Comparative effectiveness studies to improve clinical outcomes in end stage renal disease: the DEcIDE patient outcomes in end stage renal disease study.

BACKGROUND: Evidence is lacking to inform providers' and patients' decisions about many common treatment strategies for patients with end stage renal disease (ESRD). METHODS/DESIGN: The DEcIDE Patient Outcomes in ESRD Study is funded by the United States (US) Agency for Health Care Research and Quality to study the comparative effectiveness of: 1) antihypertensive therapies, 2) early versus later initiation of dialysis, and 3) intravenous iron therapies on clinical outcomes in patients with ESRD. Ongoing studies utilize four existing, nationally representative cohorts of patients with ESRD, including (1) the Choices for Healthy Outcomes in Caring for ESRD study (1041 incident dialysis patients recruited from October 1995 to June 1999 with complete outcome ascertainment through 2009), (2) the Dialysis Clinic Inc (45,124 incident dialysis patients initiating and receiving their care from 2003-2010 with complete outcome ascertainment through 2010), (3) the United States Renal Data System (333,308 incident dialysis patients from 2006-2009 with complete outcome ascertainment through 2010), and (4) the Cleveland Clinic Foundation Chronic Kidney Disease Registry (53,399 patients with chronic kidney disease with outcome ascertainment from 2005 through 2009). We ascertain patient reported outcomes (i.e., health-related quality of life), morbidity, and mortality using clinical and administrative data, and data obtained from national death indices. We use advanced statistical methods (e.g., propensity scoring and marginal structural modeling) to account for potential biases of our study designs. All data are de-identified for analyses. The conduct of studies and dissemination of findings are guided by input from Stakeholders in the ESRD community. DISCUSSION: The DEcIDE Patient Outcomes in ESRD Study will provide needed evidence regarding the effectiveness of common treatments employed for dialysis patients. Carefully planned dissemination strategies to the ESRD community will enhance studies' impact on clinical care and patients' outcomes.

Commandeering Aesop’s Bamboo Canon: A 19th Century Confederacy of Creole Fugitive Fables

In my thesis, “Commandeering Aesop’s Bamboo Canon: A 19th Century Confederacy of Creole Fugitive Fables,” I ask and answer the ‘Who? What? Where? When? Why?” of Creole Literature using the 19th century production of Aesopian fables as clues to resolve a set of linguistic, historical, literary, and geographical enigmas pertaining the ‘birth-place(s)’ of Creolophone Literatures in the Caribbean Sea, North and South America, as well as the Indian Ocean. Focusing on the fables in Martinique (1846), Reunion Island (1826), and Mauritius (1822), my thesis should read be as an attempt capture the links between these islands through the creation of a particular archive defined as a cartulary-chronicle, a diplomatic codex, or simply a map in which I chart and trace the flight of the founding documents relating to the lives of the individual authors, editors, and printers in order to illustrate the articulation of a formal and informal confederation that enabled the global and local institutional promotion of Creole Literature. While I integrate various genres and multi-polar networks between the authors of this 19th century canon comprised of sacred and secular texts such as proclamations, catechisms, and proverbs, the principle literary genre charted in my thesis are collections of fables inspired by French 17th century French Classical fabulist, Jean de la Fontaine. Often described as the ‘matrix’ of Creolophone Literature, these blues and fables constitute the base of the canon, and are usually described as either ‘translated,’ ‘adapted,’ and even ‘cross-dressed’ into Creole in all of the French Creolophone spaces. My documentation of their transnational sprouting offers proof of an opaque canonical formation of Creole popular literature. By constituting this archive, I emphasize the fact that despite 200 years of critical reception and major developments and discoveries on behalf of Creole language pedagogues, literary scholars, linguists, historians, librarians, archivist, and museum curators, up until now not only have none have curated this literature as a formal canon. I also offer new empirical evidence in order to try and solve the enigma of “How?” the fables materially circulated between the islands, and seek to come to terms with the anonymous nature of the texts, some of which were published under pseudonyms. I argue that part of the confusion on the part of scholars has been the result of being willfully taken by surprise or defrauded by the authors, or ‘bamboozled’ as I put it. The major paradigmatic shift in my thesis is that while I acknowledge La Fontaine as the base of this literary canon, I ultimately bypass him to trace the ancient literary genealogy of fables to the infamous Aesop the Phrygian, whose biography – the first of a slave in the history of the world – and subsequent use of fables reflects a ‘hidden transcript’ of ‘masked political critique’ between ‘master and slave classes’ in the 4th Century B.C.E. Greece.

