IMPROVING DETECTION AND TREATMENT OF SUB-CLINICAL KETOSIS IN DAIRY COWS

• Sponsoring Institution: National Institute of Food and Agriculture
• Project Status: COMPLETE
• Funding Source: AFRI COMPETITIVE GRANT
• Reporting Frequency: Annual
• Accession No.: 1006077
• Grant No.: 2015-67028-23572
• Cumulative Award Amt.: $149,922.00
• Proposal No.: 2014-09656
• Project Start Date: Jun 1, 2015
• Project End Date: May 31, 2018
• Grant Year: 2015
• Program Code: [A1701]- Critical Agricultural Research and Extension: CARE

Recipient Organization
UNIV OF WISCONSIN
21 N PARK ST STE 6401
MADISON,WI 53715-1218

Performing Department
DAIRY SCIENCE

Non Technical Summary
Sub-clinical ketosis (SCK) is a metabolic disease that occurs at the beginning of the lactation period 40 to 60% of dairy cows, and negatively impacts milk production and animal health. The overall goal of the proposed research is to develop and validate practical tools for use by producers to aid in identification and treatment of SCK. We will take a two-fold approach to this goal. First, we will collect blood (to determine SCK diagnosis) and milk samples from 500 cows within 5 to 20 days of the start of lactation and collect cow data that the farm typically collects. We will use these samples to derive a set of regression equations that will allow us to predict SCK from milk data which will provide a low-labor means of detection. We will also analyze genotypes for all cows to identify genetic markers associated with SCK phenotype risk. As a growing percentage of the dairy cows in the US are genotyped, this will provide markers that can be used to identify cows predisposed to SCK onset and can thus influence management and pre-treatment protocols for those cows.The other aspect of this project is an extension program that will focus on disseminating current knowledge regarding SCK etiology, detection, and treatment to producers, veterinarians, and nutritionists. This will be done through face-to-face seminars and webinars. We will also conduct farm visits with farms that would like to implement a detection protocol. During the visit, we will meet with the producer, herdsman, nutritionist, and veterinarian, provide them with a "start-up kit" that includes the tools necessary to detect SCK, and assist them in adapting a detection protocol to their specific farm. As the project progresses, we will incorporate the research findings into the seminars, webinars, and visits.

Animal Health Component

100%

Research Effort Categories

Basic

(N/A)

Applied

100%

Developmental

(N/A)

Classification

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
311	3410	1010	75%
304	3410	1080	25%

Knowledge Area
311 - Animal Diseases; 304 - Animal Genome;

Subject Of Investigation
3410 - Dairy cattle, live animal;

Field Of Science
1010 - Nutrition and metabolism; 1080 - Genetics;

Keywords

dairy cattle

ketosis

Goals / Objectives
The goals of this project are to: 1. Develop and validate a sub-clinical ketosis (SCK) predictor index using (a.) milk BHBA and acetone concentrations determined during milk testing and (b.) genetic risk scores correlated with SCK incidence.2.Design and execute an extension program that (a.) disseminates recent research on individual cow detection and treatment protocols, as well as, ongoing research on pen and herd level SCK management and detection tools and (b.) aids dairy producers in updating testing and treatment protocols on-farm.

