101 research outputs found

    Pre-Sleep Casein Protein Ingestion Does Not Impact Next-Day Appetite, Energy Intake and Metabolism in Older Individuals

    Get PDF
    Maintaining adequate daily protein intake is important to maintain muscle mass throughout the lifespan. In this regard, the overnight period has been identified as a window of opportunity to increase protein intake in the elderly. However, it is unknown whether pre-sleep protein intake affects next-morning appetite and, consequently, protein intake. Therefore, the purpose of the current study was to investigate the effects of a pre-sleep protein drink on next-morning appetite, energy intake and metabolism. Twelve older individuals (eight males, four females; age: 71.3 ± 4.2 years) took part in a single-blind randomised cross-over study. After a standardised dinner, participants consumed either a 40-g protein drink, isocaloric maltodextrin drink, or placebo water control before bedtime. Next-morning appetite, energy intake, resting metabolic rate (RMR), respiratory exchange rate (RER), and plasma acylated ghrelin, leptin, glucose, and insulin concentrations were assessed. No between-group differences were observed for appetite and energy intake at breakfast. Furthermore, RMR, RER, and assessed blood markers were not significantly different between any of the treatment groups. Pre-sleep protein intake does not affect next-morning appetite and energy intake and is therefore a viable strategy to increase daily protein intake in an older population

    CAR T manufacturing: process modifications for a transformational autologous product on a rapid path to licensure

    Get PDF
    The transformational impact of CAR T cell therapies on serious diseases demands a rapid path to licensure in order to establish widespread availability to desperate patients. In addition, the complex, labor intensive, and costly patient-specific manufacturing processes for CAR T cell therapies demand process modifications that enable scalability and affordability to maximize availability to patients. There are many options to improve CAR T processes ranging from automation to improved medium composition to simplified closed-system tubing sets. However, the dramatic dose-dependent safety and efficacy activities of these therapies amplifies the need for maintaining product comparability across process changes. This assessment of comparability is challenged by limited knowledge of product Critical Quality Attributes as well as limited availability of patient cells for process development studies. We have developed a comprehensive analytical toolbox that enables the assessment of product impact of process changes along with a risk-based approach to applying a matrix of appropriate tools for each change. This risk-based approach involves the most extensive product analysis for high-risk changes and a relatively restricted product analysis for low-risk changes. In all cases, the product analysis includes assessments of product characteristics that can hypothetically be impacted by the process change. We describe our approach to identifying, prioritizing, and assessing feasibility of process changes along with generating a suitable product comparability dataset to implement the most impactful process changes on an expedited timeline to licensure. We share examples of comparability data and its application to decision making

    Emulating Natural Disturbances for Declining Late- Successional Species: A Case Study of the Consequences for Cerulean Warblers (Setophaga cerulea)

    Get PDF
    Forest cover in the eastern United States has increased over the past century and while some late-successional species have benefited from this process as expected, others have experienced population declines. These declines may be in part related to contemporary reductions in small-scale forest interior disturbances such as fire, windthrow, and treefalls. To mitigate the negative impacts of disturbance alteration and suppression on some late-successional species, strategies that emulate natural disturbance regimes are often advocated, but large-scale evaluations of these practices are rare. Here, we assessed the consequences of experimental disturbance (using partial timber harvest) on a severely declining late-successional species, the cerulean warbler (Setophaga cerulea), across the core of its breeding range in the Appalachian Mountains. We measured numerical (density), physiological (body condition), and demographic (age structure and reproduction) responses to three levels of disturbance and explored the potential impacts of disturbance on source-sink dynamics. Breeding densities of warblers increased one to four years after all canopy disturbances (vs. controls) and males occupying territories on treatment plots were in better condition than those on control plots. However, these beneficial effects of disturbance did not correspond to improvements in reproduction; nest success was lower on all treatment plots than on control plots in the southern region and marginally lower on light disturbance plots in the northern region. Our data suggest that only habitats in the southern region acted as sources, and interior disturbances in this region have the potential to create ecological traps at a local scale, but sources when viewed at broader scales. Thus, cerulean warblers would likely benefit from management that strikes a landscape-level balance between emulating natural disturbances in order to attract individuals into areas where current structure is inappropriate, and limiting anthropogenic disturbance in forests that already possess appropriate structural attributes in order to maintain maximum productivity

