December 19, 2024 • 18 mins
An interview on innovations in automated insulin delivery with José Garcia-Tirdado, MSc, PhD, Assistant Professor of Smart Algorithms in Diabetes Technology at the University of Bern.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
David Klonoff (00:14):
Welcome to Diabetes Technology Report.
I'm David Klonoff.
I'm an endocrinologist atSutter Health and UCSF.
I'm here with my co-host, DrDavid Kerr, who will introduce
our guest today.
David Kerr (00:28):
Thank you, David.
This is David Kerr.
As usual, I'm speaking to youfrom Santa Barbara, California.
Today's special guest is DrJose Garcia-Tirado.
Welcome to Diabetes TechnologyReports.
One of the things we like tobegin with in these podcasts is
to get a feel about you as aperson and how you ended up in
(00:51):
diabetes and diabetes technology.
So can you just give us alittle thumbnail sketch of your
day job and how you arrivedthere?
José Garcia-Tirado (01:00):
So, first of all, thank you so much, david
Klonoff and David Kerr, for thiskind invitation into the
Diabetes Technology Report.
Well, I myself am a type 1diabetes person.
I was diagnosed 11 years agowhen I was doing my first
(01:20):
postdoctoral fellowship inGermany.
Back at the time I didn't knowanything about diabetes, but my
background has always been incontrol systems engineering.
So I have bachelor's, master'sand PhD degrees in control
systems engineering.
So I was fascinated back at thetime to controlling biochemical
(01:45):
and chemical processes that arevery, very complex in nature.
So then, when I got diagnosed, Iremember my diabetes educator
telling me something that stillkeeps in my head.
Keeps in my head If you want tosucceed with this tough disease
(02:06):
, you need to know more thanyour medical doctors, you need
to educate yourself, you need toread a lot and you need to
become a master in this disease.
And then I started to read andthen, some months after, I went
to a control systems conferenceand, to my surprise, I found Dr
(02:33):
Graham Goodwin from Australiadoing a keynote presentation
about how control systemsengineering could help shape
artificial pancreas technology.
That was 2014.
And then I got fascinatedbecause I have my two main
passions one because lifebrought to me and the other
(02:55):
because I choose to be together.
So I decided that I wanted toknow more and more and more and
I started to conduct research inmy hometown in Colombia and,
right like shortly after, Ijoined UVA with Marc Breton.
And then my life continueddoing research in type 1
(03:18):
diabetes and diabetes in general.
David Kerr (03:21):
And so what is it?
I mean, I know there's tradesecrets and everything, but just
give us a feel about what areyou working on today and in the
near future.
What's what gets you up in themorning?
José Garcia-Tirado (03:33):
sure.
So, um, as a as a engineer, uh,I hear a lot of things with
from medical doctors and frompractitioners, of course.
You hear a lot from yourcolleagues.
You hear a lot from theflagship conferences ATTD and
ADA and EASD.
So you find a group ofphysicians say, well, aad
(03:54):
systems are done, there's notmuch to do, they work pretty
well, they work for everyone.
Then you find another group ofphysicians say, no, we can do
better.
We can still do better.
Now, there are a lot of thingsthat are not resolved in type 1
diabetes.
One of the things that wakes meup every morning is knowing
(04:18):
that, disregarding how good wedo glucose control, we have
still 10 times more risk than ahealthy person to have a stroke
or to have a cardiovascular orrenal disease.
We have no current therapyprotecting people with type 1
diabetes from cardiovascular orrenal disease, and that's why,
(04:44):
apart from my passion in AIDsystems, I believe I strongly
believe that we need to do morewith adjunctive therapies.
We need to bring thosefascinating adjunctive therapies
that we know work for otherpopulations close to the type 1
population and see what happenswith, of course, with thorough
(05:05):
research.
David Klonoff (05:07):
Jose, you're working on trying to normalize
glucose levels.
What do you think is moreimportant to have a normal mean
glucose or to eliminatevariability?
José Garcia-Tirado (05:20):
So that's a very tricky question.
I feel glucose control is notenough.
I feel, from several documentsand papers out there, Pratik
Chhatrik himself has written alot about glucose variability.
(05:41):
It's very impactful, but wedon't have long-term studies
showing us that.
So I might believe it's a hunch, but we haven't been able to
demonstrate that actually,disregarding that you have 6.0%
(06:02):
A1c or an outstanding 70, 70, 80percent I mean range, you still
have risks of down there, soretinopathy or other macro and
micro vascular related diseases.
So I feel we need to addressglycemic variability.
David Klonoff (06:26):
One way to address glycemic variability
would be to eliminate the hybridpart of the hybrid closed loop,
make it fully closed loop.
How close do you think we areto that type of system?
José Garcia-Tirado (06:40):
Well, I myself worked very hard with
Mark Breton back in Virginia tomake that happen.
We made that happen in pilotstudies, so we know it is
possible, even with thelimitations we have with
technology, with current CGMsand current insulin analogs.
I believe that we can even makeit better or best with
(07:12):
adjunctive therapies like GLP-1sor dual GLP-GLP-1s, because
that gives us some time torespond to meals, to react to
meals.
So I feel it's doable and Ifeel more studies are warranted,
of course, and we need to go inthat direction.
David Kerr (07:26):
Jose, I'm intrigued by your point about.
You come across clinicians,some of whom say, well, type 1
diabetes, give everyone aclosed-loop system and
everything's going to be great.
And then there's clinicians,like me actually, who kind of
worry that, okay, it's not allabout glucose.
There's a whole lot of otherstuff going on, but just from
the glucose perspective, whatare the next areas of progress
(07:50):
we need to make with a closedloop?
I mean, I know about a fullyautomated, but is there anything
else?
I mean, the burden is stillthere for people with type 1
diabetes.
What are you working on andwhat are you thinking about that
could reduce the day-to-dayburden for people?
José Garcia-Tirado (08:05):
Yeah, I might need to push back a little
bit on the previous commentfrom David Klanov, because I
don't think necessarily withfull automation we will reduce
glucose variability.
We might have even broaderglucose variability and that's
something that we need toaddress.
So one thing is removing thepatient from the loop.
(08:27):
I also believe that we can eventry to have systems that work
in the background that are notannoying the person so often,
just in the cases that we needaction from the user.
I am of the thing that youdon't even need to show the CGM
(08:52):
if you're not in danger, unlessthe person is like a control
freak and want to see everything.
Because we also need topersonalize and there are some
people that needs to becontrolling every aspect of
their disease and the treatment,but there might be others that
can live their lives in a coolerway, if I may say, and then
(09:15):
just bring their attention whenthey really need to react and
they need to intervene.
So I think one of the thingsthat we're working very hard in
our lab is to try to remove theuser from the loop, not only
from the meals perspective butalso from the physical activity
perspective.
That is also very challenging.
So this is one thing.
(09:36):
The other thing is try to workin playotropic effects, try to
work in other aspects of thedisease that we haven't been
successful, like trying toadhere more to physical activity
, and try to improve risks.
This is, in my opinion, thingsthat we need to address in the
(09:59):
next few years.
David Kerr (10:01):
I mean that's very interesting.
So the idea being that peoplewith type 1 diabetes being
brought up with CGM and the wordcontinuous and continuously
reviewing their data but whatyou're saying here is that it
doesn't have to be like that.
We can remove that burden andallow people.
Free up time for people to geton.
That's absolutely fascinating.
Free up time for people to geton that's absolutely fascinating
(10:22):
.
I've got to ask you, becauseit's the hottest subject in my
world what's AI going to do forclosed-loop system?
I mean, is it all hype or areyou excited, or are you going to
buy shares in an AI company?
José Garcia-Tirado (10:39):
Definitely it's stirring things up.
Definitely I'm not an AI expert, but I work very close with AI
(11:03):
experts to really deploy bigtasks to AI, and I want to be a
little bit more cautious, but Ithink we're going to get into a
point where AI is going to makebig things, especially because
we're getting more specializedand more smart, in the sense
that not only the algorithms arecapable of doing fantastic
(11:25):
things, but they are also beingcapable of diagnose themselves
and, like adapt to changing andyou know, difficult environments
.
So I believe, if you ask me, Iprefer more a hybrid approach
where you have AI systems wherewe know they work best and we
(11:53):
also have other engineeringstrategies or approaches where
we have years and years ofexperience and we know what they
can do best.
So I'm a little bit cautious,but I feel AI is going to make a
big impact in the future.
David Klonoff (12:12):
Jose, could you tell our audience what is your
current position?
Where are you working?
What type of a lab do you have?
I know you are in Virginia andnow you're in Switzerland.
Could you explain it so peopleknow where you are, what you're
doing?
José Garcia-Tirado (12:38):
group, I think one of the best equipped
technology-related ortechnology-oriented groups in
the world, with two fantasticleaders, mac Breton and Boris
Kovachev, which I'm verygrateful for allowing me to work
with them.
But two years ago I moved inBern, in a fascinating city in
Switzerland, to start my owngroup and to start my tenure
(12:59):
track journey.
Let's say I started fromscratch.
So I started from scratch,hiring students, postdoctoral
fellows, software developers, totry not only to get our
technological infrastructure butalso to try to work very
(13:22):
closely with clinicians to gofor clinical trials.
That's, I think, as an engineer, knowing my limitations that's
a thing that I love to support,jose.
David Klonoff (13:44):
many people want to use an accurate continuous
glucose monitor, but I've alsoheard people say that if it's
part of an AID system, itdoesn't even matter with the
products on the market, becauseeven if the monitor is not
extremely accurate, the insulindelivery system and the
algorithm will make up for it.
So therefore, people don't haveto search for the most accurate
monitor.
Now, I'm not sure if that'scorrect, but I've heard people
(14:07):
say that.
What do you think?
José Garcia-Tirado (14:10):
Well, I need to be against that claim in a
sense.
One of the things I learnedfrom school, from my control
systems background, is youcannot control what you don't
know, and it's very difficultfor an AD system to know where
(14:34):
it stands if there is noaccurate measurement of the
environment, and the only thingwe can measure nowadays is
glucose.
I'm of the thought that we needto push for more biomarkers,
like if we had, like, amulti-sensing technology that we
can have ketones and CGA, orglucose and lactate and other
(15:00):
species that can help us to knowwhere the body is at the moment
.
I think that will be best, inmy opinion.
David Kerr (15:13):
Jose, just following on from that, this is a kind of
philosophical question.
But are we stuck with the formfactor for closed-loop
artificial pancreas systems?
As we add more analytes, arethese just going to get bigger
and uglier, or do you thinkwe're going to get into the
miniaturization soon?
(15:34):
Is it going to be implantableever, or do we even need that?
What's your kind of thoughtsfrom the perspective of someone
with diabetes?
What to look forward to?
José Garcia-Tirado (15:47):
Yeah, that's a very, very interesting
question.
I think there are two sides ofthe coin.
So one is injecting more thanone hormone like insulin and
glucagon and insulin and otherhormone.
That makes the system bulkierbecause you need to pump in, or
more pumping mechanisms, andthat gets difficult In the side
(16:11):
of the sensing.
I believe that technologieslike laser technology and
optical technology have a strongpotential to make an all-in-one
and miniaturize the technology.
Of course that doesn't happenovernight, but we need to get
into a point where we know whattechnology is capable of
(16:34):
detecting several metabolitesand then we can extract that
technology and miniaturize.
I'm more in favor of that onethan into the multi-pumping
technology, if I may say.
David Klonoff (16:49):
Jose, which project that you're working on
now would you say is your mostinteresting or impactful?
José Garcia-Tirado (16:58):
Well, the artificial pancreas project is
dear to my heart, but I thinkthe one that is most impactful
nowadays is one that we gotaccepted and approved by the
authorities in Switzerland topair Munjaro with current AID
systems.
So we would like to know whathappens if a person with type 1
(17:19):
diabetes, and whatever system,is in the market.
What happens if we add a lowdose of Munjar?
So we want to collect that dataand see if we can truly see an
impact in glycemic control andsome markers of cardiovascular
and renal disease.
David Klonoff (17:41):
We published a consensus report on that topic
in Journal of Diabetes Scienceand Technology recently.
Viral Shah from Indiana was thefirst author.
Well, Jose, I would like tothank you for speaking with us.
I've learned a lot aboutautomated insulin delivery
systems.
Diabetes Technology Report isavailable at the Apple Store and
(18:02):
Spotify and at the DiabetesTechnology Society website.
So to our listeners.
So long for now, and we lookforward to the next podcast,
Jose.
Thank you, David, thank you.
David Kerr (18:14):
Thank you very much, Jose Sure.
José Garcia-Tirado (18:17):
Thank you so much for having me.
Welcome to Diabetes Technology Report.
I'm David Klonoff.
I'm an endocrinologist atSutter Health and UCSF.
I'm here with my co-host, DrDavid Kerr, who will introduce
our guest today.
David Kerr (00:28):
Thank you, David.
This is David Kerr.
As usual, I'm speaking to youfrom Santa Barbara, California.
Today's special guest is DrJose Garcia-Tirado.
Welcome to Diabetes TechnologyReports.
One of the things we like tobegin with in these podcasts is
to get a feel about you as aperson and how you ended up in
(00:51):
diabetes and diabetes technology.
So can you just give us alittle thumbnail sketch of your
day job and how you arrivedthere?
José Garcia-Tirado (01:00):
So, first of all, thank you so much, david
Klonoff and David Kerr, for thiskind invitation into the
Diabetes Technology Report.
Well, I myself am a type 1diabetes person.
I was diagnosed 11 years agowhen I was doing my first
(01:20):
postdoctoral fellowship inGermany.
Back at the time I didn't knowanything about diabetes, but my
background has always been incontrol systems engineering.
So I have bachelor's, master'sand PhD degrees in control
systems engineering.
So I was fascinated back at thetime to controlling biochemical
(01:45):
and chemical processes that arevery, very complex in nature.
So then, when I got diagnosed, Iremember my diabetes educator
telling me something that stillkeeps in my head.
Keeps in my head If you want tosucceed with this tough disease
(02:06):
, you need to know more thanyour medical doctors, you need
to educate yourself, you need toread a lot and you need to
become a master in this disease.
And then I started to read andthen, some months after, I went
to a control systems conferenceand, to my surprise, I found Dr
(02:33):
Graham Goodwin from Australiadoing a keynote presentation
about how control systemsengineering could help shape
artificial pancreas technology.
That was 2014.
And then I got fascinatedbecause I have my two main
passions one because lifebrought to me and the other
(02:55):
because I choose to be together.
So I decided that I wanted toknow more and more and more and
I started to conduct research inmy hometown in Colombia and,
right like shortly after, Ijoined UVA with Marc Breton.
And then my life continueddoing research in type 1
(03:18):
diabetes and diabetes in general.
David Kerr (03:21):
And so what is it?
I mean, I know there's tradesecrets and everything, but just
give us a feel about what areyou working on today and in the
near future.
What's what gets you up in themorning?
José Garcia-Tirado (03:33):
sure.
So, um, as a as a engineer, uh,I hear a lot of things with
from medical doctors and frompractitioners, of course.
You hear a lot from yourcolleagues.
You hear a lot from theflagship conferences ATTD and
ADA and EASD.
So you find a group ofphysicians say, well, aad
(03:54):
systems are done, there's notmuch to do, they work pretty
well, they work for everyone.
Then you find another group ofphysicians say, no, we can do
better.
We can still do better.
Now, there are a lot of thingsthat are not resolved in type 1
diabetes.
One of the things that wakes meup every morning is knowing
(04:18):
that, disregarding how good wedo glucose control, we have
still 10 times more risk than ahealthy person to have a stroke
or to have a cardiovascular orrenal disease.
We have no current therapyprotecting people with type 1
diabetes from cardiovascular orrenal disease, and that's why,
(04:44):
apart from my passion in AIDsystems, I believe I strongly
believe that we need to do morewith adjunctive therapies.
We need to bring thosefascinating adjunctive therapies
that we know work for otherpopulations close to the type 1
population and see what happenswith, of course, with thorough
(05:05):
research.
David Klonoff (05:07):
Jose, you're working on trying to normalize
glucose levels.
What do you think is moreimportant to have a normal mean
glucose or to eliminatevariability?
José Garcia-Tirado (05:20):
So that's a very tricky question.
I feel glucose control is notenough.
I feel, from several documentsand papers out there, Pratik
Chhatrik himself has written alot about glucose variability.
(05:41):
It's very impactful, but wedon't have long-term studies
showing us that.
So I might believe it's a hunch, but we haven't been able to
demonstrate that actually,disregarding that you have 6.0%
(06:02):
A1c or an outstanding 70, 70, 80percent I mean range, you still
have risks of down there, soretinopathy or other macro and
micro vascular related diseases.
So I feel we need to addressglycemic variability.
David Klonoff (06:26):
One way to address glycemic variability
would be to eliminate the hybridpart of the hybrid closed loop,
make it fully closed loop.
How close do you think we areto that type of system?
José Garcia-Tirado (06:40):
Well, I myself worked very hard with
Mark Breton back in Virginia tomake that happen.
We made that happen in pilotstudies, so we know it is
possible, even with thelimitations we have with
technology, with current CGMsand current insulin analogs.
I believe that we can even makeit better or best with
(07:12):
adjunctive therapies like GLP-1sor dual GLP-GLP-1s, because
that gives us some time torespond to meals, to react to
meals.
So I feel it's doable and Ifeel more studies are warranted,
of course, and we need to go inthat direction.
David Kerr (07:26):
Jose, I'm intrigued by your point about.
You come across clinicians,some of whom say, well, type 1
diabetes, give everyone aclosed-loop system and
everything's going to be great.
And then there's clinicians,like me actually, who kind of
worry that, okay, it's not allabout glucose.
There's a whole lot of otherstuff going on, but just from
the glucose perspective, whatare the next areas of progress
(07:50):
we need to make with a closedloop?
I mean, I know about a fullyautomated, but is there anything
else?
I mean, the burden is stillthere for people with type 1
diabetes.
What are you working on andwhat are you thinking about that
could reduce the day-to-dayburden for people?
José Garcia-Tirado (08:05):
Yeah, I might need to push back a little
bit on the previous commentfrom David Klanov, because I
don't think necessarily withfull automation we will reduce
glucose variability.
We might have even broaderglucose variability and that's
something that we need toaddress.
So one thing is removing thepatient from the loop.
(08:27):
I also believe that we can eventry to have systems that work
in the background that are notannoying the person so often,
just in the cases that we needaction from the user.
I am of the thing that youdon't even need to show the CGM
(08:52):
if you're not in danger, unlessthe person is like a control
freak and want to see everything.
Because we also need topersonalize and there are some
people that needs to becontrolling every aspect of
their disease and the treatment,but there might be others that
can live their lives in a coolerway, if I may say, and then
(09:15):
just bring their attention whenthey really need to react and
they need to intervene.
So I think one of the thingsthat we're working very hard in
our lab is to try to remove theuser from the loop, not only
from the meals perspective butalso from the physical activity
perspective.
That is also very challenging.
So this is one thing.
(09:36):
The other thing is try to workin playotropic effects, try to
work in other aspects of thedisease that we haven't been
successful, like trying toadhere more to physical activity
, and try to improve risks.
This is, in my opinion, thingsthat we need to address in the
(09:59):
next few years.
David Kerr (10:01):
I mean that's very interesting.
So the idea being that peoplewith type 1 diabetes being
brought up with CGM and the wordcontinuous and continuously
reviewing their data but whatyou're saying here is that it
doesn't have to be like that.
We can remove that burden andallow people.
Free up time for people to geton.
That's absolutely fascinating.
Free up time for people to geton that's absolutely fascinating
(10:22):
.
I've got to ask you, becauseit's the hottest subject in my
world what's AI going to do forclosed-loop system?
I mean, is it all hype or areyou excited, or are you going to
buy shares in an AI company?
José Garcia-Tirado (10:39):
Definitely it's stirring things up.
Definitely I'm not an AI expert, but I work very close with AI
(11:03):
experts to really deploy bigtasks to AI, and I want to be a
little bit more cautious, but Ithink we're going to get into a
point where AI is going to makebig things, especially because
we're getting more specializedand more smart, in the sense
that not only the algorithms arecapable of doing fantastic
(11:25):
things, but they are also beingcapable of diagnose themselves
and, like adapt to changing andyou know, difficult environments
.
So I believe, if you ask me, Iprefer more a hybrid approach
where you have AI systems wherewe know they work best and we
(11:53):
also have other engineeringstrategies or approaches where
we have years and years ofexperience and we know what they
can do best.
So I'm a little bit cautious,but I feel AI is going to make a
big impact in the future.
David Klonoff (12:12):
Jose, could you tell our audience what is your
current position?
Where are you working?
What type of a lab do you have?
I know you are in Virginia andnow you're in Switzerland.
Could you explain it so peopleknow where you are, what you're
doing?
José Garcia-Tirado (12:38):
group, I think one of the best equipped
technology-related ortechnology-oriented groups in
the world, with two fantasticleaders, mac Breton and Boris
Kovachev, which I'm verygrateful for allowing me to work
with them.
But two years ago I moved inBern, in a fascinating city in
Switzerland, to start my owngroup and to start my tenure
(12:59):
track journey.
Let's say I started fromscratch.
So I started from scratch,hiring students, postdoctoral
fellows, software developers, totry not only to get our
technological infrastructure butalso to try to work very
(13:22):
closely with clinicians to gofor clinical trials.
That's, I think, as an engineer, knowing my limitations that's
a thing that I love to support,jose.
David Klonoff (13:44):
many people want to use an accurate continuous
glucose monitor, but I've alsoheard people say that if it's
part of an AID system, itdoesn't even matter with the
products on the market, becauseeven if the monitor is not
extremely accurate, the insulindelivery system and the
algorithm will make up for it.
So therefore, people don't haveto search for the most accurate
monitor.
Now, I'm not sure if that'scorrect, but I've heard people
(14:07):
say that.
What do you think?
José Garcia-Tirado (14:10):
Well, I need to be against that claim in a
sense.
One of the things I learnedfrom school, from my control
systems background, is youcannot control what you don't
know, and it's very difficultfor an AD system to know where
(14:34):
it stands if there is noaccurate measurement of the
environment, and the only thingwe can measure nowadays is
glucose.
I'm of the thought that we needto push for more biomarkers,
like if we had, like, amulti-sensing technology that we
can have ketones and CGA, orglucose and lactate and other
(15:00):
species that can help us to knowwhere the body is at the moment
.
I think that will be best, inmy opinion.
David Kerr (15:13):
Jose, just following on from that, this is a kind of
philosophical question.
But are we stuck with the formfactor for closed-loop
artificial pancreas systems?
As we add more analytes, arethese just going to get bigger
and uglier, or do you thinkwe're going to get into the
miniaturization soon?
(15:34):
Is it going to be implantableever, or do we even need that?
What's your kind of thoughtsfrom the perspective of someone
with diabetes?
What to look forward to?
José Garcia-Tirado (15:47):
Yeah, that's a very, very interesting
question.
I think there are two sides ofthe coin.
So one is injecting more thanone hormone like insulin and
glucagon and insulin and otherhormone.
That makes the system bulkierbecause you need to pump in, or
more pumping mechanisms, andthat gets difficult In the side
(16:11):
of the sensing.
I believe that technologieslike laser technology and
optical technology have a strongpotential to make an all-in-one
and miniaturize the technology.
Of course that doesn't happenovernight, but we need to get
into a point where we know whattechnology is capable of
(16:34):
detecting several metabolitesand then we can extract that
technology and miniaturize.
I'm more in favor of that onethan into the multi-pumping
technology, if I may say.
David Klonoff (16:49):
Jose, which project that you're working on
now would you say is your mostinteresting or impactful?
José Garcia-Tirado (16:58):
Well, the artificial pancreas project is
dear to my heart, but I thinkthe one that is most impactful
nowadays is one that we gotaccepted and approved by the
authorities in Switzerland topair Munjaro with current AID
systems.
So we would like to know whathappens if a person with type 1
(17:19):
diabetes, and whatever system,is in the market.
What happens if we add a lowdose of Munjar?
So we want to collect that dataand see if we can truly see an
impact in glycemic control andsome markers of cardiovascular
and renal disease.
David Klonoff (17:41):
We published a consensus report on that topic
in Journal of Diabetes Scienceand Technology recently.
Viral Shah from Indiana was thefirst author.
Well, Jose, I would like tothank you for speaking with us.
I've learned a lot aboutautomated insulin delivery
systems.
Diabetes Technology Report isavailable at the Apple Store and
(18:02):
Spotify and at the DiabetesTechnology Society website.
So to our listeners.
So long for now, and we lookforward to the next podcast,
Jose.
Thank you, David, thank you.
David Kerr (18:14):
Thank you very much, Jose Sure.
José Garcia-Tirado (18:17):
Thank you so much for having me.
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