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thepianistfroggollum , in We Know Where New Weight Loss Drugs Came From, but Not Why They Work

I mean, not knowing how a drug works really isn’t news. Hell, we don’t know for sure how Acetaminophen and Aspirin work.

Gsus4 OP ,
@Gsus4@feddit.nl avatar

really, even Aspirin? But then, how do they design testing to ensure that it’s safe long-term? Without a model, all you have is “just test every possibility you can think of and pray”.

SheeEttin ,

They test in animals with various doses. Then they test in humans.

Of course this can’t demonstrate that it’s safe over long periods of time, but we do the best we can with the tools we have.

DRx ,
@DRx@lemmy.world avatar

No, not aspirin. We know aspirin very well in the medical community.

TBF there are drugs out there that we do not know the MOA of, like methocarbamol (from the national institute of health: “The exact mechanism of action of methocarbamol remains unknown; similarly unknown is the relationship between musculoskeletal pain and muscle spasm” lol)

So for long term safety, it is based on animal and human studies. These studies happen for multiple years prior to being put on the market (for the most part, though that is a story for a different day). Then after the drug is on the market, the drug company is required to do “Postmarket Clinical Studies” to show that their drug is still doing what it was initial shown to do; furthermore, to look for safety events of said drug.

A really famous case of a bungled postmark study was Vioxx. Vioxx is/was a Cox-2 specific pain medication. In the initial and postmarket studies they found that it had an increased risk of heart attack (in some cases up to 88% increased risk). The company Merck held the information from the public and FDA. They were forced to take the drug off the market in 2004. Technically in short bursts Vioxx was probably safe, but long term it was not.

thepianistfroggollum ,

Yes, that’s how modern medicine works. Much of how the body functions, especially when it comes to the brain, is largely unknown. There are just an almost insurmountable amount of variables to control for.

For every drug that makes it to market, there are hundreds if not thousands of similar drugs that failed at some point in testing. No one knows the longterm effects of any drug in humans until humans have been taking it for a long time.

Hazdaz ,

It isn’t just drugs. A whole ton of scientific things that we just accept are kind of unknowns. We can use them. We can even manipulate them to our will, we even have equations that can define their magnitudes and predict results, but we don’t fully understand them. In fact the more you know about some of these subjects, the more uncertainty there is. A layperson might think the subject is fully understood.

Here’s a scary example: Lift (like the kind a wing creates on an airplane).

douglasg14b ,
@douglasg14b@lemmy.world avatar

Isn’t lift entirely understood?

If you’re arguing that the underlying behavior and existence of matter isn’t understood, and by extension lift isn’t, then that applies to anything and everything.

Hazdaz ,

No, lift is not entirely understood. The mechanism of why it happens is still a mystery.

schroedingershat ,

What are you even trying to say? That CFD doesn’t even exist? Just because a bad abstraction taught in schools isn’t really tethered to reality, doesn’t mean large laminar uncompressible fluid dynamics is unfathomable.

Hazdaz ,
schroedingershat , (edited )

Those are both bad schoolbook abstractions. And that article is about how the full mathematical treatment (which is known) doesn’t fit a neat pat thought-terminating-cliche explanation. Plenty of people develop an intuitive understanding so it’s not rote symbolic formalism.

Air goes down. Plane goes up. The exact details of air goes down are complex and nuanced, but not at all unknown.

DRx ,
@DRx@lemmy.world avatar

Well how specific is enough to say we do or don’t know how a drug works?

In particular we do know that ASA and other NSAIDS work by inhibiting the activity of the enzyme called cyclooxygenase which leads to the formation of prostaglandins that cause inflammation, swelling, pain and fever. It blocks both COX 1 and 2, though only COX 2 is responsible inflammation. Furthermore, The antithrombotic action of aspirin is due to inhibition of platelet function by acetylation of the platelet cyclooxygenase at the functionally important amino acid serine529.

Now contrast ASA with Acetaminophen …

We know that Acetaminophen also inhibits COX, but only in the CNS and not peripherally. Also, it is only thought that it potentially blocks pain signals via the serotonergic pain pathway.

I would say we know a hell of a lot about aspirin … Acetaminophen not so much on the MOA side of things, however it has been studied so much that we know the safety/toxicity profile like the back of our hands. Either way probably not the best 2 examples to use for your argument.

frozen , in We Know Where New Weight Loss Drugs Came From, but Not Why They Work
@frozen@lemmy.frozeninferno.xyz avatar

“The era of ‘just go out and diet and exercise’ is now gone,’”

Horseshit. Especially if they can’t manufacture the drugs fast enough. I’m type 1, so I follow the hashtag on Mastodon, and the number of people complaining that they can’t get their GLP-1 drug refilled because of shortages is ridiculous.

FrankTheHealer ,

Yeah, I have family members who are diabetic. They’ve haven’t been able to get their Ozempic for a couple of months now

febra , in Two brands suspend advertising on X after their ads appeared next to pro-Nazi content

Apple still advertises on Twitter. We need a website that tracks all of these companies that still advertise on that pro-nazi platform.

zer0 ,

Found one it’s called google, seem like all companies in the world advertise on twitter except for these two in the title that pulled out

ILikeBoobies ,

Companies don’t have ethics, they have profits

You shouldn’t read too much into it

ComradePorkRoll ,

Disagree on not reading into it. You should be appalled by the fact that profit comes at the sacrifice of ethics.

ILikeBoobies ,

Yes but not enough people will boycott everything that supports things they are against. A lot of people will have a brand that they say “yeah but I really like them”

And all corporations are evil, it’s not really a surprise

Asymptote ,

Companies don’t have ethics.

DragonTypeWyvern ,

Companies aren’t real, they’re just people organized into a collective, and people do have ethics.

And contrary to Internet wisdom, corporations do not have a legal obligation to pursue profit at all cost.

One might ask what the point of spreading that particular lie was.

Asymptote ,

The company boards would gladly stuff you into Gaza if there was a profit to be made.

DragonTypeWyvern ,

Sure. But I find it strange that people act like those evil fucks are a faceless building and not individuals you can point to and say, “Hey, no, it’s that guy, he enslaved those kids.”

Asymptote ,

What are we going to do? What recourse did the girls raped by Epstein have?

DragonTypeWyvern , (edited )

I’m not going to say join a radical militia, but maybe see if any in your area look cool.

febra ,

I don’t see why I shouldn’t look into it. Are there any good reasons not to?

ILikeBoobies ,

You can look into it but it doesn’t mean company supports X

Look at pride month or the bud light thing

NathanielThomas ,

It would be funny if they were all the same ones that supported Adolf

FollyDolly , in Trump supporters post names and addresses of Georgia grand jurors online
@FollyDolly@lemmy.world avatar

Fuck

zazaserty , in We Know Where New Weight Loss Drugs Came From, but Not Why They Work
@zazaserty@discuss.tchncs.de avatar

Instead of trying to get better food to americans lets just use more pills to keep their weight under control

AbouBenAdhem ,

Part of the problem is access to better foods, but another part is addiction to bad foods. If we can remove the craving for bad foods, people can make better choices between the foods available to them.

Semi-Hemi-Demigod ,
@Semi-Hemi-Demigod@kbin.social avatar

Ah, yes, just remove the natural human craving for fats and sugars. Simple as.

PeleSpirit ,

That’s not what they’re talking about, it’s the designer foods that make you crave more and more. MSG makes you crave more, salt and sugar combined make you crave more, etc.

Semi-Hemi-Demigod ,
@Semi-Hemi-Demigod@kbin.social avatar

I agree that highly refined foods are designed to make you eat more of them. What I don't agree with is that we fix it by removing our craving for them, rather than restricting them at the source.

One thing that would help a lot is limiting food advertising. The more you eat these superfoods the more you're conditioned to want them, and seeing pictures and video of them prompt increased consumption like Pavlov ringing a bell.

PeleSpirit ,

I think we’re on the same page.

azertyfun ,

It’s not just Americans. The obesity epidemic is a worldwide problem, and is still worsening in Europe for instance despite increasingly tighter regulations and an actual, significant improvement in eating habits for the past ~15 years.

Truth is, we have no fucking clue what truly causes obesity. Sure, eating less means less weight gained, but why do some people crave so much more food, and/or why does their body work so much harder to accumulate/not burn fat than others? We do know that several chemicals will change a person’s “natural BMI” (or whatever you wanna call it). But we don’t know how these chemicals work.

(More reading on this in A Chemical Hunger, which is absolutely fantastic)

Of course American food is terribly regulated, but there are good reasons to think this is largely unrelated to obesity. Which is not to discount the health benefits that would be reaped if you didn’t stuff tons of corn syrup, hormones, and antibiotics into everything of course.


I think we should definitely try to understand the fundamental processes of weight gain/loss, because the idea that it’s all based on willpower is demonstrably wrong. And I do not think that, in the absence of finding the root cause of the obesity epidemic, providing patients with medication is obviously the right move to improve their quality of life. It’s not their fault that we don’t understand jack shit about why their bodies are rebelling or why the medication works, but the health benefits are undeniable.

douglasg14b ,
@douglasg14b@lemmy.world avatar

Understanding why I crave food, constantly and aggressively would do so much towards helping with weight loss goals.

I’m sure sugars and the like have lots to do with it, but even abandoning sugars (Which I did for a good 4 months) didn’t seem to change it.

azertyfun ,

My understanding is taking sugars/carbs off is good because they don’t seem to count towards the body’s “I’m full!” detection, unlike actual fat, despite being highly caloric and easily metabolized. If you’re eating till you’re full, fat is better, because you’ll be full sooner.

But yeah intuitively I can see how that wouldn’t do so much if the internal fat control system is fucked up to a point that you’re never full. (Though I’d assume that metabolization rates still matter? IDK I’m no dietetician).

Hopefully we can get some progress on the science side of things now that academic views on obesity are finally shifting. The medications in the OP also sound interesting, if they actually reduce the source of the problem (the cravings), but that’s a discussion to be had with your GP, not an unqualified internet stranger.

Hazdaz , in Trump supporters post names and addresses of Georgia grand jurors online

You know what… GOOD.

Not that I want to see it, but time and time and time and time again these right wing fucks have proven that they can’t be reasoned with, they can’t be trusted and they have zero morals or plans to follow societal norms… AND YET WE CONTINUE TO TREAT THEM LIKE INNOCENT PEOPLE.

We have been asking for shit like this to happen every time we give a J6th traitor a light sentence or every time Trump or one of his clown supporters tweets some fairly obvious call for violence and we do nothing.

When the fuck is the Left going to wake up and realize that we are at war?

The Right has seen this as a war for a long, long time now. They have been stockpiling weapons, creating closely tied groups and training militias. They are radicalizing the youth. They see this as a life-and-death situation where there will be victims and bloodshed.

What the fuck has the Left done? Written a few memes? A few snarky comments on Twitter? They have treated this as a joke or just business-as-usual when dealing with politics. We give the other side every chance to bully their way into a position of power by constantly compromising on things. And when it comes to punishments, the usual bleeding-heart stereotype comes into play and we give these traitors the lightest of sentences when instead they should be facing the same kind of corporal punishment that they would face in any other country for treason.

sirlington ,

The US can not afford to be divided like this right now, but what the hell can you guys do. Fucked situtation, I feel you

Hazdaz , (edited )

what the hell can you guys do

Well for one, treat it with the seriousness that it deserves.

That alone would and should change many people’s view on this.

This is not that different than when these Republicans ship illegal immigrants to CA or Washington or Boston. It has happened time and time again, and every time Liberals want to play it down in the hopes that it won’t happen again. And then it happens again! And this latest time some little kid died because of it. What is it going to take for the Left to take it serious enough to where human trafficking charges are brought up on the people that planned it? Ruin the lives of some of the people who were involved in treating humans like property by getting them inundated with federal charges and endless legal fees. You better believe that when someone might be held liable for helping DeSatan plan a trick, they might think twice. But Liberals in the US are just a bunch of pussies that would rather becomes targets for some gun crazed redneck than ever go on the offensive.

PeleSpirit , in We Know Where New Weight Loss Drugs Came From, but Not Why They Work

That’s a wild read. I’m surprised so many people would take the pill without anyone knowing the side effects but I guess it’s worth it to them.

Z4rK ,

The known risks with obesity are so severe that it does make sense.

PeleSpirit ,

As compared to unknown risks of taking a pill that they don’t know how or why it works? Obviously a lot of people are, but it strikes me as wild.

Z4rK ,

It is. I’m not willing to try it myself. I wouldn’t like an untested drug that works in unknown ways and that goes into unwanted regions of my brain. But I still can very well understand it, especially when a doctor recommends it.

PeleSpirit ,

I agree with you on except the doctor recommended part. They are sold to by drug manufacturers and get a cut so always make the final decision after you’ve checked reputable sources on the drug, unless they’re a relative or something.

Z4rK ,

Not in Norway, Denmark or Germany, the other three countries where the main drug from the article is sold.

PeleSpirit ,

Yeah, I guess I’m talking about American doctors. But do they actually recommend them in Norway, Denmark or Germany, or do they sell them there?

Z4rK ,

Good question, I may have worded that too strongly. But if they’ll approve it upon request that is pretty close to a recommendation still, even if they didn’t bring it up themselves. Keep in mind that all medicine will be subsidized and cost the government money, and afaik the medicine in question is fairly expensive, so doctors are in general supposed to be restrictive in prescribing medicine willy nilly - if they prescribe it, patients will trust that it will have effect and be safe.

NOT_RICK ,
@NOT_RICK@lemmy.world avatar

We’re able to know what the side effects of drugs like this are as that is a measurable output. SSRIs are another example where we’re not fully sure how they work mechanically, but we still have a good sense of potential side effects.

PeleSpirit ,

They said in the article that they don’t.

Dr. Susan Yanovski, a co-director of the office of obesity research at the National Institute of Diabetes and Digestive and Kidney Diseases, warned that patients would have to be monitored for rare but serious side effects, especially as scientists still don’t know why the drugs work.

Also, why are executives deciding how our bodies work?

She faced resistance in part because some company executives were convinced that obesity resulted from a lack of willpower. One of the champions of investigating GLP-1 for weight loss, Mads Krogsgaard Thomsen, the current chief executive of the Novo Nordisk Foundation and former chief scientific officer of the company, said in the video posted by the foundation that he “had to spend half a year convincing my C.E.O. that obesity is not just a lifestyle condition.”

NOT_RICK ,
@NOT_RICK@lemmy.world avatar

They don’t know them all for sure, which is why that monitoring is important. The same happened with SSRIs and other drugs that are not fully understood. After Vioxx gave thousands of people heart attacks, pharma companies now have to monitor drugs safety and efficacy even past FDA approval. I used to pull reports from the HCO I worked for so the pharma company that made the drug could measure side effects. Still, those potential side effects are often less severe than the cost of non-treatment; in this example diabetes and heart disease.

As for your second question, in my view that’s just because our society puts too much stake in wealth. It’s assumed the rich are rich because they’re better and smarter. When they get all the way up to CEO their heads have gotten so big they think they know better than scientists because obviously they’re in their position out of their own personal work ethic and not thanks in part to other factors like luck and those that supported them along the way.

PeleSpirit ,

I can see why some people want to take the risk even though the risks potentially could be fatal in rare cases OR there might not be any side effects at all. It’s a crapshoot either way.

SkyeStarfall ,

There are a lot of drugs that we use without really knowing why they work. It’s actually not that uncommon. The human body is complex.

Pixlbabble , in Two brands suspend advertising on X after their ads appeared next to pro-Nazi content

How about a disclaimer for companies like people have when they play online. “Statements and opinions made by users do not reflect those of X” ESRB for ad companies to get it.

HikingVet ,

Why?

These companies don’t have to do business with twitter.

Now because their logo was next to some Nazi shit when they were promised it wouldn’t be, they are pulling their dollars because of broken promises.

thisbenzingring ,

if there is one thing you can count on from Musk, its broken promises

Pixlbabble ,

Because it’s annoying when a lot of good shit goes to dog shit when ad companies get involved with the creative side of things. Just have it in the contract up front if it’s not already and they can agree to be on the platform all in or all out.

HikingVet ,

Who said the ad companies are making it go to dog shit by not wanting to be seen next to fascist content?

CheeseNoodle ,

Something like that is already in law as a kind of default. Companies are not responsible for the content posted by their users on the basis that no entity could possibly police that much content, with two exceptions:
-Content must be removed if it is illegal and has been specifically pointed out by appropriate authorities for removal.
-If an organisation willingly polices their own content in any way then they also take on responsibility for it.

sndmn ,

How about no.

MedicPigBabySaver , in Trump supporters post names and addresses of Georgia grand jurors online

I’m literally running out of horrific descriptions of Trump & his cult.

pinkdrunkenelephants , in Trump supporters post names and addresses of Georgia grand jurors online

So who wants to place bets on when people involved in the trial start to get bumped off?

I would comfortably place a $10 bet that either one of these jurors, a prosecutor or a judge will get attacked or killed by a right wing cultist and/or one of Trump’s or Bannon’s hired goons by the 2024 election.

Chocrates , in Air Force awards a start-up company $235 million to build an example of a sleek new plane

We have been trying to make flying wings work for decades, since the jet engine I think. The stealth bomber is one, but afaik they are horribly unstable.
What makes this different from any other attempt?

Aliendelarge , (edited )

Blended wing is slightly different than flying wing but they both date to the early 20th century before jets even. Computer advancements in controls has generally been the change over the last few decades for control of the flying wings. Blended wings are a pretty wide range and include things like the SR-71, B1 Lancer, and quite a few UAVs.

Chocrates ,

Oh interesting, what is the different? Blended wing has more of a fuselage?

Aliendelarge ,

Exactly. The flying wing is a pretty specific design but the blended wings have a much broader spectrum of wing to fuselage ratio.

ikidd , in Texas woman charged over threat to kill judge overseeing Trump case
@ikidd@lemmy.world avatar
ineedaunion , in 'Hell on wheels': Teen convicted of crashing car at 100 mph, killing boyfriend and friend

More of this. Also let’s start holding rich people accountable of crimes also.

Catasaur , in Trump, co-defendants in Georgia election case expected to be booked in Fulton County jail, sheriff says
@Catasaur@lemmy.catasaur.xyz avatar

I won’t hold my breath.

Stinkywinks , in 'You're kind of raised to hate tourists': Maui fires fan tensions on Hawaiian island

They sure like the money from them though

girlfreddy OP ,
@girlfreddy@lemmy.ca avatar

When those are the only jobs available, what else would you have them do?

Stinkywinks ,

…so then if the tourists leave because they hate them so? Too many people have 0 logic

girlfreddy OP ,
@girlfreddy@lemmy.ca avatar

You don’t seem to have much either.

rab ,
@rab@lemmy.ca avatar

If there are no tourists, what jobs are left?

It’s like if Iceland didn’t get tourists anymore, there would be nothing for locals to do.

girlfreddy OP ,
@girlfreddy@lemmy.ca avatar

… except enjoy their beautiful nation.

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