Project Methods
Specific Aim #1: Develop and validate a SCK predictor index using (a.) milk BHBA and acetone concentrations determined during milk testing and (b.) genetic risk scores correlated with SCK incidence. Under specific aim 1a, repeated blood samples will be collected from 500 cows at commercial dairy farms to determine the incidence of SCK. Our collaborative group has been performing SCK testing at more than 10 dairy herds and has an ongoing relationship with these herds. At each farm, blood and milk sampling will be conducted twice a week after morning milking, during morning feeding. Blood samples will be collected for blood BHBA concentrations at four timepoints between 4 and 17 DIM for each cow. Blood samples will be collected via venipuncture of the coccygeal vein or artery into evacuated tubes (Becton Dickinson, Franklin Lakes, NJ). Determination of blood BHBA cowside will be by Precision Xtra meter (Abbott Laboratories, Abbott Park, IL) using blood (100 μL) from the evacuated tube. Use of the cowside test will allow for same-day feedback of information regarding SCK status to the producer.Milk samples will be collected in the parlor on the day of each blood sample (within 4 h of blood testing) for quantification of milk components and milk BHBA and acetone by Foss FTIR analysis (AgSource Cooperative Services, Verona, WI). Herd DairyComp 305 records and individual cow health and treatment records will also be collected. While there is variation in the consistency and accuracy of recorded data in DairyComp 305 across farms, the data still presents a useful insight into possible risk factors and impacts of SCK. Objective data (parity, calving date, pregnancy confirmed by veterinarian, services to conception, etc.) will be considered reliable inputs into the regression models. These datapoints will be included in the inital regression model. Subjective and less consistently recorded information, such as health events, calf body weight, DA (with or without veterinarian confirmation), presence of dystocia, etc. will be included in the regression model with caution through inclusion into a secondary model.Correlations between laboratory blood BHBA and milk BHBA acetone during the testing period will be determined (PROC CORR, SAS 9.3) to ensure that the sensitivity of the cowside meter is maintained throughout the testing period. A stepwise regression model (PROC REG, SAS 9.3) will be used to determine the best set of variables for prediction of blood BHBA using input variables of milk BHBA, acetone, fat, and protein from milk test, as well as parity, DIM, previous lactation milk production, length of previous lactation, days dry, days calf carried, presence of dystocia or other fresh cow disorders, and age at first calving. Regression equations will be used to generate a ketosis predictor for use in herd and pen level management. Specific aim 1b will utilize genomic data from cows tested in aim 1a to determine genetic risk scores that correlate with SCK risk. In addition to the blood and milk samples, a hair sample will be collected for genotyping (Genex, Verona, WI). Low-density genotypes (19K SNP chip) will be analyzed against SCK status, as a continuous variable (blood BHBA concentration) and a categorical variable (healthy, sub-clinical ketosis, ketosis), to determine loci associated with SCK. These genetic risk scores can then be used to identify animals that are at increased risk for developing SCK.Specific Aim #2: Design and execute an extension program that (a.) disseminates recent research on individual cow detection and treatment protocols as well as ongoing research on pen and herd level SCK management and detection tools and (b.) aids dairy producers in updating testing and treatment protocols on-farm.Throughout the study, extension programs (specific aim 2a) will take a two-fold approach. First, traditional in-person seminars will be offered, in conjunction with PDPW, other University Extension programs, and AgSource Cooperative Services. These face-to-face opportunities are a valuable venue to present information regarding the recent research regarding SCK etiology, detection, and treatment and later, the results of the current proposed research including milk ketone testing, genomic contributions, and the SCK Predictor Index. These seminars will target producers, nutritionists, veterinarians, and consultants, as those are the individuals that contribute to SCK management, detection, and treatment on-farm. We will also offer seminars in webinar venue through PDPW and Dairy Extension. Webinars offer a more flexible option for professionals that cannot travel within specific timeframes and provide the opportunity to watch (or re-watch) the seminar at later dates.. The PDPW is a producer-led organization that strives to help producers succeed. Although PDPW started in Wisconsin, members now come from 18 different states, 1,600 farms, and represent every type and size of dairy operation, all with one common goal: to continue learning and improving. World Class Webinars are open to producers, nutritionists, veterinarians, and consultants across the country. Each webinar typically has 45 computers registered for the "live" presentation and then countless views of the archived webinar. We will also be working with eXtension: America's Research-based Learning Network. Spanning producers and professionals across the country, eXtension packages with research-based information in all areas of Cooperative Extension will be made available in articles and webinars.As a key stakeholder group in this project, AgSource Cooperative Services will also be integrally involved with disseminating the outcomes of this research to their clients. AgSource Cooperative Services has a comprehensive mechanism for communicating with their members to relay new tools and research findings. Currently, AgSource Cooperative Services has 3,659 member producers in their milk testing program. All of which serve as individual stakeholders in this research and have been involved in the ongoing research, either directly (by allowing on-farm testing) or indirectly (by allowing access to milk testing results and DairyComp305 data). The farms involved in the preliminary and proposed research are industry-leaders and are influential on other regional farms. In order to quickly get information back to the producers involved in the project, we will hold additional seminars for participating farms and AgSource Cooperative members throughout the project. Specific aim 2b involves a more applied benefit to stakeholders. During outreach programs under specific aim 2a, we will collect information regarding farms that are interested in having on-farm instruction on SCK testing and treatment. Producers, with their nutritionists, consultants, or veterinarians, who would like to learn more about testing and treating SCK will be able to enroll in specific aim 2b, which will involve visits to individual farms. Under this aim, we will prepare twenty SCK testing and treatment kits which will include a Precision Xtra meter, a startup quantity of 100 BHBA strips, blood drawing supplies, and a propylene glycol administration equipment which we will provide to the producer. We will also bring a testing protocol and aid in tailoring the protocol to fit the needs of the farm during the visit. These visits will be done primarily by Drs. Oetzel and White, who are doing similar outreach through their veterinary and research programs, respectively. These individual farm visits will specifically address how to reduce incidence of SCK, early detection, and recommended treatment. We will also discuss how data from milk tests and (once available) the SCK Predictor Index can be used in decision-making and management. This aim will allow for ground-level dissemination of how to apply the recent and on-going research.

