Right, you're not paying for C# you're paying for an IDE. You don't need VS to use C#. Especially now with Roslyn a the c# language server a lot of other IDEs can do a lot of the same things VS can do.
Indie devs and small businesses (<5 installs) can use the community edition for commercial purposes, too. I use VS Code & the C# extension most of the time, and that's free as in beer for use by anybody.
> The only thing I had to deal with it slightly is my Ritalin...only so slightly I can "normally" focus for an hour. I just hope things go right in the rest of my life.
Talk to your doctor, there have been many advances in ADHD meds and they all work differently on different people. Some people respond well to Ritalin, Some respond well to the generic. Some respond well the Adderal, or Vyvanse. For some people only the name brand formulation works. Some people any formulation works. Also, make sure you are at the right dosage. You can and do build up a tolerance over time. I try to take weekends off when I don't have anything in particular I need to do, and at least one or two weeks a year (normally when I go on vacation).
respectfully, I disagree with this. The last new therapy was atomoxetine, which is almost 20 years old now and not seen as terribly efficacious.
Everything else new has been some variation on mixed dextroamphetamine/amphetamine salts or methylphenidate. Vyvanse is just a pro-drug for dextroamphetamine.
The only novel thing in the pipeline is SPN-812, which may work similar to atomoxetine.
Lisdexamfetamine is profoundly different than other variants of amphetamine in utility and experience. It’s not just a prodrug – it has a rather clever molecular time-release mechanism. It comes in very slowly over a period of two hours, with plasma concentration plateau of two more. This makes a big difference; I experience no cravings or drug-seeking for more of the drug at any point. It’s also less of a “jolt”; The slow, steady increase in effect is much more conductive to steady yet limber focus. It’s just incredibly functional medicine. Also, the description of a 14-hour effective duration is accurate in my experience.
It’s definitely a relatively new development and a much more humanely effective drug than previous options.
— It is dextroamphetamine, which I’m inclined to believe is the more useful handedness. Levoamphetamine has more “body” effects. To the dextroamphetamine is bound a lysine molecule, and this together is an inactive powder. Enzymes in red blood cells are needed to cleave the lysine off and activate the dextroamphetamine. I’m quite certain that the dopamine rate-of-change detection mechanisms in the central nervous system cause very different behavioral and cognitive pattern cascades when it’s an almost imperceptively slow change, compared to an unhindered uptake of free amphetamine. Compare the difference in addiction potentials between faster and slower routes of administration of, say, nicotine - smoking fast, patches slow.
> Lisdexamfetamine is profoundly different than other variants of amphetamine in utility and experience. It’s not just a prodrug – it has a rather clever molecular time-release mechanism
I'm not sure how much truth there is to this claim. As you mentioned, Lisdexamfetamine is just Dextroamphetamine bound to the amino acid, l-Lysine.
Once your stomach cleaves the l-Lysine, it yields free-floating D-Amp.
This mechanism of action isn't any different than most formulations of extended-release Dextroamphetamine, like Dexedrine ER spansules.
Additionally, Adderall and other standard mixed-isomer amphetamine salt formulations are a 75/25 mix of D-Amp/L-Amp, and the peripheral nervous system stimulation that L-Amp produces at that kind of dose (5mg for a 20mg pill) I would think to most wouldn't feel very noticeable at all.
Having gone through Adderall IR, Adderall ER, Vyvanse, and Dexedrine IR over the years, to me they all felt more or less the same (besides IR vs ER).
If for whatever reason Vyvanse happens to work better for some people, that's fantastic and more power to you, but the hype behind this is all marketing IMO. And, it's absurdly expensive without insurance.
It was the difference between $250/mo and $20/mo using Good Rx between generic Adderall/Dexedrine and Vyvanse.
Sure, technically, but read the FDA paper on it's pharmacokinetics.
Smoking, shooting, or squirting it up your ass won't do the trick. But injecting it would put it in direct contact with red blood cells, and so would rectal administration via absorption through rectal mucosa.
Lisdexamfetamine needs to pass through the GI tract where there's proper enzymatic activity.
"The environment in the rectum is considered relatively constant and stable and has low enzymatic activity in comparison to other sections of the gastrointestinal tract. In addition, drugs can partially bypass the liver following systemic absorption, which reduces the hepatic first-pass effect."
"Oral absorption of LDX was assessed in rat portal and jugular blood, and perfusion of LDX into isolated intestinal segments of anesthetized rats was used to assess regional absorption. .... LDX and d-amphetamine were detected in blood following perfusion of the rat small intestine but not the colon"
"The intact prodrug, LDX, was readily absorbed from the GI tract after oral administration, with relatively high levels of LDX detected in the portal blood of rats. When LDX was perfused into isolated segments of rat duodenum, jejunum, and ileum, it was absorbed into the systemic circulation; however, LDX was not absorbed during perfusion into colonic segments. These findings indicate that absorption of LDX occurs via carrier-mediated transport in the small intestines and are consistent with the physicochemical properties of LDX (ie, high aqueous solubility of greater than 0.85 g/mL within the physiologically relevant pH range of 1 to 812 and low lipophilicity [logP–1.75, unpublished data]), which would predict poor passive diffusion across biologic membranes"
But hey, here I am arguing on my weekend about why exactly putting a certain amphetamine prodrug up your ass won't work. What are we doing with our lives?
