All posts by admin

Software

At its heart

43 folders writes:

Remember that your blog is only incidentally a publishing system or a public website. At its heart, your blog represents the evolving expression of your most passionately held ideas. It’s a conversation you’re holding up with the world and with yourself — a place where you can watch your own thoughts take different shapes and occasionally surprise you with where they end up…

wow – couldn’t say that in a better way.

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Allergy, Joke

Something in the air

New studies further question the hygiene hypothesis of allergy induction. One study shows that a household bacterial elimination strategy does not lead to more — it even leads to less asthma.

Children living in a house regularly cleaned with bleach were less likely to have asthma (OR, 0.10; CI, 0.02-0.51), eczema (OR, 0.22; CI, 0.06-0.79) and of being sensitized to indoor aeroallergens (OR, 0.53; CI, 0.27-1.02)

Another study, by designing a 16S rRNA chip, examined a snapshot of urban air in San Antonio — the aerosol harbored at least 1,800 diverse bacterial types

a richness approaching that of some soil bacterial communities

You probably know the joke that before taking a deep breath think where the air has been before…

Addendum

The ecology of human skin has now been also reported – highly diverse, well conserved but low-level interpersonal consensus: scienceblog:doi:10.1073/pnas.0607077104

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Genetics

Flip-Flop

The AJHG discusses an interesting phenomenon that I noticed too. While replicating a disease marker association the risk allele suddenly reversed which led me believe that there was an error in allele coding. As the authors of this new paper now show these flip-flop association may indeed a true positive association to a non causal variant.

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Philosophy

Delusion or poor scientific hypothesis

Delusion is a common symptom of paranoid schizophrenia ICD10 F20.0, usually combined with hallucinations (either auditory – noises or voices, visual or other perceptions of smell or taste). The most common paranoid symptoms are delusions of persecution, reference, exalted birth, special mission, bodily change, or jealousy. It has been most impressing (and harrowing) to see these patients as a medical student in Vienna at Baumgartner Höhe. Of course I visited Berggasse 19 but there have been more pioneers in Vienna like Krafft-Ebing).

We are arriving now at my main question: What is the difference between delusion and a scientific hypothesis? This question stems from a recent appraisal of the “TH17 revision” of the TH1/TH2 hypothesis by Lawrence Steinman

A historical perspective on the TH1/TH2 hypothesis is illuminating, both for its insights into important immunological phenomena and for its revelations about how groups of highly trained intellectuals, in this case immunologists, can adhere to an idea for so many years, even in the face of its obvious flaws.

He refers mainly to predictions of EAE outcomes – as an allergologist I could add more examples where the simple TH1/TH2 paradigma did not work. What is the difference between delusion and a scientific hypothesis? In my opinion the answer is context dependent as there is not so much difference – delusion will not be so persistent over time (although it is nearly impossible to convince somebody that he is captured by a delusion) while a poor hypothesis is usually more persistent (but there is a good chance to convince somebody that a hypothesis is wrong). Steinman also has some advice

We should not become fixated on the hypothesis, as if it were a ‘Law’, which in any case may fall in the face of new data that such a Law cannot explain. Most importantly, we should not ignore aberrant data that cannot be explained by a concept, whether it is deemed a Law or, more modestly, a Hypothesis. We should always be careful to explain those quirky aberrant points in the data and those annoying blemishes and flaws in the scientific theory. They may be hiding a tremendous new insight.

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Theology

Ab initio creata sum

Hymne an das Ewig-Weibliche / 19. – 25. März 1918 – Verzy / Teilhard de Chardin / An Beatrix / Ab initio creata sum…(Proverbs 8:22)

Seit Weltbeginn bin ich erschienen. Vor den Ewen (Äonen) ging ich hervor aus Gottes Händen – umrißhaft, um im Gang der Zeit an Schönheit zu gewinnen, Mitwirkerin seines Werkes.
Alles im Universum erfolgt durch Vereinigung und Befruchtung – durch Zusammenschluß der Elemente, die zueinander suchen, paarweise verschmelzen und neugeboren werden in einem Dritten.
Gott hat mich in das ursprüngliche Viele hinein ergossen als die Kraft, die verdichtet und den Dingen zu ihrer Mitte verhilft.
Ich bin das einigende Antlitz der Seienden – bin der Duft, der sie herbeilockt und sie in Freiheit und Leidenschaft mitzieht auf den Weg ihrer Einigung.
Durch mich gerät alles in Bewegung und ordnet sich zueinander.
Ich bin der Zauber, der in die Welt gemischt ist, auf daß sie sich sammle – das über ihr schwebende Ideal, auf daß sie emporsteige.
Ich bin das wesenhaft Weibliche.

Teilhard de Chardin was one of the few theologians who had also a sound scientific background. He worked in the paleontology laboratory of the Musée National d’Histoire Naturelle; in 1913 he took part in excavations in the prehistoric painted caves in the northwest of Spain – more information at

teilhard.png

His verses reminds me to Jeremiah 1:5 who already expressed 628 BC a clear view of our pre-existence: Before I formed thee in the belly I knew thee; and before thou camest forth out of the womb I sanctified thee. Is there really so much difference to what we currently believe about meiotic events?

Philosophy

Meeting abstract versus full paper

JACI has an interesting letter comparing the number of meeting abstracts and the subsequent publication of a full paper. It seems that there is a large variation from from 11% to 78% – does this really mean that at some meetings half of the talks is not worth to write them up? This would explain why at some conferences nobody is taking notes – I am usually playing sudoku, backgammon or go but have also interesting podcasts with me.

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Allergy

Say no

German Ärzteblatt has some important suggestions “Mehr Mut zum Nein-sagen” how the German healthcare system may be improved. In brief,
(1) patients need to be empowered to make their own health decision – Norwegians have on average only 3 but Germans 16 physician contacs per year
(2) during professional contact patients need more trust in doctor, nurse, pharmacist and physical therapist
(3) more money for the ill, less for the health people

sayno.png

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Genetics

NHANES R data parser

NHANES is a great ressource for doing epidemiological research. As the NIH website provides only data import for commercial software here is my rewrite in R. First load from their site

adult.exe
youth.exe
lab.exe
lab2.exe
exam.exe

put everything in one directory and expand the self-extracting archives. Then create from each SAS file a new variable content file that will only contain variable name and tab separated start position in the .dat file. Adult.var for example would read like this:

SEQN 1
DMPFSEQ 6
DMPSTAT 11
DMARETHN 12
DMARACER 13
...
HAZNOK5R 3345

Then start the following R job with the datasets and variables that you are interested in

|wj_nhanes.R|

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Genetics

Undo button

–Day 7 of Just Science Week–

Wouldn´t it be nice to have also a CTRL+Z action in the laboratory? For example when you have confused pellet and supernatant during pipetting? Biology at least seems to have some kind of undo action – see a series of nice papers in Cell Research. It´s not about demethylation of the parental genome, it’s about stopping and rebuilding the zygotic transcription program during the first meiotic division (that creates the haploid set of chromosomes that will be passed to the progeny).

At present there are 3 hypothesis around, how transcription is being silenced – simply by the speed up of the cell cycle, by active inhibitory (transcription) factors, or the passive deficiency of critical factors. Sun et al. now show that there is a genome-wide disscociation of chromatin factors leading to a naive state in preparing the new life cycle. Critical transcription factors and regulators remain separated for a prolonged time period and become reassociated only after pronuclear formation. It is still unclear if the second or third hypothesis fits best this process as the absence of even 1 essential transcription factor can inactivate transcription. Deletion of TBP for example will inactivate both PolI and PolII; TBP is found to dissociate among other factors.

Only a couple of structural proteins remain bound persistently (HP1alpha, HP1beta, TOPIIalpha and AcH4, with acetylated histone 4 as a positive control. Of course methyl-binding proteins, topisozymerases, and other heterochromatin binding stuff is required for normal chromatin structure where it would be nice to know which of these remain bound during this reprogramming step. So, this looks more like a reinstalling the OS than a simple undo action.

Thanks and good bye to all guest readers of the science week.

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Joke

Random news, oxymorons and paper generator

–Day 6 of Just Science Week–

No idea, what to write in your next scientific paper? Use the random medical news for some ideas. Here are also some expressions ready for cut & paste. Or you may want to go directly to SCIGEN (thanks to Christine for that link).

randompaper.png

This page took 0.134 seconds of computer labor to produce. No computers were harmed in the making of this page. Some browsers whose name starts with Internet may be though (from Matt s blog).

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Philosophy

Poll: Are most published research findings wrong?

–Day 5 of Just Science Week–

John Ioannides has published a rather influential paper (that will not so often be cited as read): “Why Most Published Research Findings Are False”. In principle his arguments are (numbering by me):

1. a research finding is less likely to be true when the studies conducted in a field are smaller
2. when effect sizes are smaller
3. when there is a greater number and lesser preselection of tested relationships
4. where there is greater flexibility in designs, definitions, outcomes, and analytical modes
5. when there is greater financial and other interest and prejudice
6. and when more teams are involved in a scientific field in chase of statistical significance

According to good scientific practice, this could be tested – the only problem is to recognize if the result of a single study is wrong. To be continued in 20 years…

{democracy:2}

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Genetics

My compliments

My compliments to Nicole, the latest Ph.D. student from our lab who succesfully passed her final exam today in Freising at TU München-Weihenstephan. Here is the semi-official document:

p1000650.JPG

The title of her thesis is High-resolution snp scan of chromosome 6p21 in pooled samples from patients with complex diseases , a topic that has recently attracted new interest.

We apply a high-throughput protocol of chip-based mass spectrometry (matrix-assisted laser desorption/ionization time-of-flight; MALDI-TOF) as a method of screening for differences in single-nucleotide polymorphism (SNP) allele frequencies. Using pooled DNA from individuals with asthma, Crohn’s disease (CD), schizophrenia, type 1 diabetes (T1D), and controls, we selected 534 SNPs from an initial set of 1435 SNPs spanning a 25-Mb region on chromosome 6p21. The standard deviations of measurements of time of flight at different dots, from different PCRs, and from different pools indicate reliable results on each analysis step. In 90% of the disease-control comparisons we found allelic differences of <10%. Of the T1D samples, which served as a positive control, 10 SNPs with significant differences were observed after taking into account multiple testing. Of these 10 SNPs, 5 are located between DQB1 and DRB1, confirming the known association with the DR3 and DR4 haplotypes whereas two additional SNPs also reproduced known associations of T1D with DOB and LTA. In the CD pool also, two earlier described associations were found with SNPs close to DRB1 and MICA. Additional associations were found in the schizophrenia and asthma pools. They should be confirmed in individual samples or can be used to develop further quality criteria for accepting true differences between pools. The determination of SNP allele frequencies in pooled DNA appears to be of value in assigning further genotyping priorities also in large linkage regions.

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