domenica 31 marzo 2013

Cattiva Condotta Scientifica






Dopo avere postato solo alcuni dei falsi commessi un po' dovunque nel mondo, vorrei cominciare a trarre almeno qualche considerazione generale... Naturalmente, accetto suggerimenti e critche, visto che la materia è del tutto nuova ed in formazione. Specialmente in Italia, questo argomento sembra essere attivamente trascurato: ma sarebbe veramente strano che in tutto il mondo si possa commettere il peccato di miscondotta scientifica e proprio in Italia non esista: sinceramente, io credo che la si sia inventata noi.

Prima o poi, spero molto che i 'blabbermouths' che parlano troppo e sempre a sproposito saranno puniti anche in Italia: per questo motivo riporto questa sintesi dei regolamenti stranieri a riguardo non solo dei falsari, ma anche dei loro complici (corresponsabili dei fatti o delle idee) e dei loro fiancheggiatori (che li difendono, senza direttamente avere compiuto alcunché: un particolare tipo di ignavi). All'estero essi sono tutti punibili, seppure per reati differenti. 

Per esempio: dato che - per uno scienziato - il nascondere 
dati non in accordo con le proprie idee configura il reato 
di 'soppressione', che è diffamante e punibile, dovrebbe per 
contro essere punibile (per diffamazione) anche chi muove ingiustamente tale accusa verso un ricercatore onesto. 
Eppure, in Italia, assistiamo proprio a continue ed abituali 
accuse di questo genere nei confronti degli archeologi, 
spesso disegnati come perfidi artefici di un complotto tutti insieme.
Questo è fin troppo spesso un comportamento proprio dei 
falsari, dei contraffattori e dei fabbricatori di evidenze archeologiche false (tu sai a chi mi riferisco precisamente
vero, Pasuco?), che lo usano per spacciarsi per paladini 
della Vera Scienza, calpestata con spregio dagli improbi.
Inoltre, esiste una precisa responsabilità di chi sa e tace.
Come esiste una precisa responsabilità di Riviste e 
Pubblicazioni che pubblicano materiale discutibile e 
di chi le finanzia.
Sì, è vero: non possiamo ignorare di essere in Italia. Ci 
sono certamente alcuni problemi ben più urgenti di questo. 

Intanto, però, posto egualmente questo interessante contributo - con tutti i links necessari ad un excursus completo nel vasto argomento - che potrà anche richiedere tempo, ma è da considerarsi prezioso. 
Si noterà che la Medicina offre anch'essa i suoi agnelli sacrificali: neurologi, psichiatri, psicologi etc. e credo che alcuni volontari siano già disponibili in Italia (isole comprese).


Scientific misconduct


Scientific misconduct is the violation of the standard codes of scholarly conduct and ethical behavior in 
professional scientific research. A Lancet review on Handling of Scientific Misconduct in Scandinavian 
countries provides the following sample definitions:[1] (reproduced in The COPE report 1999.)[2]

Danish definition: "Intention or gross negligence leading to fabrication of the scientific message or a false credit or emphasis given to a scientist"

Swedish definition: "Intention[al] distortion of the research process by fabrication of data, text, 

hypothesis, or methods from another researcher's manuscript form or publication; or distortion of the 

research process in other ways.

Italian definition: "seems to still be lost somewhere on the way of translation".

The consequences of scientific misconduct can be damaging for both perpetrators[3][4] and any individual 
who exposes it.[5] In addition there are public health implications attached to the promotion of medical 
or other interventions based on dubious research findings.
Contents








Motivation to commit scientific misconduct
According to David Goodstein of Caltech, there are motivators for scientists to commit misconduct, which are 
briefly summarised here.[6]
Career pressure
Science is still a very strongly career-driven discipline. Scientists depend on a good reputation
to receive ongoing support and funding, and a good reputation relies largely on the publication 
of high-profile scientific papers. Hence, there is a strong imperative to "publish or perish". Clearly, 
this may motivate desperate (or fame-hungry) scientists to fabricate results.
To this category may also be added a paranoia that there are other scientists out there who are close
 to success in the same experiment, which puts extra pressure on being the first one. It is suggested as 
a cause of the fraud of Hwang Woo-Suk.[7] A main source of detection comes when other research 
teams in fact fail or get different results.
Ease of fabrication
In many scientific fields, results are often difficult to reproduce accurately, being obscured by 
noiseartifacts, and other extraneous data. That means that even if a scientist does falsify data, he 
can expect to get away with it or at least claim innocence if his results conflict with others in the 
same field. There are no "scientific police" who are trained to fight scientific crimes; all investigations 
are made by experts in science but amateurs in dealing with criminals. It is relatively easy to cheat 
although difficult to know exactly how many scientists fabricate data.[8]

Forms of scientific misconduct
The U.S. National Science Foundation defines three types of research misconduct: fabrication, falsification, 
and plagiarism[9][10]

Fabrication is making up results and recording or reporting them. This is sometimes referred to as 
 "drylabbing".[11]  A more minor form of fabrication is where references are included to give arguments the 
appearance of widespread acceptance, but are actually fake, and/or do not support the argument.[12]

Falsification is manipulating research materials, equipment, or processes or changing or omitting data or 
 results such that the research is not accurately represented in the research record.

Plagiarism is the appropriation of another person's ideas, processes, results, or words without giving 
 appropriate credit. One form is the appropriation of the ideas and results of others, and publishing as to 
make it appear the author had performed all the work under which the data was obtained. A subset is 
citation plagiarism willful or negligent failure to appropriately credit other or prior discoverers, so as to 
give an improper impression of priority. This is also known as, "citation amnesia", the "disregard syndrome" 
and "bibliographic negligence"[13] Arguably, 
this is the most common type of scientific misconduct. Sometimes it is difficult to guess whether authors 
intentionally ignored a highly relevant cite or lacked knowledge of the prior work. Discovery credit 
can also be inadvertently reassigned from the original discoverer to a better-known researcher. This is a 
special case of the Matthew effect.[14]

-Plagiarism-Fabrication - the act of taking an unrelated figure from an unrelated publication and 
 reproducing it exactly in a new publication (claiming that it represents new data). Recent papers from 
the University of Cordoba have come to light showing how this can go undetected and unchallenged 
for years.[15][16]

-Self-plagiarism or multiple publication of the same content with different titles and/or in different 
journals is sometimes also considered misconduct; scientific journals explicitly ask authors not to do this. 
It is referred  to as "salami" (i.e. many identical slices) in the jargon of medical journal editors (MJE). 
According to some MJE this includes publishing the same article in a different language.[17]

The violation of ethical standards regarding human and animal experiments such as the standard that 
a human subject of the experiment must give informed consent to the experiment.[18] Failure to obtain
 ethical approval for clinical studies characterised the case of Joachim Boldt.

Ghostwriting the phenomenon where someone other than the named author(s) makes a major contribution. 
Typically, this is done to mask contributions from drug companies. It incorporates plagiarism and has an 
additional element of financial fraud.

Conversely, research misconduct is not limited to NOT listing authorship, but also includes the conferring 
authorship on those that have not made substantial contributions to the research.[19][20] This is done by 
senior researchers who muscle their way onto the papers of inexperienced junior researchers[21] as well as 
others that stack authorship in an effort to guarantee publication. This is much harder to prove due to a lack 
of consistency in defining "authorship" or "substantial contribution".[22][23][24]

In addition, some academics consider suppression the failure to publish significant findings due to the 
results 
being adverse to the interests of the researcher or his/her sponsor(s) to be a form of misconduct as well.
 ** Bare assertions making entirely unsubstantiated claims - may also be considered a form of research 
misconduct 
although there is no evidence that cases of this form have ever led to a finding of misconduct.
In some cases, scientific misconduct may also constitute violations of the law, but not always. Being accused 
of the activities described in this article is a serious matter for a practicing scientist, with severe consequences 
should it be determined that a researcher intentionally or carelessly engaged in misconduct. However in most countries, committing research misconduct, even on a large scale, is not a legal offence.
Three percent of the 3,475 research institutions that report to the US Department of Health and Human 
Services' Office of Research Integrity, indicate some form of scientific misconduct.[25] However the ORI 
will only investigate allegations of impropriety where research was funded by federal grants. They routinely
 monitor such research publication for red flags. Other private organizations like the Committee of Medical 
Journal Editors (COJE) can only police their own members.
The validity of the methods and results of scientific papers are often scrutinized in journal clubs. In this venue, members can decide amongst themselves with the help of peers if a scientific paper's ethical standards are met.

Responsibility of authors and of coauthors
Authors and coauthors of scientific publications have a variety of responsibilities. Contravention of the rules 
of scientific authorship may lead to a charge of scientific misconduct. All authors, including coauthors, 
are expected to have made reasonable attempts to check findings submitted to academic journals for 
 publication. Simultaneous submission of scientific findings to more than one journal or duplicate publication 
of findings is usually regarded as misconduct, under what is known as the Ingelfinger rule, named after the 
 editor of the New England Journal of Medicine 1967-1977, Franz Ingelfinger.[26]
Guest authorship (where there is stated authorship in the absence of involvement, also known as gift authorship) 
and ghost authorship (where the real author is not listed as an author) are commonly regarded as forms of 
research misconduct. In some cases coauthors of faked research have been accused of inappropriate behavior 
 or research misconduct for failing to verify reports authored by others or by a commercial sponsor. Examples 
include the case of Gerald Schatten who co-authored with Hwang Woo-Suk, the case of Professor Geoffrey Chamberlain named as guest author of papers fabricated by Malcolm Pearce,[27] (Chamberlain was exonerated 
from collusion in Pearce's deception)[28] - and the coauthors with Jan Hendrik Sch n at Bell Laboratories. More 
recent cases include that of Charles Nemeroff,[29] then the editor-in-chief of Neuropsychopharmacology, and 
a well-documented case[30] involving the drug Actonel.
Authors are expected to keep all study data for later examination even after publication. The failure to keep 
 data may be regarded as misconduct. Some scientific journals require that authors provide information to 
allow readers to determine whether the authors might have commercial or non-commercial conflicts of interest. Authors are also commonly required to provide information about ethical aspects of research, particularly 
where research involves human or animal participants or use of biological material. Provision of incorrect 
information to journals may be regarded as misconduct. Financial pressures on universities have encouraged 
this type of misconduct. The majority of recent cases of alleged misconduct involving undisclosed conflicts 
of interest or failure of the authors to have seen scientific data involve collaborative research between scientists 
and biotechnology companies (Nemeroff,[29] Blumsohn).[31]

Responsibilities of research institutions
In general, defining whether an individual is guilty of misconduct requires a detailed investigation by the 
 individual's employing academic institution. Such investigations require detailed and rigorous processes 
and can be extremely costly. Furthermore, the more senior the individual under suspicion, the more likely it 
is that conflicts of interest will compromise the investigation. In many countries (with the notable exception 
of the United States) acquisition of funds on the basis of fraudulent data is not a legal offence and there is consequently no regulator to oversee investigations into alleged research misconduct. Universities therefore 
have few incentives to investigate allegations in a robust manner, or act on the findings of such investigations 
if they vindicate the allegation.
Well publicised cases illustrate the potential role that senior academics in research institutions play in 
 concealing scientific misconduct. A King's College (London) internal investigation showed research findings
 from one of their researchers to be 'at best unreliable, and in many cases spurious' [32] but the college took 
no action e.g. retracting relevant published research, or preventing further episodes from occurring. It was only 
10 years later,  when an entirely separate form of misconduct by the same individual was being investigated 
by the General  Medical Council, that the internal report came to light.
In a more recent case[33] an internal investigation at the National Centre for Cell Science (NCCS), Pune 
determined that there was evidence of misconduct by Dr. Gopal Kundu, but an external committee was then 
organised which dismissed the allegation, and the NCCS issued a memorandum exonerating the authors of 
all charges of misconduct. Undeterred by the NCCS exoneration, the relevant journal (Journal of Biological Chemistry) withdrew the paper based on its own analysis.

Responsibilities of scientific colleagues who are "bystanders"
Some academics believe that scientific colleagues who suspect scientific misconduct should consider taking 
informal action themselves, or reporting their concerns.[34] This question is of great importance since much 
research suggests that it is very difficult for people to act or come forward when they see unacceptable behavior, 
unless they have help from their organizations. A "User-friendly Guide," and the existence of a confidential organizational ombudsman may help people who are uncertain about what to do, or afraid of bad 
consequences for their speaking up.[35]

