Monday, 24 December 2012

Review of 2012

Christmas is coming round again, and I thought I'd just review and summarise what I've discovered this year, and think about how different my symptoms are since the start of the year.

The main knowledge change this year is the discovery of the PubMed database and the wealth of information  out there. I'm starting to digest this information (so there'll be no shortage of bits of info to post about!)

My main observation this year is that I've spotted wear and tear on my shoes and in the car, so even if I didn't perceive it my symptoms must be getting slightly worse. I've also had the odd comment about 'limping'. I've also found that I need to keep exercising in order to keep my flexibility for a long as possible.

This Blog:
This year I've added an index and started to develop the blog so it's more than a list of posts. I've also started to become an "active" writer than a "passive" one, and I've joined various HSP communities. In the last month or so I've also started tweeting, and I think that 2013 will be the year where I join up my various on-line presences together.

The filming project:
In July 2011 I started my 'filming' project. I paused from that when our second son arrived, after about a years worth of footage. It is my intention to re-commence that project in 2013 as well.

Monday, 10 December 2012

The need to urinate (go to the loo)

Part of my digest of papers found a fairly recent one on the bladder side of the symptoms, and is my first look into this side of things. 
Title: Bladder dysfunction in hereditary spastic paraplegia: a clinical and urodynamic evaluation
Authors: M Fourtassi, S Jacquin-Courtois, M C Scheiber-Nogueira, A Hajjioui, J Luaute, K Charvier, D Maucort-Boulch and G Rode
Published in: Spinal Chord, Volume 50, Issue 7 (July 2012)
The link is here:

I've only read the abstract so far, but the principal findings appear to be: a large series (29) of HSP patients were analysed. Ultrasound examination revealed no upper urinary tract complications.

Symptom Pecentage Patients
Urinary urgency 72.4% 21
Urinary frequency 65.5% 19
Urinary incontinence 55.2% 16
Urinary hesitancy 51.7% 15
Neurogenic bladder 82.7% 24
Detrusor overactivity 51.7% 15
Detrusor sphincter dysynergia 65.5% 19
Post-void residual >10% of voided volume 41.4% 12

This abstract gets quite "heavy" in its terms - so I've tried to find out what all of these mean, and I've described them below. My take on the paper is that more than 80% of HSP patients have some kind of urinary symptoms, the most common of which is "urgency" - a sudden need to wee. 

In order to allow a bit of self-diagnosis I tried to find out what is "normal". The bladder normally holds 400-600ml although the urge to urinate is usually felt at about 150 ml. Most people go to the toilet four to eight times a day. Most people can sleep for 6 to 8 hours without having to urinate. 

It would seem that bladder problems normally increase with age. Middle aged and older men often wake to urinate once in the early morning hours. Up to 35% of the female population over the age of 60 years is estimated to be incontinent. 17% percent of men over age 60 experience urinary incontinence, with this percentage increasing with age.

My attempt at describing the terms used: 
Detrusor - The bladder muscle
Urination is also known as micturitionvoidingpeeingweeing
Urinary urgency - is a sudden, compelling urge to urinate.
Urinary frequency -  the need to urinate more often than usual
Nocturia - the need to get up in the night to urinate
Urinary incontinence - any involuntary leakage of urine
Urinary hesitancy - a delay between trying to urinate and the flow actually beginning
Neurogenic bladder - dysfunction of the bladder due to disease of the nervous system or nerves
Detrusor overactivity - when the bladder muscle contracts unexpectedly during bladder filling
Detrusor sphincter dysynergia - instead of the urethral sphincter muscle relaxing completely during voiding it contracts causing the flow to be interrupted and the bladder pressure to rise
Post-void residual - the amount of urine retained in the bladder after urination.

As usual, most of my facts are courtesy of Wikipedia with a few other medical sites thrown in for good measure. Having written this I'm reminded of the two Ronnies I want to go to the lavatory sketch about going to the loo with the various smallest room, spend a penny references....

Tuesday, 20 November 2012

Research - the start of the detailed trawl

So, if you've been wondering what on earth I could do with information about 1162 research papers you're not alone. I've been wondering myself as well!

The short answer is that I'm going to read them!

Naturally, many of the papers themselves are only accessible through subscription websites, and so the initial trawl is to look at the abstracts of the papers. I'm doing four things with this:
1) I'm adding the text of the abstract to my database
2) The abstract also includes the location of the research for the paper, so I'm adding that as well (there's a side analysis I'd thought about for looking at research locations)
3) I'm giving all of the papers a "relevance" score, out of 10 - where a low number is that the paper isn't particularly relevant (perhaps HSP is mentioned when the paper is looking at something else) and a high number is where the paper is very relevant.
4) I'm adding tags to the papers so that I can search on those tags, perhaps in combination with the relevance to get a set of papers.

This is going to be a slow process. I've done 10 papers so far, so I'm not 1% through the list yet. Oh, and the search results now gives 1185 papers, so there's another ~25 papers which have been published since August, but I think I'll leave the compilation of those until next year. It might be that I add a few extra fields into the database to group the papers further, but I'll get a few more papers through the list first. To save you reading about this every few weeks and marvelling at the snails pace that I do this, I'll wait till I get a sensible way through and provide some highlight information, and perhaps once I've got through this data pass I'll dig out the most relevant papers and try to get the full papers.

Sunday, 18 November 2012

Symptoms Update - Movements I cannot make

OK, an update on things I cannot do...

The Pilates group that I am a member of is an intermediate level. This week we did two different moves which I found particularly challenging, one simple and one quite complicated.

The simple one is easy to describe - sit with my legs crossed and my back straight, and then rotate each way with my arms out straight. I've commented here before about sitting with my legs crossed, and doing without holding on to my knees was enough of a challenge, so much so that I couldnt get any further. I need to sit on a block to get this to work.

The other move was the Pilates star, which we started to work on for the first time this week. If you look on youtube you'll see various people doing this competently, we were only trying part of this - to raise our leg and circle it. My problem was not being able to raise my leg sufficiently off the floor - I'd have been able to circle it if there was a hole in the ground.....

It makes me wonder how long I can go on saying "no significant symptoms" for. I guess its all in the definition of significant.....

Thursday, 18 October 2012

More Web Pages

So, I realised that I'd been doing all of my internet browsing using Google, and I thought that it would be useful to try some of the other search engines (Bing and Yahoo) and see if they gave rise to any other pages which I'd not seen or listed before. Here is a digest of what I've found: 
A search on "paraplegia" in the "Expert Centres" tab will give a result of clinics/hospitals/organisations which have specific expertise in HSP/FSP

Here are some links to other pages with further details on HSP. These pages do tend to get linked from on other HSP pages, so I tend to regard them as containing something unique.

This site perhaps out to be listed in a "communities" page, and provides another route for people to connect up with others with the condition.

Finally, as part of my "getting side-tracked" functionality, I was very interested to read here that HSP can skip a generation:
"In some types of HSP, an affected person can have an unaffected child and an affected grandchild. The most likely way for it to appear as if HSP has skipped a generation, is if the type of HSP has autosomal dominant or X-linked recessive inheritance.

In some conditions with autosomal dominant inheritance, a person can inherit the genetic change that causes the disorder but not develop the condition. This phenomenon is called incomplete or reduced penetrance. If this person's children also inherits the genetic change, they may or may not be affected with the disorder. When a disorder has reduced penetrance, it may appear as if the disorder has skipped a generation if the disorder is only penetrant in the grandparent and the grandchild. Reduced penetrance has been reported for some types of autosomal dominant HSP.

X-linked HSP can appear to skip a generation because an affected male can only pass his X chromosome to his daughters and not his sons. All of his sons will be unaffected and his daughters will be unaffected carriers. For example, if a man with X-linked HSP has a daughter, she will be an unaffected carrier of HSP. This woman's sons each have a 50% chance of inheriting the condition."

Oh, there's a load of other info here too....

Sunday, 7 October 2012

Index Arrival - Going "Tabular"

This blog is a couple of years old, and I realised that it was getting difficult for me to remember quite what I had found out and where I had posted it, so I decided to make an index. This index is available on new tabs on the blog, allowing you to switch between the blog posts and the index.

In the fullness of time I'll add further tabs for other information - particularly the results of my research papers analysis.

Sunday, 30 September 2012

My thoughts when I was at school

When I was much younger, and hadn't properly understood the how chromosomes combine at conception, I had thought that since I was physically very similar to my dad there was a much smaller chance that I would have inherited the condition (despite being told that it is 50/50).

I had several ideas in my head about how it might work, and I hadn't really appreciated that for each of my pairs of chromosomes one half came from my mum and the other from my dad. As we're looking for something that affects one half of one pair of chromosomes it becomes obvious that its 50/50 irrespective of any other observations.

These days I like to think that I dont take things at face value, and I always try to understand and explore the limits of my knowledge.

Monday, 17 September 2012

Symptoms Update - Use it or Lose it

This post has been a couple of months in gestation. You may have noted that back in June we had a new arrival in the family. For the first few weeks back after my paternity leave I was taking our older son to and from nursery in the car and I opted out of pilates for a similar period. This meant that I did very little exercise for about 6 weeks.

At the end of the six week period I noticed that my legs felt stiffer. Particularly I found that sitting down and standing up were more tricky, with me 'flopping' down into my seat and having to lean forward to change my weight distribution/balance before standing up.

After this time I returned to cycling to work and re-commenced my pilates course, and after another 6-ish week period with my previous level of activity I now appear to be more or less back to where I was before.

Note to self - exercise is important, and I need to keep as active as possible to keep my mobility for as long as possible. On reflection, this is effectively what the neurologist said to me back in Feb 2010, so I'm pleased to be able to confirm that advice.

I'm not sure why, but I had expected that the first muscle groups to go would be those in my lower leg, with my perception being that those would have the longest nerves. I'm certainly going to need to read some of the abstracts of those papers I've found for more info!

Saturday, 25 August 2012

HSP Research - Updated Numbers

OK, so I've done some similar number crunching on the revised set of data as mentioned earlier in the month.

The search adds 553 papers to the 589 that were there before (there are 20 papers in the search where information doesn't appear to be complete, so I'm not including those for now)

The analyses were papers per year - which I've now graphed:

Number of papers per journal. This time I've restricted it to the journals where there have been at least 10 papers published, including "translations" to the full journal titles:

Number of Papers Per Journal
Journal Title Papers Most Recent
Neurology 66 2010
Journal of Neurology, Neurosurgery, and Psychiatry 47 2012
Journal of the Neurological Sciences 36 2012
neurogenetics 34 2012
American Journal of Human Genetics 33 2012
Archives of Neurology 30 2012
Journal of Neurology 29 2012
Human Molecular Genetics 28 2012
Journal of Medical Genetics 28 2009
Brain 26 2010
Rinsho Shinkeigaku (Clinical Neurology) 24 2011
Annals of Neurology 23 2010
European Journal of Neurology 22 2012
Clinical Genetics 22 2012
American Journal of Medical Genetics 21 2002
Movement Disorders 17 2011
Acta Neurologica Scandinavica 16 2009
European Journal of Human Genetics 15 2012
Human Mutation 14 2011
Human Genetics 14 2010
Brain and Nerve / No to Shinkei 12 2003
Neuromuscular Disorders 10 2009

These additional papers add more names to the researchers list, there now being over 4,400 researchers. The number of authors with more than 10 papers published goes up from 39 to 64. This list now looks like this:

Authors of at least 10 papers
Author Papers  1st Yr Last Yr Papers 1st Auth
Brice A 47 1996 2012
Stevanin G 38 1995 2012 4
Fink JK 29 1995 2010 13
Reid E 27 1997 2012 11
Durr A 26 2000 2012 1
Hazan J 23 1993 2010 4
Crosby AH 22 2001 2010 1
Schöls L 22 2002 2012
Dürr A 21 1994 2009 2
Rouleau GA 20 1989 2012
Fontaine B 20 1994 2010 2
Blackstone C 19 2003 2012 2
Santorelli FM 19 2000 2011 1
Klebe S 18 2004 2012 6
Hedera P 18 1999 2011 10
Schüle R 17 2006 2012 6
Auer-Grumbach M 17 1999 2012 1
Pericak-Vance MA 16 1994 2012
Beetz C 16 2004 2012 7
Warner TT 16 2001 2011 1
Nielsen JE 15 1997 2011 4
Bernardi G 15 1993 2012
Tessa A 15 2000 2011 2
Klimpe S 15 2002 2012 2
Rugarli EI 15 2002 2012 1
Kawarai T 14 2002 2011
Depienne C 14 2006 2012 4
Forlani S 14 2006 2011
Hutchinson M 14 1997 2009
Proukakis C 14 2002 2011 4
Orlacchio A 14 2002 2011 9
Casari G 13 1998 2009 2
Weissenbach J 13 1993 2007
Elleuch N 13 2006 2010 2
Deufel T 12 2000 2009
Paternotte C 12 1996 2007 1
Patton MA 12 2001 2010
Boukhris A 12 2007 2011 4
Rainier S 12 1998 2008 5
Sperfeld AD 12 2004 2010 3
Patel H 12 2001 2008 3
Coutinho P 11 1996 2012 1
Bruyn RP 11 1990 2009 6
Bouslam N 11 2005 2007 2
De Jonghe P 11 1996 2012 1
Bertini E 11 1998 2011 1
Martinuzzi A 11 2003 2012
Feki I 11 2000 2011 1
Filla A 11 1998 2010
Kassubek J 11 2004 2012 1
De Michele G 11 1998 2011 1
Shen L 11 2004 2011
Azzedine H 10 2000 2012
Bassi MT 10 1999 2012
Tang BS 10 2001 2011 1
Tallaksen CM 10 2001 2010 2
Ruberg M 10 2003 2009
Iwabuchi K 10 1990 2008 7
Patrono C 10 2000 2010 2
Kobayashi H 10 1995 2003 3
Burgunder JM 10 1996 2010 1
Zatz M 10 1976 2010 1
Goizet C 10 2006 2012 4
Prud'homme JF 10 1996 2007

The top three most published authors remain the same as in the first set of results - A Brice, G Stevanin and JK Fink, but there are other authors appearing in the updated "top ten". I believe that  "Dürr A" should be "Dürr A" which I think is the same person as "Durr A", which would have been first last time, and equal first this time. Another avenue of data cleansing opens....

The latest search is this: There is only one paper which was in my first search which was not returned in this later search. I'll leave the why of this for another day.

Saturday, 11 August 2012

Updated search results - more papers!

Having started to look into the PubMed results a bit more, I wondered if I could find any references to those original Strumpell and Lorrain papers, and started searching around for them.

No joy, but I did manage to find some earlier papers on HSP/FSP, and I realise that the search I was using is limited.

So, the previous search:,%20Hereditary%22[Majr] now reveals 599, suggesting another 10 papers have been added. The earliest paper is from 1978, which I now realise means theres not far off 100 years worth of potentially published research missing.

So, I've spent a while messing about trying to get better results. It seems there's a balance to be struck. For example, a simple search on spastic paraplegia reveals some 17,000 results, and thats because the simple search brings back every paper with both words somewhere in the entry.

A better search result happens when you put quotes round "spastic paraplegia", giving some 1500 results. If the term "strumpell lorrain" is added you add a few more, including some back to the late 1800's.

However, its clear from browsing some of the abstracts that not all of these appear to be obviously relevant, so I added in the words hereditary and familial to the search. This gives a total of 1162 papers. Search here: Earliest paper - 1946.

Next stage - to update my previous analyses of data and find out the most popular journals, years of research and published authors. Note - I have a feeling that this will end up being an iterative process, so I think I'll post this data on a page rather than in a post.

Sunday, 15 July 2012

Current Research Highlights

I was having a read around the other week, and I found a link on the rareconnect website to this article:

The article, written by Allen Bernard (whose daughter has HSP), is based on his discussions with five of the world's leading HSP researchers: 
  • Dr. Craig Blackstone at the National Institutes of Health in Bethesda, Maryland; 
  • Dr. Evan Reid at the University of Cambridge in the UK;
  • Dr. Gerardo Morfini at the University of Illinois, Chicago;
  • Dr. Joanna Bakowska at Loyola University, Chicago; and 
  • Dr. Michael Hanna at the Texas A&M University, Commerce.
Of course, its difficult to abbreviate a 13 page document into a single blog post, but here we go - I've lifted various paragraphs from the document here:

Researchers working on hereditary spastic paraplegia, better known as HSP, know more today than ever before. They are uncovering new linkages between the proteins that are at the heart of the disorder all the time. If you rewind the clock just five years, almost nothing was known about the proteins involved in HSP, how they interacted, what they did or why they did it. Since then much has been learned. If you go back 10 years, some of the proteins involved where just being uncovered. Go back 15 and HSP was almost a complete mystery.

One of things that HSP has going for it from a treatment point of view is the proteins like atlastin are fundamental to how cells work. Because of this, cell biologists are becoming increasingly interested in studying them so they can increase their knowledge of basic biology. This greatly expands the base of very smart people exploring what these proteins do and how they do it. For a very rare disease like HSP, this is like hitting a walk-off homerun because it opens the door to unlooked-for-discoveries by researchers outside of the HSP field that could lead to significant breakthroughs in how HSP is understood and treated.

Researchers are finding more and more targets - functions like axonal transport and structures called microtubules, for example - to focus on for potential treatments.  To find a 'wonder drug', you might think that money is the end all, but perhaps the biggest inhibitor to finding a treatment is lack of good animal models.

While HSP-like symptoms can be created in mice, for example, the phenotype that mice exhibit is less severe than in people and, therefore, harder to measure. Also, mice are just a few inches from head to tail while the cells involved in human HSP are up to a meter long. Mice also take a long time to mature. So when you work with mice, it can take up to a year or more for symptoms to show. 

That is why researchers often turn to fruit flies, which share the majority of their genes with humans (they just have fewer variations of them) and they reproduce very quickly so you can see results much sooner. But, fruit flies are not people. They can point you in the right direction; give you an idea of what to look for or what questions to ask but they won't serve as a stand in for us. 

Researchers like Dr. Morfini also work with squid since their axons can be removed, viewed under a microscope, and react to HSP similarly to our own. Squid have long been used to study other central nervous system (CNS) diseases like ALS and Parkinson's so a lot is known about their basic structure. 

This makes squid an important source of information since 99 percent of a motor neuron cell is actually made up of its axon. So axonal transport, or the movement of molecules and proteins up and down the long thin tube that is the axon, is also considered by many in the field to be an good place to look for a cause of HSP. Any disruption of this very finely tuned architecture could result in disease.

HSP could be a a "Gateway Disease," a disease that leads to treatments and cures for some of today's most intractable illnesses. There are  conditions like Charcot Marie Tooth Type 2b and some neuropathies (a loss of sensation in the feet and hands that can lead to amputations) that involve the same proteins as HSP and yet, on the outside, look completely different. This is the type of thing that gets researchers from other fields interested because there must be something very fundamental going on.

ALS and its cousin primary lateral sclerosis (PLS) also have something in common with HSP because of proteins. So, at some point in the future, a researcher in one of these fields or an HSP researcher could uncover a strong bond that could lead to a treatment for both. Multiple sclerosis (MS) is another disease where there appears to be some overlap but all of these connection need to be explored much more deeply.

Current research highlights:
Bone Morphogenic Protein (BMP) signaling

One of the more promising areas of research is being pursued by Dr. Reid at the University of Cambridge. He and his team are looking at something called the BMP signaling. While BMP stands for bone morphogenic protein, what's really important is it appears that atlastin (SPG3A), spastin (SPG4), maspardin (SPG21), spartin (SPG20), and NIPA1 (SPG6) are all part of the same functional pathway within the motor neuron. 

BMP signaling appears to play a key role in how axons grow and what they look like as they branch out into synapses. It is this distal end of the axon, the one at the base of the spine, that connects the neurons in your motor cortex to your legs. If BMP signaling causes HSP's symptoms, then you have a target to go after with drugs. Dr. Reid strongly believes this could be the case but more research needs to be done; particularly in animals; especially in mammals.

