Welcome
Fourth Symposium bridges clinical/research gap
NA Research moves to a new level with debut of patient database
MRI scans could assist ChAc diagnosis
NA Advocacy reaches out to French speaking patients
NA in knowledge exchange with Huntington's Disease Network
PATIENT FOCUS
Ed Ayala...Pete Clark...Alex Irvine

IN MEMORIAM
Mark Parry...Theo Koutsis 

RESEARCH UPDATE
FUNDRAISING UPDATE
:: You can

A personal message from Glenn, Ginger and Alex Irvine

NA is a devastating disease of the brain, and researchers can only understand its causes and its damage by in-depth examination of brain tissue, which cannot be conducted during our lives. Both patients and their families, who are carriers of the gene mutations, can provide invaluable assistance to NA research by pledging to donate brain tissue after their death.

In our family we've already pledged to do whatever we can to overcome the destruction of NA. We hope you will join us and contact your doctor about tissue donation, as we have done. NA patients themselves sometimes come to the end of their lives completely unexpectedly, but we all face similar uncertainty; pledging your tissue donation now can help ensure your wishes are carried out and will reduce the stress upon family members at a most difficult time. 

Your gift will be a vital legacy to all of us affected by NA and may even advance research into other brain disorders such as Alzheimer’s, Huntington’s and Parkinson’s diseases. Find out more about tissue and organ donation on our website www.naadvocacy.org in the Patients’ Centre under “How can I help Research?



:: How to recognise Neurocanthocytosis


The first signs of the diseases in the neuroacanthocytosis (NA) group are subtle and easily overlooked. Initial symptoms, which often occur in the person’s mid 20’s, may include grunts or tic noises made unconsciously in the throat, progressing to drooling and problems in controlling the tongue from ejecting food. Involuntary biting of the tongue, lips and/or cheeks may follow.

At the beginning there can be a general, slight physical awkwardness. Things on a shelf are knocked off for no apparent reason. Difficulty with walking and balance can also be early symptoms. Problems controlling trunk, leg and arm movements are often barely noticeable at the beginning, but become increasingly difficult as the disease progresses. Several patients find it difficult to sleep at night and others report fatigue and weakness.

Personality change may also be an early indication. The carefree young adult becomes obsessive-compulsive and uncharacteristically forgetful or just loses confidence or drive. Fainting or epileptic seizures may also occur. Mood changes may happen and a person often becomes isolated, in part out of embarrassment.

There are several reports of the problems beginning after a traumatic event including physical attack, unexpected failure of an exam and birth of a child.

CLINICAL SIGNS

A defining symptom that is not apparent is the spiky red blood cells, or acanthocytes, from which the NA disease group takes its name. These unusual blood cells can be observed with a microscope in some circumstances. Still more difficult to observe are the alterations or mutations in patients’ genes. Each of the NA group diseases has a different genetic characteristic that can be determined only by blood tests.

A person showing some of this pattern of symptoms should see a neurologist. Clinicians and patients can also visit www.naadvocacy.org for links to further scientific reports. Full details are also available on the free blood testing service offered by the Advocacy for Neuroacanthocytosis Patients, aimed at helping determine a definitive diagnosis for NA.



:: Useful NA Resources

  • Neuroacanthocytosis Syndromes II, published December 2007, the book provides a profound insight into recent developments within the field of neuroacanthocytosis syndromes. Edited by Ruth H. Walker, Shinji Saiki and Adrian Danek. Available at amazon.com
  • A Western blot test for the presence of chorein in the membranes of red blood cells can be offered free of charge due to support of the Advocacy for Neuroacanthocytosis Patients'. Download instructions on the blood sampling and specimen shipment as a PDF or get more information on the method at PubMed
  • The entry for chorea acanthocytosis in GeneReviews is the most complete, readily available report on ChAc. Published by the University of Washington with the support of the National Institutes of Health
  • A dedicated Patient & Families Support Group at Yahoo Groups offers patients and families information, advice, support or just an understanding ear
  • Visit PubMed for access to NA research in English from the Medline database.
  • Search Google for the latest on NA
  • Visit the NA page on WeMove, the Movement Disorder Societies charitable and educational associate



:: naadvocacy.org

naadvocacy.org is the website of the The Institute for Neuroacanthocytosis. It is the Advocacy's international centre for supporting patients and promoting clinical and basic research. The following links provide access to resources found on the website.




