Oligoclonal bands: what are they doing?

Oligoclonal bands (OB) are a characteristic hallmark of MS.

They occur from disease onset. But what are they doing?


Despite much wishful thinking by researchers that OB are producing the pathogenic antibody (which they may well do) it has to be said that people have looked and looked, but no consistent antibody has yet been found in MS.

However, do the antibodies in the OB have to be specific for a target in MS?

MD2 suggests not, but they may play a role in progressive damage.





Read the paper free of charge (for the next 50 days)

Click on this link
https://authors.elsevier.com/c/1XTgS7skoexb7E

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Pryce G, Baker D. Oligoclonal bands in multiple sclerosis; functional significance and therapeutic implications. Does the specificity matter?. Mult Scler Rel Disord 2018.DOI

Highlights



  • Immunoglobulins in oligoclonal bands secreted by plasma cells in the CNS can contribute to worsening pathology in MS
  • Secreted immunoglobulin can interact with microglial Fc receptors in an antigen non-specific manner.
  • Microglia and astrocytes may create a survival niche for long-term plasma cell survival.
  • Plasma cells, microglia and astrocytes may interact to establish a locally neurotoxic or dystrophic environment.
  • Bruton's tyrosine kinase inhibitors may be therapeutic agents for the potential elimination of plasma cells and OCB from the CNS in MS.

Since their discovery, the existence of secreted oligoclonal immunoglobulin in the central nervous system in people with multiple sclerosis has been the subject of scientific investigation and debate over several decades. Although autoantibodies can be detected in some individuals, probably secondary to release of neo-antigens after damage, evidence for a major, primary involvement of damaging antibodies is still relatively lacking. However it is possible to construct a working hypothesis that establishes the interaction of plasma cells, which are the source of oligoclonal bands, microglia and astrocytes to create a self-perpetuating activated phenotype. This may generate an environment conducive to long-term plasma cell survival and the initiation and perpetuation of neurotoxicity that may contribute to disease worsening in multiple sclerosis. Therapeutic strategies to re-establish a homeostatic environment conducive to repair/recovery are indicated to control progressive multiple sclerosis.

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Antibodies in the CNS tend to be targeting things within the cells (intracellular targets). This suggests that the antibodies are occurring after damage and the liberation of cellular proteins rather than being the primary problem themselves.

We know that antibodies in the CNS of people with MS are pathogenic (causing disease) just as some in the blood are potentially pathogenic if they can get in the brain. 


We know this because some people respond to plasmapheresis (
the removal, treatment, & return or exchange of blood plasma) and immunoadsorption (where immunoglobulins in the blood are removed). This indicates that the problem is caused by the antibodies in the periphery.

Likewise we can take the peripheral antibodies, and the antibodies in the CNS, and inject them into animals. There, they can cause neurological problems or augment the damage driven by T cells.


However, this is not a problem for all.


Maybe one thing that OB do is to juice-up microglia (which are believed to the central problem of progressive MS) and keep them in an activated state, such that damage caused by the immune response is perpetuated into a slow-burning neurodegeneration.

Antibodies simply bind to receptors on the microglia to activate them, and their specificity may well be irrelevant.


If this is true, targeting the plasma cell response within the CNS may be the linchpin to control progression by the glial responses and metabolic problems.


Bruton's tyrosine kinase (BTK) inhibitors can block plasma cell function, but they also inhibit microglial/macrophage function.  A number of companies have these drugs. 


Other treatments may be proteosome inhibitors, which have also been used to target B cell lymphomas/myelomas (plasma cell cancers) in the brain and will be tested in MS soon.


Yes, there many other conditions with OB that are not MS, but it does indicate a way that OB can contribute to MS and other conditions.

Guest post: Has the MS Society woken up?

Finally the MS Society is embracing people with progressive MS and mobility issues in a positive way. There will be a walk of one kilometre at the next sponsored walk in Battersea Park on September 2018.





Sport is an area of society in which ableism is seen only too often. It is only within the last ten to fifteen years that society no longer perceives athletes with disabilities as being inferior. Look at the success of the recent Paralympic games. Yes it’s fantastic that we recognise and support these people but almost all of them have a fixed disability.

“Aha” I hear you saying, “Aren’t people with MS often sponsored to run in a marathon?”

“Yes there are lots of people with MS who can run a marathon but you hardly ever see a world champion who has multiple sclerosis”.

The exception is Stephanie Millward who won five swimming medals at the Paralympics at Rio in 2016.

For many years the MS Society has organised a sponsored walk in London. The walk could be one of three distances 5 or 6km, 10km or 20km. It is not a competitive event; you can walk it, stroll it, or use your mobility scooter.

The MS Society encourages us all to take exercise. I really wanted to take part in the walk but 6km was going to be 5km too far. Eventually I decided to do the short walk on my mobility scooter. Sadly when I finished there was no sense of achievement for me.

Last year I wrote an article about this problem and how I felt. It was posted on my website and here on the blog. I did this to overcome my sense of frustration at the ableism of the MS Society. I very recently received an email from the MS Society stating that on Sunday 23 September this year a walk of 1 km has been added to the event. Hey, that is a great result!

It is fair to add that I did speak to Michelle Mitchell when she was chief executive of the MS Society on this issue. Did this help? Who knows but someone somewhere told the MS Society to wake up.

This is a win-win result for the MS Society and people with progressive MS. Training for and undertaking a walk of 1km is going to be hard work for people with balance and mobility problems. Trust me. When you have been sponsored to walk a mere 1000 metres there is a genuine sense of achievement when you finish. I do hope enough people walk this distance so the MS Society feels obliged to include a 1km walk next year and the year after.

Unfortunately I’m going to be on holiday in Australia so I am unable to do the walk this year.



I am Patrick Burke, I was diagnosed with RRMS in 1995 but I believe the symptoms started in 1972.The disease turned into SPMS in about 1999/2000. I took medical retirement in 2012 and setup the website Aid4Disabled in the same year. The website is the story of my MS since retirement and it also identifies a wide range of objects that are readily available and can improve quality of life. I am also a member of the Barts-MS Advisory Group.

On What We Tell Pollsters

Barry Lam’s podcast Hi-Phi Nation has a new episode on “information silos” and what we tell pollsters. Partway through the episode, I am briefly interviewed about the nature of belief.

Lam is always fun, and the episode has a few twists you might not expect. One theme throughout the episode is a critique of the view generally accepted as implicit background in polling and in popular reports of poll results: that people tell pollsters what they actually believe. Lam explores an empirical challenge to this and a more philosophical challenge.

Empirical challenge: People who feel uncertain might answer by "cheerleading" for their side, Republicans for example simply saying whatever they think will make Trump look good, Democrats saying whatever they think makes Trump look bad. If this is going on, when the incentives are changed (for example by paying respondents for right answers, including a smaller payment for admitting that they don’t know), they might instead reveal their true opinion. Even if they are not uncertain, they might simply lie to the pollster, saying what they plainly know to be false, to help or express support for their side.

A more philosophical challenge explores the question of what it is, really, to have a political, or politically loaded, belief. On some questions, there might not be a single straightforward fact about what you believe, hidden in a “secret compartment”, which you choose either to reveal or not reveal to the pollster. On climate change, or racial equality, or on what accommodations society owes to people with disabilities, you might be inclined to answer one way in one context or to one audience, and in quite a different way in another context or to another audience; you might wager thus-and-so when X is at stake, but quite differently when Y is at stake; your spontaneous reactions and your more guarded reactions might splinter in different directions; and so on. Among all these various thoughts and reactions, there needn’t be some privileged set that reflects your true belief while others are somehow misleading or inauthentic.

That, at least, is my view of belief. If you are sufficiently splintered, fragmented, or in-betweenish in your dispositional profile, then what you tell pollsters, even sincerely, will be only one element of a complicated picture. If what you say is misaligned with some other aspects of your speech and behavior, you might be merely cheerleading or lying, but you needn’t necessarily be. You might be answering as sincerely as you can, with the fragment of you that is called forth at the moment.

Full episode here.

[image source]

Sunday Digest

Here are links to a few papers that some of you may find interesting


This is one for the neuros reading or anyone interested in imaging 


Arevalo O, Riascos R, Rabiei P, Kamali A, Nelson F.


The advent of magnetic resonance imaging has improved our understanding of the pathophysiology and natural course of multiple sclerosis (MS). The ability of magnetic resonance imaging to show the evolution of MS lesions on sequential scans has brought it to be one of the endpoints in clinical trials for disease-modifying therapies. Based on the most updated consensus guidelines from the American (Consortium of MS Centers) and European (Magnetic Resonance Imaging in MS) boards of experts in MS, this document shows the most relevant landmarks related to imaging findings, diagnostic criteria, indications to obtain a magnetic resonance, scan protocols and sequence options for patients with MS. Although incorporating the knowledge derived from the research arena into the daily clinical practice is always challenging, in this article, the authors provide useful recommendations to improve the information contained in the magnetic resonance report oriented to facilitate communication between radiologists and specialized medical teams involved in MS patients' multidisciplinary care.

Brain iron and disability is a theme, we have agents that block iron induced toxicity should we do try them?

