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BACKGROUND: Despite the tremendous therapeutic advances that have stemmed from somatic oncogenetics, survival of some cancers has not improved in 50 years. Osteosarcoma still has a 5-year survival rate of 66%. We propose the natural canine osteosarcoma model can change that: it is extremely similar to the human condition, except for being highly heritable and having a dramatically higher incidence. Here we reanalyze published genome scans of osteosarcoma in three frequently-affected dog breeds and report entirely new understandings with immediate translational indications. RESULTS: First, meta-analysis revealed association near FGF9, which has strong biological and therapeutic relevance. Secondly, risk-modeling by multiple logistic regression shows 22 of the 34 associated loci contribute to risk and eight have large effect sizes. We validated the Greyhound stepwise model in our own, independent, case-control cohort. Lastly, we updated the gene annotation from approximately 50 genes to 175, and prioritized those using cross-species genomics data. Mostly positional evidence suggests 13 genes are likely to be associated with mapped risk (including MTMR9, EWSR1 retrogene, TANGO2 and FGF9). Previous annotation included seven of those 13 and prioritized four by pathway enrichment. Ten of our 13 priority genes are in loci that contribute to risk modeling and thus can be studied epidemiologically and translationally in pet dogs. Other new candidates include MYCN, SVIL and MIR100HG. CONCLUSIONS: Polygenic osteosarcoma-risk commonly rises to Mendelian-levels in some dog breeds. This justifies caninized animal models and targeted clinical trials in pet dogs (e.g., using CDK4/6 and FGFR1/2 inhibitors).
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Neoplasias Ósseas/veterinária , Doenças do Cão/genética , Estudo de Associação Genômica Ampla , Genômica/métodos , Modelos Estatísticos , Herança Multifatorial , Osteossarcoma/veterinária , Animais , Neoplasias Ósseas/genética , Cruzamento , Estudos de Casos e Controles , Estudos de Coortes , Modelos Animais de Doenças , Doenças do Cão/patologia , Cães , Predisposição Genética para Doença , Genoma , Osteossarcoma/genética , Medição de Risco/métodosRESUMO
Dynamic modeling of mechanisms driving volatile fatty acid and hydrogen production in the rumen microbial ecosystem contributes to the heuristic prediction of CH4 emissions from dairy cattle into the environment. Existing mathematical rumen models, however, lack the representation of these mechanisms. A dynamic mechanistic model was developed that simulates the thermodynamic control of hydrogen partial pressure ( [Formula: see text] ) on volatile fatty acid (VFA) fermentation pathways via the NAD+ to NADH ratio in fermentative microbes, and methanogenesis in the bovine rumen. This model is unique and closely aligns with principles of reaction kinetics and thermodynamics. Model state variables represent ruminal carbohydrate substrates, bacteria and protozoa, methanogens, and gaseous and dissolved fermentation end products. The model was extended with static equations to model the hindgut metabolism. Feed composition and twice daily feeding were used as model inputs. Model parameters were estimated to experimental data using a Bayesian calibration procedure, after which the uncertainty of the parameter distribution on the model output was assessed. The model predicted a marked peak in [Formula: see text] after feeding that rapidly declined in time. This peak in [Formula: see text] caused a decrease in NAD+ to NADH ratio followed by an increased propionate molar proportion at the expense of acetate molar proportion, and an increase in CH4 production that steadily decreased in time, although the magnitude of increase for CH4 emission was less than for [Formula: see text] . A global sensitivity analysis indicated that parameters that determine the fractional passage rate and NADH oxidation rate altogether explained 86% of the variation in predicted daily CH4 emission. Model evaluation indicated over-prediction of in vivo CH4 emissions shortly after feeding, whereas under-prediction was indicated at later times. The present rumen fermentation modeling effort uniquely provides the integration of the [Formula: see text] controlled NAD+ to NADH ratio for dynamically predicting metabolic pathways that yield VFA, H2 and CH4.
