In my search for different on-line HSP communities I found "patientslikeme". This site has an HSP community with 56 people with the condition.
Personally, I'm reluctant to join this community as they sell users information in order to make profit, therefore I'll just mention this for information.
http://www.patientslikeme.com/conditions/493-hereditary-spastic-paraplegia
Saturday, 19 May 2012
Sunday, 6 May 2012
Joining Communities
In the last few weeks I've changed my policy slightly - from a passive to an active contributor.
Previously, other than telling my immediate family, I'd been staying silent about my blog. Naturally I'd been keeping my eyes out to see if had been popping up anywhere. And, until a month or two ago it seemed to be 'under the radar' then I spotted it on rarediseasecommunity - now called rareconnect.
So, I joined up with rareconnect, and posted a link to this blog: http://www.rareconnect.org/en/community/hereditary-spastic-paraplegia/article/link-to-my-fsp-hsp-blog
I also joined the hsp support group http://hspgroup.org/, and am starting off letting members know about this blog. With hindsight, I cant find a good reason why I hadn't sign up here earlier, but done now.
I'm not one for 'shouting from the rooftops', so this will be a gradual process.
Sunday, 29 April 2012
Researchers - Initial Numbers
So, Thanks to a post from Rob from EURODIS on Rarediseasecommunity, I have been looking at PubMed, which has a directory of medical publications. On 20th April there were 589 different papers listed for HSP. I'm doing a bit of number crunching on this information. There are two simple sets of numbers - number of papers per year and number of papers per journal which are easy to find out:
Papers per year:
Papers per journal - note that I've yet to decipher the abbreviations:
More details in a later post - the link with all this lovely info is here: http://www.ncbi.nlm.nih.gov/pubmed?term=%22Spastic%20Paraplegia,%20Hereditary%22[Majr]
Papers per year:
| Year | Papers |
|---|---|
| 2012 | 4 |
| 2011 | 35 |
| 2010 | 38 |
| 2009 | 49 |
| 2008 | 45 |
| 2007 | 45 |
| 2006 | 48 |
| 2005 | 28 |
| 2004 | 36 |
| 2003 | 36 |
| 2002 | 30 |
| 2001 | 27 |
| 2000 | 18 |
| 1999 | 25 |
| 1998 | 24 |
| 1997 | 13 |
| 1996 | 4 |
| 1995 | 9 |
| 1994 | 10 |
| 1993 | 16 |
| 1992 | 8 |
| 1991 | 13 |
| 1990 | 18 |
| 1989 | 6 |
| 1988 | 3 |
| 1978 | 1 |
Papers per journal - note that I've yet to decipher the abbreviations:
| Journal | Papers | Most Recent |
|---|---|---|
| Neurology | 48 | 2010 |
| J Neurol Neurosurg Psychiatry | 24 | 2010 |
| J Neurol Sci | 23 | 2011 |
| J Neurol | 22 | 2011 |
| Arch Neurol | 22 | 2009 |
| Neurogenetics | 21 | 2011 |
| Am J Hum Genet | 20 | 2008 |
| Eur J Neurol | 17 | 2012 |
| J Med Genet | 16 | 2009 |
| Ann Neurol | 15 | 2007 |
| Mov Disord | 13 | 2011 |
| Clin Genet | 13 | 2011 |
| Hum Mutat | 12 | 2011 |
| Hum Mol Genet | 12 | 2010 |
| Brain | 10 | 2010 |
| Hum Genet | 10 | 2010 |
| No To Shinkei | 9 | 2003 |
| Acta Neurol Scand | 9 | 2002 |
| Zhonghua Yi Xue Yi Chuan Xue Za Zhi | 8 | 2009 |
| Am J Med Genet | 8 | 2002 |
| Clin Neurol Neurosurg | 6 | 2011 |
| Eur J Hum Genet | 6 | 2009 |
| Nat Genet | 6 | 2007 |
| Neuromuscul Disord | 5 | 2009 |
| Ryoikibetsu Shokogun Shirizu | 5 | 2001 |
| J Child Neurol | 4 | 2010 |
| Chin Med J (Engl) | 4 | 2009 |
| J Cell Biol | 4 | 2009 |
| Neuropediatrics | 4 | 2006 |
| Rinsho Shinkeigaku | 4 | 2001 |
| Dev Med Child Neurol | 4 | 1993 |
| Can J Neurol Sci | 3 | 2012 |
| Neurol Sci | 3 | 2011 |
| Pediatr Neurol | 3 | 2011 |
| Prenat Diagn | 3 | 2010 |
| Brain Dev | 3 | 2010 |
| Arq Neuropsiquiatr | 3 | 2010 |
| J Neurochem | 3 | 2009 |
| Funct Neurol | 3 | 2007 |
| Curr Opin Neurol | 3 | 2007 |
| Muscle Nerve | 3 | 2007 |
| Eur Neurol | 3 | 2007 |
| Neuroradiology | 3 | 2006 |
| Cell | 3 | 2005 |
| Curr Biol | 3 | 2005 |
| Zh Nevropatol Psikhiatr Im S S Korsakova | 3 | 1991 |
| Clin Neurophysiol | 2 | 2011 |
| Acta Neuropathol | 2 | 2011 |
| Genome Res | 2 | 2011 |
| J Clin Neuromuscul Dis | 2 | 2011 |
| BMC Biol | 2 | 2010 |
| J Clin Invest | 2 | 2010 |
| BMC Neurol | 2 | 2010 |
| Am J Med Genet B Neuropsychiatr Genet | 2 | 2009 |
| Arch Phys Med Rehabil | 2 | 2009 |
| Hong Kong Med J | 2 | 2009 |
| J Inherit Metab Dis | 2 | 2008 |
| Lancet Neurol | 2 | 2008 |
| Neurosci Lett | 2 | 2008 |
| J Biol Chem | 2 | 2008 |
| Expert Opin Pharmacother | 2 | 2007 |
| Int J Obstet Anesth | 2 | 2007 |
| Am J Med Genet A | 2 | 2005 |
| Neuropathology | 2 | 2005 |
| Amyotroph Lateral Scler Other Motor Neuron Disord | 2 | 2005 |
| Neuropathol Appl Neurobiol | 2 | 2004 |
| Nervenarzt | 2 | 2003 |
| Genomics | 2 | 2003 |
| Semin Neurol | 2 | 1999 |
| Nat Med | 2 | 1998 |
| Pediatr Neurosurg | 2 | 1995 |
| Genet Couns | 2 | 1994 |
| Ital J Neurol Sci | 2 | 1993 |
| Eur Arch Psychiatry Neurol Sci | 2 | 1990 |
| Psychosomatics | 1 | 2012 |
| Spinal Cord | 1 | 2011 |
| Eur J Paediatr Neurol | 1 | 2011 |
| Curr Mol Med | 1 | 2011 |
| Eur J Med Genet | 1 | 2011 |
| Orphanet J Rare Dis | 1 | 2011 |
| Nat Rev Neurosci | 1 | 2011 |
| PLoS Genet | 1 | 2011 |
| Genet Med | 1 | 2011 |
| Gait Posture | 1 | 2011 |
| Amyotroph Lateral Scler | 1 | 2011 |
| Rev Esp Anestesiol Reanim | 1 | 2011 |
| Mol Cell Neurosci | 1 | 2011 |
| Neurologist | 1 | 2011 |
| Mitochondrion | 1 | 2011 |
| Zh Nevrol Psikhiatr Im S S Korsakova | 1 | 2010 |
| No To Hattatsu | 1 | 2010 |
| PLoS Biol | 1 | 2010 |
| Toxicol Lett | 1 | 2010 |
| Dis Model Mech | 1 | 2010 |
| J Lipid Res | 1 | 2010 |
| Ann Clin Lab Sci | 1 | 2010 |
| Hum Brain Mapp | 1 | 2010 |
| Neuroepidemiology | 1 | 2009 |
| Rom J Morphol Embryol | 1 | 2009 |
| Clin Rehabil | 1 | 2009 |
| AJNR Am J Neuroradiol | 1 | 2009 |
| Ann Anat | 1 | 2009 |
| Adv Exp Med Biol | 1 | 2009 |
| Synapse | 1 | 2009 |
| Nature | 1 | 2008 |
| Acta Neurol Scand Suppl | 1 | 2008 |
| SEB Exp Biol Ser | 1 | 2008 |
| BMC Med Genet | 1 | 2008 |
| J Neurosci | 1 | 2008 |
| J Neurogenet | 1 | 2008 |
| J Intellect Disabil | 1 | 2008 |
| Neuroscience | 1 | 2008 |
| Med Arh | 1 | 2007 |
| Mol Cell Biol | 1 | 2007 |
| Mol Neurobiol | 1 | 2007 |
| Brain Res Bull | 1 | 2007 |
| Pediatr Radiol | 1 | 2007 |
| Tidsskr Nor Laegeforen | 1 | 2007 |
| Curr Neurol Neurosci Rep | 1 | 2006 |
| Anesth Analg | 1 | 2006 |
| J Hum Genet | 1 | 2006 |
| Trends Mol Med | 1 | 2006 |
| Ren Fail | 1 | 2006 |
| Panminerva Med | 1 | 2006 |
| Proc Natl Acad Sci U S A | 1 | 2006 |
| Pharmacol Ther | 1 | 2006 |
| Cell Mol Neurobiol | 1 | 2005 |
| Ceylon Med J | 1 | 2005 |
| Biochem Biophys Res Commun | 1 | 2005 |
| J Clin Neurosci | 1 | 2004 |
| Ned Tijdschr Geneeskd | 1 | 2004 |
| Parkinsonism Relat Disord | 1 | 2004 |
| Neuroreport | 1 | 2003 |
| IUBMB Life | 1 | 2003 |
| Exp Neurol | 1 | 2003 |
| Nihon Rinsho | 1 | 2002 |
| Masui | 1 | 2002 |
| Int Rev Neurobiol | 1 | 2002 |
| Neurol Clin | 1 | 2002 |
| Curr Opin Genet Dev | 1 | 2001 |
| Rev Prat | 1 | 2001 |
| Pharmacogenomics | 1 | 2001 |
| Retina | 1 | 2000 |
| Rev Neurol (Paris) | 1 | 2000 |
| Neurophysiol Clin | 1 | 2000 |
| Can J Anaesth | 1 | 1999 |
| Biochim Biophys Acta | 1 | 1999 |
| Electromyogr Clin Neurophysiol | 1 | 1999 |
| Physiother Res Int | 1 | 1999 |
| Neurochirurgie | 1 | 1998 |
| Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi | 1 | 1998 |
| Schweiz Med Wochenschr | 1 | 1998 |
| Hum Hered | 1 | 1998 |
| Am J Phys Med Rehabil | 1 | 1998 |
| J Clin Epidemiol | 1 | 1997 |
| Epilepsia | 1 | 1997 |
| Acta Paediatr | 1 | 1996 |
| Acta Neurochir Suppl | 1 | 1995 |
| Brain Pathol | 1 | 1995 |
| Aust N Z J Psychiatry | 1 | 1995 |
| Vojnosanit Pregl | 1 | 1993 |
| Electroencephalogr Clin Neurophysiol | 1 | 1993 |
| Paraplegia | 1 | 1993 |
| J Neurosurg Sci | 1 | 1993 |
| Neurourol Urodyn | 1 | 1993 |
| Aust Vet J | 1 | 1993 |
| Orthop Rev | 1 | 1992 |
| Minerva Med | 1 | 1992 |
| Clin Neuropharmacol | 1 | 1991 |
| Clin Exp Neurol | 1 | 1991 |
| Fortschr Neurol Psychiatr | 1 | 1991 |
| J Assoc Physicians India | 1 | 1990 |
| Am J Hematol | 1 | 1990 |
| N Engl J Med | 1 | 1990 |
| Prog Clin Biol Res | 1 | 1989 |
| J Med Assoc Thai | 1 | 1989 |
| Medicina (B Aires) | 1 | 1988 |
| Ann Pediatr (Paris) | 1 | 1978 |
More details in a later post - the link with all this lovely info is here: http://www.ncbi.nlm.nih.gov/pubmed?term=%22Spastic%20Paraplegia,%20Hereditary%22[Majr]
Tuesday, 17 April 2012
Spastic Gait
I realised that I've been blogging for a while and haven't really touched upon the primary outcome of FSP/HSP - the spastic gait. This is also identified on some FSP sites as a scissor gait.
There are a number of references which give descriptions of a spastic gait - here's part of one I like:
When a person has a spastic gait, his legs are typically weak and abnormally stiff. As he walks, he holds his legs closer together than normal, drags his feet or toes, and lacks the typical flexibility in his ankles and knees. When a person has a spastic gait, his legs, toes, and feet are stiffer than normal. He typically does not flex his muscles and bend his legs as he walks. Instead, long-term muscle contractions usually cause him to drag one foot or his toes when he walks. Sometimes medications may also be used to treat this gait problem. For example, medicines may be used to reduce muscle contraction, but the effects of many medications are still being studied. (http://www.wisegeek.com/what-is-a-spastic-gait.htm)
Here is a description of scissor gait http://www.gpnotebook.co.uk/simplepage.cfm?ID=818937856: Scissor gait is the term used to describe the manner of walking that is seen in patients with spastic paraplegia, the features are:
Of course, the shortest definitions are often the best: http://medical-dictionary.thefreedictionary.com/Scissors+gait:
scissors gait a crossing of the legs while advancing with slow, small steps.
spastic gait a walk in which the legs are held together and move in a stiff manner, the toes seeming to drag and catch. A slow, shuffling gait in which the patient appears to be wading in water. Knee and hip movements are restricted.
What I'm looking for is the sequence. It would appear to start like this: Initial symptoms are typically difficulty with balance, stubbing the toe or stumbling. (symptoms: http://en.wikipedia.org/wiki/Hereditary_spastic_paraplegia) but there doesnt seem to be much around which describe the next steps. Perhaps this is something I'll have to note myself in my symptoms updates.
I also found these exercises which claim to improve gait:
http://www.ncpad.org/exercise/fact_sheet.php?sheet=566§ion=2632
There are a number of references which give descriptions of a spastic gait - here's part of one I like:
When a person has a spastic gait, his legs are typically weak and abnormally stiff. As he walks, he holds his legs closer together than normal, drags his feet or toes, and lacks the typical flexibility in his ankles and knees. When a person has a spastic gait, his legs, toes, and feet are stiffer than normal. He typically does not flex his muscles and bend his legs as he walks. Instead, long-term muscle contractions usually cause him to drag one foot or his toes when he walks. Sometimes medications may also be used to treat this gait problem. For example, medicines may be used to reduce muscle contraction, but the effects of many medications are still being studied. (http://www.wisegeek.com/what-is-a-spastic-gait.htm)
Here is a description of scissor gait http://www.gpnotebook.co.uk/simplepage.cfm?ID=818937856: Scissor gait is the term used to describe the manner of walking that is seen in patients with spastic paraplegia, the features are:
- rigidity and excessive adduction of the leg in swing
- plantar flexion of the ankle
- flexion at the knee
- adduction and internal rotation at the hip
- contractures of all spastic muscles
The individual is thus forced to walk up on tip-toe, the other contractures resulting in the knees rubbing together and crossing in a manner analogous to scissors.
Of course, the shortest definitions are often the best: http://medical-dictionary.thefreedictionary.com/Scissors+gait:
scissors gait a crossing of the legs while advancing with slow, small steps.
spastic gait a walk in which the legs are held together and move in a stiff manner, the toes seeming to drag and catch. A slow, shuffling gait in which the patient appears to be wading in water. Knee and hip movements are restricted.
What I'm looking for is the sequence. It would appear to start like this: Initial symptoms are typically difficulty with balance, stubbing the toe or stumbling. (symptoms: http://en.wikipedia.org/wiki/Hereditary_spastic_paraplegia) but there doesnt seem to be much around which describe the next steps. Perhaps this is something I'll have to note myself in my symptoms updates.
I also found these exercises which claim to improve gait:
http://www.ncpad.org/exercise/fact_sheet.php?sheet=566§ion=2632
Friday, 23 March 2012
Symptoms update - beer
Here's one from the 'not sure' category.
I went to the pub one evening this week with a friend for a couple of beers and a chat. That was good, but I think I noticed that I was finding it marginally more difficult to walk home than on the way there. Certainly I managed to trip up on a perfectly flat surface just outside the pub, but I think I felt that I needed more muscle effort to make my legs walk. I've also been quite tired too this week.
This made me think that my post back in November where I talked about emotional effects might have had an alcohol effect too - after all I had had "a couple" of drinks that night too.
I'm going to have to pay attention to these three factors: alcohol, emotions and tiredness to see if I can decide if one plays a stronger influence than the others.
Booze barometer - this week was a genuine couple - I had 3 pints. In November I had had considerably more than this.
I went to the pub one evening this week with a friend for a couple of beers and a chat. That was good, but I think I noticed that I was finding it marginally more difficult to walk home than on the way there. Certainly I managed to trip up on a perfectly flat surface just outside the pub, but I think I felt that I needed more muscle effort to make my legs walk. I've also been quite tired too this week.
This made me think that my post back in November where I talked about emotional effects might have had an alcohol effect too - after all I had had "a couple" of drinks that night too.
I'm going to have to pay attention to these three factors: alcohol, emotions and tiredness to see if I can decide if one plays a stronger influence than the others.
Booze barometer - this week was a genuine couple - I had 3 pints. In November I had had considerably more than this.
Sunday, 11 March 2012
Another Name - Jean-Martin Charcot
One of my objectives is to generate a list of current researchers working with HSP, and I suspect that is going to take a while to do. I've a few starting points, and a vague approach in my mind, but I'm going to need to concentrate so I try not to miss any avenues.
In the mean time my brain was turning to the discovery of the condition, and I remember reading on the SP Foundation website: http://www.sp-foundation.org/hsp.html the reference to another name - a Frenchman called Charcot, with another alternative name for the condition: hereditary charcot disease. This post seeks more info - I Hadn't picked up Charcot before.
More info doesn't seem to be easy to find. I suspect that Charcot would be Jean-Martin Charcot, who was French and lived 1825-1893, so would have been around at the time of Strumpells 1880 paper but not Lorrains 1898 paper. Also in his favour was that he was a neurologist. Charcot is much better known for work in MS and Parkinsons, and for his approach to neurological examination. You can read more at wikipedia: http://en.wikipedia.org/wiki/Jean-Martin_Charcot. These higher profile conditions, and CMT tend to flood the search results.
Another supporting observation is that Pierre Marie was a student of Charcot, who also worked with Adolph Strumpell - leading to Marie–Strümpell disease.
It would be nice to find references to Charcots work, which would be from the last three years of his life. If anyone has details, I would be pleased to receive.
In the mean time my brain was turning to the discovery of the condition, and I remember reading on the SP Foundation website: http://www.sp-foundation.org/hsp.html the reference to another name - a Frenchman called Charcot, with another alternative name for the condition: hereditary charcot disease. This post seeks more info - I Hadn't picked up Charcot before.
More info doesn't seem to be easy to find. I suspect that Charcot would be Jean-Martin Charcot, who was French and lived 1825-1893, so would have been around at the time of Strumpells 1880 paper but not Lorrains 1898 paper. Also in his favour was that he was a neurologist. Charcot is much better known for work in MS and Parkinsons, and for his approach to neurological examination. You can read more at wikipedia: http://en.wikipedia.org/wiki/Jean-Martin_Charcot. These higher profile conditions, and CMT tend to flood the search results.
Another supporting observation is that Pierre Marie was a student of Charcot, who also worked with Adolph Strumpell - leading to Marie–Strümpell disease.
It would be nice to find references to Charcots work, which would be from the last three years of his life. If anyone has details, I would be pleased to receive.
Wednesday, 22 February 2012
Some more website links
During my surfing, I've found a few more links to useful things:
A federation of national HSP support groups covering Denmark, France,Italy, The Netherlands, Norway, Spain and the UK:
http://sites.google.com/site/eurohsp/who-we-are
The HSP entry in the rare diseases community - links to support groups and plenty of recent posts with peoples stories. I'm pleased to see that there's a link to this blog here!
http://www.rarediseasecommunities.org/en/community/hereditary-spastic-paraplegia?
Some 2011 research giving a detailed account of the biochemical workings of atlastin, a protein produced by one of the genes linked to HSP:
http://www.sciencedaily.com/releases/2011/07/110708124544.htm
A blog post reporting some research from 2004 into how spastin is involved in neuronal communication.
http://scienceblog.com/community/older/2004/2/20041849.shtml
Another site with a summary of the condition:
http://www.asktheneurologist.com/hereditary-spastic-paraparesis.html
And just for fun, the misspellin version of wikipedia. p.s. its not may fault of you spend hours just looking up other stuff on this page!
http://www.wikipeetia.org/Hereditari_spastic_paraplegia
Friday, 10 February 2012
Location for variants, and more on genes
Before I undertook my trawl of the different variants of HSP, I had in my mind that I would be able to find a "translation" between the detailed results of genetic tests and the variant of the condition. I thought it would be quite a simple exercise - listing the known genetic variations by SPG number and making something clear which I thought wasn't too clear when I got my test results.
