18 research outputs found
A new model for workforce development: university of Nevada Las Vegas educator externship program
Educators and future educators must be a part of the continual career awareness and experience process of students and future students. Teachers need to know how their subjects can add to the employability of their students. This program provides a vehicle for school curriculum to be developed and implemented in all academic disciplines
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
COVID-19 vaccination hesitancy among health care workers, communication, and policy-making
Background: Coronavirus disease 2019 (COVID-19) vaccine hesitancy in healthcare workers (HCWs) contributes to personal and patient risk in contracting COVID-19. Reasons behind hesitancy and how best to improve vaccination rates in HCWs are not clear.
Methods: We adapted a survey using the Health Belief Model framework to evaluate HCW vaccine hesitancy and reasons for choosing for or against COVID-19 vaccination. The survey was sent to three large academic medical centers in the Chicagoland area between March and May 2021.
Results: We received 1974 completed responses with 85% of HCWs receiving or anticipating receiving COVID-19 vaccination. Multivariable logistic regression found HCWs were less likely to receive COVID-19 vaccination if they were Black (OR 0.34, 95% CI 0.15-0.80), Republican (OR 0.54, 95% CI 0.31-0.91), or allergic to any vaccine component (OR 0.27, 95% CI 0.10-0.70) and more likely to receive if they believed people close to them thought it was important for them to receive the vaccine (OR 5.2, 95% CI 3-8).
Conclusions: A sizable number of HCWs remain vaccine hesitant one year into the COVID-19 pandemic. As HCWs are positively influenced by colleagues who believe COVID-19 vaccination, development of improved communication across HCW departments and roles may improve vaccination rates
Data, modeling, or policy approaches used to inform equitable public health interventions while responding to emergent viral pathogens with pandemic potential: a scoping review protocol.
A first step in improving the use of mathematical modeling for current and future potential viral pandemics includes cataloging the types of modeling strategies employed, parameters estimated and associated uncertainties, and the assumptions made in the models. This scoping review will enable us to systematically catalog such features of models used in the current SARS-CoV-2 pandemic, clarify how modeling parameters are defined and estimated, better understand how viruses with pandemic potential should be modeled, and how modeling approaches may need to change throughout the course of a pandemic. The review will also enable us to identify and analyze existing knowledge gaps in the application of mathematical modeling to viruses with pandemic potential.
** See PDF file for full scoping review protoco
Genetic influences on handedness: Data from 25,732 Australian and Dutch twin families
Handedness refers to a consistent asymmetry in skill or preferential use between the hands and is related to lateralization within the brain of other functions such as language. Previous twin studies of handedness have yielded inconsistent results resulting from a general lack of statistical power to find significant effects. Here we present analyses from a large international collaborative study of handedness (assessed by writing/drawing or self report) in Australian and Dutch twins and their siblings (54,270 individuals from 25,732 families). Maximum likelihood analyses incorporating the effects of known covariates (sex, year of birth and birth weight) revealed no evidence of hormonal transfer, mirror imaging or twin specific effects. There were also no differences in prevalence between zygosity groups or between twins and their singleton siblings. Consistent with previous meta-analyses, additive genetic effects accounted for about a quarter (23.64%) of the variance (95%CI 20.17, 27.09%) with the remainder accounted for by non-shared environmental influences. The implications of these findings for handedness both as a primary phenotype and as a covariate in linkage and association analyses are discussed.Sarah E. Medland, David L. Duffy, Margaret J. Wright, Gina M. Geffen, David A. Hay, Florence Levy, Catherina E.M. van-Beijsterveldt, Gonneke Willemsen, Grant C. Townsend, Vicki White, Alex W. Hewitt, David A. Mackey, J. Michael Bailey, Wendy S. Slutske, Dale R. Nyholt, Susan A. Treloar, Nicholas G. Martin, Dorret I. Booms
Loss of the Martian atmosphere to space: Present-day loss rates determined from MAVEN observations and integrated loss through time
International audienceObservations of the Mars upper atmosphere made from the Mars Atmosphere and Volatile Evolution (MAVEN) spacecraft have been used to determine the loss rates of gas from the upper atmosphere to space for a complete Mars year (16 Nov 2014 – 3 Oct 2016). Loss rates for H and O are sufficient to remove ∼2-3 kg/s to space. By itself, this loss would be significant over the history of the planet. In addition, loss rates would have been greater early in history due to the enhanced solar EUV and more-active Sun. Integrated loss, based on current processes whose escape rates in the past are adjusted according to expected solar evolution, would have been as much as 0.8 bar CO2 or 23 m global equivalent layer of H2O; these losses are likely to be lower limits due to the nature of the extrapolation of loss rates to the earliest times. Combined with the lack of surface or subsurface reservoirs for CO2 that could hold remnants of an early, thick atmosphere, these results suggest that loss of gas to space has been the dominant process responsible for changing the climate of Mars from an early, warmer environment to the cold, dry one that we see today
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Subretinal Hyperreflective Material in the Comparison of Age-Related Macular Degeneration Treatments Trials
PurposeTo evaluate the association of subretinal hyperreflective material (SHRM) with visual acuity (VA), geographic atrophy (GA), and scar in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).DesignProspective cohort study within a randomized clinical trial.ParticipantsThe 1185 CATT participants.MethodsMasked readers graded scar and GA on fundus photography and fluorescein angiography and graded SHRM on time-domain and spectral-domain (SD) optical coherence tomography (OCT) throughout 104 weeks. Measurements of SHRM height and width in the fovea, within the center 1 mm(2), or outside the center 1mm(2) were obtained on SD OCT images at 56 (n = 76) and 104 (n = 66) weeks.Main outcome measuresPresence of SHRM, as well as location and size, and associations with VA, scar, and GA.ResultsAmong CATT participants, the percentage with SHRM at enrollment was 77%, decreasing to 68% at 4 weeks after treatment and to 54% at 104 weeks. At 104 weeks, scar was present more often in eyes with persistent SHRM than in eyes with SHRM that resolved (64% vs. 31%; P < 0.0001). Among eyes with detailed evaluation of SHRM at weeks 56 (n = 76) and 104 (n = 66), mean VA letter score was 73.5 (standard error [SE], 2.8), 73.1 (SE, 3.4), 65.3 (SE, 3.5), and 63.9 (SE, 3.7) when SHRM was absent, present outside the central 1 mm(2), present within the central 1 mm(2) but not the foveal center, or present at the foveal center (P = 0.02), respectively. When SHRM was present, the median maximum height under the fovea, within the central 1 mm(2) including the fovea and anywhere within the scan, was 86 μm, 120 μm, and 122 μm, respectively. Visual acuity was decreased with greater SHRM height and width (P < 0.05).ConclusionsIn eyes with neovascular age-related macular degeneration (AMD), SHRM is common and often persists after anti-vascular endothelial growth factor treatment. At 2 years, eyes with scar were more likely to have SHRM than other eyes. Greater SHRM dimensions were associated with worse VA. In eyes with neovascular AMD, SHRM is an important morphologic biomarker
Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data
Background:
General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care.
Methods:
For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered.
Findings:
Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09–2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75–3·10, p<0·0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1·53, 95% CI 1·14–2·04, p=0·0044). The risk of bias and variability between studies was assessed to be low.
Interpretation:
Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons