<tnt>
mithro: I actually recently read another app note by lattice stating that when using the LVDS input as comparators, one of the input should stay within the Vcm (common mode) range ... not sure why that is.
<azonenberg_work>
I was looking at that among other options
<azonenberg_work>
TCP socket interface over gig-e (for the scaled-down prototype)
<azonenberg_work>
10G for the full version
<azonenberg_work>
32 MB hyperram in prototype, 4GB DDR3 for full
<rqou>
also in other news apparently my parents aren't very good at maintaining their decorative fountain things and today i found that they're all fouled with biofilms
<rqou>
how fun
<azonenberg_work>
then four QTH-030 I/O modules (or one in the prototype)
<rqou>
i'm attempting to fix them by putting some copper wire into all of them
<azonenberg_work>
prpplague: The io card i have at fab is a 2-channel digital io bank
<azonenberg_work>
the full digital io card will be 8 bits per bank but i couldnt fit that on a sane sized PCB on only four layers
<azonenberg_work>
as is, i had to make significant use of 0201s and WLCSPs
<azonenberg_work>
The output buffer is (per channel) six decoupling caps, two analog switches, and two level shifters
<prpplague>
interesting
<prpplague>
found your github
<azonenberg_work>
The protection circuit is one channel of a 4-channel ESD diode, a capacitor, two resistors, two inductors, and two schottkies
<azonenberg_work>
Then the input buffer is one channel of a dual comparator, six resistors, four caps
<azonenberg_work>
Plus the switchable termination is an analog switch, cap, resistor, and one channel of a dual fet
<azonenberg_work>
All that has to fit in ~1.5mm wide (3 pins on an 0.5mm connector) by "not unreasonably long"
<prpplague>
nice
<azonenberg_work>
22 passives, a fet, two diodes plus the ESD clamp, and like half a dozen ICs
<azonenberg_work>
:p
<azonenberg_work>
The full io card will be six layers for sure, may be 8
<prpplague>
azonenberg_work: how long did it take you to get the layout to a point you were happy with ordering?
<azonenberg_work>
prpplague: Layout only? not counting sch capture or the architecture?
<prpplague>
yea
<azonenberg_work>
I taped out to fab 2 days ago (oshpark), looks like i started layout on the 13th
<azonenberg_work>
The output buffer is the ultra dense area to the botom right of the big green connector
<azonenberg_work>
for the full 8-bit io bank, there will be four copies of that filing the whole right side of the connector
<azonenberg_work>
And eight diffpairs coming from the input buffer instead of two like i have now
<azonenberg_work>
The diffpairs will have to go *right through* the output buffer area since the PCB can't be comfortably made much bigger (I'm trying to keep the whole unit to a sane size)
<azonenberg_work>
So i see no alternative to a 6-8 layer pcb
<azonenberg_work>
I really want another power plane too, the current one is swiss cheese and I had to use extra decoupling caps when crossing reference planes a couple of times
<prpplague>
azonenberg_work: you should try pcbway in the future
<azonenberg_work>
i've used them for flex and was not happy with quality
<prpplague>
azonenberg_work: interesting
<prpplague>
azonenberg_work: i've only had a quality issue once with them in 4 years
<azonenberg_work>
Doing high end digital design on a DIY-er's budget has made me a master of fitting obscene numbers of power rails into a single plane layer, without violating any high speed layout constraints like crossing ref planes bad
<azonenberg_work>
:p
<azonenberg_work>
rqou: anyway, i got a bit of a surprise in an amazon box yesterday
<azonenberg_work>
Either i misread the listing or the listing was inaccurate
<azonenberg_work>
I'm volunteering with the WFRs on bainbridge to run the first aid station at a music festival, complete with beer and wine gardens
<azonenberg_work>
I figured at an event like that, there would be some folks getting drunk and barfing up their kidneys
<azonenberg_work>
So some puke bags would be a good thing to have on hand
<azonenberg_work>
... and now i have a case of 144 of them :D
<azonenberg_work>
I thought i was getting like ten
<sorear>
is there a target probe-to-probe latency?
<azonenberg_work>
sorear: Not at this time, no
<rqou>
azonenberg_work: now what are you going to do with 144 puke bags? :P
<azonenberg_work>
I'm mostly planning to use this for things like logic analyzers (where latency doesnt matter)
<rqou>
bring them to defcon? :P :P
<azonenberg_work>
or synchronous protocols like GMII where a clock comes along with the data
<azonenberg_work>
So as long as *skew* is well controlled i'm good
<azonenberg_work>
rqou: lol i'm not quite sure
<azonenberg_work>
i might try and share them out to the other folks in the group
<azonenberg_work>
a lot of med supplies are hard to get in low volume so somebody has to bite the bullet and get a case
<azonenberg_work>
Ever tried buying two gauze pads or two single-dose benadryl packets?
<rqou>
hmm yeah that's true
<azonenberg_work>
And then you share it out to other people in a similar situation
<azonenberg_work>
the next guy gets a case of instant cold packs
<azonenberg_work>
or a case of triangular bandages
<azonenberg_work>
and shares one with you
<rqou>
so... with so many med supplies are you on a list yet? :P
<azonenberg_work>
Define "list"
<azonenberg_work>
The list of people that COBI will call for help if the SHTF? Definitely
<rqou>
i meant "have you had to tell DEA to go fuck off and DIAF yet?"
<azonenberg_work>
I dont have any controlled substances
<azonenberg_work>
the only meds i have are OTC
<rqou>
but you have med supplies, syringes, and chemicals :P
<rqou>
those are all scary things you know :P :P
<azonenberg_work>
I think technically nasal airways might be Rx-only, but i'm trained on how to use them and have a legitimate reason to keep them around
<azonenberg_work>
Whenever we're activated we're under (indirect) supervision of BIFD's medical director so we're kosher
<rqou>
but but but don't you know, syringes are "paraphernalia" :P
<azonenberg_work>
That and, if anyone did complain who is going to come and raid me? Back when i lived on bainbridge i was on a first-name basis with the deputy chief of police
<rqou>
and beakers and stuff are what bad people use to cook meth or whatever :P :P
<azonenberg_work>
I still have his personal cell number in my phone
<azonenberg_work>
If anyone did complain about me, the folks who would act on the complaint probably already know me
<rqou>
but DEA/ATF are federal level so don't have to work with local police?
<azonenberg_work>
rqou: But when you call 911 and report your neighbor is building a meth lab
<azonenberg_work>
DEA doesn't pick up the phone
<rqou>
ah that's true
<rqou>
but you never know if you've triggered a "machine learning" list :P
<azonenberg_work>
DEA doesnt go out and raid random people for no reason, they go for the big fish based on solid intel etc
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<azonenberg_work>
And worst case if i do get raided i have a valid reason for everything i have
<azonenberg_work>
i have a PhD, a city business license, publications at conferences on silicon reverse engineering
<rqou>
doesn't mean you're not "on a list somewhere" just like me and bunnie and pretty much all "hardware people" :P
<sorear>
only a matter of time before "solid intel" gets turned over to the latest SV wunderkind :P
<azonenberg_work>
rqou: Oh i am certain i am on lots of lists
<azonenberg_work>
I just think that getting raided is relatively unlikely in my case compared to, say, $PEDOPHILE_EX_COFOUNDER
<azonenberg_work>
(who i later found out did *not* have permission from the landlord to use the basement he had set up the lab in...)
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<azonenberg_work>
honestly, if i am not on a bunch of watchlists somebody at NSA should be fired
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<gruetzkopf>
over here in germany you have to have a ID card or a passport, though it is not mandantory to carry it and i have last shown it to any official during the last federal election (the people overseeing the last state level election knew me, that's a valid form of voter id)
<gruetzkopf>
i don't carry my passport, i don't have a valid ID card, and i've shown my drivers license to someone like twice in the last 5 years
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<feuerrot>
gruetzkopf: is a driver license a sufficient identification method for the ham exam at bnetza?
<gruetzkopf>
Not officially
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<felix_>
last time i went voting they even didn't want to see my id card; only my voting card (which is a piece of normal paper with some stuff printed on it and no real card). i was like "but you should check my id card to see if i'm the person who belongs to that voting card
<feuerrot>
felix_: at least in DE the voting card is sufficient. You only need some sort of ID if you forgot it
<felix_>
just had a look and that doesn't violate the protocol if they keep the voting card o_O
<whitequark>
rqou: yes
<whitequark>
rqou: i also disagree with putin's politics
<feuerrot>
in most cities you can actually get the postal ballot papers if you know someones address and date of birth. The Lord Mayor of Aachen had to visit the CCC Aachen a few years(?) ago to get his ballot papers back…
<felix_>
oops. inb4: cccac gets raided /o\
<daveshah>
interestingly in the GB although you get a voting card in the post it is informative only, you only need to provide your name and address to vote
<felix_>
(context: 2 german hackerspaces got raided recently and at least one of the raids was definitely illegal; not sure about the other one)
<q3k>
in my neck of the woods you need to have an id card, you need to carry it on you and you need to show it when voting
<q3k>
id it weird that i don't find this weird?
<q3k>
*is it
<awygle>
that does sound .. ominous
<awygle>
specifically "carry it on you"
<q3k>
and i don't even think a driver's license is officially a valid form of id
<q3k>
mostly because until a few years ago it was literally a laminated piece of cardboard with unlimited expirey
<q3k>
dunno, just carry it in my wallet next to my bank cards
* awygle
suddenly remembers he needs to renew his license
<reportingsjr>
In ohio you can use like 5 different forms of ID
<reportingsjr>
I use my utility bill since I've been too lazy to update by license since I moved to ohio
<awygle>
i need to renew mine for *driving* purposes
<q3k>
utility bills are a de facto official proof of residency in iteland
<q3k>
*ireland
<q3k>
which boggles my mind
<reportingsjr>
anyone here know if building a board with a GPS patch antenna would be more accurate than phone GPS?
<awygle>
thats more or less true here
<reportingsjr>
q3k: yes, they are in the US as well
<q3k>
that's just stupid
<q3k>
might as well have no proof at all, considering how easy you can fake them
<awygle>
reportingsjr: i'd be surprised if it was, except in marginal cases where it lets you see more satellites
<reportingsjr>
awygle: hmm, I wonder if I need to buy an active gps antenna (one of those big white disks) to get better reception
<q3k>
all of the bills I showed as proof of residence _i printed myself_
<azonenberg_work>
q3k: thats actually annoying for people who have an "all utilities included" lease
<q3k>
because I opt out of paper bills wherever possible
<q3k>
that too
<azonenberg_work>
Because they never have utility bills
<reportingsjr>
awygle: I map out trails and I'm sick and tired of my phone making crappy GPS traces :P
<awygle>
reportingsjr: if your problem is "can't see enough sats", that'll almost certainly help yeah. even the discrete patch might.
<awygle>
active is gonna be better tho
<reportingsjr>
I honestly don't know what the main issue is
<awygle>
on a trail it's probably visibility
<reportingsjr>
a big part of it is that I'm under tree cover. GPS does not do well with this.
