The Problem of Ethical Vagueness for Expressivism

Ethical vagueness has garnered little attention. This is rather surprising since many philosophers have remarked that the science of ethics lacks the precision that other fields of inquiry have. Of the few philosophers who have discussed ethical vagueness the majority have focused on the implications of vagueness for moral realism. Because the relevance of ethical vagueness for other metaethical positions has been underexplored, my aim in this paper is to investigate the ramifications of ethical vagueness for expressivism. Ultimately, I shall argue that expressivism does not have the resources to adequately account for ethical vagueness, while cognitivism does. This demonstrates an advantage that cognitivism holds over expressivis

COUNTERFACTUALS AND THE ANALYSIS OF NECESSITY *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73782/1/j.1520-8583.2006.00108.x.pd

The polygenic nature of telomere length and the anti-ageing properties of lithium

Telomere length is a promising biomarker for age-related disease and a potential anti-ageing drug target. Here, we study the genetic architecture of telomere length and the repositioning potential of lithium as an anti-ageing medication. LD score regression applied to the largest telomere length genome-wide association study to-date, revealed SNP-chip heritability estimates of 7.29%, with polygenic risk scoring capturing 4.4% of the variance in telomere length in an independent cohort (p = 6.17 × 10-5). Gene-enrichment analysis identified 13 genes associated with telomere length, with the most significant being the leucine rich repeat gene, LRRC34 (p = 3.69 × 10-18). In the context of lithium, we confirm that chronic use in a sample of 384 bipolar disorder patients is associated with longer telomeres (p = 0.03). As complementary evidence, we studied three orthologs of telomere length regulators in a Caenorhabditis elegans model of lithium-induced extended longevity and found all transcripts to be affected post-treatment (p  0.05). Consequently, this suggests that lithium may be catalysing the activity of endogenous mechanisms that promote telomere lengthening, whereby its efficacy eventually becomes limited by each individual's inherent telomere maintenance capabilities. Our work indicates a potential use of polygenic risk scoring for the prediction of adult telomere length and consequently lithium's anti-ageing efficacy

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

Background: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer, but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome. Methods: 176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT\ubcT0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2), and 4\u20138 months after surgery (T3) time points. Plasma TERT mRNA levels and total cell-free RNA were determined using real-time PCR. Results: Plasma levels of TERT were significantly lower at T2 (Po0.0001) in responders than in non-responders. Post-CRT TERT levels and the differences between pre- and post-CRT TERT levels independently predicted tumour response, and the prediction model had an area under curve of 0.80 (95% confidence interval (CI) 0.73\u20130.87). Multiple analysis demonstrated that patients with detectable TERT levels at T2 and T3 time points had a risk of disease progression 2.13 (95% CI 1.10\u20134.11)-fold and 4.55 (95% CI 1.48\u201313.95)-fold higher, respectively, than those with undetectable plasma TERT levels. Conclusions: Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal cancer patients who undergo neoadjuvant therapy

Finding Our Way through Phenotypes

Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility

The algebra of lexical semantics

Abstract. The current generative theory of the lexicon relies primar-ily on tools from formal language theory and mathematical logic. Here we describe how a different formal apparatus, taken from algebra and automata theory, resolves many of the known problems with the gener-ative lexicon. We develop a finite state theory of word meaning based on machines in the sense of Eilenberg [11], a formalism capable of de-scribing discrepancies between syntactic type (lexical category) and se-mantic type (number of arguments). This mechanism is compared both to the standard linguistic approaches and to the formalisms developed in AI/KR. 1 Problem Statement In developing a formal theory of lexicography our starting point will be the informal practice of lexicography, rather than the more immediately related for-mal theories of Artificial Intelligence (AI) and Knowledge Representation (KR). Lexicography is a relatively mature field, with centuries of work experience an