Aggregate damages: why the whole might not be the sum of the parts

Many legal regimes allow for the award of aggregate damages in collective or class claims. That is to say, an award may be made reflecting the losses of the class as a whole, with little or no information as to the losses suffered by individual class members. Economists are able to calculate damages at a class level without complete individual data by applying two different but not mutually exclusive sets of methodologies, which we refer to as ‘top-down’ and ‘sample-based’ approaches. This article discusses some of the advantages and pitfalls that may arise in estimating aggregate damages under each approach, and illustrates some circumstances in which the process of aggregation may lead to upward or downward bias in the estimate of total loss. We also compare the relative merits of each approach, and consider some of the practical steps by which such biases may be avoided.

Mixed two- and four-level experimental designs for interchangeable parts with different degrees of assembly difficulty

Purpose The purpose of this paper is to show how to properly use the method of replacement to construct mixed two- and four-level minimum setup split-plot type designs to accommodate the presence of hard-to-assemble parts. Design/methodology/approach Split-plot type designs are economical approaches in industrial experimentation. These types of designs are particularly useful for situations involving interchangeable parts with different degrees of assembly difficulties. Methodologies for designing and analyzing such experiments have advanced lately, especially for two-level designs. Practical needs may require the inclusion of factors with more than two levels. Here, the authors consider an experiment to improve the performance of a Baja car including two- and four-level factors. Findings The authors find that the direct use of the existing minimum setup maximum aberration (MSMA) catalogs for two-level split-plot type designs may lead to inappropriate designs (e.g. low resolution). The existing method of replacement for searching exclusive sets of the form (α, β, αβ) available in the literature is suitable for completely randomized designs, but it may not provide efficient plans for designs with restricted randomization. Originality/value The authors provide a general framework for the practitioners and have extended the algorithm to find out the number of generators and the number of base factor at each stratum, which guide the selection of mixed two-level and four-level MSMA split-plot type designs.

Identification of distinct mutational patterns and new driver genes in oesophageal squamous cell carcinomas and adenocarcinomas

ObjectivesOesophageal squamous cell carcinoma (OSCC) and adenocarcinoma (OAC) are distinct cancers in terms of a number of clinical and epidemiological characteristics, complicating the design of clinical trials and biomarker developments. We analysed 1048 oesophageal tumour-germline pairs from both subtypes, to characterise their genomic features, and biological and clinical significance.DesignPreviously exome-sequenced samples were re-analysed to identify significantly mutated genes (SMGs) and mutational signatures. The biological functions of novel SMGs were investigated using cell line and xenograft models. We further performed whole-genome bisulfite sequencing and chromatin immunoprecipitation (ChIP)-seq to characterise epigenetic alterations.ResultsOSCC and OAC displayed nearly mutually exclusive sets of driver genes, indicating that they follow independent developmental paths. The combined sample size allowed the statistical identification of a number of novel subtype-specific SMGs, mutational signatures and prognostic biomarkers. Particularly, we identified a novel mutational signature similar to Catalogue Of Somatic Mutations In Cancer (COSMIC)signature 16, which has prognostic value in OSCC. Two newly discovered SMGs, CUL3 and ZFP36L2, were validated as important tumour-suppressors specific to the OSCC subtype. We further identified their additional loss-of-function mechanisms. CUL3 was homozygously deleted specifically in OSCC and other squamous cell cancers (SCCs). Notably, ZFP36L2 is associated with super-enhancer in healthy oesophageal mucosa; DNA hypermethylation in its super-enhancer reduced active histone markers in squamous cancer cells, suggesting an epigenetic inactivation of a super-enhancer-associated SCC suppressor.ConclusionsThese data comprehensively contrast differences between OSCC and OAC at both genomic and epigenomic levels, and reveal novel molecular features for further delineating the pathophysiological mechanisms and treatment strategies for these cancers.

A Robust Newcomb-Benford Account Screening Profiler: An Audit Decision Support System

The best practices execution of the audit is conditioned by the facility with which Decision Support Systems [DSS] can be created using simple Excel™ programming tools and functionalities. Such DSS can aid in the exclusive binary triage of the many of the client’s accounts each of which typically has tens of thousands of items into: {Accounts that may warrant Extended Procedures Testing [EPT]} or {Accounts that may not warrant EPT}. We use the Newcomb-Benford first-digit-profile as a triage platform to screen client accounts into the above mentioned exclusive sets. We call this DSS: The Newcomb-Benford Robust Screening:DSS [NBRS:DSS]. We report on the details of its development & vetting, and illustrate its functionalities using one of the historical Benford Datasets. The NBRS:DSS employs four account screening platforms each of which has been reported in the literature. The NBRS:DSS is available from the authors free as a download without restrictions to its use.

Generating Questions: Processing Time Changes Between Early Adolescence and Young Adulthood

Information seeking by asking questions is fundamental to solving some problems. How quickly it proceeds can be important, especially if stakes are high. This experiment compared the processing times of three question types generated by early adolescents, middle adolescents, and young adults who sought to identify unknown target exemplars in a series of test arrays. Category questions, which eliminate alternatives based on their membership in contrasting mutually exclusive sets, were of two types: conceptual and perceptual. Conceptual category questions took longer to generate than perceptual category questions for all age groups. Syncretic questions, which refer to more than one category, took longer to generate than perceptual category questions for early adolescents, although they did not take longer to generate than perceptual category questions for the two older groups. Age-related changes in cognitive processing, syncretic thinking, and experience with hypothesis testing provide a framework for interpreting these results.

Peptide partitions and protein identification: a computational analysis

Peptide sequences from a proteome can be partitioned into N mutually exclusive sets and used to identify their parent proteins in a sequence database. This is illustrated with the human proteome (http://www.uniprot.org; id UP000005640), which is partitioned into eight subsets KZ*R, KZ*D, KZ*E, KZ*, Z*R, Z*D, Z*E, and Z*, where Z ∈ {A, N, C, Q, G, H, I, L, M, F, P, S, T, W, Y, V} and Z* ≡ 0 or more occurrences of Z. If the full peptide sequence is known then over 98% of the proteins in the proteome can be identified from such sequences. The rate exceeds 78% if the positions of four internal residue types are known. When the standard set of 20 amino acids is replaced with an alphabet of size four based on residue volume the identification rate exceeds 96%. In an information-theoretic sense this last result suggests that protein sequences effectively carry nearly the same amount of information as the exon sequences in the genome that code for them using an alphabet of size four. An appendix discusses possible in vitro methods to create peptide partitions and potential ways to sequence partitioned peptides.