Progress 06/01/15 to 05/31/18

Outputs
Target Audience:The target audiences during this period were dairy cattle producers, herdsmen, nutritionists, and veterinarians. We targeted researchers through scientific presentations. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Graduate students have been very involved in this research. Training opportunities have included learning to collect the samples, organize and analyze data within large sample sets, statistical analysis, and summary of the data. One graduate student has become very versed in GWAS methodology through working with Drs. White and Weigel (PD and co-PD) and a postdoctoral fellow in Weigel's laboratory group. Professional development opportunities for these students have included the opportunity to write research abstracts that have been accepted for presentation at scientific meetings, as well as the opportunity to present extension-type talks to producer groups. Additionally, during the individual farm visits, we take graduate students and veterinary students (not just the student working directly on the grant) so that they are exposed to different farm systems and can see what goes into an on-farm consulting evaluation. We go through the farm information, dairy herd improvement reports, and diets with the students prior to the visit and challenge them to troubleshoot and identify potential concerns based on the data. We then involve them in the discussions with the management team during the visit and have them contribute to the summary that we later provide the farm. This is a great opportunity for students as many of the students involved would not have had this type of experience otherwise. During this past year, we have also been able to continue involving undergraduate students in the sample analysis. Most notably, two students were involved while in their senior year of undergraduate program and are now continuing onto graduate and veterinary schools where they will be able to apply the skills and knowledge learned from this research. How have the results been disseminated to communities of interest?Results have been disseminated through oral presentations to producer/nutritionist/veterinarian audiences through outreach talks and during individual farm visits (detailed in the other products section). Additionally, two abstracts have been accepted for presentation at the ADSA meetings during the summer of 2018, which allowed for communication of results to the scientific community. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Sub-clinical ketosis (SCK) is associated with an impaired transition to the lactation period, occurs in 15 to 60% of dairy cows, and negatively impacts milk production and animal health. The overall goal of the research is to develop and validate practical tools for use by producers to aid in identification and treatment of SCK. The anticipated short-term impacts of this project are to improve awareness to the negative impacts and risks for subclinical ketosis (SCK), improve knowledge about detection and treatment of SCK, and to development new low-labor detection tools. At the end of one year of this grant, we have made great strides to achieve these short-term impacts, as discussed below. The medium-term impacts are to improve management to reduce SCK, implement use of new low-labor tools for SCK detection, and to improve SCK detection and treatment. The long-term impacts are to decrease SCK incidence in the US through improved management, decrease negative impacts of SCK through quicker detection and treatment, and improve animal health and longevity. Within the third/final year, we worked to achieve progress under both goals of the project. 1. To develop and validate a SCK predictor index using (a) milk BHBA and acetone concentrations determined during milk testing and (b.) genetic risk scores correlated with SCK incidence. Under this goal, we used advanced modeling techniques to publish a paper with prediction models for determining SCK from milk samples based on the abstract presented last year. We have sampled additional cows to add to the genetic analysis and have completed a genome-wide association study. A manuscript of this work is being prepared now. Changes in knowledge have occurred through analysis of this large, comprehensive sample set that was previously not available. 2. Design and execute an extension program that disseminates recent research on individual cow detection and treatment protocols and aids dairy producers in updating testing and treatment protocols on-farm. Extensive accomplishments have been achieved under the extension goal again in the second year. The extension component of this grant maximizes the collaborative team which includes extension specialists and a dairy herd improvement cooperative (AgSource) to reach more audiences. Conveying the most current information to producers, nutritionists, and veterinarians was the first part of this goal and began immediately since it included propagating information and best-practices that were already established prior to this grant. Tools that were established by the team prior to the grant included individual cow blood detection protocols, treatment protocols for SCK and clinical ketosis, management and nutritional suggestions to reduce SCK prevalence, and the use of the KetoMonitor to monitor herd SCK prevalence. The team has worked to pass this information on to the target audiences through talks, farm visits, and meetings with nutrition/veterinarian/ consultant groups. Several farm visits have been made by the collaborative team to help specific farms that are seeking assistance with high SCK prevalence. These visits are more in depth (~4 hours) and involve a walk through, assistance with ration and management concerns, recommendations on updating detection and treatment protocols, etc. Changes in action have occurred as many farms have updated their detection and treatment protocols, as well as making management and nutrition changes to lower SCK prevalence.

