How to Make Forex Trading Easier to Earn More Money

The common misconception around Forex trading remains constant: it is a get-rich-quick scheme. From the outset, all that people see is rich traders and posh lifestyles. However, the difficulties involved in becoming successful and reaching the peak of currency trading are arduous! In fact, Forex can be a lose-money-quick scheme in the hands of a ill-equipped trader! With consistent learning, the foreign exchange market can be gradually mastered.
 
Forex isn't easy, but it isn't rocket-science either. Here's how you can get better at trading currencies:
 
Tips to Make Forex Easier
Tips to Make Forex Easier

1) Tailor-make Your Strategy: The initial thought of a currency trader is to follow what professionals do, with a belief of making the same profits as them. Herd mentality doesn't work out much on the long run! Each trader has a different mentality, and trading capacity. Not everyone can day-trade and not everyone has the patience to position trade. Observe yourself keenly and devise a Forex trading strategy that is best suited for your interests. Explore the advantages of Forex demo account here.
 
2) Explore All Timeframes: Keeping all your eggs in one basket is an unwise move. From currency pairs to timeframes to Forex trading strategies, there's a lot of freedom in currency trading. Though each type of strategy requires a certain amount of practice, success is possible only when you're comfortable walking a mile in all shoes! Try out different timeframes, learn each strategy and don't be afraid to exploit the choices foreign exchange offers.
 
3) Be Emotionally Sound: An underrated factor - emotions play a huge role in your trading career. The outcome of several of your endeavors depend hugely on how you approach the markets! It is common to see traders holding losing positions out of frustration or becoming over-confident and investing all their capital in a bad trade. Knowing where to draw the line is incredibly necessary in Forex trading, without this restriction, you won't last a day!
 
4) Don't Overtrade: Currency pairs, no matter how strong, have to come down at a point. Overtrading is a huge mistake several traders make, out of emotion or out of badly channeled confidence! Every trade has a lifetime, extending which will result in bad outcomes. Set a mental and physical limit on how much to trade and how much to risk.
 
Intimidating on the outside, and extremely challenging inside - that's how Forex is! However, bearing these troubles pays off. It is one of the most lucrative markets and there's immense profits to be made. With the assistance of a good Forex broker, you can dominate the game - call WesternFX! Our unparalleled services will ensure you climb to the top and stay there!

Guest post: Primary Progressive MS Research: Treatment Outcomes

This is a repost from MStranslate, with kind permission from Brett Drummond.

PPMS is characterised by a steady worsening of disease or accumulation of disability from onset without any lengthy periods of stability or ‘remission’. Some people with primary progressive MS may also experience acute attacks of active disease, commonly referred to as relapses, during which symptoms are exacerbated or new symptoms develop.


Up until the clinical trial results for ocrelizumab (Ocrevus), none of the current MS therapies appeared to have any benefits for pwPPMS. However, a recently published study in JAMA Neurology has provided some stunning new insights that may change this theory. The research was conducted using the large international multiple sclerosis clinical database, known as MSBase, and performed by researchers in the Clinical Outcomes Research (CORe) Unit associated with the Melbourne Brain Centre at the Royal Melbourne Hospital and The University of Melbourne.



In the featured video above, Associate Professor Tomas Kalincik (Research Leader, Clinical Outcomes Research Unit) describes the results of the published study. In a very logical and easy to understand way, Tomas walks us through how the study was performed and clearly illustrates the findings. Importantly, Tomas also discusses the potential outcomes of this work. In particular, he mentions how this research may provide evidence that can be used to initiate conversations with regulators in order to change the way some people with primary progressive MS access multiple sclerosis treatments. 

It is also worth noting that we are one of the first people to get access to be able to provide coverage of this research – this is due to Tomas’ desire and excitement to share the findings of the CORe team with the MStranslate community. 

Tomas approached us and offered his time and expertise to explain these findings and we are extremely appreciative of that. I think it is really important that we not only highlight when researchers do amazing work, but also when they make it a priority to ensure that their results are made accessible to the MS community.  Thank you Tomas and the CORe team!

ProfG a Week in TwitterLand

ProfG has taken to twitter to comment on posts.Should we consider a feature on his comments on the blog as it is is clear many people can't we bothered with Twitter?

Gavin GiovannoniThis study suggest that the anti-JC virus antibody index will be difficult to interpret and use to risk profile MSers on rituximab or ocrelizumab as it affects antibody production.
Anti-JC virus antibody index changes in rituximab-treated multiple sclerosis patients.
Baber U, Bouley A, Egnor E, Sloane JA. J Neurol. 2018 Aug 14. doi: 10.1007/s00415-018-8996-3. [Epub ahead of print]

Gavin GiovannonAgeing is a big problem in MS. This paper suggest it contributes to falls as well as cerebellar and cognitive dysfunction in MS.
Cerebellum and cognition in multiple sclerosis: the fall status matters.Schreck LM, Ryan SPP, Monaghan PG.J Neurophysiol. 2018 Aug 15. doi: 10.1152/jn.00245.2018. [Epub ahead of print]

Gavin Giovannoni.As a community of MS stakeholders we need to take care to produce better and more practical guidelines, particularly in relation to lifestyle issues such as physical activity. A systematic critical review of physical activity aspects in clinical guidelines for multiple sclerosis. Geidl W, Gobster C, Streber R, Pfeifer K.Mult Scler Relat Disord. 2018 Aug 3;25:200-207.


Gavin Giovannoni MSers with hypertension and/or heart disease have a much greater loss of brain volume than MSers without these comorbid diseases. Not surprising considering what we know about hypertension and brain reserve. Do you know your blood pressure?Hypertension and heart disease are associated with development of brain atrophy in multiple sclerosis: a 5-year longitudinal study.Jakimovski D, Gandhi S, Paunkoski I, Bergsland N, Hagemeier J, Ramasamy DP, Hojnacki D, Kolb C, Benedict RH, Weinstock-Guttman B, Zivadinov R.Eur J Neurol. 2018 Aug 13. doi: 10.1111/ene.13769. [Epub ahead of print]

Gavin Giovannoni‏ Instilling a small amount of ice water into the bladder of MSers and measuring the change in pressure allows urologists to diagnosis overactivity of the detrusor muscle. Low tech but potentially useful. Ice water test in multiple sclerosis: A pilot trail.Hüsch T, Reitz A, Ulm K, Haferkamp A. nt J Urol. 2018 Aug 13. doi: 10.1111/iju.13786. [Epub ahead of print]

Gavin Giovannoni‏ Another piece of dogma bites the dust. #NeuroSpeak Visual prognosis in seronegative idiopathic optic neuritis finally elucidated: as bad as that in anti-AQP4-Ab (+) optic neuritis. Visual prognosis in seronegative idiopathic optic neuritis finally elucidated: as bad as that in anti-AQP4-Ab (+) optic neuritis. Akaishi T, Nakashima I. Eur J Neurol. 2018 Aug 13. doi: 10.1111/ene.13772. [Epub ahead of print]

Gavin Giovannoni Another depressing study showing the impact a diagnosis of MS has on young adults. Why aren't we doing more to prevent this disease. 
Young adults' adjustment to a recent diagnosis of multiple sclerosis: The role of identity satisfaction and self-efficacy. Calandri E, Graziano F, Borghi M, Bonino S. isabil Health J. 2018. pii: S1936-6574(18)30139-0.

Gavin Giovannoni‏  A paper showing that cerebrospinal fluid GAP-43 (a recovery marker) is raised in early multiple sclerosis. Will it be down in more advanced MS?. Cerebrospinal fluid GAP-43 in early multiple sclerosis. Rot U, Sandelius Å, Emeršič A, Zetterberg H, Blennow K.Mult Scler J Exp Transl Clin. 2018 4(3):2055217318792931.

Gavin Giovannoni‏ No wonder the early burden of MS is related cognitive impairment. The shredder damages connectivity in the MS brain. Are you surprised? Another reason to treat early and effectivelyMagnetic resonance markers of tissue damage related to connectivity disruption in multiple sclerosis. Solana E, Martinez-Heras E, Martinez-Lapiscina EH, Sepulveda M, Sola-Valls N, Bargalló N, Berenguer J, Blanco Y, Andorra M, Pulido-Valdeolivas I, Zubizarreta I, Saiz A, Llufriu S.Neuroimage Clin. 2018;20:161-168.

Gavin Giovannoni‏ Another elephant in the room (immunosuppression) is making things crowded. #ClinicSpeak Infectious complications of MS DMTs: implications for screening, prophylaxis, and management. Infectious Complications of Multiple Sclerosis Therapies: Implications for Screening, Prophylaxis, and Management.Epstein DJ, Dunn J, Deresinski S.Open Forum Infect Dis. 2018 ;5(8):ofy174.

Gavin Giovannoni‏ TEVA fights back and shows major physicochemical, biological, functional and toxicological differences between the European follow-on glatiramer acetate compared to Copaxone. Will this impact efficacy?Physicochemical, biological, functional and toxicological characterization of the European follow-on glatiramer acetate product as compared with Copaxone. Melamed-Gal S, Loupe P, Timan B, Weinstein V, Kolitz S, Zhang J, Funt J, Komlosh A, Ashkenazi N, Bar-Ilan O, Konya A, Beriozkin O, Laifenfeld D, Hasson T, Krispin R, Molotsky T, Papir G, Sulimani L, Zeskind B, Liu P, Nock S, Hayden MR, Gilbert A, Grossman I.eNeurologicalSci. 2018 May 30;12:19-30.

Gavin Giovannoni‏ Is creating a walled garden the way to deal with fake news in the MS space? Influencers and health-related professional participation on the Web: A pilot study on a social-network of MS
Fake news, influencers and health-related professional participation on the Web: A pilot study on a social-network of people with Multiple Sclerosis. Lavorgna L, De Stefano M, Sparaco M, Moccia M, Abbadessa G, Montella P, Buonanno D, Esposito S, Clerico M, Cenci C, Trojsi F, Lanzillo R, Rosa L, Morra VB, Ippolito D, Maniscalco G, Bisecco A, Tedeschi G, Bonavita S.Mult Scler Relat Disord. 2018 Jul 31;25:175-178. 

Gavin Giovannoni‏ Mental health is a big problem for MSers. Another hidden problem highlighting how large the burden of disease we are missing by focusing on the physical. Factors associated with perceived need for mental health care in multiple sclerosis. Orr J, Bernstein CN, Graff LA, Patten SB, Bolton JM, Sareen J, Marriott JJ, Fisk JD, Marrie RA; CIHR Team in Defining the Burden and Managing the Effects of Immune-mediated Inflammatory Disease.Mult Scler Relat Disord. 2018;25:179-185
Gyllensten H, Kavaliunas A, Alexanderson K, Hillert J, Tinghög P, Friberg E. Mult Scler J Exp Transl Clin. 2018;4(3):2055217318783352.

 Gavin Giovannoni‏  MRI and CIS outcomes. Surely baseline lesion number simply indicates that CISers have had asymptomatic MS longer, hence the MS-shredder has had more time to reduce brain reserve and hence they do worse? How do we capture the time vector? Cerebrospinal fluid GAP-43 in early multiple sclerosis. Rot U, Sandelius Å, Emeršič A, Zetterberg H, Blennow K.Mult Scler J Exp Transl Clin. 2018;4(3):205521731879293

Gavin Giovannoni‏ We now have the biomarkers for microglial activation. The question is whether or not inhibiting microglia will make MS better or worse? I suspect worse. The microglial response in MS may be a positive not a negative.Comparison of two different methods of image analysis for the assessment of microglial activation in patients with multiple sclerosis using (R)-[N-methyl-carbon-11]PK11195. Kang Y, Schlyer D, Kaunzner UW, Kuceyeski A, Kothari PJ, Gauthier SA. LoS One. 2018;13(8):e0201289.

