Estimating the stochastic uncertainty in sample-based estimates of infant mortality in Ghana

The Infant Mortality Rate (IMR) is an important population health statistic often used as one of the indicators of the health status of a nation. In many countries lacking adequate vital registration systems, sample methods are used to estimate IMRs. However, evaluations of this approach are rare and the literature contains no assessments of the stochastic uncertainty underlying these estimated IMRs. Stochastic uncertainty reflects the fact that even where the underlying IMR is constant in a small population over time, there is a likelihood of yearly fluctuation in its empirical observations even if it is measured from a complete count of the events of interest. In this study a method is presented that can be used to assess this stochastic uncertainty. We use the country of Ghana as a case study for this purpose. The method, a beta-binomial model, is described, tested for validity, and illustrated using 2014 sample-based estimates of IMR for 13 sample regions in Ghana. As such, the approach we described regarding the revision of sample-based IMR estimates is aimed at taking into account of the stochastic uncertainty while preserving the information concerning the uncertainty due to sampling. In applying the method to Ghana, we find that the sample-based IMR estimates perform well in accounting for stochastic uncertainty and could be applied elsewhere

Towards understanding Regge trajectories in holographic QCD

We reassess a work done by Migdal on the spectrum of low-energy vector mesons in QCD in the light of the AdS-QCD correspondence. Recently, a tantalizing parallelism was suggested between Migdal's work and a family of holographic duals of QCD. Despite the intriguing similarities, both approaches face a major drawback: the spectrum is in conflict with well-tested Regge scaling. However, it has recently been shown that holographic duals can be modified to accomodate Regge behavior. Therefore, it is interesting to understand whether Regge behavior can also be achieved in Migdal's approach. In this paper we investigate this issue. We find that Migdal's approach, which is based on a modified Pade approximant, is closely related to the issue of quark-hadron duality breakdown in QCD.Comment: 17 pages, 1 figure. Typos fixed, references added, improved discussion. Minor changes to match the journal versio

Primary structure and sexual stage-specific expression of a LAMMER protein kinase of Plasmodium falciparum.

We have isolated a LAMMER-like gene from Plasmodium falciparum by vectorette technique. The gene consists of 3316 bp encoding a protein 881 amino acids with a predicted molecular mass of approximately 106.7 kDa. The encoded protein, termed PfLAMMER, is composed of two distinct domains. The N-terminal domain is not related to any previously described protein kinases and has several interesting features including multiple consensus phosphorylation sites for a range of protein kinases, a number of RS/SR dipeptides, a large proportion of charged amino acids, two putative nuclear localisation signals and 14 copies of a tetramer DKYD repeats. The C-terminal domain is characteristic of a kinase in the LAMMER family with the highest homology to the Arabidopsis thaliana AFC3 kinase. Genomic restriction analysis showed that PfLAMMER is encoded by a single copy gene in the parasite genome. A single transcript of approximately 3800 nucleotides is expressed specifically in the sexual stage, indicating that PfLAMMER may be important in regulating the processes of sexual differentiation of the parasite

Estimating the underlying infant mortality rates for small populations, including those reporting zero infant deaths: A case study of counties in California

Infant mortality is an important population health statistic that is often used to make health policy decisions. For a small population, an infant mortality rate is subject to high levels of uncertainty and may not indicate the “underlying” mortality regime affecting the population. This situation leads some agencies to either not report infant mortality for these populations or report infant mortality aggregated over space, time or both. A method is presented for estimating “underlying” infant mortality rates that reflect the intrinsic mortality regimes of small populations. The method is described and illustrated in a case study by estimating IMRs for the 15 counties in California where zero infant deaths are reported at the county level for the period 2009-2011. We know that among these 15 counties there are 50 infant deaths reported at the state level but not for the counties in which they occurred. The method’s validity is tested using a synthetic population in the form of a simulated data set generated from a model life table infant mortality rate, representing Level 23 of the West Family Model Life Table for both sexes. The test indicates that the method is capable of producing estimates that represent underlying rates. In this regard, the method described here may assist in the generation of information about the health status of small populations

Human epicardial adipose tissue expresses a pathogenic profile of adipocytokines in patients with cardiovascular disease

Introduction: Inflammation contributes to cardiovascular disease and is exacerbated with increased adiposity, particularly omental adiposity; however, the role of epicardial fat is poorly understood. Methods: For these studies the expression of inflammatory markers was assessed in epicardial fat biopsies from coronary artery bypass grafting (CABG) patients using quantitative RT-PCR. Further, the effects of chronic medications, including statins, as well as peri-operative glucose, insulin and potassium infusion, on gene expression were also assessed. Circulating resistin, CRP, adiponectin and leptin levels were determined to assess inflammation. Results: The expression of adiponectin, resistin and other adipocytokine mRNAs were comparable to that in omental fat. Epicardial CD45 expression was significantly higher than control depots (p < 0.01) indicating significant infiltration of macrophages. Statin treated patients showed significantly lower epicardial expression of IL-6 mRNA, in comparison with the control abdominal depots (p < 0.001). The serum profile of CABG patients showed significantly higher levels of both CRP (control: 1.28 ± 1.57 μg/mL vs CABG: 9.11 ± 15.7 μg/mL; p < 0.001) and resistin (control: 10.53 ± 0.81 ng/mL vs CABG: 16.8 ± 1.69 ng/mL; p < 0.01) and significantly lower levels of adiponectin (control: 29.1 ± 14.8 μg/mL vs CABG: 11.9 ± 6.0 μg/mL; p < 0.05) when compared to BMI matched controls. Conclusion: Epicardial and omental fat exhibit a broadly comparable pathogenic mRNA profile, this may arise in part from macrophage infiltration into the epicardial fat. This study highlights that chronic inflammation occurs locally as well as systemically potentially contributing further to the pathogenesis of coronary artery disease

Photochemically re-bridging disulfide bonds and the discovery of a thiomaleimide mediated photodecarboxylation of C-terminal cysteines

Described in this work is a novel method for photochemically manipulating peptides and proteins via the installation of cysteine-selective photoactive tags. Thiomaleimides, generated simply by the addition of bromomaleimides to reduced disulfide bonds, undergo [2 + 2] photocycloadditions to reconnect the crosslink between the two cysteine residues. This methodology is demonstrated to enable photoactivation of a peptide by macrocyclisation, and reconnection of the heavy and light chains in an antibody fragment to form thiol stable conjugates. Finally we report on an intriguing thiomaleimide mediated photochemical decarboxylation of C-terminal cysteines, discovered during this study

Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

The authors acknowledge the support of the Barts and the London Charity, the Multiple Sclerosis Society of Great Britain and Northern Ireland, the National Multiple Sclerosis Society, USA, notably the National Centre for the Replacement, Refinement & Reduction of Animals in Research, and the Wellcome Trust (grant no. 092539 to ZA). The siRNA was provided by Quark Pharmaceuticals. The funders and Quark Pharmaceuticals had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript