Lawyering-up Medicine Research integrity

Aguzzi and the Lowlifes

The prion researcher Adriano Aguzzi used to describe his Pubpeer critics as "lowlifes", and himself as a victim of a lynch mob. But after Elisabeth Bik helped him find even more mistakes in his papers, Aguzzi changed his stance.

Adriano Aguzzi is prion researcher, director of the Institute for Neuropathology at the University Hospital (Universitätsspital) Zürich in Switzerland, member of several academies and a self-professed champion of publication ethics. Critics of his papers are described as a lynch mob and “lowlifes”, because apparently all those data irregularities do not matter in the greater scheme of things. Aguzzi’s prion research namely saved many lives. Or so he says.

The image integrity sleuth Elisabeth Bik now followed up on some year-old whistleblower concerns once posted on PubPeer. Back then, Aguzzi and his coauthors reacted with aggressive insults towards his critics. That said, every group leader can unknowingly become victim of a rogue PhD student or postdoc. But evading responsibility when faced with evidence of data manipulation, refusing to correct the scientific record while viciously attacking your critics is not an ethical response. Some define it as research misconduct. It seems, however, that Aguzzi has changed his stance now.

Update 14. and 21.12.2019: Aguzzi now announced to sue me for defamation. His inspiration comes from my sentencing in Berlin court over the deadly trachea transplants performed by Paolo Macchiarini and assisted by Philipp Jungebluth (the plaintiff). Aguzzi wrote this in the comment below:

I will have no option but a lawsuit. Get prepared for another conviction, and start saving for your legal expenses. You may learn your lesson this time.

Now Aguzzi made his threat official. He demands an immediate removal of this article and all tweets referencing him, my lifelong commitment never to say anything critical about him, otherwise he will pursue a lawsuit, with damage compensation of €15,000. A translation of this letter is provided at the end.

Readers of my site might recall that Aguzzi as panel member recently awarded the France-based German cancer and ageing researcher Guido Kroemer with the €1mn “Nobel Lombardo” (read here), despite or maybe actually because of Kroemer’s notoriety as peddler of Photoshopped research data. When awarding Kroemer, Aguzzi had no problem joining a quasi-all-male panel with the most toxic peer of all: Carlo Croce, with 9 retractions so far and a lost lawsuit against his critic David Sanders and the New York Times. To be fair, Aguzzi left the panel afterwards, officially to make room for women next year.

Aguzzi is advisory board member at Mercaptor. He has a PhD there, even in press releases.

Aguzzi’s world is weird. The Zürich professor occasionally claims having both MD and PhD degrees, but his own CV proves that he never did any PhD training, but graduated as MD in 1983, while on leave in USA during his medicine studies in Switzerland and Germany. In fact, Aguzzi explained that he sees his Doctor honoris causa (Dr h.c.) from University of Bologna as a kind of quasi-valid PhD degree. It is not really the same, years of researching in a lab and defending a doctorate thesis versus dressing up in a fancy hat for a party organised by admiring peers.

Update 27.12.2019. Aguzzi insists his Bologna degree is a PhD, even if a honorary one. Actually, what his own diploma says is that he received a “diploma di Laurea”, which is equivalent either to a Bachelor or a Master degree. In Italy, laurea graduates are traditionally addressed as “dottore” (or dottoressa), but a PhD degree is called in Italy “dottere di ricerca”, and is not to be confused with the dottore of the laurea. Hence, according to the diploma he posted, Aguzzi seems to have only a BSc h.c. or a MSc h.c. title from the University of Bologna, and not the honorary PhD at all.

Aguzzi’s laurea h.c. diploma, as posted by Aguzzi himself on Twitter

But now, let’s discuss Aguzzi’s scientific record. It seems, his worst enemies are the envious lynch mob “lowlifes” who discuss his papers on PubPeer. Like here:

Johannes Haybaeck , Mathias Heikenwalder , Britta Klevenz , Petra Schwarz , Ilan Margalith , Claire Bridel , Kirsten Mertz , Elizabeta Zirdum , Benjamin Petsch , Thomas J. Fuchs , Lothar Stitz , Adriano Aguzzi Aerosols transmit prions to immunocompetent and immunodeficient mice PLoS Pathogens (2011) doi: 10.1371/journal.ppat.1001257

In July 2013, an anonymous PubPeer critic voiced these concerns:

Figure 6D: Splice between lanes 6 and 7.

Figs 3 and 4 use four differently cropped, exposed and rotated images for the JH-/- (Fig. 3) and c3c4-/- (Fig. 4) mice. Is one of these mice both the same?

Fig. 5E left lane has been spliced onto the gel.

Fig. 5G right panel. Oddly blotchy pale, pixellated background with less detail than for the dark matter in the lanes. Multiple straight line effects at edges of bands. This gel appears to have been composed from multiple individual components inserted into a lower resolution background.

Fig. 6C left panel. Right vertical edge has a jaggie revealing that a shorter lane has been spliced in.

Fig. 6D right panel. strong splice between lanes 6/7″

The commenter also wondered if it made sense to declare that every single author has contributed everything to the paper.

Aguzzi immediately announced to investigate, and promised to share the results:

My policy is that all raw data be kept securely for at least 10 years, hence I foresee no problems with data retrieval. I will post the results of the audit.

More than two years, passed, and in November 2015 Aguzzi replied again:

I desisted from my original intent to publish further materials on this forum once it became clear that some of the self-appointed “peers” are more interested in mud-slinging than in post-publication review and quality control of science. I see no need to defend my work against a group of anonymous detractors who negate a priori my integrity, yet are not even prepared to identify themselves. Suffice it to say that Mathias Heikenwälder and I have gone carefully through all original data and we confirm that none of the alleged “manipulations” were performed. We stand fully by the findings which we have reported. Both Mathias and I will be prepared to make additional materials available to whoever will contact us directly and identify himself/herself, be it the Editor of PLoS Pathogens or anybody else. What we are NOT going to do is to engage in shouting match with anonymous individuals who make libelous and unfounded accusations. Please note that I will NOT make any further comments or communications on this forum.

The anonymous commenters pleaded with Aguzzi to reply again, and eventually the paper’s first author Johannes Haybäck (now director of Institute of Pathology at the University of Magdeburg in Germany, with a second affiliation at University of Graz in Austria), did:

I apologize for not having reacted earlier, but I had not understood the precise nature of the issue with the contested histology figures. I agree with that a mistake may have occurred while preparing the histology panel for publication. These are BSL4 experiments, which are carefully documented for reasons of both biosafety and animal welfare. I have planned to travel to Zurich on Dec. 7th in order to re-inspect all histology together with a coworker from the Aguzzi lab. The paraffin blocks from which the histology was prepared are certainly still existent, and I am confident that the issue can be clarified. If indeed there are errors, a correction will be published in the PLoS Pathogens paper.

In February 2015, PLOS Pathogens issued a Correction, for figures 3, 5 and 6. On PubPeer, Aguzzi then posted a lengthy comment, where he shared his views on anonymous post-publication peer review. He regretted that his “former student Johannes Haybäck committed an error while mounting Fig. 3A” , but saw little responsibility on his own part. Instead, this:

Now, I have been active in research since 1982. Over the past 34 years, I have published >450 paper. Notwithstanding the error in Fig. 3A, the Haybäck paper is one of those that I am proudest of. Our discovery of aerosols as prion vectors has led to a significant reassessment of the safety procedures for lab work with prions. By drastically improving the safety of lab workers, this work will likely save human lives. […]

In summary, if my scientific legacy will turn out to be a better protection from occupational hazards for students, postdocs, and lab technicians, well, that is a legacy that was worth working for, and one that I am proud of.”

Well, it is not like lab personnel used to get sick and die from prion exposure in epidemic proportions until Aguzzi’s life-saving paper came along. Come to think of it, there never were any cases of a dangerous prion infection in the lab. Aguzzi was exaggerating his scientific legacy, again.

That same whistleblower flagged in July 2013 other Aguzzi papers on PubPeer, but not even corrections have happened. Like here:

Brady Michel , Adam Ferguson , Theodore Johnson , Heather Bender , Crystal Meyerett-Reid , Bruce Pulford , Adriana Von Teichman , Davis Seelig , John H. Weis , Glenn C. Telling , Adriano Aguzzi, Mark D. Zabel Genetic depletion of complement receptors CD21/35 prevents terminal prion disease in a mouse model of chronic wasting disease Journal of immunology (2012) doi: 10.4049/jimmunol.1201579 

Bik provided good visualisation of the problem, namely some very insolent reuse of western blot bands in Figure 4:

The last author Mark Zabel, prion researcher at Colorado State University in USA, replied immediately with this comment:

We have commissioned an independent forensic analyses of the figures in this manuscript and will update this post with a report when it is complete. For now, we are sharing all of the raw data images used for these experiments and to create the figure here https://www.sugarsync.com/pf/D6450680_0347642_9170813

We are committed to the highest scientific rigor and integrity in our research. We stand by the data and the conclusions drawn from them in the paper, and will submit an errata to this paper to update the figure if these duplications are confirmed.”

Another PubPeer critic however retorted:

the problem already exists in the raw data since the two first Ig H blots (page 7 of above pdf) are actually manipulated versions of the same blot.”

Zabel then provided his final decision in October 2014 that nothing at all wrong was with the paper. He explained that loading controls were irrelevant anyway, and even accused the whistleblowers of having fabricated evidence in Photoshop:

An independent analysis of the files and blots, as well as interviews with authors of the original paper, concluded that “duplication or manipulation of raw blots was deemed unlikely, unintentional or inconclusive. Explanations given by the technicians who performed the experiments are plausible and no further action was recommended. In fact, it was demonstrated that unrelated blots could actually be made to look extremely similar by the same manipulations that raised concern about the images published in the manuscript.

In short, it could not be determined definitively whether these images were inadvertently duplicated blots, but that it was unlikely that any intentional manipulation of the blots had occurred. Moreover, the bands in question were mainly controls, which would not have significantly altered data interpretation. We therefore stand by the data and the conclusions drawn from them in the manuscript.

Of course the paper was not corrected, and rest assured it never will be. Journal of Immunology made it their business model of doing nothing at all about falsified research (read here and here). How else can infectious diseases be cured if not with the modern technology of Photoshop?

Another coauthor of Aguzzi was more constructive, after Bik flagged a badly manipulated figure. Background patches were copy-pasted, presumably to cover up results which stood in the way of the fight against a deadly infectious prion disease.

Ciriaco Ligios, Maria Giovanna Cancedda , Antonello Carta , Cinzia Santucciu , Caterina Maestrale , Francesca Demontis , Mariangela Saba , Cristiana Patta , James C DeMartini , Adriano Aguzzi, Christina J Sigurdson Sheep with scrapie and mastitis transmit infectious prions through the milk Journal of Virology (2011) doi: 10.1128/jvi.02022-10

Christina Sigurdson of UC San Diego in USA replied 2 days later:

We are looking into these blots as a high priority.”

Let’s hope Sigurdson will not pull a Zabel on this one, and that Journal of Virology is more ethical than Journal of Immunology, which is actually not that difficult. In the next case however, it is perfectly clear that the society journal Blood is not interested in a correction: Blood has a policy of ignoring everything older than a year or so, regardless of how bad. Hence, no need for Aguzzi or his Universitätsspital Zürich colleagues to bother about this reused and shifted image:

Stefan Baenziger , Mathias Heikenwalder , Pål Johansen , Erika Schlaepfer , Ursula Hofer , Regina C. Miller , Simone Diemand , Kenya Honda , Thomas M. Kundig , Adriano Aguzzi , Roberto F. Speck Triggering TLR7 in mice induces immune activation and lymphoid system disruption, resembling HIV-mediated pathology Blood (2009) doi: 10.1182/blood-2008-04-151712

“The polyl:C/F4.80 panel in Figure S2B (21 days) appears to show an overlap with the polyl:C/F4.80 panel in Figure S3B (42 days)”

Being such an important man, and likely unbothered by the journals, Aguzzi so far saw no reason whatsoever to address the concerns posted in parallel in 2013 regarding this paper:

Megan Larson , Mathew A Sherman , Fatou Amar , Mario Nuvolone , Julie A Schneider , David A Bennett, Adriano Aguzzi, Sylvain E Lesné The complex PrP(c)-Fyn couples human oligomeric Aβ with pathological tau changes in Alzheimer’s disease Journal of Neuroscience (2012) doi: 10.1523/jneurosci.1858-12.2012 

“The two top right panels in Figure 2B share many similarities. Thin red circles and ellipses highlight specks and spacings patterns between lanes with characteristic shapes and positions. “

Also the last author Sylvain Lesné of University of Minnesota in USA did not reply. Maybe he or Aguzzi will now, after Bik provided some illustrations? Or is this evidence also falsified in Photoshop, like previously uncovered by Zabel? How is this approach to curing Alzheimer’s to explain:

“two areas, highlighted with yellow boxes, look much, much more similar than expected.
Thin magenta arrow. A sudden, sharp vertical line between the two right-most lanes suggests an undisclosed splicing.” “similarity between figure 2D, lane 1 and Figure 4B left panel, as shown with thick blue boxes.”

Bik’s concerns about this Nature paper from Aguzzi lab were so far not dignified with a comment:

Michael B. Fischer , Christiane Roeckl , Petra Parizek , Hans Peter Schwarz , Adriano Aguzzi Binding of disease-associated prion protein to plasminogen Nature (2000) doi: 10.1038/35044100

A paper containing such a falsified figure would not be not reliable anymore. Falsifying data in Photoshop, regardless which of the authors did it, does affect the conclusions, and it is the responsibility of the corresponding author to act upon the evidence. It does not matter how many lives Aguzzi thinks he has saved with his prion research.

Update 13.12.2019. Aguzzi has discussed this Nature figure in the comment section below, and now first author Michael Fischer replied by email:

We had been able to answer questions about the paper to the satisfaction of everyone (Nature and University of Zurich) 4 years ago. I therefore do not want to comment again.

Aguzzi did reply to this commenter, who raised unspecified concerns about “Figures 1, 3, 4, 5” in March 2017. The first author was meanwhile finally tasked with retrieving raw data.

Caihong Zhu, Uli S. Herrmann , Jeppe Falsig , Irina Abakumova , Mario Nuvolone , Petra Schwarz , Katrin Frauenknecht , Elisabeth J. Rushing , Adriano Aguzzi A neuroprotective role for microglia in prion diseases The Journal of Experimental Medicine (2016) doi: 10.1084/jem.20151000

Back in 2017, the PubPeer critic also voiced concerns about shifted baselines, high mortality among the alleged healthy controls mice, and also this bizarre approach to statistics:

Experiments are largely underpowered: serve as examples N=4 or 3 from figures 3, 4, which are central to the argument of the paper. The dispersion of the data indicates extensive variability, calling for a substantial increase of the N. I am very surprised these datasets comply with the requirements for normality and homocesdasticty needed for the ANOVA“.

Original band photo, borrowed and modified for satire purposes, here.

The editors and reviewers at the elite journal somehow missed all that, or just trusted Aguzzi to know what he is doing. Aguzzi’s reply arrived years later, in July 2019, typos his:

The sentence “I wonder if somebody more expert could have a look at westerns at Figures 1, 3, 4, 5? Some of them look odd to me, but I’m not an expert in picking up image manipulation” provides a vivid demonstratin of everything that’s wrong with PubPeer.

The commenter is unhappy with this publication, most likely because he has some personal beef with one of the authors. However, as much as he would wish to prove the paper wrong, he cannot find any flaws in the figures. Therefore, he claims that they “look odd” to him, hoping that the mob will rise and lynch the authors – or at the very least that something disreputable will stick.

Sadly (but unsurprisingly), the world of research is not devoid of lowlifes. The meanness, spite, the posturing and the defamation under the protection of anonymity, you find them on Reddit and you find them on PubPeer as well.

That professorial reply to the lynch mob “lowlifes” actually provides a vivid demonstration of everything that’s wrong with Aguzzi. The statistics concerns are actually very much valid, and as for western blots: the loading controls do not always look like they show same gel. Despite Aguzzi et al having written in the methods section:

“To avoid variation in loading, the same blots were stripped and incubated with an anti-actin antibody”

That was apparently a fib, or an honest error of oversight, for the noble purpose of saving lives. Like here, in Figure 5, where an grid was placed to visualise that, sadly, and unlike Aguzzi et al explicitly wrote, GFAP signal and Actin loading control did not derive from same gel:

” With the risk of being labled as a lowlife or part of a lynch mob I would suggest that perhaps the oddity referred to by the original commenter is that some of the gels seem to radically change shape between stainings.”

But as we learned before from Aguzzi’s colleague Zabel, loading controls are irrelevant anyway, presumably in prion research at least. Although, Figure 1E does contain undisclosed splicing, in a paper from 2016:

Aguzzi eventually understood that maybe it was he who was wrong. The gels are possible not what they are presented to be. Hence this new reply:

I agree that this is weird. I’ll try to retrieve whatever original materials are around. My former postdoc Caihong Zhu has recently moved to Shanghai, but his records are meticulous and we are in touch every week. In fact we are still doing a lot of experiments together and he is still maintaining a large mouse colony in my institute. I am confident that he can shed light on this issue.”

With a paper barely 3 years old, the raw data should be available. Different with Aguzzi’s 11 year old paper, flagged by Bik for some very naughty Photoshoppery aimed at extirpating prion disease transmission.

Nicolas Genoud , David Ott , Nathalie Braun , Marco Prinz , Petra Schwarz , Ueli Suter , Didier Trono , Adriano Aguzzi Antiprion prophylaxis by gene transfer of a soluble prion antagonist American Journal Of Pathology (2008) doi: 10.2353/ajpath.2008.070836

Such things as in Figure 1C and 5h do not happen by mistake, those are intentional data manipulations. Regardless of who did it, as as corresponding last author and lab head Aguzzi is very much responsible for what he publishes. And no, having published many papers in Science, Nature and Cell is not an excuse.

Aguzzi warned however:

Thank you for pointing out these issues. I agree with your concern and I will try to retrieve the original histology slides. I cannot promise that I will find anything though. These experiments were performed >15 years ago. My policy is to retain all original materials for at least 10 years. Older materials have been occasionally retained, but not in a systematic manner.

Aguzzi also replied in similar vein on another paper, where an image was duplicated without change. That might be one of the rare cases of an honest mistake.

Update: Aguzzi now provided hi-res Figure 1 of the Genoud et al 2008 paper in a comment below. It makes the matter worse, there are even more manipulations in that figure than previously assumed.

Mathias Heikenwalder , Christian Federau , Lotta Von Boehmer , Petra Schwarz , Mareike Wagner , Nicolas Zeller , Johannes Haybaeck , Marco Prinz , Burkhard Becher , Adriano Aguzzi Germinal center B cells are dispensable in prion transport and neuroinvasion Journal of Neuroimmunology (2007) doi: 10.1016/j.jneuroim.2007.09.022

Aguzzi now announced to recover original data and correct the literature. Great start! He also promised to stop calling himself a PhD (something he used to do even in papers and book chapters as corresponding author).

Aguzzi also claims a PhD in Austria, where he is foreign Academy member.

Update 12.12.2019. For completeness, I decided to discuss this collaborative paper from Christian Haass lab at LMU Munich in Germany, coauthored by Aguzzi.

Armgard Uelhoff , Jörg Tatzelt , Adriano Aguzzi , Konstanze F. Winklhofer, Christian Haass A pathogenic PrP mutation and doppel interfere with polarized sorting of the prion protein Journal of Biological Chemistry (2005) doi: 10.1074/jbc.c400560200 

What we see here, is a western blot experiment where the “no signal” analysis was probed on one gel (Dpl in A and PrP in B), but the “with signal” analysis was made on a different, or maybe even several different gels, spliced together. There is therefore no positive control or evidence that any protein at all was loaded on the “no signal” gel. The authors might want to correct this figure, which is otherwise meaningless.

Before reading Aguzzi’s comments below, you might want to prepare yourself with this eulogy in Tagesanzeiger.

“A postdoc of his held last week a lecture at the Institute of a Nobel laureate in Israel, as the neuropathologist Adriano Aguzzi posted recently on Facebook. After the talk, the Nobel laureate told the postdoc: “Adriano should have received the Nobel Prize together with Stanley Prusiner”. This is not correct, Aguzzi continues in his post, “but my ego grew enormously, today it does not fit through the door anymore. “

The article continues to decry the tragedy that Aguzzi was not given the deserved Nobel Prize.

Update 16.12.2019. Another Aguzzi paper is discussed on PubPeer:

M Nuvolone , N Schmid , G Miele , S Sorce , R Moos , C Schori , RR. Beerli , M Bauer , P Saudan , K Dietmeier , I Lachmann , M Linnebank , R Martin , U Kallweit , Ve Kana , EJ. Rushing , H Budka , A Aguzzi Cystatin F is a biomarker of prion pathogenesis in mice PLoS ONE (2017) doi: 10.1371/journal.pone.0171923

9 years lie between these papers, is the loading control for Cst7 still valid? Aguzzi however says that Cst7 blot was done already back then, but unpublished. Saved for the distant future.

Aguzzi’s reply was:

It is simply one of the many attacks ad personam that Leonid Schneider (who was recently convicted and sentenced to a stiff pecuniary fine for slander by a German court, and was in addition ordered to pay all legal expenses to the person whom he slandered) is launching against me.

I could ask PubPeer to remove the slanderous comments by Schneider and others. But I will not, because I prefer everybody to see and judge for themselves the level of absurdity, incompetence and meanness of his latest smear campaign. Schneider, don’t delude yourself that I will not fight back.”

Aguzzi sees every attempt to critically discuss his papers as a personal attack, a smear campaign and slander, for which he threatens to sue his critics. This is unfortunately a kind of retaliation which every whistleblower has to deal with. Not sure what kind of signal University of Zürich wants to be sending here.

Update 21.12.2019.

Aguzzi sent me today me this registered letter, the original is shown at the beginning of the article:


Dear Mr. Schneider

You spread untrue claims about me and my employees. I request of you now, informally and extrajudicially, the following acts:

  • Please delete your blog entry “https://forbetterscience.com/2019/12/12/aguzzi-and-the-lowlifes”
  • Please delete all of your tweets and other online posts which mention my person and my employees
  • To refrain lifelong from mentioning my person in the future, from judging, attacking, hinting, speaking of, coercing, and publicising in any form online or otherwise.

This letter is meant as a friendly, unprejudiced request. If you comply with this request I will consider this unfortunate matter as settled and will undertake no further steps.

However, should you do not comply with my request within the next 10 days, you will receive from my legal representative a cease and desist declaration with penalty clause.

As you know from your previous experiences, this will be combined with compensation demands which correspond to the severity of your law violation. We envision a compensation of €15,000, which we intend to donate to a charitable foundation. You probably also know that repeat offenders can expect little understanding from the judiciary.

I sincerely hope that you recognize my benevolent willingness to settle out of court, will comply with my request and save you a lot of trouble.

Sincerely

Adriano Aguzzi

Update 24.12.2019

Christian Schwarzenegger, Univerity of Zürich’s Vice-Rector for faculty affairs and law professor, informed me on 22 December 2019 that the university is not involved with Aguzzi’s announced legal action against me. He however declared:

the university leadership has initiated an investigation of the accusations you raised. The procedure is as usual based on the presumption of innocence. As soon as we have a report, we will inform you about the next steps.”

Update 22.05.2020

Aguzzi has now been threatening a peer reviewer of his manuscript currently submitted to a journal. The original tweet, where Aguzzi mentioned some gel splicing, has been deleted. But here are screenshots and his follow-up comments:

The questionable Twitter behaviour prompted some PubPeer users to have another look at Aguzzi papers:

AM. Thackray , MA. Klein , A Aguzzi , R Bujdoso Chronic Subclinical Prion Disease Induced by Low-Dose Inoculum Journal of Virology (2002) doi: 10.1128/jvi.76.5.2510-2517.2002

Whoever did that gel, has a lot to answer for. But also the senior authors liek Aguzzi and Raymond Bujdoso in Cambridge should they think it is not a problem. Another problematic paper was done in collaboration with Max-plank-Institute in Frankfurt, Germany: Heber et al J Neuroscience 2000, other works are straight from Aguzzi’s lab though: Polymenidou et al PNAS 2004 and the vintage paper with his mentor and patron Charles Weissmann, Brandner et al PNAS 1996.


