WHEN TO SPAY/NEUTER?

Our Sire Jack At 8 weeks old.

Below, Scout and Rock
(​Jack x Lulu)

The article below, shows evidence through recent studies to suggest that veterinarians, and owners working with canine athletes should revisit the standard protocol in which all dogs be spayed or neutered at or prior to six months old if they are not intended for breeding purposes.

Assisting Decision-Making on Age of Neutering for 35 Breeds of Dogs: Associated Joint Disorders, Cancers, and Urinary Incontinence
Benjamin L. Hart1*, Lynette A. Hart2, Abigail P. Thigpen2 and Neil H. Willits3

• 1Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States
• 2Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States
• 3Department of Statistics, University of California, Davis, Davis, CA, United States​

​
Neutering (including spaying) of male and female dogs in the first year after birth has become routine in the U.S. and much of Europe, but recent research reveals that for some dog breeds, neutering may be associated with increased risks of debilitating joint disorders and some cancers, complicating pet owners' decisions on neutering. The joint disorders include hip dysplasia, cranial cruciate ligament tear or rupture, and elbow dysplasia. The cancers include lymphoma, mast cell tumor, hemangiosarcoma, and osteosarcoma. In previous studies on the Golden Retriever, Labrador Retriever and German Shepherd Dog, neutering before a year of age was associated with increased risks of one or more joint disorders, 2–4 times that of intact dogs. The increase was particularly seen with dogs neutered by 6 months of age. In female Golden Retrievers, there was an increase in one or more of the cancers followed to about 2–4 times that of intact females with neutering at any age. The goal of the present study was to expand and use the same data collection and analyses to cover an additional 29 breeds, plus three varieties of Poodles. There were major breed differences in vulnerability to neutering, both with regard to joint disorders and cancers. In most cases, the caregiver can choose the age of neutering without increasing the risks of these joint disorders or cancers. Small-dog breeds seemed to have no increased risks of joint disorders associated with neutering, and in only two small breeds (Boston Terrier and Shih Tzu) was there a significant increase in cancers. To assist pet owners and veterinarians in deciding on the age of neutering a specific dog, guidelines that avoid increasing the risks of a dog acquiring these joint disorders or cancers are laid out for neutering ages on a breed-by-breed and sex basis.
​
Introduction
In the U.S. and much of Europe, the practice of neutering male and spaying female dogs (herein both referred to as neutering) has become routine (1) and is increasingly being performed at, or before, 6 months of age. At the same time, several investigations have revealed that joint disorders and some cancers may increase in association with neutering of males and/or females. For example, in studies that did not focus on specific breeds or ages of neutering, one found that hip dysplasia and cranial cruciate ligament tears or ruptures were significantly more likely in neutered than intact males and females (2). Another study found that neutering was associated with a 3-fold increase in excessive tibial plateau angle (3), which is a risk factor for development of cranial cruciate ligament tears or rupture. Neutering is reported to be a risk factor for canine intervertebral disc herniation in Dachshunds (4). Certain cancers are also known to be more likely in neutered than intact dogs. The occurrence of lymphoma was found to be higher in spayed than intact females (5), as was the occurrence of mast cell tumors (6) and hemangiosarcoma (7). A study of over 40,000 dogs utilizing the Veterinary Medical Database found that neutered males and females were more likely to die of cancer than intact dogs (8). A recent finding was that the absence of estrogen from spaying females was associated with accelerated brain aging (9). Another recent report from the Golden Retriever Lifetime Project is that neutering at <6 months increases the risk of cranial cruciate ligament injury (10). Most of the studies cited above offer no useful clinical information or guidelines with regard to the various diseases that may occur in association with neutering in a specific breed.
In an attempt to address the absence of breed-specific information on joint disorders and cancers associated with neutering, we undertook a project focusing on various specific breeds using data collection and analyses with our extensive veterinary hospital database where the same diagnostic criteria could be applied to all breeds. We started with popular breeds well-represented in the database, initially with the Golden Retriever (11, 12), Labrador Retriever (12) and German Shepherd Dog (13). The joint disorders examined included cranial cruciate ligament tears or rupture (CCL), hip dysplasia (HD) and elbow dysplasia (ED). The cancers examined, which previous studies found could be affected by neutering, were lymphoma/lymphosarcoma (LSA), hemangiosarcoma (HSA), mast cell tumors (MCT), and osteosarcoma (OSA).
In the Labrador Retrievers, Golden Retrievers, and German Shepherd Dogs, there was an increase in the incidence of one or more of the joint disorders with neutering in the first year in males and females to 2–4 times >3–5% incidence in intact dogs. In female Golden Retrievers, neutering at any age was associated with an occurrence of one or more of the cancers followed to 2–4 times higher than the 5 percent incidence in intact females. But in male Golden Retrievers, and in male and female Labrador Retrievers and German Shepherd Dogs, there was no evident increase in cancers above that of the dogs left intact. Preliminary analyses from some small-dog breeds revealed no apparent increased risks of joint disorders with neutering. Thus, the research that had been undertaken revealed a wide range of breed-specific differences in disease vulnerability to neutering.
The purpose of this study was to analyze, in a variety of additional breeds, the increased risks, if any, of the above specified joint disorders and cancers associated with neutering male and female dogs at various ages, so as to increase the information available to pet owners and veterinarians for consideration when making decisions regarding neutering specific dogs. We added 29 new breeds to the study, separating three varieties of Poodles, for a total of 32 breed groups (referred to as breeds); this made a total of 35 breeds with the Goldens, Labs and German Shepherds included. The goal was to use the same veterinary hospital database and diagnostic criteria for the diseases as was used with the published studies on the retrievers and German Shepherds so as to allow for direct comparisons among various breeds. The primary purpose was to offer readers some evidence-based information on breed-specific differences with vulnerability to neutering, including suggested guidelines for neutering ages to avoid increasing long-term health risks of neutering, if any. A secondary, unforeseen, purpose was to document breed-specific differences in the increases in some cancers associated with removal of gonadal hormones, as an area for possible research on genetic aspects of cancer occurrence.
Methods Ethics Statement Hospital records of the Veterinary Medical Teaching Hospital (VMTH) provided the retrospective dataset used. In conformity with the campus policy, faculty of the University of California-Davis, School of Veterinary Medicine, are allowed use of the record system for research purposes. No animal care and use committee approval was required, and strict confidentiality of the owners and their dogs was maintained.
Subjects Breed CategoriesIn addition to the Golden Retriever, Labrador Retriever, and German Shepherd Dog, the other breeds chosen for this project included those most frequently occurring in the database and those chosen to obtain a sampling of giant breeds or small-dog breeds. The final list of 35 (including three varieties of Poodle) represented in the present study are, alphabetically, the: Australian Cattle Dog, Australian Shepherd, Beagle, Bernese Mountain Dog, Border Collie, Boston Terrier, Boxer, Bulldog, Cavalier King Charles Spaniel, Chihuahua, Cocker Spaniel, Collie, Corgi (Pembroke and Cardigan combined), Dachshund, Doberman Pinscher, English Springer Spaniel, German Shepherd Dog, Golden Retriever, Great Dane, Irish Wolfhound, Jack Russell Terrier, Labrador Retriever, Maltese, Miniature Schnauzer, Pomeranian, Poodle-Miniature, Poodle-Standard, Poodle-Toy, Pug, Rottweiler, Saint Bernard, Shetland Sheepdog, Shih Tzu, West Highland White Terrier, and Yorkshire Terrier.
