Thursday, May 30, 2013

Still reeling around post-Moseley

Just not yet. I'm still reeling around a little bit, post-Moseley. ]

Moseley blogpost 1
Moseley blogpost 2

I think I've got a few more bits to say about all this Moseley business. 

Carol Lynn Chevrier, with Lorimer Moseley.
Lorimer Moseley with Carol Lynn Chevrier.
First of all, Carol Lynn Chevrier, massage therapist in Montreal and a friend, did some nice conceptual post-Moseley digesting of her own, on Facebook. Here is a link to her post. [I don't know if everyone will be able to read it.] 

Holy hell, as Carol herself often says. 
That's her tag. 
Her neurotag. 

It's a great post. Here is an excerpt:

"Moseley is ALL about the brain. ALL about science. In one of the most reasonable, logical, science based 15 minutes I've ever had the pleasure to experience, he deconstructed that antibiotics for back pain study. For me, it was a very clear reminder of why I paid 300 bucks to attend that seminar. This man is a scientist, first and foremost, hilarious anecdotes notwithstanding. I doubt the people at Oxford really gave a shit about his charisma. This man knows his stuff, holy hell does he ever. Let's not forget that at the heart of his research, there is the Neuromatrix. He always comes back to it. He's beefed it up. Designed studies around it. He knows enough about it to know that changing a human being's pain experience sure in hell ain't *just* about method. '' About what you do with your hands. He's beyond that and soldiering on to convince clinicians-psychologists-nurses-PT's-OT's among others, that pain is always, one hundred percent of the time, a production of the brain. How you as a clinician will work out and figure out a way to import that to your field is up to you. Science, good science will eventually determine what we should keep and what should phase out. This will take time. Such is the scientific endeavor. Pain neuroscience should make your job harder, not easier. '' Moseley told us says Mick Thacker once said to him. No shit."


Here is an additional neurotagged thought from me:

Just yesterday I saw this from Nortin Hadler in Scientific American: The Scientific Basis for Choosing to Be a Patient: Forearmed Is Forewarned. Brilliant. 

Here's an excerpt. 
"Today health is a commodity, disease is a product line and physicians are a sales force in the employ of a predatory enterprise... Health, disease, and “the doctor” are constructions peculiar to a particular culture at a particular time. Each is supported by pronouncements, theories, claims, and recriminations. The difference today is the availability of a body of scientific information that can question, even discard, whatever in the din has been shown to be fatuous...  Health is not the absence of symptoms; all of us will suffer symptoms repeatedly, symptoms which give us pause without compromising our belief that we are basically well. Episodes of backache, headache, heartache, heartburn, “colds”, “flu” and much more are predicaments of life for which most are a match most of the time. Despite such predicaments, we remain in “good health.”... “Health” is a reflection of the degree to which we feel complete in our bodies tempered by the degree to which we perceive that sense to be threatened.... An effective doctor-patient interaction commences with the intertwining of 3 strands of interpretation in order to arrive at mutual understanding:
  • the context that engendered the consultation,
  • the nature of the complaint, and
  • the limitations of causal inferences.
The interpretations are always laden with presupposition and prejudice by both parties. Until very recently, there was little about this interaction that was equitable. Earlier generations of patients were largely in awe of the rituals, ignorant of the details of the clinical process, and desirous of pronouncements. That is no longer the rule.”

My thought is, PT is well positioned to alleviate the planet of biomedical harm, done onto people by otherwise well-meaning people who have been trained to carve up human flesh for a living, and think they can carve it to get rid of pain. 
If PT learns these lessons well, that is. 
The ones that Moseley and all his colleagues are trying very hard to deliver out into the world in a timely manner. Well-developed and rigorously scientific. Pretty much scientifically bullet-proof, even. Go Moseley. 

And a couple screenshots of my handy-dandy powerpoint art. 

Modulators of pain

Moseley: use of terms, "pain receptors, pain fibers, pain pathways" = ERRONEOUS
From "Teaching People About Pain"

Wednesday, May 29, 2013


The day before yesterday was a one-day seminar with Lorimer Moseley. I managed to live tweet quite a bit of it. So I thought I might take a slightly longer break from the Melzack paper, bring the tweets, try to match them with the papers. I didn't always get the papers tweeted in the heat of the moment. Here is a list of all articles related to the seminar. (Some parts of the presentation were about material not yet  published, so tweeting about them was disallowed.)

Anyway, here is the tweet list as it happened.

  • Sensory feelings - "I feel like my arm doesn't belong to me" etc.
[I.e, it isn't always necessarily about "pain" - there are disturbances in sensation in general and interoception, proprioception.]
  • Ming from Singapore helped Lorimer obtain some rubber limbs. This story was told at also. "Uhhhhhhhhhhhhhhhh.."
[Hilarious yarn about stealing rubber arms from some facility - Ming created a distraction by making a loud Uhhh sound, then abruptly stopped and ran away.]
  • Rubber hand illusions - posterior parietal cortex will quickly shift ownership of sensation to the rubber hand - vision overrides
  • Do you end up with 3 limbs in the brain? One hand will be disowned. "How vivid was the illusion? Hand temp reduces substantially
  • Temperature change could start to implicate tissue health. Brain's rejection of a body part. Dis-ownership
  • A cool arm is more easily disowned. You have to cool the arm but not the rest of the body.
  • With histamine injections under the skin: placebo antihistamines work quite well.
[References included Henrik Ehrsson. See Ed Yong's blogpost, Out-of-body experience: Master of illusion, with a podcast interview embed to learn more about Ehrsson's fascinating work on dislocating sense of self from various brain systems, including the autonomic nervous system.] This just in May 29: Extending the self: some cold truths on body ownership [includes a video, about 3 minutes]. 
"Last year, researchers Lorimer Moseley, Alberto Gallace and Charles Spence introduced the idea of the “body matrix” in relation to this question. The body matrix, as they described it, is a multisensory representation of our whole body and the immediate space around it."
  • Brain gauges effortfulness or perceived ease of an effort, and will recalibrate reality
  • Brain recalibrates its perception of reality every fraction of a second
  • Brain always is calculating "How threatening is this?" or "How safe is this?"
[The brain will literally make obstacles seem larger, heavier, higher - goals seem further away. This is all in accordance with large amounts of perception research.]
  • Protection and regulation of the body are connected deeply - we can change blood flow by changing how much you own a body part. (Moseley et al 2012 Neurosci reviews)
  • Cooling effect takes minutes.. histamine effect is a cascade that takes awhile to occur.
  • More rapid changes are made visually. Visual illusions are also the most difficult to shift.
It's VERY hard to un-see a visual illusion. The brain decides quickly, based on clues it has internalized through evolutionary time, such as light source, where the ground is, etc. This applies to all systems, not just visual, because of built and sustained neurotags.
[By the way, "neurotag" is just Aussie for "Neurosignature," coined by Melzack. Neurotags look like graffiti tags, or doodles in the brain - hard to remove.. is that a buried linguistic connection? I think it might be..]
  • Change the body of knowledge inside someone; it will shift.. maybe not rapidly, but it will shift over time.
  • Cortical body maps consist of all neurotags involved in protection/reg. of body
  • "Cortical body map" really... includes anything above level of foramen magnum
  • ...including everything in brain that is subcortical
  • Cortical body matrix: "network of neural loops subserving protection and regulation of body, physiologically & psychologically"
There isn't any specific cut off neuroanatomically. I asked. I would call these loops the relationship between critter brain and human brain, myself. "Cortical" isn't limited to merely cortex, in other words - it can refer to anything, any loop above foramen magnum, but I think we have to remember that long dock out into the ocean of the body and the body's physiology, also known as the spinal cord. It's still CNS after all..
  • Wipe out cingulate cortex, pain will go away for a few months but returns eventually.. unfortunately..
  • All neurotags rely on inhibition. This is key for any kind of precision.
  • Recruiting brain cells is easy. Turning them off is the hard part. Inhibiting them is the hard part, to get precision.
  • Migraines involve a sweeping activation over the brain - not enough inhibition
  • Pain isn't a thing, it's an output produced -big lip after visiting the dentist feels big because of inhibition of sensory input
Pain isn't a noun - it's a verb! And it looms, because normal precision-creating inhibition decreases.
  • Re: manual therapy - giving the brain a new input will change pain easily.
  • What do we do with conflicting conceptual paradigms? They change anyway. Slowly.
  • Less back surgery is being done (for pain).
  • The evidence is against surgery for mere garden variety back pain.
  • We have to let go of causality fantasies in therapy (Leake et al 2012 proprioception, neck..)
Yes.. there are quite a few papers related to how abnormal findings shouldn't be an excuse for surgery, because they can be found in asymptomatic people too - just like grey hair or wrinkles.
  • Systematic reviews on "proprioceptive deficits in the neck"
  • Is the "cause" to do with the proprioceptive organs? Just because there's a deficit doesn't mean the receptors aren't working
  • Disruption of motor maps. Only interrogate the map of the neck, not the neck itself - looking at a laterality picture.
  • Again, precision deficit, at the OTHER end of the NS, not at the peripheral end
  • Imprecise proprioceptive response - implies lack of inhibition. Not a deficit of proprioception.
  • Disinhibition, loss of precision: Does this apply to CRPS?
  • CRPS, hand size precision is impaired - precision is way reduced. Feels bigger than it really is. Sometimes feels missing.
Such a lot of exciting possibilities for mapping of space.
  • The better your tactile acuity the better your performance on tasks
  • Accuracy of left/right judgements goes down with decreased tactile acuity
  • Tactile acuity deficit goes with proprioceptive deficiency
  • Tactile acuity and motor imagery are linked. Stanton et al Rheumatology 2012
  • Painful knee osteoarthritis - won't likely get much improvement by training two-pt discrimination.
  • Works better for backs
  • Brain likes to know where is something according to the midline
  • With stim, tactile neglect of painful hand.. hands crossed over, they still neglect the space, but NOT the hand. That's from Moseley et al Brain 2009
  • Moseley et al 2012 Neurology
  • Spatial maps and autonomic control
  • A painful hand seen through a magnifier to make it look bigger makes it hurt more. Moseley et al 2008
  • ... and the swelling increases!
  • When the hand is seen through a minimizing lens, the swelling DE-creases. (Isn't that cool?)
This is from work done on CRPS, I think.
On to glia!
  • Every synapse is hugged by a glial cell.
This relates to the exciting work done by Seth Grant who showed that synapses (with their glial control) may drive evolution.
  • When the glial cell releases inflammatory cytokines, which affects the next neuron, creates disinhibition and loss of precision.
This happens when a synapse is used way too much. [Maybe the glia cell starts to get tired? Anyway, this is like in the PNS, where Schwann cells can start to impersonate immune cells by producing cytokines, etc. File under "Neural crest derived cells are brilliant but can get weird"]
  • Rumination on how bad something is. Like life..
  • ....keep running neurotags, whole body becomes sensitive. Imprecision will create a spread.
  • Ornithology hijacked amazing grace - the clarinet story from Painful Yarns
I finally understood what this story was about. I think in the book, a big (and critical) chunk must have been accidentally chopped.
It had to do with a music neurotag that was augmented by leaning back against a door handle in a truck, and the position of leaning, and darkness... then playing in a club where the clarinet player (Lorimer) sat on a truck seat replica inside the club, leaned back, and was surprised to find himself playing Orthinology instead of what he should have been playing, which was Amazing Grace.
  • If brain cells are used to turning on repeatedly, they might stay turned on. That's one type.
  • Another type is, the cells stay turned on with less cueing.
That would be, central sensitization.
  • Lack of turning off because of disinhibition/loss of precision. It's bad if in the motor cortex.
Focal dystonia in musicians is a common problem.
  • How we use pain as an informant to state of nervous system. There are different qualities and patterns which provide clues
The poster outlining guide to contributing mechanisms.
  • Axon reflex: clinical nugget. Heat will increase mechanically evoked pain if it's primary nociceptive.
  • [But why would we do that to people anyway?? = first law of human primate social grooming]
  • Sensitivity to do with behaviour: Immediately or next day, flareup - pretty much CNS derived in a sensitive system.
  • [Long philosophical sidetrack into what manual therapy does at a biological and interactive level]
  • The best pain stuff has come along in the last 25 years
  • We know the immune system is a big player in pain. A problem is that we don't know what to do about it.
Antibiotics for back pain: hope or hype? BMJ May 17 G Lorimer Moseley
  • About that study about antibiotics and LBP....
  • About 90 finished the study. It was an RCT. Conclusions don't really match the results.
  • Placebo group had no result whatsoever. Suggests they weren't blinded.. and there were side effects.
  • Treatment FX could be explained by placebo. Disappointingly overplayed by the media group.
  • We need to be precise and honest as researchers and as clinicians. It's easy to slip up on communication. Very disappointing.
  • All the LBP patients will hear about it because of the buzz. Poor patients. Poor researchers.
  • New topic: Recognize, training the brain. It takes about 50 photographs to get past the explicit learning system into implicit
Graded Motor Imagery (Book Review)
  • So far, no reports of hurt with GMI. There have been a few incidents of inc. pain with mirrors. Some mirrors were distorted
  • Management plan: Target pathological findings
  • Target cognitions. Meaning and mood. Consider conceptual grains - "I shouldn't hurt if I move" - D Butler
  • Dethreaten them. Provide info to dissolve the neg neurotags
  • Change "I have pain therefore I am damaged" to "I have pain therefore my brain is trying to protect me."
Look to other fields for how they reduce threatening cognitions. Look to Cognitive Behavioural Therapy, Adult Education, etc.
  • Offer evidence, twice. Provide an alternative. Give novel examples, twice.
  • Got to get them engaged. Activate emotional systems. Provide novel reinforcements. Practice.
  • Change "I have pain therefore I am damaged" to "I have pain therefore my brain is trying to protect me."

It was a wonderfully full and interesting day. Lots of SomaSimplers were there, all the ones who live in Montreal, anyway: here they are standing with Lorimer Moseley.

From left to right: Moseley, Eric Ouellet, Carol Lynn Chevrier, Randall Lightbrown.

The room was packed, mostly PTs. Susan Tupper thought there were at least 10 rows of ten people each, which would be roughly 100 attending.

MORE: Neuroanthropology on Brain Science Podcast Excellent, excellent podcast - Ginger Campbell interviews the authors of the new book, The Encultured BrainNeuroanthropology: What Is It and Why Should You Care?

The authors point out that the brain is where culture and biology come together and influence each other. An example; about an hour into the podcast one of the authors describes how his vestibular system had to adapt to his training in capoeira. The challenge in capoeira is that it's a martial art form, fought with an opponent, while standing on your head or your hands. Gymnasts do this all the time but they exploit their visual system by always looking to see where the ground is. In capoeira you have to look at your opponent, or risk getting thumped by him/her. The vestibular system is forced to neuroplasticize in other ways. It has to make unusual neurotags.

What does this have to do with pain? It has everything to do with how brains neuroplasticize themselves in relation to inputs. Pain is an output, just like movement is an output. Brains practice and practice until their predictive ability matches what they produce as output. This occurs once surrounding inhibition produces accuracy, precision. After that, the brain has "got it." It has a sturdy neurotag built. Norman Doidge called pain "the dark side of neuroplasticity."

I think, first, you have to pick your parents well. They will be your world for much of the time your brain is busy soaking up your world. Not to mention, you don't want to end up with funky genetics, particularly, or epigenetics. It will help if you are not born into relative poverty/low social status. Emphasis on the word "relative." As long as most of your neighbours are in the same boat, and you have basics (food, clothing, shelter) covered, there won't be any social stigma.
Then you have to not be exposed to violence or abuse in the home, either to yourself or of any primary caregivers you depend on. Your vulnerable child brain will totally load up on stress from watching your mother be battered, for example.
It's great if your primary caregivers hold you a lot, provide long loving sessions of direct skin contact to you when you are an infant. It will help your brain develop.
It's great if you don't get seriously injured too much, yet get lots of exposure to your environment in terms of graded challenge to your immune system, and to your nociceptive system. If you're having fun playing with your peers, your brain will build up robust pathways dedicated to descending modulation of all the right kinds. Having educational opportunities is a very very nice bonus. Brains need to learn how to distract themselves. They need things to practice thinking about. Some sort of music training in addition to cognitively delivered cultural input is great. Lots of exercise too.
If all goes well you will grow up into an adult with a nervous system in good shape, able to do what it needs to do from a bank of successfully mounted resolutions to physically and emotionally generated experiences and challenges.

As long as you have genes that can make all the necessary proteins, your nervous system should be able to get itself out of pain. Sometimes it might need a bit of help, from the culture, just to get it started, but after that, it should be good to go.

Philosophically speaking, it will never be able to be "the way it was before the thing happened", but it should be able to get back to coping easily with struggles and strains without hurting you in the process.

Sunday, May 26, 2013

Lorimer Moseley spoke to the Canadian physiotherapy profession today

It might have been noticed by followers of this blog (both of you...) that I haven't blogged about the Melzack paper over the last few days. This is because I'm here in Montreal, attending CPA Congress 2013 (#CPACongress2013 on twitter). 

As long as I'm part of the PainScienceDivision, I'll need to attend meetings at Congress. Which is great. Especially when Lorimer Moseley (@bodyinmind on twitter) is doing a plenary session! 

Lorimer Moseley, holding his rubber hand
His hour long session was this morning. It was titled, "200 billion reasons to train your brain." (I have no idea where that figure came from..) Let's face it. Moseley is a PT rockstar. He has done more to move PT along toward taking on and dealing directly with pain science than any other PT in our profession's history. I mean, there are many distinguished PTs in pain research, but somehow this goofy self-deprecating Aussie with a lopsided grin, many droll stories about pain, knack for telling them, and a canny way of inserting them into presentations to serve as teaching tools, has charmed the profession out of the mesodermal coma it was born into - at least it looks like he might have.
Moseley was quite open in his admiration of the way the Canadian Physiotherapy Association is well-run, well-organized; he judged this by how its outgoing president Rob Werstine received a standing ovation today as he ended his term. Moseley is pleased that CPA has taken on pain this decade! How it's willing to learn that pain's in the brain! 

I think everyone there was WELL-convinced by Moseley's exemplary plenary session: in just a single hour, Moseley was able to reach the profession's entire political leadership in Canada. 

PSD laid dry kindling under the profession when we became a division in 2008, all set to ignite: this weekend Lorimer lit the match!!* CPA gets it now - it really gets what we were going on about almost 10 years ago, why our little group (Neil Pearson, Dave Walton, and I) were on about, when we said, "We want to start a pain division." One could hear snatches of conversation in the elevators after - "Pain - in the brain.. wow.."

Of the top 10 major health issues thought to be the biggest challenges to our (rapidly aging!) population in the near future, chronic pain and associated conditions occupy four slots. Cancer is 40th down the list.

PT in Canada is positioned for advance - we have direct access in place everywhere, we have the organizational steam to continue, we're in good shape as THE profession most ready to take on the challenge of pain, publicly and privately, in a cost-effective manner: this will be important as our economy shrinks, or barely holds its own.

[Next step, according to me: CPA galvanizes to convince government and the public to place even more trust in PT than they already have, persuades them to consider less biomedical explanatory models of pain, and treatment for pain].

Pain Science Division is in position. We saw this coming a long time ago. We are ready, willing, able to help the profession on-goingly meet the challenge. We started out in 2004 with three people, one of whom was in the process of acquiring a PhD. We became 8 people, 4 with PhDs and another on his way to attaining it. [Alas, we are losing two PhDs this weekend, but they said they'll stay close.]

At first CPA said no, but later (2008) they said yes. 

Before then we had Mike Sangster, Eric Matheson, Deb Patterson, Lesley Singer, Bas Asselbergs in addition to the original trio. A few people withdrew. When the group was recognized as a division, it morphed: Neil was chair, Dave chair elect and newsletter editor. When Dave took over chair, Susan Tupper became newsletter editor. Geoffry Bostick came along when research representative position was added. Bas rejoined as secretary, and Timothy Wideman was elected chair elect. Lesley Singer was re-elected as treasurer. I am still part of the exec, as communications liaison. 

This weekend we added Jordan Miller (new newsletter editor, as Susan's term ended). Tim is now acting chair and Dave is past chair. We have about 500 paying members. We have about 1800 (rough guess) members when we include all the student members in Canada who receive our newsletters.

I am beyond thrilled to travel with such a great group of people into the future of PT in Canada. I am in awe that such a great team self-assembled to move PT into its future of being organized to deal with the complexity of people in pain. I'm really proud of the way this group grew itself up.

Pain Science Division, past and current members**, with Lorimer Moseley, CPA Congress May 2013

After I return home I'll resume my meander where I left off. Today is a bit of a lazy day, hanging out in the hotel room. Tomorrow I'll attend Lorimer's day long session at PhysioActif here in Montreal. An entire day of Lorimer - that should keep me going for quite awhile.

*We (PSD) aren't sure quite how Lorimer got the gig, or how CPA got Lorimer... It wasn't arranged through us, but no matter - we were ecstatic when we heard the news, and managed to arrange for him to come early to address our own division AGM for a half hour or so, yesterday afternoon before the big dinner dance party, Local Flavour Night. He had lovely things to say about how advanced Canadian PT was to have our division up and running, that we were inspiration for PT elsewhere in the world, etc.etc.. nice things. Confirmation. Affirmation. Every meeting, every connection, every reunion, every newsletter, email, skype meeting, every talk, presentation, slideshow, every little drop helps. Maybe even every little blogpost.

**CPA Pain Science Division with Lorimer Moseley, May 2013. 
Left to right: 
  • Bas Asselbergs, Barrie Ont. (Secretary)
  • Susan Tupper, Saskatoon Sask. (Past newsletter ed.)
  • Geoff Bostick, Edmonton Alt. (Division Research Rep.)
  • Lorimer Moseley, Adelaide, Australia (International PT Pain Research rockstar)
  • Dave Walton, London, Ont. (Past chair)
  • Tim Wideman, Montreal, PQ (Current chair)
  • Lesley Singer, Montreal, PQ (Treasurer)
  • Diane Jacobs, Weyburn, Sask. (Communications Liaison)
  • Jordan Miller, Orangeville, Ontario (Newsletter Editor)
  • In front: Neil Pearson, Vernon, BC (past chair)
  • Missing: Deb Patterson, Sharon, Ont. (past secretary)

Tuesday, May 21, 2013

Melzack and Katz, Pain. Part 6a: History of Pain Science: Descartes and his era

The paper, Pain.

Part 1 First two sentences

Part 2 Pain is personal

Part 3a Pain is more than sensation: Backdrop

Part 3b Pain is not receptor stimulation

Part 3c: Pain depends on everything ever experienced by an individual

Part 4: Pain is a multidimensional experience across time
Part 5: Pain and purpose

The next chunk of this paper is called, "A Brief History of Pain." It starts out,
"The theory of pain we inherited in the 20th century was proposed by Descartes three centuries earlier. The impact of Descartes’ specificity theory was enormous. It influenced experiments on the anatomy and physiology of pain up to the first half of the 20th century (reviewed in Ref 4). This body of research is marked by a search for specific pain fibers and pathways and a pain center in the brain. The result was a concept of pain as a specific, direct-line sensory projection system."

So, I thought, I'm no historian, but it might just be interesting to go back to that period with the help of Google, and check out the era, learn a bit about who was fighting with who and who was wearing what

Rene Descartes
So.. good old Wikipedia. It tells me that Descartes was born in 1596 and died in 1650. He was French. 

Right around then, every country in Europe seemed to be out rampaging all over the world, setting up colonies and looting the surrounding lands of anything that could be carried on a sailing ship. All this stuff ended up in Europe and created wealth that had never previously been known to exist.  It wasn't called the Renaissance for nothing. More like economic resuscitation. Suddenly a lot more people had a lot more money to spend on things like commissioned art and music. Descartes lifespan bridged the change from renaissance to baroque. It must have seemed a bit unsettling. He looks like he was a plain and simple type, even as fashion all around him changed a bit. (Maybe he was lucky he died before Rococo hit the scene. Eyew.) 

From Terminartors:
One of Bernini's last sculptures, judging by the date.
All that drapery is carved from red marble.
Oh yeah.  Stone bling. 

The art was like rock and roll. The money made everything and everybody dance, including the church. Money made anything seem possible. Music and architecture exploded too. 

That is a sizeable chunk of North America that France
controlled, over Descartes lifespan... 
Meanwhile, over in North America, colonies were popping up. France in particular had laid claim to a huge chunk of North America and called it New France. In 1608, Champlain founded Quebec City. In 1642, the mission forerunner of Montreal came into existence. In 1651, a year after Descartes died, its population was still less than 50. A Scot, James McGill, came along quite a bit later, made a fortune dealing in fur (which everyone was doing in those days), then turned some of it into a university named after himself in 1829

Much, much later on, Ronald Melzack would study and work there, and would come to four essential conclusions that would change ideas about pain that had lain unexamined from the time they had popped into the head of Descartes, way back in the 1600's. Way back when science first exploded.