64 research outputs found

    Advancing Inclusion in the Geosciences: An Overview of the NSF-GOLD Program

    Get PDF
    Here we report on five pilot projects working to develop effective professional development aimed at improving diversity, equity, and inclusion within the geosciences. All five projects were funded by the NSF GEO Opportunities for Leadership in Diversity (GOLD) program, which was designed to bring together geoscientists and social scientists to create innovative pilot programs for preparing and empowering geoscientists as change agents for increasing diversity. Each project has different objectives and applies different combinations of methods, but focuses on professional development, bystander intervention training, and the formation of new networks in the pursuit of systemic, institutional change. This article describes the origins, aims, and activities of these projects, and reflects on lessons learned to date. These projects are still ongoing, but in their first two years they have received more interest than anticipated and more demand than can be fulfilled, suggesting an unserved need in the field. We have also found that teams with varied backgrounds, experiences, and expertise are vital to overcoming common struggles in facing inequalities. Coaching from experts in diversity, equity, and inclusion keeps the teams motivated, particularly when many team members are accustomed to typical scientific research. Finally, institutional change requires time to catalyze, develop, and institutionalize, highlighting the importance of sustained effort over years

    The META tool optimizes metagenomic analyses across sequencing platforms and classifiers

    Get PDF
    A major challenge in the field of metagenomics is the selection of the correct combination of sequencing platform and downstream metagenomic analysis algorithm, or “classifier”. Here, we present the Metagenomic Evaluation Tool Analyzer (META), which produces simulated data and facilitates platform and algorithm selection for any given metagenomic use case. META-generated in silico read data are modular, scalable, and reflect user-defined community profiles, while the downstream analysis is done using a variety of metagenomic classifiers. Reported results include information on resource utilization, time-to-answer, and performance. Real-world data can also be analyzed using selected classifiers and results benchmarked against simulations. To test the utility of the META software, simulated data was compared to real-world viral and bacterial metagenomic samples run on four different sequencers and analyzed using 12 metagenomic classifiers. Lastly, we introduce “META Score”: a unified, quantitative value which rates an analytic classifier’s ability to both identify and count taxa in a representative sample

    NSAIDs Modulate CDKN2A, TP53, and DNA Content Risk for Progression to Esophageal Adenocarcinoma

    Get PDF
    BACKGROUND: Somatic genetic CDKN2A, TP53, and DNA content abnormalities are common in many human cancers and their precursors, including esophageal adenocarcinoma (EA) and Barrett's esophagus (BE), conditions for which aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed as possible chemopreventive agents; however, little is known about the ability of a biomarker panel to predict progression to cancer nor how NSAID use may modulate progression. We aimed to evaluate somatic genetic abnormalities with NSAIDs as predictors of EA in a prospective cohort study of patients with BE. METHODS AND FINDINGS: Esophageal biopsies from 243 patients with BE were evaluated at baseline for TP53 and CDKN2A (p16) alterations, tetraploidy, and aneuploidy using sequencing; loss of heterozygosity (LOH); methylation-specific PCR; and flow cytometry. At 10 y, all abnormalities, except CDKN2A mutation and methylation, contributed to EA risk significantly by univariate analysis, ranging from 17p LOH (relative risk [RR] = 10.6; 95% confidence interval [CI] 5.2–21.3, p < 0.001) to 9p LOH (RR = 2.6; 95% CI 1.1–6.0, p = 0.03). A panel of abnormalities including 17p LOH, DNA content tetraploidy and aneuploidy, and 9p LOH was the best predictor of EA (RR = 38.7; 95% CI 10.8–138.5, p < 0.001). Patients with no baseline abnormality had a 12% 10-y cumulative EA incidence, whereas patients with 17p LOH, DNA content abnormalities, and 9p LOH had at least a 79.1% 10-y EA incidence. In patients with zero, one, two, or three baseline panel abnormalities, there was a significant trend toward EA risk reduction among NSAID users compared to nonusers (p = 0.01). The strongest protective effect was seen in participants with multiple genetic abnormalities, with NSAID nonusers having an observed 10-y EA risk of 79%, compared to 30% for NSAID users (p < 0.001). CONCLUSIONS: A combination of 17p LOH, 9p LOH, and DNA content abnormalities provided better EA risk prediction than any single TP53, CDKN2A, or DNA content lesion alone. NSAIDs are associated with reduced EA risk, especially in patients with multiple high-risk molecular abnormalities

    Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

    Get PDF
    Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

    Finishing the euchromatic sequence of the human genome

    Get PDF
    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

    Bionic bodies, posthuman violence and the disembodied criminal subject

    Get PDF
    This article examines how the so-called disembodied criminal subject is given structure and form through the law of homicide and assault. By analysing how the body is materialised through the criminal law’s enactment of death and injury, this article suggests that the biological positioning of these harms of violence as uncontroversial, natural, and universal conditions of being ‘human’ cannot fully appreciate what makes violence wrongful for us, as embodied entities. Absent a theory of the body, and a consideration of corporeality, the criminal law risks marginalising, or altogether eliding, experiences of violence that do not align with its paradigmatic vision of what bodies can and must do when suffering its effects. Here I consider how the bionic body disrupts the criminal law’s understanding of human violence by being a body that is both organic and inorganic, and capable of experiencing and performing violence in unexpected ways. I propose that a criminal law that is more receptive to the changing, technologically mediated conditions of human existence would be one that takes the corporeal dimensions of violence more seriously and, as an extension of this, adopts an embodied, embedded, and relational understanding of human vulnerability to violence

    The Law and Economics of Liability Insurance: A Theoretical and Empirical Review

    Full text link
    corecore