Category Archives: Allergy

New England Journal of Medicine Retractions

Retraction Watch says on Jan 30, 2020 that

Until yesterday the New England Journal of Medicine had retracted only 24 papers. Now that tally is 25.

While the retracted paper has been cited 190 times, here are inaccuracies in a NEJM paper that has been cited 1961 times. Full details are at PubPeer.

FIG 2C
FIG 1A

Is it justified to speak of a “protective” effect just by a  negative association?

In addition to the problems with the math, I don’t get the point – farming should be leading to a generally reduced capacity for numerous pleiotropic cytokines?

There are even reports that LPS induces TH2 dependent senstization – exactly the opposite of what this paper wants us to believe with soem cryptic smoother run over a heterogenous population.

Staatliche Milchwerbung (2 von 2)

Als Alternative zu der staatlichen geförderten Milchwerbung (siehe Teil 1), lohnt es sich, das neue Review von Willett und Ludwig  anzusehen (NEJM 13.2.2020), das Milch ebenfalls auf Gesundheitseffekte untersucht. Der Artikel – von dem wohl bekanntesten Ernährungsepidemiologen der Welt verfasst – kommt zu ganz anderen Aussagen als die staatliche bayrische Milchwerbung.

Wachstum und Entwicklung. Um die Milchproduktion anzukurbeln wurden Tiere gezüchtet, die mehr anabole Hormone und vor allem höhere IGF-1 Spiegel haben. Dazu sind die Muttertiere meist schwanger und haben hohe Progesteron und Östrogenspiegel. In der Summe führt das übr die Milch bei Kindern zu einem vermehrten Grössenwachstum. Leider wird damit aber auch der mTOR Pathway aktiviert, der Zellteilung fördert und damit nicht nur Krebs, sondern auch Schenkelhalsfrakturen und Lungenembolien begünstigt.

Knochenbrüche. Auch wenn die Korrelation mit den Frakturen nicht unbedingt kausal sein muss, so ist der Zusammenhang von wenig Milchtrinken und wenig Frakturen doch gesichert.

Übergewicht. Hier gibt es keine belegten Zusammenhänge.

Blutdruck, Blutfett, KHK. Der relativ hohe Kaliumgehalt der Milch liess vermuten, dass damit der Blutdruck gesenkt werden kann. Leider konnte das nicht gezeigt werden, dagegen scheint Milchtrinken LDL zu erhöhen was seinerseits wieder ein Risikofaktor für die koronare Herzkrankheit ist. Allerdigs gibt es keinen nachgewiesenen Zusammenhang mit der Häufigkeit von Herzinfarkten oder Schlaganfällen.

Diabetes. Hier sieht es gemischt aus: mehr Antikörper bei Typ 1 Diabetes, weniger Typ2 Diabetes.

Krebs. Sollte man vielleicht wörtlich zitieren (siehe auch 1.) um keine Unklarheiten aufkommen zu lassen:

In international comparisons, consumption of dairy products is strongly correlated with rates of breast cancer, prostate cancer, and other cancers […] In prospective cohort studies, milk consumption is most consistently associated with a greater risk of prostate cancer, especially aggressive or fatal forms, but not with a greater risk of breast cancer. Total dairy intake has been associated with a greater risk of endometrial cancer, particularly among post- menopausal women who are not receiving hormone therapy, a finding possibly related to the sex-hormone content of dairy products. […] In contrast, in meta-analyses and pooled analyses of primary data, milk consumption was inversely associated with the risk of colorectal cancer, potentially owing to its high calcium content.

Der geringer Vorteil bei Darmkrebs, wird mit einem hohen Krebsrisiko  vieler anderer Organe erkauft.

Allergien. Auch hier am besten wörtliches Zitat:

Scattered reports suggest that milk consumption may exacerbate atopic tendencies, conferring a predisposition to asthma, eczema, and food allergies. Over a period of 10 years, infants with a family history of atopy who were randomly assigned to receive hydrolyzed protein formula had a lower risk of any allergic disease and of eczema than did infants who were randomly assigned to receive cow’s milk. […] Beyond childhood, cow’s milk may precipitate asthmatic exacerbations and related conditions.

Auch wenn ich nicht an den protektiven Effekt hydroysierter Formulanahrungen glaube, so würde es ohne Milch auch keine Milchallergie geben.

Wichtig ist ein weiterer Punkt, den die bayrische Milchwebrung komplett unterschlägt, 5-10x mal mehr Treibhausgase, Wasserverbrauch und Antibiotika Resistenzen.

The effects of dairy production, particularly industrial-scale production, on greenhouse gas production and climate change, water use and pollution, and antibiotic resistance are large — potentially 5 to 10 times greater per unit of protein than the effects from production of soy foods, other legumes, and most grains.

Kein Freispruch!

“what a shit-show life-sciences have (at least partially) become”

quoting another blog from my current reading list

an application specialist …  gave a day of training on qPCR applications in general and these instruments specifically. The scientist got to a point in her presentation where she was describing frequent errors and pitfalls in qPCR methods for quantitating gene expression, and she gave about 10 different examples that started out “I visited this one lab, and upon discussing their workflow with them it turned out they were making huge error such-and-such.” At this point, I raised my hand and asked for her honest estimation of how much confidence she places in qPCR or RT-PCR data that appear in standard journals. She paused for a few seconds and then tentatively admitted “maybe 25%.”

Fake pictures and paper mills

There is an increasing awareness of faked scientific papers, not just in predatory journals but also renowned publishing companies like Wiley, Karger, Elsevier. Even German Spiegel reported now on that based on an excellent article by@schneiderleonid that is itself based on work of Indigofera Tanganyikensis, @MicrobiomDigest, @SmutClyde, and many others.

In China, clinicians are expected to publish a certain number of research papers in international journals if they want to be promoted. The easiest way is to pay a paper mill, which seem to provide a full service: an English-speaking research paper containing Photoshop-generated fake research data, in a respectable peer-reviewed journal, with your name on it.

identified by https://twitter.com/MicrobiomDigest/status/1219525169288368133
identified by https://twitter.com/MicrobiomDigest/status/1219525169288368133

The big problem is the move now from isolated ghostwriters to big paper mills:

We have also witnessed the submission of identical template‐style manuscripts to multiple journals at the same time, presumably to increase the likelihood that the manuscript will be accepted. This practice could greatly amplify the burden of paper mill manuscripts on journals and peer reviewers. A high‐throughput approach to manuscript generation in the absence of experimentation could also result in paper mill manuscripts and publications presenting with features that are rarely found in genuine manuscripts.

Asthma GWAS

http://big.stats.ox.ac.uk/pheno/biobank_22127 10Feb20

http://pheweb.sph.umich.edu/SAIGE-UKB/pheno/495 10Feb20

http://r2.finngen.fi/pheno/ASTHMA_CHILD_EXMORE 10Feb20

https://www.ebi.ac.uk/gwas/efotraits/EFO_0000270 10Feb20

some paper 2018

first genomewide linkage scan 1996

second genomewide linkage scan 1997

third genomewide linkage scan my thesis 1998

While I believe now mainly in UK Biobank, we found more than 2 decades earlier hits on chr 2, 6, 9, 12 (but missed chr17). Maybe our marker coverage at chr17 wasn’t good enough? Nevertheless the indentification was possible with just 415 individuals instead of 500,000 individuals nowadays (see asthma genetics timeline).

Ärzteblatt Literaturübersicht

Burney P, Amaral AFS. Air pollution and chronic airway disease: is the evidence always clear? The Lancet 2019; 394: 2198-2200

Atkinson RW, Butland BK, Anderson HR, Maynard RL. Long-term concentrations of nitrogen dioxide and mortality: A meta-analysis of cohort studies. Epidemiology 2018; 29:460-472

Peter Morfeld, Thomas Erren. Attributable Fraktionen und vorzeitige Todesfälle: Wichtige Klärung von Missverständnissen. Gesundheitswesen 2019; 81(05): 448-452

Tollefson J. Air pollution science under siege at US environment agency. Nature 2019; 568:15-16

Ioannidis JPA. Evidence-based medicine has been hijacked: a report to David Sackett. J Clin Epid 2016;73:82

Taubes G. The Soft Science of Dietary Fat. Science  2001:291:2536-2545

sowie die folgenden Blog Einträge.

Unbelehrbar? (6000 Tote exhumiert XXXV)

Einen mehrseitigen Kommentar, den ich im letzten Sommer an Environmental Epidemiology geschickt habe, wurde von Bert Brunekreef mit einer Email abgelehnt “das Thema sei nur von lokalem Interesse in Deutschland”. Wie ich aber erst jetzt erfahren habe, sollte das nur die Kritik mundtot machen, denn gleichzeitig wurde mit derselben Story international Politik gemacht, als im Lancet alle deutschen Kritiker pauschal diffamiert werden und ihre Stellungnahme als “fake news and denial” bezeichnet werden (Lancet vom 7.8.2019). Wer die dubiosen NO2 Studien nicht nachvollziehen kann, wird in die Nähe von Zigarettenindustrie und Klimaleugnern gesetzt.

the debate had all of the features that Farrell and colleagues discuss in relation to the misinformation campaigns on climate change or the well known strategies used decades ago by the tobacco industry.

Auch in dem Lancet Artikel wird die NO2 Mortalität noch einmal wiederholt

The scientific evidence that links ambient air pollution—in particular, fine particles (PM2.5 …) and nitrogen dioxide (NO2)—to disease and mortality was questioned by a small group of lung physicians and engineers.

Eine “kleine” Gruppe wären ein Dutzend und nicht 140 Pulmologen gewesen, dazu kommen diverse Epidemiologen und Toxikologen, die den verstiegenen Aussagen nicht gefolgt sind. Letztendlich hat auch die Leopoldina widersprochen [1, 2, 3];

Die drei aus der Arbeitsgruppe Luftschadstoffe entsandten Professoren, Martin Lohse, Wissenschaftlicher Vorstand des Max-Delbrück-Centrums für Molekulare Medizin, Manfred Hennecke, ehemaliger Präsident der Bundesanstalt für Materialforschung und -prüfung, und Jos Lelieveld, Direktor am Max-Planck-Institut für Chemie, zumindest sagten recht wenig und eher Versöhnliches zur Person Köhler. Sein Vorstoß sei in mancherlei Hinsicht sicher sogar “sinnvoll” gewesen, weil er zu einer Debatte geführt habe, hieß es. Bei Teilen seiner Kritik aber habe Köhler sich “vergaloppiert”.

Das ist eine echte Nummer, da mit dem Lancet Letter auch die Leopoldina angegriffen wird als “misinformation campaign”.

Der Bundestag hat – kontraproduktiv, aber das war zu erwarten – dann leider auch noch höhere Grenzwerte und Ausnahmeregelungen beschlossen.

A basic measurement in epidemiology is wrong

Eric Topol highlighted a WSJ feature on BMI (or body mass index). The article basically says

The idea behind BMI was proposed in 1832 by the statistician Adolphe Quetelet, who wasn’t trying to define a healthy weight but to model a bell curve or normal distribution of human body sizes. He studied heights and weights and observed that weight tended to increase not according to the cube of height but with its square. The Quetelet index was renamed the body-mass index in 1972 by physiologist Ancel Keys, but it still wasn’t meant to measure the health of individuals, only to show trends among populations.

BMI calculation is wrong as an area increases according to length squared, but volumes according to length cubed.
Maybe it would be a nice bachelor etc thesis just ask 500 passengers during one busy morning at Munich airport and correlate their BMI with the body mass measured by a millimeter wave full body scanner?

Or using a laser scanner as a colleague recommended recently to me?

Mikroskopische Anatomie (Bewusstseinsmodelle VII)

Was gibt es für Mechanismen für den interaktionalen Dualismus von Bewusstsein & Körper oder Leib & Seele? Etwa Quantenverschränkung und Kopenhagener Deutung?

Von Verschränkung spricht man in der Quantenphysik, wenn ein zusammengesetztes physikalisches System, z. B. ein System mit mehreren Teilchen, als Ganzes betrachtet einen wohldefinierten Zustand einnimmt, ohne dass man auch jedem der Teilsysteme einen eigenen wohldefinierten Zustand zuordnen kann. Im Bereich der klassischen Physik kann es dieses Phänomen nicht geben. Dort sind zusammengesetzte System stets separabel, d. h. jedes Teilsystem hat zu jeder Zeit einen bestimmten Zustand, der sein jeweiliges Verhalten bestimmt, wobei die Gesamtheit der Zustände der einzelnen Teilsysteme und deren Zusammenwirken das Verhalten des Gesamtsystems vollständig erklärt.

Physiker sind skeptisch, so Sean Carroll in einem Interview und Vortrag

oder auch Peter Clarke, der insbesondere die von Eccles favorisierte “open modules” an spezifischen Synapsen untersucht hat. Schwierig bleibt, das Konzept mit dem Energieerhaltungssatz der klassischen Physik zusammenzubringen. Noch schwieriger ist es, quantitativ die Vorgängen an den vielen Kontaktpunkten (etwa Ca, K, Na-Kanäle) mit Quantenverschränkung zu erklären, so Clarke 2004

Even if quantum phenomena could occasionally affect calcium flow through channels, it seems very unlikely that this could have a significant effect on synaptic transmission, because the numbers of calcium ions involved are sufficiently large to swamp any quantum effects. Smith has argued this in a detailed discussion of the possibility of quantum effects at synapses, stating that the number of ions involved is 10^18 – 10^19. The numbers going through a given channel at a single opening are much smaller, of the order of one thousand, but this would still be enough to swamp the effects of a 10 ms change in the channel due to quantum fluctuations.

Direkten Widerspruch habe ich bisher nicht dazu gefunden. Es beginnt da aber erst die Diskussion, siehe Jedlicka 2017

The recent rise of quantum biology as an emerging field at the border between quantum physics and the life sciences suggests that quantum events could play a non-trivial role also in neuronal cells.

und Pitts 2019, einer der rising stars aus Cambridge

The new general relativistic objection provides some support for realism about gravitational energy-momentum in General Relativity

Can criticial thinking been teached?

Yes, it can.

Already in 2017 there was a Lancet paper with the super-long title “Effects of the Informed Health Choices primary school intervention on the ability of children in Uganda to assess the reliability of claims about treatment effects: a cluster-randomised controlled trial”. The paper is extensively discussed at vox.com

Andy Oxman is obsessed with the study of bullshit health claims and how to prevent them from spreading.
For decades, he’s been trying to find ways to get adults to think critically about the latest diet fads, vaccine rumors, or “miracle cures.” But he realized these efforts are often in vain: Adults can be stubborn old dogs — resistant to learning new things and changing their minds.

So not only Germany but also Uganda has its own bullshit hypothesis.

Blaming genes for resistance to environmental stressors

This something that I always avoided in human research – blaming genes for resistance to environmental stressors.

Nevertheless a Californian group (https://doi.org/10.1371/journal.pgen.1008528) now tested 101 mouse strains for lung resistance with exposure to diesel exhaust particles (DEP). After sensitizing the animals with dust mite and aluminium they could also test metacholine hyperreactivity (AHR).

Strains that exhibited the highest lung resistance after control exposure were not necessarily the same as those with high lung resistance after DEP exposure. It is unclear which strain was used for the consecutive GWAS. Did they put all mice into one cage for that?

The metacholine AHR GWAS results are not very impressive. And there seem to be also errors, as for example the lead SNP on chr 19 (rs51547574, near IL33) is shown with different allele frequencies in text and Fig 2.  As the expression quantitative trait locus (eQTL) for Il33 is not in the lung, I think there is nothing to memorize here – IL33 is just a gatekeeper for surface integrity.

In a next step I wouldhave expected a GWAS for resistance change after DEP but FIG 3 only gives the result of Δ AHRDEP—AHRPBS data at an abitrary methacholine dose of 10mg/ml. The identifed locus could be interesting but as the LD there is rather high without any corresponding eQTL (I always wondered why there has never been a significance threshold for LD blocks, only for isolated SNPs?), the logic of the paper is broken here. Induction of lung resistance by DEP was significantly blunted in Dapp1-/- female mice? What about male Gm5105-/- Mttp-/- , and Lamtor3-/- animals?

Hopefully nobody else will now try to find diesel, ozone, NOx resistance genes in humans as this is not a a scientific but a political issue…