Publications

• Type: Conference Papers and Presentations Status: Published Year Published: 2018 Citation: Fourdraine, R. The Future of Milk-Based Diagnostics  Part 2. Cooperative Resources International Annual Meeting. January 2018.
• Type: Other Status: Published Year Published: 2018 Citation: AgSource Recaps Successful Year. Press Release. March 13, 2018. AgSource, Cooperative Resources International.
• Type: Journal Articles Status: Published Year Published: 2018 Citation: Pralle, R. S., K. W. Weigel, and H. M. White. 2018. Predicting blood beta-hydroxybutyrate using milk Fourier transform infrared spectrum, milk composition, and producer-reported variables with multiple linear regression, partial least squares regression, and artificial neural network. J. Dairy Sci. 101:4378-4387.
• Type: Conference Papers and Presentations Status: Published Year Published: 2017 Citation: Oetzel, G. Update on ketosis management in dairy herds. Veterinarian's Role in the Dairy Fresh Pen, Pre-Convention Seminar at the 50th Annual Meeting of the American Association of Bovine Practitioners, Omaha, NE, September, 2017.
• Type: Conference Papers and Presentations Status: Published Year Published: 2017 Citation: Oetzel, G. Evaluating the diagnosis and treatment of ketosis in a dairy herd. Veterinarian's Role in the Dairy Fresh Pen, Pre-Convention Seminar at the 50th Annual Meeting of the American Association of Bovine Practitioners, Omaha, NE, September, 2017.
• Type: Conference Papers and Presentations Status: Published Year Published: 2017 Citation: Oetzel, Gary. Fresh cow metabolic diseases: Old myths and new data. Dairy Split Session at the 50th Annual Meeting of the American Association of Bovine Practitioners. Omaha, NE, September, 2017.

Progress 06/01/16 to 05/31/17

Outputs
Target Audience:The target audiences during this period were dairy cattle producers, herdsmen, nutritionists, and veterinarians. We also targeted researchers through scientific presentations. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Graduate students have been very involved in this research. Training opportunities have included learning to collect the samples, organize and analyze data within large sample sets, statistical analysis, and summary of the data. Professional development opportunities for these students have included the opportunity to write research abstracts that have been accepted for presentation at scientific meetings, as well as the opportunity to present extension-type talks to producer groups. Additionally, during the individual farm visits, we take graduate students and veterinary students (not just the student working directly on the grant) so that they are exposed to different farm systems and can see what goes into an on-farm consulting evaluation. We go through the farm information, dairy herd improvement reports, and diets with the students prior to the visit and challenge them to troubleshoot and identify potential concerns based on the data. We then involve them in the visit and discussions with the management team during the visit and have them contribute to the summary that we later provide the farm. This isa great opportunity for students and we have had many involved that would not have this type of experience otherwise. During this past year, we have also been able to continue involving undergraduate students in the sample analysis. Most notably, two students were involved during their senior year of undergraduate program and are now continuing onto graduate and veterinary schools where they will be able to apply the skills and knowledge learned from this research. How have the results been disseminated to communities of interest?Results have been disseminated through oral presentations to producer/nutritionist/veterinarian audiences through outreach talks and during individual farm visits (detailed in the other products section). Additionally, two abstracts have been accepted for presentation at the ADSA meetings during the summer of 2017, which will allow for communication of results to the scientific community. What do you plan to do during the next reporting period to accomplish the goals?During the next year, we will continue working with the advanced ketosis prediction models (PLS, machine learning, etc.) to try to improve the predictive capacity of these models. We also plan to continue the outreach program.

