Analyze Diet

Topic:Horses

"Horses" is a broad topic that encompasses various aspects of equine biology, behavior, and management. This category includes studies on the anatomy, physiology, and genetics of horses, as well as their behavior, nutrition, and care. Research in this area may also cover the historical and cultural significance of horses, their roles in agriculture, sport, and therapy, and the challenges associated with their conservation and welfare. The page aggregates peer-reviewed research articles and scholarly studies that explore the multifaceted relationships between humans and horses, examining both scientific and socio-economic perspectives.
Diffusion of contrast medium after four different techniques for analgesia of the proximal metacarpal region: an in vivo and in vitro study.
Equine veterinary journal    April 4, 2012   Volume 44, Issue 6 668-673 doi: 10.1111/j.2042-3306.2012.00564.x
Nagy A, Bodó G, Dyson SJ.There is limited information on potential diffusion of local anaesthetic solution after various diagnostic analgesic techniques of the proximal metacarpal region. Objective: To document potential distribution of local anaesthetic solution following 4 techniques used for diagnostic analgesia of the proximal metacarpal region. Methods: Radiodense contrast medium was injected around the lateral palmar or medial and lateral palmar metacarpal nerves in 8 mature horses, using 4 different techniques. Radiographs were obtained 0, 10 and 20 min after injection and were analysed subjectively. A mixture ...
Social relations in a mixed group of mules, ponies and donkeys reflect differences in equid type.
Behavioural processes    April 3, 2012   Volume 90, Issue 3 337-342 doi: 10.1016/j.beproc.2012.03.012
Proops L, Burden F, Osthaus B.Donkeys and mules are frequently kept as companion animals for horses and ponies, with these different equids often being considered a homogenous group. However, the extent to which domestic equids form inter-specific bonds and display similar social behaviour when living in a mixed herd has not previously been studied. Here we compare the social organization of these three (sub)species when housed together, providing the first systematic analysis of how genetic hybridization is expressed in the social behaviour of mules. A group of 16 mules, donkeys and ponies was observed for 70h and preferr...
Equine insect bite hypersensitivity: what do we know?
Veterinary immunology and immunopathology    April 3, 2012   Volume 147, Issue 3-4 113-126 doi: 10.1016/j.vetimm.2012.03.017
Schaffartzik A, Hamza E, Janda J, Crameri R, Marti E, Rhyner C.Insect bite hypersensitivity (IBH) is an allergic dermatitis of the horse caused by bites of insects of the genus Culicoides and is currently the best characterized allergic disease of horses. This article reviews knowledge of the immunopathogenesis of IBH, with a particular focus on the causative allergens. Whereas so far hardly any research has been done on the role of antigen presenting cells in the pathogenesis of IBH, recent studies suggest that IBH is characterized by an imbalance between a T helper 2 (Th2) and regulatory T cell (T(reg)) immune response, as shown both locally in the skin...
Influence of an active stable system on the behavior and body condition of Icelandic horses.
Animal : an international journal of animal bioscience    April 3, 2012   Volume 6, Issue 10 1684-1693 doi: 10.1017/S1751731112000699
Hoffmann G, Bentke A, Rose-Meierhöfer S, Berg W, Mazetti P, Hardarson GH.Horses are often stabled in individual boxes, a method that does not meet their natural needs and may cause psychical and musculoskeletal diseases. This problem is particularly evident in Iceland, where horses often spend the long winter periods in cramped boxes. The aim of this study was to analyze the suitability of a group housing system in Iceland, but the results are also applicable to horses of other regions. Eight Icelandic horses were observed in an active stable system, and their behavior and time budget were recorded. Movement and lying behavior were studied with ALT (Activity, Lying...
Efficacy of major anthelmintics against horse cyathostomins in France.
Veterinary parasitology    April 3, 2012   Volume 188, Issue 3-4 294-300 doi: 10.1016/j.vetpar.2012.03.048
Traversa D, Castagna G, von Samson-Himmelstjerna G, Meloni S, Bartolini R, Geurden T, Pearce MC, Woringer E, Besognet B, Milillo P, D'Espois M.This paper reports a survey conducted in France during 2011 to evaluate the efficacy of commonly used anthelmintics against horse cyathostomins. A total of 40 farms and 1089 horses were screened for the presence of cyathostomins. All farms but one were positive, with an overall animal infection rate of 53.7%, ranging from 9% to 83% on individual farms. On 445 horses from 30 of these farms, a faecal egg count reduction test (FECRT) was performed to evaluate the efficacy of oral formulations of fenbendazole (FBZ), pyrantel embonate (PYR), ivermectin (IVM) and moxidectin (MOX). Calculation of the...
Successful induction of lactation in a barren Thoroughbred mare: growth of a foal raised on induced lactation and the corresponding maternal hormone profiles.
The Journal of veterinary medical science    April 2, 2012   Volume 74, Issue 8 995-1002 doi: 10.1292/jvms.12-0035
Korosue K, Murase H, Sato F, Ishimaru M, Harada T, Watanabe G, Taya K, Nambo Y.The purpose of this study was to demonstrate that a barren parous Thoroughbred mare with lactation induced by hormonal treatment can be introduced to an orphan foal at the same farm and that the mare can become pregnant after the end of the hormonal treatment. An additional purpose was to investigate the changes in the plasma concentrations of prolactin, estradiol-17β, progesterone, follicle-stimulating hormone, and luteinizing hormone before, during, and after hormonal treatment. The difference in body weight between the adopted foal and the control foals, which were at the same farm and rai...
Investigation of the role of mules as silent shedders of EHV-1 during an outbreak of EHV-1 myeloencephalopathy in California.
The Veterinary record    April 2, 2012   Volume 170, Issue 18 465 doi: 10.1136/vr.100598
Pusterla N, Mapes S, Wademan C, White A, Estell K, Swain E.No abstract available
Reproductive characteristics of stallions during the breeding and non-breeding season in a tropical region.
Tropical animal health and production    April 1, 2012   Volume 44, Issue 7 1703-1707 doi: 10.1007/s11250-012-0127-z
Leme DP, Papa FO, Roser JF.The objective of this study was to investigate reproductive characteristics of stallions at a tropical zone in the breeding and non-breeding seasons. The following parameters were assessed: testicular volume; semen quality; and serum concentrations of LH, FSH, and testosterone; in addition to the percentages of germ cells and proportions of germ cells/Sertoli cells by testicular cytology in stallions. Semen was collected from eight adult stallions twice a week during a 12-week period in both seasons (6 weeks before and 6 weeks after the summer and winter solstices). Jugular blood samples were ...
Antioxidant effect of different vitamins on methemoglobin production: An in vitro study.
Veterinary research forum : an international quarterly journal    April 1, 2012   Volume 3, Issue 2 97-101 
Atyabi N, Yasini SP, Jalali SM, Shaygan H.Nitrite intoxication occurs frequently in ruminants and equines. The most common treatment of this disorder is administration of 1% methylene blue, although the use of some antioxidant agents e.g. vitamins and complementary treatment may also be useful. The aim of this study was to evaluate the in vitro antioxidative effects of some vitamins on methemoglobinemia induced by sodium nitrite. For this purpose the blood sample of a healthy dairy cattle was pre-incubated with three different concentrations (5, 10, 20 mmol L(-1)) of each vitamin (E, C, B1, A and a combination of vitamin E and vitamin...
Expression of essential B cell development genes in horses with common variable immunodeficiency.
Molecular immunology    March 30, 2012   Volume 51, Issue 2 169-176 doi: 10.1016/j.molimm.2012.03.018
Tallmadge RL, Such KA, Miller KC, Matychak MB, Felippe MJ.Common variable immunodeficiency (CVID) is a heterogeneous disorder of B cell differentiation or function with inadequate antibody production. Our laboratory studies a natural form of CVID in horses characterized by late-onset B cell lymphopenia due to impaired B cell production in the bone marrow. This study was undertaken to assess the status of B cell differentiation in the bone marrow of CVID-affected horses by measuring the expression of genes essential for early B cell commitment and development. Standard RT-PCR revealed that most of the transcription factors and key signaling molecules ...
Local anesthesia and hydro-distension to facilitate cystic calculus removal in horses.
