Category Archives: Allergy

Censorship in science

24.11.2023 admin

Popular narratives suggest that scientific censorship is driven by authoritarian officials with dark motives, such as dogmatism and intolerance. Our analysis suggests that scientific censorship is often driven by scientists, who are primarily motivated by self-protection, benevolence toward peer scholars, and prosocial concerns for the well-being of human social groups.

Having experienced also censorship with a scientific hypothesis I would rate the arguments just by gut feeling like so

Allergy

Die Asthma-Kinderheilstätte Bad Reichenhall

15.11.2023 admin

Von den Ereignissen in der 1986 geschlossenen Asthma-Kinderheilstätte in Bad Reichenhall höre ich heute morgen zum ersten Mal in einem Podcast von BR24. Der Missbrauch geht dabei weit über die unsäglichen Verschickungsheime der 50er und 60er Jahre hinaus, die für Ihre Erziehungsmethoden berüchtigt waren. Continue reading Die Asthma-Kinderheilstätte Bad Reichenhall →

Allergy, Philosophy, Software

The problem is getting exponentially worse

14.11.2023 admin

Last Word on Nothing writing about ChatGPT

What initiated my change of mind was playing around with some AI tools. After trying out chatGPT and Google’s AI tool, I’ve now come to the conclusion that these things are dangerous. We are living in a time when we’re bombarded with an abundance of misinformation and disinformation, and it looks like AI is about to make the problem exponentially worse by polluting our information environment with garbage. It will become increasingly difficult to determine what is true.

Is “derivate work” now equal to reality? Here is Geoff Hinton

“Godfather of AI” Geoff Hinton, in recent public talks, explains that one of the greatest risks is not that chatbots will become super-intelligent, but that they will generate text that is super-persuasive without being intelligent, in the manner of Donald Trump or Boris Johnson. In a world where evidence and logic are not respected in public debate, Hinton imagines that systems operating without evidence or logic could become our overlords by becoming superhumanly persuasive, imitating and supplanting the worst kinds of political leader.

At least in medicine there is an initiative underway where the lead author can be contacted at the address below.

In my field, the first AI consultation results look more than dangerous with one harmful response out of 20 questions.

A total of 20 questions covering various aspects of allergic rhinitis were asked. Among the answers, eight received a score of 5 (no inaccuracies), five received a score of 4 (minor non-harmful inaccuracies), six received a score of 3 (potentially misinterpretable inaccuracies) and one answer had a score of 2 (minor potentially harmful inaccuracies).

Within a few years, AI-generated content will be the microplastic of our online ecosystem (@mutinyc)

Allergy, Genetics, Joke

Did the Neanderthal hominid suffer from asthma?

4.11.2023 admin

Maybe this is a largely irrelevant question – basically as relevant as building a museum on top of some Neanderthal 1 bones – as we can never reliable predict a complex trait just by genetics and some broken bones.

Already Virchow was wrong believing that the “Neanderthaler” was a modern human suffering from senility and malformations … Anyway, new research wants to answer this question:

Here we show that of the 51 asthma-associated loci that we surveyed, 39 carry variants that were derived in the Neanderthal lineage. The shared sequences suggest that some asthma variants may have originated from the Neanderthal genome after admixture and subsequent introgression into the Eurasian population. Of note, one variant, rs4742170, previously linked to asthma and childhood wheezing, was shown in a recent study to disrupt glucocorticoid receptor binding to a putative IL33 enhancer, and elevate enhancer activity of this key asthma gene.

Sorry to say that there are now >3000 variants associated with asthma including at least 354 coding variants while the authors used only 51 loci in their study derived from an outdated 2016 review. So we could already end up writing up a review here but the paper continues with omissions and misunderstandings

most of the Neanderthal-derived SNPs we identified, including those near the lead variants for the asthma GWAS signals, are in non-coding regions of the gene

Unfortunately we need to be exact here – not just “near” some variants. The SNP rs4742170 that they showed from the EVA database had indeed the T allele in the Vindija Neanderthal

https://bioinf.eva.mpg.de/jbrowse/?loc=9%3A6242936..6242991&tracks=hg19_1000g%2Cvindija_hc_bam%2CAltai

but unfortunately when going then to dbSNP it is also found in the African genome.

https://www.ncbi.nlm.nih.gov/snp/?term=rs4742170

So the whole conclusion

Our findings here … add asthma to the list of diseases that could be traced back to Neanderthals

is wrong.

Allergy, Genetics, Joke, Software

Google Scholar ranking of my co-authors is completely useless

23.10.2023 admin

The title says it already while a new r-blogger post helped tremendously to analyze my own scholar account for the first time.

I always wondered how Google Scholar ranked my 474 earlier co-authors. Continue reading Google Scholar ranking of my co-authors is completely useless →

Allergy, Vitamins

No news from the trials that I am waiting for

9.10.2023 admin

I tried to update today an earlier blog post but neither VIDI (started in 2012) nor VITALITY (started in 2014) posted or published any allergy result so far.

VITALITY seems to have some 2,681 participants under observation according to their study website while VIDI published only unrelated stuff about 801 participants.

https://classic.clinicaltrials.gov/ct2/history/NCT02112734?B=7&A=8&C=merged#StudyPageTop

If the recruitment phase lasted 2-3 years, the observation phase 1 year, results could have been published within 4 years. Instead the study is prolonged now until December 2028(!) while adding 26(!) secondary outcome measures. Two emails to previous and current PI about that remain unaswered.

It is a pain if public funded studies do not publish their results.

Allergy, Genetics, Vitamins

sun + wind + allergy

7.10.2023 admin

New work by Harvard colleagues shows how sunshine hormone D constrains inflammation by modulating the expression of key genes on chr17q. It builds on earlier collaborative work on the vitamin D receptor in 2004 (see their ref 5) as well on my annotation of IKZF3 (aka aiolos aka god of winds) in 2008 and again in 2022.

While our focus on allergy development was on vitamin D supplementation of newborns, the interest of Weiss et al. was on vitamin D deficiency in pregnancy. Vitamin D deficiency may not be attributed to the rise of the asthma and allergy epidemic although this remains the never ending obsession of Weiss et al.

Nevertheless, also a wrong hypothesis may lead to new insights. IKZF3 clearly is a key player where more recently heterozygous missense/LOF variants have been found in families with B-lymphopenia and EBV-associated lymphoma while the allergy proning effect is more in the 5-prime region.

The new study shows (again) that cholecalciferol suppresses the activation of the IL-2 pathway. But what is the net effect of artifical cholecalciferol exposure on naive T cells? Unfortunately the new paper narrowly focuses on cytokine production in Th2 cells only and even misses the famous Cantorna review that clearly says

Since 1983 it has been described that 1,25(OH)₂D inhibited T cell proliferation and the secretion of select cytokines after mitogen stimulation. Moreover, 1,25(OH)₂D directly inhibited IL-2 and IFN-γ transcription [17,18]. More recently 1,25(OH)₂D has also been shown to inhibit IL-17 secretion by Th17 cells. The effects of 1,25(OH)₂D on Th2 cells is more controversial with evidence that 1,25(OH)₂D inhibits IL-4 transcriptionally as well as evidence that 1,25(OH)₂D upregulates IL-4 in mouse and human T cells.

So we need to rephrase the finding of an “immune protective effect of vitamin D in allergic lung inflammation” to an overall “immune suppressive effect of vitamin D” which is basic textbook knowledge. Unfortunately the early origin of allergy induction remains a mystery.

Allergy, Philosophy

Der Grenznutzen von Wissenschaft

27.09.2023 admin

Kann man:frau unbegrenzt Wissen schaffen?

Die Wirtschaftswissenschaften beschreiben den Grenznutzen wo der Zuwachs nur noch durch den Einsatz enorm hohe Aufwands erzielt werden kann – wenn trotz des hohen ökonomischen Aufwandes der Nutzenzuwachs gering ist oder sogar gegen Null geht.

Der Grenznutzen liesse sich im Prinzip auch von der DFG bestimmen, von Universitäten und Forschungsorganisationen wenn sie nur Interesse daran hätten.

Haben Sie aber nicht.

Allergy, Software

Data security nightmare

11.09.2023 admin

A Mozilla Foundation analysis

The car brands we researched are terrible at privacy and security Why are cars we researched so bad at privacy? And how did they fall so far below our standards? Let us count the ways […] We reviewed 25 car brands in our research and we handed out 25 “dings” for how those companies collect and use data and personal information. That’s right: every car brand we looked at collects more personal data than necessary and uses that information for a reason other than to operate your vehicle and manage their relationship with you.

Allergy

Mann kann es nicht oft genug sagen

5.09.2023 admin

https://twitter.com/ApothekerDer/status/1696527768895520863

Allergy, Password

Martha Study

28.08.2023 admin

This content has restricted access, please type the password below and get access.

Allergy, Vitamins

Second look: Again U-shaped vitamin D effects

27.08.2023 admin

It is again an U, no doubt.

we have now at least 36 studies…

Allergy

PPPR

16.08.2023 admin

PPPR is not only the abbreviation of “pandemic preparedness prevention research” but also of “post publication peer review”. PPPR is particular important in a scenario described in an excellent commentary of an excellent article that highlights the strategy

for a “team of rivals” in which you “invite your academic rivals to work with you.” It still depends too much on the goodwill and honesty of people with too much to lose. Also, Kahneman, who is quoted/paraphrased, seems to be missing the point when he says that “With competing hypotheses and theories in play, the rivals will quickly spot flaws such as hypothesis myopia, asymmetric attention or just so storytelling, and cancel them out with similar slants favouring the other side.”

No, they wont’t, they would have to leave the club. Without independent PPPR any bias cannot be discovered as can be seen in the classical examples of synchronized groups in GWAS or farming studies – crushing opponents by hugging.

Allergy

Farming and allergy

7.08.2023 admin

Hopefully the thread here on “farming and allergy” is now coming to an end. I tried to refute it for many years – last attempt in 2020

the main objection against the farming hypothesis is the interpretation of a negative statistical association as a “protective” effect. Only after thorough exclusion of alternative explanations, this interpretation may be justified.

but unfortunately missed another paper from the literature that had already been published in 2011, sorry for that.

With environmental exposures aside, at least 2 profound differences between farming and nonfarming families could be a threat to the validity of such investigations. One of these is the long-term selection of traits and genes in favor of the demanding living conditions of farmers because the agricultural lifestyle is often handed down within families. Referring to the “healthy worker effect,” we could expect certain disadvantages to be underrepresented in a farming population, giving rise to the concept of a “healthy farmer effect.”

Also the second point of Grabenhenrich has never been assessed

The other area expected to be different when comparing farming and nonfarming families constitutes behavioral patterns, lifestyle, and knowledge. For example, “soft factors,” such as health care use, symptom perception, and labeling, as well as access to and interest in health-related information, are most likely to be distributed dissimilarly. This disparity, in turn, could severely affect the response pattern in studies basing their case definition mainly on questionnaires. A temporal shift of these soft factors toward increased cautiousness and awareness has been assumed to contribute to the worldwide increase in symptoms of allergic diseases and, to a lesser extent, to the increase in clinically apparent disease.10, 11 Why should such a change be uniform in all parts of a population? Particular subgroups might be susceptible to catch up more rapidly. This phenomenon could be studied by identifying outliers in otherwise homogenous populations.

in the hope that journalists and politicians will never find it?

Is this “pioneering epidemiology” as judged by MP Dr. Söder?

Promoting a stolen idea (the original was published in German only) where the source was never cited?

Is it any good science ignoring all objections?

True heroes in epidemiology and public health are Semmelweis, Snow, von Pettenkofer, Doll & Hill, Hesse & Rehn but not a MD who can not even explain an Odds Ratio…

Allergy, Genetics

An update on the asthma exome

12.05.2023 admin

Here is a quick update on some genes of my recent asthma exome paper coming now from the 1 M exome paper published yesterday as a preprint.

loss of function variants IL1RL1. https://rgc-mcps.regeneron.com/gene/IL1RL1, 12 May 2023

Also ClinVar shows that the IL33 receptor is not “essential” making anti IL33 receptor antibodies like etokimab, itepekimab, tozorakimab a safe therapy although not being effective in any LOF mutation carrier.

The most interesting thing in the preprint is in supplemental table 2 with the s-het values for 16,704 genes. From that table I have selected my favorite target IL33 receptor together with TLR1, ALOX15, GSDMA, IL13 and IKZF3 ( BTNL2 could not be found in the list).

asthma exome https://rgc-mcps.regeneron.com/gene/IL1RL1, 12 May 2023

IKZF3 would be dangerous to be touched (see my 2008 commentary) while in the 2022 exome paper I also found only protective variants in the 5′-UTR but not any LOF variant – probably as IKZF3 is the only essential gene in the list.

So what’s next? I am still thinking how to reduce my exome set to the causal variants as half of the mutations are probably LD artefacts. And well, it would be super interesting to examine now two extreme inbred populations for their mutation spectrum, loosing either asthma variants by healthy (Amish) or diseased founders (Tristan da Cunha). Unfortunately there is little hope that this will happen – current science is built more on competition than collaboration.