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Dynamical model of the Milky Way using APOGEE and Gaia data
No full textWe construct a dynamical model of the Milky Way disk from a data set that combines Gaia EDR3 and APOGEE data throughout galactocentric radii in the range 5.0 kpc ≤ R ≤ 19.5 kpc. We make use of the spherically aligned Jeans anisotropic method to model the stellar velocities and their velocity dispersions. Building upon our previous work, our model is now fitted to kinematic maps that have been extended to larger galactocentric radii due to the expansion of our data set, probing the outer regions of the Galactic disk. Our best-fitting dynamical model suggests a logarithmic density slope of αDM = −1.602 ± 0.079syst for the dark matter halo and a dark matter density of ρDM(R⊙) = (8.92 ± 0.56syst) × 10−3 M⊙ pc−3 (0.339 ± 0.022syst GeV cm3). We estimate a circular velocity at the solar radius of vcirc = (234.7 ± 1.7syst) km s−1 with a decline toward larger radii. The total mass density is ρtot(R⊙) = (0.0672 ± 0.0015syst) M⊙ pc−3 with a slope of αtot = −2.367 ± 0.047syst for 5 kpc ≤ R ≤ 19.5 kpc, and the total surface density is Σ(R⊙, ∣z∣ ≤ 1.1 kpc) = (55.5 ± 1.7syst) M⊙ pc−2. While the statistical errors are small, the error budget of the derived quantities is dominated by the three to seven times larger systematic uncertainties. These values are consistent with our previous determination, but the systematic uncertainties are reduced due to the extended data set covering a larger spatial extent of the Milky Way disk. Furthermore, we test the influence of nonaxisymmetric features on our resulting model and analyze how a flaring disk model would change our findings
Defining service catchment areas in low-resource settings
No full textDefining an accurate, representative service catchment area is important for computing population denominators for disease mapping and efficient public planning, including health, education and social care.
The growth in population settlement modelling techniques and provision of geocoded service databases has fuelled an increase in local and regional service access mapping to examine coverage and equity in much of sub-Saharan African countries.
However, metrics of service access and catchments are often implemented based on convenience, disregarding the implications on accuracy of the catchment population, complexities of service use and the likely implications for public service planning.
Lack of high spatial resolution geolocated data on residential locations of the service users has led to the use of rudimentary, inexact approaches to complex processes that define service catchment areas and should be used with caution.
The improved collection of residential addresses of service users and service providers has increased the ability to develop new innovative models of service catchment.
Improved data availability and data sharing must be accompanied by better models of service use.
In this commentary, we revisit the issue by considering common approaches, key issues and best practices in defining a reliable service catchment area.
We hope this will lead to further granular studies to populate and compare methods to improve the definition of service catchment areas in sub-Saharan Africa, ultimately improving efficiencies and equity in service use and more reliable interpretations of routine service use data
Nucleophilic vinylic substitution in bicyclic methyleneaziridines: SNVπ or SNVσ?
No full textA stereodefined monodeuterated methylene aziridine is shown to be prepared via coordinated reductive ring-opening of an alkynyl epoxide and diastereoselective tethered allene aziridination. Ring-opening of this aziridine with copper-based organometallics follows a pathway that results in stereoretentive substitution, replacing the exo-C–N bond with a corresponding C–C bond; this stereochemical outcome supports either an overall SNVπ mechanism or a C–N insertion / reductive coupling process
The challenge of equipoise in trials with a surgical and non-surgical comparison: a qualitative synthesis using meta-ethnography
No full textBackground
Randomised controlled trials in surgery can be a challenge to design and conduct, especially when including a non-surgical comparison. As few as half of initiated surgical trials reach their recruitment target, and failure to recruit is cited as the most frequent reason for premature closure of surgical RCTs. The aim of this qualitative evidence synthesis was to identify and synthesise findings from qualitative studies exploring the challenges in the design and conduct of trials directly comparing surgical and non-surgical interventions.
Methods
A qualitative evidence synthesis using meta-ethnography was conducted. Six electronic bibliographic databases (Medline, Central, Cinahl, Embase and PsycInfo) were searched up to the end of February 2018. Studies that explored patients’ and health care professionals’ experiences regarding participating in RCTs with a surgical and non-surgical comparison were included. The GRADE-CERQual framework was used to assess confidence in review findings.
Results
In total, 3697 abstracts and 49 full texts were screened and 26 published studies reporting experiences of patients and healthcare professionals were included. The focus of the studies (24/26) was primarily related to the challenge of recruitment. Two studies explored reasons for non-compliance to treatment allocation following randomisation. Five themes related to the challenges to these types of trials were identified: (1) radical choice between treatments; (2) patients’ discomfort with randomisation: I want the best treatment for me as an individual; (3) challenge of equipoise: patients’ a priori preferences for treatment; (4) challenge of equipoise: clinicians’ a priori preferences for treatment and (5) imbalanced presentation of interventions.
Conclusion
The marked dichotomy between the surgical and non-surgical interventions was highlighted in this review as making recruitment to these types of trials particularly challenging. This review identified factors that increase our understanding of why patients and clinicians may find equipoise more challenging in these types of trials compared to other trial comparisons. Trialists may wish to consider exploring the balance of potential factors influencing patient and clinician preferences towards treatments before they start recruitment, to enable issues specific to a particular trial to be identified and addressed. This may enable trial teams to make more efficient considered design choices and benefit the delivery of such trials
BCL-2 inhibitor ABT-737 effectively targets leukemia-initiating cells with differential regulation of relevant genes leading to extended survival in a NRAS/BCL-2 mouse model of high risk-myelodysplastic syndrome
No full textDuring transformation, myelodysplastic syndromes (MDS) are characterized by reducing apoptosis of bone marrow (BM) precursors. Mouse models of high risk (HR)-MDS and acute myelogenous leukemia (AML) post-MDS using mutant NRAS and overexpression of human BCL-2, known to be poor prognostic indicators of the human diseases, were created. We have reported the efficacy of the BCL-2 inhibitor, ABT-737, on the AML post-MDS model; here, we report that this BCL-2 inhibitor also significantly extended survival of the HR-MDS mouse model, with reductions of BM blasts and lineage negative/Sca1+/KIT+ (LSK) cells. Secondary transplants showed increased survival in treated compared to untreated mice. Unlike the AML model, BCL-2 expression and RAS activity decreased following treatment and the RAS:BCL-2 complex remained in the plasma membrane. Exon-specific gene expression profiling (GEP) of HR-MDS mice showed 1952 differentially regulated genes upon treatment, including genes important for the regulation of stem cells, differentiation, proliferation, oxidative phosphorylation, mitochondrial function, and apoptosis; relevant in human disease. Spliceosome genes, found to be abnormal in MDS patients and downregulated in our HR-MDS model, such as Rsrc1 and Wbp4, were upregulated by the treatment, as were genes involved in epigenetic regulation, such as DNMT3A and B, upregulated upon disease progression and downregulated upon treatment
The global multidimensional poverty index (MPI) 2021
No full textThis 51st Methodological Note presents the methodology and technical decisions behind the global Multidimensional Poverty Index (MPI) 2021 and the results presented in Tables 1–8. This document is part of OPHI MPI Methodological Notes series. A Methodological Note is published for every release of the global MPI.
The 2021 global MPI presents results on multidimensional poverty, using the most recent data from 109 countries, covering 5.9 billion people, and including trends over time in 84 countries. The estimation of MPI and its partial indices are further disaggregated by age groups, rural/urban areas, and subnational regions. A new element in this 2021 round is that we have disaggregated by gender of household head (female and male) and present results for three points in time for 28 of the 84 countries with harmonised estimates. This document jointly presents the policies that underlie our current margin estimates and the harmonised over time estimates.