<reportingsjr>
supposedly the next block of GPS sattelites will use an updated version of GPS that will help with tree cover significantly.
<reportingsjr>
... I want to see proof first though. :)
<awygle>
get an active antenna and a big pole to tape it to :p
* q3k
zeroes counter for 'days since i've made the shocking re-discovery that my workstation is not grounded while my oscilloscope is'
<q3k>
smps y capacitors are the devil
<awygle>
lol "shocking"
<kc8apf>
Phone GPS receivers are pretty terrible. A uBlox module will tend to do much better.
<reportingsjr>
kc8apf: really? niicceee
<reportingsjr>
I don't know much about GPS at the moment. Can you connect a uBlox module to an active antenna?
<kc8apf>
Shouldn't need a crazy antenna. The hockey pucks are usually active and do quite well.
<reportingsjr>
sweeet
<kc8apf>
Depends on the module. All of them can use active antennas but only some include the supply circuitry
<kc8apf>
Challenge with heavy tree cover is limited sky view. Generally, you need satellites from a few different angles to get a good fix. 4 satellites right overhead won't work.
<reportingsjr>
yeah, it is also pretty hilly around here so that doesn't help.
<kc8apf>
If you mostly want accurate paths after the hike, getting raw measurements and running RTK later is gonna be better
<kc8apf>
Ideally, set up a fixed base station in an open area to use as the reference station
<reportingsjr>
huh, how does that work?
<reportingsjr>
My budget definitely isn't big enough for that. I already looked at surveying GPS units on ebay, haha.
<reportingsjr>
but I haven't heard of using reference stations
<kc8apf>
RTK uses measurements from a reference station with a known location to account for local atmospheric and ionospheric errors
<reportingsjr>
reading about it now, I have heard about its main mechanism of locking on the phase of the gps carrier for higher accuracy.
<reportingsjr>
Did not know that was called RTK
<reportingsjr>
looks like ublox has a family of modules that use RTK
<kc8apf>
Yup.
<reportingsjr>
yowch, $120 each with a minimum qty of 250.
<kc8apf>
Though on drives with heavy tree cover where i had a $15k novatel receiver/imu, I'd still lose most of the satellites.
<reportingsjr>
kc8apf: I guess worst case I can just wait until late fall for some of these trails
<azonenberg_work>
awygle: its not just tree cover thats the issue on trails
<reportingsjr>
reflections are the other big issue
<azonenberg_work>
Not multipath either
<azonenberg_work>
Just plain old occlusion
<reportingsjr>
which GPS block 3 supposedly helps with
<azonenberg_work>
When you are at the bottom of a valley with mountains on all sides your clear LOS to the sky is quite narrow
<azonenberg_work>
The other issues make it even worse
<kc8apf>
Streetview's backpacks use a pair of uBlox modules in differential mode, an IMU for deadreckoning, and then run RTK after the fact
<reportingsjr>
Huh, I didn't realize we were up to 4 separate navigation systems
<reportingsjr>
kc8apf: interesting, is there somewhere I could read about that?
<azonenberg_work>
kc8apf: i thought that was differential gps
<kc8apf>
reportingsjr: probably not. I only know because I worked with the team developing it
<reportingsjr>
that's awesome
<kc8apf>
azonenberg_work: terminology hell. There's a technique for using 2 antennas, both moving but a fixed distance apart usually 2m. It helps with some of the error correction and provides a decent solution for heading.
<kc8apf>
Using a fixed base and resolving after the fact is RTK
<azonenberg_work>
kc8apf: oh
<azonenberg_work>
my understanding was that dGPS was a fixed base that transmitted deltas in real time to remote locations
<reportingsjr>
the state of non-road mapping is pretty piss poor currently. Its really a shame google hasn't improved on this much.
<azonenberg_work>
i.e. surveyed location minus calculated gps location
<kc8apf>
There's that too.
<azonenberg_work>
re non-road mapping we encountered that not long ago on a sar call
<kc8apf>
You can do that real-time if they broadcast or after the fact if you record raw measurements
<azonenberg_work>
We were following a ridgeline off-trail in hopes of finding an alternate way our missing person might have come down from a mountaintop
<kc8apf>
There are quite a few well-known fixed stations that offer measurement feeds over the internet.
<azonenberg_work>
The contour map showed it being a fairly steep ridge off to the sides, but as you go down the ridge it was supposed to not be that steep
<azonenberg_work>
Yoiu see the place marker for Elk Creek?
<reportingsjr>
yep
<azonenberg_work>
To the west-northwest, see the little summit at the end of the ridgeline?
<azonenberg_work>
at like 3700 feet or so
<reportingsjr>
yep
<kc8apf>
TL;DR: if you're in a valley with mountains around you, nothing is going to help because you are only getting measurements from satellites in one direction. If you are fighting tree cover, active antennas can help. Either way, recording raw measurements gives you more options to clean up the data later.
<azonenberg_work>
Continue down the ridge t othe norhteast
<azonenberg_work>
it comes to a point then dips down, then goes up to another tiny peak
<reportingsjr>
yeah
<azonenberg_work>
On the contour map we had, the end of that point didnt look too steep
<azonenberg_work>
IRL it's nearly vertical :p
<reportingsjr>
yeah, to me that looks like a cliff face
<reportingsjr>
facing almost directly east
<azonenberg_work>
We knew it was almost vertical to the NW / SE
<azonenberg_work>
We were hoping the NE face was passable, the map *we* had made it look like it
<azonenberg_work>
This map seems to have more accurate data than what we had
<reportingsjr>
definitely rough terrain
<reportingsjr>
on another note, Google Map's topo rendering is gorgeous
<azonenberg_work>
Yeah that was a crazy day
<azonenberg_work>
We tried to get helo dropped on the ridge to scout it out
<azonenberg_work>
The pilot couldnt find anywhere to land :p
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<gruetzkopf>
i really want a galileo E5 receiver
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<rqou>
hmm i just realized why my oshpark order seems to be taking the scenic route:
<rqou>
the path between Oregon and the bay is currently on fire :P
<gruetzkopf>
feuerrot: weird pcie solutions computer club :P
<feuerrot>
I got ~10 Sun blade center expansion cards (2x 10G each) and they've got a PCIe connector, but the pinout doesn't match
<whitequark>
rqou: lol nope
<whitequark>
there's a small but nonzero chance SSRIs will give you permanent brain damage, too
<whitequark>
ironically
<rqou>
why do people not talk about this?
<whitequark>
the drugs people get the most scared about
<whitequark>
like amphetamines and opiates
<whitequark>
are some of the safest ones
<rqou>
yeah, that's what I've been noticing
<whitequark>
like the only side effects from taking therapeutic doses of dextroamphetamine that i'm aware of were in like
<whitequark>
people with serious preexisting conditions like schizophrenia
<whitequark>
that predictably directly interact with the drug
<whitequark>
though all of the really nasty permanent side effects for common drugs like SSRIs and SNRIs and (yes) benzos are in the long tail
<whitequark>
benzos will give you withdrawal and panic attacks after two weeks or so but it's not permanent
<whitequark>
just, well, withdrawal
<rqou>
remind me again why amphetamines and opiates are ridiculously controlled?
<rqou>
why do we love SSRIs so much?
<whitequark>
amphetamines and opiates: because some people will use them to get high
<whitequark>
so what your politicians do is poison opiates with paracetamol
<rqou>
yeah i know about that
<whitequark>
SSRIs: because unlike with TCAs (which have severe cardiotoxicity in overdose, and also give you absolutely brutal multi day hallucinations if you survive the cardiotoxicity)
<whitequark>
you can give away SSRIs like candy
<whitequark>
well, you actually can't
<whitequark>
because you'll hurt some people and don't do much of anything for most others
<whitequark>
but you won't have a lot of corpses directly attributable to your actions, which is considered success in modern psychiatry
<whitequark>
basically SSRIs solve the problem of "what can I give the depressed patient without actually finding out any of the causes, getting them to do any meaningful changes, or getting them dead when they overdose"
<whitequark>
SSRIs are "antidepressants" but are not more effective than placebo in mild to moderate depression
<rqou>
that seems more or less completely useless
<whitequark>
and only slightly more effective than placebo in severe depression
<whitequark>
well, it's more complex than that
<whitequark>
"antidepressants" don't exist
<whitequark>
it's a made up category and no drug in it is specifically effective at treating depression
<gruetzkopf>
reading this channel makes me so glad that i only work with the "fix mechanical damages aquired during runtime" part of medicine
<whitequark>
"antidepressants" are used to treat a whole slew of psychiatric conditions
<whitequark>
actually it'd be easier to enumerate conditions psychiatrists won't try to solve with antidepressants, because that's an empty set
<rqou>
wat
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<whitequark>
but they're prescribed for, say, anxiety, enuresis, anorexia, and premature ejaculation
<rqou>
wat wat
<whitequark>
what
<whitequark>
is any of this news to you
<rqou>
those seem like they should be completely unrelated conditions
<whitequark>
well the last one is mostly using the side effect of SSRIs, which is a hyperprolactinemia-induced impotence
<gruetzkopf>
(and then i'm only doing data handling and process and building automation
<rqou>
I don't interact with the healthcare system very much so i don't really know much about this
<whitequark>
but the first three are thought to have something to do with the serotonin system
<whitequark>
no one has any clue what
<rqou>
i just see glimpses of people tweeting about bad experiences
<whitequark>
oh have i mentioned also like
<whitequark>
multiple sclerosis and fibromyalgia
<whitequark>
also ssris
<rqou>
w h a t
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<rqou>
are we just throwing stuff at the problem and seeing if it works?
<gruetzkopf>
don't think that's a thing here, can ask people
<whitequark>
that's how neuropharmacology worked since its inception yes
<whitequark>
well there's also the thing where
<whitequark>
we don't know jack shit about fibromyalgia
<whitequark>
like there's a good number of doctors who don't even believe it exists
<whitequark>
because it's a diagnosis of exclusion
<rqou>
but i thought we had fancy things where we can design molecules to fit receptors and stuff
<whitequark>
hahahahaha
<whitequark>
no
<whitequark>
you don't get it
<whitequark>
we do have rational drug design.
<whitequark>
what we don't have is a rational understanding of most biological feedback loops
<gruetzkopf>
you'd need to know *what* you're messing with
<whitequark>
i mean have you looked at that sick shit, have you *seen* the renin-angiotensin system?
<whitequark>
When renal blood flow is reduced, juxtaglomerular cells in the kidneys convert the precursor prorenin (already present in the blood) into renin and secrete it directly into the circulation. Plasma renin then carries out the conversion of angiotensinogen, released by the liver, to angiotensin I.[2] Angiotensin I is subsequently converted to angiotensin II by the angiotensin-converting enzyme (ACE)
<whitequark>
found on the surface of vascular endothelial cells, predominantly those of the lungs.[3] Angiotensin II is a potent vasoconstrictive peptide that causes blood vessels to narrow, resulting in increased blood pressure.[4] Angiotensin II also stimulates the secretion of the hormone aldosterone[4] from the adrenal cortex. Aldosterone causes the renal tubules to increase the reabsorption of sodium and
<whitequark>
water into the blood, while at the same time causing the excretion of potassium (to maintain electrolyte balance). This increases the volume of extracellular fluid in the body, which also increases blood pressure.
<whitequark>
yep. your blood pressure is regulated by kidneys... but it still needs to go through lungs for literally no reason whatsoever
<rqou>
lol
<feuerrot>
whitequark: so the current 'psilocybin could treat depression'-hype is just another side effect?
<rqou>
but we seem to have "working" high blood pressure medication?
<whitequark>
feuerrot: *sigh* ok let me grab something to eat
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<whitequark>
rqou: oh yeah, though it was an epic struggle to get it and it took decades
<whitequark>
the thing about psychiatry is
<whitequark>
everything interacts with everything else and it doesn't actually break down into systems very well
<whitequark>
so we can rationally design a molecule that hits SERT.
<whitequark>
sure.
<awygle>
it seems like it's also very personal
<whitequark>
the fuck we do with it now?
<rqou>
oh yeah whytf is psilocybin illegal?
<whitequark>
inhibiting SERT doesn't do anything *specific*.
<rqou>
can we please just declare the war on drugs a failure already?
<awygle>
no because it still enriches the rich
<whitequark>
the closest thing inhibiting SERT does to something meaningful is basically "whack your brain with a wrench to the side"
<whitequark>
if it kicks you out of a rut, good, you've cured someone's depression
<whitequark>
that's how most cases go. for all the others when it does work, we don't have a faintest clue how it works at all
<whitequark>
we don't know why TCAs work better than SSRIs or SNRIs
<whitequark>
we don't even really know which one of them works best because the effect sizes are so goddamn small and the side effects they give people can easily make them feel just as bad or worse
<rqou>
wait, so does this mean that it doesn't necessarily work any better than things that don't involve drugs at all like "just upend your life and move across the country?"
<whitequark>
like clomipramine is the only thing i found that reliably does something with my anxiety but at the right dose of clomipramine i have to stand up very carefully and slowly or else i black out, and the thermoregulation goes so out of whack that i have to dress for like an adjacent season
<whitequark>
rqou: absolutely correct
<whitequark>
as far as i know, there's no evidence that pharmacological treatments of depression, in general, work better than non-pharmacological
<whitequark>
in particular, SSRIs are about as effective as therapy
<sorear>
i did the "upend your life and move across the country" thing, so far I have very little to show for it
<whitequark>
and that's also (ok, this is my personal theory) why psilocybin and ketamine work
<whitequark>
ketamine breaks your rumination. thought loops, etc. does so very effectively
<awygle>
meanwhile i also did that and it was hugely effective
<whitequark>
if you manage to not fall back into them, it'll work well
<whitequark>
if you don't, well, you better dump that and find a therapise
<whitequark>
awygle, sorear: hence "in general"
<whitequark>
individual people respond very differently to different treatments
<whitequark>
for some, SSRIs work *really well*.
<awygle>
yup. this is the fundamental issue that i have. there doesn't seem to be much of an effort to figure that stuff out ahead of time.
<whitequark>
there is, it's just completely intractable
<awygle>
i want a machine that pricks my finger and tastes my blood and tells me whether SSRIs will solve all my problems or blow my head off
<whitequark>
no one has ever discovered any way to prescribe psych medication other than through trial and error
<whitequark>
it's common to spend literally decades figuring out how to manage bipolar disorder
<awygle>
i know. but i didn't know that ~12 months ago, and i'm still shook.
<whitequark>
like you can find case reports that follow a single person on the order of 8-15 years
<whitequark>
and still don't solve their problem, sometimes
<whitequark>
also your body adapts to medication and they stop working sometimes.
<whitequark>
like there's more or less three things you can get for BDII (valproate, lamotrigine, lithium) and once they all stop working, welp, antipsychotics time
<whitequark>
(don't get me started on antipsychotics. even "safe" ones will reliably give you brain damage on prolonged use. especially in dosages that psychs in the US think it's acceptable to use them.)
<rqou>
why di i keep hearing about "psychs in the US" horror stories?
<rqou>
*do
<awygle>
because a) psychs in the US are terrible, and/or b) whitequark thinks psychs in the US are terrible. pick a non-empty subset.
<whitequark>
because the entire US healthcare system is chock full of people on power trips, and the US mental healthcare system is composed of them practically exclusively
<whitequark>
without exaggeration, in many cases it would be more humane to just shoot the patient on spot
<awygle>
my anecdotal evidence is that about 50% of psychologists i've met are raging egomaniacs
<awygle>
i have only met one psychiatrist so percentages are not useful
<rqou>
whitequark: why have most of my experiences (and experiences of people i know) been reasonably ok? just lucky?
<whitequark>
rqou: no
<whitequark>
what sort of problem did you have
<whitequark>
was it something that fell exactly into one branch of their standard script
<rqou>
got some nasty fevers quite a few times :P
<rqou>
so yeah, standard
<whitequark>
like each practicing psych has a decision tree in their head where most branches end up in "give SSRIs"
<whitequark>
oh you mean a GP
<rqou>
yeah
<whitequark>
US GPs are mostly just useless
<awygle>
i have never been to a visit with a gp that didn't end in "go home, come back if you're still sick next week"
<whitequark>
precisely
<awygle>
eh that's not quite literally true but it's close
<rqou>
hey, they also prescribe antibiotics
<awygle>
sometimes they give me antibiotics
<whitequark>
... for virus infections, i wonder
<awygle>
sometimes the antibiotics do nothing
<rqou>
... hmm thinking about it that's not really something that you really need a fancy expensive piece of paper to understand how to do
<awygle>
sometimes i get "here's a scrip for azithromycin, start it and stop if this test comes back negative"
<awygle>
sometimes i get "here's a scrip for azithromycin, 2000mg of augmentin, and a shot in the ass" and then symptoms still come back a year later
<pie_>
something something folk healers know more than doctors
* awygle
has Issues with Doctors
<whitequark>
pie_: that's not really true
<rqou>
not exactly, but see for example artemisinin
<whitequark>
rqou: ok but artemisinin monotherapy isn't very effective
<rqou>
that's true
<whitequark>
what folk healers lack is a systematic approach
<rqou>
definitely agree
<awygle>
so my question is, are non-us GPs less useless?
<awygle>
and if so, why / hoe
<awygle>
*how
<whitequark>
awygle: depends on the country
<whitequark>
I don't remember the specific reasons GPs are so bad in the US
<whitequark>
maybe it's something to do with insurance, maybe it's something to do with bureaucracy
<rqou>
insurance is always a clusterfuck here
<awygle>
I just don't know what a good experience with a doctor would be at this point
<rqou>
hmm maybe the GPs that my family uses/used when i was younger were better (at least for us) because they were all Chinese
<awygle>
Walk in, get tested until you have a concrete diagnosis, get specific drugs, pay nothing, I guess.
<awygle>
But the two middle steps don't seem... Possible.
<whitequark>
there's a lot of things we don't have dianostic tests for
<whitequark>
and many things we do have diagnostic tests for but there's like 3 places in the entire US that do it
<whitequark>
for example, the definitive test for malignant hyperthermia.
<whitequark>
you need to do cut a chunk from your ass and dunk it into some halothane and coffee
<awygle>
...wow
<whitequark>
no seriously, that's the gold standard
<gruetzkopf>
uuh..
<awygle>
This actually reminds me of OSS, except with much higher stakes
<whitequark>
genetic testing exists but isn't definitive
<whitequark>
"Following a surgical muscle biopsy, live muscle specimens are exposed to defined concentrations of halothane or caffeine."
<awygle>
There's tons of low hanging usability fruit that never gets addressed because the reward structures are not set up to reward it.
<awygle>
At least that's the vibe I get without any insider knowledge
<whitequark>
so the thing about malignant hyperthermia is.
<rqou>
see for example: epipens?
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<whitequark>
there's the correct ryanodine receptor genetic code, and there's mutated RYR1 variants.
<whitequark>
and the set of mutated RYR1 variants that cause MH is both large and open
<whitequark>
we currently know 31 specific mutations that cause MH
<whitequark>
but that only covers about 50% of cases of MH.
<whitequark>
and there can always be novel ones.
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<whitequark>
so the gold standard is and will for foreseeable future involve cutting a chunk of your ass.
[X-Scale] is now known as X-Scale
<whitequark>
at least with MH, you have a federal rule that all hospitals should stock something like 50 doses of dantrolene
<whitequark>
which is an absurdly large amount for how likely you are to encounter MH
<whitequark>
but... in RU, dantrolene isn't approved at all.
<whitequark>
so if a public clinic has a case of MH, they go and beg for a nearby private one with stock (imported at an absurd price) to give them a dose.
<whitequark>
if they don't do it fast enough, well, the patient dies.
<whitequark>
oops.
<rqou>
brilliant /s
<whitequark>
also the salary of a GP is something like $150 per month
<whitequark>
give or take
<rqou>
so, question for the non-USians: how do you all feel about our problems with affording epipens or insulin?
<gruetzkopf>
de wikipedia seems to suggest it's approved in germany
<whitequark>
yes, all sane countries approve and mandate use of dantrolene
<rqou>
e.g. the nonzero number of stories of people who died at exactly 26 due to not having insulin
<whitequark>
rqou: a lot of it has to do with regulatory capture
<gruetzkopf>
what's the cost of insulin in the US?
<rqou>
yeah that's true
<rqou>
good question lol
<rqou>
good luck finding out
<gruetzkopf>
my data suggests monthly cost in germany is ~60€, of which your health insurance will pick up at least 2/3, if not all
<whitequark>
gruetzkopf: from what i recall from the recent news articles, on the order of $1k per month
<gruetzkopf>
wow.
<rqou>
whitequark: ok, how do non-USians feel about our even dumber problem of having a saline shortage?
<whitequark>
so the thing about healthcare in the US is that the pharmacy or hospital will bill the insurer that insane amount, the insurer will call back, ask "are you fucking nuts" and they both duke it out between themselves to something more reasonable
<feuerrot>
rqou: how?
<whitequark>
but you still have to pay your deductible
<whitequark>
and if you don't have insurance, you're fucked
<whitequark>
rqou: of course you have a saline shortage.
<whitequark>
by which i mean, fucking what?
<rqou>
feuerrot: so the US has this territory called Puerto Rico. a lot of saline was manufactured there
<rqou>
but then there was a hurricane
<rqou>
and The Dorito decided that he didn't like Puerto Rico very much because it was full of brown people
<whitequark>
oh god.
<rqou>
cue shortage
<gruetzkopf>
and they *still* didn't respin that process?
<whitequark>
well it's not just trump. it's the entire chain of presidents before him too
<whitequark>
or PR would have been a proper state
<gruetzkopf>
that's like sub-2M€ setup cost including getting the process approved..
