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
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.
Jan 9, 2024 update
According to an email yesterday, Vitality will publish primary outcome data in Q3 2024.
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.
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.
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.
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It is again an U, no doubt.
we have now at least 36 studies…
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.
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…
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.
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).
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.
1905 entdeckte Nettie Stevens das Y Chromosom und die geschlechtsgebundene Vererbung. Wenn das 2023 in Frage gestellt wird, kann man nur auf das lange TAZ Interview aus dem letzten Jahr mit Alexander Korte weiterleiten
Die neurobiologische Forschung ist definitiv den Beleg schuldig, dass Geschlechtsidentität genetisch bedingt sein könnte. Auch aus der Sicht der Entwicklungspsychologie ist es abwegig, davon auszugehen, dass Identität etwas ist, mit dem man zur Welt kommt. Aus meiner Sicht ist Identität stets das Resultat einer individuellen Bindungs- und Beziehungs- und auch Körpergeschichte.
It is an interesting question – does social distancing influence later allergy ? Lawler et al. in November 2021
report the impact of COVID‐19 lockdown in 365 Irish babies at 6 months of age enrolled in the CORAL study. These were a subset of 3773 infants born in two participating major maternity hospitals in Dublin between March and May 2020. Unfortunately only 10% of children participated, so families were self-selected. Allergic rhinitis was common in both mothers (36%) and fathers (30%) which is higher than reported by Allergy Ireland (26%) and explained by the authors that parental allergy is “higher than the general population, which may have contributed to parental desire to enrol in this study.”
A follow-up in March 2022 in 344 children consecutively shows higher food allergy (4.7% vs 3.5%, NS) when compared to an earlier cohort (BASELINE 2008). Atopic dermatitis increased of 15.5% in the BASELINE study to 25.3% in CORAL (no P reported) which is not unexpected given the interest of parents in an allergy study.
Maybe a short questionnaire at 2026 school entry would be informative than the current study? Nevertheless the authors needed now to analyze their stool samples sitting in the shelves. This is the content of the March 2023 preprint that has just been published. There may be an association of some bacteria with atopic dermatitis but in the end it is a useless result as the strongest risk factors for atopic dermatitis – parental history and/or FLG mutations – are missing from the presented models
At the end we can safely assume that the 2020 lockdown did not have any influence on allergy prevalence in Ireland.
The final statement came by email this morning statement-from-the-organising-committee-of-the-third-international-summit-on-human-genome-editing
Remarkable progress has been made in somatic human genome editing, demonstrating it can cure once incurable diseases. To realise its full therapeutic potential, research is needed to expand the range of diseases it can treat, and to better understand risks and unintended effects. The extremely high costs of current somatic gene therapies are unsustainable. A global commitment to affordable, equitable access to these treatments is urgently needed. Heritable human genome editing remains unacceptable at this time.
And well, my subjective selection of the best talks is also here (unfortunately the video quality is poor and there is no way to timestamp the URL, so you have to recall the time marks below).
As always masterful moderation by Robin Lovell-Badge including the fire alarm ;-) My top 5 talks are
(Jennifer Doudna 4:25:17 was a bit disappointing when talking about my research field involving asthma and microbiome.
The two father mouse of Katsuhiko Hayashi that gained wider attention [Guardian, Nature, …] is found at 3:14:02.
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