Responsibility of journals
Journals are responsible for safeguarding the research record and hence have a critical role in dealing with suspected misconduct. This is recognised by the Committee on Publication Ethics (COPE) which has issued clear guidelines[36] on the form (e.g. retraction) that concerns over the research record should take.
  • The COPE guidelines state that journal editors should consider retracting a publication if they have clear evidence that the findings are unreliable, either as a result of misconduct (e.g. data fabrication) or honest error (e.g. miscalculation or experimental error). Retraction is also appropriate in cases of redundant publication, plagiarism and unethical research.
  • Journal editors should consider issuing an expression of concern if they receive inconclusive evidence of research or publication misconduct by the authors, there is evidence that the findings are unreliable but the authors' institution will not investigate the case, they believe that an investigation into alleged misconduct related to the publication either has not been, or would not be, fair and impartial or conclusive, or an investigation is underway but a judgement will not be available for a considerable time.
  • Journal editors should consider issuing a correction if a small portion of an otherwise reliable publication proves to be misleading (especially because of honest error), or the author / contributor list is incorrect (i.e. a deserving author has been omitted or somebody who does not meet authorship criteria has been included).
Recent evidence has emerged that journals learning of cases where there is strong evidence of possible
 misconduct, with issues potentially affecting a large portion of the findings, frequently fail to issue an expression
 of concern or correspond with the host institution so that an investigation can be undertaken. In one case the 
Journal of Clinical Oncology issued a Correction despite strong evidence that the original paper was invalid.[16] 
 In another case,[37] Nature allowed a Corrigendum to be published despite clear evidence of image fraud. 
Subsequent Retraction of the paper required the actions of an independent whistleblower.[38]
The recent cases of Joachim Boldt and Yoshitaka Fujii[39] in anaesthesiology have focussed attention on the 
role that journals play in perpetuating scientific fraud as well as how they can deal with it. In the Boldt case, the Editors-in-Chief of 18 specialist journals (generally anaesthesia and intensive care) made a joint statement 
regarding 88 published clinical trials conducted without Ethics Committee approval. In the Fujii case, involving nearly 200 papers, the journal Anesthesia & Analgesia, which published 24 of Fujii's papers, has accepted that
 its handling of the issue was inadequate. Following publication of a Letter to the Editor from Kranke and 
colleagues in April 2000,[40] along with a non-specific response from Dr. Fujii, there was no follow-up on the allegation of data manipulation and no request for an institutional review of Dr. Fujii's research. Anesthesia & Analgesia went on to publish 11 additional manuscripts by Dr. Fujii following the 2000 allegations of research 
fraud, with Editor Steven Shafer stating[41] in March 2012 that subsequent submissions to the Journal by Dr. 
Fujii should not have been published without first vetting the allegations of fraud. In April 2012 Shafer led a 
group of editors to write a joint statement,[42] in the form of an ultimatum made available to the public, to a 
large number of academic institutions where Fujii had been employed, offering these institutions the chance 
to attest to the integrity of the bulk of the allegedly fraudulent papers.

Photo manipulation
Compared to other forms of scientific misconduct, image fraud (manipulation of images to distort their meaning) 
is of particular interest since it can frequently be detected by external parties. In 2006, the Journal of Cell Biology gained publicity for instituting tests to detect photo manipulation in papers that were being considered for publication.[43] This was in response to the increased usage of programs by scientists such as Adobe Photoshop
 which facilitate photo manipulation. Since then more publishers, including the Nature Publishing Group, have instituted similar tests and require authors to minimize and specify the extent of photo manipulation when a manuscript is submitted for publication. However there is little evidence to indicate that such tests are applied rigorously. One Nature paper published in 2009[37] has subsequently been reported to contain around 20 separate instances[44] of image fraud.
Although the type of manipulation that is allowed can depend greatly on the type of experiment that is presented 
and also differ from one journal to another, in general the following manipulations are not allowed:
  • splicing together different images to represent a single experiment
  • changing brightness and contrast of only a part of the image
  • any change that conceals information, even when it is considered to be aspecific, which includes:
    • changing brightness and contrast to leave only the most intense signal
    • using clone tools to hide information
  • showing only a very small part of the photograph so that additional information is not visible
Suppression/non-publication of data
A related issue concerns the deliberate suppression, failure to publish, or selective release of the findings of 
scientific studies. Such cases may not be strictly definable as scientific misconduct as the deliberate falsification 
of results is not present. However, in such cases the intent may nevertheless be to deliberately deceive. Studies 
may be suppressed or remain unpublished because the findings are perceived to undermine the commercial, 
political or other interests of the sponsoring agent or because they fail to support the ideological goals of the researcher. Examples include the failure to publish studies if they demonstrate the harm of a new drug, or 
truthfully publishing the benefits of a treatment while omitting harmful side-effects.
This is distinguishable from other concepts such as bad science, junk science or pseudoscience where the 
criticism centres on the methodology or underlying assumptions. It may be possible in some cases to use 
statistical methods to show that the datasets offered in relation to a given field are incomplete. However this 
may simply reflect the existence of real-world restrictions on researchers without justifying more sinister 
conclusions.
Some cases go beyond the failure to publish complete reports of all findings with researchers knowingly making 
false claims based on falsified data. This falls clearly under the definition of scientific misconduct, even if 
the result was achieved by suppressing data. In the case of Raphael B. Stricker, M.D.,[45] for instance, the U.S. 
 Office of Research Integrity has found the removal of samples from a data set in order to reach a desired 
conclusion to be grounds for disbarment from funding.

Consequences for science
The consequences of scientific fraud vary based on the severity of the fraud, the level of notice it receives, and 
how long it goes undetected. For cases of fabricated evidence, the consequences can be wide ranging, with 
others working to confirm (or refute) the false finding, or with research agendas being distorted to address the fraudulent evidence. The Piltdown Man fraud is a case in point: The significance of the bona-fide fossils' being 
found was muted for decades because they disagreed with Piltdown Man and the pre-conceived notions that 
those faked fossils supported. In addition, the prominent paleontologist Arthur Smith Woodward spent time at Piltdown each year until he died trying to find more Piltdown Man remains. The misdirection of resources kept 
others from taking the real fossils more seriously and delayed the reaching of a correct understanding of human evolution. (The Taung Child, which should have been the death knell for the view that the human brain evolved 
 first, was instead treated very critically because of its disagreement with the Piltdown Man evidence.)
In the case of Dr Alfred Steinschneider, two decades and tens of millions of research dollars were lost trying to 
find the elusive link between infant sleep apnea, that Steinschneider said he had observed and recorded in his laboratory and claimed was a precursor of sudden infant death syndrome (SIDS). The cover was blown in 1994, 
22 years after Steinschneider's 1972 Pediatrics paper claiming such an association,[46] when Waneta Hoyt, the
 mother of the patients in the paper, was arrested, indicted and convicted on 5 counts of second degree 
manslaughter for the smothering deaths of her five children.[47] While that in itself was bad enough, the paper, presumably written as an attempt in trying to save infants' lives, ironically was ultimately used as a defense in 
cases where parents were suspected in multiple deaths of their own children in cases of M nchausen syndrome 
by proxy. The 1972 Pediatrics' paper was cited by 404 papers in the interim and is still listed on Pubmed 
without comment.[48]

Consequences for those who expose misconduct
The potentially severe consequences for individuals who are found to have engaged in misconduct also reflect 
on the institutions that host or employ them and also on the participants in any peer review process that has 
allowed the publication of questionable research. This means that a range of actors in any case may have a 
motivation to suppress any evidence or suggestion of misconduct. Persons who expose such cases, commonly 
called whistleblowers, can find themselves open to retaliation by a number of different means.[27] These 
negative consequences for exposers of misconduct have driven the development of whistle blowers charters - 
designed to protect those who raise concerns. A whistleblower is almost always alone in his fight - his career 
becomes completely dependent on the decision about alleged misconduct. If the accusations prove false, his 
career is completely destroyed, but even in case of positive decision the career of the whistleblower can be 
under question: his reputation of "troublemaker" will prevent many employers from hiring him. There is no international body where a whistleblower could give his concerns. If a university fails to investigate suspected
fraud or provides a fake investigation to save their reputation the whistleblower has no right of appeal. High 
profile journals like Nature and Science usually forward all allegations to the university where the authors 
are employed, or may do nothing at all.