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Ácidos Graxos Voláteis/biossíntese , Hidrogênio/metabolismo , Metano/biossíntese , Modelos Biológicos , Rúmen/metabolismo , Animais , Teorema de Bayes , Bovinos , Ritmo Circadiano/fisiologia , Fermentação , Cinética , Termodinâmica , IncertezaRESUMO
Agriculture has a key role in food production worldwide and it is a major component of the gross domestic product of several countries. Livestock production is essential for the generation of high quality protein foods and the delivery of foods in regions where animal products are the main food source. Environmental impacts of livestock production have been examined for decades, but recently emission of methane from enteric fermentation has been targeted as a substantial greenhouse gas source. The quantification of methane emissions from livestock on a global scale relies on prediction models because measurements require specialized equipment and may be expensive. The predictive ability of current methane emission models remains poor. Moreover, the availability of information on livestock production systems has increased substantially over the years enabling the development of more detailed methane prediction models. In this study, we have developed and evaluated prediction models based on a large database of enteric methane emissions from North American dairy and beef cattle. Most probable models of various complexity levels were identified using a Bayesian model selection procedure and were fitted under a hierarchical setting. Energy intake, dietary fiber and lipid proportions, animal body weight and milk fat proportion were identified as key explanatory variables for predicting emissions. Models here developed substantially outperformed models currently used in national greenhouse gas inventories. Additionally, estimates of repeatability of methane emissions were lower than the ones from the literature and multicollinearity diagnostics suggested that prediction models are stable. In this context, we propose various enteric methane prediction models which require different levels of information availability and can be readily implemented in national greenhouse gas inventories of different complexity levels. The utilization of such models may reduce errors associated with prediction of methane and allow a better examination and representation of policies regulating emissions from cattle.
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Poluentes Atmosféricos/análise , Criação de Animais Domésticos , Monitoramento Ambiental/métodos , Metano/análise , Modelos Teóricos , Animais , Bovinos , Indústria de Laticínios , FemininoRESUMO
The integration and intensification of modern swine production has amplified the importance of biosecurity, as diseases are more easily able to spread and persist in large swine farms, resulting in economic losses. Advancements in accessible technology and computational methods offer new applications for precision livestock farming, such as monitoring internal movements to better understand biosecurity compliance on farm. In this study, a beacon-sensor based internal movement system (PigChamp Pro Europa®) was utilized to investigate the association between weekly within-farm movements of workers and an important production parameter: average weekly number of pigs weaned per sow (PWS), on three US swine farms. Sensors were installed in each room of each farm and Bluetooth-based beacons were distributed individually to farm employees. Movement data was collected for approximately one year and production data was extracted from each farm retrospectively. A linear mixed effects model was fit in STATA 15 with the primary outcome as the average weekly number of pigs weaned per sow and farm included as a random effect. The main predictors included the weekly frequency of three movement types thought to be risky with respect to disease transmission and maintenance in the herd. The frequency values of the three movements were categorized based on the tertile values for each farm. The movement with the highest average frequency was between farrowing rooms for all three farms. The medium frequency of movements category between farrowing rooms the two-weeks preceding the outcome was significantly associated with a decrease in PWS by nearly 1-pig for every 5-sows after controlling for farm, pre-weaning mortality, PWS the week prior, and season (p = 0.03). The random effect variance estimate for the model was 0.21 with a standard error of 0.18. The intraclass correlation coefficient was 0.67 with a standard error of 0.19, indicating that 67% of the unexplained variability in PWS could be attributed to the farm level. This study demonstrates the application of beacon-sensor technology to monitor internal personnel movements in swine production. Technological applications to monitoring trends of within farm movements of farm personnel, such as the system used here, may have the potential to identify specific movements related to farm-specific biosecurity protocol allowing corrective measures and facilitating focused efforts on disease control and mitigation; in turn maintaining productivity and improving overall animal health.