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Welcome
Welcome to Issue 11 of NA News, the periodical dedicated to bringing researchers, patients and research sponsors up to date with the latest news about neuroacanthocytosis (NA) related diseases, a rare group of diseases affecting the brain. NA News is part of our coordinated effort for better information and scientific exchange about these conditions, which, while rare, bear similarities to and can shed light on common neurodegenerative disorders such as Alzheimer's, Huntington's and Parkinson's diseases.

In this issue we are honoured to announce the launch of the long-awaited Neuroacanthocytosis Patients’ Registry, a groundbreaking new reference tool for NA clinicians and researchers. We also report on the excellent response to the Fourth International Neuroacanthocytosis Symposium, and we welcome our new liaison for French-speaking patients and families. You'll also find our latest Research Update, Patient News and Fundraising Roundup.

Please forward NA News to anyone who may find it of interest. You can always find the latest issue online at http://www.geocities.com/nanews2003/ where you can add a friend to the list or unsubscribe from the publication in the area marked "Join or Leave NA News" or on our own website at www.naadvocacy.org where a Japanese translation as well as past editions can be found.


Fourth Symposium bridges clinical/research gap
Prof. Edmund Critchley (left) and Prof. Anthony Monaco
The Fourth International Neuroacanthocytosis Symposium this past July illustrates the key developmental stage NA research has now reached: dialogue and information exchange among clinicians and researchers is strong and growing, and the diversity of attendees proved just how attractive NA research is becoming to a broader community of specialists, from fields including cell biology and genetics.

Supported by the Advocacy and organised by Antonio Velayos-Baeza, PhD, the Symposium was privileged to have as guest of honour Prof. Edmund Critchley, an NA pioneer who helped establish the diagnosis in medical literature. NA was originally described as Levine-Critchley syndrome following Critchley's two encounters with symptomatic patients in the 1960s, one in the US and the other in Lancashire in the UK. The patients both conformed clinically to the typical picture of autosomal recessive chorea-acanthocytosis (ChAc) as now defined by mutations of the VPS13A gene.  

Prof Adrian Danek and Prof Alexander Storch
Subtitled "Bridging clinical and basic aspects," the Fourth Symposium did exactly this, addressing the connections between, and the pathogenesis of the NA syndromes chorea-acanthocytosis (ChAc), McLeod syndrome (MLS), Huntington’s disease-like 2 (HDL2) and neurodegeneration with brain iron accumulation (NBIA). Opening with a day-long review of the clinical features of the syndromes organised by Susanne Schneider, MD, Day One at The Institute of Neurology, London was chaired by Prof. Kailash Bhatia and Dr. Richard Hardie, and also featured Dr. Patricia Limousin's round table on the application of deep brain stimulation.
 
Prof. Edmund Critchley, Prof. Bernhard
Landwehrmeyer and Dr Akira Sano
Tackling the basic science aspects of NA syndromes, Day Two opened at the Department of Pharmacology, Oxford, chaired by Prof. Anthony P. Monaco, Head of the Neurogenetics Laboratory at the Wellcome Trust Centre for Human Genetics, University of Oxford.  Potential roles for VPS13A were examined in the model organisms yeast and tetrahymena, and include a potential function in phagocytosis, which has recently been proposed to be involved in the pathogenesis of a number of neurodegenerative conditions.

Processes involved in red cell membrane shape and physiology were reviewed, with an emphasis on the limited understanding of the proteins which are prominently involved in the cell shape changes of the NA syndromes, including those which make it remarkably deformable under normal circumstances.
 
The symposium was endorsed by The Movement Disorder Society and was supported by The Institute of Neurology, London; The Brain Research Trust, London; The National Hospital for Neurology and Neurosurgery, London; The Wellcome Trust Centre for Human Genetics, Oxford; Glaxo Smith Kline; and Livability (John Grooms/The Shaftesbury Society).

In addition to the Advocacy, the members of the Organizing and Program Committees were Benedikt Bader, Germany; Kailash Bhatia, UK; Adrian Danek, Germany; Sonia Gandhi, UK; Glenn Irvine, UK; Hans H. Jung, Switzerland; Clotilde Levecque, UK; Anthony P. Monaco, UK; Susanne Schneider, UK; Antonio Velayos-Baeza, UK, and Ruth H. Walker, USA.  

Our thanks goes to all attendees and supporters. Watch NA News for updates on research progress as we move toward the Fifth Symposium.


NA Research moves to a new level with debut of patient database
A wealth of anonymised NA case information is now available online to authorised researchers following the final release this autumn of the Neuroacanthocytosis Patients’ Registry. Launched in October on the website of the European Huntington Disease Network, the registry includes the latest updates to several scales which will assess the outcome of deep brain stimulation therapy in neuroacanthocytosis patients, which was done in partnership with Prof. Dr. Lars Timmermann from the University of Cologne in Germany.

The database was released to a limited number of physicians caring for ChAc patients in early October and by the end of October the first sets of patients were entered. Physicians caring for patients suffering neuroacanthocytosis syndromes worldwide are being continuously contacted to expand the database. The case reports are pseudonymous and only available to qualified professional researchers.

A public section of the database internet homepage at www.euro-hd.net/html/na/submodule provides  useful information about NA. Future use of this database mainly focuses on comparison between existing therapies and the evaluation of new therapeutic strategies to improve the efficacy on one hand and to increase the number of options on the other. We expect that the comparison of the development of the diseases and the outcome of therapies such as deep brain stimulation will lead to an improvement of the quality of life of all neuroacanthocytosis patients.

The international database was conceived in 2003 by Adrian Danek to allow researchers around the world to have ”virtual” experience of many more cases than would ever be found in one hospital or indeed one country. Patients and their families can promote research by encouraging their neurologist to enter their cases on the data base by contacting Adrian Danek at danek@lmu.de or Benedikt Bader at benedikt.bader@med.uni-muenchen.de


MRI scans could assist ChAc diagnosis
Results of innovative work at an Australian clinical/research centre suggest that clinicians may be able to begin using MRI scans to correctly diagnose ChAc. 

Katie Kotschet, Dr. Anthony Hannan and Dr. Mark Walterfang
Using expertise in structural imaging, and the application of shape analysis to brain structures, Dr Mark Walterfang from the Melbourne Neuropsychiatry Centre was able to examine the size and shape of the caudate nucleus in 15 scans from patients with chorea-acanthocytosis, and compare these to scans from matched controls and matched patients with Huntington's chorea drawn from the Centre's imaging database.

The group at MNC demonstrated not only significant differences in size of these brain structures in patients with ChAc compared to Huntington's Disease, but also key differences in shape. Given that Huntington's Disease is one of the key differential diagnoses in cases of ChAc, these findings should assist clinicians in correctly diagnosing ChAc from MRI scans.

Headed by Professor Christos Pantelis and Dr Dennis Velakoulis, the Melbourne Neuropsychiatry Centre specialises in combining structural and functional imaging with neuropsychology and behavioural neuroscience. It has developed strong research streams in schizophrenia and allied disorders, adolescent and early adult neurodevelopment, addiction neuroscience and research into uncommon neuropsychiatric disorders.


NA Advocacy reaches out to French speaking patients
The Advocacy is delighted to welcome Anne Depaulis, who has joined us in our drive to communicate with as many patients worldwide as possible in their own language.
Anne Depaulis
Anne will correspond with all French speaking NA patients and their families and can be reached directly at annedepaulis@bluewin.ch Born in France and now residing in Geneva, Anne is truly international; she started her travels in America, where she was an exchange student, and subsequently relocated to London and Hong Kong for business; she is a personal friend of the Irvine family. Don't hesitate to contact Anne directly with any queries or comments en français. Louise Dreher at He.Dreher@aol.com continues to make a valuable contribution as advocate for German speakers.


NA in knowledge exchange with Huntington's Disease Network
Here at the Advocacy for NA Patients we were fortunate to attend a key event in September for researchers and support groups for Huntington's Disease, a rare condition that, symptomatically, closely resembles NA.

At the kind invitation of G. Berhard Landwehrmeyer, president of the European Huntington's Disease Network, Glenn and Ginger Irvine attended the network's 5th Annual Plenary Meeting in Lisbon from 5-6 September 2008. The event was exceptionally well attended, with 250 people expected but close to 500 attending. Clinicians, scientists, fundraisers and representatives of country support groups met to discuss recent research, results of working group activities and to foster the feeling of inclusivity of all people affected by this rare disease.

Ruth Walker's "The Flow Chart for the Diagnosis of Chorea" at the Fourth Symposium
HD is a rare autosomal dominant disease that is more common than NA. As NA most closely resembles HD symptomatically, it behooves us to pay attention to the evolution of the European Huntington's Disease Network, both as a support group and in terms of research advancements. Also discussed were some therapies as they have been tried with HD patients.

Many posters were displayed including NA researcher Ruth Walker's "The Flow Chart for the Diagnosis of Chorea". Ruth's work drew much admiration and allowed us to explain both the NA group of diseases and how our two organisations might be mutually beneficial by sharing ideas and processes.

The European Huntington’s Disease Network (EHDN) is a truly impressive group founded in 2006 that brings together clinicians, research scientists and patients’ advocacy organisations around Europe in the drive to discover a therapy that will relieve, retard or stop Huntington’s Disease.  EHDN is closely associated with the CHDI Foundation Inc., a powerful international network of research laboratories from academia and industry pursuing novel ways to treat HD with drugs and doing it as quickly as possible. 

A central tool of the EHDN is a Huntington's Disease case database that will aid future research. As described elsewhere in this issue ("NA Research moves to a new level"), Ludwig-Maximilian's University in Munich has used this facility to create a specialised neuroacanthocytosis case database.  We are grateful to the EHDN and hope to find opportunities to share both scientific and therapeutic insights with them.


PATIENT FOCUS
Ed Ayala...Pete Clark...Alex Irvine

Ed Ayala
Ed Ayala writes to tell us about his early success with the Palmtop3 by DynaVox Technologies, a handheld device that "speaks" words, phrases and sentences, and so makes it easier to communicate. Ed says he's been able to create phrases and questions, as well as use preprogrammed material on the device. Despite early difficulty, Ed says he's getting there. "I still have a lot to learn about my new friend, but for now it has made a huge difference," he writes. "I can use it as a backup whenever someone does not understand what I am trying to say. Unfortunately this is happening more often than not."

For Ed, speech has been the aspect of life most affected by NA, followed by chewing and eating. His loss of clear speech, he says, left him feeling low and increasingly withdrawn. "I became extremely introverted, frequent phone calls to family and friends began to stop. I knew what I wanted to say but what came out would be slurred or mumbled. It became more and more difficult for me to communicate with friends, family, and co-workers. Speech therapy was helpful but I needed something else, something I could use as a backup when I was not understood." So far, he says, the Palmtop3 seems to be a good backup. "My wish is that with lots of practice on the device, I can regain my confidence and self esteem. On a side note while serving in the U.S. Army I was a communications specialist -- talk about ironic!"

Pete Clark, another NA patient struggling to cope with the painful and difficult symptoms of this disease, writes to tell us of a new outlook he has tried to adopt as his physical abilities retreat. "I am slowly beginning to learn to think in terms of what I have achieved in a day, rather than the long list of things I could have done in the past – reducing my expectations also reduces my levels of stress," he says. "Taking things more slowly definitely improves the clarity of my speech and the quality of my handwriting. I recently went to an exhibition of local woodworkers and this has inspired me to renew my efforts at woodcarving."

Like many others, Pete experiences increasing difficulty with eating and movement. "Mealtimes can be slow and messy," he says. "I do admit to enjoying cake, which goes down a treat when moistened with milk. Ever since my walking has been getting worse it has restricted my mobility and I have been using the wheelchair much more (I feel that the bumpy ride just shows the poor state of our pavements); this is just a minor point as my mobility has improved so that I can now get around the shops without falling over!"
 
Pete also offers the insight that his mouth is "much more active during thunderstorms – is anyone else affected in a similar way?" Write to us here at NA News or share your thoughts in the Patients' Yahoo Group at http://health.groups.yahoo.com/group/Neuroacanthocytosis/
 
Alex Irvine with her lovely cat, KC
In London Alex Irvine would like to convey her thanks to the many friends and relatives who have contributed to the NA cause and who have communicated with her throughout the last year. She has made a remarkable recovery from her knee replacement surgery in March and now is more confident in moving around the house. She was able to visit friends in Boston, Massachusetts in June and is proud of her finished embroidery.

When Alex was bothered by copious drooling this autumn, her doctor prescribed scopoderm, a patch often used to prevent motion sickness which has been of help. She has been receiving physio, speech and occupational therapy support from her local council which has encouraged her to practice standing correctly, make better use of her curled hand and introduced the idea of a Lightwriter voice machine to help communication. This ongoing attention to the day-to-day well-being of patients should be available to all patients.


IN MEMORIAM
Mark Parry...Theo Koutsis


In memory of Mark Parry - a tribute by Fiona Maguire

"Life is a blessing. Not being born, and not dying at one's time, these are great misfortunes." - Lie Zi, Zhou Dynasty

The Mark I knew and loved was always aware that life was for living.

We met at Art College in Dundee just over 20 years ago. We were together there, and subsequently in Edinburgh for 11 years. This tribute is about remembering Mark at his best. He was tall, dark and handsome with a sunny personality; confident, happy and full of life. Never far from his guitar, whether playing in bars or busking on the street, Mark loved an audience. But mostly, he just loved music. To play his guitar and sing were his passions. Although he chose graphic design as his profession, I often wonder what would have happened if he had followed a musical path instead.

Mark loved to laugh and had an idiosyncratic sense of humour which would have got most people into trouble but somehow everyone accepted Mark as he was. I have so many memories of Mark with friends laughing till we cried. He had a "Peter Pan" quality, which never left him. Mark had a lot of friends and made friends easily wherever he went. His longest and best friend, Ian, was close to him right to the last.

Mark unfortunately had to face so many difficulties with epilepsy, NA and the loss of his sister Sian and brother Dave. In spite of his degenerative condition and his suffering in the last few years, Mark knew how lucky he was to have the unconditional love of his parents Gill and Gordon.

None of us ever know how long we will be for this world and Mark's time was certainly cut cruelly short. But in his time, Mark touched many people's lives and I was lucky to have been one of those people whose life he touched the most.

Fiona Maguire
The Strathearn Gallery,
Crieff, Scotland




In memory of Theo Koutsis

The family and friends of Theo Koutsis are saddened to report his passing in Melbourne, Australia on 28 February 2008. Theo was a typical Melbournian: football-mad, with an infectious smile, a laconic sense of humour and happy-go-lucky personality and always putting others' needs before his own. Theo had involvement with the Neuropsychiatry Unit at the Royal Melbourne Hospital for approximately 5 years. In memory of his passing, the Greek community in Melbourne raised AUD2,240 for the Melbourne Neuropsychiatry Centre, who are conducting neuroimaging research on chorea-acanthocytosis and comparing brain regions with sufferers of other basal ganglia disorders such as Huntington's disease. The results of this work were presented at the Fourth Symposium in July. 



RESEARCH UPDATE
Dr. Antonio Velayos-Baeza and Prof. Anthony P. Monaco
Wellcome Trust Centre for Human Genetics, University of Oxford, UK

The objective of this project is to obtain antibodies against the four members of the human VPS13 protein family. VPS13A is altered in chorea-acanthocytosis. This will not only improve specific diagnosis, but also be vital to determining the location and function of these proteins in healthy individuals and thus lead to therapies that will correct or replace the function of the mutated proteins.

We have performed the first three of five steps. By testing protein segments in bacteria we have selected 3 fragments from each protein. Next we have to make the protein segments soluble. We should have the first protein fragments ready this month. The fragments will then be used for the immunisation of animals that will produce the antibodies. We will have antibodies against these fragments between 3 and 5 months later.

At that point we will characterise them and select those that work for different applications (immunofluorescence, immunoblotting, immunohistochemistry). At the end of this research project we expect to have a panel of antibodies that can be used to detect all the VPS13 proteins.


Benedikt Bader, Adrian Danek

Diagnostic testing for Chorea-acanthocytosis (ChAc): Since 2005 156 samples of suspected patients and 42 controls were sent for analysis. In total, 55 (35%) patients were diagnosed with ChAc. There was a large increase in samples in the first quarter of 2007 following an important article by Ruth Walker et al. appeared in the prestigious journal Neurology. As technical experience grew, the mean time between sample receipt and final diagnosis was reduced from 9 months in 2005 to 9 weeks in 2008.




Prof Giel Bosman PhD
Neijmegen Univesity
Netherlands
 
The first year’s work:

  • succeeded in setting up a reliable, robust methodology for determination of the proteome  (i.e. protein composition) of the red blood cell plasma membrane, that is suitable for a comparative analysis of multiple samples as planned for the second phase of the project.
  • using this method discovered that the membrane protein composition of two different NA patients indicate a common change in the band 3-ankyrin complex.

This data, together with material presented at the Fourth Symposium in Oxford and a newly developed biophysical model for red blood cell membrane stability, may lead to a molecular identification of the mechanism of formation of spiky red blood cells.
 



Lucia De Franceschi MD
Associate  Professor of Internal Medicine
Department of Clinical and Experimental Medicine,
University of Verona, Italy

In the first year, we carried out systematic analysis of the proteome (protein composition) from red cell membranes of normal and of ChAC erythrocytes (red blood cells) identifying proteins that are differently expressed. Since no data are available on systematic analysis of the red cell membrane proteome of ChAC erythrocytes, we had to carry out this analysis to evaluate whether morphological and functional differences between normal and ChAC red cells were related to quantitative and/or qualitative differences between the red cell membrane proteomes. The identified proteins are not only descriptive data, but they also indicate that the major differences between red cell membrane proteomes are related to possible post-translational modifications in the protein. In fact, the preliminary data on the phosphotyrosine proteome supported this observation.
 
Now, we plan to complete the analysis of the phospho-tyrosine proteome in normal and ChAC red cells as well as on MLS erythrocytes. The phospho-data will be then used for computational analysis of phospho-networks in order to identify novel signalling pathways to be validated in diseased red cells. This strategy will allow us to highlight new potential regulatory mechanisms to be validated as markers in disease pathophysiology this may also be useful to clinical practice in patient diagnosis or follow-up.



FUNDRAISING UPDATE

Run and jump for NA

We are tremendously grateful to the individual and corporate sponsors who help support NA research. The Advocacy's work would be impossible without the substantial donations from The Carlbetz Foundation, The Blavatnik Charitable Foundation, the J. Macy Foundation, and the Mary Kinross Charitable Trust. We also thank Glaxo Smith Kline, which gave important support for the Fourth Symposium in July 2008.

Camille Cook
The sponsorship work of individuals is especially precious to us, and we are continually inspired by those of you who are personally committing yourselves to helping the patients and families affected by NA. With your help, NA research will progress -- and, we believe, may also contribute to the understanding of Alzheimer's, Huntington's and Parkinson's diseases.

This issue our thanks go out to all the many runners and parachute jumpers who are literally going the extra mile to support NA! We send hearty thanks to Camille Cook, the Assistant Minister at St Columba's Church in London who traveled to Atlanta, Georgia to run her first ever marathon, a 42-kilometer race on Thanksgiving Day. Supporting Camille is easy and quick to do - just log on today and give what you can at http://www.justgiving.com/camillecook 

Also in the UK, Andrew, Chantal & Sam from the real estate desk of the leading executive search firm, Whitehead Mann, completed the 16-kilometer Great South Run around Portsmouth on October 26 for NA. Their sponsorship page remains open, so there's still time to support their huge effort on behalf of NA -- just log on at http://www.justgiving.com/realestateinarealstate 
 
Mark Over completed a parachute jump, raising over STG200 for NA
Mark Over, a friend of NA patient Mark Parry who sadly died earlier this year, completed a parachute jump in the summer as a tribute to Mark. He managed to raise over STG200 for NA. Thanks from all of us who are so affected by NA.

We're also pleased to report that a mail distribution fundraising effort in the UK helped raise more than STG5500 in October and November. These funds, like the other help we receive, will be used exclusively to offset the small operational and significant research costs of the Advocacy.
 

We're delighted to give you a further report on Chris Hamilton of Portland, Oregon, who we introduced in the last issue. Chris's sponsored "April for Alex" walk was a great success:
Chris walked over 80 miles, collecting over USD3000 for NA
Chris walked more than 80 miles and collected over USD3000 for NA (http://aprilforalex.blogspot.com/). Many thanks, Chris!

Donations may be sent to the Advocacy for Neuroacanthocytosis Patients, 32 Launceston Place, London W8 5RN, UK. Please do contact us for the appropriate account to pay depending on your currency, by emailing either Ginger or Glenn Irvine.