Study Parameters The present study examined the occurrence in both sexes of the joint disorders: HD, CCL and ED. Also examined in both sexes were the cancers LSA, HSA, MCT, and OSA, because these had been shown in some multi-breed studies to be increased in risks with neutering. In addition, mammary cancer (MC), pyometra (PYO), and urinary incontinence (UI) were examined in female dogs. Of interest was the possible association of early neutering and the occurrence of intervertebral disc disorders (IDD) in the Corgi and Dachshund, two breeds known to be at risk for these diseases. All of the above diseases were examined with regard to dogs neutered in one of the age periods of: <6 mo., 6–11 mo., 1 year (12 to <24 mo.) or 2–8 years, or left intact. The diseases were tracked until the dogs were last seen at the hospital, or through 11 years of age, if seen past their 12th birthday.
Mammary cancer is a late occurring cancer with the median age of diagnosis being 10.1 years in one study (14). Tracking cancers through 11 years of age would be presumably sufficient to catch most cases of MC if the case record had information extending to that age. However, most case records did not extend to that age. As an additional point of comparison, percentages of MC occurrence were looked at in just females tracked through 8 years of age or beyond, including diagnosed MC cases beyond the 12th birthday cut-off, which was the cut-off used for all other data.
Data Collection and Presentation The computerized hospital record system of the VMTH provided the dataset. The hospital, with currently over 50,000 cases admitted per year, is a secondary and tertiary facility as well as being a primary care facility. The statistical evaluations, with standardized diagnostic criteria applied to various diseases and taking into account sex and different ages of neutering, required a large database with a computerized record system. The study focused on proportional differences in disease occurrences between the neuter age groups and intact dogs of the same breed and sex.
The study period represented 15 years of data for most breeds. The inclusion criteria were date of birth, age at neutering (if neutered), and age of diagnosis or onset of clinical signs for diseases of interest. As mentioned, age at neutering was designated as <6 mo., 6–11 mo., 1 year (12 to <24 mo.), and 2–8 years (2 to <9 years). The term “early neutering” is sometimes used below to refer to neutering in the first year, combining cases for both the <6 mo. and 6–11 mo. neuter periods. For MC, PYO, and UI, only females were examined. While UI does occur in males, it is predominantly an issue in females.
For all neutered dogs that developed a disease of interest, records were examined to confirm that the dog was neutered prior to the diagnosis or signs of the disease. If the dog developed signs of the disease prior to neutering, the dog was considered intact for analysis of that disease. However, for any disease that occurred after neutering, the dog was considered neutered for analysis of that disease. For any disease of interest that occurred before 12 months of age, the dog was removed from that disease analysis, but included in analyses of other diseases. Therefore, the number of cases for various diseases varied in the analyses for different disease occurrences.
The age at neutering was sometimes not included in the hospital records, so telephone calls to the referring veterinarians were made to obtain the neutering dates or ages. Nonetheless, there were many neutered dogs where age at neutering was not available from the VMTH records or the referring veterinarian, so these dogs were excluded from the study. Of course, this was not an issue with the sample of intact dogs, so there were proportionately more intact cases in the final dataset for each breed than would be expected in the general population. However, the proportion of dogs with a disease, whether intact or neutered, was not affected by the overrepresentation of intact dogs in the database.
The criteria for disease diagnoses were the same as in previous studies on the retrievers and German Shepherd Dog (11–13). A dog was considered as having a disease of interest if the diagnosis was made at the VMTH, or by a referring veterinarian and later confirmed at the VMTH. For joint disorders (HD, ED, and/or CCL), dogs typically presented with signs of lameness, difficulty in moving, and/or joint pain. The diagnosis was confirmed by orthopedic examination, radiographic evidence, and/or surgery. In Dachshunds and Corgis, where intervertebral disc disorders (IDD) is a concern, the diagnosis included herniation, rupture, extrusion, protrusion, fracture, compression, stenosis, or spinal cord injury. For cancers (LSA, HSA, MCT, OSA, MC), the diagnosis was based on the presence of a tissue mass, lumps on the skin or enlarged lymph nodes, and confirmed by chemical panels, appropriate blood cell analyses, imaging, histopathology, and/or cytology. PYO was confirmed by ultrasonic evidence and/or post-surgically after removal of the uterus. UI was confirmed by clinical signs of abnormally frequent urination, urinalyses and exclusion of urinary tract infection and/or other disease. If a diagnosis was listed in the record as “suspected” based on some clinical signs but not confirmed, the case was excluded from the analysis for that specific disease, but the dog was included in other disease analyses.