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Fazendeiros , Fazendas/estatística & dados numéricos , Movimento , Sus scrofa/fisiologia , Desmame , Criação de Animais Domésticos , Animais , Fazendeiros/estatística & dados numéricos , Tecnologia de Sensoriamento Remoto , Estudos Retrospectivos , Estados UnidosRESUMO
Mitochondrial function is essential for sperm viability, not only from a sperm metabolism perspective, but also for improvement of sperm storage in liquid and frozen states. Bull sperm have notable metabolic variability with energy production for motility and subsequently for fertilizing capacity resulting from both glycolysis and oxidative phosphorylation. The objective of this study was to determine mitochondrial function of sperm using high-throughput Seahorse Analyzer technology in fresh semen and subsequent to freezing-thawing when there was incubation in media commonly used for sperm storage (relatively large glucose concentration) and female tract (relatively small glucose concentration). Additionally, there were determinations whether there were differences in values for fertility variables by regressing sire conception rate on values for mitochondrial variables when there was evaluation of semen from bulls with varying fertility. Media with larger concentrations of glucose inhibited mitochondrial function in fresh sperm, as indicated by less maximal oxygen consumption, spare respiratory capacity and coupling efficiency when compared to sperm in the media containing less glucose. Furthermore, there was greater (Pâ¯<⯠0.05) mitochondrial function in cryopreserved-thawed compared to fresh samples with there being no effect of incubation media. These results indicate that mitochondrial damage from cryopreservation cannot be simply overcome post-thawing with glucose supplementation of bull semen incubation media. The increase in mitochondrial function is likely due to "non-productive" oxygen consumption to maintain the mitochondrial proton gradient. Furthermore, there was a negative association of mitochondrial proton leakage with sire conception rate indicating this could be a potential biomarker of bull fertility.
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Bovinos , Criopreservação/veterinária , Glucose/farmacologia , Preservação do Sêmen/veterinária , Espermatozoides/efeitos dos fármacos , Animais , Fertilidade , Glucose/administração & dosagem , Masculino , Preservação do Sêmen/métodos , Motilidade dos Espermatozoides , Espermatozoides/fisiologiaRESUMO
In the current study, a simulated online parturition detection model is developed and reported. Using a machine learning (ML)-based approach, the model incorporates data from Global Navigation Satellite System (GNSS) tracking collars, accelerometer ear tags and local weather data, with the aim of detecting parturition events in pasture-based sheep. The specific objectives were two-fold: (i) determine which sensor systems and features provide the most useful information for lambing detection; (ii) evaluate how these data might be integrated using ML classification to alert to a parturition event as it occurs. Two independent field trials were conducted during the 2017 and 2018 lambing seasons in New Zealand, with the data from each used for ML training and independent validation, respectively. Based on objective (i), four features were identified as exerting the greatest importance for lambing detection: mean distance to peers (MDP), MDP compared to the flock mean (MDP.Mean), closest peer (CP) and posture change (PC). Using these four features, the final ML was able to detect 27% and 55% of lambing events within ±3 h of birth with no prior false positives. If the model sensitivity was manipulated such that earlier false positives were permissible, this detection increased to 91% and 82% depending on the requirement for a single alert, or two consecutive alerts occurring. To identify the potential causes of model failure, the data of three animals were investigated further. Lambing detection appeared to rely on increased social isolation behaviour in addition to increased PC behaviour. The results of the study support the use of integrated sensor data for ML-based detection of parturition events in grazing sheep. This is the first known application of ML classification for the detection of lambing in pasture-based sheep. Application of this knowledge could have significant impacts on the ability to remotely monitor animals in commercial situations, with a logical extension of the information for remote monitoring of animal welfare.
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Castration is a painful procedure routinely performed on piglets. Specific periods relative to castration and time sampling rules are used widely to quantify deviations in piglet's behavior associated with castration rather than assessing behavior for the entire trial period. However, very limited work has evaluated time sampling recording rules to quantify behavioral changes to piglets undergoing castration. Therefore, the objective of this study was to validate the accuracy of six continuous time sampling periods (5, 10, 15, 20, 30, and 45 min), to quantify piglet behavior post-castration when compared with a full 60-min observation period. Sixteen Yorkshire-Landrace x Duroc piglets were surgically castrated. Data were collected using continuous observation (recording rule) of each individual male piglet per litter for 60-min post-castration. The 60-min continuous behavioral data set was then subdivided into six data subsets for each defined continuous time sampling period (5, 10, 15, 20, 30, and 45 min). Data from each continuous time sampling period and the full period data were analyzed using both a generalized linear mixed model and linear regression analysis. For the generalized linear mixed model, 30- and 45-min continuous time sampling periods were not different (P > 0.05) when compared with the full observation period data for all behaviors. For the linear regression analysis, affiliative interaction, sitting, walking, huddled up, prostrated, scratching, spasms, and trembling behaviors met the pairwise comparison accuracy criteria: [1) the coefficient of determination (R2) was > 0.90, 2) the intercept did not differ from 0 (P > 0.05), and 3) the slope did not differ from 1 (P > 0.05)] at the 45-min continuous time sampling period compared to full observation period. Results from this study suggest that a 45-min continuous time sampling period would be necessary to accurately investigate piglet behavior during the acute pain sensitivity time post-castration when considering both maintenance and pain-associated behaviors.
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Comportamento Animal , Orquiectomia , Animais , Masculino , Orquiectomia/veterinária , Dor/veterinária , SuínosRESUMO
This study investigated the effects of partially substituting soybean meal (SBM) with incremental amount of urea on rumen fermentation, nutrient digestion, plasma metabolites, and growth performance in fattening lambs. Seventy fattening male lambs were sorted into two blocks according to body weight (BW) and assigned to one of five dietary treatments in a randomized block design: SBM at 170 g/kg dry matter (DM) or reduced SBM (40 g/kg DM) plus 0, 10, 20, or 30 g urea/kg DM. Compared with the lambs receiving the SBM diet, the lambs fed the reduced SBM diet plus urea had higher (p < 0.01) concentrations of ruminal ammonia, and the ruminal concentration of ammonia also increased linearly (p < 0.01) with the increasing urea supplementation. Linear and quadratic effects (p < 0.01) on the crude protein (CP) intake and digestibility were observed with the increasing urea addition to the diet. The concentrations of plasma ammonia and blood urea nitrogen (BUN) increased (linear, p < 0.01; quadratic, p < 0.01) with the increasing urea supplementation. The final BW, DM intake (DMI), average daily gain (ADG), and gain efficiency were similar (p ≥ 0.42) between the SBM group and the urea-supplemented groups. However, the DMI and ADG increased quadratically (p ≤ 0.03) with the increasing urea addition to the diet, with the 10 g urea/kg DM diet resulting in the highest DMI and ADG. The results of this study demonstrated that 10 g urea could substitute 130 g soybean meal per kg feed DM without any adverse effect on growth performance or health in fattening lambs when fed a high concentrate diet.
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This study investigated the effects of dietary protein sources and nisin on rumen fermentation, nutrient digestion, plasma metabolites, N utilization, and growth performance in growing lambs. Thirty-two male Hu lambs (23 ± 2 kg initial BW) were assigned to four dietary treatments in a randomized block design with a 2 × 2 factorial arrangement. Two protein sources, soybean meal (SBM) and dried distillers grains with solubles (DDGS), and two levels of nisin, 0 and 30.5 mg of nisin/kg of feed, were used to formulate four isonitrogenous and isoenergetic diets. No interaction (P ≥ 0.16) of protein × nisin was found except on apparent digestibility of DM, OM, NDF, and ADF (P ≤ 0.02). Lambs receiving DDGS had lower (P ≤ 0.04) concentrations of ruminal acetate and butyrate, but propionate concentrations did not differ (P = 0.39), compared with those fed SBM, leading to a trend for reduced total VFA concentration (P = 0.07). Ruminal NH3-N and total branched-chain VFA concentrations were lower (P ≤ 0.01) in the lambs fed DDGS than in those fed SBM. The DDGS-fed lambs had less (P < 0.01) CP, but greater (P < 0.01) ether extract apparent digestibility than those fed SBM. For plasma metabolites, only blood urea N and albumin concentrations were lower in the DDGS-fed lambs (P < 0.01) than in those fed SBM. Nitrogen excretion pathway was altered when DDGS replaced SBM, with fecal N excretion (% of N intake) being greater (P < 0.01), while urinary N excretion (% of N intake) tending to be less (P = 0.06) from the DDGS-fed lambs than those fed SBM. Protein sources affected growth performance in an age/time-dependent manner. From weeks 1 to 4, DDGS resulted in less (P = 0.03) DMI and ADG than SBM. From weeks 5 to 8, DDGS did not affect (P ≥ 0.23) DMI or ADG but resulted in a greater (P = 0.04) G:F than SBM. Final BW did not differ (P = 0.58) duo to protein source. Providing nisin had no impact on DMI (P = 0.44), ADG (P = 0.84), or G:F (P = 0.73). Nisin addition only affected plasma uric acid concentration (P = 0.04). It was concluded that DDGS could substitute for SBM as a nitrogen source to growing Hu lambs to reduce N excretion via urine without adverse effects on animal performance, but nisin supplementation probably had no additional benefits.
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Proteínas Alimentares/farmacologia , Nisina/farmacologia , Nitrogênio/metabolismo , Ovinos/fisiologia , Ração Animal/análise , Animais , Análise Química do Sangue/veterinária , Nitrogênio da Ureia Sanguínea , Dieta/veterinária , Digestão/efeitos dos fármacos , Fermentação , Masculino , Rúmen/efeitos dos fármacos , Rúmen/metabolismo , Ovinos/sangue , Ovinos/crescimento & desenvolvimento , Glycine maxRESUMO
Cyanobacteria have the potential to produce bulk and fine chemicals and members belonging to Nostoc sp. have received particular attention due to their relatively fast growth rate and the relative ease with which they can be harvested. Nostoc punctiforme is an aerobic, motile, Gram-negative, filamentous cyanobacterium that has been studied intensively to enhance our understanding of microbial carbon and nitrogen fixation. The genome of the type strain N. punctiforme ATCC 29133 was sequenced in 2001 and the scientific community has used these genome data extensively since then. Advances in bioinformatics tools for sequence annotation and the importance of this organism prompted us to resequence and reanalyze its genome and to make both, the initial and improved annotation, available to the scientific community. The new draft genome has a total size of 9.1 Mbp and consists of 65 contiguous pieces of DNA with a GC content of 41.38% and 7664 protein-coding genes. Furthermore, the resequenced genome is slightly (5152 bp) larger and contains 987 more genes with functional prediction when compared to the previously published version. We deposited the annotation of both genomes in the Department of Energy's IMG database to facilitate easy genome exploration by the scientific community without the need of in-depth bioinformatics skills. We expect that an facilitated access and ability to search the N. punctiforme ATCC 29133 for genes of interest will significantly facilitate metabolic engineering and genome prospecting efforts and ultimately the synthesis of biofuels and natural products from this keystone organism and closely related cyanobacteria.
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Mitochondrial DNA (mtDNA) copy number has been utilized as a measure of sperm quality in several species including mice, dogs, and humans, and has been suggested as a potential biomarker of fertility in stallion sperm. The results of the present study extend this recent discovery using sperm samples from American Quarter Horse stallions of varying age. By determining copy number of three mitochondrial genes, cytochrome b (CYTB), NADH dehydrogenase 1 (ND1) and NADH dehydrogenase 4 (ND4), instead of a single gene, we demonstrate an improved understanding of mtDNA fate in stallion sperm mitochondria following spermatogenesis. Sperm samples from 37 stallions ranging from 3 to 24 years old were collected at four breeding ranches in north and central Texas during the 2015 breeding season. Samples were analyzed for sperm motion characteristics, nuclear DNA denaturability and mtDNA copy number. Mitochondrial DNA content in individual sperm was determined by real-time qPCR and normalized with a single copy nuclear gene, Beta actin. Exploratory correlation analysis revealed that total motility was negatively correlated with CYTB copy number and sperm chromatin structure. Stallion age did not have a significant effect on copy number for any of the genes. Copy number differences existed between the three genes with CYTB having the greatest number of copies (20.6 ± 1.2 copies, range: 6.0 to 41.1) followed by ND4 (15.5 ± 0.8 copies, range: 6.7 to 27.8) and finally ND1 (12.0 ± 1.0 copies, range: 0.4 to 26.6) (P < 0.05). Varying copy number across mitochondrial genes is likely to be a result of mtDNA fragmentation and degradation since downregulation of sperm mtDNA occurs during spermatogenesis and may be important for normal sperm function. Beta regression analysis suggested that for every unit increase in mtDNA copy number of CYTB, there was a 4% decrease in the odds of sperm movement (P = 0.001). Influential analysis suggested that results are robust and not highly influenced by data from individual stallions despite the low number of stallions sampled with low sperm motility. Further genome sequencing is necessary to investigate if mutations or deletions are the underlying causes of inconsistent copy numbers across mitochondrial genes. In conclusion, we show, for the first time, that increased mtDNA copy number is associated with decreased total sperm motility in stallions. We therefore suggest that mtDNA copy number may be an indicator of defective spermatogenesis in stallions.
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Variações do Número de Cópias de DNA , DNA Mitocondrial , Cavalos/genética , Análise do Sêmen/veterinária , Espermatozoides/fisiologia , Animais , Masculino , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Análise de Regressão , Motilidade dos Espermatozoides/genéticaRESUMO
SUMMARY: The use and importance of cone beam computed tomography (CBCT) in the diagnostic, treatment and long term follow up of odontogenic tumours, as well as one reconstruction and dental implants rehabilitation is reported. This clinical series shows diagnosis of odontogenic tumors using selected and used CBCT for initial diagnosis, morphological characterization, and follow up for 5 to 10 years. The CBCTs showed the size and form of the tumor and the follow up showed a satisfactory remodelling of bone and the success in the rehabilition with dental implants. No signs of recurrence were observed. The conventional radiographies, Fan Beam CT, Cone Beam CT and Magnetic Resonance Imaging (MRI) are discussed in the use for follow up of odontogenic tumors. It is concluded that CBCT is an efficient tool for diagnosis, follow up and assessment of the morphology and size of the tumor in order to achieve the best treatment plan, returning the functional conditions to the patients.
RESUMEN: Se reporta el uso y la importancia de la tomografía computarizada de haz cónico (CBCT) en el diagnóstico, tratamiento y seguimiento a largo plazo de tumores odontogénicos, tal como en una reconstrucción y rehabilitación de implantes dentales. Esta serie clínica muestra el diagnóstico de tumores odontogénicos utilizando CBCT seleccionados y usados para el diagnóstico inicial, caracterización morfológica y seguimiento durante 5 a 10 años. Los CBCT mostraron el tamaño y la forma del tumor y el seguimiento mostró un remodelamiento óseo satisfactorio y el éxito de la rehabilitación con implantes dentales. No se observaron signos de recurrencia. Las radiografías convencionales, el uso de TAC, TAC de haz cónico y resonancia magnética nuclear (RMN) se consideran para el seguimiento de tumores odontogénicos. Se concluye que CBCT es una herramienta eficaz en el diagnóstico y seguimiento a largo plazo para evaluar la morfología del tumor y de su tamaño, y además, para obtener los mejores resultados en el tratamiento y eventuales condiciones funcionales de los pacientes.
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Humanos , Masculino , Feminino , Adolescente , Pessoa de Meia-Idade , Tumores Odontogênicos/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico , Radiografia Panorâmica , Tumores Odontogênicos/reabilitação , Implantes Dentários , Seguimentos , Imageamento Tridimensional , Tratamento ConservadorRESUMO
BACKGROUND: Hematologic and biochemical reference intervals depend on many factors, including age. A review of the literature highlights the lack of reference intervals for 6-wk-old specific pathogen free (SPF) Hampshire-Yorkshire crossbred pigs. For translational research, 6-wk-old pigs represent an important animal model for both human juvenile colitis and diabetes mellitus type 2 given the similarities between the porcine and human gastrointestinal maturation process. The aim of this study was to determine reference intervals for hematological and biochemical parameters in healthy 6-wk-old crossbred pigs. Blood samples were collected from 66 clinically healthy Hampshire-Yorkshire pigs. The pigs were 6 wks old, represented both sexes, and were housed in a SPF facility. Automated hematological and biochemical analysis were performed using an ADVIA 120 Hematology System and a Cobas 6000 C501 Clinical Chemistry Analyzer. RESULTS: Reference intervals were calculated using both parametric and nonparametric methods. The mean, median, minimum, and maximum values were calculated. CONCLUSION: As pigs are used more frequently as medical models of human disease, having reference intervals for commonly measured hematological and biochemical parameters in 6-wk-old pigs will be useful. The reference intervals calculated in this study will aid in the diagnosis and monitoring of both naturally occurring and experimentally induced disease. In comparison to published reference intervals for older non SPF pigs, notable differences in leukocyte populations, and in levels of sodium, potassium, glucose, protein, and alkaline phosphatase were observed.