wjs018

joined 1 year ago
 

Breakthrough here is the ability to image embryos comprised of living cells as opposed to post-mortem embryos.

original doi: https://doi.org/10.1016/j.cell.2023.06.003

 

The issue seems to be how the data was collected in the Phase 3 trial:

Clinical trials of most drugs and vaccines supporting FDA approval are mainly conducted in the U.S. and Europe, where clinical trial protocols are well recognized. The phase 3 TIDES trial used for Qdenga’s application was run in several less well-off, dengue-endemic regions in Latin America and Southeast Asia.

However, it should be noted that Takeda's drug, Qdenga, is already approved by the EMA in the EU and a couple other agencies. It is just the FDA that is holding things up in the US.

[–] [email protected] 1 points 1 year ago

Please, please let Ooyama's accidental confession mean something. Imo, this series has really pushed the "do they like me" bit to the breaking point. If Akutsu goes back to questioning it, then it's clear this series is never going to see real relationship progress.

 

Continued fallout from the explosion of the Centaur upper stage on ULA's test stand as Vulcan's launch continues to slip.

In a statement, ULA described the work needed on the Centaur V upper stage as “minor reinforcement at the top of the forward dome,” or the uppermost section of the liquid hydrogen tank. The changes will add strength to the tank, which contains super-flammable fuel chilled to minus 423° Fahrenheit (minus 253° Celsius).

The pressure is on as the DOD is eagerly waiting for Vulcan.

The US Space Force is eager for the Vulcan rocket to enter service. The Pentagon selected ULA and SpaceX in 2020 to launch around 40 of the military’s most critical surveillance, communications, and navigation satellites from 2022 through 2028. ULA won the rights to launch about 60 percent of the missions, primarily using the new Vulcan rocket, with SpaceX taking the remaining 40 percent with its Falcon rocket family.

 

"The postponement is motivated by obligatory compliance with the prevention of forest fires... as well as the high temperatures" in southern Spain "to ensure the safety of the area where the launch is carried out".

First time I have seen this cited as a reason for a launch delay.

 

I haven't editorialized the title, but I don't like it since the desired protein structure was thought up by the grad student and the "digitally designed" piece just seems to be some MD modelling to confirm the desired outcome before synthesis.

That being said, I thought this was interesting since freeze/thaw (F/T) stress is ubiquitous in the life sciences and something that is especially important to the emerging field of cell therapy. Typically, excipients like sucrose, trehalose, or glycerol are used to preserve biological molecules during F/T, but they are not protective in every case. Developing alternative means to protect during F/T gives people like me that develop therapeutic formulations more options to turn to in the case of difficult molecules.

doi: https://dx.doi.org/10.1073/pnas.2220380120

 

This is about a recent study looking at the rheology of fondant. Essentially, fondant is created from a supersaturated solution of sucrose that is agitated (kneaded). This causes the fondant to experience a sequence of events:

  1. First, the agitation induces crystal nucleation and growth. In the early stages of crystal formation, the surrounding solution is depleted of sucrose, reducing the bulk viscosity.
  2. However, as the crystals grow in size, they are large enough to push against one another in hard sphere-like interactions. This causes a sharp increase in viscosity at this critical crystal size.
  3. As agitation continues, sucrose crystals fracture and the system reaches an equilibrium crystal size distribution, causing the viscosity to decrease from its peak. This is the final state of a smooth, pliable fondant.

There is a doi provided by the article, but as of my posting this, the doi hasn't been activated yet.

[–] [email protected] 2 points 1 year ago (1 children)

Agree that the ending felt a bit weak. I think that picking up the pace in the show a bit more and getting further in the story would have helped things. At the moment, Raeliana is still a character without much agency, and it would be great to see a bit of her future character growth.

[–] [email protected] 2 points 1 year ago (1 children)

So, it has been a while since I read the manhwa (I haven't read the original webnovel), but I am overall pleased with how the adaptation has gone so far. You could definitely tell that there were very limited budgets. There are so many instances of slideshow animations or just still images, but they seemed to invest heavily in making beautiful stills and backgrounds.

My major complaint about the show is that, in general, it has gone very slowly. I expected them to be further along in the story after 12 episodes, but the pacing has been plodding at best. If my memory serves, I think they adapted 3 of the 7 volumes of the manhwa. I understand that a lot of shows tend to go too quickly, but this show just seems to drag out every conversation like it is padding for time (maybe to help stretch the animation budget too).

Overall happy with the show so far and hope that if it gets a second season it gets a bit more resources thrown its way.

[–] [email protected] 1 points 1 year ago

That is true. Vertex claims that some of the follow-up therapies to this do not require immunosuppressants, so time will tell.

