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FASEB this week: Findings from the University of Colorado Boulder Nicotinamide Riboside Human Clinical Trial

nicotinamide riboside

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#31 bluemoon

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Posted 14 August 2017 - 03:18 AM

 

ChromaDex posted on its homepage that the next meeting where quarterly financial results will be reported is on August 10th at 1:30 Pacific Time. This should be  an interesting meeting... 

 

With this date passed, were there any interesting news related to this? 

 

 

I posted the summary on another thread but haven't seen anything new in the past few days. The stock fell 20% in the two weeks prior to the meeting but went up 10% the next day. It looks like both ChromaDex and Elysium will be the two major NR sellers unless someone else enters. CromaDex said last year that it intends to sell NR as a boutique product just as Elysium has been but now that Elysium has a new source of NR, ChromaDex may be forced to sell at a cheaper price. NMN might replace NR next year or 2019 and Elysium announced it is readying 6 human trials on its next pill or pills.



#32 Bryan_S

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Posted 14 August 2017 - 08:35 AM

 

 

 

 Still no word on the study findings. https://clinicaltria...how/NCT02921659

 

Bryan,  you interviewed  dr. Brenner and mailed questions to him sometime ago. What about mailing him asking him for some preliminary info on the trial?

 

 

Results can't be accessed before publication. I've been down this path before. I was hoping some preliminary results would be forthcoming from the FASEB but that didn't happen.



#33 bluemoon

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Posted 14 August 2017 - 09:32 AM

 

 

 

Bryan,  you interviewed  dr. Brenner and mailed questions to him sometime ago. What about mailing him asking him for some preliminary info on the trial?

 

 

Results can't be accessed before publication. I've been down this path before. I was hoping some preliminary results would be forthcoming from the FASEB but that didn't happen.

 

 

But ChromaDex reported on its findings for its previous studies long before being published in online Nature. Elysium also put part of its results on its website in December and said it intended to publish the full results. Also, the CEO of ChromaDex couldn't have known in March that the publication would be out in June/July when he thought the "top line results" would be given then pushed back twice. For whatever reason, both companies don't want the results of their trials announced yet.     


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#34 Harkijn

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Posted 14 August 2017 - 05:00 PM

Those of us who, like me, struggle to understand the biology of NAD+, also in it's wider context, will be interested in this very comprehensive study about aging in general. In another thread earlier today, Albedo pointed to this article:

http://www.cell.com/...8674(16)30981-3

It really reads like a compendium of aging science, but in the context of this NR thread I quote:

 

Some of the best-studied human progerias, ataxia telangiectasia, Cockayne syndrome, and xeroderma pigmentosum, are disorders of nucleotide excision repair characterized by severe neurodegeneration. These diseases are accompanied by the hyperactivation of poly(ADP-ribose) polymerase 1 (PARP1), a nicotinamide adenine dinucleotide (NAD+)-dependent enzyme involved in DNA repair. PARP1 hyperactivation leads to NAD+ depletion, hence inhibiting the NAD+-dependent deacetylase sirtuin 1 (SIRT1) (Fang et al., 2014). These events lead to mitochondrial abnormalities, including reactive oxygen species (ROS) generation, increased transmembrane potential, and limited mitochondrion-selective autophagy (mitophagy), all of which can be rescued in mice by PARP1 inhibition or external supply of the NAD+ precursor nicotinamide riboside (Fang et al., 2014Scheibye-Knudsen et al., 2014). Mechanistically, these effects (which result in the accumulation of dysfunctional mitochondria) stem from reduced peroxisome proliferator-activated receptor gamma (PPARG) coactivator 1 alpha (PPARGC1A; best known as PGC1α) activity and consequent uncoupling protein 2 (UCP2) downregulation (Fang et al., 2014). Thus, genomic instability may trigger different metabolic alterations that favor cellular senescence and organismal aging.


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#35 stefan_001

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Posted 14 August 2017 - 07:26 PM

Those of us who, like me, struggle to understand the biology of NAD+, also in it's wider context, will be interested in this very comprehensive study about aging in general. In another thread earlier today, Albedo pointed to this article:

http://www.cell.com/...8674(16)30981-3

It really reads like a compendium of aging science, but in the context of this NR thread I quote:

 

Some of the best-studied human progerias, ataxia telangiectasia, Cockayne syndrome, and xeroderma pigmentosum, are disorders of nucleotide excision repair characterized by severe neurodegeneration. These diseases are accompanied by the hyperactivation of poly(ADP-ribose) polymerase 1 (PARP1), a nicotinamide adenine dinucleotide (NAD+)-dependent enzyme involved in DNA repair. PARP1 hyperactivation leads to NAD+ depletion, hence inhibiting the NAD+-dependent deacetylase sirtuin 1 (SIRT1) (Fang et al., 2014). These events lead to mitochondrial abnormalities, including reactive oxygen species (ROS) generation, increased transmembrane potential, and limited mitochondrion-selective autophagy (mitophagy), all of which can be rescued in mice by PARP1 inhibition or external supply of the NAD+ precursor nicotinamide riboside (Fang et al., 2014Scheibye-Knudsen et al., 2014). Mechanistically, these effects (which result in the accumulation of dysfunctional mitochondria) stem from reduced peroxisome proliferator-activated receptor gamma (PPARG) coactivator 1 alpha (PPARGC1A; best known as PGC1α) activity and consequent uncoupling protein 2 (UCP2) downregulation (Fang et al., 2014). Thus, genomic instability may trigger different metabolic alterations that favor cellular senescence and organismal aging.

 

Thanks for posting. Related on the personal experience board there is this quote:

I am 50 years old and have Spinocerebellar Ataxia Type 1.  My father and my aunt also have SCA1.  They were in wheelchairs.  SCA1 is like Huntington's Disease.  Last month I started all of us on a regimen of 80g of trehalose and 500 mg daily of nicotinamide riboside.  My father has gone from exclusive use of a wheel chair to now using a walker.  I have gone from not being able to stand on one leg to now balancing no problem.  Also I have been running 3 to 4 times a week for 30 minutes since I was age 14.  In the last month my pace fell from 10 minutes per mile to 9 minutes per mile.  I also have a home gym and have been working out 3 times a week for more than 2 decades.  I had fallen to 4 chin ups at 5 sets and have returned to 5 sets of 7 so far.  I'm not sure what a healthy person would expect to see from taking NR, but I can tell you for someone who has extensive cellular damage that is in need of repair the results are nothing less than astonishing.  This is a n=3 study, but it is almost impossible for this to be placebo effect given the unrelenting nature of SCA1.
I intend to take the time to read all 34 pages, but what I'm curious about is are there any other people on this thread who have a diagnosed neurological disorder that have tried NR?
Joe in NY
 


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#36 bluemoon

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Posted 14 August 2017 - 08:34 PM

   Last month I started all of us on a regimen of 80g of trehalose and 500 mg daily of nicotinamide riboside.  My father has gone from exclusive use of a wheel chair to now using a walker.  I have gone from not being able to stand on one leg to now balancing no problem.  Also I have been running 3 to 4 times a week for 30 minutes since I was age 14.  In the last month my pace fell from 10 minutes per mile to 9 minutes per mile.  I also have a home gym and have been working out 3 times a week for more than 2 decades.  I had fallen to 4 chin ups at 5 sets and have returned to 5 sets of 7 so far.  I'm not sure what a healthy person would expect to see from taking NR, but I can tell you for someone who has extensive cellular damage that is in need of repair the results are nothing less than astonishing.  This is a n=3 study, but it is almost impossible for this to be placebo effect given the unrelenting nature of SCA1. 

 

 

 

If they are also taking 80g of trehalose, then how does he know that NR contributed to the improvements?


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#37 bluemoon

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Posted 21 August 2017 - 07:18 PM

 

 

Agree, the eternal "soon to be released" study will help here.

 

 

Five studies have been completed without results made public:

 

* U of Washington: a nine day trial of 8 people raising NR levels to 2,000 mg of NR on the last day two days.

 

* U of Copenhagen: a three month trial of 12 people taking NR at 500 mg and 1,000 mg. The trial ended in February 2015, but not published.

 

* Elysium: an eight week trial of 120 people aged 60 to 79 taking 250 mg, 500 mg and a placebo. The trail ended July 2016, but not made public.

 

* Chromadex: an eight week trial of 140 people taking 250 mg, 500 mg and 1,000 mg and a placebo. Release of trial results pushed

                                                back from June/July to July to September to "within the next few months".

 

* U of Colorado / Chromadex: The about.nr page says 8 people but the study says 30 people, 1,000 mg of NR for six weeks,

                                                 completed in  October 2016

 

 

Is it possible the U of Copenhagen study was rejected for publication since over two years since completion? 