Ah - I understand these passages such that they describe the passage of the intact LDX molecule into the bloodstream, and I don't see mention of the lysine-amphetamine cleavage action. This describes what part of the intestine is able to pull the whole LDX molecule into the blood. Note the distinction between absorption and metabolism. Later passages:
LDX was not metabolized in vitro by SGF, SIF, or trypsin, [so] any conversion of LDX to d-amphetamine in the GI tract in vivo is likely to be minimal. [...,] consistent with a model of absorption of predominantly intact LDX with subsequent enzymatic conversion to active d-amphetamine and l-lysine.
LDX was metabolized to d-amphetamine in rat and human whole blood but not in plasma. [Red blood cells] are responsible for the presystemic conversion of LDX to d-amphetamine.
LDX was metabolized to d-amphetamine by human RBCs but not by other blood fractions, such as white blood cells or platelets. Moreover, RBCs had a very high capacity for the metabolism of LDX. The rate of metabolism was not substantially reduced until concentrations of RBCs were reduced to 10% of normal hematocrit. Lysis of the RBCs also had little impact on the rate of metabolism of LDX, and nor did EDTA (a calcium chelator that inhibits the activity of calcium-dependent enzymes).
In conclusion, LDX is absorbed as the intact prodrug and converted to inactive l-lysine and active d-amphetamine primarily in the blood by RBCs.
New formulations are advances. I'm on Vyvanse and it has way fewer side effects than other amphetamine formulations. I could see someone deciding meds are not for them based on side effects or short duration and the come-down lows, and then have those go away entirely by taking Vyvanse.
There was also some work on repurposing fasoracetam for individuals with glutamate receptor issues, though I think they started with teens instead of adults. [0]
> The last new therapy was atomoxetine, which is almost 20 years old now and not seen as terribly efficacious.
I think it's more that it doesn't work for as many people as does stimulant medication. But while it works on fewer people, for those that it does work on (myself and my partner included), it's very effective.
Speaking of tolerance, I really wish there was an “antidote” that could be taken at night. It would encourage better sleep and I would think would help fight tolerance a ton.
I take stimulants for idiopathic hypersomnia and I know things are a bit different for ADD folks, though.
There are many things here that concern me from a system view.
1. They need guaranteed delivery, but chose to use UDP
2. They jacked up the default rmem buffer to ~2GB which is insane. Also, applies to all sockets not just UDP, so I wouldn't be surprised if they where also running into issues with memory pressure especially under load
3. Support didn't seem to let them know that's a pretty unconventional configuration
That was an interesting debugging story, and catching a bug like this is always good IMO. But, there is just so much WTF in this setup.
Wireguard needs to put actual logging into the product before anyone should consider using it in production.
I have to deal with it via a vendors product and have spend about 4 weeks in the past 6 months trying to fix a flaky connection by guessing and restarting a lot. Just like anything things will go wrong. But, with wireguard you have no idea what it could even be if it's not an obvious thing that you can diagnose with ping.
Wireguard also needs a better auth mechanism. I really like the simple secure key-based auth for small-scale stuff, but it's not viable for scaling at production levels. Things like user/pass auth (even if as an additional layer of security rather than displacing existing keys), 2FA, etc. will be important to get adoption at scale. I hope wireguard creates a module interface of sorts so people can extend the protocol as needed.
The thing about simple, key-based authentication is that it's very extensible, without changing the actual protocol.
What?
Well, what Wireguard's auth actually means is that you can use whatever authentication you want to communicate a shared secret to both ends.
Want to authenticate with, say, SSH keys? Sure- SSH into a server, run a command that generates a new Wireguard key, connect in with that key.
LDAP? Same situation. Whatever SSO you want- as long as you can stick up authentication in front of a service that's able to pull bits from /dev/urandom. Multifactor? Sure.
Wireguard does one thing well. What's missing is not features in Wireguard- it's the ecosystem around it to actually handle key management. For enterprises, Hashicorp Vault or something should probably look into supporting Wireguard; for smaller situations, some SSH-based key exchange, like the way Mosh handles things, seems reasonable.
Complex, pluggable authentication is sometimes necessary...but you want as few implementations of it as possible, and you sure don't want it in the kernel if you can help it.
The problem is that a Wireguard key isn't a session token -- it isn't revoked when the connection ends or goes idle. It's more like an authorized SSH key which in most environments meets the bar for 1FA even if it requires 2FA to set up the key.
WG has the concept of sessions already, the only change would be allowing a process in userspace to instrument the sessions directly without going through the key system.
The the default key-routing system would be just one method of issuing and managing sessions making the core protocol even simpler!
By sessions, do you mean the key agreement/initiation protocol, that is re-run every 2 or so minutes (with the keys having moderately overlapping validity)?
