A Corrective to Bovens and Hartmann's Measure of Coherence

Bovens and Hartmann (2003a, 2003b) propose to analyze coherence as a confidence-boosting property. On the basis of this idea, they construct a new probabilistic theory of coherence. In this paper, I will attempt to show that the resulting measure of coherence clashes with some of the intuitions that motivate it. Also, I will try to show that this clash is not due to the view on coherence as a confidence-boosting property or to the general features of the model that Bovens and Hartmann use to analyze coherence. It will turn out that there is at least one other measure that is similarly based on the concept of a confidence-boosting property, but does not have the same counterintuitive results

Walter the Banker: The Conjunction Fallacy Reconsidered

In a famous experiment by Tversky and Kahneman (1983), featuring Linda the bank teller, the participants assign a higher probability to a conjunction of propositions than to one of the conjuncts, thereby seemingly committing a probabilistic fallacy. In this paper, we discuss a slightly different example featuring someone named Walter, who also happens to work at a bank, and argue that, in this example, it is rational to assign a higher probability to the conjunction of suitably chosen propositions than to one of the conjuncts. By pointing out the similarities between Tversky and Kahneman's experiment and our example, we argue that the participants in the experiment may assign probabilities to the propositions in question in such a way that it is also rational for them to give the conjunction a higher probability than one of the conjuncts

Probabilistic Measures of Coherence

Het onderwerp van dit proefschrift bevindt zich op het raakvlak van kennisleer en wetenschapsfilosofie. Meer in het bijzonder staat het geven van een precieze analyse van onze intuïtieve notie van coherentie centraal. Er wordt in de wetenschapsfilosofie veel gesproken over de coherentie van een theorie en over de vraag of coherentie in het algemeen een indicator van waarheid kan zijn. Echter, een veel gehoorde klacht in deze discussies is dat het begrip coherentie hopeloos vaag is. In de laatste jaren zijn er een aantal voorstellen gedaan voor een formele explicatie van het begrip coherentie. In het eerste hoofdstruk van dit proefschrift benadruk ik dat dit concept op verschillende intuïties berust en dat we niet uit kunnen sluiten dat elk van deze intuïtieve concepten op verschillende wijze geformaliseerd dient te worden. Ik onderscheid (zonder te willen beweren dat dit de enige of zelfsde belangrijkste noties van coherentie zijn )drie verschillende betekenissen van het begrip coherentie zoals dit in de wetenschapsfilosofie gebruikt is. Deze zijn coherentie als een epistemische deugd, coherentie als een waarheids-bevorderende eigenschap en coherentie als een relatie tussen theorie en evidentie

Resectability and Ablatability Criteria for the Treatment of Liver Only Colorectal Metastases:Multidisciplinary Consensus Document from the COLLISION Trial Group

The guidelines for metastatic colorectal cancer crudely state that the best local treatment should be selected from a 'toolbox' of techniques according to patient- and treatment-related factors. We created an interdisciplinary, consensus-based algorithm with specific resectability and ablatability criteria for the treatment of colorectal liver metastases (CRLM). To pursue consensus, members of the multidisciplinary COLLISION and COLDFIRE trial expert panel employed the RAND appropriateness method (RAM). Statements regarding patient, disease, tumor and treatment characteristics were categorized as appropriate, equipoise or inappropriate. Patients with ECOG≤2, ASA≤3 and Charlson comorbidity index ≤8 should be considered fit for curative-intent local therapy. When easily resectable and/or ablatable (stage IVa), (neo)adjuvant systemic therapy is not indicated. When requiring major hepatectomy (stage IVb), neo-adjuvant systemic therapy is appropriate for early metachronous disease and to reduce procedural risk. To downstage patients (stage IVc), downsizing induction systemic therapy and/or future remnant augmentation is advised. Disease can only be deemed permanently unsuitable for local therapy if downstaging failed (stage IVd). Liver resection remains the gold standard. Thermal ablation is reserved for unresectable CRLM, deep-seated resectable CRLM and can be considered when patients are in poor health. Irreversible electroporation and stereotactic body radiotherapy can be considered for unresectable perihilar and perivascular CRLM 0-5cm. This consensus document provides per-patient and per-tumor resectability and ablatability criteria for the treatment of CRLM. These criteria are intended to aid tumor board discussions, improve consistency when designing prospective trials and advance intersociety communications. Areas where consensus is lacking warrant future comparative studies.</p

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

Walter the Banker: The Conjunction Fallacy Reconsidered

In a famous experiment by Tversky and Kahneman (1983), featuring Linda the bank teller, the participants assign a higher probability to a conjunction of propositions than to one of the conjuncts, thereby seemingly committing a probabilistic fallacy. In this paper, we discuss a slightly different example featuring someone named Walter, who also happens to work at a bank, and argue that, in this example, it is rational to assign a higher probability to the conjunction of suitably chosen propositions than to one of the conjuncts. By pointing out the similarities between Tversky and Kahneman's experiment and our example, we argue that the participants in the experiment may assign probabilities to the propositions in question in such a way that it is also rational for them to give the conjunction a higher probability than one of the conjuncts