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Cancer StemCells in Head and Neck Squamous Cell Cancer

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Four key characteristics define the CSC subpopulation: (1) only a small portion of the cancer cells within a tumor have tumorigenic potential when transplanted into immunodeficientmice; (2) the CSC subpopulation can be separated from the other cancer cells by distinctive cell surface markers; (3) tumors resulting from the CSCs contain the mixed tumorigenic and nontumorigenic cells of the original tumor; and (4) theCSC subpopulation can be serially transplanted through multiple generations, indicatingthatitisa self-renewing population.
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Nagele
lidocaine 2% for peribulbar anaesthesia in terms of speed of Acknowledgement
onset of anaesthesia. This surprising ®nding was in contrast We gratefully acknowledge the support of Abbott Pharmaceuticals, who
to other studies, which found no difference between the two provided supplies of L-bupivacaine and ®nancial assistance.
compounds in terms of time to satisfactory extradural block5
or peribulbar block.6 In the latter study, however, large
volumes of
References
L-bupivacaine 0.75% were used as a single agent
and patients received up to three injections of local
1 Wong DHW. Regional anaesthesia for intraocular surgery. Can J
anaesthetic. In this study, we used a single injection
Anaesth 1993; 40: 635±57
technique and equal volumes of lidocaine 2% and either
2 Albright GA. Cardiac arrest following regional anaesthesia with
etidocaine or bupivacaine. Anesthesiology 1979; 52: 285±7
bupivacaine or L-bupivacaine, thereby reducing its concen-
3 Heath M. Deaths after intravenous regional anaesthesia. Br Med J
tration to 0.375%.
1983; 285: 913±14
We were unable to assess the duration of motor block as
4 McLeod GA, Burke D. Levobupivacaine. Anaesthesia 2001; 56:
patients' eyes were bandaged and covered postoperatively
331±41
and they were discharged home 1±2 h after surgery. If a
5 Cox CR, Faccenda KA, Gilhooly C, Bannister J, Scott NB.
shorter duration of motor block occurs with L-bupivacaine,
Extradural S(±)-bupivacaine: comparison with racemic RS-
this could be advantageous as prolonged paralysis from
bupivacaine. Br J Anaesth 1998; 80: 289±93
6 McLure HA, Rubin AP. Comparison of 0.75% levobupivacaine
local anaesthesia leaves the eye vulnerable to drying and
with 0.75% racemic bupivacaine for peribulbar anaesthesia.
trauma.
Anaesthesia 1998; 53: 1160±4
Peribulbar anaesthesia requires relatively large volumes
7 Brahma AK, Pemberton CJ, Ayeko M, Morgan LH. Single medial
Downloaded from
of local anaesthetic and concerns have been expressed about
injection peribulbar anaesthesia using prilocaine. Anaesthesia
the potential for systemic toxicity. The incidence of
1994; 49: 1003±5
peribulbar blocks requiring supplementary anaesthesia has
8 Loots JH, Koorts AS, Venter JA. Peribulbar anesthesia. A
been reported to be as high as 54%.8 However,
prospective statistical analysis of the ef®cacy and predictability
L-
of bupivacaine and a lidocaine/bupivacaine mixture. J Cataract
bupivacaine is less toxic to the myocardium and central
Refract Surg 1993; 19: 72±6
bja.oxfordjournals.org
nervous system.9 10 While L-bupivacaine may have theor-
9 Kopacz DJ, Allen HW. Accidental intravenous levobupivacaine.
etical advantages in elderly patients with coexisting cardiac
Anesth Analg 1999; 89: 1027±9
disease, the present study did not show any untoward effects
10 Bardsley H, Gristwood R, Baker H, Watson N, Nimmo W.
with either drug. L-Bupivacaine did not demonstrate any
Comparison of the cardiovascular effects of levobupivacaine and
advantages over racemic bupivacaine when used for
rac-bupivacaine following intravenous administration to healthy
peribulbar anaesthesia.
