

so good: gastonsanchez.com Continue reading The best dataRtists
I will have a paper in the next issue of the MMW describing a case report of Ciguatera in Cienfuegos / Cuba. Seems to be a common phenomenon there but unfortunately there is nothing in the Cuba guide books so far.
The pathology is extremely interesting – sodium channel activation by P-CTX. I only wonder why there are no therapeutic attempts with long-lasting class Ia aNa channel blockers Chinidin, Procainamid, Ajmalin, Disopyramid, Propafenon, Prajmalin. Or valproate for CNS activity.
When working for an exhibition in 2017, I found a new R library that allows nearly every image modification you could think of.
install.packages("magick")
library(magick)
magick_config()
gives you
image_read(path, density = NULL, depth = NULL)
image_write(image, path = NULL, format = NULL, quality = NULL, flatten = FALSE)
image_display(image, animate = TRUE)
image_browse(image, browser = getOption("browser"))
image_append(image, stack = FALSE)
image_average(image)
image_coalesce(image)
image_flatten(image, operator = NULL)
image_fft(image)
image_map(image, map, dither = FALSE)
image_montage(image)
image_morph(image, frames)
image_mosaic(image, operator = NULL)
image_join(...)
image_info(image)
image_animate(image, fps = 10, loop = 0, dispose = c("background","previous", "none"))
It’s always difficult if you can’t see all calendar entries on the road. So I am setting up new dates at wjst.de/dudel, cut + paste the subscription link to the Nextcloud/Owncloud calendar web frontend.
“Doodle” dates will then magically appear on all other devices.
I very much liked the “Window of Opportunity” in the Nestle Nutrition Workshop Series 61, published by Karger in 2008. Page 180 has an interesting account of the hygiene hypothesis:
Dr. Bier: … The other is the issue of the hygiene hypothesis, the cleaner environment. We are just in a somewhat less dirty environment, we are not in a clean environment, and that is the problem I have with that particular approach.
So, I am not alone
Dr. Barker:… I am guilty of inventing the term “hygiene hypothesis” as an explanation of the epidemic of appendicitis that followed the introduction of running hot water into housing of Western countries.
According to Sozanska et al. the hygiene hypothesis has more fathers
In 1970, Peter Preston1 posed the following question: ''Is the atopic syndrome a consequence of good hygiene?'' If this was the case, he argued that ''the manifestations of atopy . would have appeared in given areas only after standards of hygiene . had been raised to high levels.''
while David Strachan calls it a misnomer since I know him. The last occasion was in the BMJ in August 2014
As the authors correctly point out, the term “hygiene hypothesis”, which is often attributed to my BMJ 1989 paper, is actually shorthand for a line of argument established much earlier. When presenting my own work, I regularly remind my audience that the ideas presented in the BMJ 1989 paper were inspired by David Barker’s publications on acute appendicitis a year or two before. However, as the authors acknowledge, Barker’s “hygiene hypothesis for appendicitis” was in turn influenced by earlier thinking.
I also recount that the inclusion of “hygiene” in the title of my paper (along with “hay fever” and “household size”) owed more to an alliterative tendency than to my aspiration to claim a new scientific paradigm. What interested me over the subsequent years was how, after initial disdain on grounds of implausibility, the immunological community enthusiastically endorsed the concept of the “hygiene hypothesis” as soon as they had proposed a cellular mechanism to explain it!
[…]
Indeed, the frustration over 25 years of epidemiological and immunological investigation is that so little progress has been made in identifying the biologically relevant exposures which “explain” the frequently replicated epidemiological observations linking allergic sensitisation and atopic disease (inversely) to family size and to “unhygienic” environments such as farming, separately and in combination…
Even with thousands of studies, one of the most basic questions in vitamin D research is being unanswered. Low serum 25(OH)D3 – is it reverse causation or a true risk factor? As plasma 25(OH)D3 can be easily determined, it became the standard measurement for vitamin D supply. Unfortunately numerous other factors – season, genetics, sex, age, race – all influence serum 25(OH)D3 levels.
Then in 2011 David Reid et al. published a paper of 25(OH)D3 following up changes during acute inflammatory response after knee surgery. In essence, plasma concentrations of 25(OH)D decreased after an inflammatory insult and are not a reliable measure of 25(OH)D status in subjects with a significant systemic inflammatory response. This observation is being confirmed in the meantime by 2 further studies (Barker 2012 and Waldron 2013). I think this is a clear result now.
I have never been convinced that Mendelian randomization will help here at all – as done in earlier studies. These are clearly situations where Mendelian randomization does not work as shown by Smith and Ebrahim back in 2004
-failure to establish reliable genotype (seldom)
-intermediate phenotype genotype-disease associations (frequent)
-confounding of genotype-intermediate phenotype-disease associations (unclear)
-horizontal pleiotropy and multi-functional genes (frequent)
-canalization and developmental compensation (unclear, but expected to be frequent)
-Lack of suitable polymorphisms for studying modifiable exposures of interest (no more a problem)
So, 25(OH)D3 is more an acute phase indicator where low levels in inflammatory diseases is effect not a cause but an effect. A recent review concludes therefore
Reversed causality is described as a possible factor interfering with the correct assessment of the Vit D status. It is concluded that further widespread fortification of foods and stimulation of supplement use should be reconsidered.
It is, however, unclear if low 25(OH)D levels is due to an increased demand (as the vitamin D lobby argues), a shift in free/bioavailable metabolite by hemodilution, binding protein capacity (what I am expecting) or just some unknown further factors.
Ein einprĂ€gsames Bild. Lady Gaga, ĂŒbernĂ€chtigt, am Aussenspiegel eines Trucks hĂ€ngend, mit einem Schild in der Hand “Love trumps hate”.
Was das Wahlergebnis mit Wissenschaft zu tun hat? Vielleicht niedrigere StudiengebĂŒhren? Vielleicht mehr Geld fĂŒr Penn State? Sicher erstmal Stundentendemos an der WestkĂŒste.
Sind wir nun fehl “am Platz in unserer Social-Media-Zerrwelt, in der bildungsferne Reality-Stars mehr Macht haben als Intellektuelle”? Wo Populismus mehr Ăberzeugungskraft als gute Argumente?
Wir werden abwarten mĂŒssen.
Outstanding discoveries are often preceded by publications of less memorable impact. However, despite the increasing desire to identify early promising scientists, the temporal career patterns that characterize the emergence of scientific excellence remain unknown [..]. We find that the highest-impact work in a scientist's career is randomly distributed within her body of work. That is, the highest-impact work can be, with the same probability, anywhere in the sequence of papers published by a scientist-it could be the first publication, could appear mid-career, or could be a scientist's last publication. This random-impact rule holds for scientists in different disciplines, with different career lengths, working in different decades, and publishing solo or with teams and whether credit is assigned uniformly or unevenly among collaborators.
What does this mean? If high impact research is being randomly distributed, that means that research success cannot be planned, neither by a scientist, nor by a research or funding organization. It means that all the overhead money that goes into reviews and organization is being lost if their goal is being “excellence” and not just building a broad research landscape with good weather conditions.
More references www.spiegel.de/wissenschaft / Quantifying the evolution of individual scientific impact How much of your publication success is due to dumb luck? New tool ranks researchers’ influence
More recently, I have updated http:/cycleplanner.wjst.de with many more custome layers. It’s a bit cumbersome to find the best data sets out there while using it in leaflet is usually straightforward.
Openstreetmap items work great with the overpass api which has a bit complicated syntax. Here is an example of an OR (union) query
var fuel = new L.OverPassLayer({
query: "(node['amenity'='fuel'](BBOX);node['amenity'='fast_food'](BBOX);node['amenity'='kiosk'](BBOX););(._;>;);out;"
});

Presseschau Welt
Pöppel: “Nach meiner EinschĂ€tzung sind sehr viele der Erstsemester gar nicht studierfĂ€hig. Es ist extrem frustrierend zu sehen, was da alles an grundlegendem Wissen fehlt. Eigentlich mĂŒssten sich da die Hochschullehrer auf die zehn Prozent Besten konzentrieren. Durch die Verschulung der UniversitĂ€ten geht das aber nicht. Der Bologna-Prozess ist eine Katastrophe. Die meisten Studierenden belegen nur noch Kurse, wenn die betreffenden Scheine vorgeschrieben sind. Das fĂŒhrt dann im doppelten Wortsinn zu einer Scheinbildung.”
Presseschau SPON
Auch in der Vorlesung habe ich oft das GefĂŒhl: Da wurde auswendig gelernt und abgespult. Die verschulten BachelorstudiengĂ€nge fördern diese passive Lernhaltung.
Presseschau Der Tagesspiegel:
Das Promotionsrecht an Fachhochschulen - das nĂ€mlich ist die "Hochschule Fulda" - ist ebenso ĂŒberflĂŒssig wie schĂ€dlich. Unnötig ist es, weil mit der Konstruktion der kooperativen Promotion dem Anliegen, befĂ€higten Absolventen von Fachhochschulen den Weg zur Promotion zu ermöglichen, entsprochen wird. SchĂ€dlich ist es, weil damit das deutsche Wissenschaftssystem durcheinandergerĂ€t.
…
Es wird ohnehin zu viel “herumpromoviert”
Promotionen sind durch PlagiatsaffĂ€ren in Misskredit geraten; auĂerdem wird zu viel ĂŒber nicht relevante Themen "herumpromoviert". Wenn jetzt auch noch Institutionen und Fachgebiete hinzukommen, ist dies der falsche Weg. Eher sollte das Promotionsrecht eingeschrĂ€nkt werden.
…
Sind es zunĂ€chst einzelne Promotionszentren, die mit dem Recht ausgestattet werden, den Dr. zu verleihen, wird bald jede kleine Klitsche zur Doktor-Schmiede. Aus PrestigegrĂŒnden wird davon auch reichlich Gebrauch gemacht werden.
Presseschau SPON II
SpĂ€testens seit den UniversitĂ€tsreformen im Zuge des Bologna-Prozesses, der eine europĂ€ische Vereinheitlichung bringen sollte, ĂŒbernimmt die Promotion eine undankbare Scharnierrolle zwischen einer Post-Bologna-RealitĂ€t im Studienalltag – der in diesen Tagen ĂŒberall wieder beginnt – und dem Humboldt’schen Ideal von Wissenschaft. Ein bis ins Detail ausdefiniertes Studium, das schnell fit machen soll fĂŒr den Arbeitsmarkt, trifft auf eine extrem uneinheitlich organisierte UniversitĂ€tswelt. Bei der Promotion mĂŒssen diese inkompatiblen Vorstellungen von Wissen und Wissenschaft irgendwie zusammenfinden; mit gravierenden Folgen nicht nur fĂŒr die Promovierenden, sondern auch fĂŒr die Produktion von Wissenschaft.
Was passiert ist: Am Fundort der sterblichen Ăberreste von Peggy Knobloch in einem WaldstĂŒck wurde 15 Jahres spĂ€ter DNA gefunden, die mit dem Mikrosatelliten Muster Uwe Böhnhardts ĂŒbereinstimmt. Eine journalistische Sensation, die beiden bekanntesten KriminalfĂ€lle in Verbindung zu bringen! VerblĂŒffend wie schnell hier Kontamination ausgeschlossen wurde und das obwohl es dieselben Ermittler und dieselben Labore waren, welche mit der DNA gearbeitet haben?
Wie erst jetzt bekannt wurde, handelte es sich bei dem zustĂ€ndigen Chefermittler im Fall Peggy als auch beim Leiter der spĂ€teren “SoKo Bosporus” im Fall der NSU-Morde um ein und dieselbe Person: Den mittlerweile pensionierten Wolfgang Geier.
Die Ermittlungspanne im “Heilbronner Phantom” durch kontaminierten WattestĂ€bchen ist gerade mal 7 Jahre her. Das sollte auch ein emeritierte Rechtsmediziner im wohlverdienten Ruhestand wissen. Den Vogel aber abgeschossen hat die FAZ mit ausgefeilten Theorien von Böhnhardts Verbindung zu Kindermorden.

Doch es geht noch dĂŒmmer, so der ZEIT Titel heute:

Kontamination ist nicht schier unglaublich, sondern die naheliegendste ErklĂ€rung. Vielleicht hĂ€tte aber auch das forensische Labor mal etwas innovativeres machen mĂŒssen, als immer nur die ewig gleichen Panels zu fahren. Zum Beispiel Degradation untersuchen, ein bisschen weiter sequenzieren, miRNAs, Methylierungsmuster bestimmen, 17S RNA, etc., bevor man an die Presse geht?
Es gibt eine kindliche Erkrankung, die nur bei Vitamin D Prophylaxe auftritt: die idiomatische infantile HyperkalzÀmie Lightwood (OMIM 143880). Die Ursache, eine oder mehrere Mutationen im Vitamin besser Hormon D abbauenden Enzym CYP24A1, wurden erstmals durch Schlingmann 2011 charakterisiert. Diese Kinder leiden an einer HyperkalzÀmie, Wachstumsverzögerung, Erbrechen, Dehydration und Nephrokalzinose. Mittlerweile sind noch mehr Mutationen bekannt:
| Schlingmann, NEJM 2011 | Clinvar 2016 | Funktion |
|---|---|---|
| A475fsX490 | pathogen | |
| E143del | NM_000782.4(CYP24A1):c.428_430delAAG (p.Glu143del) GRCh38: Chr20:54172928-54172930 | pathogen |
| E151X | NM_000782.4(CYP24A1):c.451G>T (p.Glu151Ter) GRCh38: Chr20:54171669 | pathogen |
| L409S | NM_000782.4(CYP24A1):c.1226T>C (p.Leu409Ser) GRCh38: Chr20:54158096 | schwach pathogen |
| R396W | NM_000782.4(CYP24A1):c.1186C>T (p.Arg396Trp) GRCh38: Chr20:54158136 | pathogen |
| R159Q | NM_000782.4(CYP24A1):c.476G>A (p.Arg159Gln) GRCh38: Chr20:54171644 | pathogen |
| E322K | NM_000782.4(CYP24A1):c.964G>A (p.Glu322Lys) GRCh38: Chr20:54162743 | pathogen |
| c.445_449(+1) delATCCTg-het | pathogen | |
| NM_000782.4(CYP24A1):c.1039C>T (p.Gln347Ter) GRCh38: Chr20:54159075 | vermutlich pathogen | |
| NM_000782.4(CYP24A1):c.1426_1427delCT (p.Cys477Leufs) GRCh38: Chr20:54157395-54157396 | pathogen |
Offensichtlich gibt es hier auch benigne Formen. Ob ein Mutationsscreening vor einer Vitamin D Prophylaxe Sinn macht (“PrĂ€zisionsmedizin“)? Dazu mĂŒsste man erstmal die PrĂ€valenz der CYP24A1 Varianten in der Bevölkerung kennen, Schlingmann schĂ€tzt zumindest 100 FĂ€lle / Jahr in England.
"I am very astonished that the scientific picture of the real world around me is very deficient. It gives us a lot of factual information, puts all of our experience in a magnificently consistent order, but it is ghastly silent about all and sundry that is really near to our heart, that really matters to us. It cannot tell us a word about red and blue, bitter and sweet, physical pain and physical delight; it knows nothing of beautiful and ugly, good or bad, God and eternity. Science sometimes pretends to answer questions in these domains, but the answers are very often so silly that we are not inclined to take them seriously." - Erwin Schroedinger