Zivadinov R, Tavazzi E, Bergsland N, Hagemeier J, Lin F, Dwyer MG, Carl E, Kolb C, Hojnacki D, Ramasamy D, Durfee J, Weinstock-Guttman B, Schweser F. Brain Iron at Quantitative MRI Is Associated with Disability in Multiple Sclerosis. Radiology. 2018 Jul 17:180136. doi: 10.1148/radiol.2018180136. [Epub ahead of print].
Purpose To study deep gray matter susceptibility in multiple sclerosis (MS) by using quantitative susceptibility mapping (QSM) and to assess the relationship between susceptibility and clinical disability. 
Materials and Methods For this prospective study between March 2009 and November 2013, 600 participants with MS (452 with relapsing-remitting MS and 148 with secondary progressive MS) and 250 age- and sex-matched healthy control participants were imaged with 3.0-T MRI to measure magnetic susceptibility. Deep gray matter susceptibility (in parts per billion) was analyzed by using region of interest and voxelwise methods. QSM and MRI volumetric differences between study groups and associations with clinical outcomes were assessed. Analysis of covariance, multivariable linear regression, and voxelwise analyses, controlling for age and sex, were used to compare study groups and to explore associations between MRI and clinical outcomes. 
Results Compared with control participants, participants with MS presented with lower thalamic susceptibility (-7.5 ppb vs -1.1 ppb; P < .001) and higher susceptibility of basal ganglia (62 ppb vs 54.8 ppb; P < .001). Lower thalamic susceptibility was associated with longer disease duration (β = -0.42; P = .002), higher degree of disability (β = -0.64; P = .03), and secondary-progressive course (β = -4.3; P = .009). Higher susceptibility of the globus pallidus was associated with higher disability (β = 2; P = .03). After correcting for each individual structural volume in voxelwise analysis, lower thalamic susceptibility and higher susceptibility of the globus pallidus remained associated with clinical disability (P < .05). 
Conclusion Quantitative susceptibility mapping (QSM) suggests that altered deep gray matter iron is associated with the evolution of multiple sclerosis (MS) and on disability accrual, independent of tissue atrophy.

BoTox is good for alleivating bladder problems. You know all of this already, but here is a phase III study to demonstrate it.


Tullman M, Chartier-Kastler E, Kohan A, Keppenne V, Brucker BM, Egerdie B, Mandle M, Nicandro JP, Jenkins B, Denys P. Low-dose onabotulinumtoxinA improves urinary symptoms in noncatheterizing patients with MS. Neurology. 2018 Jul 20. pii: 10.1212/WNL.0000000000005991. OBJECTIVE:To evaluate the efficacy and safety of onabotulinumtoxinA 100 U in noncatheterizing patients with multiple sclerosis (MS) with urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO).
METHODS:In this randomized, double-blind phase III study, patients received onabotulinumtoxinA 100 U (n = 66) or placebo (n = 78) as intradetrusor injections via cystoscopy. Assessments included changes from baseline in urinary symptoms, urodynamics, and Incontinence-Quality of Life (I-QOL) total score. Adverse events (AEs) were assessed, including initiation of clean intermittent catheterization (CIC) due to urinary retention.
RESULTS:OnabotulinumtoxinA vs placebo significantly reduced UI at week 6 (-3.3 vs -1.1, p < 0.001; primary endpoint). Significantly greater proportions of onabotulinumtoxinA-treated patients achieved 100% UI reduction (53.0% vs 10.3%, p < 0.001). Significant improvements in urodynamics (p < 0.01) were observed with onabotulinumtoxinA. Improvements in I-QOL score were significantly greater with onabotulinumtoxinA (40.4 vs 9.9, p < 0.001) and ≈3 times the minimally important difference (+11 points). The most common AE was urinary tract infection (25.8%). CIC rates were 15.2% for onabotulinumtoxinA and 2.6% for placebo.
CONCLUSION: In noncatheterizing patients with MS, onabotulinumtoxinA 100 U significantly improved UI and quality of life with lower CIC rates than previously reported with onabotulinumtoxinA 200 U



You want to know about myelination. We know that clearing of debris is central to repair and macrophages/microglia are important in this process. In this study they show that macrophage colony stimulating factor can influence macrophages so they don't cause so much demyelination and so they promote repair. Could this be used in MS. I would have to say I think very cautiously as you have macrophages all over the body and giving them a growth and survival factor may be bad news. However without doing the experiment we will never know.

Laflamme N, Cisbani G, Préfontaine P, Srour Y, Bernier J, St-Pierre MK, Tremblay MÈ, Rivest S. mCSF-Induced Microglial Activation Prevents Myelin Loss and Promotes Its Repair in a Mouse Model of Multiple Sclerosis. Front Cell Neurosci. 2018;12:178.

A pathological hallmark of multiple sclerosis (MS) is myelin loss in brain white matter accompanied by compromised remyelination. Demyelinated lesions are deeply associated with oligodendrocyte apoptosis and a robust inflammatory response. Although various studies point towards a noxious role of inflammation in MS, others emphasize a positive role for the innate immune cells in disease progression. A cytokine well-known to stimulate cell survival, proliferation and differentiation of myeloid cells, macrophage colony-stimulating factor (mCSF), was administered to mice during a 5 week-long cuprizone diet. Treated mice exhibited reduced myelin loss during the demyelination phase, together with an increased number of microglia and oligodendrocyte precursor cells in lesion sites. Tamoxifen-induced conditional deletion of the mCSF receptor in microglia from cuprizone-fed mice caused aberrant myelin debris accumulation in the corpus callosum and reduced microglial phagocytic response. mCSF therefore plays a key role in stimulating myelin clearance by the brain innate immune cells, which is a prerequisite for proper remyelination and myelin repair processes.

Pre-natalizumab vs. after-natalizumab

I view MS as having two eras, the pre-natalizumab era and after-natalizumab era. Natalizumab has been a transformational therapy for so many reasons and this study provides a little more evidence to support this position. 


I have always said that flipping the pyramid is the best way to maximise outcomes for a population of MSers. This study shows that MSers on high-efficacy DMTs are much more likely to work and when they do work their work is more productive. 

The Australians, where this study was done, are fortunate to have all high-efficacy DMTs 1st-line. Their healthcare system leaves the decision-making up to the HCP and patient and they don't prescribe strict rules. If I had MS I would want to be living in Australia. 

This study also supports my demand to Biogen to please get the EMA marketing authorisation for natalizumab changed; we need it first-line for MSers who are JCV seronegative. Please! 

Chen et al. Effects of multiple sclerosis disease-modifying therapies on employment measures using patient-reported data. JNNP 2018; http://dx.doi.org/10.1136/jnnp-2018-318228

Background: The direct comparative evidence on treatment effects of available multiple sclerosis (MS) disease-modifying therapies (DMTs) is limited, and few studies have examined the benefits of DMTs on employment outcomes. We compared the effects of DMTs used in the previous 5 years on improving the work attendance, amount of work and work productivity of people with MS.

Methods: The Australian MS Longitudinal Study collected data from participants on DMTs usage from 2010 to 2015 and whether DMTs contributed to changes in employment outcomes. We classified 11 DMTs into three categories based on their clinical efficacy (β-interferons and glatiramer acetate as category 1; teriflunomide and dimethyl fumarate as category 2; fingolimod, natalizumab, alemtuzumab and mitoxantrone as category 3). Each DMT used by a participant was treated as one observation and analysed by log-multinomial regression.

Results: Of the 874 participants included, 1384 observations were generated. Those who used category 3 (higher efficacy) DMTs were 2–3 times more likely to report improvements in amount of work, work attendance and work productivity compared with those who used category 1 (classical injectable) DMTs. Natalizumab was associated with superior beneficial effects on patient-reported employment outcomes than fingolimod (RR=1.76, 95% CI 1.02 to 3.03 for increased work attendance and RR=1.46, 95% CI 1.02 to 2.10 for increased work productivity).

Conclusions: Those using the higher efficacy (category 3) DMTs, particularly fingolimod and natalizumab, reported significant increases in amount of work, work attendance and work productivity, suggesting they have important beneficial effects on work life in people with MS.

ProfG    

Futures Trading 2018: What is it & How to Trade | Beginners Guide


The Futures trading can be defined as a contract between two parties (buyer and seller), to buy and sell a particular asset at a fixed price and on a very specific date. Though a trading trend today, futures contracts were created to aid farmers when crop prices fluctuated, during the period between planting and harvesting. This grew into a trend for traders to speculate on and predict an asset's profit/loss. 

What are Futures Trading?

Futures are essentially a derivative - their value is derived from another commodity's price movements. Only the instrument's price will affect the value of a derivative, and it doesn't have an inherent value by default. Futures can be traded by anticipating the instrument's price movements. This is done by going long (buying) or going short (selling). Several traders speculate on this rise/fall and try to profit from the changing price of the contract. Right from eggs, to precious metals - futures contracts exist for several commodities! 

Futures Trading 2018: How to Do it?
How to do Futures Trading in Vietnam

Futures are unlike other financial assets, solely because of their lack of inherent value. Additionally, a particular commodity can't be speculated for a long time because each futures contract has an expiration date. This makes futures trading a very sophisticated and volatile field to delve in. 

Basics of Futures Trading in 2018:


Futures trading are more than just a means to hedge; it is a provision to speculate on financial assets. The risks involved are very high - while the profits you make might just put you at a breakeven position, the losses will leave you tumbling! Intense amounts of research are required to ensure a healthy trade in futures. Several traders consider taking help from a professional broker when it comes to futures, because of the immense risks involved and the high levels of precision needed to avoid losses.

While trading futures, there is always an underlying element of risk. The second you decide to take a risk, you must be ready to sacrifice all your investments! It has happened on one too many occasions where the losses suffered were more than the investments put in. Futures brokers provide leverage, since buying a commodity is not financially doable; this leverage can be your downfall if you don't trade carefully! Only trade with your risk capital. Incurring leveraged losses will leave you drained of funds in no time! Only utilize money that you can afford to risk losing. 

Tips for Trading Futures in 2018:


1) Study the Asset Completely: The crux of futures trading lies in understanding the underlying asset completely. Traders fail to realize it isn't just the asset that's on the line; it's the accompanying factors as well! Handpick the instruments/commodities you think will move as you predict, then go on to study the factors that affect its movements. For example, if you're a wheat futures trader, just knowing the harvest duration won't help. You must know who the prominent wheat-buyers are, how the weather affects the crop market and the price patterns of all previous years. These are some of the various governing factors for a crop. Similarly, for other commodities, observe and research on the factors that will affect its presence in the market and govern how long it is on the top. 

2) Move on Your Own: Futures trading may look hard to conduct, but with ample research, you can definitely profit! Trading independently has a number of advantages; you can trade at your time, devise your own trading strategy, and other than the facilitation fee, there won't be a dime to pay anyone! However, this requires immense responsibility and attentiveness to pull off. Right from managing funds, to researching, to devising a strong plan - the entire ordeal will have to be handled by you and you alone! This hasn't prevented traders from pursuing it. Several traders are solo players in futures and are more than just successful at it.

