia    May 11, 2012   Volume 39, Issue 4 335-344 doi: 10.1111/j.1467-2995.2012.00727.x
Brosnan RJ, Steffey EP, Escobar A.To test the hypothesis that hypercapnic hyperpnea produced using endotracheal insufflation with 5-10% CO(2) in oxygen could be used to shorten anesthetic recovery time in horses, and that recovery from sevoflurane would be faster than from isoflurane. Methods: Randomized crossover study design. Methods: Eight healthy adult horses. Methods: After 2 hours' administration of constant 1.2 times MAC isoflurane or sevoflurane, horses were disconnected from the anesthetic circuit and administered 0, 5, or 10% CO(2) in balance O(2) via endotracheal tube insufflation. End-tidal gas samples were collect...
Bioassay for follicle stimulating activity of equine gonadotropic hormone in mare serum using frozen/thawed transiently transfected reporter cells.
Theriogenology    May 11, 2012   Volume 78, Issue 4 724-730 doi: 10.1016/j.theriogenology.2012.03.015
Sahmi F, Nicola E, Price CA.The objective was to establish a cell line-based bioassay for FSH in horse serum for screening samples with high eCG bioactivity. A cell line (HEK293) was transiently cotransfected with an FSH reporter expression plasmid and a cAMP-responsive β-galactosidase reporter plasmid. Cells were bulk frozen, and thawed for assay purposes. This assay was specific for FSH, with no cross-reaction with LH or insulin-like growth factor-1. Standard curves (eCG) and serum samples from pregnant mares passed parallel line bioassay validity tests (linearity and parallelism). Estimates of bioactivity with this b...
Early detection of chronic progressive lymphoedema susceptibility in Belgian draught horse stallions by means of ELISA.
Communications in agricultural and applied biological sciences    May 9, 2012   Volume 77, Issue 1 183-187 
De Keyser K, Oosterlinck M, Raes E, Ducatelle R, Janssens S, Buys N.No abstract available
Effects of mesenchymal stem cells isolated from amniotic fluid and platelet-rich plasma gel on severe decubitus ulcers in a septic neonatal foal.
Research in veterinary science    May 9, 2012   Volume 93, Issue 3 1439-1440 doi: 10.1016/j.rvsc.2012.04.008
Iacono E, Merlo B, Pirrone A, Antonelli C, Brunori L, Romagnoli N, Castagnetti C.This paper documents the treatment of severe decubitus ulcers with amniotic fluid mesenchymal stem cells and platelets rich plasma (PRP) gel in a septic neonatal foal. The colt needed 25 days of hospitalization: during this period ulcers were treated for 15 days with mesenchymal stem cells (MSCs) plus PRP, PRP gel alone, or aloe gel. Healing was faster using MSCs+PRP, and at 7 months an ulcer treated with aloe gel was still not completely healed.
Use of pelvic flexure biopsy scores to predict short-term survival after large colon volvulus.
Veterinary surgery : VS    May 9, 2012   Volume 41, Issue 5 582-588 doi: 10.1111/j.1532-950X.2012.00994.x
Levi O, Affolter VK, Benak J, Kass PH, Le Jeune SS.To (1) determine if histologic scores of pelvic flexure biopsies can predict short-term survival in horses with large colon volvulus (LCV) and (2) identify clinical variables predictive of short-term survival. Methods: Case series. Methods: Horses (n = 28) with LCV (≥ 360°). Methods: Medical records (January 2000-February 2008) of 28 horses were reviewed and clinical data recorded. Pelvic flexure biopsies were reviewed by 2 board-certified veterinary pathologists, unaware of clinical history and outcome, using 2 scoring systems. Exact logistic regression analysis was used to determine the r...
Use of serial measurements of peritoneal fluid lactate concentration to identify strangulating intestinal lesions in referred horses with signs of colic.
Journal of the American Veterinary Medical Association    May 9, 2012   Volume 240, Issue 10 1208-1217 doi: 10.2460/javma.240.10.1208
Peloso JG, Cohen ND.To determine the value of serial measurements of peritoneal fluid lactate concentration (PFL) for detecting strangulating intestinal lesions (SLs) in referred horses with signs of colic. Methods: Retrospective cohort study. Methods: 94 horses with signs of colic. Methods: Medical records of horses evaluated between September 2006 and February 2010 because of signs of colic were reviewed. All included horses had ≥ 2 peritoneal fluid samples collected, including one at admission and another within 1 to 6 hours after admission. Of the 94 horses, 26 were assigned to the SL group on the basis of ...