Evidence against oligoclonal bands being important?

As you may realise, I am sometimes critical of my colleagues who tend to follow dogma, without question.

This of course does me no favours with my colleagues. Maybe I should just say everything is "Great" or "Super", like I'm part of  some 1970s Sitcom :-0

For many, many years my colleagues have been hunting for the autoantigen in MS. They have got nowhere fast and we have seen more false dawns than I've had tequila sunrises.

MD2 has stuck his neck out and has suggested that we are wasting our time hunting for the causative antibody.

Indeed MD2 has suggested that the antibodies produced in the CNS are not inert and that they may simply bind to microglia via their tails rather than their heads that bind to their targets. These would serve to stimulate the microglia possibly to maintain a damaging phenotype that could drive degeneration in damaged nerves.


Paper

Pryce G, Baker D. Oligoclonal bands in multiple sclerosis; Functional significance and therapeutic implications. Does the specificity matter? Mult Scler Relat Disord. 2018;25:131-137.
********************************************

So you set up an idea and you don't try to prove it but you try to disprove it. This is called Popperian Science, after Karl Popper.

Therefore, thanks to one of the readers who did some reading and found this paper. 

It is a case of some one with MS who had a B cell cancer. They were given a stem cell cell transplant (HSCT) and they became oligoclonal band negative. However, disease activity continued.

Therefore, oligoclonal bands can't be a driver of progression, can they?


Paper


BACKGROUND:Allogeneic hematopoietic cell transplantation (allo-HCT) has been proposed as treatment for multiple sclerosis (MS) and other autoimmune diseases.
AIMS:To describe the effects of allo-HCT on the course of MS in a 49-year-old woman with longstanding progressive MS who was treated with allo-HCT for follicular lymphoma.
METHODS:Non-myeloablative conditioning allo-HCT, examination for IgG oligoclonal bands and measurement of CXCL13 and matrix metalloproteinase-9 (MMP-9) concentration in the cerebrospinal fluid (CSF).
RESULTS:Despite the disappearance of oligoclonal bands in CSF, disease progression and CSF inflammation was observed.
CONCLUSIONS:We hypothesize that CXCL13 and MMP-9 detected in CSF may reflect ongoing, pathogenic immune activation even after the eradication of intrathecal IgG synthesis. This suggests that progressive MS may depend more on innate than on adaptive immune activation.

**************************************

Maybe, but we have to figure out what could be happening before we give up on the idea. In this study the person had a B cell lymphoma and is treated with cyclophosphamide (CNS penetrant) and fludarabine (CNS penetrant) immunosuppressive agents capable of killing dividing (B) cells. The lymphoma is put under control and the person does a stem cell transplant. 

The transplant then starts to attack the body (Graft verses host disease). This means that the graft will attack anything that expresses transplantion antigens called the human leucocyte antigens (HLA) or major histocompatibility complex (MHC) antigens. 

B cells express high amounts of both class I and class II MHC and so will be targeted by the new immune system coming from the transplant. This could easily destroy B cells in the CNS that produce oligoclonal bands, especially as the MS would have made the CNS more leaky to immune cells. Also because of the MS, nerve cells sometimes express MHC class I and so could get attacked and damage too.

Indeed the graft immune system can target and kill any host cell expressing MHC class II and MHC class I antigens. These (MHC class I) are expressed by the skin and other tissues, which why the graft verse host disease occurs can be easily visible (I'd show you a picture but it is rather gross and will put you off your food). 

To treat this the person gets more immunosuppression  (cyclosporin A, mycophenylate) including anti-TNF. This latter agent has been associated with triggering the development of MS in some people.


This person started developing new lesions (i.e. sub-clinical relapsing MS), but when tested they had become oligoclonal band negative. But would this mean that the cells causing graft verses host disease were entering the CNS and causing damage. Could this be the cause of the lesions? However, it could certainly cause the production of cytokines that keep microglia activated, meaning that you don't need oligoclonal bands to do this job.

However, the the person was having spinal cord lesions and their movement got worse.  They got graft verses host disease again and this goes chronic for months before it is put under control. 

Then the person gets tacrolimus, or FK506, which is an immunosuppressive agent. Although this may have neuroprotective potential,  it can also cause neurological problems in some people. Is this part of the problem and the worsening of neurological problems for this person? I don't know. However there are a lot of confounding possibilities so that we can not be sure if this kills off the B cell ideas.

The idea but forward by MD2 was that activated microglia may be a central part of progressive MS. There are probably different routes to achieve this.  In this study they find CXCL13 (CXCL13 is a small chemokine  that chemokine is selectively chemotactic for B cells , such as memory B cells, by interacting with chemokine receptor CXCR5) and MMP9 (a metalloprotease associated with inflammation) Would we want this.

Do you have any ideas, I may be talking tosh.

Keep the anti views coming.

Guest post: Does degradation of brain fats cause MS?

This is to let you know about a research project based on a novel idea of how MS develops. I am a pathologist, and have spent most of my career on medical research. I am returning to researching on MS after a long period of working on the arterial disease that causes heart attacks and strokes. The reason for my return to MS work is that I believe that MS may develop in a way similar to arterial disease when the details of the process, the molecules concerned, are considered. 


I have sent a grant application to the MS Society to support this work. Also I have been able to start it right away with the help of QMUL science students doing laboratory projects.

In arterial disease, the particles carrying fats through the blood to all parts of the body become lodged in the walls of arteries. There the fats in them degrade, and it is known that they are then treated by the body as foreign. As a consequence an inflammatory response develops, in which white cells from the blood accumulate. The walls of the artery then thicken, so much so that the flow of blood is impeded, and supply to vital organs such as the heart is diminished.

In the brain, there is much fat in the myelin covering of nerves. In MS, this nerve coating and the cells making it are attacked by inflammation. Other researchers have found that there is an immune response against damaged fats in MS. This has been found in the fluid surrounding the brain, the cerebrospinal fluid. 

Furthermore, one particular type of antibody immune response against damaged fats predicts a severe future course of the disease. I therefore propose that some initial local damage to the myelin coat of a nerve, perhaps by a common or transient infection, results in the formation of damaged fats in the brain. Then in individuals that are predisposed, perhaps for genetic reasons, an immune response is generated against the damaged fats. It is known that some immune responses generate disease rather than protect against it, and in MS more damaged fats may be formed. So this response itself may result in more local damage to the myelin and in this way an expanding MS plaque develops in the brain. It is interesting that both arterial and MS disease grow in a similar way as expanding local plaques.

The research project is in two parts. At the moment we are testing samples of cerebrospinal fluid from MS patients, obtained from the MS Brain Bank, for an immune response of antibodies to damaged fats. We have developed a straightforward assay for this. Later we shall look using powerful microscopic techniques for the presence of the damaged fats and the immune response against them in MS. This will be done in brain tissue, particularly in the MS plaques. The tissue has been obtained from MS patients who have died and donated their brains to the MS Tissue Bank.

The significance of this research is that if it is successful, it will help the understanding of how MS develops. This will mean that the direction of work on the development of drugs can be focused better. Already it fits with recent developments, as drugs designed to destroy the cells that make the antibodies are effective in some people with MS. The assay we are currently developing may be useful in the diagnosis of MS and the prediction of its future course.

by Dr Robin Poston, Centre for Microvascular Research, William Harvey Research Institute, Queen Mary University of London.



Dr Robin Poston is a pathologist who has spent much of his career in research, and has worked on atherosclerosis almost throughout. He was a student at King’s College, Cambridge University, where he first studied physical sciences and then medicine. Clinical training followed at the Middlesex Hospital, London, where he joined the Immunology laboratory at the Middlesex Hospital Medical School to start research on the immunology of atherosclerosis. Subsequently he was appointed a Lecturer in the Department of Pathology, Guy’s Hospital Medical School, and in 1979 presented some of the early ideas about atherosclerosis as an inflammatory disease to the Royal Society of Medicine.

At Guy’s Hospital, he trained as a pathologist in immunology and histopathology, and in the 1980s set up a diagnostic immunohistochemistry service. In 1992-6 he published seminal work on the involvement of leukocyte adhesion molecules in atherosclerosis: his paper on ICAM-1 has been one of the most cited in the American Journal of Pathology. For this study he introduced colour image analysis, which since has been used extensively for the quantitation of histological research. Other fields of research around that time were multiple sclerosis and asthma.

Teaching of medical students was another extensive facet of his work, and he organised many pathology courses. In 2004 he set up the Graduate and Professional Entry Course for the medical school of King’s College London, which involved compressing the normal first two years of teaching into one.


In 2008 he moved to the William Harvey Research Institute of the Barts and the London Medical and Dental School, part of Queen Mary University of London. Although now officially retired, he continues with research on atherosclerosis, and recently again on multiple sclerosis.

To Reduce the Risk of Moral Catastrophes, Should Society Hire Lots of Philosophers?

In June, I wrote a post arguing that future generations might find our generation especially morally loathsome, even if we don't ourselves feel like we are morally that bad. (By "we" I mean typical highly educated, middle-class people in Western democracies.) We might be committing morally grievous wrongs -- atrocities on par with the wrong that we now see in race-based slavery or the Holocaust or bloody wars of conquest -- without (most of us) recognizing how morally terrible we're being.

In Facebook discussion, Kian MW pointed me to a fascinating article by Evan G. Williams, which makes a similar point and adds the further thought, bound to be attractive to many philosophers, that the proper response to such a concern is to hire lots of philosophers.

Okay, hiring lots of philosophers isn't the only remedy Williams suggests, and he doesn't phrase his recommendation in quite that way. What he says with that we need to dedicate substantial societal resources to (1) identifying our moral wrongdoing and to (2) creating social structures to implement major changes in light of those moral discoveries. Identifying our moral wrongdoing will require progress, Williams says, both in moral theory and in related applied fields. (For example, progress in animal ethics requires progress both in moral theory and in relevant parts of biology.) Williams' call for dedicating substantial resources toward making progress in moral theory seems like a call for society to hire many more philosophers, though I suppose there are a variety of ways that he could disavow that implication if he cared to do so.

The annual U.S. military budget is about $700 billion. Suppose that President Trump and his allies in Congress, inspired by Williams' article, decided to divert 2% of U.S military spending toward identifying our society's moral wrongdoing, with half of that 2% going to ethicists and the other half to other relevant disciplines. Assuming that the annual cost of employing a philosopher is $150,000 (about half salary, about half benefits and indirect costs), the resulting $7 billion could hire about 50,000 ethicists.

[With 50,000 more ethicists, these empty chairs could be filled!]

Two percent of the military budget seems like a small expenditure to substantially reduce the risk that we unwittingly perpetrate the moral equivalent of institutionalized slavery or the Holocaust, don't you think? A B2 bomber costs about $1-$2 billion. The U.S. government might want to consider a few bomber-for-philosopher swaps.

I write this partly in jest of course, but also partly seriously. If society invested more in moral philosophy -- and it needn't be a whole lot more, compared to the size of military budgets -- and if society took the results of that investment seriously, giving its philosophers prestige, attention, and policy influence, we might be morally far better off as a people.