Veterinary surgery : VS    March 29, 2012   Volume 41, Issue 5 638-642 doi: 10.1111/j.1532-950X.2012.00986.x
Russell T, Pollock PJ.To report a technique for improving surgical access to the bladder for removal of cystic calculi in male horses. Methods: Retrospective case series. Methods: Geldings (8) with cystic calculi. Methods: After catheterization of the bladder through the penis, 100 mL 2% lidocaine hydrochloride solution was instilled. After 10 minutes, the bladder was distended with sterile, warmed Hartmann's solution to a pressure of ≈ 40 cm H(2) O, using gravity feed. This was left in place until abdominal access was gained at surgery, then the fluid siphoned off via the catheter. Results: Calculi were 3-11 cm ...
Evaluation of a midazolam-ketamine-xylazine infusion for total intravenous anesthesia in horses.
American journal of veterinary research    March 29, 2012   Volume 73, Issue 4 470-475 doi: 10.2460/ajvr.73.4.470
Hubbell JA, Aarnes TK, Lerche P, Bednarski RM.To evaluate the use of midazolam, ketamine, and xylazine for total IV anesthesia (TIVA) in horses. Methods: 6 healthy Thoroughbred mares. Methods: Horses were sedated with xylazine (1.0 mg/kg, IV). Anesthesia was induced with midazolam (0.1 mg/kg, IV) followed by ketamine (2.2 mg/kg, IV) and was maintained with an IV infusion of midazolam (0.002 mg/kg/min), ketamine (0.03 mg/kg/min), and xylazine (0.016 mg/kg/min). Horses underwent surgical manipulation and injection of the palmar digital nerves; duration of the infusion was 60 minutes. Additional ketamine (0.2 to 0.4 mg/kg, IV) was administer...
Changes in heart rate, heart rate variability, and atrioventricular block during withholding of food in Thoroughbreds.
American journal of veterinary research    March 29, 2012   Volume 73, Issue 4 508-514 doi: 10.2460/ajvr.73.4.508
Ohmura H, Boscan PL, Solano AM, Stanley SD, Jones JH.To determine whether withholding of food affects autonomic nervous system balance by analysis of heart rate (HR), HR variability (HRV), and frequency of second-degree atrioventricular block in horses. Methods: 5 healthy Thoroughbreds. Methods: For two 24-hour periods in a crossover study, food was withheld from horses or horses were maintained on their regular feeding schedule (control conditions) in their stalls and Holter monitor ECG recordings were obtained. The ECGs were analyzed by use of fast-Fourier transformation, and power spectrum densities were calculated for low-frequency (0.01 to ...
Conception rate, uterine infection and embryo quality after artificial insemination and natural breeding with a stallion carrier of Pseudomonas aeruginosa: a case report.
Acta veterinaria Scandinavica    March 29, 2012   Volume 54, Issue 1 20 doi: 10.1186/1751-0147-54-20
Tiago G, Júlio C, António R.Pseudomonas aeruginosa may cause venereal disease and infertility in horses. A Pseudomonas aeruginosa - carrier stallion, often unresponsive to artificial vagina collection, was used to naturally breed mares. Semen collected from the same stallion was also used to perform artificial inseminations. Pregnancy rates, embryo quality and incidence of uterine infection were compared between inseminated or naturally-bred mares. Methods: P. aeruginosa was isolated from swabbing of the penis, prepuce and distal urethra of the stallion. Before being bred or inseminated, clitoral/vestibular samples were ...
Electromyographic evaluation of masseter muscle activity in horses fed (i) different types of roughage and (ii) maize after different hay allocations.
Journal of animal physiology and animal nutrition    March 29, 2012   Volume 97, Issue 3 515-521 doi: 10.1111/j.1439-0396.2012.01292.x
Vervuert I, Brüssow N, Bochnia M, Cí·¯ord D, Coenen M.The aims of this study were to monitor electromyographic (EMG) activity of masseter muscle in healthy horses fed (i) different types of roughage and (ii) maize after different hay allocations. Four horses were offered the following three diets ad libitum: hay, haylage or straw/alfalfa chaff (SAC). In a second trial, four horses were fed cracked maize (CM) and hay in three different orders: (i) CM after a 12-h overnight fast; (ii) CM immediately after restricted hay intake (0.6 kg hay/100 kg BW); or 3) CM after hay intake ad libitum. The activity of the masseter muscle was determined by EMG...
Inflammatory responses to induced infectious endometritis in mares resistant or susceptible to persistent endometritis.
BMC veterinary research    March 29, 2012   Volume 8 41 doi: 10.1186/1746-6148-8-41
Christoffersen M, Woodward E, Bojesen AM, Jacobsen S, Petersen MR, Troedsson MH, Lehn-Jensen H.The objective of the study was to evaluate the gene expression of inflammatory cytokines (interleukin [IL]-1β, IL-6, IL-8, IL-10, tumor necrosis factor [TNF]-α, IL-1 receptor antagonist [ra] and serum amyloid A (SAA) in endometrial tissue and circulating leukocytes in response to uterine inoculation of 105 colony forming units (CFU) Escherichia coli in mares. Before inoculation, mares were classified as resistant or susceptible to persistent endometritis based on their uterine inflammatory response to infusion of 109 killed spermatozoa and histological assessment of the endometrial quality. ...
Lameness and performance evaluation in ambulatory practice.
The Veterinary clinics of North America. Equine practice    March 29, 2012   Volume 28, Issue 1 101-115 doi: 10.1016/j.cveq.2012.01.007
Mitchell JS.Lameness and performance evaluation can be one of the most rewarding aspects of equine veterinary practice. There is a misconception that it depends on new sophisticated and expensive diagnostic modalities, when the reality is that knowing where and when to use these modalities form the real art of equine lameness practice. The most expensive ultrasound machine in the world is not very diagnostic if applied to the wrong limb. The art of lameness practice is vested in knowledge of horsemanship, an understanding of anatomy and function, and inquiring senses to sort out what the horse and his han...
Endoscopic-assisted electrohydraulic shockwave lithotripsy in standing sedated horses.
Veterinary surgery : VS    March 29, 2012   Volume 41, Issue 5 620-624 doi: 10.1111/j.1532-950X.2012.00977.x
Röcken M, Fürst A, Kummer M, Mosel G, Tschanz T, Lischer CJ.To report use of transendoscopic electrohydraulic shockwave lithotripsy for fragmentation of urinary calculi in horses. Methods: Case series. Methods: Male horses (n = 21). Methods: Fragmentation of cystic calculi (median, 6 cm diameter; range, 4-11 cm diameter) was achieved by transurethral endoscopy in standing sedated horses using an electrohydraulic shockwave fiber introduced through the biopsy channel of an endoscope. The fiber was advanced until it contacted the calculus. Repeated activation of the fiber was used to disrupt the calculus into fragments <1 cm diameter. Visibility within...
Changes in heart rate and heart rate variability during transportation of horses by road and air.
American journal of veterinary research    March 29, 2012   Volume 73, Issue 4 515-521 doi: 10.2460/ajvr.73.4.515
Ohmura H, Hobo S, Hiraga A, Jones JH.To determine the influence of transportation by road and air on heart rate (HR) and HR variability (HRV) in horses. Animals-6 healthy horses. Methods: ECG recordings were obtained from horses before (quarantine with stall rest [Q]; 24 hours) and during a journey that included transportation by road (RT; 4.5 hours), waiting on the ground in an air stall (W; 5.5 hours), and transportation by air (AT; 11 hours); HR was determined, and HRV indices of autonomic nervous activity (low-frequency [LF; 0.01 to 0.07 Hz] and high-frequency [HF; 0.07 to 0.6 Hz] power) were calculated. Results: Mean ± SD H...
Effect of head and neck position on intrathoracic pressure and arterial blood gas values in Dutch Warmblood riding horses during moderate exercise.
American journal of veterinary research    March 29, 2012   Volume 73, Issue 4 522-528 doi: 10.2460/ajvr.73.4.522
Sleutjens J, Smiet E, van Weeren R, van der Kolk J, Back W, Wijnberg ID.To evaluate the effect of various head and neck positions on intrathoracic pressure and arterial oxygenation during exercise in horses. Methods: 7 healthy Dutch Warmblood riding horses. Methods: The horses were evaluated with the head and neck in the following predefined positions: position 1, free and unrestrained; position 2, neck raised with the bridge of the nose aligned vertically; position 4, neck lowered and extremely flexed with the nose pointing toward the pectoral muscles; position 5, neck raised and extended with the bridge of the nose in front of a vertical line perpendicular to th...
[Occurence of the hindgut ciliates Paraisotricha colpoidea and P. minuta (Ciliophora: Paraisotrichidae) in horses in Turkey].
Turkiye parazitolojii dergisi    March 28, 2012   Volume 36, Issue 1 28-32 doi: 10.5152/tpd.2012.07
Gürelli G, Göçmen B.The aim of this study was to determine the cytological features of 2 endocommensal ciliates, P. colpoidea and P. minuta belonging to genus Paraisotricha found in the hindgut of 15 Turk rahvan and 15 English and Arabic horses from Izmir, compare the morphological characters of species with their original descriptions and previous reports and discuss the similarities and differences. Methods: The cytological features of two endocommensal ciliates were investigated with the pyridinated silver carbonate impregnation and silver nitrate impregnation techniques at the level of light microscopy. Resul...
Founder and present maternal diversity in two endangered Spanish horse breeds assessed via pedigree and mitochondrial DNA information.
Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie    March 28, 2012   Volume 129, Issue 4 271-279 doi: 10.1111/j.1439-0388.2012.00995.x
Álvarez I, Fernández I, Lorenzo L, Payeras L, Cuervo M, Goyache F.Pedigree information and 179 mtDNA sequences from two endangered Spanish horse breeds, the Asturcón pony (143) and the Mallorquí horse (36), were analysed to asses: (i) the pedigree and molecular maternal genetic diversity of the two breeds; (ii) the concordance between the dam lines recorded in the corresponding studbooks and the mtDNA haplotypes identified; and (iii) to assess the losses of maternal genetic variability occurred from the foundation of the studbooks to present. Up to 50 Asturcón and 18 Mallorquí founder dam lines were identified in the studbooks analysed. Up to 315 Asturc...
Effect of sample storage on blood crossmatching in horses.
Journal of veterinary internal medicine    March 28, 2012   Volume 26, Issue 3 662-667 doi: 10.1111/j.1939-1676.2012.00913.x
Harris M, Nolen-Walston R, Ashton W, May M, Jackson K, Boston R.Blood samples banked for up to 1 month are typically used to perform pretransfusion testing in humans and small animals, but this has not been validated using blood from horses. Objective: Compatibility of equine blood samples is repeatable using fresh samples, and reproducible using donor blood samples stored for up to 4 weeks. Methods: Six healthy adult horses. Methods: Randomized, blinded experimental study. Immunologic compatibility of the blood of all horses was assessed using a major and minor saline agglutination and hemolysin crossmatch using blood samples refrigerated for 0-4 weeks an...
Hydrallantois in the mare–a report of five cases.
Reproduction in domestic animals = Zuchthygiene    March 27, 2012   Volume 48, Issue 1 e1-e6 doi: 10.1111/j.1439-0531.2012.02013.x
Govaere JL, De Schauwer C, Hoogewijs MK, Chiers K, Lefère L, Catry B, Roels K, van Heerden M, Broeckx S, de Kruif A.Hydrallantois in the mare is a very rare condition, and clinical reports help to gather information to elucidate its pathogenesis, treatment options and prognosis. Five different cases of hydrallantois in the mare are reported in this article, all with the involvement of placentitis. The five mares were presented because of acute distention of the abdomen, dyspnoea, stiff gait and a lack of appetite. After a gradual release of the excessive amount of allantoic fluid, an abortion was induced in all five mares. The foals were either born dead or euthanized. The mares recovered quickly. One mare ...
Comparison of two approaches to performing an inferior alveolar nerve block in the horse.
Australian veterinary journal    March 27, 2012   Volume 90, Issue 4 146-150 doi: 10.1111/j.1751-0813.2012.00897.x
Harding PG, Smith RL, Barakzai SZ.To compare two approaches to performing the inferior alveolar nerve block in the horse and to evaluate the consistency of described topographical landmarks. Methods: Experimental cadaver model. Methods: Eleven cadaver heads were positioned to mimic a standing sedated horse and the position of the mandibular foramen approximated. The vertical approach to the approximate location of the mandibular foramen was undertaken and red dye was deposited. The angled approach was then undertaken and blue ink was used to identify it. The heads were then dissected to determine the location of the dye. Place...
Nigropallidal encephalomalacia in horses grazing Rhaponticum repens (creeping knapweed).
