Reply to Rouder (2014) : good frequentist properties raise confidence

Established psychological results have been called into question by demonstrations that statistical significance is easy to achieve, even in the absence of an effect. One often-warned-against practice, choosing when to stop the experiment on the basis of the results, is guaranteed to produce significant results. In response to these demonstrations, Bayes factors have been proposed as an antidote to this practice, because they are invariant with respect to how an experiment was stopped. Should researchers only care about the resulting Bayes factor, without concern for how it was produced? Yu, Sprenger, Thomas, and Dougherty (2014) and Sanborn and Hills (2014) demonstrated that Bayes factors are sometimes strongly influenced by the stopping rules used. However, Rouder (2014) has provided a compelling demonstration that despite this influence, the evidence supplied by Bayes factors remains correct. Here we address why the ability to influence Bayes factors should still matter to researchers, despite the correctness of the evidence. We argue that good frequentist properties mean that results will more often agree with researchers’ statistical intuitions, and good frequentist properties control the number of studies that will later be refuted. Both help raise confidence in psychological results

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

Ion‐Selective Sensors Based on Laser‐Induced Graphene for Evaluating Human Hydration Levels Using Urine Samples

Complex graphene electrode fabrication protocols including conventional chemical vapor deposition and graphene transfer techniques as well as more recent solution‐phase printing and postprint annealing methods have hindered the wide‐scale implementation of electrochemical devices including solid‐state ion‐selective electrodes (ISEs). Herein, a facile graphene ISE fabrication technique that utilizes laser induced graphene (LIG), formed by converting polyimide into graphene by a CO2 laser and functionalization with ammonium ion (NH4+) and potassium ion (K+) ion‐selective membranes, is demonstrated. The electrochemical LIG ISEs exhibit a wide sensing range (0.1 × 10−3–150 × 10−3 m for NH4+ and 0.3 × 10−3–150 × 10−3 m for K+) with high stability (minimal drop in signal after 3 months of storage) across a wide pH range (3.5–9.0). The LIG ISEs are also able to monitor the concentrations of NH4+ and K+ in urine samples (29–51% and 17–61% increase for the younger and older patient; respectively, after dehydration induction), which correlate well with conventional hydration status measurements. Hence, these results demonstrate a facile method to perform in‐field ion sensing and are the first steps in creating a protocol for quantifying hydration levels through urine testing in human subjects.This is the peer-reviewed version of the following article: Kucherenko, Ivan S., Delaney Sanborn, Bolin Chen, Nate Garland, Michael Serhan, Erica Forzani, Carmen Gomes, and Jonathan C. Claussen. "Ion‐Selective Sensors Based on Laser‐Induced Graphene for Evaluating Human Hydration Levels Using Urine Samples." Advanced Materials Technologies 5, no. 6 (2020): 1901037, which has been published in final form at DOI: 10.1002/admt.201901037. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Posted with permission.</p