volunteers. Br J Clin Pharmacol 1998; 46: 245±9
by guest on February 15, 2011
British Journal of Anaesthesia 90 (4): 514±16 (2001)
DOI: 10.1093/bja/aeg087
Misuse of standard error of the mean (SEM) when reporting
variability of a sample. A critical evaluation of four anaesthesia
journals
P. Nagele*
Department of Anesthesiology and General Intensive Care, University of Vienna, Austria and Department of
Anesthesiology, Washington University School of Medicine, St Louis, MO, USA
*Address for correspondence: Department of Anesthesiology and General Intensive Care, University of Vienna,
WaÈhringer GuÈrtel 18±20, A-1090 Vienna, Austria. E-mail: peter.nagele@univie.ac.at
Background. In biomedical research papers, authors often use descriptive statistics to
describe the study sample. The standard deviation (SD) describes the variability between
individuals in a sample; the standard error of the mean (SEM) describes the uncertainty of how
the sample mean represents the population mean. Authors often, inappropriately, report the
SEM when describing the sample. As the SEM is always less than the SD, it misleads the reader
into underestimating the variability between individuals within the study sample.
Ó The Board of Management and Trustees of the British Journal of Anaesthesia 2003

Misuse of SEM
Methods. The aim of this study was to evaluate the frequency of inappropriate use of the SEM
in four leading anaesthesia journals in 2001. The journals were searched manually for
descriptive statistics reporting either the mean (SD) or the mean (SEM), and inappropriate use of
the SEM was noted.
Results. In 2001, all four anaesthesia journals published articles that used the SEM incorrectly:
Anesthesia & Analgesia 27.7%, British Journal of Anaesthesia 22.6%, Anesthesiology 18.7% and
European Journal of Anaesthesiology 11.5%. Laboratory reports and clinical studies were equally
affected, except for Anesthesiology where 90% were basic science reports.
Conclusions. One in four articles (n=198/860, 23%) published in four anaesthesia journals in
2001 inappropriately used the SEM in descriptive statistics to describe the variability of the
study sample. Anaesthesia journals are encouraged to provide clearer statistical guidelines on
how to report data variability in descriptive statistics.
Br J Anaesth 2003; 90: 514±16
Keywords: statistics
Accepted for publication: December 3, 2002
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When reporting data in biomedical research papers, authors precise our estimate of the mean is.3 It is therefore
often use descriptive statistical methods to describe their inappropriate and incorrect to present data only as the
study sample. Descriptive statistics aim to describe a given mean (SEM).
study sample without regard to the entire population;
This evaluation was designed to identify the frequency of
bja.oxfordjournals.org
inferential statistics generalize about a population on the this statistical error in articles published in 2001 in four
basis of data from a sample of this population.
leading anaesthesia journals: two from the USA
If normally distributed, the study sample can be described (Anesthesiology and Anesthesia & Analgesia), and two
entirely by two parameters: the mean and the standard from Europe (British Journal of Anaesthesia and European
deviation (SD). The SD represents the variability within the Journal of Anaesthesiology).
sample; the larger the SD, the higher the variability within
by guest on February 15, 2011
the sample.1 Although it is clear that samples should always
be summarized by the mean and
Methods and results
SD,2±5 authors often use the
standard error of the mean (SEM) to describe the variability All articles published in Anesthesiology, Anesthesia &
of their sample. The SEM is used in inferential statistics to Analgesia, British Journal of Anaesthesia or European
give an estimate of how the mean of the sample is related to Journal of Anaesthesiology in 2001 were searched manually
the mean of the underlying population. As the SEM is always for descriptive statistics reporting either mean (SD) or mean
smaller than the SD, the unsuspecting reader may think that (SEM). Inappropriate use of the SEM in text, ®gures and
the variability within the sample is much smaller than it tables was noted when the SEM was used to describe the
really is. Although the SD and the SEM are related (SEM=SD/ variability of the study sample (instead of SD). Excluded
Ön), they give two very different types of information.6 from this analysis were articles using median and range, and
Whereas the SD estimates the variability in the study sample, articles that solely used inferential statistics such as
the SEM estimates the precision and uncertainty of how the con®dence intervals (CI). Case reports and review articles
study sample represents the underlying population.1 7 In were not considered, except for case series comprising
other words, the SD tells us the distribution of individual several cases and using descriptive statistics to describe the
data points around the mean, and the SEM informs us how study sample.
Table 1 Frequency of use of standard error of the mean (SEM) and standard deviation (SD) in four anaesthesia journals, listed in order of decreasing
percentage misuse. Data are numbers of articles (%). *Some of these articles used both the SD and the SEM to describe the study sample
Incorrect use of
Laboratory studies
Correct use of SD
Total
SEM;total*
using SEM incorrectly
Anesthesia & Analgesia
112 (27.7)
66 (59)
293 (72.3)
405
British Journal of Anaesthesia
31 (22.6)
15 (47)
106 (77.4)
137
Anesthesiology
48 (18.7)
43 (90)
209 (81.3)
257
European Journal of Anaesthesiology
7 (11.5)
3 (43)
54 (88.5)
61
515

Nagele
A total of 257 articles ful®lled the search criteria in statistical error by requiring authors to adhere to statistical
Anesthesiology, 405 articles in Anesthesia & Analgesia, 137 recommendations, for instance through a more stringent
in the British Journal of Anaesthesia, and 61 in the statistical review process. The goal should be to have one
European Journal of Anaesthesiology. Detailed results are standard method to describe the distribution of a study
given in Table 1, where the four journals are listed in order sample, thereby reducing confusion among the readers of
of decreasing percentage misuse of SEM. Eight articles each biomedical research papers.
in Anesthesiology and Anesthesia & Analgesia even failed
to state which parameter was used. It must be noted that in
some of the articles that incorrectly used the
Acknowledgements
SEM, both
parameters, SEM and SD, were used. In these articles, the SD The author wishes to thank C. Michael Crowder MD PhD for his helpful
was mostly found in the text and the
comments on the manuscript, and Dennis M. Fisher MD and Doug Altman
SEM in the ®gures.
DSc for valuable comments on biomedical statistics.
The author was supported by the Fonds zur FoÈrderung der
Wissenschaftlichen Forschung (FWF)ÐAustrian Science FundÐas the
Discussion
recipient of an Erwin-SchroÈdinger research fellowship.
This evaluation of four leading anaesthesia journals
shows clearly that a signi®cant number of published References
articles (mis-)use the SEM in descriptive statistics, which
1 Glantz S. Primer of Biostatistics, 4th Edn. New York: McGraw-Hill,
may be misinterpreted as showing the variability within
1997
the study sample. This use is not only statistically
2 Fisher DM. Research design and statistics in anesthesia. In: Miller
Downloaded from
inappropriate, it also makes the reader assume a much
RD, ed. Anesthesia, 5th Edn, Vol. 1. Philadelphia: Churchill
smaller variability of the sample. In general, the use of
Livingston, 2000; 753±92
the SEM should be limited to inferential statistics where
3 Streiner DL. Maintaining standards: differences between the
the author explicitly wants to inform the reader about
standard deviation and standard error, and when to use each.
the precision of the study, and how well the sample
Can J Psychiatry 1996; 41: 498±502
4 Altman DG, Gore SM, Gardner MJ, et al. Statistical guidelines for
bja.oxfordjournals.org
truly represents the entire population. Thus, in inferential
contributors to medical journals. Br Med J 1983; 286: 1489±93
statistics, the use of SEM is valid but the CI is more
5 Lang TASM. How to report statistics in medicine: annotated guidelines
valuable. In graphs and ®gures, use of SD is preferable
for authors, editors, and reviewers. Philadelphia: American College
to the SEM but the SEM can be used to improve the
of Physicians, 1997
interpretation of the ®gure if the number of individuals/
6 Carlin JB, Doyle LW. Basic concepts of statistical reasoning:
experiments and the CI are clearly stated.
standard errors and con®dence intervals. J Paediatr Child Health
In conclusion, in spite of clear recommendations, the
2000; 36: 502±5
SEM
by guest on February 15, 2011
7 Webster CS, Merry AF. The standard deviation and the standard
is still widely and inappropriately used in the anaesthesia
error of the mean. Anaesthesia 1997; 52: 183
literature. Anaesthesia journals could easily avoid this
516

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