Quantifying within-city inequalities in child mortality across neighbourhoods in Accra, Ghana: a Bayesian spatial analysis

Objective Countries in sub-Saharan Africa suffer the highest rates of child mortality worldwide. Urban areas tend to have lower mortality than rural areas, but these comparisons likely mask large within-city inequalities. We aimed to estimate rates of under-five mortality (U5M) at the neighbourhood level for Ghana’s Greater Accra Metropolitan Area (GAMA) and measure the extent of intraurban inequalities. Methods We accessed data on >700 000 women aged 25–49 years living in GAMA using the most recent Ghana census (2010). We summarised counts of child births and deaths by five-year age group of women and neighbourhood (n=406) and applied indirect demographic methods to convert the summaries to yearly probabilities of death before age five years. We fitted a Bayesian spatiotemporal model to the neighbourhood U5M probabilities to obtain estimates for the year 2010 and examined their correlations with indicators of neighbourhood living and socioeconomic conditions. Results U5M varied almost five-fold across neighbourhoods in GAMA in 2010, ranging from 28 (95% credible interval (CrI) 8 to 63) to 138 (95% CrI 111 to 167) deaths per 1000 live births. U5M was highest in neighbourhoods of the central urban core and industrial areas, with an average of 95 deaths per 1000 live births across these neighbourhoods. Peri-urban neighbourhoods performed better, on average, but rates varied more across neighbourhoods compared with neighbourhoods in the central urban areas. U5M was negatively correlated with multiple indicators of improved living and socioeconomic conditions among peri-urban neighbourhoods. Among urban neighbourhoods, correlations with these factors were weaker or, in some cases, reversed, including with median household consumption and women’s schooling. Conclusion Reducing child mortality in high-burden urban neighbourhoods in GAMA, where a substantial portion of the urban population resides, should be prioritised as part of continued efforts to meet the Sustainable Development Goal national target of less than 25 deaths per 1000 live births

Maximally incompressible neutron star matter

Relativistic kinetic theory, based on the Grad method of moments as developed by Israel and Stewart, is used to model viscous and thermal dissipation in neutron star matter and determine an upper limit on the maximum mass of neutron stars. In the context of kinetic theory, the equation of state must satisfy a set of constraints in order for the equilibrium states of the fluid to be thermodynamically stable and for perturbations from equilibrium to propagate causally via hyperbolic equations. Application of these constraints to neutron star matter restricts the stiffness of the most incompressible equation of state compatible with causality to be softer than the maximally incompressible equation of state that results from requiring the adiabatic sound speed to not exceed the speed of light. Using three equations of state based on experimental nucleon-nucleon scattering data and properties of light nuclei up to twice normal nuclear energy density, and the kinetic theory maximally incompressible equation of state at higher density, an upper limit on the maximum mass of neutron stars averaging 2.64 solar masses is derived.Comment: 8 pages, 2 figure

Adenoviral-mediated correction of methylmalonyl-CoA mutase deficiency in murine fibroblasts and human hepatocytes

<p>Abstract</p> <p>Background</p> <p>Methylmalonic acidemia (MMA), a common organic aciduria, is caused by deficiency of the mitochondrial localized, 5'deoxyadenosylcobalamin dependent enzyme, methylmalonyl-CoA mutase (MUT). Liver transplantation in the absence of gross hepatic dysfunction provides supportive therapy and metabolic stability in severely affected patients, which invites the concept of using cell and gene delivery as future treatments for this condition.</p> <p>Methods</p> <p>To assess the effectiveness of gene delivery to restore the defective metabolism in this disorder, adenoviral correction experiments were performed using murine <it>Mut </it>embryonic fibroblasts and primary human methylmalonyl-CoA mutase deficient hepatocytes derived from a patient who harbored two early truncating mutations, E224X and R228X, in the <it>MUT </it>gene. Enzymatic and expression studies were used to assess the extent of functional correction.</p> <p>Results</p> <p>Primary hepatocytes, isolated from the native liver after removal subsequent to a combined liver-kidney transplantation procedure, or <it>Mut </it>murine fibroblasts were infected with a second generation recombinant adenoviral vector that expressed the murine methylmalonyl-CoA mutase as well as eGFP from distinct promoters. After transduction, [1-¹⁴C] propionate macromolecular incorporation studies and Western analysis demonstrated complete correction of the enzymatic defect in both cell types. Viral reconstitution of enzymatic expression in the human methylmalonyl-CoA mutase deficient hepatocytes exceeded that seen in fibroblasts or control hepatocytes.</p> <p>Conclusion</p> <p>These experiments provide proof of principle for viral correction in methylmalonic acidemia and suggest that hepatocyte-directed gene delivery will be an effective therapeutic treatment strategy in both murine models and in human patients. Primary hepatocytes from a liver that was unsuitable for transplantation provided an important resource for these studies.</p

Metabolic phenotype of methylmalonic acidemia in mice and humans: the role of skeletal muscle

<p>Abstract</p> <p>Background</p> <p>Mutations in methylmalonyl-CoA mutase cause methylmalonic acidemia, a common organic aciduria. Current treatment regimens rely on dietary management and, in severely affected patients, liver or combined liver-kidney transplantation. For undetermined reasons, transplantation does not correct the biochemical phenotype.</p> <p>Methods</p> <p>To study the metabolic disturbances seen in this disorder, we have created a murine model with a null allele at the methylmalonyl-CoA mutase locus and correlated the results observed in the knock-out mice to patient data. To gain insight into the origin and magnitude of methylmalonic acid (MMA) production in humans with methylmalonyl-CoA mutase deficiency, we evaluated two methylmalonic acidemia patients who had received different variants of combined liver-kidney transplants, one with a complete liver replacement-kidney transplant and the other with an auxiliary liver graft-kidney transplant, and compared their metabolite production to four untransplanted patients with intact renal function.</p> <p>Results</p> <p>Enzymatic, Western and Northern analyses demonstrated that the targeted allele was null and correctable by lentiviral complementation. Metabolite studies defined the magnitude and tempo of plasma MMA concentrations in the mice. Before a fatal metabolic crisis developed in the first 24–48 hours, the methylmalonic acid content per gram wet-weight was massively elevated in the skeletal muscle as well as the kidneys, liver and brain. Near the end of life, extreme elevations in tissue MMA were present primarily in the liver. The transplant patients studied when well and on dietary therapy, displayed massive elevations of MMA in the plasma and urine, comparable to the levels seen in the untransplanted patients with similar enzymatic phenotypes and dietary regimens.</p> <p>Conclusion</p> <p>The combined observations from the murine metabolite studies and patient investigations indicate that during homeostasis, a large portion of circulating MMA has an extra-heptorenal origin and likely derives from the skeletal muscle. Our studies suggest that modulating skeletal muscle metabolism may represent a strategy to increase metabolic capacity in methylmalonic acidemia as well as other organic acidurias. This mouse model will be useful for further investigations exploring disease mechanisms and therapeutic interventions in methylmalonic acidemia, a devastating disorder of intermediary metabolism.</p

Disability activism in the new media ecology: campaigning strategies in the digital era

This article examines the changing nature of disability activism through the influence of social media. As disabled people in the UK have been subjected to acute austerity, this has coincided with a new era of disability activism channelled through increased social media participation. Drawing on the analysis of one group's online activities and a qualitative content analysis of disability protest coverage in traditional news media during the 2012 Paralympic Games, this article positions this shift in the broader framework of ‘new media ecology’ (Hoskins and O’Loughlin, 2010). We explore how emerging structures of disability activism have begun to offer a more visible profile to challenge government policy and negative stereotypes of disabled people. This highlights the usefulness of campaigning strategies for generating favourable news coverage for disability protest

Hard X-ray Variations in the Crab Nebula

In the first two years of science operations of the Fermi Gamma-ray Burst Monitor (GBM), August 2008 to August 2010, a approx.7% (70 mcrab) decline was discovered in the overall Crab Nebula flux in the 15 - 50 keV band, measured with the Earth occultation technique. This decline was independently confirmed with four other instruments: the RXTE/PCA, Swift/BAT, INTEGRAL/IBIS, and INTEGRAL/SPI. The pulsed flux measured with RXTE/PCA from 1999-2010 was consistent with the pulsar spin-down, indicating that the observed changes were nebular. From 2001 to 2010, the Crab nebula flux measured with RXTE/PCA was particularly variable, changing by up to approx.3.5% per year in the 15-50 keV band. These variations were confirmed with INTEGRAL/SPI starting in 2003, Swift/BAT starting in 2005, and Fermi GBM starting in 2008. Before 2001 and since 2010, the Crab nebula flux has appeared more stable, varying by less than 2% per year. I will present updated light curves in multiple energy bands for the Crab nebula, including recent data from Fermi GBM, Swift/BAT, and MAXI, and a 16-year long light curve from RXTE/PCA