Validation of Tool Mark Comparisons Obtained Using a Quantitative, Comparative, Statistical Algorithm

At the beginning of a new millennium it seems a good idea to stop for a moment and take stock of the current state of forensic science. As a field of scientific research and scientific application, forensic science is a little more than a century old. Forensic science may be said to have begun in 1887 with the simultaneous publication of A. Conan Doyle’s A Study in Scarlet and Hans Gross’s Handbuch für Untersuchungsrichter. Conan Doyle’s novel introduced to the world the character of Sherlock Holmes, whose literary career would popularize the use of physical evidence in criminal investigations. Gross’s manual for examining magistrates suggests ways in which the expertise of chemists, biologists, geologists, and other natural scientists could contribute to investigations. Gross’s book was translated into a number of languages and went through various updated editions during the course of the century. The intervening century saw the development and application of fingerprinting, firearm and tool mark identification, forensic chemistry, forensic biology, forensic toxicology, forensic odontology, forensic pathology, and forensic engineering. Increasingly, the judicial systems of the industrial nations of the world have come to rely upon the expertise of scientists in a variety of disciplines. In most advanced countries, virtually all criminal prosecutions now involve the presentation of scientific testimony. This has had the beneficial effect of diminishing the reliance of courts on eyewitness testimony and defendant confessions.

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Response to Comment on “Circadian rhythms in the absence of the clock gene Bmal1”

Science ◽

10.1126/science.abf1941 ◽

2021 ◽

Vol 372 (6539) ◽

pp. eabf1941

Author(s):

Sandipan Ray ◽

Utham K. Valekunja ◽

Alessandra Stangherlin ◽

Steven A. Howell ◽

Ambrosius P. Snijders ◽

...

Keyword(s):

Circadian Rhythms ◽

Clock Gene ◽

Statistical Significance ◽

Statistical Measures ◽

Statistical Algorithm ◽

Low Amplitude ◽

Lines Of Evidence

Abruzzi et al. argue that transcriptome oscillations found in our study in the absence of Bmal1 are of low amplitude, statistical significance, and consistency. However, their conclusions rely solely on a different statistical algorithm than we used. We provide statistical measures and additional analyses showing that our original analyses and observations are accurate. Further, we highlight independent lines of evidence indicating Bmal1-independent 24-hour molecular oscillations.

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Clinical Importance of Myc Family Oncogene Aberrations in Epithelial Ovarian Cancer

JNCI Cancer Spectrum ◽

10.1093/jncics/pky047 ◽

2018 ◽

Vol 2 (3) ◽

Cited By ~ 1

Author(s):

MoonSun Jung ◽

Amanda J Russell ◽

Catherine Kennedy ◽

Andrew J Gifford ◽

Kylie-Ann Mallitt ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Mrna Expression ◽

Clinical Significance ◽

Copy Number ◽

Family Members ◽

Activity Score ◽

Gene Copy ◽

Myc Oncogene ◽

Statistical Algorithm

Abstract Background The Myc oncogene family has been implicated in many human malignancies and is often associated with particularly aggressive disease, suggesting Myc as an attractive prognostic marker and therapeutic target. However, for epithelial ovarian cancer (EOC), there is little consensus on the incidence and clinical relevance of Myc aberrations. Here we comprehensively investigated alterations in gene copy number, expression, and activity for Myc and evaluated their clinical significance in EOC. Methods To address inconsistencies in the literature regarding the definition of copy number variations, we developed a novel approach using quantitative polymerase chain reaction (qPCR) coupled with a statistical algorithm to estimate objective thresholds for detecting Myc gain/amplification in large cohorts of serous (n = 150) and endometrioid (n = 80) EOC. MYC, MYCN, and MYCL1 mRNA expression and Myc activity score for each case were examined by qPCR. Kaplan–Meier and Cox-regression analyses were conducted to assess clinical significance of Myc aberrations. Results Using a large panel of cancer cell lines (n = 34), we validated the statistical algorithm for determining clear thresholds for Myc gain/amplification. MYC was the most predominantly amplified of the Myc oncogene family members, and high MYC mRNA expression levels were associated with amplification in EOC. However, there was no association between prognosis and increased copy number or gene expression of MYC/MYCN/MYCL1 or with a pan-Myc transcriptional activity score, in EOC, although MYC amplification was associated with late stage and high grade in endometrioid EOC. Conclusion A systematic and comprehensive analysis of Myc genes, transcripts, and activity levels using qPCR revealed that although such aberrations commonly occur in EOC, overall they have limited impact on outcome, suggesting that the biological relevance of Myc oncogene family members is limited to certain subsets of this disease.

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