Connecting the Milky Way potential profile to the orbital timescales and spatial structure of the Sagittarius Stream

Recent maps of the halo using RR Lyrae from Pan-STARRS1 have clearly depicted the spatial structure of the Sagittarius stream. These maps show the leading and trailing stream apocenters differ in galactocentric radius by a factor of two, and also resolve substructure in the stream at these apocenters. Here we present dynamical models that reproduce these features of the stream in simple Galactic potentials. We find that debris at the apocenters must be dynamically young, in the sense of being stripped off in the last two pericentric passages, while the Sagittarius dwarf is currently experiencing a third passage. The ratio of apocenters is sensitive to both dynamical friction and the outer slope of the Galactic rotation curve. These dependences can be understood with simple regularities connecting the apocentric radii, circular velocities, and orbital period of the progenitor. The effect of dynamical friction on the stream can be constrained using substructure within the leading apocenter. Our ensembles of models are not intended as statistically proper fits to the stream. Nevertheless, out of the range of models we consider, we consistently find the mass within 100 kpc to be $\sim 7 \times 10^{11} \, M_{\odot}$, with a nearly flat rotation curve between 50 and 100 kpc. This points to a more extended Galactic halo than assumed in some current models. As in previous work, we find prolate or triaxial halos ease agreement with the track of the leading stream. We display the behavior of our models in various observational spaces and characterize the substructure expected within the stream. In particular, the young trailing stream visible near trailing apocenter should exhibit a tight trend of velocity with distance separate from the older debris, and we suggest that this will serve as an especially useful probe of the outer Galactic potential.Comment: Submitted to MNRA

'Transformations towards sustainability':Emerging approaches, critical reflections, and a research agenda

Over the last two decades researchers have come to understand much about the global challenges confronting human society (e.g. climate change; biodiversity loss; water, energy and food insecurity; poverty and widening social inequality). However, the extent to which research and policy efforts are succeeding in steering human societies towards more sustainable and just futures is unclear. Attention is increasingly turning towards better understanding how to navigate processes of social and institutional transformation to bring about more desirable trajectories of change in various sectors of human society. A major knowledge gap concerns understanding how transformations towards sustainability are conceptualised, understood and analysed. Limited existing scholarship on this topic is fragmented, sometimes overly deterministic, and weak in its capacity to critically analyse transformation processes which are inherently political and contested. This paper aims to advance understanding of transformations towards sustainability, recognising it as both a normative and an analytical concept. We firstly review existing concepts of transformation in global environmental change literature, and the role of governance in relation to it. We then propose a framework for understanding and critically analysing transformations towards sustainability based on the existing ‘Earth System Governance’ framework (Biermann et al., 2009). We then outline a research agenda, and argue that transdisciplinary research approaches and a key role for early career researchers are vital for pursuing this agenda. Finally, we argue that critical reflexivity among global environmental change scholars, both individually and collectively, will be important for developing innovative research on transformations towards sustainability to meaningfully contribute to policy and action over time

Publications on Clinical Research in Otolaryngology–A Systematic Analysis of Leading Journals in 2010

Background: We wanted to asses and characterize the volume of Otolaryngology publications on clinical research, published in major journals.Methods and Material: To assess volume and study type of clinical research in Otolaryngology we performed a literature search in high impact factor journals. We included 10 high impact factor Otolaryngology journals and 20 high impact factor medical journals outside this field (2011). We extracted original publications and systematic reviews from 2010. Publications were classified according to their research question, that is therapy, diagnosis, prognosis or etiology.Results: From Otolaryngology journals (impact factor 1.8 to 2.8) we identified 694 (46%) publications on original observations and 27 (2%) systematic reviews. From selected medical journals (impact factor 6.0 to 101.8) 122 (2%) publications related to Otolaryngology, 102 (83%) were on original observations and 2 (0.04%) systematic reviews. The most common category was therapy (40%).Conclusion: Half of publications in Otolaryngology concerns clinical research, which is higher than other specialties. In medical journals outside the field of Otolaryngology, a small proportion (2%) of publications is related to Otolaryngology. Striking is that systematic reviews, which are considered high level evidence, make up for only 2% of publications. We must ensure an increase of clinical research for optimizing medical practice

Connecting the Milky Way potential profile to the orbital time-scales and spatial structure of the Sagittarius Stream

Recent maps of the halo using RR Lyrae from Pan-STARRS1 depict the spatial structure of the Sagittarius stream, showing the leading and trailing stream apocentres differ in Galactocentric radius by a factor of 2, and also resolving substructure in the stream at these apocentres. Here we present dynamical models that reproduce these features of the stream in simple Galactic potentials. We find that debris at the apocentres must be dynamically young, being stripped off in pericentric passages either one or two orbital periods ago. The ratio of the leading and trailing apocentres is sensitive to both dynamical friction and the outer slope of the Galactic rotation curve. These dependencies can be understood with simple regularities connecting the apocentric radii, circular velocities, and orbital period of the progenitor. The effect of dynamical friction can be constrained using substructure within the leading apocentre. Our models are far from final; the errors allowed when sampling parameter space are deliberately generous, not every stream feature is reproduced, and we explore a limited set of potentials. Still, it is interesting that we consistently find the mass within 100 kpc to be ∼7×10^(11) M⊙⁠, with a nearly flat rotation curve between 50 and 100 kpc. This points to a more extended Galactic halo than assumed in some current models. We show one example model in various observational dimensions. A plot of velocity versus distance separates younger from older debris, and suggests that the young trailing debris will serve as an especially useful probe of the outer Galactic potential