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137 comments on “Aguzzi and the Lowlifes

  1. Not having earned a real PhD, it should not be a surprise that Dr. Dr. Dr. Aguzzi has limited competence in supervising and communicating basic research, as shown by the abundant errors in publications. What a treat it must be for his trainees to work with someone whose bag of supervisory tricks consists of an insistence on running blots 3 times (or at least showing the boss the 3 that fit his theory) and spouting quotes from Feyrabend (or maybe Popper on a good day). And of course the eventual ritual of being thrown under the bus. He has glommed on to a popular subject and ridden the donkey well, but the outputs seem of modest practical import to me regardless of paper impacts, where the transgressions identified so far do not amount to much more than corner cutting. Aguzzi is to be given great credit for wading into the fray here and in other fora. A refreshing change from the truly fraudulent monsters who never say boo, or sometimes appear with a lawyer at each arm.

    Like

    • Aguzzi Adriano

      You criticize me for demanding that important experiments be reproduced thrice before publishing. So, should “successful” experiments not be repeated? Lest they may not be reproducible? Sorry, but that’s not how I run my lab, and I shall never heed such disgraceful advice.

      As to the “modest practical import” of my research, I completely agree with you. I have not entered research to resolve practical problems. Instead, I have only devoted myself to those problems that I deemed intellectually stimulating.

      I started my work on prions when nobody cared about them (a neurologist asked me once why I’d work on a “non-existing disease”. Then the mad-cow crisis came, and for a short time I became a kind of B-series celebrity. And then BSE was gone, but I continued to work on prions and nothing else. The facts show that I have never ridden any donkey, but have always stayed true to my own research interest.

      Like

      • Rex Rictor

        There are hundreds of people working on prions since their dawn….no idea what reality you refer to when claiming you are one of the first in the field…it simply false. Seems like an enlarged sense of own ego…..dangerous perception, could indicate problematic personality.

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  2. Aguzzi Adriano

    Let it be known that Schneider preventing my reponses from appearing on the internet. The self-proclaimed paladin of open science is exercising censorship because he does not wish to be contradicted. I will nevertheless continue to answer every comment,. My blocked comments will be presented in court and will serve as forensic evidence of Schneider’s intent to slander me without having to tolerate the inconvenience of my responses.

    Like

    • I am releasing certain comments of yours, so your UZH can use them as a public record of your bullying and intimidation when faced with evidence of data manipulation in your papers.
      You can use PubPeer as your public forum, this is where all evidence and quotes presented in the above article were originally posted in the first place.

      Like

      • Aguzzi Adriano

        Let’s examine the facts:
        1. you have slandered me on your blog
        2. to your great disappointment, I have responded and defended myself
        3. this has annoyed you, so you have blocked my opportunity to defend myself against your slander with the ridiculous pretext that I would have insulted Macchiarini (I don’t even know who that is).
        4. then, you have continued to slander me unencumbered by the inconvenience of having to acknowledge my objections.
        5. you have allowed a mob of your anonymous friends (half of whom may just be pseudonyms of yourself for all I know) to continue to slander me, while still preventing me from responding.

        Schneider, as a convicted felon you certainly have a lot of experience with the rule of law. Therefore you know how this is going to end. You advised me to defend myself in hospital toilets, but instead I will do so in a court of law, as is the inalienable right of every citizen of democratic countries.

        You may try to paint me as intimidating, but the facts listed above speak louder than your words. Read again all you wrote. How do you think your words will look like in court? You have dug yourself a big hole, and you should have known better. Enough said.

        Like

      • Regardless of how much you support Macchiarini & Jungebluth, Mr Aguzzi, I was never a “convicted felon” as you maintain, that would mean under German law that I served at least 1 year jail time. I lost a libel case, against your doctor colleagues, true. Most people say that sentencing was unfair, given the facts which court wilfully mistranslated and misinterpreted, and the official misconduct findings in Sweden which the court refused to admit as evidence. But in any case, “convicted felon” is a libellous claim against me and I am advised it might be worth suing you over that.

        Like

  3. How can the Hayback Figs. 3A and 4A not be cheating? If it was the first author responsible for these figures, the paper should be retracted because the study loses all its credibility.
    By the institute cheating might easily be proved by studying the original micrographs. If the same micrograph was used for Fig. 3A and Fig. 4A, it most definitely was cheating. If different micrographs from the same tissue slide but only turned compared to the original angle in one figure set (for example Fig. 4A), it should also be considered cheating. According to Prof. Aguzzi’s description of his lab the uncropped micrographs should still be available, so this is easy to check.

    Like

  4. Aguzzi Adriano

    Doctored blots worry me a lot, but frankly I worry much more about other things. ELISA reader results are simply excel sheets. How can I ensure that they are correct? After everything was said and done, the edifice of science rests upon reciprocal trust. I do trust my coworkers, but I am not naïve and I am of course aware that anybody who realls sets out to deceive will succeed – in my lab as well as in any other lab.

    My strategy to minimize the danger of such things happening is (1) try to inspire interest and gratification in studying the phenomena of nature, (2) install weekly open discussions of everything that worked and that didn’t, and solicit groupwork as a means to reduce the latter, (3) NEVER EVER penalize those who, despite working hard, did not achieve their research goals, (4) share everything with everybody, (5) very clearly state that I neither condone nor incentivize, implicitly or explicitly, any fraudulent research claims, and (6) help meritorious students and postdocs in their career, irrespective of whether they have produced a high-impact publication or they have failed to publish anything (maybe because the hypothesis was wrong – something that happens very often to scientists and also to me).

    Again, these are soft, culture-based strategies that may at best reduce the danger of fraud by making it clear that honesty pays while fraud may terminate a career. But they are not airtight, and fraud may still happen even under such auspices. Indeed I have terminated a postdoc in 2012 because of fraud. The story was quite surreal. This person had submitted a paper to Science, but a reviewer noted an image duplication. I then asked him to prepare a set of histology slides, which I would then randomly check for consistency. I did this as a formal exercise to make sure that we would follow due process, and had zero doubts on the postdoc’s honesty. Little did I knew! Upon my request, the guy broke down and confessed that he had faked the whole thing. Fortunately, nothing had been published – for which I thank my guardian angel!

    While I immediately sacked the guy, I thought that I shouldn’t completely ruin his life. Offense and punishment should be commensurate. I told him that I would publicized this story if he attempted to get back into academia, but I would not expose him if he left science. And the latter is what happened, and that’s the reason why I am withholding his name.

    Like

    • Nobody doubts that you once “terminated a postdoc”, or a plural of postdocs, for reasons third parties cannot know. We only have your version of events, completely unverifiable. Maybe you also saved a whole kindergarten from a burning building, or you prevented a terror attack by knocking out an armed gang of Mujahideen in Zürich with your bare hands. Also there, you can’t say more because you swore secrecy.
      But how about that time when you secretly modified figures in a manuscript with the result that it got rejected for sloppiness? I have this from first-hand source, Mr Aguzzi.

      Like

    • Rex Rictor

      Above “1. you have slandered me on your blog” and similar statement.

      One should be aware that these are accusations of criminal conduct. If this are demonstrably false then it is indeed a crime to make such a claim.

      Also, if Prof. Aguzzi is intending to sue Dr. Schneider then it is incredible stupid to preempt it by making a public statement, in fact this will damage or destroy the lawsuit.

      Like

    • What a regrettable incident. In this instance the only way is to terminate a contract. Though I personally think that blackmailing somebody that you will tell the case to others if that person remains in academia is not a professional act. Once I also had to dismiss a coworker for misconduct. However, legally I am not allowed to share the details with anyone. When I was asked for reference letter about that person, I was allowed to provide little information to the potential employer about the reason led to the termination of contract. But I cannot do more. Albeit I know that that person has continued work in research, and does not indicate in the CV that was ever working in my lab. Still, what can I do? I cannot blackmail the person and ask to change profession.

      Like

      • Aguzzi Adriano

        I respectfully (but completely) disagree with so-called “Weiss”. I don’t know what “Weiss”‘s coworker did, but in my case the facts of the matter are crystal-clear, there is an amply documented trail, and there is even a signed confession. I could have easily exposed the guy, and I do not see why that would be legally problematic.

        But I did not, because I do not think that anybody – no matter what they did – should be subjected to the kind of shitstorm that Schneider has unleashed on me. The internet never forgets, the fact do not matter to anybody, and similar things are known to have driven people into suicide (think of revenge porn). If the guy wants to become an Uber driver or something else, that’s fine with me. If he wanted to stay in science, he would have had to disclose his misconduct and to make amends.

        This is the exact opposite of blackmail. It is simply a proof that I am not as reckless as Schneider.

        Like

      • “there is even a signed confession”

        Uh-uh. This is a potentially criminal act, Mr Aguzzi, coercion or even worse. You forced a postdoc to sign a confession before “terminating” him? It does not matter if you claim he signed the confession voluntarily. There were no witnesses, it was just you and him alone in the room, and at the end you got your signed confession. Also: you demanded money from me, for mentioning your mismatched western blots (something which proved a fact). Was that postdoc also coerced to financially compensate you, or else you will publish the confession you made him sign?
        You are indeed a “fiery, dangerous beast”, Mr Aguzzi. Whistleblowers beware.

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    • A “quite surreal” story:

      1.Reviewer of a high impact journal points to an image duplication.
      2.A responsible person checks the case.
      3.A fake is uncovered.

      The usual story:

      1.Reviewer of a high impact journal overlooks an image duplication.
      2.PubPeer asks to check the case.
      3.PubPeer activists are insulted as “lowlifes” and “lynchmob”.

      Like

    • “I told him that I would publicized this story if he attempted to get back into academia, but I would not expose him if he left science. And the latter is what happened, and that’s the reason why I am withholding his name.”

      Do you think that cases like his are unredeemable and can’t change and improve?

      Like

  5. Dear Leonid,

    Let’s try to bring some calm into this discussion.
    The essence is that, so far, and at least declaredly so for the Hayback study, Prof. Aguzzi sees no dishonesty, whereas most readers would consider intentional research misconduct as the most likely explanation.

    Therefore, first the question on the precise relationship between Hayback Fig. 3A and Fig. 4A pictures. Are they the same pictures, are they different pictures from the same tissue slide, or could they represent different serial cuts; thus, what level of similarity is certain? Can you ask some experts about this?

    The second question, related to the first, is whether the microscope described in the paper has an option for rotating the slides, rather than only forward-backward-left-right.

    Like

  6. “Favouring elite scientists when evaluating papers and proposals is like giving Usain Bolt a 10-metre head start in his next race because he won his last five. It incentivizes scientists to present themselves and their results in the best light possible, to shun transparency and to deflect criticism. Those tendencies contribute to reproducibility problems.”

    https://www.nature.com/news/our-obsession-with-eminence-warps-research-1.22251?WT.mc_id=TWT_NatureNews&sf95536360=1

    Our obsession with eminence warps research by Simine Vazire

    Like

  7. Rex Rictor

    @Aguzzi ‘shitstorm’ ‘unleashed’ ‘signed confession’ ‘slander’ ‘lawsuit’ ‘forced’ ‘punish’ ‘dead’ ‘suicide’………………….

    Drama, dramatic and victimhood.

    It is one huge victim crusade.

    Science is not about victimhood; it’s about the facts and the truth….cold plain simple and raw.

    You are trying to turn this into a theater play; its not, it’s about whether crimes have been committed against science, knowledge, patients and ultimately mankind.

    The reaction with drama and fireworks indicate guilt above all. Pack it up now – bitte.

    Let the independent investigations begin – all the cases above smell of fraud to me.

    Like

  8. Adriano Aguzzi

    OK Schneider, I am outta here. I will no longer comment your delirious fantasies. Everybody who has a minimum of balance and objectivity sees that you have lost all sense of reality. You shall have the last word – on the internet. See you soon at the Kammegericht (German Superior Criminal Court). Click, click (that’s the sound of locked handcuffs). 🙂

    Like

    • Rex Rictor

      @Aguzzi if Dr. Schneider would be concerned about your empty legal threats (they are empty because nobody who is serious would announce them publicly) he would not have presented the evidence would he now…..

      Also should you sue Dr. Schneider we are a group of individuals who will be forced to consider to counter sue for potential fraud and crimes against science.

      Like

    • Why did you as corresponding author “modify” figures in a manuscript by your lab member, behind his back? I have this from first-hand source. But why did you do that? Did that person refuse to sign a confession before escaping your lab? I asked you that before, Mr Aguzzi, but you prefer to keep threatening me. I am not your postdoc.

      Like

  9. All this verbal violence.
    Let’s go back to Haystack Figs. 3A and 4A.
    I am now sure that at least they are from the same tissue slides. I can’t prove that they are from the same picture, but the institute can find that out if the picture originals are still there or if the microscope has no rotation option (the latter would also prove that they are from the same picture). If they are from the same pictures, it definitely was intentional cheating.
    But imagine the microscope had a rotation option, and several pictures of the same slide were taken. Then, by mistake, one picture could have been incorrectly labeled. But how could four times pictures of mouse A be mislabeled as pictures of mouse B?
    If someone sees any possibility of how this maybe was not intentional cheating, please explain.

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  10. Rex Rictor

    Could you please send this to the Rectorate/Presidency of the corresponding author?

    This is plain and simple [not OK]

    Liked by 1 person

  11. Technician

    I worked as a technician years ago for this lab. We witnessed all sort of crazy things. We never understood why mobbing and other types of unethical behaviour were totally accepted by everybody. It will be nice if someone investigate the reported case and other things that happened in that lab.

    Like

    • Well, it may be vague the description “all other crazy thing” and “mobbing” (maybe you can give examples?); however his style is contrasting his academic career stage for me. I feel it immature to go crazy in public. I think it is better to communicate professionally, and keep the public face.

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      • Rex Rictor

        Mobbing/bullying/fraud all goes hand in hand with threats of “suicide” “force” and the megalomania of even thinking oneSELF should get the Nobel……these are all indicators of a malignant personality structure (DSM 301.81 Narcissistic Personality Disorder).

        Like

      • well, thinking on Nobel or other appreciation of own work may be OK. Probably I would not write an article about that sort of thoughts, since that would most likely make me look hilarious. 🙂

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  12. Prof. Aguzzi is obsessed with the Nobel prize, which he will never receive.

    Like

  13. Jeffrey Hall , Nobel’s interview on luminaries of science in 2007 before he was awarded NP in 2017 , Very frank.
    https://www.cell.com/current-biology/fulltext/S0960-9822(07)02369-X

    Like

  14. I find the style of the discussion in this thread highly unpleasant. All parties are involved in extensive framing, exaggerations, insinuations, gossip, and unfounded accusations.

    The real issue addressed in this thread is that Prof. Aguzzi’s group has produced a number of picture duplications. I feel that the number and character of these duplications are, unfortunately, quite normal for any research group, and they seem to exist of a number of mistakes, minor misconduct (loading controls), and also a few cases of major misconduct.
    For many of the addressed issues, Prof. Aguzzi had no time to react yet, or is not directly responsible as he is neither first nor last author.

    The only case where he can be held accountable for is the Haybaeck et al. 2011 paper, because it looks like major misconduct and the authors did officially respond to it. Their claim of the Fig. 3A and 4A issue being a “mistake” lacks credibility, because no explanation was given, and it took them apparently more than two years to “understand the concern”; the latter is fully unbelievable since the Pubpeer concern was very well expressed. Do we have to believe that neither Dr. Haybaeck nor Prof. Aguzzi understood the concern? Yet, that is what they said, two years after the concerns were initially voiced. Given how this evolved, the most logical explanation would be that Dr. Haebaeck lied about not understanding and that Prof. Aguzzi did not give it a serious look (which would be bad leadership).
    If a first author cheats, or shows neglect beyond acceptability, the whole article loses its credibility and should be retracted because it is indicative of the style with which the paper was forged (it breaks the bond of trust between author and reader).

    So, I urge Dr. Haybaeck and/or Prof. Aguzzi to give a reasonable explanation for the Figs. 3A and 4A issue, or Prof. Aguzzi’s institute to do a serious investigation in this matter.

    If the possible spread of prions through aerosols is an important issue, this paper should be trustworthy or be retracted.

    Like

    • “I feel that the number and character of these duplications are, unfortunately, quite normal for any research group, and they seem to exist of a number of mistakes, minor misconduct (loading controls), and also a few cases of major misconduct.”

      It would be interesting if you gave other examples in the prion field.
      I believe that there may be some, but that would not make them normal.

      Like

  15. Rex Rictor

    I do not agree that these duplications are “quite normal for any research group”

    There is no evidence for this if you look at PubPeer or read the work from Dr. Bik et al.

    Misconduct is not prevalent across the entire literature with most estimates pointing to specific groups and fields and with biases from institutions and countries. Its also important to consider secondary effects, ie other groups trying to follow up on fraudulent science….they may ‘forcefit’ their data to totally bogus claims…that is still bad science but its really aggravated because of the original false claim…something that should be analysed more carefully.

    Like

  16. Pingback: Avvenimenti 2019 - Ocasapiens - Blog - Repubblica.it

  17. I used “normal” in the sense of “usual”.
    Dr. Bik once reported that 4% of papers that can be screened for such have problematic images. Prof. Aguzzi has >450 publications of which 12 were reported on Pubpeer. Not all of the >450 papers probably can be screened for picture duplications, so the percentage is higher than 12/450, but I can’t see why Prof. Aguzzi’s work is exceptional in the number of duplications.
    Moreover, cheating PIs or PIs that force or promote cheating have a very different smell about them, although I realize that such is not a useful argument in a public discussion. I just can point out that even Leonid, currently not a close friend of Prof. Aguzzi, is not accusing him of cheating or of promoting cheating. Leonid’s accusation, and that seems to be a correct accusation, is that Prof. Aguzzi has not acted properly when faced with accusations of cheating by members of his group.

    Back to the core.
    Actually, Prof. Aguzzi kind of lied about the Haybaeck study, when after the initial accusations he said that he checked those accusations with the second first author Dr. Heikenwalder and found them to be untrue:
    “Suffice it to say that Mathias Heikenwälder and I have gone carefully through all original data and we confirm that none of the alleged “manipulations” were performed.”
    I guess that Dr. Heikenwaelder was responsible for the gel studies, and that Dr. Haybaeck who was responsible for the histology pictures Fig. 3A and 4A for some reason did not want to communicate on this with Prof. Aguzzi. Thus, Prof. Aguzzi here seems to claim innocence of all figures whereas he did not investigate Figs. 3A and 4A. Actually, this is very suggestive for Figs. 3A and 4A being product of intentional misconduct, because this would have been a good time for clarifying any innocent mistake.

    There has never been an explanation for the Figs. 3A and 4A duplication with rotation, just:
    First: We don’t understand the accusations (which is fully unbelievable)
    Later: We went back to the original paraffin blocks

    If Figs. 3A and 4A are the product of cheating, it would be very unlikely that the culprit has only cheated once. If you can find additional evidence that the person who made these figures is a cheater, you would make a pretty convincing case.

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  18. Aguzzi has consistently misled others into thinking he has a legit PhD, which he does not. He seems to think that the few papers he published on prions during the 2-3 years before Prusiner got the Nobel merit him a share of that prize, which they do not. He is demonstrably a fabulist, but from what I have seen his papers stop short of fraud, which no-one here has accused him of despite the howling (another aspect of his fabulism). Unless the hints of irregular practices can be substantiated, he stands guilty of semi-competence and of sopping up research resources that could have been put to better use. Thankfully for his national research system he will soon be out of the game, and have more time to devote to suing Leonid, etc.

    Like

    • Nah. He’ll just move to the USA, get a faculty position, and “direct” post-docs until he is 80 or so. With plenty of humble brags on twitter for the next 20 years sigh.

      Like

  19. Adriano Aguzzi

    Sehr geehrter Herr Schneider Ich stelle fest, dass Sie weiterhin verleumderische Unwahrheiten über mich verbreiten und damit meine Unterlassungsaufforderung missachten. Ihre Tweets sind enorm schmerzhaft für mich. Seit einer Woche kann ich nur noch mit Pharmaka einschlafen. Sie haben mir das Leben zur Hölle gemacht und meine Reputation irreparabel geschädigt. Zwar werde ich jede Ihrer Lügen mit dokumentierten Fakten widerlegen, aber Sie wissen genau, dass im Internet die Fakten niemanden interessieren. Und nun spielen Sie Ihre Macht aus, indem sie immer absurdere Behauptungen machen.

    Auf jedem Fall hatte ich gehofft, dass Sie sich besinnen würden und meinen freundlichen Vorschlag annehmen würden, welcher Ihnen erlauben würde, das Gesicht zu wahren und uns beiden viel Aerger und Geld erspart hätte. Sie wollen aber offenbar um jeden Preis eine rechtliche Auseinandersetzung provozieren. Der Rechtsweg war nicht was ich wollte, aber Sie haben mir keine Wahl gelassen. Ich habe nun die Anwaltkanzlei mit meiner Rechtsvertretung, in Deutschland beauftragt, welche bereits gegen Sie erfolgreich geklagt hat und mit Ihren Taktiken erfahren ist. Sie werden in den nächsten Tagen von ihnen hören. Es war hilfreich, dass Sie alle relevanten Gerichtsdokumente ins Internet gestellt haben.

    Ich bin zwar sicher, dass ich Gerechtigkeit vor Gericht bekommen werde. Den ungeheuren Schaden, den Sie mir angetan haben, wird allerdings damit nicht getilgt.

    Warum Sie sich gegen mich ereifern, ist mir völlig unklar. Ich bin kein schlechter Mensch und kein schlechter Leader. Ich habe niemanden jemals gemobbt, und ich bin kein Wissenschaftsbetrüger. Ich habe nie behauptet, dass ich den Nobelpreis verdienen würde (eine Ihrer vielen Lügen) aber meine Forschungsergebnisse sind gewichtig und von vielen reproduziert worden.

    Sie haben mich aus keinem ersichtlichen Grund in den Ruin getrieben. Vernutlich ist das alles eine absurde Rache weil ich Sie auf Twitter gesperrt habe. Es ist sehr wahrscheinlich, dass auch Sie am Ende dieser Auseinandersetzung ruiniert dastehen werden – aber das ist kein Trost für mich und es wird mir mein Leben auch nicht zurückgeben.

    Like

    • Dear Prof. Aguzzi,

      Get a grip. Everyone has a shadow called caricature of himself, and indeed it is cruel and stupid to reduce each other to that. But that’s what enemies do. You may have had one or two prizes which you did not fully deserve, and now you have been ridiculed beyond a level that you may deserve. Just live with it. You are not exactly a choir boy yourself, as you called Leonid’s court verdict fully deserved, although you did not even know what you were talking about since you didn’t know Macchiarini. If you would take a serious look into that case, you might get more sympathy for Leonid. Probably, that statement made it personal for Leonid, and I feel that some things he wrote after that statement of yours shouldn’t have been written.
      On the other hand, Leonid outdid himself in regard to satire (ridiculing), so he shouldn’t be surprised by you not reacting in a polite and reasonable manner. As I expressed before, I find that the ridiculing went too far this time. That is because I like to keep things humane, but also because it distracts from the real issue.
      But, you also have to understand that ridiculing is the only weapon that the “we want cheating in science to stop” community has. We are all coming from a place in which we simply and “properly” addressed cheating issues, and then simply were told that there was no cheating and that 1+1=3.
      Leonid is a crusader, and we love him for it. If he sees some indications of cheating, he sees evil. You can’t negotiate with him or scare him by court actions. Court actions will only increase the public nature of the issue, and because of your colorful character the case will be a nice target for the press. I am much milder than Leonid, but I can see that his unwavering stand is necessary to get anything done.

      There is only one thing you can logically do:
      – Make sure that there is a SERIOUS committee that addresses all listed duplication issues (even the Haybaeck study, although the journal already accepted a correction)
      – Promise to follow their suggestions, whatever it may be, and to release their findings
      – For the rest, forget about this

      As I see it, there is a maximum of two retractions (maybe only one) and a few corrections among the papers for which you are responsible. If you have >450 publications, such is within expectation, and you can easily bear such “losses”.

      If this relaxes your mind:
      -Most similarly aged leaders of similarly sized labs, if under the same scrutiny as you have been put under, would find themselves accused of a similar number of wrongdoings.
      -The treatment that you have received here is still relatively mild, probably because most of “us” feel that there are much worse people than you.

      Like

    • ScienceWhistleBlower

      Dear Mr Aguzzi.

      It seems very unwise for your reputation (what’s left of it) to threaten with legal actions against Mr Schneider. Especially since you refer to a doubtful case involving the surgeon Macchiarini. It’s very inappropriate to use the threats and bad language, given that you work at a medical facility. I’m sure it is very embarrassing for a university hospital to have an employee referring to Macchiarini given that this man performed unethical human experiments that killed people. I would be very careful about that. I’ve taken note of this conduct of yours and will notify the hospital about this. Ethically, this is very troubling for a hospital and university to have such employees.
      Aside from this lack of moral and ethical compass of yours, it is very troubling to see that you have falsely used the title PhD in so many different instances. It cannot be accidental for PhD to occur with your name without you taking note of this.

      Like

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