YTCAF Donor Program

You can make a memorial to remember a very special friend or special pet or you can honor someone or their accomplishments or just make a donation via our donor program.  You can:

  • Make a donation by check or money order, using this form, mailed to our Treasurer at:
    Gloria Lyon, Treasurer
    YTCA Foundation
    526 N West Avenue PMB 46
    Arlington, WA 98223
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2009 Research Funded by YTCAF


Each year the AKC Canine Health Foundation send the YTCA Foundation a list of grant requests for funding that they have screened and think would be of interest to breeders and owners of Yorkshire Terriers as well as dog fanciers in general. As an independent entity spun off from the Parent club to preserve our tax exempt status, the YTCAF receives no financial support from the YTCA's participating in efforts such as the Purina Circles program. Instead all of our funding comes from memorials made by individual donors and fund raising efforts such as the online auctions and breeding calendar sales. 

The Board members carefully consider these factors in each of the requests in order to optimize research dollars:

  1. Potential of the research to benefit Yorkshire Terriers in particular and all dogs in general.

  2. Previous research success of the primary investigators

  3. Use of the grant project to help veterinary students, new veterinarians and academicians get started in their chosen field of research (Acorn projects).

The Board voted to support the following CHF grants for 2009.

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MAF* Grant D08CA-001 Genetics of Portosystemic Vascular Anomalies and Microvascular Dysplasia in Small Breed Dogs

$3,000

Cornell University
Sharon A. Center, DVM, DiplACVIM

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Project Abstract

Small, purebred terrier-type dogs are at risk of developing two genetically related disorders that cause abnormal liver functions. These disorders, known as portosystemic vascular anomalies (PSVA) and microvascular dysplasia (MVD), can occur either alone or in combination. Dogs with PSVA suffer from the liver's inability to remove toxins from food and many are overtly ill, while dogs with MVD may only demonstrate intolerance to standard drug dosages. The researchers hope to identify genetic markers for these disorders and use these markers to develop a test for detecting at-risk dogs. This test would help breeders eliminate these disorders from affected breeds.

UPDATE 12-08-2014

RESULTS: Researchers Identify Potential Breed-Specific Genetic Regions for Inherited Liver Disorders in Small-Breed Dogs

Portosystemic vascular anomalies (PSVAs) and microvascular dysplasia (MVD) are related inherited disorders that compromise the way the liver filters blood; specifically, blood returning from the intestine bypasses the liver. When blood is not processed by the liver, substances reach the general circulation that can be detrimental to other organs. In addition, when the blood supply is diverted around the liver, the liver does not develop normally, rendering it incapable of performing other normal functions, such as drug metabolism.

These conditions afflict a number of small purebred dogs, including such terrier breeds as Tibetan Spaniels, Cairn Terriers, Maltese, Yorkshire Terriers, Norfolk Terriers, Miniature Schnauzers and Papillons. Affected dogs may show mild to severe symptoms depending on the degree to which blood is bypassing the liver. Symptoms include poor growth, poor coat quality, lethargy, vomiting, diarrhea, seizures and even liver failure.

In search of genetic markers to help reduce the incidence of PSVA/MVD in dogs, Morris Animal Foundation funded researchers from Cornell University who compared DNA from PSVA-affected purebred dogs and their unaffected siblings. Using extensive genetic mapping strategies, they discovered that the PSVA/MVD syndrome is complex; that is, it results from more than one mutation and varies between breeds. Based on these findings, the development of a simple, one gene-based diagnostic test that can screen multiple breeds is unlikely. However, the research team did identify several breed-specific, disease-risk regions that house potential candidate genes (genes with known functions that may play a role in the disease process). In addition, there is a modest region overlap among some breeds. With further testing, these regions may prove useful in designing custom genetic tests for specific breeds and for identifying carrier dogs.

The researchers also found that a specific blood test measuring total serum bile acid concentrations should not be used as the sole screen to select healthy breeding partners. Some dogs carrying genetic determinants for PSVA/MVD have normal serum bile acid concentrations, so selection of breeding partners based only on total serum bile acid concentrations will not eliminate the birth of affected puppies.

