Our Charitable Children - Engaging Children in Charities and Charitable Giving

Why charitable donors give has been a topic of much debate among practitioners, policy makers and academics alike. Recent efforts to grow and strengthen the culture of charitable giving in the UK have focused on increasing people’s propensity to give and the total amounts they are likely to give. However little attention has been paid to how people learn to give at a younger age. Given early education is fundamental in securing individuals long-term social and political orientations, this is a critical oversight. The absence of much commentary on, or significant research into, how individuals are socialised into giving, specifically younger children, means we have little knowledge about how people come to be the donors we pay so much attention to later in life. In this report we situate charitable giving as part of much larger debate on children’s active engagement within civil society and their role as competent and active social actors. This research report engages the voices of over 150 young children aged 4-8 years old. Through participative action research methods, we explore their perceptions and preferences of charity and charitable giving. We explore the trends across the age group and discuss how children may develop philanthropic behaviours. We start our findings celebrating children’s knowledge and involvement in charities. We found they have a wide and varied range of opportunities to engage in fundraising and charitable giving through schools, communities and the family. However, we also suggest that children have relatively limited spaces to meaningfully engage in these charitable behaviours, often associating giving as a transactional process without critically engaging with the cause. Nonetheless, when given opportunity to meaningfully engage in giving decisions children demonstrated a heightened critical consciousness and desire for increased social justice in their giving decisions. Importantly we argue that conscious, active and participative engagement in giving decisions helps children develop a critical consciousness about the world around them and increases social orientated behaviours. We promote the idea that children, as present citizens (as opposed to viewed as future citizens only), are capable and competent of selecting and assessing the charities they wish to support, and in turn this helps them develop a greater understanding of the world around them

Our Charitable Children: Engaging Children in Charities and Charitable Giving

Why charitable donors give has been a topic of much debate amongst practitioners, policy makers and academics alike. Recent efforts to grow and strengthen the culture of charitable giving in the UK have focused on increasing people's propensity to give and the total amounts they are likely to give. However little attention has been paid to how people learn to give at a younger age. Given early education is fundamental in securing individuals long-term social and political orientations, this is a critical oversight. The absence of much commentary on, or significant research into, how individuals are socialised into giving, specifically younger children, means we have little knowledge about how people come to be the donors we pay so much attention to later in life.In this report we situate charitable giving as part of much larger debate on children's active engagement within civil society and their role as competent and active social actors.This research report engages the voices of over 150 young children aged 4-8 years old. Through participative action research methods, we explore their perceptions and preferences of charity and charitable giving. We explore the trends across the age group and discuss how children may develop philanthropic behaviours.We start our findings celebrating children's knowledge and involvement in charities. We found they have a wide and varied range of opportunities to engage in fundraising and charitable giving through schools, communities and the family. However, we also suggest that children have relatively limited spaces to meaningfully engage in these charitable behaviours, often associating giving as a transactional process without critically engaging with the cause. Nonetheless, when given opportunity to meaningfully engage in giving decisions children demonstrated a heightened critical consciousness and desire for increased social justice in their giving decisions.Importantly we argue that conscious, active and participative engagement in giving decisions helps children develop a critical consciousness about the world around them and increases social orientated behaviours. We promote the idea that children, as present citizens (as opposed to viewed as future citizens only), are capable and competent of selecting and assessing the charities they wish to support, and in turn this helps them develop a greater understanding of the world around them

Systemic inflammation, body composition, and physical performance in old community-dwellers

Background Chronic inflammation, changes in body composition, and declining physical function are hallmarks of the ageing process. The aim of the present study was to provide a preliminary characterisation of the relationship among these age-related phenomena via multivariate modelling. Methods Thirty-five old adults (OAs) and 17 young adults (YAs) were enrolled. The volume of skeletal muscle, subcutaneous adipose tissue (SAT), and intermuscular adipose tissue (IMAT) of the thigh was quantified by three-dimensional magnetic resonance imaging. Muscle strength was measured by knee extension strength testing. In OAs, physical performance was further assessed via the Short Physical Performance Battery (SPPB). Multi-block partial least squares-discriminant analysis (PLS-DA) was employed to explore the relationship among inflammatory profiles and functional and imaging parameters. Double cross-validation procedures were used to validate the predictive ability of the PLS-DA model. Results The optimal complexity of the PLS-DA model was found to be two latent variables. The proportion of correct classification was 92.3% in calibration (94.1% in YAs and 91.4% in OAs), 84.6% in internal validation (95.3% in YAs and 78.5% in OAs), and 82.6% in external validation (94% in YAs and 76.9% in OAs). Relative to YAs, OAs were characterised by smaller muscle volume, greater IMAT volume, lower muscle strength, and higher levels of myeloperoxidase, P-selectin, soluble intercellular adhesion molecule 1, and vascular cell adhesion molecule 1. Compared with OAs with SPPB >8, those scoring 8 were characterised by smaller muscle volume, greater SAT volume, lower muscle strength, and higher levels of interleukin 1 beta, 6, 10, 12, 13, tumour necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor. Conclusions Multi-block PLS-DA identified distinct patterns of relationships among circulating cytokines and functional and imaging parameters in persons of different ages and varying levels of physical performance. The longitudinal implementation of such an innovative strategy could allow for the tracking of health status over time, the early detection of deviations in health trajectories, and the monitoring of response to treatments

IL-1β Production through the NLRP3 Inflammasome by Hepatic Macrophages Links Hepatitis C Virus Infection with Liver Inflammation and Disease

Chronic hepatitis C virus (HCV) infection is a leading cause of liver disease. Liver inflammation underlies infection-induced fibrosis, cirrhosis and liver cancer but the processes that promote hepatic inflammation by HCV are not defined. We provide a systems biology analysis with multiple lines of evidence to indicate that interleukin-1β (IL-1β) production by intrahepatic macrophages confers liver inflammation through HCV-induced inflammasome signaling. Chronic hepatitis C patients exhibited elevated levels of serum IL-1β compared to healthy controls. Immunohistochemical analysis of healthy control and chronic hepatitis C liver sections revealed that Kupffer cells, resident hepatic macrophages, are the primary cellular source of hepatic IL-1β during HCV infection. Accordingly, we found that both blood monocyte-derived primary human macrophages, and Kupffer cells recovered from normal donor liver, produce IL-1β after HCV exposure. Using the THP-1 macrophage cell-culture model, we found that HCV drives a rapid but transient caspase-1 activation to stimulate IL-1β secretion. HCV can enter macrophages through non-CD81 mediated phagocytic uptake that is independent of productive infection. Viral RNA triggers MyD88-mediated TLR7 signaling to induce IL-1β mRNA expression. HCV uptake concomitantly induces a potassium efflux that activates the NLRP3 inflammasome for IL-1β processing and secretion. RNA sequencing analysis comparing THP1 cells and chronic hepatitis C patient liver demonstrates that viral engagement of the NLRP3 inflammasome stimulates IL-1β production to drive proinflammatory cytokine, chemokine, and immune-regulatory gene expression networks linked with HCV disease severity. These studies identify intrahepatic IL-1β production as a central feature of liver inflammation during HCV infection. Thus, strategies to suppress NLRP3 or IL-1β activity could offer therapeutic actions to reduce hepatic inflammation and mitigate disease

Which objective sleep elements predict children’s perceptions of good sleep quality? A preliminary investigation based on polysomnography and actigraphy

Objectives: Objective sleep elements that underlie child ratings of sleep quality are largely unknown. Child-based sleep recommendations, therefore, typically focus on duration. An expert panel recently provided specific recommendations regarding objective sleep parameters that correspond with higher quality sleep, but child-based studies from which to draw conclusions were notably limited. The present study used actigraphy and polysomnography to explore sleep continuity and architectural variables that correspond with higher ratings of sleep quality in a sample of school-aged children.  Methods: Fifty-two healthy, prepubertal children (aged 7–11 years) completed one night of unattended ambulatory polysomnography at home with concurrent actigraphy and provided sleep quality ratings the following morning. Associations between sleep variables and subjective ratings were examined using polynomial regression models to examine potential linear and nonlinear relationships.  Results: In contrast to findings among adults, total sleep time, sleep onset latency, and sleep efficiency values were unrelated to child ratings of sleep quality. Wake after sleep onset (WASO) showed a curvilinear (reversed j-shaped) relationship such that perceptions of sleep quality were high when WASO values were less than approximately 30 minutes. For sleep architecture, N1% showed a significant quadratic association with sleep quality such that N1% between 2% and 6% corresponded with high sleep quality ratings.  Conclusions: Our findings support expert recommendations regarding WASO values that predict high quality sleep in children, but also await replication. There is need for additional research aimed at understanding objective sleep elements and other influences of children's perceptions of sleep quality using linear and nonlinear models

Quasars Probing Quasars. VI. Excess H I Absorption within one Proper Mpc of z ~ 2 Quasars

With close pairs of quasars at different redshifts, a background quasar sightline can be used to study a foreground quasar's environment in absorption. We use a sample of 650 projected quasar pairs to study the H I Lyα absorption transverse to luminous, z ~ 2 quasars at proper separations of 30 kpc 10^(17.3) cm^(-2) at separations R_⊥ < 200 kpc, which decreases to ~20% at R_⊥ ≃ 1 Mpc, but still represents a significant excess over the cosmic average. This excess of optically thick absorption can be described by a quasar-absorber cross-correlation function ξ_(QA)(r) = (r/r_0)^γ with a large correlation length r_0=12.5^(+2.7)_(-1.4)h^(-1)Mpc(comoving) and y =1.68^(+0.14)_(-0.30). The H I absorption measured around quasars exceeds that of any previously studied population, consistent with quasars being hosted by massive dark matter halos M_(halo) ≈ 10^(12.5) M_☉ at z ~ 2.5. The environments of these massive halos are highly biased toward producing optically thick gas, and may even dominate the cosmic abundance of Lyman limit systems and hence the intergalactic opacity to ionizing photons at z ~ 2.5. The anisotropic absorption around quasars implies the transverse direction is much less likely to be illuminated by ionizing radiation than the line-of-sight

Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus-immortalized cells

Epstein-Barr virus (EBV) is implicated in the pathogenesis of multiple human tumours of lymphoid and epithelial origin. The virus infects and immortalizes B cells establishing a persistent latent infection characterized by varying patterns of EBV latent gene expression (latency 0, I, II and III). The CDK1 activator, Response Gene to Complement-32 (RGC-32, C13ORF15), is overexpressed in colon, breast and ovarian cancer tissues and we have detected selective high-level RGC-32 protein expression in EBV-immortalized latency III cells. Significantly, we show that overexpression of RGC-32 in B cells is sufficient to disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC-32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at high levels in latency I Burkitt's lymphoma (BL) cells and in some EBV-negative BL cell-lines, although RGC-32 protein expression is not detectable. We show that RGC-32 mRNA expression is elevated in latency I cells due to transcriptional activation by high levels of the differentially expressed RUNX1c transcription factor. We found that proteosomal degradation or blocked cytoplasmic export of the RGC-32 message were not responsible for the lack of RGC-32 protein expression in latency I cells. Significantly, analysis of the ribosomal association of the RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts were associated with multiple ribosomes in both cell-types implicating post-initiation translational repression mechanisms in the block to RGC-32 protein production in latency I cells. In summary, our results are the first to demonstrate RGC-32 protein upregulation in cells transformed by a human tumour virus and to identify post-initiation translational mechanisms as an expression control point for this key cell-cycle regulator

Development and characterization of a Yucatan miniature biomedical pig permanent middle cerebral artery occlusion stroke model

BACKGROUND: Efforts to develop stroke treatments have met with limited success despite an intense need to produce novel treatments. The failed translation of many of these therapies in clinical trials has lead to a close examination of the therapeutic development process. One of the major factors believed to be limiting effective screening of these treatments is the absence of an animal model more predictive of human responses to treatments. The pig may potentially fill this gap with a gyrencephalic brain that is larger in size with a more similar gray-white matter composition to humans than traditional stroke animal models. In this study we develop and characterize a novel pig middle cerebral artery occlusion (MCAO) ischemic stroke model. METHODS: Eleven male pigs underwent MCAO surgery with the first 4 landrace pigs utilized to optimize stroke procedure and 7 additional Yucatan stroked pigs studied over a 90 day period. MRI analysis was done at 24 hrs and 90 days and included T2w, T2w FLAIR, T1w FLAIR and DWI sequences and associated ADC maps. Pigs were sacrificed at 90 days and underwent gross and microscopic histological evaluation. Significance in quantitative changes was determined by two-way analysis of variance and post-hoc Tukey’s Pair-Wise comparisons. RESULTS: MRI analysis of animals that underwent MCAO surgery at 24 hrs had hyperintense regions in T2w and DWI images with corresponding ADC maps having hypointense regions indicating cytotoxic edema consistent with an ischemic stroke. At 90 days, region of interest analysis of T1 FLAIR and ADC maps had an average lesion size of 59.17 cc, a loss of 8% brain matter. Histological examination of pig brains showed atrophy and loss of tissue, consistent with MRI, as well as glial scar formation and macrophage infiltration. CONCLUSIONS: The MCAO procedure led to significant and consistent strokes with high survivability. These results suggest that the pig model is potentially a robust system for the study of stroke pathophysiology and potential diagnostics and therapeutics

Heterogeneities in leishmania infantum infection : using skin parasite burdens to identify highly infectious dogs

Background: The relationships between heterogeneities in host infection and infectiousness (transmission to arthropod vectors) can provide important insights for disease management. Here, we quantify heterogeneities in Leishmania infantum parasite numbers in reservoir and non-reservoir host populations, and relate this to their infectiousness during natural infection. Tissue parasite number was evaluated as a potential surrogate marker of host transmission potential. Methods: Parasite numbers were measured by qPCR in bone marrow and ear skin biopsies of 82 dogs and 34 crab-eating foxes collected during a longitudinal study in Amazon Brazil, for which previous data was available on infectiousness (by xenodiagnosis) and severity of infection. Results: Parasite numbers were highly aggregated both between samples and between individuals. In dogs, total parasite abundance and relative numbers in ear skin compared to bone marrow increased with the duration and severity of infection. Infectiousness to the sandfly vector was associated with high parasite numbers; parasite number in skin was the best predictor of being infectious. Crab-eating foxes, which typically present asymptomatic infection and are non-infectious, had parasite numbers comparable to those of non-infectious dogs. Conclusions: Skin parasite number provides an indirect marker of infectiousness, and could allow targeted control particularly of highly infectious dogs