Although body condition scores have been reported to be a factor in the occurrence of joint disorders (3, 15), our previous studies on the retrievers and German Shepherd Dog found no significant relationship when body condition scores were compared between dogs with and without a joint disorder. Therefore, in the current paper the body condition score is not reported for each breed.
Statistical Analyses Survival analysis was used to test for differences with respect to the hazard of a disease in the neutered and intact groups, while adjusting for the differences in time at risk for a disease. The groups were initially compared using a Kaplan Meier life table analysis. Post-hoc comparisons among the subgroups were based on least squares means of the hazard within each subgroup. For comparisons where the Kaplan Meier test showed significance at the p <0.05 level, both the log-rank and Wilcoxon tests were used for further analyses. Because joint disorders are expected to be seen at a similar risk throughout a dog's lifespan, regardless of age, the log-rank test was used initially for the joint disorders. If the log-rank test did not show significance but the Wilcoxon test did for joint disorders, the Wilcoxon test result was reported with significance level and an asterisk. The reverse rule of thumb was used with cancers where the first test examined was the Wilcoxon test, since the risk of cancer is expected to be higher in older dogs. If the Wilcoxon test did not show significance but the log-rank test did for cancers, the log-rank test result was reported with significance level and an asterisk. For all statistical tests, the two-tailed statistical level of significance was set at p <0.05 and reported as either p < .05 or p <0.01. Each breed was analyzed separately, and there were no statistical comparisons between breeds. However, the overall findings with each breed allow for some general comparisons.
Data Presentation For each breed represented on a separate page in Appendix 1, the numbers of intact and neutered males and females are given. In the tables, the percentage of dogs with each of the diseases and the percentage having at least one of the joint disorders and at least one of the cancers (except MC) was calculated for intact males and intact females as well as those neutered at various age ranges. Statistical analyses compared the occurrences of joint disorders and cancers between each neuter period and intact dogs. If the comparison was significant at either the p <0.05 or p <0.01 level, the data were bolded and the p-value was given. The detailed datasets are available online (Figshare, doi: 10.6084/m9.figshare.7231010). Three breeds for which findings have been previously published (Golden Retriever, Labrador Retriever, German Shepherd Dog) are included to present an overall picture in the same Appendix 1. The data for these three breeds were expanded through 11 years of age, to provide continuity among breeds and diseases.
For each breed, a short paragraph summarizes the main findings on joint disorders (HD, CCL, ED), cancers (LSA, HSA, MCT, OSA) for both males and females, and MC, PYO and UI for females. For Dachshunds and Corgis, the occurrence of IDD is listed for both sexes. Survival analyses were not done on IDD occurrence because the condition represented so many different disease diagnoses. Also included in the breed summary information is a suggested guideline for neutering age for males and females to avoid increasing the risks of a disease under consideration. When there was no noticeable occurrence of an increase in joint disorders or cancers with neutering, the guideline statement was made that those wishing to neuter should decide on the appropriate age (or briefly stated as choice in Table 1). When neutering at <6 months was associated with an increased disease risk but no increased risk was evident with neutering beyond 6 months, the default recommended guideline was neutering beyond, 6 months.
​(Click To Read Full Article).

