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.
Science-in-brief: Clinical highlights from BEVA Congress 2016.
Equine veterinary journal    December 17, 2016   Volume 49, Issue 1 10-12 doi: 10.1111/evj.12644
Chauché C, Kennedy R.No abstract available
Making research accessible.
Equine veterinary journal    December 17, 2016   Volume 49, Issue 1 6-7 doi: 10.1111/evj.12642
Marr CM, Morgan R.No abstract available
Translation of a laboratory-validated equine herpesvirus-1 specific real-time PCR assay into an insulated isothermal polymerase chain reaction (iiPCR) assay for point-of-need diagnosis using POCKIT™ nucleic acid analyzer.
Journal of virological methods    December 16, 2016   Volume 241 58-63 doi: 10.1016/j.jviromet.2016.12.010
Balasuriya UB, Lee PA, Tsai YL, Tsai CF, Shen YH, Chang HG, Skillman A, Wang HT, Pronost S, Zhang Y.Equine herpesvirus myeloencephalopathy (EHM), a major problem for the equine industry in the United States, is caused by equine herpesvirus-1 (EHV-1). In addition, EHV-1 is associated with upper respiratory disease, abortion, and chorioretinal lesions in horses. Here we describe the development and evaluation of an inexpensive, user-friendly insulated isothermal PCR (iiPCR) method targeting open reading 30 (ORF30) to detect both neuropathogenic and non-neuropathogenic strains on the field-deployable POCKIT™ device for point-of-need detection of EHV-1. The analytical sensitivity of the EHV-1 ...
Intra- and interobserver reliability estimates for identification and grading of upper respiratory tract abnormalities recorded in horses at rest and during overground endoscopy.
Equine veterinary journal    December 15, 2016   Volume 49, Issue 4 433-437 doi: 10.1111/evj.12653
McGivney CL, Sweeney J, David F, O'Leary JM, Hill EW, Katz LM.Previous studies support good intra- and interobserver agreements for endoscopic evaluation of various upper respiratory tract (URT) diseases in horses. However, these studies mainly assessed resting endoscopic examination videos and/or focussed on a single URT abnormality. Objective: To estimate intra- and interobserver agreement for identification and grading of all URT abnormalities from resting and overground endoscopy (OGE) videos of Thoroughbreds. Methods: Blinded, fully crossed design. Methods: Resting and OGE URT videos for n = 43 Thoroughbreds were retrospectively chosen based on iden...
Validation of the bispectral index as an indicator of anesthetic depth in Thoroughbred horses anesthetized with sevoflurane.
Journal of equine science    December 15, 2016   Volume 27, Issue 4 169-173 doi: 10.1294/jes.27.169
Tokushige H, Kakizaki M, Ode H, Okano A, Okada J, Kuroda T, Wakuno A, Ohta M.To evaluate the bispectral index (BIS) as an indicator of anesthetic depth in Thoroughbred horses, BIS values were measured at multiple stages of sevoflurane anesthesia in five horses anesthetized with guaifenesin and thiopental following premedication with xylazine. There was no significant difference between the BIS values recorded at end-tidal sevoflurane concentrations of 2.8% (median 60 ranging from 47 to 68) and 3.5% (median 71 ranging from 49 to 82) in anesthetized horses. These BIS values during anesthesia were significantly lower (P<0.01) than those in awake horses (median 98 ranging ...
Effects of a single use of the GnRH analog buserelin on the induction of ovulation and endocrine profiles in heavy draft mares.
Journal of equine science    December 15, 2016   Volume 27, Issue 4 149-156 doi: 10.1294/jes.27.149
Miki W, Oniyama H, Takeda N, Kimura Y, Haneda S, Matsui M, Taya K, Nambo Y.We observed structural changes in the follicles and uterus of heavy draft mares during estrus and examined the effect of a single injection of the gonadotropin-releasing hormone analog buserelin on ovulation and endocrine profiles. Twenty-two heavy draft mares were divided into a buserelin-treated group (n=8) and a control group (n=14). Mares were given an intramuscular injection of 40 µg buserelin when they presented signs of estrus to a teaser stallion, had ≥45 mm diameter follicles, and presented decreased uterine edema compared with the previous examination. The follicles and uterus wer...
Evaluation of housekeeping genes for quantitative gene expression analysis in the equine kidney.
Journal of equine science    December 15, 2016   Volume 27, Issue 4 165-168 doi: 10.1294/jes.27.165
Azarpeykan S, Dittmer KE.Housekeeping genes (HKGs) are used as internal controls for normalising and calculating the relative expression of target genes in RT-qPCR experiments. There is no unique universal HKG and HKGs vary among organisms and tissues, so this study aimed to determine the most stably expressed HKGs in the equine kidney. The evaluated HKGs included 18S ribosomal RNA (18S), 28S ribosomal RNA (28S), ribosomal protein L32 (RPL32), β-2-microglobulin (B2M), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), succinate dehydrogenase complex (SDHA), zeta polypeptide (YWHAZ), and hypoxanthine phosphoribosyltran...
Molecular epidemiology of Corynebacterium pseudotuberculosis isolated from horses in California.
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases    December 13, 2016   Volume 49 186-194 doi: 10.1016/j.meegid.2016.12.011
Haas DJ, Dorneles EM, Spier SJ, Carroll SP, Edman J, Azevedo VA, Heinemann MB, Lage AP.Corynebacterium pseudotuberculosis biovar Equi is an important pathogen of horses. It is increasing in frequency in the United States, and is responsible for various clinical forms of infection, including external abscesses, internal abscesses of the abdominal or thoracic cavities, and ulcerative lymphangitis. The host/pathogen factors dictating the form or severity of infection are currently unknown. Our recent investigations have shown that genotyping C. pseudotuberculosis isolates using enterobacterial repetitive intergenic consensus (ERIC)-PCR is useful for understanding the evolutionary g...
Validation of distal limb mounted inertial measurement unit sensors for stride detection in Warmblood horses at walk and trot.
Equine veterinary journal    December 13, 2016   Volume 49, Issue 4 545-551 doi: 10.1111/evj.12651
Bragança FM, Bosch S, Voskamp JP, Marin-Perianu M, Van der Zwaag BJ, Vernooij JCM, van Weeren PR, Back W.Inertial measurement unit (IMU) sensor-based techniques are becoming more popular in horses as a tool for objective locomotor assessment. Objective: To describe, evaluate and validate a method of stride detection and quantification at walk and trot using distal limb mounted IMU sensors. Methods: Prospective validation study comparing IMU sensors and motion capture with force plate data. Methods: A total of seven Warmblood horses equipped with metacarpal/metatarsal IMU sensors and reflective markers for motion capture were hand walked and trotted over a force plate. Using four custom built algo...
Risk factors for equine fractures in Thoroughbred flat racing in North America.
Preventive veterinary medicine    December 12, 2016   Volume 139, Issue Pt B 99-104 doi: 10.1016/j.prevetmed.2016.12.006
Georgopoulos SP, Parkin TD.The aim of this paper is to identify risk factors associated with equine fractures in flat horse racing of Thoroughbreds in North America. Equine fractures were defined as any fracture sustained by a horse during a race. This was a cohort study that made use of all starts from the racecourses reporting injuries. The analysis was based on 2,201,152 racing starts that represent 91% of all official racing starts in the USA and Canada from 1st January 2009-31st December 2014. Approximately 3,990,000 workout starts made by the 171,523 Thoroughbreds that raced during that period were also included i...
[Injury to the upper limbs and prevention in equestrian sports].
Der Unfallchirurg    December 10, 2016   Volume 121, Issue 2 152-158 doi: 10.1007/s00113-016-0288-8
Schröter C, Bielefeld M, Bielefeld D, Macke C, Winkelmann C, Mommsen P, Krettek C, Zeckey C.The upper limb is one of the most frequently injured body regions in equestrian sports, but it is unclear which injuries are involved, and there are no data on the associated accident mechanism. The present study is aimed at evaluating the accident mechanisms, injuries of the upper limbs, and the circumstances of the accident in equestrian sports. We included 218 patients who were all treated between 2006 and 2014 at the level I trauma center at the Medical University in Hannover because of equestrian-related accidents. The most frequent injuries were fractures and bruising in the shoulder ...
Multimodality scoring of chondral injuries in the equine fetlock joint ex vivo.
Osteoarthritis and cartilage    December 10, 2016   Volume 25, Issue 5 790-798 doi: 10.1016/j.joca.2016.12.007
Sarin JK, Brommer H, Argüelles D, Puhakka PH, Inkinen SI, Afara IO, Saarakkala S, Töyräs J.We investigate the potential of a prototype multimodality arthroscope, combining ultrasound, optical coherence tomography (OCT) and arthroscopic indentation device, for assessing cartilage lesions, and compare the reliability of this approach with conventional arthroscopic scoring ex vivo. Areas of interest (AIs, N = 43) were selected from equine fetlock joints (N = 5). Blind-coded AIs were independently scored by two equine surgeons employing International Cartilage Repair Society (ICRS) scoring system via conventional arthroscope and multimodality arthroscope, in which high-frequency ul...
Clinical indications, complications, and long-term outcome of esophageal surgeries in 27 horses.
The Canadian veterinary journal = La revue veterinaire canadienne    December 9, 2016   Volume 57, Issue 12 1257-1262 
Koenig JB, Silveira A, Cribb NC, Piat P, Laverty S, Sorge US.The main objective of this retrospective study was to describe clinical findings, management, and short- and long-term outcome in 27 horses that underwent various surgical techniques for esophageal disease. Surgical techniques (sometimes concurrently) performed were: esophagostomy ( = 14), esophagotomy with primary closure ( = 6), esophagomyotomy ( = 3), and esophagoplasty ( = 2). Esophageal perforation in 5 horses was treated by ventral drainage; 3 horses had the esophageal defect sutured ( = 3). Feeding tubes were placed in 15 horses. Postoperative complications occurred in 52% (14/27) with ...
Incidence of post-anesthetic colic in non-fasted adult equine patients.
The Canadian veterinary journal = La revue veterinaire canadienne    December 9, 2016   Volume 57, Issue 12 1263-1266 
Bailey PA, Hague BA, Davis M, Major MD, Zubrod CJ, Brakenhoff JE.The purpose of this study was to determine the incidence of post-anesthetic colic in non-fasted adult horses undergoing isoflurane inhalant anesthesia for an elective, non-abdominal procedure at a single referral center. Medical records were searched from May 1, 2012 to May 31, 2014. Inclusion criteria included non-fasted patients ≥ 2 years of age that were anesthetized for an elective, non-abdominal procedure. The incidence of post-anesthetic colic for this study population was 2.5%. None of the risk factors examined (season, age, gender, breed, surgeon, procedure, recumbency, butorphanol a...
Metalloproteinases and their inhibitors are influenced by inhalative glucocorticoid therapy in combination with environmental dust reduction in equine recurrent airway obstruction.
BMC veterinary research    December 9, 2016   Volume 12, Issue 1 282 doi: 10.1186/s12917-016-0915-1
Barton AK, Shety T, Bondzio A, Einspanier R, Gehlen H.Overexpression of matrix-metalloproteinases (MMPs) has been shown to lead to tissue damage in equine recurrent airway obstruction (RAO), as a misbalance with their natural inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), occurs. This favors irreversible pulmonary fibrosis formation. Increased levels of MMPs, TIMPs or altered ratios between them can be used as biomarkers of respiratory disease. We hypothesized that levels of MMPs, TIMPs and their ratios correlate with improvement in clinical findings and bronchoalveolar lavage fluid (BALF) cytology after 10 days of inhalative g...
Effect of concentrate feeding sequence on equine hindgut fermentation parameters.
Animal : an international journal of animal bioscience    December 8, 2016   Volume 11, Issue 7 1146-1152 doi: 10.1017/S1751731116002603
Sadet-Bourgeteau S, Philippeau C, Julliand V.Feeding a diet with a small amount of hay and a high proportion of concentrate given in large meals entails a risk of colic to horses as this can impact the hindgut microbial ecosystem. To counteract this potential negative effect, one feeding strategy is to modify the distribution sequence of concentrate and hay. The purpose of the present study was to assess the impact of feeding the concentrate meal before or with the hay meal on fermentative parameters postprandial variations in caecum and right ventral colon contents and faeces. We focused on the comparison of pH value and volatile fatty ...
Transrectal Ultrasonography of Equine Lumbosacral Nerves: Pilot Study in 28 Healthy Warmblood Horses. Espinosa P, Benoit P, Salazar I, de la Fuente J, Heiles P.A noninvasive method for visualizing lumbosacral nerves would be helpful for horses with suspected lumbosacral plexopathy or injury. The aim of this prospective descriptive pilot study was to characterize the ultrasonographic appearance of the lumbosacral nerves in a sample of healthy horses, and expand on the technique for image acquisition. Horses were recruited for inclusion if they were determined to be healthy and sound based on clinical and lameness evaluation. Transrectal ultrasound images of the lumbosacral nerves (L6, S1, and S2) were obtained for both sides. Landmarks for localizatio...
Effects of dobutamine hydrochloride on cardiovascular function in horses anesthetized with isoflurane with or without acepromazine maleate premedication.
American journal of veterinary research    December 3, 2016   Volume 77, Issue 12 1318-1324 doi: 10.2460/ajvr.77.12.1318
Schier MF, Raisis AL, Secombe CJ, Hosgood G, Musk GC, Lester GD.OBJECTIVE To determine the effects of acepromazine maleate premedication on cardiovascular function before and after infusion of dobutamine hydrochloride for 30 minutes in isoflurane-anesthetized horses. ANIMALS 6 healthy adult horses. PROCEDURES Each horse was anesthetized once following premedication with acepromazine (0.02 mg/kg, IV) administered 30 minutes prior to anesthetic induction (ACP+ treatment) and once without premedication (ACP- treatment). Anesthesia was induced with IV administration of xylazine hydrochloride (0.8 mg/kg), ketamine hydrochloride (2.2 mg/kg), and diazepam (0.08 m...
Effects of various antiplatelet drugs on ex vivo platelet activation induced by equine herpesvirus type 1.
American journal of veterinary research    December 3, 2016   Volume 77, Issue 12 1366-1373 doi: 10.2460/ajvr.77.12.1366
Hernandez D, Yeo WM, Brooks MB, Ness SL, Divers TJ, Stokol T.OBJECTIVE To evaluate the effects of treatment of horses with standard platelet inhibitors on ex vivo inhibition of platelet activation by equine herpesvirus type I (EHV-I). ANIMALS II healthy adult horses. PROCEDURES In a double-blinded, placebo-controlled crossover study, horses were treated orally for 5 days with theophylline (5 mg/kg, q 12 h), pentoxifylline (10 mg/kg, q 12 h), clopidogrel bisulfate (4 mg/kg, q 24 h), acetylsalicylic acid (20 mg/kg, q 24 h), or placebo. Horses received all treatments, each separated by a 3-week washout period. Platelet-rich plasma was prepared from citrate...
Comparison of four methods for generating decellularized equine synovial extracellular matrix.
American journal of veterinary research    December 3, 2016   Volume 77, Issue 12 1332-1339 doi: 10.2460/ajvr.77.12.1332
Reisbig NA, Hussein HA, Pinnell E, Bertone AL.OBJECTIVE To evaluate 4 methods for generating decellularized equine synovial extracellular matrix. SAMPLE Villous synovium harvested from the femoropatellar and medial femorotibial joints of 4 healthy adult horses 25,000 base pair) DNA fragments. Incubation in Triton and incubation in NaCl resulted in low DNA content and short (< 200 base pair) DNA fragments, but destroyed the synovial villous architecture. Incubation in PAA twice resulted in low DNA content and short DNA fragments while retaining the synovial villous architecture. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that...
Effect of neostigmine on contractility of equine pre-ovulatory follicles: An in vitro study.
Theriogenology    November 29, 2016   Volume 90 74-77 doi: 10.1016/j.theriogenology.2016.11.025
Piccinno M, Rizzo A, Cariello G, Sciorsci RL.In this study, the Authors investigated the modulatory effect of three single doses (10, 10, and 10 M) of neostigmine on the spontaneous contractility of equine pre-ovulatory follicles in an isolated organ bath, to establish the relationship between this acetylcholinesterase inhibitor and ovulation, in the mare. The results indicate that neostigmine increases pre-ovulatory contractility in equine follicles at each dose, but in a different manner. Indeed, the rise in contractility induced by neostigmine at 10 M and 10 M was phasic, while at 10 M it was tonic. The data obtained indicate poss...
A Quantitative Real-Time RT-PCR Assay for the Detection of Venezuelan equine encephalitis virus Utilizing a Universal Alphavirus Control RNA.
BioMed research international    November 29, 2016   Volume 2016 8543204 doi: 10.1155/2016/8543204
Vina-Rodriguez A, Eiden M, Keller M, Hinrichs W, Groschup MH. (VEEV) is an from the family that causes epizootic outbreaks in equids and humans in Central and South America. So far, most studies use conventional reverse transcriptase PCR assays for the detection of the different VEEV subtypes. Here we describe the development of a TaqMan quantitative real-time reverse transcriptase PCR assay for the specific detection and quantitation of all VEEV subtypes which uses in parallel a universal equine encephalitis virus control RNA carrying target sequences of the three equine encephalitis viruses. The control RNA was used to generate standard curves for t...
Spinal intradural hydatid cyst causing arachnoiditis: A rare etiology of cauda equina syndrome.
Journal of craniovertebral junction & spine    November 29, 2016   Volume 7, Issue 4 282-284 doi: 10.4103/0974-8237.193257
Singh S, Sardhara J, Singh AK, Srivastava AK, Bhaisora KS, Das KK, Mehrotra A, Sahu RN, Jaiswal AK, Behari S.This study aims to focus on a rare presentation of spinal hydatid cyst as cauda equine syndrome and misdiagnosed as intradural extramedullary (IDEM) benign lesion on magnetic resonance imaging. In this article, we report a case of spinal hydatid cyst masquerading as IDEM tumor, and intraoperatively, we accidently find clumped granuloma with severe arachnoiditis and hydatid cyst in lumber region, which was present as bilateral S1 radiculopathy with cauda equina syndrome. An 11-year-old boy who presented with symptoms and signs of cauda equina syndrome and planned for surgical excision. His radi...
High-throughput Detection of Respiratory Pathogens in Animal Specimens by Nanoscale PCR.
Journal of visualized experiments : JoVE    November 28, 2016   Issue 117 54781 doi: 10.3791/54781
Goodman LB, Anderson RR, Slater M, Ortenberg E, Renshaw RW, Chilson BD, Laverack MA, Beeby JS, Dubovi EJ, Glaser AL.Nanoliter scale real-time PCR uses spatial multiplexing to allow multiple assays to be run in parallel on a single plate without the typical drawbacks of combining reactions together. We designed and evaluated a panel based on this principle to rapidly identify the presence of common disease agents in dogs and horses with acute respiratory illness. This manuscript describes a nanoscale diagnostic PCR workflow for sample preparation, amplification, and analysis of target pathogen sequences, focusing on procedures that are different from microliter scale reactions. In the respiratory panel prese...
Appropriate threshold levels of cardiac beat-to-beat variation in semi-automatic analysis of equine ECG recordings.
BMC veterinary research    November 28, 2016   Volume 12, Issue 1 266 doi: 10.1186/s12917-016-0894-2
Flethøj M, Kanters JK, Pedersen PJ, Haugaard MM, Carstensen H, Olsen LH, Buhl R.Although premature beats are a matter of concern in horses, the interpretation of equine ECG recordings is complicated by a lack of standardized analysis criteria and a limited knowledge of the normal beat-to-beat variation of equine cardiac rhythm. The purpose of this study was to determine the appropriate threshold levels of maximum acceptable deviation of RR intervals in equine ECG analysis, and to evaluate a novel two-step timing algorithm by quantifying the frequency of arrhythmias in a cohort of healthy adult endurance horses. Results: Beat-to-beat variation differed considerably with he...
Modified technique for common carotid artery transposition in standing horses.
Veterinary surgery : VS    November 28, 2016   Volume 46, Issue 1 52-58 doi: 10.1111/vsu.12585
Tapio H, Argüelles D, Gracia-Calvo LA, Raekallio M.To describe a modified technique for permanent translocation of the common carotid artery (CCA) to a subcutaneous position in standing horses. Methods: Experimental study. Methods: Healthy adult Standardbred and Warmblood horses (n = 8). Methods: Surgery was performed with the horses standing under sedation and with local anesthesia. A combination of previously described techniques was used modifying the approach and closure of the incision. The right CCA was approached through a linear skin incision dorsal and parallel to the jugular vein and through the brachiocephalicus and omohyoideus ...
Reliability of breath by breath spirometry and relative flow-time indices for pulmonary function testing in horses.
BMC veterinary research    November 28, 2016   Volume 12, Issue 1 268 doi: 10.1186/s12917-016-0893-3
Burnheim K, Hughes KJ, Evans DL, Raidal SL.Respiratory problems are common in horses, and are often diagnosed as a cause of poor athletic performance. Reliable, accurate and sensitive spirometric tests of airway function in resting horses would assist with the diagnosis of limitations to breathing and facilitate investigations of the effects of various treatments on breathing capacity. The evaluation of respiratory function in horses is challenging and suitable procedures are not widely available to equine practitioners. The determination of relative flow or flow-time measures is used in paediatric patients where compliance may limit c...
Characterization of isolates of equine infectious anemia virus in Brazil.
Archives of virology    November 28, 2016   Volume 162, Issue 3 873-877 doi: 10.1007/s00705-016-3172-5
Tigre DM, Brandão CF, de Paula FL, Chinalia FA, Campos GS, Sardi SI.Equine infectious anemia is an important infectious disease that affects equids worldwide. Control of the disease is currently based on detection of anti-p26 EIAV by Agar Gel Immunodiffusion (AGID). In this work, 62 animals were examined by AGID and nested-PCR using primers for the gag gene. Fifty-three samples (85.5%) were positive by nested-PCR, whereas only 33 samples (53%) were positive for AGID. Fifteen amplicons obtained by nested-PCR were sequenced and the aligned results subjected to phylogenetic analysis. The analysis suggests that the Brazilian EIAV form a cluster with WSU5, EIAVUK a...
How to Meet the Last OIE Expert Surveillance Panel Recommendations on Equine Influenza (EI) Vaccine Composition: A Review of the Process Required for the Recombinant Canarypox-Based EI Vaccine.
Pathogens (Basel, Switzerland)    November 25, 2016   Volume 5, Issue 4 64 doi: 10.3390/pathogens5040064
Paillot R, Rash NL, Garrett D, Prowse-Davis L, Montesso F, Cullinane A, Lemaitre L, Thibault JC, Wittreck S, Dancer A.Vaccination is highly effective to prevent, control, and limit the impact of equine influenza (EI), a major respiratory disease of horses. However, EI vaccines should contain relevant equine influenza virus (EIV) strains for optimal protection. The OIE expert surveillance panel annually reviews EIV evolution and, since 2010, the use of Florida clade 1 and 2 sub-lineages representative vaccine strains is recommended. This report summarises the development process of a fully- updated recombinant canarypox-based EI vaccine in order to meet the last OIE recommendations, including the vaccine mode ...
Repeated oral administration of a cathepsin K inhibitor significantly suppresses bone resorption in exercising horses with evidence of increased bone formation and maintained bone turnover.
Journal of veterinary pharmacology and therapeutics    November 24, 2016   Volume 40, Issue 4 327-334 doi: 10.1111/jvp.12368
Hussein H, Dulin J, Smanik L, Drost WT, Russell D, Wellman M, Bertone A.Our investigations evaluated the effect of VEL-0230, a highly specific irreversible inhibitor of cathepsin K (CatK). The objectives of our study were to determine whether repeated dosing of a CatK inhibitor (CatKI) produced a desired inhibition of the bone resorption biomarker (CTX-1), and document the effect of repeated dosing on bone homeostasis, structure, and dynamics of bone resorption and formation in horses. Twelve young exercising horses were randomized in a prospective, controlled clinical trial and received 4 weekly doses of a CatKI or vehicle. Baseline and poststudy nuclear scintigr...