Exposure of fraudulent data
With the advancement of the internet, there are now several tools available to aid in the detection of plagiarism 
and multiple publication within biomedical literature. One tool developed in 2006 by researchers in Dr. Harold Garner's laboratory at the University of Texas Southwestern Medical Center at Dallas is D j Vu,[49] an open-
access database containing several thousand instances of duplicate publication. All of the entries in the database 
were discovered through the use of text data mining algorithm eTBLAST, also created in Dr. Garner's laboratory. 
The creation of D j Vu[50] and the subsequent classification of several hundred articles contained therein have 
ignited much discussion in the scientific community concerning issues such as ethical behavior, journal standards, and intellectual copyright. Studies on this database have been published in journals such as Nature and Science, among others.[51][52]
Other tools which may be used to detect fraudulent data include error analysis. Measurements generally have a 
small amount of error, and repeated measurements of the same item will generally result in slight differences in readings. These differences can be analyzed, and follow certain known mathematical and statistical properties. 
Should a set of data appear to be too faithful to the hypothesis, i.e., the amount of error that would normally be 
in such measurements does not appear, a conclusion can be drawn that the data may have been forged. Error 
analysis alone is typically not sufficient to prove that data have been falsified or fabricated, but it may provide 
the supporting evidence necessary to confirm suspicions of misconduct.

Data sharing
Kirby Lee and Lisa Bero suggest, "Although reviewing raw data can be difficult, time-consuming and expensive, having such a policy would hold authors more accountable for the accuracy of their data and potentially reduce scientific fraud or misconduct."[53]


Individual cases
Research conducted during employment by an institution or a corporation
Australia
David Copolov ,psychiatrist and Pro Vice Chancellor of Monash University was found to have plagiarized from 
Oliver Wendell Holmes in his valedictory address in 2012. The incidence was reported in the respected journal 
Nature .http://www.nature.com/news/report?article=1.11507&comment=54919
China
  • H. Zhong, T. Liu, and their co-workers at Jinggangshan University have retracted numerous papers published in Acta Crystallographica following systematic checking which revealed that the organic structures claimed 
  • in these papers were impossible or implausible. The supporting data appeared to have been taken from valid cases which had then been altered by substituting different atoms into the structures.[54][55]
Denmark
Germany
Great Britain
Japan
Romania
Netherlands
  • Henk Buck Professor at Eindhoven University, he had to end his career prematurely because of a publication in Science in 1990 that had to be retracted because of flawed research.
  • Don Poldermans
  • Diederik Stapel (social psychology) fabricated data in high-publicity studies of human behaviour.[75]
Norway
  • A researcher employed by a Norwegian hospital (Stavanger universitetssjukehus) analyzed samples of spinal fluid from patients, after the researcher had added a substance to the sample.[76]
  • Jon Sudb fabricated data for a study that reported "nonsteroidal anti-inflammatory drugs reduced the risk of oral cancer".[77]
South Africa
South Korea
Spain
Switzerland
United States
Non-institutional and non-corporate research
See also
Categories
Notes
References
External links

INOLTRE, Per chi non lo sapesse: 

circa due anni fa Diederik Stapel (noto ed influente psicologo sociale) fu sospeso dall' universita'
a Tilburg per miscondotta scientifica. Un piccolo gruppo di postdoc, dopo aver sospettato che ci
fosse qualcosa di strano nei suoi metodi di ricerca, ha raccolto per mesi prove della sua miscondotta
per poterlo denunciare al rettore di Tilburg.

Dopo un anno di indagini, e' ormai chiaro che Stapel abbia torturato, manipolato, e fabbricato dati
per diversi anni, dando luce a quasi un centinaio di pubblicazioni basate su dati manipolati o
fabbricati per intero, decine di tesi di dottorato macchiate o fabbricate anch'esse per intero su dati inesistenti.

Per sua stessa ammissione Stapel ha descritto la sua condotta scientifica grigia quando era ad Amsterdam (pubblicava articoli nascondendo alcune DV o a le condizioni sperimentali, oppure rimuoveva risultati scomodi dal dataset senza dichiararlo), nera quando era a Groningen (manipolazione dei dati e creazione di dati fasulli), e delirante quando era a Tilburg (creazione
manuale di dataset, bugie a tutte spiano a collaboratori e studenti etc.).

Questo e' il report finale dell'indagine,
vi consiglio di leggerlo, e' molto interessante
http://www.tilburguniversity.edu/nl/nieuws-en-agenda/finalreportLevelt.pdf

INFINE, guarda qui, se vuoi farti un'idea della manipolazione dei dati:
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0005738