Impacts
What was accomplished under these goals? Sub-clinical ketosis (SCK) is associated with an impaired transition to the lactation period, occurs in 15 to 60% of dairy cows, and negatively impacts milk production and animal health. The overall goal of the research is to develop and validate practical tools for use by producers to aid in identification and treatment of SCK. The anticipated short-term impacts of this project are to improve awareness to the negative impacts and risks for subclinical ketosis (SCK), improve knowledge about detection and treatment of SCK, and to development new low-labor detection tools. At the end of one year of this grant, we have made great strides to achieve these short-term impacts, as discussed below. The medium-term impacts are to improve management to reduce SCK, implement use of new low-labor tools for SCK detection, and to improve SCK detection and treatment. The long-term impacts are to decrease SCK incidence in the US through improved management, decrease negative impacts of SCK through quicker detection and treatment, and improve animal health and longevity. Within the second year, we worked to achieve progress under both goals of the project. 1. To develop and validate a SCK predictor index using (a) milk BHBA and acetone concentrations determined during milk testing and (b.) genetic risk scores correlated with SCK incidence. Under this goal, we have completed sample collected and begun working with advanced modeling techniques. We have explored use of linear regression, partial least squares, and machine learning and have an accepted abstract on this research. We have also completed the genotyping and havesetup the initial genome wide association study.Changes in knowledge have occurred through analysis of this large, comprehensive sample set that was previously not available. 2. Design and execute an extension program that disseminates recent research on individual cow detection and treatment protocols and aids dairy producers in updating testing and treatment protocols on-farm. Extensive accomplishments have been achieved under the extension goal again in the second year. The extension component of this grant maximizes the collaborative team which includes extension specialists and a dairy herd improvement cooperative (AgSource) to reach more audiences. Conveying the most current information to producers, nutritionists, and veterinarians was the first part of this goal and began immediately since it included propagating information and best-practices that were already established prior to this grant. Tools that were established by the team prior to the grant included individual cow blood detection protocols, treatment protocols for SCK and clinical ketosis, management and nutritional suggestions to reduce SCK prevalence, and the use of the KetoMonitor to monitor herd SCK prevalence. The team has worked to pass this information on to the target audiences through talks, farm visits, and meetings with nutrition/veterinarian/ consultant groups. Several farm visits have been made by the collaborative team to help specific farms that are seeking assistance with high SCK prevalence. These visits are more in depth (~4 hours) and involve a walk through, assistance with ration and management concerns, recommendations on updating detection and treatment protocols, etc. Changes in action have occurred as many farms have updated their detection and treatment protocols, as well as making management and nutrition changes to lower SCK prevalence.

Publications

• Type: Journal Articles Status: Published Year Published: 2017 Citation: Weigel, K. A., R. S. Pralle, H. Adams, K. Cho, C. Do, and H. M. White. 2017. Prediction of whole genome risk for selection and management of hyperketonemia in Holstein dairy cattle. J. Anim. Breed. Genet. Accepted.
• Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Pralle, R. S., H. A. Adams, T. L. Chandler, and�H. M. White. 2016. Genomic markers associated with hyperketonemia in Jersey cows.� J. Dairy Sci. 99, Suppl.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2017 Citation: Pralle, R. S., K. A. Weigel, and�H. M. White.�2017.�Development and evaluation of hyperketonemia prediction models. ADSA submitted abstract.
• Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Coburn/AgSource was a speaker at the 40th Biennial Session of the International Committee on Animal Recording (ICAR) held in Puerto Varas, Chile. "Measuring the prevalence and impact of subclinical ketosis on lactation performance in US dairy herds."; http://www.icar.org/wp-content/uploads/2017/05/ICAR-Technical-Series-21-Puerto-Varas-2017-Proceedings.pdf
• Type: Conference Papers and Presentations Status: Published Year Published: 2017 Citation: Weigel, Kent. Genomic Selection for Healthy Dairy Cattle. Zoetis Dairy Wellness Conference (Milwaukee, Feb 24, 2017).
• Type: Conference Papers and Presentations Status: Published Year Published: 2017 Citation: Weigel, Kent. Genomic Selection for Healthy Dairy Cattle. National Mastitis Council Meeting (Tampa, Jan 31, 2017)
• Type: Conference Papers and Presentations Status: Published Year Published: 2017 Citation: Weigel, Kent. Genomic Selection for Healthy Dairy Cattle. DBA Dairy Strong Conference (Madison, Jan 11, 2017)
• Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: White, H. M. Nutritional Strategies to Improve Transition Cow Metabolic Health and Milk Production. Cargill Technical Exchange. Phoenix, AZ. January 2016.
• Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: White, H. M. Transition cow nutrition and hepatic metabolic health. Southwest Nutrition Conference. Phoenix, AZ. February 2016.
• Type: Other Status: Published Year Published: 2016 Citation: White, H. M. Transition Cow Nutrition: Optimizing liver metabolism to support milk production. Purina Nutrition Group. October 2016.
• Type: Conference Papers and Presentations Status: Published Year Published: 2017 Citation: White, H. M. Transition Cow Nutrition and Metabolic Health. Pacific Northwest Nutrition Conference. January 2017
• Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Oetzel, G. Ketosis in dairy cattle; Animal Health Worker Course, Module 2 (Transition Cow Health), Nestle Dairy Farming Institute Level 2 Course, Shuangcheng, China, 2016.
• Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Oetzel, G. Ketosis in dairy cattle (1 1/2 hrs). Veterinary Course, Module 2 (Transition Cow Health), Nestle Dairy Farming Institute Level 3 Course, Shuangcheng, China, 2016.
• Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Oetzel, G.Understanding and preventing ketosis (1 1/4 hrs). Formuleite IV Nutrition Conference, University of Lavras, Brazil, 2016.
• Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Oetzel, G. Diagnosing and monitoring ketosis in dairy herds (3/4 hr). Webinar presented by the national DAIReXNET extension program, 2016.
• Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Oetzel, G. Managing ketosis in dairy herds Part 1: Epidemiology and prevention (1 hr); Managing ketosis in dairy herds Part 2: Diagnosis and treatment (1 hr). Midwest Veterinary Conference, Columbus, OH, 2016.
• Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Oetzel, G. Ketosis in dairy herds (1 hr). Food Animal Medicine Student Symposium, The Ohio State University, Columbus, OH, 2016.
• Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Oetzel, G. High-risk fresh cows and BHB testing update (1 hr). Zoetis Dairy Veterinary Staff Training, Detroit, MI, 2016.
• Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Oetzel, G. Update on ketosis management in dairy herds (3/4 hr); Evaluating the diagnosis and treatment of ketosis (1/2 hr). Veterinarian's Role in the Dairy Fresh Pen, 49th Annual Meeting of the American Association of Bovine Practitioners, Charlotte, NC, 2016.

Progress 06/01/15 to 05/31/16

Outputs
Target Audience:The target audiences during this period were dairy cattleproducers, herdsmen, nutritionists, and veterinarians. We also targeted the field specialists and outreach specialists at AgSource Cooperative, a DHI cooperative. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Graduate students have been very involved in this research. Training opportunities have included learning to collect the samples, organize and analyze data within large sample sets, statistical analysis, and summary of the data.Professional development opportunities for these students have included the opportunity to write research abstracts that have been accepted for presentation at scientific meetings, as well as the opportunity to present extension-type talksto producer groups. Additionally, during the individual farm visits, we take graduate students and veterinary students (not just the student working directly on the grant)so that they are exposed to different farm systems and can see what goes into an on-farm consulting evaluation. We go through the farm information,dairy herd improvement reports, and diets with the students prior to the visit and challenge them to troubleshoot and identify potential concerns based on the data. We then involve them in the visit and discussions with the management team during the visit and have them contribute to the summary that we later provide the farm. This is a great opportunity for students and we have had many involved that would not have this type of experience otherwise. How have the results been disseminated to communities of interest?Results have been disseminated through oral presentations to producer/nutritionist/veterinarian audiences through outreach talks and during individualfarm visits (detailed in the other products section). Additionally, two abstracts have been accepted for presentation at the Joint Annual ASAS and ADSA meetings during the summer of 2016 which will allow for communication of results to the scientific community. What do you plan to do during the next reporting period to accomplish the goals?The next reporting period will include continued sample collection and genotyping, data analysis, prediction modeling, and genome wide association studies. We already collected samples from 2 farms and are currently collecting samples from cows at a third farm. Milk samples are analyzed immediately and serum samplesare stored for subsequent analysis. We also do a cowside BHBA diagnostic to determine if the cow has SCK that day. After all four samples are collected during the 16 day period after calving, the cow is given a diagnosis of "healthy" or "SCK". Data from the milk samples, blood samples, and farm data (milk production, other diseases, breeding, etc.) are compiled into the growing dataset for future analysis. Over the next year we will be employing multiple linear regression, partial least squares regression, Bayesian methods, and other statistical tools to develop individual cow SCK prediction tools. We are also compiling genotypes for all the cows in the project to run genome wide associate studies. If markers can be identified that are associated with SCK predisposition, those markers could be used by producers to identify cows that may develop SCK so that those cows can be pretreated or managed more specifically for improved metabolic health during the transition to lactation period. The extension component of the grant will continue to communicate current knowledge and when appropriate, will start to include the findings of the current research. We are continuing to do individual farm visits and are involving graduate students and veterinary students in these visits as a training opportunity. Students get to see how many different farms operate and the farm gets the benefit of many different eyes helping to identify challenges that can be improved. We will be presenting the first research findings as the upcoming scientific meetings.

Impacts
What was accomplished under these goals? Sub-clinical ketosis (SCK) is associated with an impaired transition to the lactation period, occurs in 15 to 60% of dairy cows, and negatively impacts milk production and animal health. The overall goal of the research is to develop and validate practical tools for use by producers to aid in identification and treatment of SCK.The anticipated short-termimpacts of this project are to improve awareness to the negative impacts and risks for subclinical ketosis (SCK), improve knowledge about detection and treatment of SCK, and to development new low-labor detection tools. At the end of one year of this grant, we have made great strides to achieve these short-term impacts, as discussed below. The medium-term impacts are to improve management to reduce SCK, implement use of new low-labor tools for SCK detection, and to improve SCK detection and treatment. The long-term impacts are to decrease SCK incidence in the US through improved management, decrease negative impacts of SCK through quicker detection and treatment, and improve animal health and longevity. Within the first year, we worked to achieve the short-term outcomes under both goals of the project. 1. To develop and validate a SCK predictor index using (a) milk BHBA and acetone concentrations determined during milk testing and (b.) genetic risk scores correlated with SCK incidence. Under this goal, we have collected repeat blood and milk samples, as well as hair samples for genotyping, and production and healthinformation from over 1000 cows. We have worked to assemble a linear regression prediction model to predict cows with SCK (by blood diagnosis) using only milk analysis and cow data. Thus far, these models are about 90% accurate at predicting herd prevalence of SCK but need further refinement to be used as an individual cow diagnostic tool. In order to improve the tool, we have been working to analyze raw milk FTIR spectral data with more advanced statistical models to improve the prediction of milk components such as BHBA and acetone. We have also been genotyping cows within the study and have setup the initial genome wide association study. Genetic analysis cannot be completed until all sampling is completed. Changes in knowledge have occurred through analysis of this large, comprehensive sampleset that was previously not available. 2. Design and execute an extension program that disseminates recent research on individual cow detection and treatment protocols and aids dairy producers in updating testing and treatment protocols on-farm. Extensive accomplishments have been achieved under the extension goal. The extension component of this grant maximizes thecollaborative team which includes extension specialists and a dairy herd improvement cooperative (AgSource) to reach more audiences. Conveying the most current information to producers, nutritionists, and veterinarians was the first part of this goal and began immediately since it included propagating information and best-practices that were already established prior to this grant. Tools that were established by the team prior to the grant included individual cow blood detection protocols, treatment protocols for SCK and clinical ketosis, management and nutritional suggestions to reduce SCK prevalence, and the use of the KetoMonitor to monitor herd SCK prevalence. The team has worked to pass this information on to the target audiences through talks, farm visits, andmeetings with nutrition/veterinarian/consultant groups. Several farm visits have been made by the collaborative team to help specific farms that are seeking assistance with high SCK prevalence. These visits are more in depth (~4 hours) and involve a walk through, assistance with ration and management concerns, recommendations on updating detection and treatment protocols, etc. Changes in action have occurred as many farms have updated their detection and treatment protocols, as well as making management and nutrition changes to lower SCK prevalence.