​Below, are photos of two littermates, one spayed between 6-12 months, the other is not. Note: The dog on the left did not develop fully from having been spayed early.

*With our research we recommend not having your dog spayed or neutered prior to 18-24 months. If you do, your pet will have unstable joints, and be more susceptible to ACL issues, cruciate ligament tears, hyperextension, hip, and/or elbow dysplasia. Hormones will also contribute to how your dog looks.  Structural growth is complete at approximately two years of age in Alapaha Blue Blood Bulldogs. If you have your pet spayed/neutered early, they will be stunted, and will NOT look like its parents. (Many Veterinarians have been giving the HSUS (Humane Society of the United States) and PETA ‘spay/neuter early’ line for years, only caring about ‘unwanted puppies and kittens” with no consideration for the long-term health of your canine companion. If your veterinarian desires to alter your dog early, you may want to look for a vet who is knowledgeable on the latest research. You may also want to consider a Holistic veterinarian as well. *

​More On This Topic: 
AAHA AAHA publications NEWStat 2020-08 Data on the consequences of early sterilization continues to mount
Data on the consequences of early sterilization continues to mount
Tony McReynolds - 8/27/2020

References:

1. Trevejo R, Yang M, Lund EM. Epidemiology of surgical castration of dogs and cats in the United States. J Am Vet Med Assoc. (2011) 238:898–904. doi: 10.2460/javma.238.7.898
PubMed Abstract | CrossRef Full Text | Google Scholar
2. Witsberger TH, Villamil JA, Schultz LG, Hahn AW, Cook JL. Prevalence of, and risk factors for, hip dysplasia and cranial cruciate ligament deficiency in dogs. J Am Vet Med Assoc. (2008) 232:1818–24. doi: 10.2460/javma.232.12.1818
PubMed Abstract | CrossRef Full Text | Google Scholar
3. Duval JM, Budsber SC, Flo GL, Sammarco Jl. Breed, sex, and body weight as risk factors for rupture of the cranial cruciate ligament in young dogs. J Am Vet Med Assoc. (1999) 215:811–4
PubMed Abstract | Google Scholar
4. Dorn M, Seath IJ. Neuter status as a risk factor for canine intervertebral disc herniation (IVDH) in dachsunds: a retrospective cohort study. Canine Genet Epidemiol. (2018) 5:11. doi: 10.1186/s40575-018-0067-7
PubMed Abstract | CrossRef Full Text | Google Scholar
5. Villamil JR, Henry CJ, Hahn AW, Bryan JN, Tyler JW, Caldwell CW. Hormonal and sex impact on the epidemiology of canine lymphoma. J Cancer Epidemiol. (2009) 2009:591753. doi: 10.1155/2009/591753
PubMed Abstract | CrossRef Full Text | Google Scholar
6. White CR, Hohenhaus A, Kelsey J, Procter-Gray E. Cutaneous MCTs: associations with spay/neuter status, breed, body size, and phylogenetic cluster. J Am Anim Hosp Assoc. (2011) 47:210–6. doi: 10.5326/JAAHA-MS-5621
PubMed Abstract | CrossRef Full Text | Google Scholar
7. Prymak C, McKee LJ, Goldschmidt MH, Glickman LT. Epidemiologic, clinical, pathologic, and prognostic characteristics of splenic hemangiosarcoma and splenic hematoma in dogs: 217 cases. J Am Vet Med Assoc. (1985) 193:706–12.
PubMed Abstract | Google Scholar
8. Hoffman JM, Creevy KE, Promislow DEL. Reproductive capability is associated with lifespan and cause of death in companion dogs. PLoS ONE. (2013) 8:e61082. doi: 10.1371/journal.pone.0061082
PubMed Abstract | CrossRef Full Text | Google Scholar
9. Rzechorzek NM, Saunders OM, Hiscox L, Schwarz T, Marioni-Henry K, Argyle DJ, et al. Network analysis of canine brain morphometry links tumor risk to oestrogen deficiency and accelerated brain ageing. Sci Rep. (2019) 9:12506. doi: 10.1038/s41598-019-48446-0
PubMed Abstract | CrossRef Full Text | Google Scholar
10. Simpson M, Albtight S, Wolfe B, Searfoss E, Street K, Diehl K, et al. Age at gonadectomy and risk of overweight/obesity and orthopedic injury in a cohort of golden retrievers. PLOS ONE. (2019) 14:e0209131. doi: 10.1371/journal.pone.0209131
PubMed Abstract | CrossRef Full Text | Google Scholar
11. Torres de la Riva G, Hart BL, Farver TB, Oberbauer AM, Messam LL, Willits N, et al. Neutering dogs: effects on joint disorders and cancers in golden retrievers. PLoS ONE. 8:e55937. doi: 10.1371/journal.pone.0055937
PubMed Abstract | CrossRef Full Text | Google Scholar
12. Hart BL, Hart LA, Thigpen AP, Willits NH. Long-term health effects of neutering dogs: comparison of labrador retrievers with golden retrievers. PLoS ONE. (2014). 9:e102241. doi: 10.1371/journal.pone.0102241
PubMed Abstract | CrossRef Full Text | Google Scholar
13. Hart BL, Hart LA, Thigpen AP, Willits NH. Neutering of german shepherd dogs: associated joint disorders, cancers and urinary incontinence. Vet Med Sci. (2016) 2:191–9. doi: 10.1002/vms3.34
PubMed Abstract | CrossRef Full Text | Google Scholar
14. Cohen D, Reif JS, Brodey RS, Keiser H. Epidemiological analysis of the most prevalent sites and types of canine neoplasia observed in a veterinary hospital. Cancer Res. (1974) 34:2859–68.
PubMed Abstract | Google Scholar
15. Comhaire FH, Snaps F. Comparison of two canine registry databases on the prevalence hip dysplasia by breed and body weight and height. Am J Vet Res. (2008) 232:330–3. doi: 10.2460/ajvr.69.3.330
PubMed Abstract | CrossRef Full Text | Google Scholar
16. Houlihan KE. A literature review on the welfare implications of gonadectomy of dogs. J Am Vet Med Assoc. (2017) 250:1155–66. doi: 10.2460/javma.250.10.1155
PubMed Abstract | CrossRef Full Text | Google Scholar
17. Leedham DY. Prepubertal neutering of dogs – some risks and benefits. Companion Anim. (2019) 24:28–42. doi: 10.12968/coan.2019.24.1.38
CrossRef Full Text | Google Scholar
18. McGreevy PD, Wilson B, Starling MJ, Serpell JA. Behavioural risks in male dogs with minimal lifetime exposure to gonadal hormones may compromise population-control benefits of desexing. PLoS ONE. (2018) 13:e0196284. doi: 10.1371/journal.pone.0196284
CrossRef Full Text | Google Scholar
19. Perry RJ, Farquharson C, Ahmed SF. The role of sex steroids in controlling pubertal growth. Clin Endocrinol. (2008) 68:4–15. doi: 10.1111/j.1365-2265.2007.02960.x
PubMed Abstract | CrossRef Full Text | Google Scholar
20. Salmeri KR, Bloomberg MS, Scruggs SL, Shille V. Gonadectomy in immature dogs: effects on skeletal, physical, and behavioral development. J Am Vet Med Assoc. (1991) 198:1193–203.
PubMed Abstract | Google Scholar
21. Golds G, Houdek D, Arnason T. Male hypogonadisman and osteoporosis: the effects, clinical consequences, and treatment of testosterone deficiency in bone health. Int J Endocrinol. (2017) 2017:4602129. doi: 10.1155/2017/4602129
PubMed Abstract | CrossRef Full Text | Google Scholar
22. Root Kustritz MV. Determining the optimal age for gonadectomy of dogs and cats. J Am Vet Med Assoc. (2007) 231:1665–75. doi: 10.2460/javma.231.11.1665
PubMed Abstract | CrossRef Full Text | Google Scholar
23. Beauvais W, Cardwell JM, Brodbelt DC. The effect of neutering on the risk of mammary tumours in dogs – a systematic review. J Small Anim Pract. (2012) 53:314–22. doi: 10.1111/j.1748-5827.2011.01220.x
PubMed Abstract | CrossRef Full Text | Google Scholar
24. Neilson JC, Eckstein RA, Hart BL. Effects of castration on the behavior of male dogs with reference to the role of age and experience. J Am Vet Med Assoc. (1997) 211:180–2.
Google Scholar
25. Hart BL, Eckstein RA. The role of gonadal hormones in the occurrence of objectionable behaviours in dog and cats. Appl Anim Behav Sci. (1997) 52:331–44. doi: 10.1016/S0168-1591(96)01133-1
CrossRef Full Text | Google Scholar
26. California Food and Agricultural Code. (2017). Division 14. Regulation and Licensing of Dogs. https://leginfo.legislature.ca.gov/faces/codes_displaySection.xhtml?lawCode=FAC&sectionNum=2005 (accessed June 23, 2020).
Google Scholar
27. Hart BL, Hart LA, Thigpen AP, Willits NH. Assisting decision-making on age of neutering for mixed breed dogs of five weight categories: associated joint disorders and cancers. Front. Vet. Sci. (in press).
Google Scholar
Keywords: elbow dysplasia, hip dysplasia, cranial cruciate tear, lymphoma, mast cell tumor, hemangiosarcoma, osteosarcoma
Citation: Hart BL, Hart LA, Thigpen AP and Willits NH (2020) Assisting Decision-Making on Age of Neutering for 35 Breeds of Dogs: Associated Joint Disorders, Cancers, and Urinary Incontinence. Front. Vet. Sci. 7:388. doi: 10.3389/fvets.2020.00388
Received: 02 April 2020; Accepted: 01 June 2020;
Published: 07 July 2020.
Edited by:
Natali Krekeler, The University of Melbourne, AustraliaReviewed by:
Ottmar Distl, University of Veterinary Medicine Hannover, Germany
Andreas Pospischil, University of Zurich, SwitzerlandCopyright © 2020 Hart, Hart, Thigpen and Willits. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Benjamin L. Hart, blhart@ucdavis.edu
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.