Further study of the candidate genes within the breed-specific genetic regions identified in this study is ongoing and the research team hopes to find patterns of genetic variations that are associated with PSVA and MVD. Once these patterns are identified, findings will need to be verified in a larger population of dogs before a robust testing strategy can be developed. Understanding the complex genetics behind the development and progression of PSVA and MVS in specific breeds will help improve identification of carrier animals and reduce and/or eliminate the occurrence of these disorders in dogs.

UPDATE 3-5-2012

Portosystemic vascular anomalies (PSVAs) and microvascular dysplasia (MVD) are related genetic disorders where blood returning from the intestines bypasses the liver instead of being filtered through the liver. This disease is common in small terrier breeds where the prevalence ranges from 30 to 80 percent. To identify genetic mutations underlying PSVA and MVD, researchers from Cornell University, funded by Morris Animal Foundation, compared DNA from PSVA affected Cairn Terriers, Yorkshire Terriers, Tibetan Spaniels, and Norfolk Terriers, with their unaffected siblings. They found that PSVA/MVD syndrome is the result of more than one mutation. Using genetic mapping, the research team has tentatively identified several regions of interest which are common to several breeds, as well as a few breed-specific regions that are associated with PSVA/MVD. Since the last report, researchers have expanded their analysis to include a larger population of Cairn and Yorkshire Terriers afflicted with PSVA or MVD. Cairn Terriers are representative of breeds like Tibetan Spaniels and Miniature Schnauzers with lower genetic trait prevalence (approximately 30 to 35%); Yorkshire Terriers are representative of breeds like Norfolk Terriers, Maltese, Havanese and Papillon with high genetic trait prevalence (approximately 65 to 90%). Preliminary data from this expanded mapping has confirmed a common but expansive disease-risk region and has also identified several additional regions with potential candidate genes (genes with known functions that may play a role in the disease process). Once genetic mutations responsible for PSVA and MVD are identified, the investigators plan to develop genetic tests that can identify carrier animals. These tests could be used to make breeding decisions which could reduce and eventually eliminate the occurrence of these disorders. The study is providing a research associate and an assistant professor, both of whom are in the early stages of their scientific careers, with valuable training in veterinary molecular genetics and in the mapping of complex traits.

UPDATE May 2, 2011

Portosystemic vascular anomalies (PSVAs) and microvascular dysplasia (MVD) are related genetic disorders that cause abnormal liver circulation in small terrier breeds of dogs. The prevalence ranges from 30 to 80 percent. Many dogs with PSVA are overtly ill because the liver cannot remove toxins from the blood. Dogs with MVD, on the other hand, may only demonstrate intolerance to standard drug dosages. To identify genetic mutations underlying PSVA and MVD researchers from Cornell University prepared DNA from Cairn Terriers, Yorkshire Terriers, Tibetan Spaniels and Norfolk Terriers, including dogs severely affected with PSVA and matched unaffected sibling controls. They have completed genotyping of these samples, and findings suggest that PSVA/MVD syndrome is a complex trait (i.e., the result of more than one mutation). Genetic mapping has also tentatively identified several regions of interest, which are common to several breeds, on three separate chromosomes as well as a few breed-specific emerging single-nucleotide polymorphism (SNP haplotypes) in these and other chromosomes. SNP haplotypes are DNA segments containing closely linked variations that can be used to identify specific regions containing mutations associated with genetic disorders, investigators plan to expand the population studied to further clarify and possibly identify additional SNP haplotypes, and they will use these data to develop a testing strategy to detect gene carrier status. The investigators have also completed the sequencing of three candidate genes; however, none of these genes were found to be responsible for PSVA or MVD. Once genetic mutations responsible for these abnormalities are identified, the investigators plan to develop genetic tests that can identify carrier animals. These tests would be used to make breeding decisions that would reduce and eventually eliminate the occurrence of these liver disorders in these breeds. The study is also providing a research associate and an assistant professor, both of whom are in the early stages of their scientific careers, with valuable training in veterinary molecular genetics and in the mapping of complex traits.