This archive draws on, connects and critiques the methodologies of several disciplinary fields. I use post-colonial literary studies to map the literary genealogies Aesop; use a comparative historical approach to the abolitions of slavery in both the 19th century Caribbean and the Indian Ocean; and chart the early appearance of folk music in early colonial societies through Musicology and Performance Studies. Through the use of Sociolinguistics and theories of language revival, ecology, and change, I develop an approach of ‘reflexive Creolistics’ that I ultimately hope will offer new educational opportunities to Creole speakers. While it is my desire that this archive serves linguists, book collectors, and historians for further scientific inquiry into the innate international nature of Creole language, I also hope that this innovative material defense and illustration of Creole Literature will transform the consciousness of Creolophones (native and non-native) who too remain ‘bamboozled’ by the archive. My goal is to erase the ‘unthinkability’ of the existence of this ancient maritime creole literary canon from the collective cultural imaginary of readers around the globe.

Conservation, duplication, and loss of the Tor signaling pathway in the fungal kingdom.

BACKGROUND: The nutrient-sensing Tor pathway governs cell growth and is conserved in nearly all eukaryotic organisms from unicellular yeasts to multicellular organisms, including humans. Tor is the target of the immunosuppressive drug rapamycin, which in complex with the prolyl isomerase FKBP12 inhibits Tor functions. Rapamycin is a gold standard drug for organ transplant recipients that was approved by the FDA in 1999 and is finding additional clinical indications as a chemotherapeutic and antiproliferative agent. Capitalizing on the plethora of recently sequenced genomes we have conducted comparative genomic studies to annotate the Tor pathway throughout the fungal kingdom and related unicellular opisthokonts, including Monosiga brevicollis, Salpingoeca rosetta, and Capsaspora owczarzaki. RESULTS: Interestingly, the Tor signaling cascade is absent in three microsporidian species with available genome sequences, the only known instance of a eukaryotic group lacking this conserved pathway. The microsporidia are obligate intracellular pathogens with highly reduced genomes, and we hypothesize that they lost the Tor pathway as they adapted and streamlined their genomes for intracellular growth in a nutrient-rich environment. Two TOR paralogs are present in several fungal species as a result of either a whole genome duplication or independent gene/segmental duplication events. One such event was identified in the amphibian pathogen Batrachochytrium dendrobatidis, a chytrid responsible for worldwide global amphibian declines and extinctions. CONCLUSIONS: The repeated independent duplications of the TOR gene in the fungal kingdom might reflect selective pressure acting upon this kinase that populates two proteinaceous complexes with different cellular roles. These comparative genomic analyses illustrate the evolutionary trajectory of a central nutrient-sensing cascade that enables diverse eukaryotic organisms to respond to their natural environments.

Chimpanzees and bonobos exhibit divergent spatial memory development.

Spatial cognition and memory are critical cognitive skills underlying foraging behaviors for all primates. While the emergence of these skills has been the focus of much research on human children, little is known about ontogenetic patterns shaping spatial cognition in other species. Comparative developmental studies of nonhuman apes can illuminate which aspects of human spatial development are shared with other primates, versus which aspects are unique to our lineage. Here we present three studies examining spatial memory development in our closest living relatives, chimpanzees (Pan troglodytes) and bonobos (P. paniscus). We first compared memory in a naturalistic foraging task where apes had to recall the location of resources hidden in a large outdoor enclosure with a variety of landmarks (Studies 1 and 2). We then compared older apes using a matched memory choice paradigm (Study 3). We found that chimpanzees exhibited more accurate spatial memory than bonobos across contexts, supporting predictions from these species' different feeding ecologies. Furthermore, chimpanzees - but not bonobos - showed developmental improvements in spatial memory, indicating that bonobos exhibit cognitive paedomorphism (delays in developmental timing) in their spatial abilities relative to chimpanzees. Together, these results indicate that the development of spatial memory may differ even between closely related species. Moreover, changes in the spatial domain can emerge during nonhuman ape ontogeny, much like some changes seen in human children.