    Emulating Natural Disturbances for Declining Late-Successional Species: A Case Study of the Consequences for Cerulean Warblers (Setophaga cerulea)

    Get PDF
    Forest cover in the eastern United States has increased over the past century and while some late-successional species have benefited from this process as expected, others have experienced population declines. These declines may be in part related to contemporary reductions in small-scale forest interior disturbances such as fire, windthrow, and treefalls. To mitigate the negative impacts of disturbance alteration and suppression on some late-successional species, strategies that emulate natural disturbance regimes are often advocated, but large-scale evaluations of these practices are rare. Here, we assessed the consequences of experimental disturbance (using partial timber harvest) on a severely declining latesuccessional species, the cerulean warbler (Setophaga cerulea), across the core of its breeding range in the Appalachian Mountains. We measured numerical (density), physiological (body condition), and demographic (age structure and reproduction) responses to three levels of disturbance and explored the potential impacts of disturbance on source-sink dynamics. Breeding densities of warblers increased one to four years after all canopy disturbances (vs. controls) and males occupying territories on treatment plots were in better condition than those on control plots. However, these beneficial effects of disturbance did not correspond to improvements in reproduction; nest success was lower on all treatment plots than on control plots in the southern region and marginally lower on light disturbance plots in the northern region. Our data suggest that only habitats in the southern region acted as sources, and interior disturbances in this region have the potential to create ecological traps at a local scale, but sources when viewed at broader scales. Thus, cerulean warblers would likely benefit from management that strikes a landscape-level balance between emulating natural disturbances in order to attract individuals into areas where current structure is inappropriate, and limiting anthropogenic disturbance in forests that already possess appropriate structural attributes in order to maintain maximum productivity

    The interplay between host genetic variation, viral replication and microbial translocation in untreated HIV-infected individuals.

    Get PDF
    Systemic immune activation, a major determinant of HIV disease progression, is the result of a complex interplay between viral replication, dysregulation of the immune system, and microbial translocation due to gut mucosal damage. While human genetic variants influencing HIV viral load have been identified, it is unknown to what extent the host genetic background contributes to inter-individual differences in other determinants of HIV pathogenesis like gut damage and microbial translocation. Using samples and data from 717 untreated participants in the Swiss HIV Cohort Study and a genome-wide association study design, we searched for human genetic determinants of plasma levels of intestinal fatty-acid binding protein (I-FABP/FABP2), a marker of gut damage, and of soluble sCD14 (sCD14), a marker of LPS bioactivity and microbial translocation. We also assessed the correlations between HIV viral load, sCD14 and I-FABP. While we found no genome-wide significant determinant of the tested plasma markers, we observed strong associations between sCD14 and both HIV viral load and I-FABP, shedding new light on the relationships between processes that drive progression of untreated HIV infection

    The state of the Martian climate

    Get PDF
    60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

    The Interplay Between Host Genetic Variation, Viral Replication, and Microbial Translocation in Untreated HIV-Infected Individuals

    Get PDF
    Systemic immune activation, a major determinant of human immunodeficiency virus (HIV) disease progression, is the result of a complex interplay between viral replication, dysregulation of the immune system, and microbial translocation due to gut mucosal damage. Although human genetic variants influencing HIV load have been identified, it is unknown how much the host genetic background contributes to interindividual differences in other determinants of HIV pathogenesis such as gut damage and microbial translocation. Using samples and data from 717 untreated participants in the Swiss HIV Cohort Study and a genome-wide association study design, we searched for human genetic determinants of plasma levels of intestinal fatty acid-binding protein (I-FABP/FABP2), a marker of gut damage, and of soluble CD14 (sCD14), a marker of lipopolysaccharide bioactivity and microbial translocation. We also assessed the correlations between HIV load, sCD14, and I-FABP. Although we found no genome-wide significant determinant of the tested plasma markers, we observed strong associations between sCD14 and both HIV load and I-FABP, shedding new light on the relationships between processes that drive progression of untreated HIV infectio

    Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

    Get PDF
    Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations
    corecore