Means Of Error Correction Research Articles

Abstract 2440: Cancer driver mutations as quantitative biomarkers of cancer risk interspecies analyses using CarcSeq

Abstract Unmet needs in cancer risk assessment include the ability to predict rodent life-time tumor responses from short-term exposures and a scientific basis for rodent to human extrapolation. As an approach to address these needs, the use of hotspot cancer driver mutations (CDMs) as biomarkers of cancer risk was integrated with an error-corrected, next generation sequencing (NGS) approach. We have developed and investigated the sensitivity of a high-throughput NGS method capable of detecting a panel of the most prevalent point mutations observed in human oncogenes and tumor suppressor genes. This method, CarcSeq, involves performing multiple, high-fidelity PCR reactions to amplify the most prevalent mutations reported to occur in human tumors, tagging the amplicons with 9 bp unique identifier sequences at each end, constructing libraries using Illumina ChIP Seq kits, sequencing the libraries on an Illumina NextSeq500 platform and generating single-strand consensus sequences (SSCS), bioinformatically, as a means of error-correction. We validated CarcSeq mutant fraction measurements through observations related to known cancer driver tissue-specificities and mutation spectra for normal human breast and lung, ductal carcinoma, and lung adenocarcinoma samples. Performance of a reconstruction experiment established CarcSeq has a sensitivity of 104. The approach has now been adapted to analyze analogous conserved codons in rat and mouse. For each of the three species, the developed panel includes 13-15 amplicons encompassing known cancer driver genes (e.g., KRAS, PIK3CA, and TP53) encompasses the equivalent of 30 known human hotspot codons and has a combined target sequence length of ~1 kb. Amplicons were generated from DNA isolated from 16-week-old, untreated rodent tissue samples with known differences in spontaneous tumor incidence: female Wistar, Sprague Dawley, and F344 rat mammary samples and male and female B6C3F1 and CD-1 mouse lung samples. The rodent panel was optimized to generate ~100,000 SSCS/amplicon. CDMs were observed at conserved codons in young, untreated rodents, and results are consistent with what was expected based on strain differences in spontaneous tumorigenesis. Citation Format: Kelly L. Harris, Binsheng Gong, Barbara Parsons, Jennifer Faske, Joshua Xu. Cancer driver mutations as quantitative biomarkers of cancer risk interspecies analyses using CarcSeq [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2440.

Error Correction of Restrictive Measures: Appeals Made by Young People in Care

The article examines appeals against restrictive measures in child protection submitted to and decided upon by administrative courts in Finland. Restrictive measures used in care restrict children’s and young people’s fundamental and human rights considerably, meaning ‘confinement in fractions’. Therefore, young people’s access to justice is an important issue in situations in which they consider an error to have been made. We study appeals as a form of legal safety and as a means of error correction. Although young people, 12 years of age and older, have the right to appeal, the appeal system is mainly used by parents to appeal against restriction of contact. As such, the appeal system poorly protects young people’s individual access to justice, if at all. As only administrative courts can overturn the decision to apply restrictive measures, the adult-centeredness of the system and young people’s access to justice should be critically assessed and rethought.

Meiosis decreases recombination load; Mitosis increases recombination load

Chiasmata are necessary for proper chromosomal segregation, but can result in inadvertent recombination. Bernstein and Michod demonstrated that meiosis evolved as a means of error correction, not genetic mixing. Therefore meiotic recombination is not the sine qua non of sex, but is instead an epiphenomenon of imperfect meiotic error correction. By correcting against recombinant genotypes, meiosis reduces recombination load, thereby providing an unappreciated selective advantage for sex. Sex reducing recombination load should be integrated into population genetic models of multi-locus epistasis for maintenance of sex and may explain sequestration of germ lines in animals. We predict that eumetazoa have less recombination load than sexual organisms without a germ line. Mitosis largely lacks the error correction of meiosis, destroys linkage through ubiquitous mitotic recombination, and thereby increases recombination load, especially in co-adapted gene complexes. Meiosis and possibly karyogamy provide an unexpected benefit to sex, offsetting at least some of the famed costs of sex.

Reply to a Comment on “The Appeals Process as a Means of Error Correction”

In his interesting comment on my recent article, “The Appeals Process as a Means of Error Correction,” Edward Schwartz makes two criticisms of my analysis. The criticisms have essentially to do with my assumption that an appeals court judge will base his or her decisions only on what happened at trial, and not on any inference that can be drawn from the fact that an appeal was brought. Before explaining why I do not find Schwartz's criticisms problematic, it will be helpful for me to restate the main features of the model that I examined in the article.

A Comment on “The Appeals Process as a Means of Error Correction,” by Steven Shavell

In his most recent article, “The Appeals Process as a Means of Error Correction,” Steven Shavell asks a very important question: Why do we use a hierarchical court structure? The flip side of this inquiry is whether we might not be better off simply making our trial courts more efficient (in the sense of making them less error-prone). Although I certainly applaud the recent efforts of Shavell and other law and economics scholars to examine issues of institutional design, this particular attempt suffers from two major flaws. The first involves the asymmetric treatment of litigants before trial courts and appeals courts: Appellants can choose to either appeal cases or not, but the population of cases before the trial courts is assumed to be exogenous. This severely limits the ability to improve the efficiency of trial courts, leading to an overestimation of the value added from an appeals process. The second problem involves the behavior of judges, who are assumed to behave as automatons. Allowing judges to behave rationally dramatically changes the nature of the model's results, most fatally leading to the elimination of the separation equilibrium that Shavell wishes to achieve.

The Appeals Process as a Means of Error Correction

The appeals process--whereby a litigant disappointed with the decision of a first-order tribunal can seek reconsideration before a higher tribunal--is a widely observed feature of adjudication. What rationale can be offered for incorporation of an appeals process in a system of adjudication? The justification analyzed here concerns error correction: the appeals process allows society to harness information that litigants have about erroneous decisions and thereby to reduce the incidence of mistake at low cost (because the appeals tribunal convenes only in a subset of cases). This argument explains why the appeals process may be superior to the alternative of enhancing the quality of the trial process. The argument also explains why disappointed litigants are given the right to instigate appeals (instead of the higher tribunal having the right to reconsider trial outcomes). The article also discusses other justifications for the appeals process, including lawmaking.

Error correction in data transmission systems

The use of the existing telephone and telegraph networks as data transmission media is discussed with special reference to the correction of errors. These networks as they stand are far from ideal for data transmission because the high-level noise pulses and short interruptions which are relatively unimportant for normal usage cause errors in data messages. The data terminal equipment must contain some means of error correction, and various ways in which this can be done are explained. Typical error detection and correction equipments for both the telephone and telex networks are shown. Finally methods for the evaluation of the relative efficiencies of the various error correction and detection codes are described.