This document is structured as follows. Section 2 presents the global MPI structure and indicator definitions. Section 3 provides an outline of the global MPI and its partial indices that we estimate and publish. Section 4 summarises the changes over time methodology. Section 5 outlines the data management policies of the global MPI; while section 6 details the decisions that underlie our harmonisation work. Section 7 provides a summary of survey details. Section 8 summarises the country-specific technical decisions that were applied for each of these new surveys. We conclude with a couple of closing remarks
Polycyclic aromatic hydrocarbons in seyfert and star-forming galaxies
No full textPolycyclic Aromatic Hydrocarbons (PAHs) are carbon-based molecules resulting from the union of aromatic rings and related species, which are likely responsible for strong infrared emission features. In this work, using a sample of 50 Seyfert galaxies (DL < 100 Mpc) we compare the circumnuclear (inner kpc) PAH emission of AGN to that of a control sample of star-forming galaxies (22 luminous infrared galaxies and 30 H ii galaxies), and investigate the differences between central and extended PAH emission. Using Spitzer/InfraRed Spectrograph spectral data of Seyfert and star-forming galaxies and newly developed PAH diagnostic model grids, derived from theoretical spectra, we compare the predicted and observed PAH ratios. We find that star-forming galaxies and AGN-dominated systems are located in different regions of the PAH diagnostic diagrams. This suggests that not only are the size and charge of the PAH molecules different, but also the nature and hardness of the radiation field that excite them. We find tentative evidence that PAH ratios in AGN-dominated systems are consistent with emission from larger PAH molecules (Nc > 300–400) as well as neutral species. By subtracting the spectrum of the central source from the total, we compare the PAH emission in the central versus extended region of a small sample of AGN. In contrast to the findings for the central regions of AGN-dominated systems, the PAH ratios measured in the extended regions of both type 1 and type 2 Seyfert galaxies can be explained assuming similar PAH molecular size distribution and ionized fractions of molecules to those seen in central regions of star-forming galaxies
Learning differential equation models from stochastic agent-based model simulations
No full textAgent-based models provide a flexible framework that is frequently used for modelling many biological systems, including cell migration, molecular dynamics, ecology, and epidemiology. Analysis of the model dynamics can be challenging due to their inherent stochasticity and heavy computational requirements. Common approaches to the analysis of agent-based models include extensive Monte Carlo simulation of the model or the derivation of coarse-grained differential equation models to predict the expected or averaged output from the agent-based model. Both of these approaches have limitations, however, as extensive computation of complex agent-based models may be infeasible, and coarse-grained differential equation models can fail to accurately describe model dynamics in certain parameter regimes. We propose that methods from the equation learning field provide a promising, novel, and unifying approach for agent-based model analysis. Equation learning is a recent field of research from data science that aims
to infer differential equation models directly from data. We use this tutorial to review how methods from equation learning can be used to learn differential equation models from agent-based model simulations. We demonstrate that this framework is easy to use, requires few model simulations, and accurately predicts model dynamics in parameter regions where coarse-grained differential equation models fail to do so. We highlight these advantages through several case studies involving two agent-based models
that are broadly applicable to biological phenomena: a birth-death-migration model commonly used to explore cell biology experiments and a susceptible-infected-recovered model of infectious disease spread
Interpreting negative test results when assessing cancer risk in general practice
No full textStudies published over the last year have established the sensitivity of chest X-ray (CXR) for lung cancer (75%, 95% confidence interval [CI] = 68 to 83), cancer antigen 125 (CA125) for ovarian cancer (77%, 95% CI = 73 to 81), and the faecal immunochemical test (FIT) for colorectal cancer (91%, 95% CI = 85 to 96) in symptomatic people attending primary care.1–3 This research demonstrates how simple and accessible tests can be used by GPs to identify these cancers in most cases; however, it also raises questions about how GPs should respond to negative test results in situations in which there is some concern about the possibility for cancer, but criteria for an urgent suspected cancer referral are not met
