Some behavioral aspects of energy descent: How a biophysical psychology might help people transition through the lean times ahead

This article is part of the Research Topic: Nature and environment: The psychology of its benefits and its protection.We may soon face biophysical limits to perpetual growth. Energy supplies may tighten and then begin a long slow descent while defensive expenditures rise to address problems caused by past resource consumption. The outcome may be significant changes in daily routines at the individual and community level. It is difficult to know when this scenario might begin to unfold but it clearly would constitute a new behavioral context, one that the behavioral sciences least attends to. Even if one posits a less dramatic scenario, people may still need to make many urgent and perhaps unsettling transitions. And while a robust response would be needed, it is not at all clear what should be the details of that response. Since it is likely that no single response will fix things everywhere, for all people or for all time, it would be useful to conduct many social experiments. Indeed, a culture of small experiments should be fostered which, at the individual and small group level, can be described as behavioral entrepreneurship. This may have begun, hidden in plain sight, but more social experiments are needed. To be of help, it may be useful to both package behavioral insights in a way that is practitioner-oriented and grounded in biophysical trends and to propose a few key questions that need attention. This paper begins the process of developing a biophysical psychology, incomplete as it is at this early stage.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109261/1/De Young, R. (2014) Some behavioral aspects of energy descent, How a biophysical psychology might help people transition through the lean times ahead, Frontiers in Psychology, 5, 1255.pdfDescription of De Young, R. (2014) Some behavioral aspects of energy descent, How a biophysical psychology might help people transition through the lean times ahead, Frontiers in Psychology, 5, 1255.pdf : Main articl

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

Novel distal occluder washout method for prevention of no-reflow during stenting of saphenous vein grafts

This study assessed safety of the distal occlusion washout (DOW) method for prevention of no-reflow during stenting of degenerated saphenous vein grafts (SVGs). The DOW method involves protection of distal native coronary circulation with an occlusive balloon during the pretreatment and washout steps prior to stenting. Outcomes of stenting of 23 grafts in 21 patients after pretreatment with the DOW method were evaluated. The mean graft age was 7.4 ± 4.3 years. The mean treated lesion length was 53 ± 28 mm. Total occlusions were treated in 6 grafts and thrombotic lesions in 10 nontotally occluded grafts. One non-Q-wave MI and one acute stent thrombosis were observed. No deaths, Q-wave MIs, or subacute thromboses occurred. Follow-up in 18/21 (85.7%) patients at 28 ± 8 weeks demonstrated target graft revascularization in 1 (5%) patient. The DOW method prevented clinically significant no-reflow in all 23 degenerated SVGs stented

The expression of TGF-β receptors in human atherosclerosis: Evidence for acquired resistance to apoptosis due to receptor imbalance

The degree of cellularity in vascular lesions Is determined by the balance between the migration and proliferation of cells relative to their rate of egress and apoptosis. Transforming growth factor-β1, can act as a potent antiproliferative and apoptotic factor for proliferating vascular cells. Our laboratory has previously identified cells cultured from human vascular lesions that are resistant to the antiproliferative effect of TGF-β1, due to an acquired mutation in the Type II receptor for TGF-β1. In the present studies, the expression of the Type I and II receptors in coronary and carotid atherosclerotic lesions was analysed by immunostaining, RT-PCR, and in situ RT-PCR. Levels of the Type I and Type II receptors varied widely within lesions, with the highest levels in the fibrous cap and at discrete foci within the lesion. Regions of smooth muscle-like cells (SMC) were commonly found that were Type I positive but Type II receptor negative. In 43 cell lines cultured from 126 human lesions, 84% of the lesion-derived cell (LDC) cultures exhibited functional resistance to the antiproliferative effect of TGF-β1. This resistance was conferred against TGF-β1, TGF-β2, and TGF-β3, but not interferon-γ or mimosine. While normal SMC exhibited a four-fold increase in the rate of apoptosis after TGE-β1 treatment, most LDC were resistant to apoptosis in response to TGF-β1. Resistant cells exhibited selective loss of Type II receptor expression, and retroviral transfection of Type II receptor cDNA partially corrected the functional deficit. Thus, resistance to apoptosis may lead to the slow proliferation of resistant cell subsets, thereby contributing to the progression of atherosclerotic and restenotic lesions

Temporal trends in the use of intraaortic balloon pump associated with percutaneous coronary intervention in the United States, 1998-2008

BACKGROUND: With conflicting evidence regarding the usefulness of intra-aortic balloon pump (IABP), reports of IABP use in the United States (US) have been inconsistent. Our objective was to examine trends in IABP usage in percutaneous coronary intervention (PCI) in the US, and to evaluate the association of IABP use with mortality. METHODS: Retrospective, observational study using patient data obtained from the Nationwide Inpatient Sample (NIS) database from 1998 to 2008. Patients undergoing any PCI (1,552,602 procedures) for a primary diagnosis of symptomatic coronary artery disease (CAD) and acute coronary syndrome (ACS), including non-ST elevation MI (NSTEMI) and ST elevation MI (STEMI), were evaluated. RESULTS: The overall use of IABP significantly decreased during the study period from 0.99% in 1998 to 0.36% in 2008 (univariate and multivariate p for trend <.0001). Patients who received IABP had substantially higher rates of shock compared to those who did not receive IABP (38.09% vs. 0.70%, p<.0001), which was associated with markedly higher in-hospital mortality rates (20.31% vs. 0.72%, p<.0001). However, IABP use significantly decreased in patients with shock (36.5% to 13.4%) and AMI (2.23% to 0.84%) (univariate and multivariate p for trend for both <.0001). A temporal reduction in all-cause PCI-associated mortality from 1.1% in 1998 to 0.86% in 2008 (univariate and multivariate p for trend <.0001) was also observed. CONCLUSIONS: The utilization of IABP associated with PCI significantly decreased between 1998 and 2008 in the US, even amongst patients with acute myocardial infarction and shock

Vascular complications associated with arteriotomy closure devices in patients undergoing percutaneous coronary procedures: a meta-analysis.

OBJECTIVES: This study was designed to assess the safety of arteriotomy closure devices (ACDs) versus mechanical compression by meta-analysis in patients undergoing percutaneous transfemoral coronary procedures. BACKGROUND: Although ACDs are widely applied for hemostasis after percutaneous endovascular procedures, their safety is controversial. METHODS: Randomized, case-control, and cohort studies comparing access-related complications using ACDs versus mechanical compression were analyzed. The primary end point was the cumulative incidence of vascular complications, including pseudoaneurysm, arteriovenous fistula, retroperitoneal hematoma, femoral artery thrombosis, surgical vascular repair, access site infection, and blood transfusion. RESULTS: A total of 30 studies involving 37,066 patients were identified. No difference in complication incidence between Angio-Seal and mechanical compression was revealed in the diagnostic (Dx) setting (odds ratio [OR] 1.08, 95% confidence interval [CI] 0.11 to 10.0) or percutaneous coronary interventions (PCI) (OR 0.86, 95% CI 0.65 to 1.12). Meta-analysis of randomized trials only showed a trend toward less complications using Angio-Seal in a PCI setting (OR 0.46, 95% CI 0.20 to 1.04; p = 0.062). No differences were observed regarding Perclose in either Dx (OR 1.51, 95% CI 0.24 to 9.47) or PCI (OR 1.21, 95% CI 0.94 to 1.54) setting. An increased risk in complication rates using VasoSeal in the PCI setting (OR 2.25, 95% CI 1.07 to 4.71) was found. The overall analysis favored mechanical compression over ACD (OR 1.34, 95% CI 1.01 to 1.79). CONCLUSIONS: In the setting of Dx angiography, the risk of access-site-related complications was similar for ACD compared with mechanical compression. In the setting of PCI, the rate of complications appeared higher with VasoSeal