On a Pathway Towards Thriving: Evaluating the Effectiveness of Tools to Promote Positive Development and Intentional Self Regulation in Youth

This article provides initial data about the reliability and validity of tools aimed at promoting youth intentional self regulation (ISR) within mentoring programs. Based on the translation of the theory-based research about ISR and youth thriving conducted within the 4-H Study of Positive Youth Development (PYD), the GPS to Success tools use the metaphor of a car’s GPS navigational system to enhance goal-directed behaviors among youth. The core GPS tools are “growth grids,” designed to help mentors appraise ISR skill development and to link these skills to other grids assessing the Five Cs of PYD and Contribution. Data from 152 mentor and youth pairs from 4-H program sites in Oregon and North Carolina indicated that the growth grids were generally reliable. Although validity evidence was mixed, rubrics for “G” and “P” and for a global GPS score were related to a well-validated measure of ISR

On a Pathway Towards Thriving: Evaluating the Effectiveness of Tools to Promote Positive Development and Intentional Self Regulation in Youth

This article provides initial data about the reliability and validity of tools aimed at promoting youth intentional self regulation (ISR) within mentoring programs. Based on the translation of the theory-based research about ISR and youth thriving conducted within the 4-H Study of Positive Youth Development (PYD), the GPS to Success tools use the metaphor of a car’s GPS navigational system to enhance goal-directed behaviors among youth. The core GPS tools are “growth grids,” designed to help mentors appraise ISR skill development and to link these skills to other grids assessing the Five Cs of PYD and Contribution. Data from 152 mentor and youth pairs from 4-H program sites in Oregon and North Carolina indicated that the growth grids were generally reliable. Although validity evidence was mixed, rubrics for “G” and “P” and for a global GPS score were related to a well-validated measure of ISR

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK

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

US Public Attitudes Toward COVID-19 Vaccine Mandates

Ending the coronavirus disease 2019 (COVID-19) pandemic through vaccination will require sufficient uptake, possibly through mandatory vaccination. At present, certain vaccines are required for children to attend school. Although vaccine mandates for adults are legal, they have generally been applied narrowly to select groups, such as health care workers, rather than broadly enforced. We surveyed the US public to assess acceptability of COVID-19 vaccine mandates

Public Perspectives on COVID-19 Vaccine Prioritization

Importance: As COVID-19 vaccine distribution continues, policy makers are struggling to decide which groups should be prioritized for vaccination. Objective: To assess US adults\u27 preferences regarding COVID-19 vaccine prioritization. Design, Setting, and Participants: This survey study involved 2 independent, online surveys of US adults aged 18 years and older, 1 conducted by Gallup from September 14 to 27, 2020, and the other conducted by the COVID Collaborative from September 19 to 25, 2020. Samples were weighted to reflect sociodemographic characteristics of the US population. Exposures: Respondents were asked to prioritize groups for COVID-19 vaccine and to rank their prioritization considerations. Main Outcomes and Measures: The study assessed prioritization preferences and agreement with the National Academies of Science, Engineering, and Medicine\u27s Preliminary Framework for Equitable Allocation of COVID-19 Vaccine. Results: A total of 4735 individuals participated, 2730 (1474 men [54.1%]; mean [SD] age, 59.2 [14.5] years) in the Gallup survey and 2005 (944 men [47.1%]; 203 participants [21.5%] aged 55-59 years) in the COVID Collaborative survey. In both the Gallup COVID-19 Panel and COVID Collaborative surveys, respondents listed health care workers (Gallup, 93.6% [95% CI, 91.2%-95.3%]; COVID Collaborative, 80.0% [95% CI, 78.0%-81.9%]) and adults of any age with serious comorbid conditions (Gallup, 78.6% [95% CI, 75.2%-81.7%]; COVID Collaborative, 72.9% [95% CI, 70.7%-74.9%]) among their 4 highest priority groups. Respondents of all political affiliations agreed with prioritizing Black, Hispanic, Native American, and other communities that have been disproportionately affected by COVID-19 (Gallup, 74.2% [95% CI, 70.6%-77.5%]; COVID Collaborative, 84.9% [95% CI, 83.1%-86.5%]), and COVID Collaborative respondents were willing to be preceded in line by teachers and childcare workers (92.5%; 95% CI, 91.2%-93.7%) and grocery workers (85.9%; 95% CI, 84.2%-87.5%). Older respondents in both surveys were significantly less likely than younger respondents to prioritize healthy adults aged 65 years and older among their 4 highest priority groups (Gallup, 23.7% vs 39.1% [χ2= 2160.8; P \u3c001]; COVID Collaborative, 23.3% vs 28.8% [χ2= 5.0198; P =.03]). COVID Collaborative respondents believed the 4 most important considerations for prioritization were preventing COVID-19 spread (78.4% [95% CI, 76.3%-80.3%]), preventing the most deaths (72.1% [95% CI, 69.9%-74.2%]), preventing long-term complications (68.9% [66.6%-71.9%]), and protecting frontline workers (63.8% [95% CI, 61.5%-66.1%]). Conclusions and Relevance: US adults broadly agreed with the National Academies of Science, Engineering, and Medicine\u27s prioritization framework. Respondents endorsed prioritizing racial/ethnic communities that are disproportionately affected by COVID-19, and older respondents were significantly less likely than younger respondents to endorse prioritizing healthy people older than 65 years. This provides reason for caution about COVID-19 vaccine distribution plans that prioritize healthy adults older than a cutoff age without including those younger than that age with preexisting conditions, that aim solely to prevent the most deaths, or that give no priority to frontline workers or disproportionately affected communities

Beyond the deficit model: bullying and trajectories of character virtues in adolescence

Previous work on peer victimization has focused primarily on academic outcomes and negative indicators of youth involved in bullying. Few studies have taken a strength-based approach to examine attributes associated with bullies and victims of bullying. As such, we examined developmental trajectories of moral, performance, and civic character components, and their links to bully status using data from 713 youth (63% female) who participated in Wave 3 (approximately Grade 7) through Wave 6 (approximately Grade 10) of the 4-H Study of Positive Youth Development. Latent growth curve analyses indicated that moral character was stable across waves, whereas civic character increased slightly by Wave 6. Trajectories for performance character varied; some youth alternatively displayed positive versus negative growth. Youth who reported bullying behavior reported lower initial levels of moral, performance, and civic character as compared to youth not involved in bullying. Bully-victims reported lower initial levels of moral and civic character as compared to youth not involved in bullying. Implications for future work examining character-related components in the context of peer victimization are discussed