Endoplasmic Reticulum (ER)

Dr. Blackstone's work has led to the realization that spastin, atlastin, REEP1, reticulon2 and possibly NIPA1 are all involved in shaping a very important organelle inside the cell called endoplasmic reticulum (ER). And this is extremely important from a cell biology point of view because the ER sits at the heart of cell function and is believed to run the length of the axon.

Indeed, before the discovery of atlastin, no one really understood why the ER looked the way it did. Now, HSP has opened a window into this most essential part of the cell. A gateway, if you will, to this and many other areas of cellular function that are now better understood because of HSP.

Casein kinase  2 (CK2)

Working together, the research teams of Dr. Morfini and Dr. Peter Baas at Drexel University in Philadelphia have found a potential target for a treatment of SPG4, spastin. Like Dr. Reid, their findings are preliminary but, if they pan out, they might provide a new framework for the development of treatments that may help prevent motor neuron degeneration in HSP. 

Their findings indicate that the protein kinase CK2, which regulates the activity of other proteins, is abnormally activated by mutant forms of spastin. Abnormally activated CK2, in turn, negatively affects yet other proteins that are involved in the movement of materials along the axons in an important cellular process referred to as “axonal transport”

Like many other protein kinases, CK2 is a drugable target. What's exciting about Drs. Morfini's and Baas’s work is that CK2 has been studied for decades, so it is very well understood and there are currently cancer drugs in Phase I of the FDA approval process today to regulate it.

Thursday, 5 July 2012

Another new arrival - and cord blood storage

An update - a couple of weeks ago my wife gave birth to our second son. Double trouble in a few years, I'm sure!

We repeated the decision that we took for our first son, and decided to get the cord blood stored again. As a reminder for the first decision:

One of the things which the genetics team said back at the beginning was that if we had two children, one with and one without the condition, then (provided there was a treatment available) the stem cells of the one without may be more of use to the one with. This info now becomes relevant.

In case anyone is interested, we used cells 4 life The process was much easier this time as they now offer a phlebotomy service too. If anyone is thinking of doing this, then as a referral from an existing customer gets you (and me) a £50 Marks and Spencer voucher. Drop me a line....

Naturally, the HSP angle is still in the blue sky thinking zone, but there may be other uses for these as we go. Only the passing of the years will tell.

Friday, 15 June 2012

Symptoms Update - Shoe wear and 'skid marks'

I think I've spotted the next part of my symptoms. A look at my shoes shows that the heel is starting to be pushed outwards. I think this means that my gait must be changing. Interestingly it is noticeable on my left shoe more than my right shoe. The effect is slight, and I've had these shoes for a while.

Just thinking, if my heels are starting to poke out, I suppose that my knees must be getting closer together. I base this supposition on the scenario that its a walking thing, each step pushes my weight out and I dont think that my feet are further apart. I cant work out if my toes are pointing in more, and I'll need to do some more observing.

I'll also keep a lookout on my other pairs of shoes, as it's just one pair at the moment.

Also, on a similar front, I've noticed that I now have 'skid marks' on the cill of my car door where my right foot has slid over rather than me lifting it over after sitting down. I've only just noticed these marks, which perhaps suggests that its a fairly recent thing, having had the car for getting on for four years.

Overall, My conclusion is that my symptoms are starting to progress, and my wife has also noticed that my walking appears more difficult when I am tired or carrying heavy weights (3 year old boy sized). I wonder how long I'll be able to claim "no significant symptoms"....

Sunday, 3 June 2012

Researchers - Most published

OK, a bit more number crunching on the papers I downloaded. There are over 2500 researchers who have contributed to the 589 different papers - so that's on average some 4-5 people per paper. A list of 2500 researchers would be a silly thing to put here, so I've limited as follows:
* Anyone who has been an author on 10 or more papers
* Anyone who has been an author on 5 or more papers when the most recent paper is 2010 or later
* Anyone who has been an author when the most recent paper is in 2012

This gives 103 researchers, sorted by papers, last year, then name.