<rqou>
lol not in the US
<whitequark>
gruetzkopf: yes but FDA.
<whitequark>
FDA does a lot of important things but it's also an anticompetitive instrument
<whitequark>
that's pretty effectively manipulated by those who have a stake in the healthcare market
<gruetzkopf>
(of course i'm talking EU-GMP and not cGMP, though the actual rules are not too contradictory)
<whitequark>
gruetzkopf: the US also has a shortage of injectable estradiol
<whitequark>
for many, many years
<rqou>
what
<whitequark>
oh yeah
<rqou>
how?
<whitequark>
it's like $200 per bottle, and a lot of people still have to resort to gray market, at even higher prices
<whitequark>
and recently that dried up too
<whitequark>
so a bunch of people i know, say someone who has a CYP450 isoform that processes oral estradiol almost completely in first-pass metabolism, have to like
<whitequark>
straddle expiration dates and buy it on gray markets and stuff
<whitequark>
there's one vendor i think and it doesn't make or import nearly enough
<whitequark>
per bottle i mean
<whitequark>
per injection.
<sorear>
i'm waiting for someone to actually try e2+bergamottin and report results :P
<whitequark>
it's not actually safe to use one bottle for more than one injection because it doesn't have preservatives in them but people still do that
<rqou>
wait, is this shortage just for the injectable form?
<whitequark>
yes
<whitequark>
the injectable form is generally much better tolerated, to the extent that it has a significantly different therapeutic effect
<rqou>
wait why? how is it different from the oral form?
<whitequark>
first-pass metabolism.
<rqou>
but aren't they manufactured in a similar way?
<whitequark>
um.
<whitequark>
well, no, but it's also irrelevant
<whitequark>
the active ingredient is an organic ester, i think propionate usually, but it's not important
<whitequark>
because that hydrolyzes slowly in your body and releases it steadily over the course of two weeks
<whitequark>
but the main thing here is that oral estradiol is >>90% metabolized on the first pass
<whitequark>
uh
<rqou>
i see
<whitequark>
you know how the portal vein system works, right?
<sorear>
usually valerate, I know somebody who knows somebody who managed to source a kilo or so of cypionate and was going to diy compound it
<rqou>
vaguely
<rqou>
i know about the first pass problem
<whitequark>
sorear: i think i know that person too
<whitequark>
valerate is what they use in oral formulations, no?
<whitequark>
cypionate is injectable alright
<rqou>
but why is there a shortage?
<whitequark>
rqou: not enough money in it to go through FDA approval
<whitequark>
see it's a death by a thousand cuts problem
<rqou>
this doesn't seem like something that should be in shortage (but then again neither is saline)
<whitequark>
a lot of people would benefit a little bit from switching to injectables
<whitequark>
they're just much better overall. both safer and more effective.
<whitequark>
but oral also mostly works
<whitequark>
so there's one vendor and they monopolize the market
<rqou>
can people at least get it from RU/IN with bitcoins or something?
<whitequark>
this is very bad for those for whom oral formulation doesn't work but that's a very small amount of people
<whitequark>
fuck no
<whitequark>
I couldn't find a vendor
<whitequark>
well
<rqou>
what
<whitequark>
in RU estradiol injectables aren't even approved
<sorear>
meanwhile T is just enough marginally better of a cyp450 substrate that oral T doesn't work for anyone
<whitequark>
ayup
<rqou>
whitequark: so all the memes and photos of boxes that i see on trans twitter are the oral form?
<whitequark>
rqou: yep
<whitequark>
oral form is what you get once you go to planned parenthood and fill an informed consent form
<whitequark>
and spironolactone
<whitequark>
spironolactone is an amazingly shitty drug
<whitequark>
like it has three main effects and it doesn't do any of them well
<whitequark>
so depending on what you want when you prescribe it you call the others "side effects"
<rqou>
i remember reading the Wikipedia article and thinking "wtf this is supposed to be a diuretic?"
<whitequark>
all civilized countries use GnRH agonists, which specifically and exclusively target the HPG axis
<whitequark>
GnRH agonists have no side effects
<whitequark>
(there's an extremely rare side effect that's basically "your pituitary gland implodes" but no one is exactly sure why or when that happens, and it's too rare anyway)
<qu1j0t3>
SCANNERS
<sorear>
looking forward to orally active gnrhas or gnrhans becoming a thing
<sorear>
also GnRHas are godawful expensive to get through non-grey-market channels in the US, but nobody does that
<whitequark>
sorear: there's a few that are active uh nasally
<whitequark>
nasal spray.
<rqou>
whitequark: so why exactly is spironolactone amazingly shitty?
<whitequark>
but it's more of an once daily thing than an once three monthly injection (goserelin is usually formulated like that)
<whitequark>
rqou: because it does a few things that you basically never want to do simultaneously
<rqou>
and if it's so shitty why do we keep using it here?
<whitequark>
if you want a diuretic, you don't want to castrate people
<whitequark>
if you want an antiandrogen, you don't want to give people a diuretic
<whitequark>
it's also uh
<whitequark>
right, it's also an aldosterone agonist
<sorear>
there's some neat interaction between the 'bathroom bills' and the fact that a large fraction of US trans women are on diuretics
<whitequark>
rqou: so there's also cyproterone and GnRH agonists
<whitequark>
cyproterone is kind-of-but-not-really better than spironolactone
<whitequark>
it's not a diuretic but it can kill your liver if you self-med
<whitequark>
and it has other side effects because it's a steroid
<rqou>
so why do we keep using these not-good drugs?
<whitequark>
cst
<whitequark>
cost
<whitequark>
spironolactone is dirt cheap, a dose of leuprorelin (once monthly) in ru costs around uh
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<whitequark>
$120 i think
<whitequark>
in us it's like ten times that
<whitequark>
obviously.
<rqou>
oh wtf is this molecule
<rqou>
it's _huge_
<whitequark>
leuprorelin? it's a small peptide
* whitequark
takes a long drag off the blunt
<gruetzkopf>
even here it's not cheap (they'll bill your insurance ~500 for the 3month depot)
<rqou>
ah
<whitequark>
so here's how the HPG axis works
<whitequark>
gruetzkopf: it's a fair price for it tbh
<whitequark>
stuff's hard to make
<whitequark>
mostly keeping it pure
<gruetzkopf>
if you manage to get it prescribed (only available through prescription) that's clamped to 10€ out-of-pocket
<gruetzkopf>
i'll get interesting internet ads these next few weeks..
<rqou>
wtf how are your payments so low over in Germany
<whitequark>
rqou: ok so first hypothalamus releases gonadotropin-releasing hormone, aka GnRH
<whitequark>
this causes pituitary gland to release gonadotropins, which is to say FSH and LH
<whitequark>
this causes gonads to do their gonad thing, which includes releasing sex hormones, which is to say T and E2,
<whitequark>
which act on hypothalamus to close the feedback loop
<whitequark>
how here's the thing.
<rqou>
also wait gruetzkopf you can actually look up prices? with actual numbers?
<whitequark>
the concentration of that massive molecule in blood cannot be used as an analogue value in the control loop
<whitequark>
it's just too low, you'd need a massive gain, and that would inject noise
<whitequark>
so what the HPG axis does is it works via PDM.
<gruetzkopf>
yep
<whitequark>
pulse density modulation.
<gruetzkopf>
(you can also be freed of copay :P)
<rqou>
gruetzkopf: what an amazing concept /s actual numbers
<whitequark>
when you start a treatment with GnRH agonists, you basically overdrive the input stage of hypothalamus, causing it to register no pulse at all.
<pie_>
rqou, lots of taxes probably :p
<whitequark>
sorry. of pituitary gland.
<whitequark>
which causes it to not release gonadotropis, which causes gonads to not release sex hormones.
<rqou>
whitequark: wtf why does it feel like all of our pharmaceuticals are giant hacks?
<gruetzkopf>
aspirin synthesis is *extremely* simple though :D
<Bike>
yeah you just fuck up a tree
<whitequark>
lo
<whitequark>
*lol
<whitequark>
see also: pacitaxel
<Bike>
really, i guess most syntheses come down to that eventually
<whitequark>
sorry, paclitaxel
<whitequark>
you fuck up a tree and cure cancer.
<whitequark>
and now we ran out of trees to fuck up
<rqou>
heh
<Bike>
trees were holding out
<whitequark>
so can we synthesize it? we can synthesize it in, like, tons of ways
<whitequark>
in fact this molecule is so complicated to make that synthetic chemists have a sort of a leaderboard, who can make it using the most perverse pathway
<Bike>
do they have any idea why a chemical from a yew works for cancer
<whitequark>
but none of them were ever really interested in making it in industrial amounts
<Bike>
ahaha wikipedia has an article on paclitaxel total synthesis
<whitequark>
because who wants to do that when you can fuck up a perfectly good tree
<Bike>
that alone speaks of a journey
<Bike>
"By 1992, at least thirty academic research teams globally were working to achieve a total synthesis"
<rqou>
Bike: afaik we don't really know why paracetamol works lol
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<whitequark>
The total synthesis of taxol is called one of the most hotly contested of the 1990s [2] with around 30 competing research groups by 1992. The number of research groups actually having reported a total synthesis currently stands at 9 with the Holton group (article first accepted for publication) and the Nicolaou group (article first published) first and second in what is called a photo finish.
<Bike>
my basic assumption is we don't know how anything works
<whitequark>
oh my god
<Bike>
photo finish, lol.
<Bike>
i had a school project where we were supposed to work out a cure for fibromyalgia, and the best i could think of was replacing the nervous system
<rqou>
"replace humans with machines, problem solved"
<Bike>
you've seen that adversarial ANN stuff, right? we're reaching near-medical levels of completely bullshit problems
<gruetzkopf>
"By cultivating a specific Taxus cell line in fermentation tanks, they no longer need ongoing sourcing of material from actual yew tree plantations."
<Bike>
i, for one, am proud
<whitequark>
Bike: lol
<whitequark>
cure for fibromyalgia LOL
<whitequark>
what
<whitequark>
is this some sort of sisyphean task with the goal of having you accept the inevitability of defeat
<whitequark>
at least it wasn't a cure for alzheimers
<Bike>
yeah my devo profs decided to get Creative so we had a project where they gave us an incurable disease and we were supposed to figure out how to cure it with stem cells
<rqou>
cure for aging :P
<Bike>
it went about as well as you'd expect
<whitequark>
Bike: ...
<whitequark>
devo?
<Bike>
developmental biology
<rqou>
obviously the cure for aging is <insert fad of the day/month/year> /s
<Bike>
or, the band
* prpplague
checks the channel topic to make sure he is in the right channel
<Bike>
listen. a neural network is basically a generalized fpga
<rqou>
##openpharma :P
<whitequark>
rqou: there's ##whitequark
<pie_>
openbiohacking
<rqou>
wait what
<pie_>
huh
<rqou>
is there really?
<gruetzkopf>
*click*
<Bike>
also i don't have anywhere else to talk to whitequark since i quit twitter. except that channel i guess.