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The New Dirty Dozen Plus

by C.A. Sharp

First published in Double Helix Network News Spring and Summer 2013

 

In 2000 I wrote an article titled “The Dirty Dozen Plus a Few:  Frequency of Hereditary Disease in Australian Shepherds.”  Over a decade has passed and the Australian Shepherd Health & Genetics Institute (ASHGI) has since conducted its “Comprehensive Australian Shepherd Health Survey,” so it is time to review the old DD list and compile a new one.

A breed is not static; any number of things can change over time.  If you doubt that, look at early photographs of almost any breed including the Aussie and compare them to present day dogs.  Different people in different times have different visions of what a breed should be.  Changes may affect not only appearance but behavior, and – for good or for ill – they may affect the health of the breed as well.  Some of these changes arose because we know more now than we did in 2000.  Heightened awareness of what conditions can be inherited and improved veterinary diagnostic tools have led to increased reporting of previously known issues as well as new ones.  Knowing where we were a little over a decade ago and where we are now can be helpful to breeders in setting their priorities.

The Big Eight

There were eight hereditary issues that the survey indicated were extremely common in Aussies, four of which were in the top twelve on the 2000 list.

#1  Multi-Drug Resistance 1 (MDR1)

MDR1 is a gene associated with response to medications.  A mutation of this gene causes dogs to react to certain drugs at dosages that are normally safe.  Dogs with two mutations react at lower doses than do those with only one.  40% of the dogs entered in the survey had at least one copy of this mutation.  The Veterinary Clinical Pathology Lab at Washington State University, where the gene was discovered, has stated that half of the Aussies submitted for testing have the mutation.

While the MDR1 mutation is not a reason not to breed a dog – it is only a problem because we sometimes need to give our dogs drugs – it can sometimes be lethal.  The presence of even one copy of this mutation should be considered a fault and breeders should make an effort to select away from it.

Because the mutation exists at such high frequency in the breed it cannot be eradicated immediately or even over a few generations.  By breeding dogs with the mutation only to clear-tested mates and giving preference to clear-tested offspring for future breeding the frequency of the MDR1 mutation can gradually be reduced.

#2  Autoimmune Diseases

Autoimmune diseases were considered as a group because they all arise from a similar malfunction of the immune system, targeting the body’s own tissues as something to be destroyed.  Different AI diseases frequently occur within the same family of dogs – something that has also been observed in human families.  AI diseases have been a significant problem in the breed for a long time – they were #3 on the Dirty Dozen (DD) list in 2000.

Fortunately, incidence hasn’t increased markedly but its failure to decrease probably stems from a lack of awareness on the part of breeders that all AI diseases should be considered as a single breeding concern.  The most frequently reported types of AI disease in the survey were (in descending order):  Autoimmune thyroiditis – which by itself could be #5 on this list, inflammatory bowel disease (IBD), lupus, pemphigus, and diabetes mellitus.

While most of these diseases aren’t lethal, they may shorten life, clearly raise significant quality of life concerns for the dog, and can place financial burden on the owner.   Breeders should make note of AI disease cases amongst their dogs’ relatives and make efforts to breed away from them, not just disease by disease but as a class of diseases.

#3  Dental Faults

Bad bites and missing teeth combined take third position on the list.  They were second in 2000.  12% of the dogs in the survey either had or produced bad bites and/or missing teeth.  This is a huge portion of the breed and indicative of faults – in some cases disqualifying – that need a lot more attention from breeders.

#4  Allergies

Any dog has the potential to develop a minor allergy during its life but nearly half of the reported allergies were moderate to severe.  This more adversely affected group is almost certain to have an underlying genetic predisposition.  Since allergies that are moderate or worse have a quality of life impact on the dog and require extra effort and expense to the owner, breeders should make a concerted effort to breed away from this disease.

#5  Hip Dysplasia

One in ten dogs in the survey had HD and 7% of the breeding dogs had produced it at least once.  This high level of frequency for a potentially crippling disease in a breed often involved in strenuous and demanding physical activities is appalling.  OFA statistics indicate that around 6% of Aussies have abnormal hips, but many cases of HD never get reported to OFA.  HD can wash a dog out of a real job, limit a performance career, and cause some dogs a great deal of pain.  Treatment of the worst cases can be very expensive and is not necessarily effective.

