On Nietzsche’s genealogical mode of inquiry

The subject of this thesis is Friedrich Nietzsche’s methodology, the genealogical mode of inquiry, which came to fruition in On the Genealogy of Morals. The precise nature of the genealogy, as a mode of inquiry, is a site of contest amongst scholars, with the central debates pivoting around four questions which arise upon considering the methodology: (1) what is the critical import of Nietzsche’s genealogical mode of inquiry? (2) What form of critique does it take? (3) To whom does Nietzsche address his reflections? And (4) what role, if any, does history play in Nietzsche’s genealogical narratives? Accordingly, this thesis seeks to offer and to defend answers to the central questions that are generated by the consideration of Nietzsche’s methodology.In order to get a foothold into these debates and to provide the boundary within which these disagreements occur the first chapter has as its object of inquiry an examination and evaluation of Nietzsche scholars’ responses to these issues. In chapter two I defend my interpretation against these rival views, and contend that the genealogy takes the form of an immanent critique, and that it is intended, at least, to reach all of Nietzsche’s contemporaries.The adage “genealogy is history correctly practiced” is treated in the remaining three chapters, in which I attempt to morph what appears to be at present an uninformative formulation into an informative one by arguing that for Nietzsche historiography is best seen as a form of artistry. And, this I submit, serves to shed light upon the genealogical mode of inquiry, and to shape the boundary by which the equation of genealogy as methodology with history becomes instructive

Introducing the Medical Ethics Bowl

Although ethics is an essential component of undergraduate medical education, research suggests current medical ethics curricula face considerable challenges in improving students’ ethical reasoning. This paper discusses these challenges and introduces a promising new mode of graduate and professional ethics instruction for overcoming them. We begin by describing common ethics curricula, focusing in particular on established problems with current approaches. Next, we describe a novel method of ethics education and assessment for medical students that we have devised, the Medical Ethics Bowl. Finally, we suggest pedagogical advantages to MEBs when compared to other ethics curricula

The Kantian Framework of Complementarity

A growing number of commentators have, in recent years, noted the important affinities in the views of Immanuel Kant and Niels Bohr. While these commentators are correct, the picture they present of the connections between Bohr and Kant is painted in broad strokes; it is open to the criticism that these affinities are merely superficial. In this essay, I provide a closer, structural, analysis of both Bohr's and Kant's views that makes these connections more explicit. In particular, I demonstrate the similarities between Bohr's argument, on the one hand, that neither the wave nor the particle description of atomic phenomena pick out an object in the ordinary sense of the word, and Kant's requirement, on the other hand, that both 'mathematical' (having to do with magnitude) and 'dynamical' (having to do with an object's interaction with other objects) principles must be applicable to appearances in order for us to determine them as objects of experience. I argue that Bohr's 'Complementarity interpretation' of quantum mechanics, which views atomic objects as idealizations, and which licenses the repeal of the principle of causality for the domain of atomic physics, is perfectly compatible with, and indeed follows naturally from a broadly Kantian epistemological framework.Comment: Slight change between this version and previous in the wording of the first paragraph of the section 'Complementarity

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Introduction: Nietzsche's Life and Works

An introduction to Nietzsche's life and works

Nietzsche's Ethics of Affirmation

This chapter looks at Nietzsche's notion of the affirmation of life. It begins with the origins of the concept in Schopenhauer and in the Schopenhauerian philosophy known to Nietzsche. It then examines affirmation in three phases of Nietzsche's writing: early, middle and late. It relates affirmation to other key Nietzschean concepts like the Apollonian and the Dionysian, eternal recurrence, amor fati and will to power

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival