Murder in the Abstract: The First Amendment and the Misappropriation of Brandenburg

When Paladin Enterprises published Hit Man, a manual about murder for hire, it knew and intended that the book would be used for such a purpose. When James Perry used the information contained in Hit Man to murder three innocent persons, he started a legal debate about the scope of First Amendment protections for books that instruct how to commit criminal acts. Many scholars and commentators indicated that Brandenburg v. Ohio contains the applicable constitutional standard; however, in litigation against Paladin, the survivors of the decedents challenged the conventional wisdom. This Note examines the Brandenburg test for its applicability to published materials that function as instruction manuals to perpetrate crimes. Because Brandenburg is inextricably linked with the crowd context, it is inapplicable to the published materials that function not as advocacy, but as instruction. Because Hit Man was used exactly as Paladin had intended, Paladin should be held liable in tort for the wrongful deaths of Perry\u27s three victims

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

Navigating Barriers to Vocational Rehabilitation for HIV-Positive Persons

This study documented the outcomes of 108 HIV-positive persons receiving vocational rehabilitation services. Over a 12-month follow-up, participants reported significantly decreased odds of any unstable housing [Adjusted Odds Ratio (AOR) = 0.21; 95 % CI 0.05–0.90; p p < .01). However, reductions in perceived barriers to employment and increases in income were more pronounced among those not receiving disability benefits at baseline. This was consistent with findings from baseline qualitative interviews with 22 participants where those not on disability were subject to bureaucratic hurdles to rapidly accessing benefits and anticipated stigma of being on disability that propelled them to rejoin the workforce. Vocational rehabilitation could address key structural barriers to optimizing HIV treatment as prevention, and novel approaches are needed to improve outcomes among individuals receiving disability benefits

Relationship Dynamics and Partner Beliefs About Viral Suppression: A Longitudinal Study of Male Couples Living with HIV/AIDS (The Duo Project)

Accurate beliefs about partners’ viral suppression are important for HIV prevention and care. We fit multilevel mixed effects logistic regression models to examine associations between partners’ viral suppression beliefs and objective HIV RNA viral load tests, and whether relationship dynamics were associated with accurate viral suppression beliefs over time. Male couples (N=266 couples) with at least one HIV-positive partner on antiretroviral therapy completed five assessments over two years. Half of the 407 HIV-positive partners were virally suppressed. Of the 40% who had inaccurate viral load beliefs, 80% assumed their partner was suppressed. The odds of having accurate viral load beliefs decreased over time (OR=0.83; p=.042). Within-couple differences in dyadic adjustment (OR=0.66; p<.01) and commitment (OR=0.82; p=.022) were negatively associated with accurate viral load beliefs. Beliefs about a partner's viral load may factor into sexual decision-making and social support. Couple-based approaches are warranted to improve knowledge of partners’ viral load

Monitoring SARS-CoV-2 incidence and seroconversion among university students and employees: a longitudinal cohort study in California, June–August 2020

ObjectivesTo identify incident SARS-CoV-2 infections and inform effective mitigation strategies in university settings, we piloted an integrated symptom and exposure monitoring and testing system among a cohort of university students and employees.DesignProspective cohort study.SettingA public university in California from June to August 2020.Participants2180 university students and 738 university employees.Primary outcome measuresAt baseline and endline, we tested participants for active SARS-CoV-2 infection via quantitative PCR (qPCR) test and collected blood samples for antibody testing. Participants received notifications to complete additional qPCR tests throughout the study if they reported symptoms or exposures in daily surveys or were selected for surveillance testing. Viral whole genome sequencing was performed on positive qPCR samples, and phylogenetic trees were constructed with these genomes and external genomes.ResultsOver the study period, 57 students (2.6%) and 3 employees (0.4%) were diagnosed with SARS-CoV-2 infection via qPCR test. Phylogenetic analyses revealed that a super-spreader event among undergraduates in congregate housing accounted for at least 48% of cases among study participants but did not spread beyond campus. Test positivity was higher among participants who self-reported symptoms (incidence rate ratio (IRR) 12.7; 95% CI 7.4 to 21.8) or had household exposures (IRR 10.3; 95% CI 4.8 to 22.0) that triggered notifications to test. Most (91%) participants with newly identified antibodies at endline had been diagnosed with incident infection via qPCR test during the study.ConclusionsOur findings suggest that integrated monitoring systems can successfully identify and link at-risk students to SARS-CoV-2 testing. As the study took place before the evolution of highly transmissible variants and widespread availability of vaccines and rapid antigen tests, further research is necessary to adapt and evaluate similar systems in the present context

Natural Biology of Polyomavirus Middle T Antigen

“It has been commented by someone that ‘polyoma’ is an adjective composed of a prefix and suffix, with no root between—a meatless linguistic sandwich” (C. J. Dawe). The very name “polyomavirus” is a vague mantel: a name given before our understanding of these viral agents was clear but implying a clear tumor life-style, as noted by the late C. J. Dawe. However, polyomavirus are not by nature tumor-inducing agents. Since it is the purpose of this review to consider the natural function of middle T antigen (MT), encoded by one of the seemingly crucial transforming genes of polyomavirus, we will reconsider and redefine the virus and its MT gene in the context of its natural biology and function. This review was motivated by our recent in vivo analysis of MT function. Using intranasal inoculation of adult SCID mice, we have shown that polyomavirus can replicate with an MT lacking all functions associated with transformation to similar levels to wild-type virus. These observations, along with an almost indistinguishable replication of all MT mutants with respect to wild-type viruses in adult competent mice, illustrate that MT can have a play subtle role in acute replication and persistence. The most notable effect of MT mutants was in infections of newborns, indicating that polyomavirus may be highly adapted to replication in newborn lungs. It is from this context that our current understanding of this well-studied virus and gene is presented

The genome of the domesticated apple (Malus x domestica Borkh.)

We report a high-quality draft genome sequence of the domesticated apple (Malus x domestica). We show that a relatively recent (> 50 million years ago) genome-wide duplication (GWD) has resulted in the transition from nine ancestral chromosomes to 17 chromosomes in the Pyreae. Traces of older GWDs partly support the monophyly of the ancestral paleohexaploidy of eudicots. Phylogenetic reconstruction of Pyreae and the genus Malus, relative to major Rosaceae taxa, identified the progenitor of the cultivated apple as M. sieversii. Expansion of gene families reported to be involved in fruit development may explain formation of the pome, a Pyreae-specific false fruit that develops by proliferation of the basal part of the sepals, the receptacle. In apple, a subclade of MADS-box genes, normally involved in flower and fruit development, is expanded to include 15 members, as are other gene families involved in Rosaceae-specific metabolism, such as transport and assimilation of sorbitol