Patient Autonomy in Talmudic Context: The Patient’s ‘‘I Must Eat’’ on Yom Kippur in the Light of Contemporary Bioethics

In contemporary bioethics, the autonomy of the patient has assumed considerable importance. Progressing from a more limited notion of informed consent, shared decision making calls upon patients to voice the desires and preferences of their authentic self, engaging in choice among alternatives as a way to exercise deeply held values. One influential opinion in Jewish bioethics holds that Jewish law, in contradistinction to secular bioethics, limits the patient's exercise of autonomy only in those instances in which treatment choices are sensitive to preferences. Here, we analyze a discussion in the Mishna, a foundational text of rabbinic Judaism, regarding patient autonomy in the setting of religiously mandated fasting, and commentaries in the Babylonian and Palestinian Talmuds, finding both a more expansive notion of such autonomy and a potential metaphysical grounding for it in the importance of patient self-knowledge

Book Review: Charles E. McClelland. Berlin, the Mother of All Research Universities, 1860–1918.

Charles McClelland has long been one of the leading scholars of German universities and professionalism in Germany. His State, Society, and University in Germany, 1700–1914 (Cambridge, 1980), for example, is a fundamental introductory work for anyone wishing to understand the structure, growth, and development of the German universities during this period. To help celebrate its bicentennial (2010), the Humboldt-Universität zu Berlin (to use the University of Berlin’s official name since 1949) commissioned a six-volume history, of which McClelland was the co-author of Volume 1, running from 1810 to 1918 and published in German. The work under review is an augmented, English-language version of that volume. That fact perhaps helps explain why the book is so expensive. To say the very least, it far surpasses the forty pages devoted to the period 1870–1910 in the standard history of the university by Max Lenz (4 vols., 1910). The University of Berlin unexpectedly began life in 1810 as the “Berliner Universität” and as compensation for Prussia’s loss of Halle during the Napoleonic Wars. In 1828 it was renamed the Friedrich- Wilhelms-Universität, retaining that name until 1949. Located in the heart of Berlin (on Unter den Linden), during its first half-century its facilities left much to be desired and its faculty, before midcentury, was of mixed scientific distinction. It was largely in the 1860s, as Berlin became a “big” city and as Prussia took on economic and political heft, that the university, located cheek by jowl with the monarchical court, governmental headquarters (including the educational ministry), and military command, emerged as a national and, soon, international research center. Indeed, my only critique of McClelland’s study concerns its muddled, misleading title, “the Mother of All Research Universities.” As is well known, and as McClelland himself eventually points out (but only en passant), it was Halle and Göttingen in the mid-eighteenth century that first promoted research as a central feature of the university. Besides, the advancement of research at the German universities stemmed not from anyone institution but, rather, from a gradually forming system of research-oriented universities. Nonetheless, in the imperial period Berlin most definitely became an outstanding research university and, for some, a model of its kind. That point is beyond dispute

Integrated Genomics Of Susceptiblity To Therapy-Related Leukemia

Therapy-related acute myeloid leukemia t-AML is a secondary, generally incurable, malignancy attributable to the chemotherapeutic treatment of an initial disease. Although there is a genetic component to susceptibility to therapy-related leukemias in mice, little is understood either about the contributing loci, or the mechanisms by which susceptibility factors mediate their effect. An improved understanding of susceptibility factors and the biological processes in which they act may lead to the development of t-AML prevention strategies. In this thesis work, we identified expression networks that are associated with t-AML susceptibility in mice. These networks are robust in that they emerge from distinct methods of analysis and from different gene expression data sets of hematopoietic stem and progenitor lineages. These networks are enriched in genes involved in cell cycle and DNA repair, suggesting that these processes play a role in susceptibility. By integrating gene expression and genetic information we prioritized network nodes for experimental validation as contributors to expression networks and t-AML susceptibility. Network analysis and node prioritization required a comprehensive map of genetic variation in mouse, which was not available at the outset of this thesis work. Specifically, DNA copy number variations: CNVs), defined as genomic sequences that are polymorphic in copy number and range in length from 1,000 to several million base pairs, were largely uncharacterized in inbred mice. We developed a computational approach, Washington University Hidden Markov Model: wuHMM), to identify CNVs from high-density array comparative genomic hybridization data, accounting for the high degree of polymorphism that occur between mouse strains. Using wuHMM we analyzed the copy number content of the mouse genome: 20 strains) to a sub-10-kb resolution, finding over 1,300 CNV-regions: CNVRs), most of which are \u3c 10 kb in length, are found in more than one strain, and span 3.2%: 85 Mb) of the reference genome. These CNVRs, along with haplotype blocks we derived from publicly available SNP data, were integrated into susceptibility expression network analysis. In addition to addressing questions regarding t-MDS/AML susceptibility, we also used this data to assess the potential functional impact of copy number variation by mapping expression profiles to CNVRs. In hematopoietic stem and progenitor cells, up to 28% of strain-dependent expression variation is associated with copy number variation, supporting the role of germline CNVs as key contributors to natural phenotypic variation