UPDATE: May 12, 2010

Portosystemic vascular anomalies (PSVAs) and microvasculr dysplasia (MVD) are related genetic disorders that cause abnormal liver circulation in small terrier breeds of dogs. The prevalence ranges from 30 to 8- percents. Many dogs with PSVA are overtly ill because the liver cannot remove toxins from food. Dogs with MVD, on the other hand, may only demonstrate intolerance to standard drug dosages. In the first phase of the study, researchers from Cornell University prepared DNA from 44 Cairn Terriers (22 dogs affected with PSVA and 22 matched unaffected sibling controls) and 22 dogs (11 affected and 11 unaffected sibling controls) from four additional breeds - Yorkshire Terriers, Tibetan Spaniels, Maltese and Norfolk Terriers - for genotyping analysis. There have been some delays due to a robotic malfunction in the genomic analysis instrumentation, which required some DNA samples to be resubmitted for analysis. Using the incomplete data set, the researchers were able to identify four regions of interest on three different chromosomes.

Once the full data set becomes available later this summer, the researchers will begin fine-mapping these chromosomal regions in hopes of further narrowing the regions of interest. The investigators are also continuing their overlap analysis, comparing results of two different genomic analysis techniques on samples from affected and unaffected Cairn Terriers and Tibetan Spaniels. Candidate genes identified by overlap analysis will be sequenced to identify potential genetic mutations. To date, the investigators have completed the sequencing of three candidate genes; however, none of these genes was found to be responsible for PSVA or MVD. Once genetic mutations responsible for these abnormalities are identified, the investigators plan to develop affordable genetic tests that can identify carrier animals. These tests would be used to make breeding decisions that would reduce and eventually eliminate the occurence of these liver disorders in these breeds. The study is also providing a research associate and an assistant professor, both of whome are in the early stages of their scientific careers, with valuable training in veterinary molecular genetics and in the mapping of complex traits.

UPDATE: OCTOBER 27, 2009

Portosystemic vascular anomalies (PSVA) and microvascular dysplasia (MVD) are related genetic disorders that cause abnormal liver circulation in small terrier breeds of dogs. The prevalence ranges from 30 to 80 percent. Many dogs with PSVA are overtly ill because the liver cannot remove toxins from food. Dogs with MVD, on the other hand, may only demonstrate intolerance to standard drug dosages. In the first phase of the study, researchers from Cornell University prepared DNA from 44 Cairn Terriers and six additional breeds - Yorkshire Terrier, TIbetan Spaniels, Maltese, Norfolk Terriers, Miniature Schnauzers and Havanese - for genotyping analysis. Researchers hope to identify genetic markers for these disorders and then use the markers to develop an affordable genetic test that identifies carriers. This test would be a tool to reduce and eventually eliminate the occurence of these liver disorders. THe study is also providing a research associate and an assistant professor, both of whom are in the early stages of their scientific careers, with valuable training in veterinary molecular genetics and in the mapping of complex traits.

*MAF - Morris Animal Foundation

MAF Grant DO7CA-152 Real Time Polymerase Chain Reaction for Viral and Bacterial Acid Detection in Dogs with Meningioencephalitis

$3,000

University of Georgia
Scott Shatzberg, DVM PhD

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Project Abstract

This study focuses on canine brain inflammation of which two common types are granulomatous meningoencephalitis (GME) and necrotizing leukoencephalitis (NLE). This study focuses on the potential environmental factors that may contribute to the development of these disorders and specially are evaluating spinal fluid and nervous tissues for the presence of number pathogens (bacteria and viruses) that may "trigger" the development of either condition.

UPDATE February 11, 2011

Researchers from the University of Georgia used PCR to identify suspect microorganisms in canine meningoencephalitis. They identified and demonstrated two viruses that are nottypically considered to be pathogens in dogs, La Crosse virus and Merkel cel carcinoma virus, and determined that La Crosse virus may be associated with specific forms of canine meningoencephalitis. In addition, two bacteria (Mycoplasma spp. and Bartonella) were also identified. This knowledge should result in better diagnoses and allow for specific therpeutic intervention, thereby improving survival rates for affected dogs.

Schatzberg Letter

UPDATE: November 22, 2010

Meningoencephalitis, a general term for inflammation of the brain and its outer covering, is a naturally occurring disease in dogs that is believed to be caused by a combination of genetic and environmental factors. The disease has a grave prognosis when the cause is unknown, and unfortunately, the cause is unclear in 75 percent of cases in dogs. In human meningoencephalitis, the polymerase chain reaction (PCR) test is used to definitively diagnose causes of infection, and as a result, survival rates have improved. Researchers from the University of Georgia used PCR to identify suspect microorganisms in canine meningoencephalitis. They identified and demonstrated two viruses that are not typically considered to be pathogens in dogs, La Crosse virus and Merkel cell carcinoma virus, and determined that La Crosse virus may be associated with specific forms of canine meningoencephalitis. In addition, two bacteria (Mycoplasma spp. and Bartonella) were also identified. This knowledge should result in better diagnoses and allow for specific therapeutic intervention, thereby improving survival rates for affected dogs.

Results: Study identifies possible causes of brain inflammation in dogs.

UPDATE: September 8, 2009

Meningoencephalitis, a general term for inflammation of the brain and its outer covering, is a naturally occurring disease in dogs that is believed to be caused from a combination of genetic and environmental factors. The disease has a grave prognosis when the cause is unknown, and unfortunately, the cause is unclear in 75 percent of the cases in dogs. In human meningoencephalitis, a test called polymerase chain reaction (PCR) is now used to definitively diagnose causes of infection, and as a result, survival rates have improved. Researchers from the University of Georgia are using PCR to identify suspect microorganisms in canine meningoencephalitis. To date they have identified and demonstrated two viruses that are not typically considered to be pathogens in dogs, La Crosse viruses and Merkel cell carcinoma virus. In addition, two bacteria (Mycoplasma spp. and Bartonella) have also been identified that may be associated with specific forms of canine meningoencephalitis. The researchers are conducting further testing to pursue these associations. If a strong association for causality can be established, this knowledge should provide for better diagnoses and allow for specific therapeutic intervention, thereby improving survival rates for affected dogs.

CHF Grant 963: Genotyping Small Breed Dogs with Portosystemic Vascular Anomalies and Microvascular Dysplasia

$7,000

Cornell University
Sharon A. Center, DVM, DiplACV

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Project Abstract

This study is exploring PSVA and MVD with the goal to identify a genetic marker for PSVA/MVD that will allow development of a genetic test. Extensive pedigree analyses support an autosomal dominant but imcompletely penetrant mode of transmission, explaining the dismal success of attempted trait elimination based on SBA. It is important to eliminate thie trait because affected dogs cause owner dissatisfaction, financial burden, and negative bred publicity, in addition to patient suffering. We have discovered significant linkage between the PSVA/MVD trait and genetic markers on one chromosome in a large kindred of Tibetan Spaniels. Findings have been confirmed with flanking markers and demonstration of similar linkage in Cairn Terriers and Maltese, and a smaller pedigree of Havanese. THe project will pursue further genetic mapping (microsatellites, SNPs) of the PSVA/MVD trait in these and additional breeds, and undertake association mapping using DNA banked from unrelated pure breed dogs with PSVA (n - 100). We have accumulated blood for SBA measurements and DNA extraction from 1,081 dogs in informative pedigrees of 7 breeds (Tibetan Spaniel, Cairn Terrier, Maltese, Norfolk Terrier, Yorkshire Terrier, Havanese, and Miniature Schnauzer). These dogs are kindred related (3-generations) and in most circumstances involved >9 pedigrees. We have additionally accumulated samples on >2,000 dogs (SBA and DNA) in these and other breeds that will be used for assessment of identified PSVA/MVD gene loci (other breed examples: Papillon, Soft Coat Fox Terrier, Pug, Shih Tzu, Dachshund, Shetland Sheepdog, Cocker Spaniel, Lhasa Apso, Boston Terrier, Norwich Terrier, Bichon, Border Terrier, Chihuahua). The project is currently mapping newly acquired pedigrees to the chromosomal region of interest to confirm linkage needed to justify SNP analysis in our region of interest. A SNP array has been developed and the project will shortly proceed to fine gene SNP mapping.

UPDATE 12-31-2011

The present study has helped identify two promising disease risk haplotypes on the chromosome mapped. Data from collective mapping studies was used to designate regions for fine mapping by customized Sequence Capture Array. We have prelimarily discovered shared haplotypes in PSVA affected Cairn Terriers and Yorkshire Terries (the two breeds used for Sequence Capture mapping) within two important candidate genes on the mapped chromosome. The largest shared haplotype spans 12,992 bp of coding and non-coding regions in an important candidate gene, and includes an insertion shared by PSVA dogs. This area was overlooked by less dense SNP and MS mapping efforts. We are further interrogating these regions in additional dogs (of these breeds) and thereafter in other breeds using restriction fragment PCR studies. These regions suggest real potential for developing a genetic test for PSVA/NVD prediction.

Work in this project has importantly excluded a number of candidate genes and transcription factors on the mapped chromosome. Strongest SNP signals are located >20 Mb downstream of our best MS LOD scores that served as the initial start-point of fine mapping. These signals also are downstream of the initially fine mapped area (Illumina GoldenGate Custom Array). Geneomewide SNP mapping also completed on dogs involved in this study (GWA SNP supported by another agency) also has permitted identification of potential candidate genes interactive with the haplotype gene region identified on the chromosome mapped herein. Our custom Sequence Capture Array has been completed on 2 PSVA and 2 controls and is underway in an additional 3 PSVA affected and 1 control dog of the Cairn Terrier and Yorkshire Terrier breeds; (disease prevalence in these breeds ~32% and ~65-80%, (respectively). The Sequence Capture Array findings are being validated by PCR and sequencing of discovered variants in a larger number of dogs. The Sequence Capture Array was designed using information derived from mapping work in this project, information derived from a Neonatal Canine Liver transcriptome our team prepared (funded by Cornell University), and GMW A SNP mapping of PSVA/MVD dogs supported by another agency. A succinct update of findings pertinent to this project will be forwarded when the Sequence Capture Array data is fully analyzed.

UPDATE 5-31-11

Portosystemic vascular anomalies (PSVA) and microvascular dysplasia (MVD) are related genetic disorders causing amlformation of the liver circulation. THis trait affects a number of small pure breed dogs, causing high serum bile acid values (SBA) and has a prevalence ranging from 30% to 80% in various breeds and related dogs.

The goal is to identify genetic markers for PSVA/MVD that will allow development of a genetic test. This research grant focuses on the find-mapping within genomic regions of interest (ROI) found to be associated with PSVA/MVD from genome-wide association studies, and it focuses on candidate gene sequencing across several breeds and in a component of a larger cooperative research program. Extensive pedigree studies and genetic screening using several technologies (microsatellites, SNPs, transcription expression, haplotype analysis) have shown and continues to support the original theory that PSVA/MVD is a polygenic and complex trait.

There has been a delay in fine-mapping of the genome regions in order to most efficiently utilize the grant funds. New technologies allowed the researchers to build their genome-wide association data and refine the region of interest (ROI). The researchers are now using evolving technology to finish the fine mapping in all associated regions.

Several candidate genes have been investigated. The exons in the genes have been sequenced but a mutation that could alter protein structure or expression has not been found. The un-translated regions in the genes are continued to be analyzed using new sequencing technologies. The researchers also continue to pursue new candidate genes as they are identified.

UPDATE: July 3, 2010

Collateral information from our Genome-wide SNP mapping study in Cairn Terriers, crossover analysis of MSS2 markers in Cairn Terriers (a separate study), and development of our Canine Fetal Liver Transcriptome (a separate study) have identified regions to interrogate, consistent with a complex trait-multiple gene hit hypothesis. We are using this additional information to provide additional SNPs in the fine mapping region and to prioritize candidate genes. With the fine mapping SNP data, supplementary SNP information in hand, our Fetal Liver Transcriptions database, and recognition of an emerging loci haplotype, we have identified important candidate genes near each locus associating with the PSVA/MVD trait.

Several strategies may assist further refinement of loci involved with the PSVA/MVS trait and identification of the mutations. Upon discovery of putative mutations, we will investigate their consistency within related affected and non-affected dogs in our pedigrees and in normal controls. According to our multiple gene hit hypothesis, we expect all affected dogs to have at least one copy of the mutation at loci of interest whereas unaffected dogs will lack one or more loci mutations.