3) Implement Stop-losses: Futures holds a lot of liquidity, which will work against you in no time. Profits always look attractive from the distance, but the closer you go the more you realize - the path to profiting in futures is laden with risks! Several traders choose to stick to losing positions out of pride, or hoping that the market will turn in their favor! Avoid such careless acts. An amazing way to keep losses in check without pressurizing yourself each minute is by implementing a stop-loss before hand. Stop-losses are mechanisms that are hugely beneficial in trading. Implementing a stop-loss will automatically withdraw your position once a losing trend is spotted or a certain loss amount is met. Risk management and loss minimization make up a huge part of your trading strategy.

Futures are a highly lucrative field with immense prospects of profits. However, the volatile nature of futures ecosystem makes it very liable! Assisted by WesternFX - the best at futures trading in Vietnam, you will not just learn, but excel in your ventures! Call us today to hire us.

My New Book in Draft

Working title:

Jerks, Zombie Robots, and Other Philosophical Misadventures

[former working title: How to Be a Crazy Philosopher]

The book is composed of several dozen blog posts and popular articles, on philosophy, psychology, culture, and technology, updated and revised, selected from eleven hundred I published between 2006 and 2018.

The full draft is available here.

I will be revising it for the rest of the summer and into the fall, so feedback is appreciated! In addition to the usual content-level feedback, I also welcome feedback on: (a) alternative possible titles, (b) posts or articles that I should have included but didn't, (c) posts or articles that aren't up to the quality of the others and should be cut.

The book is divided into 61 chapters in 5 parts. Every chapter is free standing. No need to read them in order.

[a haphazard sample of the stacks of books in my office, consulted during revision]

Table of Contents:

Part One: Moral Psychology

1. A Theory of Jerks
2. Forgetting as an Unwitting Confession of Your Values
3. The Happy Coincidence Defense and The-Most-I-Can-Do Sweet Spot
4. Cheeseburger Ethics (or How Often Do Ethicists Call Their Mothers?)
5. On Not Seeking Pleasure Much
6. How Much Should You Care about How You Feel in Your Dreams?
7. Imagining Yourself in Another’s Shoes vs. Extending Your Love
8. Aiming for Moral Mediocrity
9. A Theory of Hypocrisy
10. On Not Distinguishing Too Finely Among Your Motivations
11. The Mush of Normativity
12. A Moral Dunning-Kruger Effect?
13. The Moral Compass and the Liberal Ideal in Moral Education

Part Two: Technology

14. Should Your Driverless Car Kill You So Others May Live?
15. Cute AI and the ASIMO Problem
16. My Daughter’s Rented Eyes
17. Someday, Your Employer Will Technologically Control Your Moods
18. Cheerfully Suicidal AI Slaves
19. We Have Greater Moral Obligations to Robots Than to (Otherwise Similar) Humans
20. Our Moral Duties to Monsters
21. Our Possible Imminent Divinity
22. Skepticism, Godzilla, and the Artificial Computerized Many-Branching You
23. How to Accidentally Become a Zombie Robot

Part Three: Culture

24. Dreidel: A Seemingly Foolish Game That Contains the Moral World in Miniature
25. Does It Matter If the Passover Story Is Literally True?
26. Memories of My Father
27. Flying Free of the Deathbed, with Technological Help
28. Thoughts on Conjugal Love
29. Knowing What You Love
30. The Epistemic Status of Deathbed Regrets
31. Competing Perspectives on One’s Final, Dying Thought
32. Profanity Inflation, Profanity Migration, and the Paradox of Prohibition (or I Love You, “Fuck”)
33. The Legend of the Leaning Behaviorist
34. What Happens to Democracy When the Experts Can’t Be Both Factual and Balanced?
35. On the Morality of Hypotenuse Walking
36. Birthday Cake and a Chapel

Part Four: Consciousness and Cosmology

37. Possible Psychology of a Matrioshka Brain
38. A Two-Seater Homunculus
39. Is the United States Literally Conscious?
40. Might You Be a Cosmic Freak?
41. Penelope’s Guide to Defeating Time, Space, and Causation
42. Choosing to Be That Fellow Back Then: Voluntarism about Personal Identity
43. How Everything You Do Might Have Huge Cosmic Significance
44. Goldfish-Pool Immortality
45. How Big the Moon Is, According to One Three-Year-Old
46. Tononi’s Exclusion Postulate Would Make Consciousness (Nearly) Irrelevant
47. What’s in People’s Stream of Experience During Philosophy Talks?
48. The Paranoid Jeweler and the Sphere-Eye God
49. The Tyrant’s Headache

Part Five: The Psychology and Sociology of Philosophy

50. Truth, Dare, and Wonder
51. Trusting Your Sense of Fun
52. Why Metaphysics Is Always Bizarre
53. The Philosopher of Hair
54. Kant on Killing Bastards, Masturbation, Organ Donation, Homosexuality, Tyrants, Wives, and Servants
55. Obfuscatory Philosophy as Intellectual Authoritarianism and Cowardice
56. Nazi Philosophers, World War I, and the Grand Wisdom Hypothesis
57. Against Charity in the History of Philosophy
58. Invisible Revisions
59. On Being Good at Seeming Smart
60. Blogging and Philosophical Cognition, or Why Blogging Is the Ideal Form of Philosophy!!! :-)
61. Will Future Generations Find Us Morally Loathsome?

Think of Your Dissertation as Your Longest Work, Not Your Best Work

You* know how to write a decent seminar paper. You've done it at least a dozen times. So why is it so hard to get going on that dissertation?

[* for values of "you" of approximately 3rd-5th year in a philosophy PhD program]

Your advisor might stink. That's rough. It can definitely slow you down. But that's probably not the main reason.

You've got to teach or TA. Yes, that consumes oodles of time if you're conscientious about it. But I doubt that's the main reason either.

I suspect that the main reason, for most students, is excessive expectations. You want your dissertation to be the best thing you've ever written. You want to finally address a big, ambitious topic. You want work that will wow your advisor and everyone else.

Sure, of course you do! Those are good things to want. The problem is that the wanting interferes with the getting.

It interferes in two ways: by leading you to take responsibility for a larger literature than you can digest in the time allotted, and by encouraging perfectionism.

Against taking on too big a literature:

How do you write a seminar paper? You read the ten or thirty things assigned for the seminar, plus maybe a few other things. You especially master one or two of them, and then you develop your critique or alternative position. Now you've got a fine little criticism, say, of Gendler's view of "alief" in light of a couple of recent review papers on implicit bias. Seminar grade: A. Lovely!

But now you're on your dissertation. Time for a big, ambitious topic. Time to throw yourself deep into something important. You want to defend the existence of moral facts. Or you want to show how it's possible to have infallible introspective knowledge of your own experience. Great! To do this responsibly, what do you need to read? Um...

... the whole entire literature on moral facts or introspection?

That might take a while. Could you possibly do it in a semester or a year (while teaching, with life happening, etc.)? How do you even get started? Meanwhile, the clock is ticking. You feel like you've got to start writing. You can't not write for two and a half years while you read every book and article that has been written about these topics. But neither can you really write in an informed way without having read all of that stuff. So are you supposed to write in an uninformed way? If you're like most of us and you think in part by writing, how are you going to even organize it all in your mind and remember it if you aren't writing?

That's a nasty little pickle.

Here's the way to duck the pickle: Choose a much smaller topic that you really can master in a dedicated couple of months. Not just any topic, of course. One relevant to the big picture you have in mind.

Suppose your big topic is the (in-)fallibility of introspection of conscious experience. You might read everything pro and con in the recent literature on "containment" models of introspection, according to which the judgment I am in conscious state S literally contains conscious state S within it as a part (and is arguably thus infallibly correct). This topic is small enough to master and write about in a semester, if you are already a well-trained graduate student in philosophy of mind who has given it some preliminary thought. Though it's a small literature, really getting it right is an ample task for a big, long chapter. And the topic is centrally related to the big-picture issue of introspective infallibility in the recent literature.

Then, for the next chapter, find something nearby that is similarly small and tractable, to which you can bring some of the insights and tools from your previous chapter. Continuing the example, maybe neo-expressivist views of the nature of introspection.

Repeat a few times, and you'll find you've actually covered a fairly large territory in sum. In the process, you'll have mastered much of the literature that seemed so impossibly large at the start.

Find the tiniest thing you can find that is relevant to your topic while also being of significant interest to specialists in the area, and become the absolute bleeding world expert on it. Then bore your advisor with sixty-plus pages of a tediously thorough treatment. This is how to duck the pickle.

Against perfectionism:

If I said, "Michelangelo, next month create the best art you've ever made" could he do it? Not likely!

Don't think of your dissertation as your best work ever. Don't hold your writing to that difficult a standard. Maybe at some point down the road, after a bunch of revision, some favorite piece of it will turn out to be your best work ever. (More on this below.) But having that kind of expectation is not the way to start writing. Reconcile yourself to the likely fact that you're not going to produce the best work of your life in the next few months.

Here's a better way to think of it: Your dissertation will be the longest and most thorough thing you've ever written. That's all. Instead of aiming for brilliant prose, aim for length. Choose that little thing and cover it so exhaustively that no one who reads your chapter on the topic could doubt that you know that tiny corner of academia as well as anyone else in the world.

Send your advisor something long and hairy. It's okay. You're not being graded on prose style. Get it out to your advisor for feedback, and to others you trust, even though it's not the most beautiful of things. You can revise it later! That's the point of getting feedback, right?

Settle. Your target should be: rough, covers the bases (except for that one thing you forgot which you'll put in later), good enough to move on to the next chapter.

After the feedback, you'll see some things that definitely need changing. But unless some radical rethinking is required, don't make those changes yet! Instead, move on. Write the next chapter. Set the feedback aside to return to later, after you've rough drafted your other chapters. In the course of writing those other chapters, you'll probably have insights that influence your thinking about the earlier chapters, so they'll need significant revising for that reason anyway.

Do this several times and you'll find that you have a few hundred pages of long, ugly chapters that take you from the beginning to the end. Then revise. Rewrite the whole thing top to bottom. Now, at the end -- not in the early drafting stage -- is the time to make it... well I won't say perfect, but better. Polished. This is the last thing you do, simultaneously with hitting the job market.

Likely you will find, at the end, once you're done polishing, that your dissertation, or at least your favorite piece of it, is the best thing you've ever written. That's not because any chapter was fantastic in its initial draft, but rather because you've never before in your life spent a few years thinking about a single topic, and as a result you now have that topic down so well that you really see to the core of it. You know everyone else's views, and you can lay out the strengths and weaknesses of those views, and your great command of the material will show in the final, polished version of your work.

Start today:

So if you're sitting there stalled out on your dissertation, take Doctor Eric's three-step remedy:

(1.) Let go of the thought that you are about to produce the best work you've ever written. Lower your ambitions.

(2.) Choose a topic so narrow that you can read everything relevant in short order, and then read that stuff.

(3.) Write out that narrow thing, long and boring and ugly, blow by blow.

At the end, you'll have several dozen long, ugly, boring, thorough pages -- exactly the kind of material from which excellent dissertations are eventually built.

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Two Ways of Being a Group Mind: Synchronic vs. Diachronic

Based on last week's post, I am now seeing ads for sunglasses everywhere, as if to say "Welcome, Eric, to the internet hypermind! Did you say SUNGLASSES?!"

Speaking of hyperminds....

I want to distinguish two ways of being a group mind, since I know you care immensely about the cognitive architecture of group minds I'm a dork. My thought is that the philosophical issues of group consciousness and personal identity play out differently in the two types of case.

Synchronic:

Examples: Star Trek's Borg (mostly), Ann Leckie's ancillaries, highly interconnected nations (according to me), Vernor Vinge's tines.

Synchronic group minds are probably the default conception. A bunch of independent, or semi-independent, or independent-enough entities remain in constant or constant-enough communication with each other. Their communication is sufficiently rich or sufficiently well structured that it gives rise to group-level mental states in the whole. In the most interesting case, the individual entities are distinct enough to have rich mental lives but also the group is well enough coordinated that it also, simultaneously, has a distinctive, rich mental life above and beyond that of its members.

Diachronic:

Examples: David Brin's Kiln People, Linda Nagata's ghosts, Benjamin Kinney's forks.

In a diachronic group mind, communication is relatively rare but high bandwidth and transformative. Post-communication, the individuals inherit mental states from the others. In the most interesting case, the inheritance process is very different from just listening credulously to someone's testimony; rather it's more like a direct transfer of memories, plans, and opinions, maybe even values or personality. Imagine "forking" into three versions of yourself, going your separate ways for the day, and then at the end of the day merging back into a single individual, integrating the memories and plans of each, and averaging any general changes in value, opinion, or personality. Tomorrow and every day thereafter, you will fork and merge in the same way.

[Cerberus might not be integrated enough to be a good example of a group mind, but I didn't want to attach another darn picture of the Borg.]

Tradeoffs Between Group-Level and Individual-Level Personhood and Autonomy:

As I have described it here, delay between information transfer episodes is the fundamental difference between these types of group minds: whether the minds are in constant or constant-enough communication, or whether instead they communicate only at long intervals. Obviously, temporal distance admits of degree, but this difference in degree creates structural pressures. If communication is infrequent, its effects have to be radical if it is to give rise to an entity sufficiently integrated to be worth calling a "group mind". If every day group of friends meets to exchange information and plan the next day's activities, in the ordinary way people sometimes do this, I suppose that in some weak sense they have formed a group mind. But they haven't done so in the radical science-fictional sense I'm imagining. For example, if there were five friends who did this, there would still be exactly five persons -- entities with serious rights whose destruction would we worth calling murder. For the emergence of something more metaphysically and morally interesting, the exchange has to be radical enough to challenge the boundaries of personal identity.

Conversely, if communication is constant and its effects are radical, it's not clear that we have a group of individuals in any interesting sense: We might just have a single non-group entity that happens to be spatially scattered (as in my Martian Smartspiders).

In other words, to be a philosophically-interesting group entity there must be some sort of interestingly autonomous mentality both at the individual level and at the group level. Massive transformative communication (as in diachronic merging of memories and values) radically reduces autonomy: If communication is both massively transformative and very frequent, there's no chance for interesting person-like autonomy at the individual level. If communication is neither massively transformative nor very frequent, there's no chance for interesting person-like autonomy at the group level.

Consciousness:

Our intuitive judgments about group-level consciousness are probably pretty crappy (as I've argued here and here). But our general theories about consciousness as they apply to the group level are probably even crappier (as I've argued here and here). At the same time, whether the group as a whole has a stream of conscious experience over and above the consciousness of its individual members seems like a very important question if we're interested in its mentality and whether it deserves moral status as a person. So we're kind of stuck. We'll have to guess.

Plausibly, in the diachronic case there is no stream of consciousness beyond that of the merging individuals. When there's one body at night, there's one stream of consciousness (at most, if it's dreaming). When there are three bodies off doing their thing, there are three streams of consciousness. We might be able to create some problematic boundary cases during the merge, but maybe that's marginal enough to dismiss with a bit of hand waving.