Australian veterinary journal    March 27, 2012   Volume 90, Issue 4 151-154 doi: 10.1111/j.1751-0813.2011.00879.x
Elliott CR, McCowan CI.Nigropallidal encephalomalacia was diagnosed in two horses in northern Victoria that had a history of long-term pasture access to a dense growth of Rhaponticum repens. The region in which the affected horses lived had received well above average rainfall for several months preceding the poisoning. Affected horses had sudden onset of subcutaneous oedema of the head, impaired prehension and mastication, dullness, lethargy and repeated chewing-like jaw movements. Diagnosis was confirmed at necropsy, with characteristic malacic lesions in the substantia nigra and globus pallidus of the brain. This...
Road transport of farm animals: effects of journey duration on animal welfare.
Animal : an international journal of animal bioscience    March 27, 2012   Volume 5, Issue 3 415-427 doi: 10.1017/S1751731110001989
Nielsen BL, Dybkjær L, Herskin MS.Transport of farm animals gives rise to concern about their welfare. Specific attention has been given to the duration of animal transport, and maximum journey durations are used in legislation that seek to minimise any negative impact of transport on animal welfare. This paper reviews the relatively few scientific investigations into effects of transport duration on animal welfare in cattle, sheep, horses, pigs and poultry. From the available literature, we attempt to distinguish between aspects, which will impair welfare on journeys of any duration, such as those associated with loading, and...
A new analytical method based on anti-EPO monolith column and LC-FAIMS-MS/MS for the detection of rHuEPOs in horse plasma and urine samples.
The Analyst    March 27, 2012   Volume 137, Issue 10 2445-2453 doi: 10.1039/c2an15662h
Bailly-Chouriberry L, Cormant F, Garcia P, Lönnberg M, Szwandt S, Bondesson U, Popot MA, Bonnaire Y.Recombinant human erythropoietin (rHuEPO) is a 30-34 kDa glycoprotein banned by the racing authorities. For some years this molecule has been detected in race horses in USA and in Europe, and even in racing camels. Although direct methods to differentiate horse endogenous EPO and rHuEPO have been developed either by LC-MS/MS or by isoelectric focusing (IEF) with double-blotting, the short confirmation time of such prohibited hormone in plasma remains a problem for horseracing doping control laboratories. In order to improve the rHuEPOs confirmation process in horse plasma or urine in terms of ...
European outbreaks of atypical myopathy in grazing equids (2006-2009): spatiotemporal distribution, history and clinical features.
Equine veterinary journal    March 26, 2012   Volume 44, Issue 5 614-620 doi: 10.1111/j.2042-3306.2012.00556.x
van Galen G, Marcillaud Pitel C, Saegerman C, Patarin F, Amory H, Baily JD, Cassart D, Gerber V, Hahn C, Harris P, Keen JA, Kirschvink N, Lefere L....Improved understanding of the epidemiology of atypical myopathy (AM) will help to define the environmental factors that permit or support the causal agent(s) to exert toxicity. Objective: This European survey of AM aimed to describe spatiotemporal distribution, survival, clinical signs, circumstances in which AM develops and its different expressions between countries and over time. Methods: The spatiotemporal distribution, history and clinical features of AM cases reported to the Atypical Myopathy Alert Group from 2006 to 2009 were described. Comparisons of data from the most severely affecte...
Disposition of desfuroylceftiofur acetamide in serum, placental tissue, fetal fluids, and fetal tissues after administration of ceftiofur crystalline free acid (CCFA) to pony mares with placentitis.
Journal of veterinary pharmacology and therapeutics    March 26, 2012   Volume 36, Issue 1 59-67 doi: 10.1111/j.1365-2885.2012.01392.x
Macpherson ML, Giguère S, Hatzel JN, Pozor M, Benson S, Diaw M, Sanchez LC, Vickroy TW, Tell L, Wetzlich S, Sims J.The objective of this study was to determine the pharmacokinetics of CCFA in mares with placentitis and evaluate the disposition of the drug in fetal fluids, fetal membranes, colostrum, and serum of foals. A secondary objective was to obtain pilot data regarding the efficacy of CCFA for improving foal survival in mares with placentitis. Twelve pregnant pony mares were enrolled in the study, inoculated with Streptococcus zooepidemicus, intracervically and assigned to one of three groups: CEFT (n = 3; administered CCFA only; 6.6 mg/kg, i.m., q96h); COMBO (n = 6; administered combination therapy ...