Health financing policies during the COVID-19 pandemic and implications for universal health care: a case study of 15 countries

Background The COVID-19 pandemic was a health emergency requiring rapid scal resource mobilisation to support national responses. The use of e ective health nancing mechanisms and policies, or lack thereof, a ected the impact of the pandemic on the population, particularly vulnerable groups and individuals. We provide an overview and illustrative examples of health nancing policies adopted in 15 countries during the pandemic, develop a framework for resilient health nancing, and use this pandemic to argue a case to move towards universal health coverage (UHC). Methods In this case study, we examined the national health nancing policy responses of 15 countries, which were purposefully selected countries to represent all WHO regions and have a range of income levels, UHC index scores, and health system typologies. We did a systematic literature review of peer-reviewed articles, policy documents, technical reports, and publicly available data on policy measures undertaken in response to the pandemic and complemented the data obtained with 61 in-depth interviews with health systems and health nancing experts. We did a thematic analysis of our data and organised key themes into a conceptual framework for resilient health nancing. Findings Resilient health nancing for health emergencies is characterised by two main phases: (1) absorb and recover, where health systems are required to absorb the initial and subsequent shocks brought about by the pandemic and restabilise from them; and (2) sustain, where health systems need to expand and maintain scal space for health to move towards UHC while building on resilient health nancing structures that can better prepare health systems for future health emergencies. We observed that ve key nancing policies were implemented across the countries— namely, use of extra-budgetary funds for a swift initial response, repurposing of existing funds, e cient fund disbursement mechanisms to ensure rapid channelisation to the intended personnel and general population, mobilisation of the private sector to mitigate the gaps in public settings, and expansion of service coverage to enhance the protection of vulnerable groups. Accountability and monitoring are needed at every stage to ensure e cient and accountable movement and use of funds, which can be achieved through strong governance and coordination, information technology, and community engagement. Interpretation Our ndings suggest that health systems need to leverage the COVID-19 pandemic as a window of opportunity to make health nancing policies robust and need to politically commit to public nancing mechanisms that work to prepare for future emergencies and as a lever for UHC.We thank the management team of the Bill & Melinda Gates Foundation and the Saw Swee Hock School of Public Health (National University of Singapore, Singapore) for all the administrative support given. This research was funded by the Bill & Melinda Gates Foundation (Investment ID INV-005598)

Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study

Nicotinamide adenine dinucleotide (NAD(+)) precursor nicotinamide riboside (NR) has emerged as a promising compound to improve obesity-associated mitochondrial dysfunction and metabolic syndrome in mice. However, most short-term clinical trials conducted so far have not reported positive outcomes. Therefore, we aimed to determine whether long-term NR supplementation boosts mitochondrial biogenesis and metabolic health in humans. Twenty body mass index (BMI)- discordant monozygotic twin pairs were supplemented with an escalating dose of NR (250 to 1000 mg/day) for 5 months. NR improved systemic NAD(+) metabolism, muscle mitochondrial number, myoblast differentiation, and gut microbiota composition in both cotwins. NR also showed a capacity to modulate epigenetic control of gene expression in muscle and adipose tissue in both cotwins. However, NR did not ameliorate adiposity or metabolic health. Overall, our results suggest that NR acts as a potent modifier of NAD(+) metabolism, muscle mitochondrial biogenesis and stem cell function, gut microbiota, and DNA methylation in humans irrespective of BMI.Peer reviewe

Retrospective cohort study on factors associated with mortality in high-risk pediatric critical care patients in the Netherlands

Background: High-risk patients in the pediatric intensive care unit (PICU) contribute substantially to PICU-mortality. Complex chronic conditions (CCCs) are associated with death. However, it is unknown whether CCCs also increase mortality in the high-risk PICU-patient. The objective of this study is to determine if CCCs or other factors are associated with mortality in this group. Methods: Retrospective cohort study from a national PICU-database (2006-2012, n = 30,778). High-risk PICU-patients, defined as patients 30% according to either the recalibrated Pediatric Risk of Mortality-II (PRISM) or the Paediatric Index of Mortality 2 (PIM2), were included. Patients with a cardiac arrest before PICU-admission were excluded. Results: In total, 492 high-risk PICU patients with mean predicted risk of 24.8% (SD 22.8%) according to recalibrated PIM2 and 40.0% (SD 23.8%) according to recalibrated PRISM were included of which 39.6% died. No association was found between CCCs and non-survival (odds ratio 0.99; 95% CI 0.62-1.59). Higher Glasgow coma scale at PICU admission was associated with lower mortality (odds ratio 0.91; 95% CI 0.87-0.96). Conclusio

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD