In recent years, U.S. politicians have selectively framed European healthcare policies to justify restrictions on transgender care, seizing on a handful of conservative policies to claim that “Europe is pulling back.” The most extreme example, the United Kingdom’s Cass Review, has been wielded to justify a near-total ban on puberty blockers and even cited in U.S. Supreme Court arguments. But new medical guidelines from Germany, Austria, and Switzerland tell a different story. These countries have reaffirmed the importance of gender-affirming care for transgender youth and issued sharp critiques of the Cass Review, calling out its severe methodological flaws and misrepresentations.

The guidelines, released Friday in German, span more than 400 pages and represent the collective expertise of 26 medical and psychotherapeutic professional organizations, along with two self-representation organizations from Germany, Austria, and Switzerland. Their stated goal is "to provide guidance to all professionals in the healthcare system who deal with young transgender and non-binary people for the best possible professionally informed care based on the current state of medical knowledge."

From the outset, the guidelines explain the importance of gender affirming care, stating that there are “no proven effective treatment alternative without body-modifying medical measures for a [person with] permanently persistent gender incongruence.”

Importantly, the guidelines were developed with those who are experts in the fields of gender affirming care having a voice at the table, unlike the Cass Review: “Current guidelines, which are published by medical societies, were predominantly developed by clinical experts for the field of application and are based on an integrated synthesis of the assessment of available evidence and the broadest possible expert consensus.”

The guidelines directly recommend puberty blockers and individualized, prioritized care for transgender youth undergoing physical changes. In the section on puberty blockers, the guidelines state with a strong recommendation: “If, in individual cases, the progressive pubertal maturation development creates a time pressure in which health damage would be expected due to longer waiting times to avert irreversible bodily changes (e.g. male voice change), access to child and adolescent psychiatric or psychotherapeutic clarification and medical treatment options should be granted as quickly as possible.”

The guidelines also deliver a strong critique of the Cass Review, the report currently being used to justify bans on gender-affirming care in the United Kingdom and leveraged in other countries to further restrictions. German medical societies deem the Cass Review largely inapplicable to their own guidelines due to its numerous methodological shortcomings. One of their sharpest criticisms focuses on the lack of transparency regarding those who advised and produced the review, as well as the limited expertise of those involved.

“Medical professional societies were not recognizably involved in the preparation of the report. A so-called “Assurance Group” was appointed, but it was explicitly not involved in the development of recommendations for the Cass Review. There are reports that an “Advisory Board” was also established. The composition and specific contribution of this “Advisory Board” are not documented (Ruuska et al., 2024; Cass, 2024),” read the guidelines.

They also criticize the Cass Review and NHS’s recommendation of “psychotherapy” for gender dysphoria as without evidence and as potentially harmful: “Psychotherapy is recommended for co-incident disorders, for which there is already an indication due to the co-incident disorder itself. However, it is also recommended or the ‘management of [GD] associated distress.’ None of the studies included in the review in question were able to show a reduction in gender dysphoria through psychotherapy.”

The guidelines are not the only critique of the Cass Review, which has faced intense scrutiny since its release. Members of its advisory board have spoken at conferences organized by anti-LGBTQ+ hate groups, raising concerns about bias. Researchers at the Integrity Project at Yale University swiftly debunked the review, and a growing number of international medical organizations have rejected its findings. This mounting criticism has had legal consequences—just last week, a U.S. judge deemed the Cass Review unworthy of consideration in federal court.

The new German, Austrian, and Swiss guidelines mark a significant advancement for transgender healthcare in those countries, reinforcing a growing trend in Europe toward expanding, not restricting, access to gender-affirming care. They join the ranks of nations like Spain and France, which have taken more progressive stances on transgender rights, including medical care. More importantly, they dismantle the false narrative that Europe is "pulling back" on transgender care. In reality, it is the United States that stands as an outlier, with its regressive policies placing it far to the right of much of the Western world.

Salt & Straw ice cream’s Snap & Crackle Marshmallow Treats flavor returns for the final weekend of the shops’ Cereal-sly Delicious series. Only available this month, the collection includes other flavors inspired by nostalgia-inducing childhood cereals: Pots of Gold & Rainbow, Peanut Butter Brownie Cereal Puffs, Cornflake Cookies with Marionberry Jam, and OffLimit  Zombie with coconut and pandan. The ice cream that Chrissy Teigen inspired is reminiscent of marshmallow cereal treats.

“The hype around this flavor is all thanks to our friend, Chrissy Teigen,” said Tyler Makek, co-founder and head ice cream maker at Salt & Straw. “We first launched this flavor in 2019, and Chrissy became obsessed. She tweeted that she wanted even more brown butter treats inside, so of course, I went straight to our R&D test kitchen to spin and handpack custom pints with double the treats that we named, fittingly, ‘Rice Chrissys.’ ”

Snap & Crackle Marshmallow is Malek’s rendition of marshmallow brown butter treats mixed and toasted into a florentine cookie. It’s churned into a malty, toasted graham-flavored ice cream.

“We love taking a high-brow, fine-dining pastry approach to a low-brow, nostalgic ingredient like Rice Krispies,” adds Malek. “Our fans fell in love with the flavor and the fun story that ensued, so we launched it again in pints during COVID to bring a little joy back into the world. We bake the cereal into a florentine cookie recipe that is an almost perfect homemade replica of the old Rice Krispie Treat Cereal (a personal fave of mine)  and then fold it into this malty, salty ice cream.”

Teigen shared on social media that at the time, her family (she currently has four kids with singer John Legend) were rationing half-bites of ice cream because she savored it so much. Teigen’s enthusiasm led to the ice cream being featured on “The Today Show.” Demand skyrocketed. Salt & Straw was urged to churn more.

“When it wasn’t on the menu the following years, fans were so upset so of course we had to get back in the kitchen. All together this recipe has a subtly decadent texture and is oozing with nostalgia, and we can’t wait to share this with all the SNAP stans out there for a limited time!” he said.

Salt & Straw announced that Snap & Crackle Marshmallow Treats will return on Friday, March 29. The chain has 13 Southern California locations including Anaheim, Culver City, Glendale, Manhattan beach, Newport Beach, Pasadena, West Hollywood and several in Los Angeles.

Information: saltandstraw.com

Let’s look at some interesting and unusual uses of antibodies that have come along recently. We are nowhere near seeing the end of such ideas, because antibodies are almost endlessly useful: privileged protein scaffolds that can last for weeks in the blood, that come in trillions of different varieties, and that can bind to almost any species you can imagine and quite a few that we probably can’t.

Here’s a recent paper with a rare use of an “antibiotic antibody” idea. I was writing here not long ago about a new antibiotic candidate that targets Acinetobacter baumannii, which is a major human pathogen (and especially so in hospital-derived infections). This new work details the generation of an antibody to an important part of the A. baumannii outer membrane, pseudaminic acid. That’s an unusual amino-sugar compound that is not found in mammals at all, so it’s a pretty clean target.

What’s unusual about this antibody is that it seems to have a direct killing effect against A. baumannii, without involving a response from the immune system. Just binding to the bacterial surface seems to do the trick - no complement proteins or white blood cells involved. It looks like this binding event triggers aggregation of the bacteria, which (for reasons still being worked out) disrupt their metabolism and lead to oxidative stress. An injection of the antibody was protective against A. baumannii infection in a rodent model,  conferring survival (instead of 100% death) with greatly reduced bacterial loads, which is pretty interesting. It looks like major resistant strains of the bacteria would also be susceptible.

We’ll now turn to a completely different field - snakebite. The longstanding therapy for most venomous snake bites has been “antivenom”, which is just a plasma antibody (immunoglobulin) fraction from animals that have been exposed to the same snake venom (or to mixtures of them). This can be a great help, but it would be even more helpful if things weren’t quite so snake-by-snake specific, not least because snakebite victims don’t always seen the snake involved (or can’t tell the species even if they do). There’s also the problem of having an immune response to the antibody dose itself (which is often produced in horses, and those proteins can set off trouble in human patients all by themselves).

So this new paper is of great interest. The authors are targeting a family of neurotoxic peptides (three-finger alpha-neurotoxins) produced by some of the most venomous snakes in the world (the Elapidae, which include kraits, cobras, mambas, death adders, coral snakes, and many poisonous sea snakes). The neurotoxins target acetylcholine signaling in the nervous system (some at muscarinic receptors, others at nicotinic receptors), and basically shut down neurotransmission to various luxury tissues such as the heart and lungs. The team expressed sixteen variants of these toxins in cell culture and did extensive screening for antibodies that targeted the widest-ranging conserved regions in the proteins, rooting through a yeast-expression collection of about ten billion human antibody types.

They narrowed down on one particular clone (LB5_95) for its broad range of activity, but noted that it had a rather fast off-rate. An optimazation/maturation screen (running variations on that particular sequence while going to lower and lower concentrations to test for affinity improvements) led to the selection of the 95Mat5 antibody. That one was then tested against another yeast-expressed library, this one containing over 800 known three-finger neurotoxin variants, which confirmed the broad activity of the antibody. It also proved to be very selective for just these 3FTx-L toxins.

Tests in mice showed that predosing of the antibody was highly effective against bungarotoxin exposure (from kraits), from Indian spitting/monocled cobra venom, and from black mamba venom. Those are some serious snakes, and the antibody also conferred survival when it was administered after the venom doses (a much more real-world situation!) It was less effective against king cobra venom, although still better than the existing antivenom. In that case, it may have been a second family of protein toxins (snake venom metalloproteases) that did the damage.

For that reason, the authors note that 95Mat5 by itself is not going to be a universal snakebite cure - they estimate that any such dose would need optimized antibodies to the other toxin classes, like those metalloproteases, along with phopholipases and serine proteases. But it’s a dramatic step toward such a thing, and the antibody-selection methods they demonstrate seem to be a real improvement over previous efforts in this area. Good news for humans in snake-y regions - and it’s not even bad news for the snakes, when you think about it.

Originally published 26 June 2023.

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1. Is the existence of the Guinness World Records a positive or a negative for humanity on net?

2. Bragging about material possessions is low-status in much of the West, forcing people to jostle through subtle wealth cues (travel, education, hobbies, food). But then why isn’t there another level where people embrace explicit materialism again to show that they are above such things? (Or is there, and it’s just invisible to me?)

3. Say that if everyone voluntarily waited a bit longer to reproduce then after a hundred generations human life expectancy would increase by 25 years (edit: by providing selection pressure for genes that code for longevity, nothing to do with parenting). Would we be morally obligated to do that?

4. Do we focus too much on classic books/music/movies/plays/art/ideas, or too little?

5. Those lists of regrets people make at the end of life—how seriously should we take them? Profound wisdom or just how one version of yourself feels on one day?

6. Generally speaking, is human progress more limited by our ability to build/orchestrate (1) technological systems or (2) social systems?

7. What should we take from the existence of acquired tastes like spicy food or whiskey? Are they “fake”? Why aren’t we more intentional about which ones we acquire?

8. If you take an octopus with most of its neurons in its arms and you cut one of the arms off and wait three months for it to regrow, what happened to the memories in those neurons? Did you destroy arm-specific memories or make all memories vaguer or is there some redundant coding scheme where the memories will be re-cached as the arm regrows? (Considered unsporting to use the scientific literature that no doubt exists in your argument although please send it to me.)

9. Does all the excitement about GLP-1 agonists imply that the gastric bypass is underrated?

10. Take this 2x2 matrix:

    	Stuff	Spicy stuff
    Tortilla	Wrap (BAD)	Burrito (GOOD)
    Bread	Sandwich (GOOD)	Torta (VERY GOOD)

    Why does the upper-left corner exist?

11. Is there any way to opt out of the signaling/counter-signaling game? If you could do it, should you, or is that pointless neuroticism?

12. Is what we call “meaning in life” really just feeling respected and liked and important?

13. Is utility one-dimensional? That is, is there just one kind of goodness/badness in subjective experience that comes mixed with neutral flavors, or can you feel immense pain and pleasure at the same time?

14. How many attractors does the utility function landscape have? Like, say you are an AI and you can reprogram yourself at will with any CIRCUMSTANCE→REWARD mapping. Depending on the mapping, you may or may not decide to change your mapping again. Where do you stop? Are the attractors always “good” ones, or might you end up miserable but dead-set against changing?

15. Mendel was only appreciated when his results were found independently decades later. So did he really achieve anything? Should we celebrate Mendel less and Carl Correns more?

16. Is there a qualitative difference between drugs and music/games/video services? How addictive would a game have to be that we’d throw people in jail for making it?

17. Why do most people seem to hold poetry and poets in high esteem yet have approximately zero interest in reading any poetry ever?

18. Do some cultures come up with food traditions that are objectively better than others, and since yes, why?

19. How is it that 100 years after zippers were invented, the high-end zipper market is almost completely controlled by a single company?

20. Were earlier generations tougher than us? If so, what’s the best level of toughness? It’s unlikely that it’s where we are now, right?

21. Say some crazy internet people do a non-randomized non-blinded trial where some other internet people self-select to try some diet and they (the latter group) report losing a massive amount of weight—how much does this change your opinion relative to a traditional RCT where people lose 0.1% of body mass with p<.001?

22. If you accept that agriculture made life worse but hunter-gatherers had to adopt it or be vanquished, then are we going through any similar changes now?

23. Of all the people who try newfangled note-taking systems like Zettelkasten or org-mode or Roam or Obsidian or Logseq, what fraction really end up getting more value out of them than they put in?

24. Why does the West insist on “authenticity” in popular music where the performers are the songwriters? Why not specialize? Or why not insist the artist masters the music and creates the album art? Does this tradition give Western musicians more bargaining power than, say, K-pop artists?

25. If people truly understood the sacrifices that are necessary to win the Tour de France (even ignoring drugs) would that increase or decrease how much they enjoy watching it?

26. Why is pie so much better than cake and given that it is why do people continue to eat cake?

27. There seems to be a core concept of a (non-religious) “Christmas spirit”, but what is it exactly? Family? Love? Giving? Appreciation? Togetherness?

28. Whatever the Christmas spirit is, it seems pretty nonmaterialistic. So how is it that Christmas is simultaneously a colossal festival of consumption?

29. Why is Christmas such a uniquely successful cultural export?

30. Christmas is (at least partly) about togetherness and there’s strong evidence that togetherness makes us happier, so why are we less together than ever?

Rate comparison sheet posted on the Southern California Edison website

When Irvine Mayor Farrah Khan, her appointed Vice Mayor Anthony Kuo and Councilman Mike Carroll established the Orange County Power Authority (OCPA) using millions of Irvine taxpayer dollars, they promised Irvine residents that we would be receiving greener energy at a lower monthly rate than what is provided by Southern California Edison (SCE).

Mayor Khan declared that OCPA would reduce costs of electricity to Irvine’s citizens and businesses. There was also a 2020 City staff report based on OCPA data that claimed the City government itself would save money on its own $5 million per year electricity bill once the City was transferred from SCE and enrolled in OCPA.

We now know those were all flat-out lies. In fact, the City’s own electricity use was transferred over to OCPA this past April, and the City is now spending $100,000 per month more for electricity — paid for with Irvine taxpayer dollars!

One of the added benefits of clean energy is that it is cheaper. The rate comparison sheet on the SCE website reflects that — SCE customers pay on average $22 per month less for the SCE 100% renewable electricity plan. However, OCPA will be charging their customers $35.95 per month more for the same 100% renewable energy provided by SCE.

In October, every Irvine resident is being transferred from SCE and automatically enrolled in the new, more expensive OCPA plan.

From the start, OCPA has been a complete disaster! Both Khan and Carroll are paid to sit on the six-member OCPA board. They voted to hire one of their political buddies to run the agency and oversee multi-million dollar energy purchasing contracts … even though he has zero experience in the electricity field. The Power Authority’s own website has forecasted a $41 million loss in its first two years of operation and OCPA has already been fined millions of dollars by State regulators for not purchasing enough electricity to prevent blackouts.

The only member of the Irvine City Council to call out the scandal-ridden OCPA is Councilman Larry Agran. Agran’s Council colleagues spent nearly a year blocking his repeated requests for a public discussion and audit of OCPA. Unwilling to be silenced, Agran began using his 3-minutes of “Announcements” during each Council meeting to update the community on the mounting evidence of corruption at the Power Authority.

Agran has also voiced his strong opposition to the City’s decision to automatically force people into the new, more costly OCPA plan, saying: “It may be legal, but to have automatically enrolled every Irvine resident into a new, more expensive electricity plan without a vote of the people was flat-out wrong!”

To opt-out of OCPA by phone, follow these steps:

1. Have your SCE bill with you. (You will need your SCE account number.)
2. Call (866) 262-7693 and select “4” to opt-out.
3. Select “2” to continue opting-out.
4. Enter your 12-digit SCE customer number followed by the pound sign (#).
5. Enter your zip code followed by the pound sign (#).
6. Hang up after receiving confirmation you have opted-out.

The post OMG! Khan-Kuo-Carroll Electricity Tax Forces Irvine Residents to Pay 18% More for the Same Renewable Electricity SCE Provides first appeared on Irvine Community News and Views.