Age distributions of Greenlandic dwarf shrubs support concept of negligible actuarial senescence

Many plants and sessile animals may not show actuarial senescence, the increase in mortality with age predicted to be ubiquitous by classic evolutionary theories of aging. Age-structured demographic information is, however, limited for most organisms. We assessed the age distributions of nine dwarf shrub species from 863 taproot samples collected in coastal east Greenland. Penalized composite link models (pclm) were used to fill gaps in the observed age ranges, caused by low species-specific sample sizes in relation to life span. Resulting distributions indicate that mortality patterns are independent of age. Actuarial senescence is thus negligible in these dwarf shrub populations. We suggest that smoothing techniques such as pclm enable consideration of noisy age data for determining age distributions. These distributions may, in turn, reveal age effects on demographic rates. Moreover, age determination from the root collars of small plants constitutes a powerful technique to further investigate age dependency of the demography of many plant species, including eudicot herbs. Using these methods for long-lived plants where long-term monitoring is unrealistic, we show that age is unlikely to be an important variable for making population projections and determining extinction risks

Ugandan and British individuals' views of refugees in their countries: An exploratory <scp>mixed‐methods</scp> comparison

Abstract: Using an exploratory mixed‐methods approach, we examined thoughts concerning refugees reported by participants from a non‐Western country, Uganda, and the United Kingdom (total N = 113). We explored whether, due to various sociocultural, political and geographic differences, critical features of refugee migration (e.g., migration forcedness and migration‐related perils) would be viewed differently by Ugandan and UK participants. An inductive qualitative content analysis of responses in an online survey yielded 11 categories with 40 subcategories revealing several similarities between Ugandan and UK participants. For instance, similar proportions of participants from both countries acknowledged refugees' suffering before their migration and the forced nature of refugees' migration. However, we also found that more British than Ugandan participants referred to perils refugees suffer during their journeys, possibly resulting from differences in refugees' migration routes (e.g., crossing other countries, travelling by dilapidated boats, migration duration). Furthermore, Ugandan but not British participants took pride in international praise their country received for its forthcoming treatment of refugees. There were no differences regarding the extent to which Ugandan and British individuals exhibited prejudice towards refugees or experienced threats from refugees. We discuss the theoretical and practical implications of our findings for refugee integration

Systematic evaluation of pembrolizumab dosing in patients with advanced non-small cell lung cancer

International audienceBACKGROUND: In the phase I KEYNOTE-001 study, pembrolizumab demonstrated durable antitumor activity in patients with advanced non-small cell lung cancer (NSCLC). We sought to characterize the relationship between pembrolizumab dose, exposure, and response to define an effective dose for these patients. METHODS: Patients received pembrolizumab 2 mg/kg every 3 weeks (Q3W) (n=55), 10 mg/kg Q3W (n=238), or 10 mg/kg Q2W (n=156). Response (RECIST v1.1) was assessed every 9 weeks. The relationship between the estimated pembrolizumab area under the concentration-time curve at steady-state over 6 weeks (AUCss-6weeks) and the longitudinal change in tumor size (sum of longest diameters) was analyzed by regression and nonlinear mixed effects modeling. This model was simultaneously fit to all tumor size data, then used to simulate response rates, normalizing the trial data across dose for prognostic covariates (tumor PD-L1 expression and EGFR mutation status). The exposure-safety relationship was assessed by logistic regression of pembrolizumab AUCss-6weeks versus occurrence of adverse events of interest based on their immune etiology. RESULTS: Overall response rates were 15% (95% confidence interval [CI] 7%-28%) at 2 Q3W, 25% (18%-33%) at 10 Q3W, and 21% (95% CI 14% to 30%) at 10 Q2W. Regression analyses of percentage change from baseline in tumor size versus AUCss-6week indicated a flat relationship (regression slope P\textgreater0.05). Simulations showed the exposure-response relationship to be similarly flat, thus indicating that the lowest evaluated dose of 2 mg/kg Q3W to likely be at or near the efficacy plateau. Exposure-safety analysis showed the adverse event incidence to be similar among the clinically tested doses. CONCLUSIONS: No significant exposure dependency on efficacy or safety was identified for pembrolizumab across doses of 2 mg/kg to 10 mg/kg. These results support the use of a 2-mg/kg Q3W dosage in patients with previously treated, advanced NSCLC.ClinicalTrials.gov registry: NCT0129582

Tree-Ring Amplification of the Early Nineteenth-Century Summer Cooling in Central Europe

Les prokinéticines sont des facteurs angiogènic potentiels qui se liant aux récepteurs couplés aux protéines G (PKR1 et PKR2) pour initier leurs effets biologiques. Nous avons montré que le transfert transitoire du gène PKR1 après ligation de l’artère coronaire réduit la mortalité et préserve la fonction du ventricule gauche en favorisant la néovascularisation et protegé des cardiomyocytes. Nous avons montré que des souris transgéniques (TG) surexprimant PKR1 dans le coeur aucune anomalie spontanée dans les cardiomyocytes, mais on observe une augmentation de néovascularization. Cependant des souris TG surexprimant PKR2 dans le coeur ont montré de l'hypertrophie excentrique et la perméabilité vasculaire. Pour la première fois nous avons montré que la balance entre l'activation de la voie de signalisation de PKR1 et de PKR2 pouvait être très importante pour protéger les cardiomyocytes des lésions causées par l'ischémie et/ou d’induire la neovascularisation dans le coeur.Cardiovascular disease is first cause of mortality worldwide. Prokineticins are potent angiogenic factors that bind to two G protein-coupled receptors (PKR1 and PKR2) to initiate their biological effects. We showed that transient PKR1 gene transfer after coronary ligation reduces mortality and preserves left ventricular function by promoting neovascularization and protecting cardiomyocytes. Next we showed that transgenic (TG) mice overexpressing PKR1 in heart exhibit neovascularization without inducing any spontaneous pathology in cardiomyocytes. However TG mice overexpressing PKR2 in heart exhibit eccentric hypertrophy in cardiomyocyte and vascular leakage. As a conclusion, for the first time we have shown that the balance between the activation of PKR1 and PKR2 signaling could be very important to prevent cardiomyocytes from ischemic insult and/or to induce neovascularization in heart

The Little Ice Age in Scientific Perspective: Cold Spells and Caveats

Contrary to the position taken by Kelly and Ó Gráda, a rich body of regional- to large-scale temperature reconstructions that span from the last millennium to almost the entire Holocene confirms the existence of several temperature depressions that occurred at different intensities and spatial ranges between c. 1350 and 1900, thus supporting the conception of a Little Ice Age. Nonetheless, the genuine uncertainties that continue to surround paleoclimatic study suggest that methodologies and findings are subject to further refinement

Segmenting the German public for targeted communication about climate change and health along different indicators of the readiness to act against climate change

Introduction: To mitigate the global health threat posed by climate change, multifaceted responses are required. As shown in previous work, older, male, and highly educated individuals exhibit greater general readiness to act against climate change; the same is true of people living in larger communities. The present study investigates the relationships between the indicators (facets) of the readiness to act against climate change—namely individual climate-friendly behavior, acceptance of climate-protection policies, and political participation—and relevant sociodemographic factors. Methods: Data from four waves (2022–2023) of the Planetary Health Action Survey (PACE) were analyzed (N = 3,830, nonprobabilistic representative German sample). Sociodemographic variables (e.g., gender, age, and education) and the three abovementioned facets of the readiness to act against climate change were assessed to examine their relationships. Results: Women and older individuals exhibited more climate-friendly behavior and policy acceptance. Political participation showed the opposite trend. Higher education was linked to less sustainable behavior, greater policy acceptance, and higher participation, while municipality size was only linked to the latter two. Additional analyses explore the relations between age and the constructs at the item level. Conclusions: The findings underscore the importance of a nuanced understanding of people’s readiness to act against climate change. There is a need for tailored communication strategies in climate action that consider communication objectives along with audience characteristics. Different target groups may be relevant when campaigners want to increase political participation rather than change individual behaviors. As older individuals exhibit greater readiness to act in some respects, it is important to include young people in climate-communication efforts