LMDA Review, volume 10, issue 2

Contents include: New Annual Membership Expiration Date, A Rose by Any Other Word, Report on Canadian Caucus, Script Exchange, Dramaturgy Focus Group ATHE 2000 Dramaturgy Conference Planner, Dramaturgy The Power in the Words, Profiles in Dramaturgy: Alexis Greene, The Early Career Dramaturgy Group, LMDA Online Listserv Instructions, New World Theater Plans Second International Conference, Black Theatre Network Conference, New Visions 2000: One Theater World, ISTA, and the LMDA Archive.https://soundideas.pugetsound.edu/lmdareview/1023/thumbnail.jp

Can Nitrogen-13 Ammonia Kinetic Modeling Define Myocardial Viability Independent of Fluorine-18 Fluorodeoxyglucose?

AbstractObjectives. The hypothesis of this study was that evaluation of myocardial flow and metabolism using nitrogen-13 (N-13) ammonia kinetic modeling with dynamic positron emission tomographic (PET) imaging could identify regions of myocardial scar and viable myocardium as defined by fluorine-18 fluorodeoxyglucose (F-18 FDG) PET.Background. Uptake of most perfusion tracers depends on both perfusion and metabolic retention in tissue. This characteristic has limited their ability to differentiate myocardial scar from viable tissue. The kinetic modeling of N-13 ammonia permits quantification of blood flow and separation of the metabolic component of its uptake, which may permit differentiation of scar from viable tissue.Methods. Sixteen patients, >3 months after myocardial infarction, underwent dynamic N-13 ammonia and F-18 FDG PET imaging. Regions of reduced and normal perfusion were defined on static N-13 ammonia images. Patients were classified into two groups (group I [ischemic viable], n = 6; group II [scar], n = 10) on the basis of percent of maximal F-18 FDG uptake in hypoperfused segments. Nitrogen-13 ammonia kinetic modeling was applied to dynamic PET data, and rate constants were determined. Flow was defined by K1; volume of distribution (VD = K1/k2) of N-13 ammonia was used as an indirect indication of metabolic retention.Results. Fluorine-18 FDG uptake was reduced in patients with scar compared with normal patients with ischemic viable zones (ischemic viable 93 ± 27% [mean ± SD]; scar 37 ± 16%, p ≤ 0.01). Using N-13 ammonia kinetic modeling, flow and VD were reduced in the hypoperfused regions of patients with scar (ischemic viable flow: 0.65 ± 0.20 ml/min per g; scar: 0.36 ± 0.16 ml/min per g, p ≤ 0.01; VD: 3.9 ± 1.3 and 2.0 ± 1.07 ml/g, respectively, p ≤ 0.01). For detection of viable myocardium in these patients, the sensitivity and specificity were 100% and 80% for N-13 ammonia PET flow >0.45 ml/min per g; 100% and 70% for VD >2.0 ml/g; and 100% and 90% for both flow > 0.45 ml/min per g and VD > 2.0 ml/g, respectively. The positive and negative predictive values for the latter approach were 86% and 100%, respectively.Conclusions. In this cohort, patients having regions with flow ≤0.45 ml/min per g or VD ≤ 2.0 ml/g had scar. Viable myocardium had both flow >0.45 ml/min per g and VD > 2.0 ml/g. Nitrogen-13 ammonia kinetic modeling permits determination of blood flow and metabolic integrity in patients with previous myocardial infarction and can help differentiate between scar and ischemic but viable myocardium.(J Am Coll Cardiol 1997;29:537–43

Conversational Grammar- Feminine Grammar? A Sociopragmatic Corpus Study

One area in language and gender research that has so far received only little attention is the extent to which the sexes make use of what recent corpus research has termed “conversational grammar.” The author’s initial findings have suggested that the majority of features distinctive of conversational grammar may be used predominantly by female speakers. This article reports on a study designed to test the hypothesis that conversational grammar is “feminine grammar” in the sense that women’s conversational language is more adapted to the conversational situation than men’s. Based on data from the conversational subcorpus of the British National Corpus and following the situational framework for the description of conversational features elaborated in the author’s previous research, features distinctive of conversational grammar are grouped into five functional categories and their normed frequencies compared across the sexes. The functional categories distinguish features that can be seen as adaptations to constraints set by the situational factors of (1) Shared Context, (2) Co-Construction, (3) Real-Time Processing, (4) Discourse Management, and (5) Relation Management. The study’s results, described in detail in relation to the biological category of speaker sex and cultural notions of gender, suggest that the feminine grammar hypothesis is valid

Breaking into BIM: Performing static and dynamic security analysis with the aid of BIM

The design and construction industry is moving towards Building Information Models (BIM) that provide all of the strengths of traditional 3D CAD with an added layer of data allowing new and powerful applications. We investigate the concept of using the data within BIM to better explore security design and considerations. We achieve this by first graphing the physical entities of BIM to capture their relational representation as nodes and links. This graph representation will facilitate the use of graph theory or agent-based simulation to assist in the analysis of the static and dynamic behaviour of the environment around the BIM. We also demonstrate an application of graphing by investigating the use of BIM to explore automated infrastructure security design and consideration via red-teaming. The intent is to make security analysis easier and a process that can be carried out during the design phase of a project, even by non-expert users

LMDA Review, volume 11, issue 2

Contents include: A Letter to the Membership from the LMDA Board Chair, Dixon to the Guthrie, Office Update, Technology Notes, News from CEAD Montreal, LMDA Affiliates with ATHE, ATHE 2001 Practice, Theory, Technology and the New Student, Report on Canadian Caucus, Note to the Editor, The Experiment Tradition, Community and the Development of Scripts for Stage and Screen, A Collaborative Workshop, An Intern on Internships, Spotlight on Early Career Dramaturgs, Exciting News from the West Coast, Coming this Way, and Playscripts.com.https://soundideas.pugetsound.edu/lmdareview/1021/thumbnail.jp

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The contribution of X-linked coding variation to severe developmental disorders

Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders