Defending legitimate epidemiologic research: combating Lysenko pseudoscience

This analysis presents a detailed defense of my epidemiologic research in the May 17, 2003 British Medical Journal that found no significant relationship between environmental tobacco smoke (ETS) and tobacco-related mortality. In order to defend the honesty and scientific integrity of my research, I have identified and addressed in a detailed manner several unethical and erroneous attacks on this research. Specifically, I have demonstrated that this research is not "fatally flawed," that I have not made "inappropriate use" of the underlying database, and that my findings agree with other United States results on this relationship. My research suggests, contrary to popular claims, that there is not a causal relationship between ETS and mortality in the U.S. responsible for 50,000 excess annual deaths, but rather there is a weak and inconsistent relationship. The popular claims tend to damage the credibility of epidemiology. In addition, I address the omission of my research from the 2006 Surgeon General's Report on Involuntary Smoking and the inclusion of it in a massive U.S. Department of Justice racketeering lawsuit. I refute erroneous statements made by powerful U.S. epidemiologists and activists about me and my research and I defend the funding used to conduct this research. Finally, I compare many aspect of ETS epidemiology in the U.S. with pseudoscience in the Soviet Union during the period of Trofim Denisovich Lysenko. Overall, this paper is intended to defend legitimate research against illegitimate criticism by those who have attempted to suppress and discredit it because it does not support their ideological and political agendas. Hopefully, this defense will help other scientists defend their legitimate research and combat "Lysenko pseudoscience.

On the Perception of Religious Group Membership from Faces

BACKGROUND: The study of social categorization has largely been confined to examining groups distinguished by perceptually obvious cues. Yet many ecologically important group distinctions are less clear, permitting insights into the general processes involved in person perception. Although religious group membership is thought to be perceptually ambiguous, folk beliefs suggest that Mormons and non-Mormons can be categorized from their appearance. We tested whether Mormons could be distinguished from non-Mormons and investigated the basis for this effect to gain insight to how subtle perceptual cues can support complex social categorizations. METHODOLOGY/PRINCIPAL FINDINGS: Participants categorized Mormons' and non-Mormons' faces or facial features according to their group membership. Individuals could distinguish between the two groups significantly better than chance guessing from their full faces and faces without hair, with eyes and mouth covered, without outer face shape, and inverted 180°; but not from isolated features (i.e., eyes, nose, or mouth). Perceivers' estimations of their accuracy did not match their actual accuracy. Exploration of the remaining features showed that Mormons and non-Mormons significantly differed in perceived health and that these perceptions were related to perceptions of skin quality, as demonstrated in a structural equation model representing the contributions of skin color and skin texture. Other judgments related to health (facial attractiveness, facial symmetry, and structural aspects related to body weight) did not differ between the two groups. Perceptions of health were also responsible for differences in perceived spirituality, explaining folk hypotheses that Mormons are distinct because they appear more spiritual than non-Mormons. CONCLUSIONS/SIGNIFICANCE: Subtle markers of group membership can influence how others are perceived and categorized. Perceptions of health from non-obvious and minimal cues distinguished individuals according to their religious group membership. These data illustrate how the non-conscious detection of very subtle differences in others' appearances supports cognitively complex judgments such as social categorization

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