The synchronic case is, I think, more conceptually challenging with respect to consciousness. If we allow that minimally interactive groups do not give rise to group level consciousness and we also allow that a fully informationally integrated but spatially distributed entity does give rise to consciousness, it seems that we can create a slippery slope from one case to the other by adding more integration and communication (for example here). At some point, if there is enough coherent behavior, self-representation, and information exchange at the group level, most standard functionalist views of consciousness (unless they accept an anti-nesting principle) should allow that each individual member of the group would have a stream of experience and also that there would be a further, different stream of experience at the group level. But it's a tricky question how much integration and information exchange, and with what kind of structural properties, is necessary for group-level consciousness to arise.

Personhood:

One interesting issue that arises is the extent to which an individual's beliefs about what counts as "self-interest" and "death" define the boundaries of their personhood. Consider a diachronic case: You are walking back home after your day out and about town, with a wallet full of money and interesting new information about a job opportunity tomorrow, and you are about to merge back together with the two other entities you forked off from this morning. Is this death? Are "you" going to be gone after the merge, your memories absorbed into some entity who is not you (but who you might care about even more than you care about yourself)? In walking back, are you magnanimously sacrificing your life to give your money and information to the entity who will exist tomorrow? Would it be more in your self-interest to run away and blow your wad on something fun for this current body? Or, instead, will it still be "you" tomorrow, post-merge, with that information and that money? To some extent, in unclear cases of this sort, I think it might depend on how you think and feel about it: It's to some extent up to you whether to conceptualize the merging together as death or not.

A parallel issue might arise with synchronic groups, though my hunch is that it would play out differently. Synchronic groups, as I'm imagining them, don't have identity-threatening splits and merges. The individual members of synchronic groups would seem to have the same types of rights that otherwise similar individuals who aren't members of synchronic group minds would have -- rights depending on (for example, but it's not this simple) their capacity to suffer and think and choose as individuals. They might choose, as individuals, to view the group welfare as much more important than their own welfare (as a soldier might choose to die for sake of country); but unless there's some real loss of autonomy or consciousness, this doesn't threaten their status as persons or redefine the boundaries of what counts as death.

Related:

Possible Architectures of Group Minds: Perception (May 4, 2016)

Possible Architectures of Group Minds: Memory (Jun 14, 2016)

Group Minds on Ringworld (Oct 24, 2012)

If Materialism Is True, the United States Is Probably Conscious (academic essay in Philosophical Studies, 2015)

Our Moral Duties to Monsters (Mar 8, 2014)

Choosing to Be That Fellow Back Then: Voluntarism about Personal Identity (Aug 20, 2016).

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5 Things To Keep in Mind While Trading CFDs

CFDs vary immensely from the other genre of trades. They are initially easy to enter but they are leveraged products. Meaning, getting the speculation off-point will lead to colossal losses. CFDs have one of the lowest initial investment rates, but this is compensated by the difficulty that follows a trade. Contracts for Difference leans more towards the speculation aspect than the technical aspect. 

If you are new to the genre, here are 5 things to remember while trading CFD:         

CFD - Things To Remember Before Investing
CFD - Things To Remember Before Investing

1)  What does CFD Mean? Contracts for Differences, these are tradable assets that allow you to speculate the movement of a particular financial commodity without actually owning it. The commodity can be stock, cryptocurrency, index, etc. A profit in CFD is obtained when your speculation for a commodity matches the outcome. What makes CFD a unique branch of trading is that you can make profits even when an asset's value is going downwards? This allows more room for profits, and subsequently losses as well. 

2) Margins and Leverages: Online trading needs an initial investment, to begin with. A margin amount is an initial amount you deposit which allows you to invest in a trade.  This amount varies from broker to broker. The only constant factor being - it is relative to your stop-loss amount. The margin requirement will be based depending on the money you're willing to lose in your stop-loss.

Leverage is a sum borrowed or given by your forex broker. Some trades involve humongous amounts of cash; this can be availed from your broker. Leverage facilitates trades for you by letting you participate in expensive trades. However keep in mind, if you are careless and incur a loss, you lose your money and you have to pay the leverage back. 

3) Buying Long and Selling Short: CFD is all about speculation. To profit in CFD trading, you need just speculate the commodity's price accurately. When you see a rising trend, buy long - this will result in you profiting from each move. Similarly when there's a downward trend, sell short. The fast-paced nature of CFDs however makes it a challenge to hold the same position for a long duration. 

4) Keep Your Spread in Your Head: CFD brokers' main source of income is the spread they charge you. While participating in CFD, it is crucial to keep the spread rates in mind. Your broker might showcase attractive trades that are more beneficial for him and you might end up losing more than you invested. 

5) Trade Closure: A key aspect to note when trading CFDs is that your account must have funds at all times. Your broker has the complete control over your account, should the said balance fall below the margin amount, he can close it. 

CFDs are easier to setup and get into, however once in the field, tread with caution! The overnight funding costs and high market volatility might throw you off track. Get yourself the best CFD broker to partner with - get yourself WesternFX. Equipped with our stellar platform and strategies, conquering CFD trading in Vietnam will be a cake-walk! Call us today to know more.