Effective Strategies to Support Advocacy Campaigns: Considerations for Funders and Advocates

This report shares collected insights from funders and advocates across the country, in the hope that their observations will helpfully contribute to other funding and campaign efforts. The respondents noted that while considerable attention has been paid to factors informing the development of sound campaign strategy, comparatively less attention has been paid to the structural and operational issues that undergird successful campaign efforts. Our research accordingly focuses on these matters

Coalitions as a Tool for Advocacy

Funders seeking to invest in broad social and system change frequently partner with advocacy organizations to advance issues through policy change rather than solely resourcing direct service organizations. Many funders take this investment further and seek to support coalition-building instead of simply resourcing individual organizations. The Bill and Melinda Gates Foundation engaged TCC Group to research coalition-building and help funders better understand key considerations in convening and supporting coalitions.TCC Group interviewed foundations and coalition experts, conducted site visits, and reviewed academic and peer-reviewed literature on coalitions. The findings are organized in a four-part framework, each representing a domain of positioning in a coalition's environment. The four domains are coalition capacity and structure, context, support, and strategy. When all four areas are being effectively developed and considered by stakeholders, it should lead to effective positioning of the coalition as a whole.This report provides insights for funders into when, how, and why to support coalitions under different circumstances. Advocates may similarly find value in some of the concepts and findings to inform their conversations with current and potential funders

Detection of enterovirus RNA in peripheral blood mononuclear cells correlates with the presence of the predisposing allele of the type 1 diabetes risk gene IFIH1 and with disease stage

Aims/hypothesis Enteroviral infection has been implicated consistently as a key environmental factor correlating with the appearance of autoimmunity and/or the presence of overt type 1 diabetes, in which pancreatic insulin-producing beta cells are destroyed by an autoimmune response. Genetic predisposition through variation in the type 1 diabetes risk gene IFIH1 (interferon induced with helicase C domain 1), which encodes the viral pattern-recognition receptor melanoma differentiation-associated protein 5 (MDA5), supports a potential link between enterovirus infection and type 1 diabetes. Methods We used molecular techniques to detect enterovirus RNA in peripheral blood samples (in separated cellular compartments or plasma) from two cohorts comprising 79 children or 72 adults that include individuals with and without type 1 diabetes who had multiple autoantibodies. We also used immunohistochemistry to detect the enteroviral protein VP1 in the pancreatic islets of post-mortem donors (n=43) with type 1 diabetes. Results We observed enhanced detection sensitivity when sampling the cellular compartment compared with the non-cellular compartment of peripheral blood (OR 21.69; 95% CI 3.64, 229.20; p Conclusions/interpretation Our data indicate that, in peripheral blood, antigen-presenting cells are the predominant source of enterovirus infection, and that infection is correlated with disease stage and genetic predisposition, thereby supporting a role for enterovirus infection prior to disease onset.Peer reviewe

The Tidal Disruption Event AT 2018hyz II: Light Curve Modeling of a Partially Disrupted Star

AT 2018hyz (=ASASSN-18zj) is a tidal disruption event (TDE) located in the nucleus of a quiescent E+A galaxy at a redshift of $z = 0.04573$, first detected by the All-Sky Automated Survey for Supernovae (ASAS-SN). We present optical+UV photometry of the transient, as well as an X-ray spectrum and radio upper limits. The bolometric light curve of AT 2018hyz is comparable to other known TDEs and declines at a rate consistent with a $t^{-5/3}$ at early times, emitting a total radiated energy of $E = 9\times10^{50}$ erg. An excess bump appears in the UV light curve about 50 days after bolometric peak, followed by a flattening beyond 250 days. The light curve shows an excess bump in the UV about 50 days after bolometric peak lasting for at least 100 days, which may be related to an outflow. We detect a constant X-ray source present for at least 86 days. The X-ray spectrum shows a total unabsorbed flux of $\sim 4\times10^{-14}$ erg cm$^{-2}$ s$^{-1}$ and is best fit by a blackbody plus power-law model with a photon index of $\Gamma = 0.8$. A thermal X-ray model is unable to account for photons $> 1$ keV, while the radio non-detection favors inverse-Compton scattering rather than a jet for the non-thermal component. We model the optical and UV light curves using the Modular Open-Source Fitter for Transients (MOSFiT) and find a best fit for a black hole of $5.2\times10^6$ M$_\odot$ partially disrupting a $0.1$ M$_\odot$ star (stripping a mass of $\sim 0.01$ M$_\odot$ for the inferred impact parameter, $\beta=0.6$). The low optical depth implied by the small debris mass may explain how we are able to see hydrogen emission with disk-like line profiles in the spectra of AT 2018hyz (see our companion paper, Short et al.~2020).Comment: 10 pages, 10 figures, published in MNRA

