Is Harry Frankfurt’s ‘Doctrine of Sufficiency’ Sufficient?

In his article, “Equality as a Moral Ideal”, Harry Frankfurt argues against economic egalitarianism and presents what he calls the “doctrine of sufficiency.” According to the doctrine of sufficiency, what is morally important is not relative economic equality, but rather, whether somebody has enough, where “having enough” is a non-comparative standard of reasonable contentment that may differ from person to person given his/her aims and circumstances. The purpose of this paper is to show that Frankfurt’s original arguments in support for his doctrine of sufficiency have critical problems that Frankfurt himself does not properly recognize. In the end, I will argue that in order to solve these problems the doctrine of sufficiency cannot help but to incorporate certain prioritarian commitments – commitments which many would view as implying economic egalitarianism. This is embarrassing for a doctrine whose raison d’être was mainly to defeat economic egalitarianism

The Well-Ordered Society under Crisis: A Formal Analysis of Public Reason vs. Convergence Discourse

A well-ordered society faces a crisis whenever a sufficient number of noncompliers enter into the political system. This has the potential to destabilize liberal democratic political order. This article provides a formal analysis of two competing solutions to the problem of political stability offered in the public reason liberalism literature—namely, using public reason or using convergence discourse to restore liberal democratic political order in the well-ordered society. The formal analyses offered in this article show that using public reason fails completely, and using convergent discourse, although doing better, has its own critical limitations that have not been previously recognized properly

Incorporating Genomic Analysis In The Clinical Practice Of Hepatology

In the past two decades, whole-exome sequencing has been successfully demonstrated as an indispensable instrument in uncovering the genetic etiology underlying numerous types of unexplained liver disease. Characterization of these illnesses into distinct molecular disease entities has revolutionized understanding of pathophysiology and has translated into improved guidance on management, treatment and prognosis for patients. However, hepatologists have been slow to welcome the technology into their mainstream clinical practice, largely due to inadequate training in genomic medicine. There thus remains a pressing need to create various forums through which clinicians can gain better appreciation for the value of genetic analysis in the field of hepatology and amass the knowledge and confidence to incorporate genetic analysis into their own clinical practice. To address this need, we aimed to facilitate the dissemination of new information on liver disease with an underlying genetic etiology through a two-pronged approach: (1) the generation of an online database housing genotype-phenotype correlation information for diseases affecting the liver, and (2) the promotion of a multidisciplinary Hepatology Genome Rounds series. In this Thesis, we detail the creation of a comprehensive database focused on genetic liver diseases, reflecting the genotypic and phenotypic profiles of more than 7,500 individuals with genetic variants across 269 genes. This newly developed database will provide clinicians and researchers a centralized source for information on genotype-phenotype correlation to aid in diagnosis and education. In addition, we demonstrate that the Hepatology Genome Rounds series, which is an interdisciplinary forum highlighting hepatology cases of clinical interest and educational value, is an important venue for the distribution of genomic knowledge within the field of hepatology and for providing ongoing education to providers and trainees in genomic medicine. We describe our single-center experience, which has led to the reconsideration of diagnoses in two patients and an improved understanding of genotype-phenotype correlations across all cases. As the value of genetic analysis continues to emerge in understanding human disease and pathophysiology, we foresee similar approaches being adopted at other institutions and in additional specialties in coming years for further propagation of genomics in clinical medicine

4,6-Di-tert-butyl-2,8-dimeth­oxy­dibenzo[b,d]furan

In the title compound, C22H28O3, the dihedral angle between the benzene rings is 3.47 (13)° and the five-membered furan ring is essentially planar with a largest deviation of 0.0052 (14) Å. The Csp 2—Csp 2 bond length between the two benzene rings [1.443 (3) Å] is considerably shorter than those between the benzene and tertiary C atoms [1.538 (3) and 1.530 (3) Å], which are sp 2–sp 3 hybridized. C—H⋯π inter­actions involving the furan and benzene rings are found in the crystal structure

19F Magnetic Resonance Imaging of Lung Ventilation Dynamics and Cell Tracking

The Fluorine isotope 19F has great potential in the use of magnetic resonance imaging (MRI) for clinical applications. 19F is inert, naturally abundant, has a close resonance frequency to proton (1H) (allowing most modern MRI scanners to work with the addition of a tuned coil), has negligible presence in the mammalian body (allowing background signal free acquisitions), and the high gyromagnetic ratio provides sufficient magnetic resonance signal to be visible without hyperpolarization. Uses for 19F MRI includes functional lung imaging, diffusion imaging, cell tracking, and oxygenation sensing among others. Although not widely used in the clinical setting at the time of writing this dissertation. The potential improvements 19F MRI could bring to healthcare are vast. 19F lung imaging has been studied in animal and human models, and has shown to be capable of producing sensitive markers for lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) by providing spatially localized functional information. In cell tracking, 19F has shown potential in drug delivery monitoring, inflammation imaging, immune cell tracking, and oxygenation measurement with the potential of spatial localization and cell quantification. This dissertation presents my work on human in-vivo multi-breath wash-in/out 19F lung imaging, and the processing of biomarkers more sensitive to CF disease progression over the current gold standard (spirometry). 19F lung MRI was compared to hyperpolarized (HP) Xenon (129Xe) ventilation defect percentage (VDP) analysis. The feasibility of free-breathing 19F lung imaging was explored using a combination of spiral acquisition and denoising. The last two chapters present preliminary work on sequence programming for diffusion imaging and cell tracking at high magnetic fields (9.4T). Preliminary work on oxygen sensing at 9.4T is also explored.Doctor of Philosoph

Integrative Survival Response Evoked by Heme Oxygenase-1 and Heme Metabolites

Heme oxygenase (HO) catalyzes the rate-limiting step in heme degradation to produce carbon monoxide (CO), iron, and biliverdin. Biliverdin is subsequently converted to bilirubin by its reductase, and iron is recycled for heme synthesis. The inducible HO isoform, HO-1, is involved in the protection of multiple tissues and organs. The mechanism of protective actions of HO-1 has not been completely elucidated, but recent evidence suggests that one or more of heme metabolites can mediate the protective effects of HO-1. Particularly, CO mimics the antioxidant, anti-inflammatory, anti-apoptotic and antiproliferative actions of HO-1. Many of these effects of CO depend on the production of cyclic guanosine monophosphate (cGMP), and the modulation of mitogen-activated protein kinase (MAPK) pathways. The transcription factors, including nuclear factor E2-related factor-2 (Nrf2), and their upstream kinases, including MAPK pathway, play an important regulatory role in HO-1 expression by dietary antioxidants and drugs. This review attempts to concisely summarize the molecular and biochemical characteristics of HO-1, with a discussion on the mechanisms of signal transduction and gene regulation that mediate the induction of HO-1 by dietary antioxidants and drugs. In addition, the cytoprotective roles of HO-1 shall be discussed from the perspective of each of the metabolic by-products