We might. But I also think about the ancient Athenians, the ancient Chinese, and the early 20th-century Germans. Despite the flourishing of philosophy in these times and places, the cultures did not appear to avoid moral catastrophe: The ancient Athenians were slave-owners who engaged in military conquest and genocide (perhaps even more than their neighbors, if we're grading on a curve), the flourishing of philosophy in ancient China coincided with the moral catastrophe of the period of the Warring States, and the Germans perpetrated the Holocaust and helped initiate World War II (with some of the greatest philosophers, including Heidegger and Frege, on the nationalistic, anti-Semitic, political right).

Now maybe these societies would have produced even worse moral catastrophes if philosophers had not also been flourishing in them, but I see no particular reason to think so. If there's a correlation between the flourishing of philosophy and the perpetration of social evil, the relationship appears to be, if anything, positive. This observation fits with my general concerns about the not-very-moral behavior of professional ethicists and philosophers' apparent skill at post-hoc rationalization.

I'm not sure how skeptical to be. I hesitate to suggest that a massive infusion of social capital into philosophical ethics couldn't have a large positive impact on the moral choices we as a society make. It might be truly awesome and transformative, if done in the right way. But what would be the right way?

[photo credit: Bryan Van Norden]

Guest Post: Language and MS: Why Our Words and Stories Matter

Question. Those with multiple sclerosis: do you remember the exact words your neurologist used to break the news of your diagnosis?


And those on the other side: MS neurologists and health professionals. Can you recall the most difficult conversation you’ve had with someone with MS and the words you used?


Thought so.


Words matter in medicine - especially with a disease like multiple sclerosis where the impact on quality of life can be catastrophic and the emotional component runs so high.


Words can also be inadequate. How does one describe pain? Or weakness? Or how does one, as a health practitioner, offer words of hope when there is almost none?


And words change  - depending on time and shifting sensitivities. Take the word ‘disease’. Before typing it out - five sentences earlier - I paused. Was it the most appropriate word to describe MS? Neurologists overwhelmingly use the term disease, but the NHS and three UK charities - the MS Society the MS Trust and Shift.ms - prefer ‘condition’ to describe MS.


“We tend to avoid the words illness and disease as we think condition is less aggressive and negative,” says Janice Sykes, Information Officer at the MS Trust, a UK charity. Miranda Olding, a Clinical Nurse Specialist in MS, also calls MS a condition though she concedes at her therapy centre “we do talk a lot about disease-modifying treatments.” She also uses words like inflammation and lesion, but avoids ‘scarring'.


There is also the semantic quandary of how best to describe someone with MS. In 2016 David Baker, Professor of Neuroimmunology at Barts and the London, looked at how people with MS preferred to be referred to in scientific publications - compared to what academics called them. After analysing three surveys, Baker and his colleagues found those with MS liked the descriptor ‘person with MS' (pwMS) followed by MSer. Academics, by contrast, generally used the term ‘patient’ - which those with MS found to be outdated and paternalistic.


I get this. However when you go on the internet, it seems a very different story. People don’t just ‘have’ MS these days. Instead they call themselves ‘MS survivor,’ a 'MS warrior’ or a ‘MS hero'. War and violence metaphors are freely appropriated. Those with MS are ‘standing up’ to it, ‘battling’ it or even single-handedly ‘slaying the MS Monster.’  


This notion of 'fighting disease’ is not new. In the mid-seventeenth century, the famous British physician Thomas Sydenham introduced the concept into western medicine when he declared that a “murderous array of disease has to be fought against, and the battle is not a battle for the sluggard.”  

Thomas Sydenham by Mary Beale

In recent years, however, the linkage of military language to MS has grown. Does anybody in the MS world wince when there is talk of the immune cells 'attacking the myelin sheath’ or mention is made of ‘breaching the blood brain barrier’? No. We accept this terminology without questioning its adversarial tone or wondering if such words are, in fact, suitable when it comes to medicine and healing.


Not surprisingly, the press, policy makers and charities have adopted these combat metaphors. They’re effective and highly motivating. A few months ago, for example, the National MS Society launched its ‘Whatever it Takes' campaign featuring posters - in stark black and white - of those with MS. Underneath are taglines: “MS broke my body. I will never stop, never quit,” says Kevin diagnosed in 1999. Or there is Yvette, in boxing gloves: “MS causes debilitating fatigue. I will knockout MS.”


Personally I find this tie-in between fighting and MS uncomfortable. Does this mean from the moment you are diagnosed you should enter the metaphorical boxing ring or the theatre of war and launch an all-out assault against MS? Isn’t coping with a serious chronic disease enough? And what happens if you ‘lose’ the fight against MS?


Others with MS have taken a very different tack when it comes to describing themselves. In her seminal essay “On Being a Cripple” (links to a PDF) Nancy Mairs defiantly labels herself a cripple - saying it accurately reflects her reality.


Mairs acknowledges this might make people wince, but “perhaps I want them to wince. I want them to see me as a tough customer, one to whom the fates/gods/viruses have not been kind, but who can face the brutal truth of her existence squarely. As a cripple, I swagger.”


Mairs also wants to be honest: “Cripple seems to me a clean word, straightforward and precise… As a lover of words, I like the accuracy with which it describes my condition: I have lost the full use of my limbs. ‘Disabled,’ by contrast, suggests any incapacity, physical or mental. And I certainly donʼt like ‘handicapped,’ which implies that I have deliberately been put at a disadvantage, by whom I canʼt imagine (my God is not a Handicapper General)…”

Nancy Mairs in 1986, by Jim Hepworth.Credn b

Along with the rise of MSers fashioning their own labels, there has also been a huge increase in the number of people writing their own MS personal stories. Go online and you will find dozens, if not hundreds, of blogs focusing on symptoms, treatment options and the challenges of living with MS.


The rise of the internet has made this largely possible. But I also believe the democratisation of medicine has played a role. Until recently physicians were pretty much the only ones writing patient’s stories or ‘illness narratives’, according to Mike Bury in his essay “Illness narratives: fact or fiction?.


Before the rise of bio-medicine in the mid to late 19th century, Bury writes, great emphasis was placed on a doctor taking a detailed history of their (usually upper class) patient - asking questions about circumstances, environment and even moral beliefs. From this they would come up with a diagnosis and treatment. To be honest, they didn’t have much else in their doctor’s bag. Understanding of anatomy and physiology was basic; physical examinations were, at best, rudimentary. Story was everything.


The advent of scientific medicine and the growth of modern hospitals and laboratories changed all this. Emphasis switched away from the patient’s experience to biological causes of illness. Blood tests replaced blood letting. In recent years, however, there has been a shift away from this medical model, Bury says. He cites several reasons: the rise in chronic diseases, the huge expansion of medical information and the shift to holistic, patient-based care. These days patients are reclaiming ownership of their bodies - and their stories.


Sociologist Arthur Frank applauds such a move. In his influential book, The Wounded Storyteller, Frank says stories written by the ‘wounded’ allow them to gain control over their illness, accept it and reflect on how it has shaped them. “Stories are a way of redrawing maps and finding destinations,” he writes. They are also key to helping - and healing - others in a similar situation. “As wounded, people may be cared for, but as storytellers, they care for others.”


Nobody understands this better than George Pepper, Co-founder and Chief Executive of Shift.ms. Told at the age of 22 he had MS, Pepper found it difficult to meet others in a similar situation: young, recently diagnosed and struggling to accept they had a life-long condition. So in 2009 with the help of friends, he set up the web-based charity and social network Shift.ms.


What makes Shift.ms unique is that it’s ‘user-led’ meaning its 17,000 members (and growing) supply and drive its content. A large chunk of the site is dedicated to members explaining how MS affects them: from their diagnosis, to their fears and onto the impact it has on relationships, families and career. “Every person with MS has a story to tell, and by telling it, it helps other understand they are not alone,” says Pepper.


The MS Trust reports a similar situation. In 2011, it set up a ‘Your Stories' section on their website. Last year the pages received about 3-4,000 views per month. That figure is looking to double this year. “There has definitely been a shift in people looking to fellow MS peers to help put things into context,” says Sykes.


I understand. Even with the best will in the world - and there is much out there - doctors and health professionals can not perform this service. It is the actual act of writing one’s own MS story that can be empowering and cathartic; a way of shaping the chaos that surrounds a disease so unpredictable as MS.


And this holds true, I believe, no matter who tells the story, from where or what time.  A case in point is Sir Augustus d’Este - the illegal grandson of King George III - and the earliest recorded person with MS. Starting in 1822 - when he first experienced blurred vision - until 1846, d’Este kept a diary detailing his symptoms and treatments which included leeching, ‘electrification’ and orders to “eat beef steaks twice a day, drink London Porter, Sherry and Madeira wines.”

Sir Augustus d'Este as a boy (it is 'possibly' d'Este, not confirmed) V&A collection

Reading a copy of the diary today is terribly poignant. Obviously the style is different, but what shines through is how similar d’Este’s experience with MS was - more than one hundred and seventy years ago - compared to today. We read of his bewilderment with his growing symptoms, his pleasure when they (temporarily) abate; his attempts to find a cure and his disappointment when they don’t work. And we can not fail to be cheered by his optimism - even when he progresses from stick, to his “chair on wheels” then finally to bed. What makes it all the more poignant is knowing, that it is unlikely d’Este will get the happy ending he wants and that we want for him.


Words and stories matter especially in MS. Sometimes they may not be the exact words we want to hear - or the stories may have a different closing than we would wish. But the importance is that we have them.


By Rachel Horne



Rachel is a journalist interested in health and women's issues. She has an Hons BA from McGill University and a Masters from Columbia University School of Journalism. Previously she covered international news in China and financial news for CNN in London. She has MS.

Neuroinflammation associated with nerve damage in progressive MS

This study looks at neuroinflammation. Specifically the fact that the development of treatments for progressive MS is hampered by the lack of suitable biomarkers that can accurately detect and monitor intrathecal inflammation (inflammation which occurs within the spinal theca, which is a sac containing the cerebrospinal fluid which provides nutrients and buoyancy to the spinal cord).

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Romme Christensen J, Komori M, von Essen MR, Ratzer R, Börnsen L, Bielekova B, Sellebjerg F. CSF inflammatory biomarkers responsive to treatment in progressive multiple sclerosis capture residual inflammation associated with axonal damage. Mult Scler. 2018 May 1:1352458518774880. doi: 10.1177/1352458518774880. [Epub ahead of print]

BACKGROUND: Development of treatments for progressive multiple sclerosis (MS) is challenged by the lack of sensitive and treatment-responsive biomarkers of intrathecal inflammation.
OBJECTIVE: To validate the responsiveness of cerebrospinal fluid (CSF) inflammatory biomarkers to treatment with natalizumab and methylprednisolone in progressive MS and to examine the relationship between CSF inflammatory and tissue damage biomarkers.
METHODS: CSF samples from two open-label phase II trials of natalizumab and methylprednisolone in primary and secondary progressive MS. CSF concentrations of 20 inflammatory biomarkers and CSF biomarkers of axonal damage (neurofilament light chain (NFL)) and demyelination were analysed using electrochemiluminescent assay and enzyme-linked immunosorbent assay (ELISA).
RESULTS: In all, 17 natalizumab- and 23 methylprednisolone-treated patients had paired CSF samples. CSF sCD27 displayed superior standardised response means and highly significant decreases during both natalizumab and methylprednisolone treatment; however, post-treatment levels remained above healthy donor reference levels. Correlation analyses of CSF inflammatory biomarkers and NFL before, during and after treatment demonstrated that CSF sCD27 consistently correlates with NFL.
CONCLUSION: These findings validate CSF sCD27 as a responsive and sensitive biomarker of intrathecal inflammation in progressive MS, capturing residual inflammation after treatment. Importantly, CSF sCD27 correlates with NFL, consistent with residual inflammation after anti-inflammatory treatment being associated with axonal damage.

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My comments

CD27 is required for the generation and long-term maintenance of T cell immunity. It binds to ligand CD70, and plays a key role in regulating B-cell activation and immunoglobulin synthesis and may play an important role in the apoptosis (cell suicide) of white blood cells. It is a marker of memory T and B cells. It can be shed to float in the blood in solution, and can be detected. When you have immune activity the CD27 marker is shed. 

In this study it shows that CD27 (a marker of immune activation) and neurofilament (a marker of nerve damage) can still be found in some people, even AFTER they have been treated with immunomodulatory drugs (drugs that modify the immune system). So there is still disease activity.

Neurologists have been using neurofilament markers in the decision making process when deciding the best treatments for patients. But not CD27.


There was a correlation between immune activity and nerve damage. Whilst these were reduced by therapy, disease was not always kept in check. So NEDA (no evidence of disease activity) is only as good as what you look for.


Other studies point towards soluble CD27 as being a useful marker of disease activity.


Another study

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Wong YYM, van der Vuurst de Vries RM, van Pelt ED, Ketelslegers IA, Melief MJ, Wierenga AF, Catsman-Berrevoets CE, Neuteboom RF, Hintzen RQ; Dutch paediatric MS and ADEM study group. T-cell activation marker sCD27 is associated with clinically definite multiple sclerosis in childhood-acquired demyelinating syndromes. Mult Scler. 2018 Jul 1:1352458518786655. doi: 10.1177/1352458518786655. [Epub ahead of print]

BACKGROUND:
Cerebrospinal fluid (CSF) levels of T-cell activation marker soluble CD27 (sCD27) are associated with subsequent disease activity after a first attack of suspected MS in adults. The predictive value for disease course in children with acquired demyelinating syndromes (ADS) is unknown.
OBJECTIVES:To assess the predictive value of sCD27 levels for clinically definite multiple sclerosis (CDMS) diagnosis in childhood ADS.
METHODS:Children <18 years with a first demyelinating event were prospectively included and followed. Soluble CD27 was determined in CSF using an enzyme-linked immunosorbent assay (ELISA). Cox regression analyses were used to calculate hazard ratios (HRs) for CDMS.
RESULTS: A total of 94 ADS children were included (ADS with encephalopathy (ADS+) n = 33 and ADS without encephalopathy (ADS-) n = 61). Of the 61 ADS- children, 21 (48%) were diagnosed with CDMS during follow-up. At baseline, sCD27 levels were higher in patients with a future CDMS diagnosis ( n = 29) than in monophasic ADS+ ( n = 30), monophasic ADS- ( n = 28) and relapsing non-MS patients ( n = 7; p < 0.001). In ADS- patients, sCD27 was associated with CDMS (HR = 1.8 per 100 U/mL increase in sCD27 levels, p = 0.031), after adjustments for age, oligoclonal bands and the presence of dissemination in space on baseline magnetic resonance imaging (MRI).
CONCLUSION: CSF sCD27 levels at first attack of demyelination were associated with CDMS diagnosis in children. This makes sCD27 a potential clinically relevant quantitative marker when performing routine CSF diagnostics.

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(CD27 is a marker of activated T and B cells)

How big is your need to exercise?

The evidence that exercise and I mean regular exercise is good for you is so overwhelming that it is hard to argue against the science. What I mean by this is that almost everyone accepts exercise as being good for the general population and for people with MS. The downside is that some MSers are so disabled and/or have so much fatigue that they find it difficult to exercise. I am prepared to accept the latter, but I am not prepared to accept this as a reason not to promote/prescribe exercise to the wider MS community. The question I have 'Is how do we get MSers and healthcare professionals (HCPs) to exercise regularly?'




Are you interested in hearing more about what you can do?


The review below argues for applying behaviour change theory in the design of exercise programs and promotion efforts. How about making it a challenge? Can you walk? Can you run? 

In collaboration with the MS Trust, we are proposing starting a national exercise challenge/competition to get the MS community walking and running. We are proposing to use the Parkrun platform. Parkruns are 5km runs that are held each Saturday in a local park near you and allow you to complete 5km and log an official time. The challenge is to get every MS team in the UK, and possibly the world, to sign-up for the challenge and collect 5km runs. The team with the most Parkruns after a certain period of time, say a 6- or 12-month period, wins the challenge. 

When I refer to teams I mean all MS stakeholders linked to a particular MS service or team. This would not only include people with MS, but their HCPs, friends and families, MS Society members, ShiftMSers and even Pharma reps. The only rule we would propose putting in place is that a member of a particular MS team can only sign-up for one team. Another idea is to combine Parkrun effort with a fundraising campaign for the MS Trust. However, the fundraising would be voluntary and not necessary for participating in the challenge. 

I have suggested to the MS Trust that they create an annual Parkrun award for the team who wins the challenge and for the individual who completes the most Parkruns in the predefined period of time. Please note you can only really do one ParkRun a week and special one held on Christmas day and New Year's day. 

Do you think this is a good idea? If yes, what should we call the challenge? With my bias, I would say #ThinkRunning. Or what about 'The Running and Proud MS Trust ParkRun Challenge'?

I know the naysayers will be saying, but I can't run. I know there are some of you who can't run but then there will be others who are simply deconditioned (the medical term for unfit). For you, I would suggest starting the 'couch to 5K' programme that is designed to get you off the couch and running 5km in just nine weeks. The plan involves three runs a week with a rest day in between and a different running schedule each week. The NHS is promoting this using an app developed by the BBC, the programme or app builds you up gradually with a mix of running and walking.



The good thing about making this initiative into a challenge is that it builds teams (people are competitive) and it will increase social participation. Theis will, in turn, enhance social capital, which should improve outcomes as well. 

We have already had a discussion with one of Parkrun's MS ambassadors and the MS Trust and they are very supportive of this initiative. Are you willing to give it a go? Please let us know even if it is helping with the naming of the challenge. Without your help, this won't happen. 

Let's Do It! 

Thank you. 




Motl et al. Promotion of physical activity and exercise in multiple sclerosis: Importance of behavioral science and theory. Mult Scler J Exp Transl Clin. 2018 Jul 9;4(3):2055217318786745.

There is an obvious disconnect between evidence of benefits and rates of participation in exercise and physical activity among people living with multiple sclerosis (MS). We propose that the problem with exercise behavior in MS (i.e. lack of broad or increasing participation by people with MS despite evidence of meaningful benefits) might be ameliorated through the inclusion of behavior change theory in the design of exercise programs and promotion efforts, as has been undertaken in other populations such as breast cancer survivors. This paper reviews Social Cognitive Theory as an example approach for informing interventions for increasing exercise and physical activity behavior outside of MS and provides an overview of current knowledge regarding the application of this theory for physical activity in MS. We then outline future research necessary for informing trials that design, implement, and test theory-based interventions for physical activity promotion in MS. If theories of behavior change are adopted for informing exercise and physical activity research in MS, we can take a major step forward in addressing the problem of exercise and physical activity participation that has plagued the field for more than 25 years.

CoI: I am a runner, albeit one with a failing right hip

My Tibetan Odyssey: In search of Gods in the highest of places



Mountain climbing as an obsession is a selfish endeavor, and there’s just no way to get around that fact
       -Beck Weathers in ‘Left for Dead' on the 1996 Everest disaster.


I spent the better half of July/August in Tibet, which boasts some of the tallest peaks on Earth. Like many before me I was inspired to witness with my own eyes what all the hype was about. But the endeavor itself in terms of the rigours of high altitude and cold nights is a huge ask for the human body - Lhasa the main airport into Tibet sits at a stupendous 4000m; 13,123f!

For the Tibetan people, their homeland is a place of the mighty gods taking material form at the tallest peaks in the Himalyan (Everest), Kailash (Kailash) and Transhimalyan (Nyenchen Tanglha) ranges. For climbers to ignore this simple fact and not to make offerings and receive blessings in return is an error not to be made whilst in Tibet, or in neighbouring Nepal. Climbers if truth be said live on a knife edge and justifiably are a superstitious bunch. I suppose, as an amateur climber, I wanted to test my mettle in one of the most raw and unbridled lands known to man. George Mallory, the first to lead a climb on Everest, when asked why he wished to climb Everest, had quipped, “Because it is there”. We don’t know if Mallory was successful as he never came down, but his body was later discovered by a team led by Conrad Anker in 1999 at 26,700f on the North Face of Everest. Sometimes, the price to pay for these tall dreams is a very steep one.

Everest base camp (top elevation 5200m; 17,060f; 10.8 %Oxygen)

Everest 8848m (29,029f), from base camp 

On the evening of day 4 in Tibet, I found myself with 6 others in a Yak tent at the base of Everest. July being the Monsoon season is not a good time to climb Everest (best being May and September) and it is often hidden from view by massive storm clouds. Although, that being said the views of Everest are supposedly better from base camp on the Tibetan side than the Nepalese side. But, luck was on my side as I discovered bright and early the following morning whilst stepping out to brush my teeth, the weather had dramatically changed and the whole of Everest in all her grandeur was visible to the naked eye (see pictures)!

Miyolangsma, the Bon goddess of Everest, is believed to sit at the peak of Everest (Everest is always called 'she' in deference to her). It is to her that Tenzig Norgay, the first to summit Everest with Sir Edmund Hillary in 1953, is said to have expressed his gratitude to when he reached the summit. Tenzig Norgay, is said to have followed her up the mountain and that she allowed him to be the first to summit Everest. Not surprisingly, on occasions that allow, it is not unusual to see Sherpas carry up various shrines to the summit for blessings (see picture below). Although, compared to the 1990s and since the commercialization of Everest, deaths on Everest have reduced, much of the risk now is taken by Sherpa's; with as many as one in three deaths being reported in some years. 

Two Sherpas at the summit of Everest with a shrine to Buddha

The thing I discovered about Everest is that once you’ve clapped your eyes on it, the possibilities are rife. 

Mount Kailash kora (top elevation 5630m; 18,471f, 9.2, 9.7 %Oxygen)

The mount Kailash kora (diagramatic representation on the left) is a circumlocution around Kailash amounting to 54km in total. It is a religious right for four of the oldest religions in the world – Hinduism, Buddhism, Bon and Jainism, but also performed by many tourists like myself every year. It holds special significance and is believed to be the center of the universe (the mythical Mount Meru); its location in synchronization with the Earth’s poles and from it stemming some of the worlds largest rivers (Sutlej on the West, Brahmaputra on the East, Indus on the North, Karnali on the South – the largest tributary of the Ganges). Hindus believe that Kailash is the home of Lord Shiva, the God of Destruction, and by destroying he creates. The scripture, the Shiva Purana, says "There is no sin in the world which cannot be destroyed by circumambulation. Hence one should dispel all sins by circumambulation alone". 

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