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#38 Michael

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Posted 22 August 2017 - 10:08 PM

I suspect that the 2015 "last modified date" and the fact that it's listed as completed (from which you're deducing a 2015 completion date) on the U Copenhagen/Aarhus University Hospital NR study is just some kind of internal disconnect. It appears that it has just recently been completed, and is probably being written up now:

 

 

Scandinavian Society for the Study of Diabetes 52nd Annual Meeting 19 - 21 May 2017 - Nyborg, Denmark

OP 1‐6

METABOLIC EFFECTS OF NICOTINAMIDE RIBOSIDE IN HUMANS – A VITAMIN B3‐A RANDOMIZED PLACEBO CONTROLLED TRIAL

Ole Lindgård Dollerup,1,2,3 Marianne Agerholm,1 Mads Svart,2 Karolina Sulek,1 Hans Stødkilde‐ Jørgensen,4 Niels Møller,2,3 Jonas Thue Treebak,1 Niels Jessen,2,5

1Section of Integrative Physiology, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2Medical Research Laboratory, Department of Clinical Medicine, Aarhus University Hospital, 3Department of Endocrinology, Aarhus University Hospital, 4The MR Research Centre, Aarhus University Hospital, 5Department of Pharmacology, Aarhus University Hospital

... We aim to determine if NR treatment can improve insulin sensitivity, substrate metabolism and body composition in obese, non‐diabetic humans.

 

Material and methods: In a randomized, double‐blinded, placebo controlled trial, 40 obese, healthy, middle‐aged men receive NR treatment 1 g twice daily or placebo for 12 weeks. We determine the effects of NR treatment on insulin sensitivity by a hyperinsulinemic euglycemic clamp and substrate metabolism by indirect calorimetry and labeled substrates. Alterations in body composition and fat mass distribution are determined by DEXA and MRI scans and measurements of intra‐hepatic and intramyocellular lipid contents are obtained by MR spectroscopy.

Furthermore analysis of mitochondrial function in permeabilized muscle fibers by mitochondrial respirometry, intestinal bacteria composition by 16S rRNA sequencing and incretin hormone response during an oral glucose tolerance test will be performed.

 

Results: Baseline characteristics (n=40) are presented as mean (±SD). BMI 32.9 (±2.7) kg/m2, fat percentage 30.7 % (±4,1), age 58.7 (±7.9) ‐ range 40‐70. Insulin clamps at baseline have a mean M‐value of 2.4 (±1.1) mg/kg/min suggesting that the study group is insulin resistant as a whole. Completion of the trial is expected in April 2017 and preliminary data, including the primary endpoint insulin sensitivity, will be ready for presentation shortly hereafter.

Conclusions: This is the first human clinical trial investigating the long‐term effects of NR supplementation on whole‐body insulin sensitivity, body composition and glucose homeostasis, and the potential role of NR as an anti‐diabetic agent.

 

He says "by April," but the conference was in May: I expect that this is just because you have to have your abstract submitted well in advance of conferences in order to give them time to get the abstract book formatted and printed up. He may even have presented his data at the conference.

 

In any case, if he completed analysis in April or May, it will still be some months before they're published in a scientific journal.

 

Similarly, I wouldn't read too much into the delay in the publication of the Chromadex and Elysium studies. Journal publication can take forever, and it's possible that they've been asked to conduct additional analyses or experimental studies (not whole new trials) to justify some claims they've made. And it is routine for journals (and higher-tier journals in particular) to insist on an embargo to the press until publication (though I'm surprised by the discipline showed by the FASEB Summit attendees on this point: in the age of social media, scientific conference results are often leaked, and clearly this one has significant scientific and public interest no matter which way the results went — and this was an NAD+ specialist conference).

 

Blue, are you sure Guarente said there  were 6 more Basis trials in the works? I seem to recall him indicating there were 6 more trials in the works, but that they were for novel products to expand Elysium's line, consistent with their originally-stated plans.



#39 bluemoon

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Posted 23 August 2017 - 12:48 AM

 

Blue, are you sure Guarente said there  were 6 more Basis trials in the works? I seem to recall him indicating there were 6 more trials in the works, but that they were for novel products to expand Elysium's line, consistent with their originally-stated plans.

 

I agree that not too much should be read into ChromaDex and Elysium not releasing results yet, although I have on occasion. At first I thought it was odd for ChromaDex to keep postponing but then thought the delay is probably due to competition with Elysium. If ChromaDex released very positive results, Elysium would presumably immediately do much better while ChromaDex ramps marketing for its Tru Niagen. Elysium stated at the beginning that they would put up all trial results, even if negative, on their website, but they didn't say how long that would take. Not to be too repetitive, but there are possible dose / marketing issues where both companies are trying to figure out how to sell NR to maximize profits.

 

On the thread "Leonard Guarente discusses new Elysium basis human trials", I posted a recent 10 minute talk where he said of last summer's study that the goals were to make sure it was safe and to see to what extent NAD+ was raised at the two doses. Note that he didn't add they were testing several additional things like blood pressure, glucose levels, walking stamina, etc.

 

At 10:45, Guarente said that they are in the middle of setting up and recruiting for "a large number of trials... probably doing six initiating this year, based on more specific health end points. And we have to do this carefully with respect to the FDA and on and so forth but that's all been taken care of.

 

The FDA was needed? Why didn't Guarente say the trial last year also looked at many health aspects? He makes it sound like this is a new second part when it is not. (Maybe more doses and more health aspects examined.)

 

Guarente: "And we really hope to show a wealth of data for the next period. So that's where we are with Basis." He added that Elysium is trying to get suppliers who will sell them other molecules that are pure and will have "several trials" for those.  


Edited by bluemoon, 23 August 2017 - 12:53 AM.

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#40 Harkijn

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Posted 10 September 2017 - 08:41 AM

Still no news, but I find it encouraging that Aboutnr.com posted a short video with a very upbeat dr. Brenner on 30 Aug mentioning studies are being finalized.

http://aboutnr.com/2...irtuin-enzymes/

 

Also some human clinical trials are listed which I for one was not aware of.


Edited by Harkijn, 10 September 2017 - 08:42 AM.

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#41 bluemoon

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Posted 10 September 2017 - 10:41 AM

Still no news, but I find it encouraging that Aboutnr.com posted a short video with a very upbeat dr. Brenner on 30 Aug mentioning studies are being finalized.

http://aboutnr.com/2...irtuin-enzymes/

 

Also some human clinical trials are listed which I for one was not aware of.

 

"Studies are being finalized" can mean any time frame since we are talking about Chromadex. My guess is that we won't get details from the ChromaDex studies until they get more NR off the market in a few more weeks. Then again, someone said that a new vendor has started to sell NR and Elysium has recently broken ChromaDex monopoly (hurray!), so I don't see why other vendors don't follow Elysium's footsteps.

 

I'm confused about the number of accute kidney patients are participating in the trial. The study say 24 but the About.nr site says 6 as does one part of the study description.



#42 Michael

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Posted 12 September 2017 - 03:06 AM

 

dr. Brenner on 30 Aug mentioning studies are being finalized.
http://aboutnr.com/2...irtuin-enzymes/
 
Also some human clinical trials are listed which I for one was not aware of.

 
I'm confused about the number of accute kidney patients are participating in the trial. The study say 24 but the About.nr site says 6 as does one part of the study description.

I take it that you mean the bit where they say "Randomized 5 subjects in active arm (Basis) : 1 subject in control (placebo)". Note the colon: it's a ratio symbol. Ie, they're randomizing 5 subjects to Basis for every 1 person they randomize to placebo.
 

 someone said that a new vendor has started to sell NR and Elysium has recently broken ChromaDex monopoly (hurray!), so I don't see why other vendors don't follow Elysium's footsteps.


Be careful what you wish for ;) . We don't of course yet know whether Elysium's current non-CDXC production will last or be barred by legal challenge — but if they're allowed to keep using the new sourrce, and if Elysium's route is non-obvious or is itself ultimately patent,  it's possible that no one will want to go to the time and expense to develop an additional synthesis, because at that point the price would plummet and the ROI wouldn't be there.

 

And, remember: they're largely funding the science now on investor money, with anticipated payback from shares. If investors flee and NR ceases to be so profitable, existing studies may be terminated prematurely, or at least new ones not be initiated.


Edited by Michael, 12 September 2017 - 03:07 AM.

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#43 bluemoon

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Posted 12 September 2017 - 11:10 PM

 

Be careful what you wish for ;) . We don't of course yet know whether Elysium's current non-CDXC production will last or be barred by legal challenge — but if they're allowed to keep using the new sourrce, and if Elysium's route is non-obvious or is itself ultimately patent,  it's possible that no one will want to go to the time and expense to develop an additional synthesis, because at that point the price would plummet and the ROI wouldn't be there.

 

And, remember: they're largely funding the science now on investor money, with anticipated payback from shares. If investors flee and NR ceases to be so profitable, existing studies may be terminated prematurely, or at least new ones not be initiated.

 

 

I'd think that if ChromaDex was going to sue Elysium, it would have said so at the August conference. As far as I know, the patents just state that one can't produce NR in the U.S. with that method. It doesn't pertain to buying it from abroad where there is no protection, like from a Chinese company.

 

Several trials are finished or will be within a year and most of those will be published. Companies will still sell NR just as some sell Vitamin D but won't have the profit markets they were expecting.  I've always thought that Elysium will develop something better than NR and pterostilbine and that those two were just a start to increase revenue for the Second Pill. Just a guess.  



#44 stefan_001

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Posted 12 September 2017 - 11:56 PM

Be careful what you wish for ;) . We don't of course yet know whether Elysium's current non-CDXC production will last or be barred by legal challenge — but if they're allowed to keep using the new sourrce, and if Elysium's route is non-obvious or is itself ultimately patent, it's possible that no one will want to go to the time and expense to develop an additional synthesis, because at that point the price would plummet and the ROI wouldn't be there.

And, remember: they're largely funding the science now on investor money, with anticipated payback from shares. If investors flee and NR ceases to be so profitable, existing studies may be terminated prematurely, or at least new ones not be initiated.

I'd think that if ChromaDex was going to sue Elysium, it would have said so at the August conference. As far as I know, the patents just state that one can't produce NR in the U.S. with that method. It doesn't pertain to buying it from abroad where there is no protection, like from a Chinese company.

Several trials are finished or will be within a year and most of those will be published. Companies will still sell NR just as some sell Vitamin D but won't have the profit markets they were expecting. I've always thought that Elysium will develop something better than NR and pterostilbine and that those two were just a start to increase revenue for the Second Pill. Just a guess.
You are not correct that importing NR from abroad circumvents the IPR. Chromadex can ask for an import injunction. If your statement would be correct then the US would be flooded with counterfit products made in China e.g. apple iphones, nike shoes. Also I dont see the relevance of it being mentioned on the confernce call. Typically ypu dont sue immediately but wait till there is more business done under the infringement so that you can sue for larger amounts. Why sue if there is nothing at stake yet?

Edited by stefan_001, 12 September 2017 - 11:59 PM.


#45 bluemoon

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Posted 13 September 2017 - 01:32 AM

 

You are not correct that importing NR from abroad circumvents the IPR. Chromadex can ask for an import injunction. If your statement would be correct then the US would be flooded with counterfit products made in China e.g. apple iphones, nike shoes. Also I dont see the relevance of it being mentioned on the confernce call. Typically ypu dont sue immediately but wait till there is more business done under the infringement so that you can sue for larger amounts. Why sue if there is nothing at stake yet?

 

 

You can bring in a counterfeit good into the U.S. every 30 days, but I don't think this is the case with Elysium. If they are buying through a Chinese company then it simplt NR and nothing fake or counterfeit about it.  

 

The conference call seemed to concede that Chromadex no longer has a monopoly on NR, and I would think they would at least say that they were considering taking legal action, but they didn't. 

 

By the way, ChromaDex's stock is up 40% since September 6th.



#46 stefan_001

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Posted 13 September 2017 - 01:43 AM

You are not correct that importing NR from abroad circumvents the IPR. Chromadex can ask for an import injunction. If your statement would be correct then the US would be flooded with counterfit products made in China e.g. apple iphones, nike shoes. Also I dont see the relevance of it being mentioned on the confernce call. Typically ypu dont sue immediately but wait till there is more business done under the infringement so that you can sue for larger amounts. Why sue if there is nothing at stake yet?


You can bring in a counterfeit good into the U.S. every 30 days, but I don't think this is the case with Elysium. If they are buying through a Chinese company then it simplt NR and nothing fake or counterfeit about it.

The conference call seemed to concede that Chromadex no longer has a monopoly on NR, and I would think they would at least say that they were considering taking legal action, but they didn't.

By the way, ChromaDex's stock is up 40% since September 6th.
Makes no difference, thats not how it works. Chromadex can simply assert it violates their ipr and request an import injunction.

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#47 bluemoon

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Posted 13 September 2017 - 02:08 AM

 

 


You can bring in a counterfeit good into the U.S. every 30 days, but I don't think this is the case with Elysium. If they are buying through a Chinese company then it simplt NR and nothing fake or counterfeit about it.

The conference call seemed to concede that Chromadex no longer has a monopoly on NR, and I would think they would at least say that they were considering taking legal action, but they didn't.

By the way, ChromaDex's stock is up 40% since September 6th.
Makes no difference, thats not how it works. Chromadex can simply assert it violates their ipr and request an import injunction.

 

 

 Then why would Eysium do this if in fact buying from China? To buy time before they attempt a takeover of ChromaDex? 

 

Is it possible that Elysium found another manufacturing method?


Edited by bluemoon, 13 September 2017 - 03:05 AM.






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