From a strategic perspective, I wonder if they will proceed with Phase 3 or not. I have worked on several programs in the past where we pushed through to Phase 2 to get a proof of concept in humans before scrapping the program because we have a better version of the molecule (using the same mechanism of action) getting ready right behind it. This therapy from Vertex may have proven the concept to allow a better version to come next.

 

This is a summary of a Phase 1/2 trial of a cell therapy meant to stimulate insulin production in diabetes patients. The top line is that it met its clinical endpoints and several of the patients no longer require external insulin dosing at all and their blood sugar is well managed. Vertex also has a number of follow-up therapies in the pipeline meant to improve upon this therapy.

I personally don't have much experience in cell therapy, but the potential of a treatment like this is clear. We will see what the data looks like as this goes through the clinical trial pipeline and expands the patient population in Phase 3.

 

Not sure if TIL-type posts are allowed here, but thought that the story of the history of this event is interesting in a "history of science" type of way. If you want a narrative style of telling, you can check out this Smithsonian piece.

Story time! I watched Jurassic Park again recently and there is a bit in the movie where there is a discussion about competing theories for how the dinosaurs met their end. I didn't realize that back in the early 90's the impact theory was just one of a competing number of theories, so I did some reading.

Turns out that while doing readings to explore for gas/oil in the Caribbean, the Mexican state oil company, Pemex, had found evidence for the Chicxulub crater way back in the 1940's, but dismissed it as volcanic activity and moved on since volcanic regions are not great for oil extraction.

Fast forward to the late 70's and geophysicists are making additional measurements for Pemex and correctly ID the ring structure of these readings as a likely impact crater. The company is not really interested but consent to allow them to present their findings.

The cruel irony is that the conference at which the findings were presented occurred the same week that there was a special, separate conference with impact crater experts to discuss the impact theory of the end of the dinosaurs. So, there were no experts in attendance to learn about Chicxulub crater's existence from the Pemex scientists or recognize it's importance.

It took another 9 years, 1990, before the two worlds connected and further action was taken to ID Chicxulub as the impact crater that corresponded to the exact time period scientists were looking for.

Then, finally, it was 2010 before scientific consensus was (generally) reached that Chicxulub is the impact that ended the dinosaurs.

[–] [email protected] 3 points 1 year ago

I love Lichtenberg Figures as much as the next nerd, but knowing even a little bit about how they are made should make all the alarm bells in your head go off that it shouldn't be done at home. If you want a safe way to play around with electricity, get a Van de Graaff generator.

 

doi for the original Science piece: https://doi.org/10.1126/science.adh3104

 

This summarizes a report from Parks Canada about the reintroduction of bison to the Banff National Park.

A Parks Canada report published this week concluded that the reintroduction was a success, and it suggested that due to their robust growth rate, this bison subpopulation—one of only five that occupy a mere 0.5 percent of their original range in North America—may no longer be considered endangered within a decade.

Original report: https://parks.canada.ca/pn-np/ab/banff/info/gestion-management/bison/rapport-mai-reintroduction-may-report

[–] [email protected] 2 points 1 year ago (1 children)

This is neither here nor there, but I just want to compliment whoever did their favicon. I didn't realize favicons could be animated like that, I am surprised I don't see it more often.

[–] [email protected] 2 points 1 year ago

I commented this in a different thread on this news story, but this approval in an interesting one in that it has been approved using the accelerated approval pathway because there was an unmet clinical need. However, if you look at the clinical landscape, there are other options for treatment (also from Sarepta I should mention). Additionally, the interim clinical data showed protein expression which is what the FDA cited in their approval, however that interim data did not show significant positive clinical benefit. From PBS:

FDA scientists detailed a long list of concerns with the company’s research, particularly a mid-stage study that the company submitted for FDA review. Overall, it failed to show that boys who received the therapy performed significantly better on measures like standing, walking and climbing than those who got a dummy treatment

Accelerated approval pathways make sense in many cases they are used, however, the agency should beware allowing accelerated approval being abused by drugmakers to get a drug to market quickly and then slow-walk the post-approval obligations (which are usually very expensive phase 3 studies). Being too liberal with accelerated approvals incentivizes questionably efficacious therapies that are simply used as a profit tool before the data shows the full extent of their clinical impact.

I recently posted an opinion piece that talks about this in some more detail and provided some additional thoughts in that thread. I am not a specialist when it comes to regulatory practices or strategy, but simply a scientist in the field that is concerned about potential abuse of a regulatory mechanism that has the potential to cause harm to patients.

 

This mission, ELSA-M, is a follow-up on the proof of concept ELSA-D mission that was launched in 2021 and successfully rendezvoused with a client's satellite.

A challenge to this company going forward I see is that their interceptor requires a proprietary plate of their design to already have been affixed to the target satellite. I just don't see how this gets wide adoption enough to help meet their lofty preventing Kessler syndrome rhetoric.

[–] [email protected] 3 points 1 year ago

Great article summarizing the BBB. The brain is one of the highest priority targets for biologics therapeutics (viral & non-viral gene therapies, antibodies, peptides, etc.) and one of the most difficult to access via traditional routes of administration (IV, subcutaneous). I have worked on programs in the past that tried to access the brain via other administration methods (intrathecal, intraparenchymal), but both of these are quite invasive and lead to adverse events purely from the procedure. Engineering ways to cross the BBB would open up a huge number of potential therapeutic options for neurological disorders.

One of the other high priority targets that is difficult to access is the eye/retina. It has a similar set of biological barriers that prevent access to sensitive areas that are medically desired. If you want more reading on the eye, see this paper.

[–] [email protected] 3 points 1 year ago (1 children)

I think that fMRI is just beginning to realize its potential. It is such a powerful technique to image the brain, that as we improve the technique and can see more, we will learn more. I like to make the analogy that modern imaging techniques (MRI, microscopy, PET, etc.) have done at least as much to expand human knowledge as the more widely known (within the general public) telescopes (Hubble, JWST, etc.).

One thing that I like about this approach is that it is looking at the brain as a complex system rather than trying to ID and characterize individual neurons. From the article:

Neuroscience has traditionally focused on interactions between neurons to understand brain function. There is a growing area of science looking at larger processes within the brain to help us understand its mysteries.

This reminds me of my statistical mechanics course when I was in grad school. You can study individual particles all you want, but when you get a large number of them, things change. One oxygen molecule behaves differently than a room full of air just like a single neuron behaves differently than a head filled with a brain. The path of neuroscience is following a similar trajectory physics did in that it could make sense of things at the individual scale, but working with large numbers of interactions is harder and requires more complex experiments/theories/models to deal with.

[–] [email protected] 3 points 1 year ago (1 children)

In my professional life, I have worked on a number of clinical phase therapeutics and authored sections of regulatory filings submitted to agencies like the FDA and EMA. Several of those assets were classified as orphan drugs and were granted accelerated approval. I think that the accelerated approval process fulfills a role that is needed in cases where there is an unmet medical need. Additionally, some indications lend themselves to proven proxy measures for efficacy that give a high level of confidence in clinical use. However, the accelerated approval process as it is currently used is prone to abuse in that the FDA is not able or willing (not sure which) to enforce post-approval actions on drugmakers in a timely fashion.

The author's example of Makena shows that over a decade can pass without showing medical efficacy in follow-up trials before marketing authorization is pulled. The author doesn't go into detail, merely linked to it, but the conditional approval granted by the EMA is much more fit for purpose. Under that process, the conditional approval is just granted for one year and must be renewed each year. I have not worked on this renewal process personally, but from experience interacting with the agencies before, they would be looking for material progress towards meeting any stated post-approval obligations. This process gives the EMA an annual chance to pull a product if there is ambiguous or no demonstrated clinical effect or if the adverse events are more severe or common than anticipated.

As an aside, I found it interesting that the impending Leqembi (lecanemab) accelerated approval is what inspired this article. Leqembi's predecessor, Aduhelm (aducanumab), was granted accelerated approval, but was so poorly received by the market/hcp's/insurance companies, that it might as well have not been approved at all.

[–] [email protected] 2 points 1 year ago

Thank you! If I am understanding right, I think my guess was pretty bang on. Fig. 3b shows the energy dissipation from the center of the vortex blob moving outward and shows a steep drop off past where they define their edge (brown line).

Also, thank you so much for the extension recommendation! I have journal access through work for journals I go to frequently, so I forget about arxiv sometimes.

[–] [email protected] 2 points 1 year ago (2 children)

I am not in academia any longer, so I don't have access to the full paper, but I would be really curious about the boundary conditions they see. They claim to have a region of isolated turbulent mixing, however, this would mean that they no longer have a no-slip boundary layer, something that I find hard to believe in a fully fluid system like this. Instead, I imagine the best they could likely do is have a boundary region over which the Reynolds number decreases rapidly as you move from the turbulent region to the non-turbulent region.

As an aside, this reminds me of some really cool research that a friend of mine did back in grad school which is kind of like the inverse of this. They created an active system in which turbulent mixing was bound to the surface of a vesicle (video)

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