Publications

• Type: Conference Papers and Presentations Status: Accepted Year Published: 2015 Citation: Kent Weigel. Management and genetic tools to reduce clinical and subclinical ketosis on dairy farms. National Institute of Animal Science, Rural Development Administration, Cheonan, Korea, April 29, 2015.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2015 Citation: Heather White. Using the KetoMonitor to access cow and milk data to manage herd-level ketosis prevalence. Four-State Nutrition Conference. Dubuque, IA. June 2015.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2015 Citation: Heather White. Integrating ketosis tools into a progressive dairy nutrition program. Purina Animal Nutrition. Madison, WI. September 2015.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2015 Citation: Heather White. Transition Cow Health: Meeting the demands of lactation while maintaining a healthy liver. Dairy Short Course, German Farmers. Madison, WI. September 2015.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2015 Citation: Kent Weigel and Tawny Chandler. Genex Dairy Genetics Conference. September 24, 2015. Verona, WI (video conference).
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2016 Citation: Heather White. Integrating Ketosis Tools to Improve Disease Detection, Treatment, and Prevention. Purina/Land OLakes Leading Dairy Producers Conference. Wisconsin Dells, WI. January 2016.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2016 Citation: Heather White. Integrating Ketosis Tools to Improve Ketosis Management on Dairy Farms. Ag. Consulting Team, Inc., Regional Producer Meeting. Prairie du Sac, WI. March, 2016.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2016 Citation: Ryan Pralle and Randy Shaver. Ag. Consulting Team, Inc., Regional Producer Meeting. Kimberly, WI. April, 2016.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2015 Citation: Gary Oetzel. Ketosis in dairy cows: Latest research. Transition Cow Management Seminar, Jackson and Trempealeau County UW-Extension, Blair WI and Hixton WI, 2015.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2015 Citation: Gary Oetzel. Evaluating overall fresh pen management. Veterinarian's Role in the Dairy Fresh Pen, 48th Annual Meeting of the American Association of Bovine Practitioners, New Orleans, LA, September, 2015.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2015 Citation: Gary Oetzel. Update on ketosis management in dairy herds Veterinarian's Role in the Dairy Fresh Pen, 48th Annual Meeting of the American Association of Bovine Practitioners, New Orleans, LA, September, 2015.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2015 Citation: Gary Oetzel. Evaluating the diagnosis and treatment of ketosis. Veterinarian's Role in the Dairy Fresh Pen, 48th Annual Meeting of the American Association of Bovine Practitioners, New Orleans, LA, September, 2015.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2015 Citation: Gary Oetzel. Integrating herd fresh pen data and making recommendations. Veterinarian's Role in the Dairy Fresh Pen, 48th Annual Meeting of the American Association of Bovine Practitioners, New Orleans, LA, September, 2015.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2015 Citation: Gary Oetzel. Key transition cow issues and ketosis in dairy herds. Applied Dairy Nutrition and Problem Solving Seminar and Proceedings, 48th Annual Meeting of the American Association of Bovine Practitioners, New Orleans, LA, September 2015.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2015 Citation: Robert Fourdraine. Managing ketosis in dairy herds: Part 1 - Epidemiology and prevention; Managing ketosis in dairy herds: Part 2  Diagnosis and treatment. Included proceedings. Canadian Veterinary Medical Association Convention, Calgary, Canada, July 2015.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2015 Citation: Robert Fourdraine. Transition cow health: Tools for your toolbox. Included proceedings. Agger Bovine Seminar, Haarby, Denmark, May 2015.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2016 Citation: Gary Oetzel. Diagnosing and Monitoring Ketosis in Dairy Herds. DAIReXNET webinar presentation open to anyone (producers, veterinarians, extension personnel, etc.). January 2016.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2015 Citation: Gary Oetzel. Preventing and understanding hypocalcaemia and ketosis in dairy herds. Included proceedings. Professional Dairy Producers of Wisconsin Transition Cow Conference, Appleton, Fennimore, and Eau Claire, WI, 2015.