Inventing "French Feminism:" A Critical History

French Feminism has little to do with feminism in France. While in the U.S. this now canonical body of work designates almost exclusively the work of three theorists—Hélène Cixous, Luce Irigaray, and Julia Kristeva—in France, these same thinkers are actually associated with the rejection of feminism. If some scholars have on this basis passionately denounced French Feminism as an American invention, there exists to date no comprehensive analysis of that invention or of its effects. Why did theorists who were at best marginal to feminist thought and political practice in France galvanize feminist scholars working in the United States? Why does French Feminism provoke such an intense affective response in France to this date? Drawing on the fields of feminist and queer studies, literary studies, and history, “Inventing ‘French Feminism:’ A Critical History” offers a transnational account of the emergence and impact of one of U.S. academic feminism’s most influential bodies of work. The first half of the dissertation argues that, although French Feminism has now been dismissed for being biologically essentialist and falsely universal, feminists working in the U.S. academy of the 1980s, particularly feminist literary critics and postcolonial feminist critics, deployed the work of Cixous, Irigaray, and Kristeva to displace what they perceived as U.S. feminist literary criticism’s essentialist reliance on the biological sex of the author and to challenge U.S. academic feminism’s inattention to racial differences between women. French Feminism thus found traction among feminist scholars to the extent that it was perceived as addressing some of U.S. feminism’s most pressing political issues. The second half of the dissertation traces French feminist scholars’ vehement rejection of French Feminism to an affectively charged split in the French women’s liberation movement of the 1970s and shows that this split has resulted in an entrenched opposition between sexual difference and materialist feminism, an opposition that continues to structure French feminist debates to this day. “Inventing ‘French Feminism:’ A Critical History” ends by arguing that in so far as the U.S. invention of French Feminism has contributed to the emergence of U.S. queer theory, it has also impeded its uptake in France. Taken as a whole, this dissertation thus implicitly argues that the transnational circulation of ideas is simultaneously generative and disabling.

Comparative immunogenicity of HIV-1 clade C envelope proteins for prime/boost studies.

BACKGROUND: Previous clinical efficacy trials failed to support the continued development of recombinant gp120 (rgp120) as a candidate HIV vaccine. However, the recent RV144 HIV vaccine trial in Thailand showed that a prime/boost immunization strategy involving priming with canarypox vCP1521 followed by boosting with rgp120 could provide significant, although modest, protection from HIV infection. Based on these results, there is renewed interest in the development of rgp120 based antigens for follow up vaccine trials, where this immunization approach can be applied to other cohorts at high risk for HIV infection. Of particular interest are cohorts in Africa, India, and China that are infected with clade C viruses. METHODOLOGY/PRINCIPAL FINDINGS: A panel of 10 clade C rgp120 envelope proteins was expressed in 293 cells, purified by immunoaffinity chromatography, and used to immunize guinea pigs. The resulting sera were collected and analyzed in checkerboard experiments for rgp120 binding, V3 peptide binding, and CD4 blocking activity. Virus neutralization studies were carried out with two different assays and two different panels of clade C viruses. A high degree of cross reactivity against clade C and clade B viruses and viral proteins was observed. Most, but not all of the immunogens tested elicited antibodies that neutralized tier 1 clade B viruses, and some sera neutralized multiple clade C viruses. Immunization with rgp120 from the CN97001 strain of HIV appeared to elicit higher cross neutralizing antibody titers than the other antigens tested. CONCLUSIONS/SIGNIFICANCE: While all of the clade C antigens tested were immunogenic, some were more effective than others in eliciting virus neutralizing antibodies. Neutralization titers did not correlate with rgp120 binding, V3 peptide binding, or CD4 blocking activity. CN97001 rgp120 elicited the highest level of neutralizing antibodies, and should be considered for further HIV vaccine development studies.