I haven't yet worked out how to convert the funny characters into proper letters. A later (potential) task for another day is to find a biography of each.

Researcher Details
Author Number Papers First Year Last Year
Brice A 28 1999 2010
Stevanin G 27 2004 2011
Fink JK 23 1995 2010
Crosby AH 20 2001 2010
Durr A 19 2003 2011
Santorelli FM 16 2000 2011
Klebe S 15 2004 2012
Hedera P 15 1999 2011
Nielsen JE 15 1997 2011
Hazan J 15 1993 2007
Reid E 14 2002 2011
Fontaine B 14 1994 2010
Dürr A 14 1994 2009
Schöls L 13 2002 2012
Beetz C 13 2006 2010
Klimpe S 12 2002 2012
Rouleau GA 12 1989 2012
Forlani S 12 2006 2011
Pericak-Vance MA 12 1994 2011
Proukakis C 12 2002 2011
Tessa A 12 2000 2011
Warner TT 12 2001 2011
Elleuch N 12 2006 2010
Patton MA 12 2001 2010
Hutchinson M 12 1997 2009
Schüle R 11 2006 2012
Kawarai T 11 2002 2011
Orlacchio A 11 2002 2011
Sperfeld AD 11 2004 2010
Patel H 11 2001 2008
Kassubek J 10 2004 2012
Bernardi G 10 2002 2011
Boukhris A 10 2008 2011
Shen L 10 2004 2011
Bruyn RP 10 1990 2009
Deufel T 10 2002 2009
Rainier S 10 1998 2008
Bouslam N 10 2005 2007
Kobayashi H 10 1995 2003
Bertini E 9 2000 2011
Depienne C 9 2006 2011
Rugarli EI 9 2002 2011
Blackstone C 8 2005 2011
De Michele G 8 1998 2011
Goizet C 8 2006 2011
Tang BS 8 2003 2011
Xia K 8 2003 2011
Zhao GH 8 2003 2011
Marchuk DA 8 2001 2010
Tallaksen CM 8 2001 2010
Feki I 7 2007 2011
Martinuzzi A 7 2003 2011
Sauter SM 7 2004 2011
Burgunder JM 7 1998 2010
Truchetto J 7 2008 2010
van de Warrenburg BP 7 2006 2010
Klopstock T 6 2006 2012
Bassi MT 6 2003 2011
Boespflug-Tanguy O 6 2002 2011
Braschinsky M 6 2009 2011
Gross-Paju K 6 2009 2011
Haldre S 6 2009 2011
Houlden H 6 1998 2011
Jiang H 6 2004 2011
Langer T 6 2003 2011
Mannan AU 6 2006 2011
De Jonghe P 6 1999 2010
Filla A 6 1998 2010
Lossos A 6 2006 2010
Mostacciuolo ML 6 2000 2010
Yang Y 6 2000 2010
Otto S 5 2006 2012
Criscuolo C 5 2004 2011
D'Angelo MG 5 2006 2011
Denora PS 5 2006 2011
Gaudiello F 5 2004 2011
Mundwiller E 5 2009 2011
Svenstrup K 5 2007 2011
Wood NW 5 2001 2011
Ludolph AC 5 1998 2010
Mhiri C 5 2008 2010
Siddique T 5 1994 2010
Zatz M 5 2002 2010
Ki CS 4 2005 2012
Brais B 3 2006 2012
Rioux MF 3 2006 2012
Dion PA 2 2007 2012
Dupré N 2 2007 2012
Karle K 2 2009 2012
Lee ST 2 2010 2012
Lee WY 2 2005 2012
Ahn JY 1 2012 2012
Caplan JP 1 2012 2012
Cho JW 1 2012 2012
Kohl Z 1 2012 2012
Levert A 1 2012 2012
Noreau A 1 2012 2012
Osmolak AM 1 2012 2012
Ratzka S 1 2012 2012
Szuto A 1 2012 2012
Thibodeau P 1 2012 2012
Wallenberg RB 1 2012 2012
Yoon WT 1 2012 2012