Of course, now I realise that there are over 270 genetic variants for SPG4 and over 70 for SPG 11 I realise that this would be a mammoth table, so not something that is easily undertaken. So, a much simpler question to ask is "which genes are affected" - It would seem that each SPG variant affects a different gene, so there are 48 answers to that question. A brief trawl of the internet identifies that the more commonly occurring variants have had their genes named:
A more detailed trawl (for another day) may get further down this line.
Which leads me to perhaps an even more basic question - which chromosomes are affected. I know the Spast gene is on Chromosome 2, but are all the SPG variants? - Quick answer: No.
This made me realise that I had described my genetic test result, and looked at the chromosomal location for other SPGs without really explaining to myself what was going on. There were various references to 'p's and 'q's, but I didn't really understand. So, here goes:
There are 23 pairs of chromosomes in the human body. The first 22 pairs are the same, whereas the last pair is different - and identifies your sex. The chromosomes are numbered by length, with number 1 being the longest and 22 being the shortest. Each chromosome has two arms either side of a narrowing (or centromere). These are the 'p' and the 'q' arms, the 'p' arm is the shortest arm (coming from the French petit - small). Starting at the centromere the locations on the gene are numbered sequentially, with the first location being given 1, the second 2 etc. etc.
So SPG4 is 2p24-2p21, meaning its on the short arm of the 2nd chromosome, between the 21st and 24th location away from the centromere.
This allows me to do a quick set of stats on my trawl of SPG variants - number of variants on each chromosome:
Of course, now I realise that there are over 270 genetic variants for SPG4 and over 70 for SPG 11 I realise that this would be a mammoth table, so not something that is easily undertaken. So, a much simpler question to ask is "which genes are affected" - It would seem that each SPG variant affects a different gene, so there are 48 answers to that question. A brief trawl of the internet identifies that the more commonly occurring variants have had their genes named:
| SPG4 | Spastin |
| SPG11 | Spastacin |
| SPG3A | Alastin |
| SPG7 | Paraplegin |
| SPG17 | Seipin |
Which leads me to perhaps an even more basic question - which chromosomes are affected. I know the Spast gene is on Chromosome 2, but are all the SPG variants? - Quick answer: No.
This made me realise that I had described my genetic test result, and looked at the chromosomal location for other SPGs without really explaining to myself what was going on. There were various references to 'p's and 'q's, but I didn't really understand. So, here goes:
There are 23 pairs of chromosomes in the human body. The first 22 pairs are the same, whereas the last pair is different - and identifies your sex. The chromosomes are numbered by length, with number 1 being the longest and 22 being the shortest. Each chromosome has two arms either side of a narrowing (or centromere). These are the 'p' and the 'q' arms, the 'p' arm is the shortest arm (coming from the French petit - small). Starting at the centromere the locations on the gene are numbered sequentially, with the first location being given 1, the second 2 etc. etc.
So SPG4 is 2p24-2p21, meaning its on the short arm of the 2nd chromosome, between the 21st and 24th location away from the centromere.
This allows me to do a quick set of stats on my trawl of SPG variants - number of variants on each chromosome:
| Chromosome | Number |
| 1 | 4 |
| 2 | 4 |
| 3 | 3 |
| 4 | 1 |
| 5 | 0 |
| 6 | 1 |
| 7 | 1 |
| 8 | 3 |
| 9 | 2 |
| 10 | 4 |
| 11 | 2 |
| 12 | 3 |
| 13 | 2 |
| 14 | 4 |
| 15 | 3 |
| 16 | 2 |
| 17 | 0 |
| 18 | 1 |
| 19 | 3 |
| 20 | 0 |
| 21 | 0 |
| 22 | 0 |
| x | 5 |
| Unspec | 2 |
| Total | 50 |
This more or less ties up with this search. Perhaps I'll look into the differences at some point!
I have 39 'q's and 13'p's - four variants including both.
Various links that helped me find out more are here:
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