Hip screening has become almost routine, but just doing x-rays isn’t going to improve hip health nor will breeding Excellent rated dogs to other excellent rated dogs.  Breeders must start tracking this disease across “vertical” pedigrees, which take in the siblings of the dogs on a standard pedigree.  The more cases of HD that are there, including unilateral HD, the higher risk your dog has for producing HD no matter what its hip grade is.  High risk dogs should be bred to low risk mates.

#6  Behavioral Issues

Behavior is a mish-mash of environmental and genetic influences.  In an active breed like the Aussie, a lack of understanding of the breed’s nature can lead to troublesome behavior.  That said, a staggering 64.5% of the dogs in the survey were reported to have some kind of behavioral issue and nearly half of those were said to have multiple issues.  Some problem behaviors, most notably sound sensitivity, are clearly inherited.  Some aspects of disposition likely carry strong genetic influence.

At the very least the overwhelming numbers of behavioral issues reported in a survey that was primarily focused on health indicate that at the very least breeders should do a better job placing puppies and following-up with the new owners.  Behavioral problems that arise from poor management may not be inherited but they can result in euthanasia, either directly or as a secondary effect of being surrendered to a shelter.  Death is a very drastic health impact for the dog.  If particular problem behaviors occur frequently in related dogs raised in different homes, minimizing that behavior should become a breeding priority.

The 2000 DD report did not address behavioral issues except for rage syndrome, an inherited neurochemical imbalance that leads to unpredictable episodes of violent behavior which, thankfully, was and remains rare in the breed.

#7  Female Reproductive Issues

Questions on reproductive issues were a feature of the survey.  For the most part, males had no significant issues.  Females, however, were another story.  Almost 11% of breeding bitches received medically necessary C-sections, some as many as three times.  13% had had difficulty whelping and 9% had at least once failed to conceive.  Reports of these issues were not frequent enough to be included in 2000.

You can’t get much more natural than having babies; without them a species goes extinct.  For this many bitches to have significant breeding issues in a breed that is physically active and has a normal canine body shape is appalling.  Bitches which cannot or will not mate, conceive, carry, whelp and raise a litter without significant human or medical intervention should be removed from breeding programs.

#8  Disqualifying Colors     

Slightly over 13.5% of the breeding dogs produced disqualifying coat colors, most of them excess white in pups that were not double merles.  Dilute (full dilute, not dilution spots on merles) and yellow, which can range from pale cream to deep chestnut in any individual dog also occurred with some frequency.  The two non-standard colors are recessive and there are DNA tests available for both, though some full dilutes have a type arising from an as yet unidentified gene or genes. Color is a largely cosmetic issue, though some excess white dogs may have hearing loss if the white is on or around the ears.  Even so, in view of the fact that incorrect color can disqualify the dog from conformation, breeders should pay more attention to it.

The Not-So-Lucky Seven

These very common health issues finish out our new Dirty Dozen and include a few more that show up often enough to warrant listing in this category.  Four were featured in the prior DD list, one was reported previously as “uncommon,” and two are new to the list.

#9  Cancer

Cancer was #8 on the 2000 DD list, but keep in mind that there are five items in the new list that are currently ranked higher than cancer which were not in the 2000 list.  Had they been, cancer might have been lower and possibly even out of the top 12. In addition, we have learned more recently that that we have two inherited cancers, hemangiosarcoma (HSA) and lymphoma.  The present ranking reflects only those.  The 2007 ASHGI cancer survey found that almost half of all cancers in Aussies are one of these two.

HSA and lymphoma were reported in 7% of the dogs in the 2010 survey, with 70% of those being HSA, a proportion similar to what was found in the cancer survey.  Both cancers are familial, meaning that inheritance plays an important role even though something environmental likely initiates the disease.  Entire litters have been largely eliminated by these cancers, which also occur generation after generation.  Both are lethal and bring heartache and financial burden to the dogs’ owners.  They should be considered a health risk for breeding.  Breeding dogs from high risk lines should be put to suitable mates from lines with low risk.

#10  Umbilical Hernia

A new addition to the DD list, umbilical hernias are present at birth.  Sometimes a hernia seen in a young puppy goes away when the opening in the abdominal wall closes on its own.  Often only a small portion of abdominal fat protrudes through the hole making a small bump.  The fat may even be an isolated pad left outside at the time of the closure.  However, if the opening is large a hernia can be dangerous; a loop of intestine that protrudes can become pinched or “strangulated,” a dangerous condition.  5% of the dogs in the survey had umbilical hernias.

Dogs with major hernias should not be bred.  Minor hernias that remain after early puppyhood should be considered faulty and an effort made to breed away from them.

#11  Cataract

Cataracts, #1 on the 2000 DD list, remain our breed’s most common inherited eye disease. 4% of the dogs in the survey had cataracts and 7% of the breeding dogs were reported to have produced them.  While increased breeder attention to this disease may play a role in its lower ranking it is important to realize that five of the things that outrank it on this list weren’t even on the radar in 2000 and the awareness of cancer as an inherited disease likely increased reporting.  Rankings aside, it is still a very common disease.

Most Aussie cataracts are associated with a genetic mutation for which there is a test, however not every dog with the mutation goes on to develop cataracts and there are clearly inherited cataracts that are not associated with the mutation.  While all of this tends to muddy the waters for breeders it is important to keep in mind that this is a very common, potentially blinding eye disease.  Breeding stock should have the DNA test and those with the mutation should be bred only to clear-tested mates with preference given to clear offspring to carry on with.  Dogs which actually have cataracts should not be bred.

#12 Epilepsy

The final entry in our new DD list, #5 in 2000, remains one of the breed’s most devastating diseases, bringing misery to affected dogs and those who love them, and no small amount of treatment expense.  4% of the dogs in the survey were epileptic.   Because of the very serious and expensive nature of this disease and the lack of a DNA screening test, affected dogs and all their first-step relatives (parents, offspring, and siblings) should not be bred.  Other relatives need to be bred to mates that carry less epilepsy risk than they do.

Because we’ve been dealing with epilepsy for so very long and it is so widespread in the breed, some have become fatalistic (“it’s everywhere”).  We cannot afford to ignore this disease and breeders should make every effort to reduce risk.  Even in a best case scenario it is going to take us generations to dig ourselves out of the hole we’ve gotten into.  The time to start is now.

Retained Testicles

#11 in 2000, if this list was confined to things reported at that time, retained testicles would have popped up to #7.  It is very likely this condition has increased significantly in frequency, possibly because breeders pay too little attention to it or perhaps because one or more popular sires may carried genes for it.

Elbow Dysplasia

This disease fell into the “rare” category in 2000.  Since that time health data from Europe, where elbow screening is routine, have indicated that we may not have been seeing it in the US because we weren’t looking.  While some affected dogs are sub-clinical, others experience significant pain.  North American breeders must start routinely screening elbows (it is a requirement for Canine Health Information Center certification) as well as making sound elbows a breeding priority.

 Natural Bobtail-related Issues

Another new item on the list, defects associated with natural bob-tail (NBT) came up far too often to be ignored, including minor defects like kinked tails and transitional vertebrae, and more serious problems like spina bifida and imperforate anus.  Fully 2% of the breeding dogs were reported to have produced NBT-related defects bad enough to require euthanasia.  Since only an NBTxNBT cross is apt to produce such severely affected puppies the percentage of NBTs that produced them is much higher than indicated here.  The take-away from this is that two NBTs should never be bred to each other.  Kinked tails are a cosmetic concern for breeders in countries where docking is banned that can also be addressed through breeding choices.

The Gang of Four

These four items, two of which were on the 2000 DD list, were found in 2-3% of the dogs in the survey which qualifies them as a common health issues.

Persistent Pupilary Membrane

Number 9 on the 2000 list, PPM hasn’t really changed in frequency; it got shoved off the DD list by ills both more recently recognized and more common.  PPMs are, for the most part, a minor eye defect.  Those that attach only to the iris cause little or no vision loss and will pass eye exams in the US.  However, attachments to the lens or cornea can cause blinding opacities and iris sheets can block the pupil and prevent vision.  These types of PPM do not pass and dogs that have them should not be bred.  Iris-to-iris PPMs should be treated as a minor fault and affected dogs not bred to each other.

Distichiasis

Another usually minor eye issue, distichiasis fell just below PPM in 2000 and is off the top twelve now for the same reasons.  These abnormal lashes aren’t a problem unless they are angled toward the cornea and stiff enough to scratch it when the dog blinks, a painful condition that can cause vision loss if the cornea becomes scarred.  These require surgical removal and affected dogs shouldn’t be bred.  Dogs with minor distichia should not be bred together.

Food Intolerance

A new addition to the list, food intolerance was reported in 3% of the dogs in the survey.  Causes can be highly varied and not necessarily inherited.  Veterinary workup would be advised in an effort to determine what exactly is going on so the dog can receive appropriate treatment.  If the cause is found to be something that can be hereditary, the dog should not be bred.

Cruciate Ligament Rupture

This is an injury that can end a dog’s performance career.  Recent research indicates that some sort of immune mediated process may be involved which further indicates possible heritability.  It should also be noted that altering prior to one year of age can increase risk for this injury.  Dogs with bilateral cruciate ruptures should not be bred.  Breeders should avoid breeding dogs with affected near relatives to each other.

Ten to Watch For

There are ten rare issues, each reported in about 1% of the dogs in the survey, which bear watching.  It only takes one popular sire carrying genes to make one of these a common breed health issue.  The list includes two formerly common eye issues, four health issues that fell in the rare or very rare categories in 2000, and four things new to the list.

Progressive Rod Cone Degeneration (PRA)

PRCD is a form of Progressive Retinal Atrophy (PRA) a group of retinal degenerative diseases which have different causes, most of them genetic.  PRCD/PRA is one of the inherited kinds and there is a DNA test.  Affected dogs shouldn’t be bred.  Dogs with two copies of the mutation will develop the disease and should be considered affected even if they haven’t started to show symptoms yet (the disease typically arises in mature adults.)  Carriers can be bred to clear-tested mates.

A word of caution:  A clear PRCD test does not mean the dog is free of all forms of PRA, only PRCD.  In 2000 PRA was considered very rare; it has increased in frequency since.  If breeders don’t pay attention it could wind up becoming common.

Collie Eye Anomaly (CEA)

CEA was DD #12 in 2000.  It is being reported less frequently but may be a sleeping dragon.  This is a disease that is easy to miss if every puppy in every litter isn’t checked early (no later than 6 weeks.)  Too often puppies don’t get eye exams early enough or only those bound for potential breeding homes are checked.  The disease is recessive so in most cases only one or two pups in a litter out of two carriers will be affected.  Most dogs have functional vision but those with the more severe CEA defects can be blind in one or both eyes.  If CEA is found in a litter, both parents are at least carriers.  They should be DNA tested to make sure neither is affected.

Dogs with two copies of the mutation are affected even if they pass eye exams; the most common defect often can’t be observed once pigment fills in within the eye.  Affected dogs should not be bred.  Carriers should be bred only to clear-tested mates.

Kidney Disease

Kidney disease, a new item, can arise from different causes but if the disease is renal dysplasia it is a recessive inherited disease that is frequently fatal.  Even in dogs that live with it for many years it likely shortens their lifespans.  Affected dogs should not be bred.  Parents of affected dogs are carriers and the healthy full siblings have a 2 in 3 chance of being carriers.  They should only be bred to dogs with no family history of renal dysplasia or any undefined kidney disease.

Pancreatitis

Pancreatitis was reported in 1% of the dogs in the survey.  Exocrine Pancreatic Insufficiency (EPI) might be described as “pancreatitis.”  EPI, which has been reported in Aussies, is inherited and is a serious, debilitating disease.  It is miserable for dog and owner alike.  Affected dogs should not be bred and their healthy relatives should not be bred to mates with a family history of pancreatic disease.

Pelger-Huet Anomaly (PHA)

PHA was categorized as rare in 2000 and remains so.  It causes minor blood cell defects that rarely affect the health of the dog, but if two PHA positive dogs are bred together small litters result because puppies which inherit two copies of the as-yet unidentified gene die during gestation.  There is a blood test that identifies PHA positive dogs.  Breeders should not breed PHA positive dogs together and should test offspring of dogs that have tested positive.  This is not a DNA test and can have false negative results, therefore grandpups of a PHA-positive dog out of a tested clear parent should be tested if they are to be bred.

Urine Crystals

Aussies have been identified as one of the breeds that can develop urate crystals.  The condition can require surgery and in the worst cases may block the ureter, the vessel that drains the bladder, a painful and potentially dangerous condition.  There is a DNA test.   Affected dogs and those with two copies of the mutation should not be bred.  Carriers may be bred to clear-tested mates.

Congenital Heart Vessel Defects

Patent Ductus Arteriosus (PDA) was also reported as a rare health issue in 2000.  PDA and Persistent Right Aortic Arch (PRAA) are developmental heart defects:  Fetal heart vessels that are supposed to go away before birth.  Both are potentially lethal.  Surgical correction is expensive and not always effective.  Affected dogs should not be bred.  If a dog produces PDA and/or PRAA with more than one mate, serious consideration should be given to removing it from breeding due to the extremely serious nature of these defects.

OCD of the Shoulder

Osteochondritis Desicans (OCD), a tiny flap of loose tissue in a joint, causes pain and lameness.  OCD can occur in any joint but in dogs this usually happens in the elbow, where it is considered a form of elbow dysplasia, or the shoulder.  Dogs with OCD should not be bred and their sound relatives should not be bred to dogs with OCD in any joint.

Iris Coloboma

Formerly #6 on the list, IC is now in the rare category.  In part this is due to several more recently recognized health issues that supersede it in this current list, but its precipitous drop in relation to items that were on the 2000 list indicates it is something we appear to be making progress with.  The fact that it is almost always clearly visible to an observer has likely contributed to the decline.

IC is a minor eye defect.  Small ones cause little or no visual problem but larger ones can interfere with the contraction of the iris making the dog light sensitive.  This can impact performance in athletic competition or working dogs.   The defect is almost always seen in merles but non-merle parents of affected dogs probably contribute to the inheritance.  Affected dogs shouldn’t be bred and their normal near relatives shouldn’t be bred to dogs with a recent family history of IC.

Cushing’s Disease

Cushing’s disease, also called hyperadrenocorticism, is usually caused by a tumor on either the pituitary gland or the adrenal gland.  Tumors on the latter can be malignant.  In either case the imbalance of cortisol levels can lead to quality of life issues for the dog.  Though still rare, reports of this disease have increased and it bears watching in case there may be an inherited component.  To play safe, stop breeding affected dogs and breed their healthy kin only to dogs with no recent family history of this disease.

Seven on the Horizon

Three of these seven very rare health and soundness issues ranked “rare” (the lowest category) on the 2000 DD list.  They require our attention to make sure they stay that way.    Fortunately four in this set have DNA tests available.  Dogs affected with any of these things should not be bred.  Where no DNA test is available to screen relatives and prospective mates, the healthy relatives should not be bred to dogs with family history for these diseases.

Patellar Luxation

The patella is the kneecap, located on the front of the stifle joint.  When it slips out of position the condition is called “patellar luxation.”  A patella can be forced out of position by trauma but in some dogs the structure of the stifle joint allows them to slip in and out of place.  Affected dogs have a characteristic hopping gate when the patella has slipped.  This is most associated with toy breeds but even large breeds, like the Great Pyrenees, may have patellar luxation.  On rare occasions it happens in an Aussie.  The cause is not entirely clear, but overly straight stifles may contribute.  Affected dogs should not be bred.  Breed their sound relatives to mates with no family history of patellar luxation and proper stifle angulation.

Muscular Dystrophy (MD)

The X-linked form of this neurodegenerative disease has been reported in Aussies.  It is ultimately fatal to the affected dog, usually very early in life.  Since this is an X-linked genetic disease, males are affected and the dam is the source of the mutation.  Dams of affected pups should be removed from breeding.  Spontaneous mutations of this gene occur, therefore the maternal grand dam and the rest of the female tail line may be free of the MD mutation.  Withhold from breeding only those females that have produced an affected puppy.

Cleft Palate

Sometimes the bones of the roof of the mount fail to come together during development, leaving a gap called a cleft palate.  In severe cases the gap will extend through the front of the muzzle and even up to the nostrils.  Affected puppies either cannot nurse or have great difficulty and risk aspiration pneumonia if they do.  They often must be euthanized.

Cleft palates can arise for a number of reasons, not all of them hereditary.  However, if related dogs produce this condition, particularly when those dogs do not live in the same home (environmental factors can cause cleft palate) then inheritance should be considered a strong possibility and efforts made to avoid producing it again.

Those searching for information on this condition in Aussies may come across research done in the 1980s and early 1990s referring to an X-linked lethal condition that included cleft palate and other skeletal defects.  In Europe this has been referred to as “skeletal lethal.”  This particular mutation arose spontaneously in a single Aussie bitch in a research colony.  All affected dogs were her descendants.  These dogs rarely appear in pedigrees today and very few, if any, direct female tail line descendants of that original bitch still exist.   Even though cleft palate was generally the cause of death, the affected male dogs had multiple gross skeletal defects.  Even the females would have minor defects, like abnormal toes or misshaped leg bones.  Lacking these other defects, no cleft palate should be assumed to be due to this extremely rare genetic disease.

Hereditary Cobalamin Malabsorbtion (HCM)

Cobalamin is Vitamin B12.  Dogs with HCM are unable to absorb the vitamin in the gut.  There is a DNA test.  CM can cause a wide range of symptoms and the disease is often misdiagnosed as something else.  One example is porto-systemic (liver) shunt.  This condition was reported in a few Aussies, leading to it being noted as rare in the 2000 DD report, however none of those dogs’ alleged shunts were ever confirmed surgically; the diagnosis was based on symptoms.  It is probable that what they actually had was HCM.  HCM can also cause intractable early-onset seizures which, in a breed riddled with epilepsy like the Aussie, might be assumed to be that disease.  Dogs with exocrine pancreatic insufficiency (EPI) can have secondary cobalamin malabsorbtion, so primary disease (HCM) needs to be ruled out in dogs thought to have EPI.  The only way to do this is with the DNA test.

Some dogs will have only moderate disease and the underlying cause may be overlooked but in severe cases the disease can be fatal.  Owners can spend a lot of money on tests and treating these dogs for diseases they don’t have when a relatively inexpensive DNA test can pinpoint the problem.  Treatment of HCM is simple and inexpensive:  Periodic injections of Vitamin B12.

HCM is a recessive disease; dogs with two copies are affected and should not be bred.  Carriers may be bred to clear tested mates and offspring which might be bred tested to identify which are themselves carriers.  Preference should be given to clear-tested offspring to carry on with.

Cone Degeneration (CD)

CD is a retinal disease.  Because it is very rare, diagnosis by exam should be confirmed with the DNA test.  This disease is recessive, so breeding advice would be the same as for Cobalamin Malabsorbtion, above.

Canine Multifocal Retinopathy (CMR)

CMR is another retinal disease and it may be more prevalent than its listing here indicates.  One of the signs is retinal folds which are reported in Aussies with some frequency.  Fortunately most Aussies with this disease have only minor defects that do not significantly impact vision.  The American College of Veterinary Ophthalmologists classifies dogs with minor CMR defects as “breeder option”:  They will pass an eye exam and it is the breeder’s choice whether or not to use them for breeding.

There is a DNA test for this recessive disease.  As with CD above, it should be used to confirm exam diagnosis.  Relatives of affected dogs should be tested to determine their status.  Affected dogs with minor defects need not be removed from breeding programs but should be bred to clear-tested mates.  The presence of the mutation should be treated as a fault and efforts made to breed away from it.

Neuronal Ceroid Lipofuscinosis (NCL)

The final disease in our 2013 DD report, NCL is a lethal recessive neurodegenerative disease.  Affected dogs generally die before they are two years old.  The disease can cause severe seizures and might be mistaken in an Aussie as epilepsy, though thorough exam and follow-up should make it clear that the dog has something else.  The only way to confirm an NCL diagnosis is through pathological exam of brain tissue collected after death or with a DNA test.

There are several genetically distinct forms of NCL and several DNA tests, one of which is available for Aussies.  However, this listing was based on a single confirmed case.  If NCL is suspected, this is the first DNA test that should be done, but if it is negative there is a possibility that the dog may have one of the other forms.

This is a horrible disease.  Affected dogs don’t live long enough to breed.  Carriers should be bred to clear-tested mates with very strong preference given to using only clear-tested offspring to carry on with.  If NCL is confirmed but is not a type for which there is a DNA test. strong consideration should be given to withholding all first-step relatives of (parents and full and half siblings) from breeding.  Other relatives should be bred away from the pedigree of the affected dog.

 

ASHGI plans to do another health survey in a few years and this report will be updated subsequent to that.