UPDATE: November 30, 2009

Portosystemic vascular anomalies (PSVA) and microvascular dysplasia (MVD) are related genetic disorders causing malformation of the liver circulation. Afflicting a large number of small pure breed dogs, this trait causes high serum bile acid (SBA) and has a prevalence ranging from 15% to 85%. The severe PSVA phenotype causes animal suffering, owner dissatisfaction, financial burden, and negative breed publicity. The less severe MVD phenotype allows silent trait perpetuation. Our goal is to identify a genetic marker for PSVA/MVD that will allow development of an affordable genetic test to guide breeding practices. SNP mapping in a region with microsatellite linkage supports an autosomal dominant, incompletely penetrant or polygenic mode of trait inheritance. Specific mathematical models for trait inheritance in different breeds are being developed. The study is fine mapping critical regions using custom designed SNP and sequencing arrays exploring for risk haplotypes that may be useful for discriminating affected from carrier dogs (test development). Genotyping samples have been acquired from >1,500 dogs from informative pedigrees of 7 breeds (Tibetan Spaniel, Cairn Terrier, Maltese, Norfolk Terrier, Yorkshire Terrier, Havanese, Miniature Schnauzer). Development of informative pedigrees (including parents and two or more siblings of a PSVA or MVD dog, including affected and unaffected dogs) are still needed from Papillons, Miniature Schnauzers, Shih Tzus and Pugs. Genotyping data is consistent with wide genetic saturdation of the trait in breeds with high disease prevalence. Individual samples from >2,000 (SBA and DNA) in multiple breeds (also including Soft Coated Fox Terrier, Pug, Shih Tzu, Dachshund, Shetland Sheepdog, Cocker Spaniel, Lhasa Apso, Boston Terrier, Norwich Terrier, Bichon Frise, Border Terrier and Chihuahua) are on hand for assessment of identified PSVA/MVD disease risk loci as the project progresses.

UPDATE: May 31, 2009

Portosystemic Vascular Anomalies (PSVA) and Microvascular Dysplasia (MVD) are related genetic disorders causing malformation of the liver circulation.Affecting a large number of small pure breed dogs, this trait causes high serum bile acid (SBA) and has a prevalence ranging from 15% to 85%. The sever PSVA phenotype causes animal suffering, owner dissatisfaction, financial burden, and negative breed publicity. The less severe MVD phenotype allows silent trait perpetuation. Our goal is to identify a genetic marker for PSVA/MVD that will allow development of an affordable genetic test to guide breeding practices. Extensive pedigree analyses supports an autosomal dominant, incompletely penetrant mode of transmission that is likely polygenic, consistent with the dismal success of attempted trait elimination based solely on SBA concentrations. Significant linkage between the PSVA/MVD trait and a critical region on a single chromosome is confirmed in small purebred dog breeds under study. Genotyping samples have been acquired from >1,500 dogs from informatice pedigrees of 7 breeds (Tibetan Spaniel, Cairn Terrier, Maltese, Norfolk Terrier, Yorkshire Terrier, Havanese, Miniature Schnauzer). Development of informative pedigrees (including parents and two or more siblings of a PSVA or MVD dog, including affected and unaffected dogs) are needed from Papillons, Miniature Schnauzers, Shih Tzus and Pugs. Individual samples from >2,000 dogs (SBA and DNA) in multiple breeds (also including Soft Coat Fox Terrier, Pug, Shih Tzu, Dachshund, Shetland Sheepdog, Cocker SPaniel, Lhasa Apso, Boston Terrier, Norwich Terrier, Bichon Frise, Border Terrier, and Chihuahua) are on hand for assessment of identified PSVA/MVD disease risk loci as the project progresses. The study is currently fine mapping a critical region using a custom designed SNP array developed for the project.

Rabies Challenge Fund

$2,500

W. Jean Dodds, DVM, Hemopet and Ronald Schultz, DVM, University of Wisconsin

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This is a long-term study that is ongoing and studying the long-term effects of the rabies vaccine over a consecutive period of time.

There are two concurrent canine rabies vaccine challenge studies (one for 5 years and one for 7 years), a study of canine rabies vaccine adjuvants, and a rabies vaccine adverse reactions reporting system. The primary purpose of the Fund is to improve the safety of canine rabies vaccines and to determine, by challenge, if they confer longer immunity than currently established.