Multi-Messenger Astronomy with Extremely Large Telescopes

The field of time-domain astrophysics has entered the era of Multi-messenger Astronomy (MMA). One key science goal for the next decade (and beyond) will be to characterize gravitational wave (GW) and neutrino sources using the next generation of Extremely Large Telescopes (ELTs). These studies will have a broad impact across astrophysics, informing our knowledge of the production and enrichment history of the heaviest chemical elements, constrain the dense matter equation of state, provide independent constraints on cosmology, increase our understanding of particle acceleration in shocks and jets, and study the lives of black holes in the universe. Future GW detectors will greatly improve their sensitivity during the coming decade, as will near-infrared telescopes capable of independently finding kilonovae from neutron star mergers. However, the electromagnetic counterparts to high-frequency (LIGO/Virgo band) GW sources will be distant and faint and thus demand ELT capabilities for characterization. ELTs will be important and necessary contributors to an advanced and complete multi-messenger network.Comment: White paper submitted to the Astro2020 Decadal Surve

Bone marrow transplantation generates T cell–dependent control of myeloma in mice

Transplantation with autologous hematopoietic progenitors remains an important consolidation treatment for patients with multiple myeloma (MM) and is thought to prolong the disease plateau phase by providing intensive cytoreduction. However, transplantation induces inflammation in the context of profound lymphodepletion that may cause hitherto unexpected immunological effects. We developed preclinical models of bone marrow transplantation (BMT) for MM using Vk*MYC myeloma-bearing recipient mice and donor mice that were myeloma naive or myeloma experienced to simulate autologous transplantation. Surprisingly, we demonstrated broad induction of T cell-dependent myeloma control, most efficiently from memory T cells within myeloma-experienced grafts, but also through priming of naive T cells after BMT. CD8+ T cells from mice with controlled myeloma had a distinct T cell receptor (TCR) repertoire and higher clonotype overlap relative to myeloma-free BMT recipients. Furthermore, T cell-dependent myeloma control could be adoptively transferred to secondary recipients and was myeloma cell clone specific. Interestingly, donor-derived IL-17A acted directly on myeloma cells expressing the IL-17 receptor to induce a transcriptional landscape that promoted tumor growth and immune escape. Conversely, donor IFN-γ secretion and signaling were critical to protective immunity and were profoundly augmented by CD137 agonists. These data provide new insights into the mechanisms of action of transplantation in myeloma and provide rational approaches to improving clinical outcomes

Detection of enterovirus RNA in peripheral blood mononuclear cells correlates with the presence of the predisposing allele of the type 1 diabetes risk gene IFIH1 and with disease stage

Aims/hypothesis Enteroviral infection has been implicated consistently as a key environmental factor correlating with the appearance of autoimmunity and/or the presence of overt type 1 diabetes, in which pancreatic insulin-producing beta cells are destroyed by an autoimmune response. Genetic predisposition through variation in the type 1 diabetes risk gene IFIH1 (interferon induced with helicase C domain 1), which encodes the viral pattern-recognition receptor melanoma differentiation-associated protein 5 (MDA5), supports a potential link between enterovirus infection and type 1 diabetes.Methods We used molecular techniques to detect enterovirus RNA in peripheral blood samples (in separated cellular compartments or plasma) from two cohorts comprising 79 children or 72 adults that include individuals with and without type 1 diabetes who had multiple autoantibodies. We also used immunohistochemistry to detect the enteroviral protein VP1 in the pancreatic islets of post-mortem donors (n=43) with type 1 diabetes.Results We observed enhanced detection sensitivity when sampling the cellular compartment compared with the non-cellular compartment of peripheral blood (OR 21.69; 95% CI 3.64, 229.20; p</p

Influence of socio-economic status on habitual physical activity and sedentary behavior in 8- to 11-year old children

<p>Abstract</p> <p>Background</p> <p>While socio-economic status has been shown to be an important determinant of health and physical activity in adults, results for children and adolescents are less consistent. The purpose of this study, therefore, is to examine whether physical activity and sedentary behavior differs in children by socio-economic status (SES) independent of body mass index.</p> <p>Methods</p> <p>Data were from two cohorts including 271 children (117 males; 154 females) in study 1 and 131 children in study 2 (63 males; 68 females). The average age was 9.6 and 8.8 years respectively. Height and body mass were assessed according to standard procedures and body mass index (BMI, kg/m²) was calculated. Parent-reported household income was used to determine SES. Habitual, free-living physical activity (PA) was assessed by a pedometer (steps/day) in study 1 and accelerometer (time spent in moderate-to-vigorous PA) in study 2. Self-reported time spent watching TV and on the computer was used as measure of sedentary behavior. Differences in PA and sedentary behavior by SES were initially tested using ANOVA. Further analyses used ANCOVA controlling for BMI, as well as leg length in the pedometer cohort.</p> <p>Results</p> <p>In study 1, mean daily steps differed significantly among SES groups with lower SES groups approximating 10,500 steps/day compared to about 12,000 steps/day in the higher SES groups. These differences remained significant (p < 0.05) when controlling for leg length. Lower SES children, however, had higher body mass and BMI compared to higher SES groups (p < 0.05) and PA no longer remained significant when further controlling for BMI. In study 2 results depended on the methodology used to determine time spent in moderate-to-vigorous physical activity (MVPA). Only one equation resulted in significant group differences (p = 0.015), and these differences remained after controlling for BMI. Significant differences between SES groups were shown for sedentary behavior in both cohorts (P < 0.05) with higher SES groups spending less time watching TV than low SES groups.</p> <p>Conclusions</p> <p>Children from a low SES show a trend of lower PA levels and spend more time in sedentary behavior than high SES children; however, differences in PA were influenced by BMI. The higher BMI in these children might be another factor contributing to increased health risks among low SES children compared to children from with a higher SES.</p

Human development index, children's health-related quality of life and movement behaviors:a compositional data analysis

Purpose: Health-related quality of life has been related to physical activity, sedentary behavior, and sleep among children from developed nations. These relationships have rarely been assessed in developing nations, nor have behaviors been considered in their true context, as mutually exclusive and exhaustive parts of the movement behavior composition. This study aimed to explore whether children's health-related quality of life is related to their movement behavior composition and if the relationship differs according to human development index. Methods: Children aged 9-11 years (n = 5855), from the 12-nation cross-sectional observational International Study of Childhood Obesity, Lifestyle and the Environment 2011-2013, self-reported their health-related quality of life (KIDSCREEN-10). Daily movement behaviors were from 24-h, 7-day accelerometry. Isometric log-ratio mixed-effect linear models were used to calculate estimates for difference in health-related quality of life for the reallocation of time between daily movement behaviors. Results: Children from countries of higher human development index reported stronger positive relationships between health-related quality of life and moderate-to-vigorous physical activity, relative to the remaining behaviors (r = 0.75, p = 0.005) than those from lower human development index countries. In the very high human development index strata alone, health-related quality of life was significantly related to the movement behavior composition (p = 0.005), with moderate-to-vigorous physical activity (relative to remaining behaviors) being positively associated with health-related quality of life. Conclusions: The relationship between children's health-related quality of life and their movement behaviors is moderated by their country's human development index. This should be considered when 24-h movement behavior guidelines are developed for children around the world.Dorothea Dumuid, Carol Maher, Lucy K. Lewis, Tyman E. Stanford, Josep Antoni Martín Fernández, Julie Ratcliffe, Peter T. Katzmarzyk, Tiago V. Barreira, Jean-Philippe Chaput, Mikael Fogelholm, Gang Hu, José Maia, Olga L. Sarmiento, Martyn Standage, Mark S. Tremblay, Catrine Tudor-Locke, Timothy Old