High dose multiple micronutrient supplementation improves villous morphology in environmental enteropathy without HIV enteropathy: results from a double-blind randomised placebo controlled trial in Zambian adults

PMCID: PMC3897937This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

Saving Planetary Systems: Dead Zones & Planetary Migration

The tidal interaction between a disk and a planet leads to the planet's migration. A long-standing question regarding this mechanism is how to stop the migration before planets plunge into their central stars. In this paper, we propose a new, simple mechanism to significantly slow down planet migration, and test the possibility by using a hybrid numerical integrator to simulate the disk-planet interaction. The key component of the scenario is the role of low viscosity regions in protostellar disks known as dead zones, which affect planetary migration in two ways. First of all, it allows a smaller-mass planet to open a gap, and hence switch the faster type I migration to the slower type II migration. Secondly, a low viscosity slows down type II migration itself, because type II migration is directly proportional to the viscosity. We present numerical simulations of planetary migration by using a hybrid symplectic integrator-gas dynamics code. Assuming that the disk viscosity parameter inside the dead zone is (alpha=1e-4-1e-5), we find that, when a low-mass planet (e.g. 1-10 Earth masses) migrates from outside the dead zone, its migration is stopped due to the mass accumulation inside the dead zone. When a low-mass planet migrates from inside the dead zone, it opens a gap and slows down its migration. A massive planet like Jupiter, on the other hand, opens a gap and slows down inside the dead zone, independent of its initial orbital radius. The final orbital radius of a Jupiter mass planet depends on the dead zone's viscosity. For the range of alpha's noted above, this can vary anywhere from 7 AU, to an orbital radius of 0.1 AU that is characteristic of the hot Jupiters.Comment: 38 pages, 14 figures, some changes in text and figures, accepted for publication in Ap

HIV infection and domestic smoke exposure, but not human papillomavirus, are risk factors for esophageal squamous cell carcinoma in Zambia: a case-control study

(c) 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

Microbiology of chronic suppurative otitis media at Queen Elizabeth Central Hospital, Blantyre, Malawi: A cross-sectional descriptive study

Background Chronic suppurative otitis media (CSOM) is still a significant health problem in developing countries. Therefore, it was pertinent to determine the local Malawian microbiology in order to guide adequate treatment, avoid complications, and provide records for future reference.Aim The study sought to determine the CSOM-causing microorganisms at Queen Elizabeth Central Hospital in Blantyre, Malawi, and establish their relationship signs and symptoms, and with the demographic pattern of the study.Methods This was a hospital-based cross-sectional descriptive study carried out at the ENT outpatient clinic and the Microbiology Department of Queen Elizabeth Central Hospital.The sample comprised 104 patients with unilateral or bilateral active CSOM, who met the inclusion criteria. All patients were evaluated through a detailed history and clinical examination. Pus samples from draining ears were collected by aspiration with a sterile pipette. The specimens were immediately sent for microbiological analysis. Data were analyzed using SPSS.version 20.Results The study found that Proteus mirabilis, Pseudomonas aeruginosa, and Staphylococcus aureus were the most prevalent aerobic bacteria, while Bacteroides spp. and Peptostreptococcus spp. were the commonest anaerobic bacteria causing CSOM. These CSOM-causing microorganisms were predominant among males aged 18 years and below. Some CSOMcausing microorganisms were—significantly more so than the others—characteristically associated with each of the following clinical features: quantity of pus drainage, mode of onset, otalgia, hearing loss, location of tympanic membrane perforation, and mucosal appearance

The Origin of Jovian Planets in Protostellar Disks: The Role of Dead Zones

The final masses of Jovian planets are attained when the tidal torques that they exert on their surrounding protostellar disks are sufficient to open gaps in the face of disk viscosity, thereby shutting off any further accretion. In sufficiently well-ionized disks, the predominant form of disk viscosity originates from the Magneto-Rotational Instability (MRI) that drives hydromagnetic disk turbulence. In the region of sufficiently low ionization rate -- the so-called dead zone -- turbulence is damped and we show that lower mass planets will be formed. We considered three ionization sources (X-rays, cosmic rays, and radioactive elements) and determined the size of a dead zone for the total ionization rate by using a radiative, hydrostatic equilibrium disk model developed by Chiang et al. (2001). We studied a range of surface mass density (Sigma_{0}=10^3 - 10^5 g cm^{-2}) and X-ray energy (kT_{x}=1 - 10 keV). We also compared the ionization rate of such a disk by X-rays with cosmic rays and find that the latter dominate X-rays in ionizing protostellar disks unless the X-ray energy is very high (5 - 10 keV). Among our major conclusions are that for typical conditions, dead zones encompass a region extending out to several AU -- the region in which terrestrial planets are found in our solar system. Our results suggest that the division between low and high mass planets in exosolar planetary systems is a consequence of the presence of a dead zone in their natal protoplanetary disks. We also find that the extent of a dead zone is mainly dependent on the disk's surface mass density. Our results provide further support for the idea that Jovian planets in exosolar systems must have migrated substantially inwards from their points of origin.Comment: 28 pages, 10 figures, accepted by Ap

Clinical, health systems and neighbourhood determinants of tuberculosis case fatality in urban Blantyre, Malawi : a multilevel epidemiological analysis of enhanced surveillance data

We investigated whether household to clinic distance was a risk factor for death on tuberculosis (TB) treatment in Malawi. Using enhanced TB surveillance data, we recorded all TB treatment initiations and outcomes between 2015 and 2018. Household locations were geolocated, and distances were measured by a straight line or shortest road network. We constructed Bayesian multi-level logistic regression models to investigate associations between distance and case fatality. A total of 479/4397 (10.9%) TB patients died. Greater distance was associated with higher (odds ratio (OR) 1.07 per kilometre (km) increase, 95% credible interval (CI) 0.99–1.16) odds of death in TB patients registered at the referral hospital, but not among TB patients registered at primary clinics (OR 0.98 per km increase, 95% CI 0.92–1.03). Age (OR 1.02 per year increase, 95% CI 1.01–1.02) and HIV-positive status (OR 2.21, 95% CI 1.73–2.85) were also associated with higher odds of death. Model estimates were similar for both distance measures. Distance was a risk factor for death among patients at the main referral hospital, likely due to delayed diagnosis and suboptimal healthcare access. To reduce mortality, targeted community TB screening interventions for TB disease and HIV, and expansion of novel sensitive diagnostic tests are required.Peer reviewe

On Physical Equivalence between Nonlinear Gravity Theories

We argue that in a nonlinear gravity theory, which according to well-known results is dynamically equivalent to a self-gravitating scalar field in General Relativity, the true physical variables are exactly those which describe the equivalent general-relativistic model (these variables are known as Einstein frame). Whenever such variables cannot be defined, there are strong indications that the original theory is unphysical. We explicitly show how to map, in the presence of matter, the Jordan frame to the Einstein one and backwards. We study energetics for asymptotically flat solutions. This is based on the second-order dynamics obtained, without changing the metric, by the use of a Helmholtz Lagrangian. We prove for a large class of these Lagrangians that the ADM energy is positive for solutions close to flat space. The proof of this Positive Energy Theorem relies on the existence of the Einstein frame, since in the (Helmholtz--)Jordan frame the Dominant Energy Condition does not hold and the field variables are unrelated to the total energy of the system.Comment: 37 pp., TO-JLL-P 3/93 Dec 199

Neighbourhood prevalence-to-notification ratios for adult bacteriologically-confirmed tuberculosis reveals hotspots of underdiagnosis in Blantyre, Malawi

Funding: This work was supported by two grants from Wellcome Trust (ELC grant number WT200901/Z/16/Z) and (PM grant number 200901/Z/16/Z). JRC was funded by UK Medical Research Council (MRC) programme grant MC_UU_00004/07. PJD was supported by a fellowship from the MRC (MR/P022081/1); this UK funded award was part of the EDCTP2 programme supported by the European Union. RMB was funded by Wellcome Trust (203905/16/Z). KCH was supported by the European Research Council (757699) and UK FCDO (Leaving no-one behind: transforming gendered pathways to health for TB). TC was supported by US NIH R01 R01AI147854.Local information is needed to guide targeted interventions for respiratory infections such as tuberculosis (TB). Case notification rates (CNRs) are readily available, but systematically underestimate true disease burden in neighbourhoods with high diagnostic access barriers. We explored a novel approach, adjusting CNRs for under-notification (P:N ratio) using neighbourhood-level predictors of TB prevalence-to-notification ratios. We analysed data from 1) a citywide routine TB surveillance system including geolocation, confirmatory mycobacteriology, and clinical and demographic characteristics of all registering TB patients in Blantyre, Malawi during 2015–19, and 2) an adult TB prevalence survey done in 2019. In the prevalence survey, consenting adults from randomly selected households in 72 neighbourhoods had symptom-plus-chest X-ray screening, confirmed with sputum smear microscopy, Xpert MTB/Rif and culture. Bayesian multilevel models were used to estimate adjusted neighbourhood prevalence-to-notification ratios, based on summarised posterior draws from fitted adult bacteriologically-confirmed TB CNRs and prevalence. From 2015–19, adult bacteriologically-confirmed CNRs were 131 (479/371,834), 134 (539/415,226), 114 (519/463,707), 56 (283/517,860) and 46 (258/578,377) per 100,000 adults per annum, and 2019 bacteriologically-confirmed prevalence was 215 (29/13,490) per 100,000 adults. Lower educational achievement by household head and neighbourhood distance to TB clinic was negatively associated with CNRs. The mean neighbourhood P:N ratio was 4.49 (95% credible interval [CrI]: 0.98–11.91), consistent with underdiagnosis of TB, and was most pronounced in informal peri-urban neighbourhoods. Here we have demonstrated a method for the identification of neighbourhoods with high levels of under-diagnosis of TB without the requirement for a prevalence survey; this is important since prevalence surveys are expensive and logistically challenging. If confirmed, this approach may support more efficient and effective targeting of intensified TB and HIV case-finding interventions aiming to accelerate elimination of urban TB.Peer reviewe

Clinical, health systems and neighbourhood determinants of tuberculosis case fatality in urban Blantyre, Malawi: a multilevel epidemiological analysis of enhanced surveillance data

Abstract We investigated whether household to clinic distance was a risk factor for death on tuberculosis (TB) treatment in Malawi. Using enhanced TB surveillance data, we recorded all TB treatment initiations and outcomes between 2015 and 2018. Household locations were geolocated, and distances were measured by a straight line or shortest road network. We constructed Bayesian multi-level logistic regression models to investigate associations between distance and case fatality. A total of 479/4397 (10.9%) TB patients died. Greater distance was associated with higher (odds ratio (OR) 1.07 per kilometre (km) increase, 95% credible interval (CI) 0.99–1.16) odds of death in TB patients registered at the referral hospital, but not among TB patients registered at primary clinics (OR 0.98 per km increase, 95% CI 0.92–1.03). Age (OR 1.02 per year increase, 95% CI 1.01–1.02) and HIV-positive status (OR 2.21, 95% CI 1.73–2.85) were also associated with higher odds of death. Model estimates were similar for both distance measures. Distance was a risk factor for death among patients at the main referral hospital, likely due to delayed diagnosis and suboptimal healthcare access. To reduce mortality, targeted community TB screening interventions for TB disease and HIV, and expansion of novel sensitive diagnostic tests are required.</jats:p

Endomicroscopic and transcriptomic analysis of impaired barrier function and malabsorption in environmental enteropathy

Introduction: Environmental enteropathy (EE) is associated with growth failure, micronutrient malabsorption and impaired responses to oral vaccines. We set out to define cellular mechanisms of impaired barrier function in EE and explore protective mechanisms. Methods: We studied 49 adults with environmental enteropathy in Lusaka, Zambia using confocal laser endomicroscopy (CLE); histology, immunohistochemistry and mRNA sequencing of small intestinal biopsies; and correlated these with plasma lipopolysaccharide (LPS) and a zinc uptake test. Results: CLE images (median 134 for each study) showed virtually ubiquitous small intestinal damage. Epithelial defects, imaged by histology and claudin 4 immunostaining, were predominantly seen at the tips of villi and corresponded with leakage imaged in vivo by CLE. In multivariate analysis, circulating log-transformed LPS was correlated with cell shedding events (β = 0.83; P = 0.035) and with serum glucagon-like peptide-2 (β = -0.13; P = 0.007). Zinc uptake from a test dose of 25mg was attenuated in 30/47 (64%) individuals and in multivariate analysis was reduced by HIV, but positively correlated with GLP-2 (β = 2.72; P = 0.03). There was a U-shaped relationship between circulating LPS and villus surface area. Transcriptomic analysis identified 23 differentially expressed genes in severe enteropathy, including protective peptides and proteins. Conclusions: Confocal endomicroscopy, claudin 4 immunostaining and histology identify epithelial defects which are probably sites of bacterial translocation, in the presence of which increased epithelial surface area increases the burden of translocation. GLP 2 and other protective peptides may play an important role in mucosal protection in EE