The problem is lots of organisations in the financial and medical worlds need 2FA. WireGuard needs a 2FA solution - It doesn’t have to be kernel based - but it does need to protect against someone grabbing a copy of the single factor auth in WireGuard (keypair). A solution that rotates/manages/provisions/etc these keypairs is still fundamentally single factor auth of the tunnel.
> WireGuard needs a 2FA solution - It doesn’t have to be kernel based - but it does need to protect against someone grabbing a copy of the single factor auth in WireGuard (keypair).
By this standard, no website supports 2FA- ultimately it's just a cookie that's used to authenticate requests, even though to get that cookie you may have to go through 2FA. Nothing prevents an attacker from just grabbing the session cookies.
In fact, I doubt any VPN supports 2FA by this definition- it would mean requiring authentication on every packet. Instead, of course, what you do is do authentication once, when setting up a tunnel, and then use bearer tokens from then on.
The session info in a browser is not persisted on disk as a long term config file that’s easy to copy and duplicate. Having a session key only ever exist in memory is completely different to storing WireGuard keys on a filesystem.
Edit: Also OpenVPN, which is the tool I’m comparing it with, only ever has session keys in memory. The 2FA part (password+OTP) isn’t saved by OpenVPN.
Nobody is arguing that there shouldn't be IdP-based WireGuard management systems. The point is that they are out of scope for the WireGuard project itself. WireGuard has an extremely straightforward configuration interface; if Okta wanted to manage WireGuard, they'd likely have no problem doing it.
You don’t need a distro for this, and WireGuard has been available and in use for several years. So in that time has anyone developed a practical 2FA solution that is compatible with it?
People have. I'm unaware of any published. It's not hard. Implementing a new IdP-integrated WireGuard authorizer is probably easier than understanding IPSEC or OpenVPN in sufficient detail to secure it.
Wireguard doesn't need to change at the protocol level to add those features and I think thats the point. Userspace programs can be written to fetch keys from a server based on SSO or w/e.
It looks quite good, but I don't see any information on:
1. Is it open-source?
2. When am I going to see the "you have to pay us now" screen, and how much will it cost? I realize it's a business and am fine with that, but want to know what I'm spending before setting stuff up.
Compared with HTTP/1.1, HTTP/2 has known regressions which can be catastrophic on poor-quality connections, mostly due to TCP head-of-line blocking. At Fastmail we found concrete performance problems for some users from deploying HTTP/2 so that we rolled it back for a while and tried again later after shuffling a couple of things around to mitigate the worst such problems (can’t remember what we actually did). But even so, a small fraction of our users will get a worse experience from HTTP/2 than from HTTP/1.1. (Don’t think I’m speaking against HTTP/2; overall it’s an improvement for performance over HTTP/1.1, often a big improvement. But for developing things like interactive apps, it’s helpful to understand the differences and their effects.)
HTTP/3, meanwhile, does not suffer from such problems (which is most of why they made it). The main risk is that it’s less likely to work at all—but browsers take that into consideration and fall back to HTTP over TCP (HTTP/1.1 or HTTP/2) smoothly.
Presuming you have capable server software, I’d honestly consider deploying HTTP/3 to be lower risk than deploying HTTP/2.
One should also consider the robustness of the HTTP/2 or HTTP/3 implementation. Consider such things as this variety of DoS attacks against HTTP/2 from the last six months: https://github.com/Netflix/security-bulletins/blob/master/ad.... It’s improbable that these are are only major attack vectors in HTTP/2 and HTTP/3 implementations.
* Medical Insurance
* 401(k) Contributions
* HSA/FSA Contributions
* Commuting Expenses
* Auto Loan
* Gas
* Auto Insurance
* Property Taxes (unless you rolled that into the mortgage)
* Home owners insurance
All of that will easily chew up that 955 left a month. And, that doesn't even take into consideration a date night or two a month, and general keep me out of a depressive state stuff.
I did mention insurances, but missing their auto loan was a big omission! I used the estimate on the linked page for mortgage, which includes property taxes and insurance.
So that leaves the optional retirement and healthcare savings, plus commuting/gas (which may have some overlap.) And again I was going really high on the debt payoff estimates, groceries, and hopefully child care (though I have seen even worse.)
But yes if have student loans, but then choose to take on a car loan and a mortgage payment that stretches you thin, you start to have to choose between savings, debt pay off and fun things including eating out and more expensive forms of entertainment.
The snapshot isn't the complete picture, but they definitely look like they are in a perfectly reasonably situation, and they could have those optional debts paid down relatively quickly, which would massively ease up their budget.
It depends on what your service looks like: CPU intensive, Memory Intensive, Storage intensive? (In reality some unique mix).
You probably won't see a huge savings year one, as you'll be spinning up a lot of new things and have a fairly large CapEx expenditure. Now if your growth pattern is steady/predictable then you should be able to plan out your hardware buys or do a hybrid solution to handle traffic bursts.
One of the nice things about running your own hardware is that there are some costs that are easier to control. Don't need new hardware? Don't need to spend on new hardware for example.
You also have much more control over your environment so you are able to really optimize your code, and infrastructure so that you don't need to scale as large system wise.
But, back to the question on how to model it? You just gotta dig in, and make some educated guesses about performance,test and repeat.
