Revealing the value of geospatial information with isochrone maps for improving the management of heart attacks in South Africa

No abstract available.http://http://tandfonline.com/toc/tica20hj2022Family MedicineGeography, Geoinformatics and Meteorolog

Fluid management in diabetic-acidosis — Ringer’s lactate versus normal saline : a randomized controlled trial

OBJECTIVE: To determine if Ringer’s lactate is superior to 0.9% sodium chloride solution for resolution of acidosis in the management of diabetic ketoacidosis (DKA). DESIGN: Parallel double blind randomized controlled trial. METHODS: Patients presenting with DKA at Kalafong and Steve Biko Academic hospitals were recruited for inclusion in this study if they were >18 years of age, had a venous pH >6.9 and 47.2, a blood glucose of >13 mmol/l and had urine ketones of 52+. All patients had to be alert enough to give informed consent and should have received <1 l of resuscitation fluid prior to enrolment. RESULTS: Fifty-seven patients were randomly allocated, 29 were allocated to receive 0.9% sodium chloride solution and 28 to receive Ringer’s lactate (of which 27 were included in the analysis in each group). An adjusted Cox proportional hazards analysis was done to compare the time to normalization of pH between the 0.9% sodium chloride solution and Ringer’s lactate groups. The hazard ratio (Ringer’s compared with 0.9% sodium chloride solution) for time to venous pH normalization (pH = 7.32) was 1.863 (95% CI 0.937–3.705, P = 0.076). The median time to reach a pH of 7.32 for the 0.9% sodium chloride solution group was 683 min (95% CI 378–988) (IQR: 435–1095 min) and for Ringer’s lactate solution 540 min (95% CI 184–896, P = 0.251). The unadjusted time to lower blood glucose to 14 mmol/l was significantly longer in the Ringer’s lactate solution group (410 min, IQR: 240–540) than the 0.9% sodium chloride solution group (300 min, IQR: 235–420, P = 0.044). No difference could be demonstrated between the Ringer’s lactate and 0.9% sodium chloride solution groups in the time to resolution of DKA (based on the ADA criteria) (unadjusted: P = 0.934, adjusted: P = 0.758) CONCLUSION: This study failed to indicate benefit from using Ringer’s lactate solution compared to 0.9% sodium chloride solution regarding time to normalization of pH in patients with DKA. The time to reach a blood glucose level of 14 mmol/l took significantly longer with the Ringer’s lactate solution.University of Pretoria, Research Development Programmehttp://qjmed.oxfordjournals.org

The correlation between C-reactive protein and toxic granulation of neutrophils in the peripheral blood

BACKGROUND: During inflammation, the serum concentrations of granulocyte colony-stimulating factor (G-CSF), plasma interleukin-6 (IL-6), and C-reactive protein (CRP) increase. A positive correlation between CRP and the percentages of neutrophils exhibiting toxic granulation during inflammation has been demonstrated, and that the fluctuations of CRP and toxic granulation of neutrophils were similar. OBJECTIVES: We studied whether grading of toxic granulated neutrophils can be used as a surrogate marker for infection or inflammation, and also be an easier method than previously described methods. MATERIALS AND METHODS: We graded 357 consecutive peripheral blood slides from patients on whom a full blood count with differential count and CRP level was performed, according to intensity of toxic granulation in the neutrophil population, according to a newly proposed grading system. RESULTS: The CRP range was between 1 and 530.3 mg/l. The results confirm the association between a rise in CRP and progressive intensity of toxic granulation in neutrophils in peripheral blood. Kruskal-Wallis equality of populations rank test showed a statistically significant difference between the graded categories (p=0.0001). The Trend test was also statistically significant (p=0.000). CONCLUSION: The proposed system can be applied to patients with inflammatory or infectious conditions, where grading of toxic granulation of neutrophils can possibly be used as a surrogate marker to assess infection or inflammation and their response to treatment. It may be of particular use in cases where traditional infectious or inflammatory markers cannot be used, owing to inherent problems associated with the respective conditions

Evolutionary distances in the twilight zone -- a rational kernel approach

Phylogenetic tree reconstruction is traditionally based on multiple sequence alignments (MSAs) and heavily depends on the validity of this information bottleneck. With increasing sequence divergence, the quality of MSAs decays quickly. Alignment-free methods, on the other hand, are based on abstract string comparisons and avoid potential alignment problems. However, in general they are not biologically motivated and ignore our knowledge about the evolution of sequences. Thus, it is still a major open question how to define an evolutionary distance metric between divergent sequences that makes use of indel information and known substitution models without the need for a multiple alignment. Here we propose a new evolutionary distance metric to close this gap. It uses finite-state transducers to create a biologically motivated similarity score which models substitutions and indels, and does not depend on a multiple sequence alignment. The sequence similarity score is defined in analogy to pairwise alignments and additionally has the positive semi-definite property. We describe its derivation and show in simulation studies and real-world examples that it is more accurate in reconstructing phylogenies than competing methods. The result is a new and accurate way of determining evolutionary distances in and beyond the twilight zone of sequence alignments that is suitable for large datasets.Comment: to appear in PLoS ON

Changes in Retinol-Binding Protein Concentrations and Thyroid Homeostasis with Nonoccupational Exposure to DDT

BACKGROUND: The insecticide dichlorodiphenyltrichloroethane (DDT) has been used for malaria vector control in the northern and eastern parts of the Vhembe District of Limpopo Province, South Africa, since 1945. Bioaccumulation of DDT raises concern because it reportedly affects thyroid function. OBJECTIVE: Our objective was to investigate the association between DDT uptake (as reflected in plasma concentrations) and thyroid homeostasis while considering related factors. METHODS: We compared dietary intake, serum retinol-binding protein (RBP), transthyretin (TTR) and albumin concentrations, and liver and thyroid function between cases with evidence of a body burden of DDT in the circulation (concentration of any DDT isomer ≥ 0.02 μg/g lipid; n = 278) and controls (concentration of all DDT isomers < 0.02 μg/g lipid; n = 40) in a cross-sectional study. Further analyses were performed to assess the relevance of changes in RBP status associated with DDT uptake. RESULTS: RBP concentrations below the reference range were more prevalent in cases (54% vs. 10% in controls; χ2 = 27.4; p < 0.001), which could not be explained by nutrient intake. We observed significantly lower thyroid hormone concentrations among cases (p ≤ 0.01). We also observed a significant linear trend for serum concentrations of free thyroxine and free triiodothyronine (p < 0.001) and a significant quadratic trend for serum thyroid-stimulating hormone (p = 0.025) and TTR (p < 0.001) across the control group and case groups with normal and relatively low RBP concentrations. Relatively low RBP concentrations were associated with significantly higher DDT and 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) isomer concentrations and with a higher DDE/DDT ratio (p ≤ 0.01), which signifies long-term exposure. Inadequate intake of vitamin A and zinc were observed in 84% and 58%, respectively, of the total study population. CONCLUSION: RBP concentrations appear to decrease in the presence of long-term DDT uptake, which may have deleterious effects on thyroid function and vitamin A nutritional status. This is of major concern in a population with poor vitamin A and zinc intake

Health and economic benefits of achieving contraceptive and maternal health targets in small island developing states in the Pacific and Caribbean

INTRODUCTION: Reducing unmet need for modern contraception and expanding access to quality maternal health (MH) services are priorities for improving women's health and economic empowerment. To support investment decisions, we estimated the additional cost and expected health and economic benefits of achieving the United Nations targets of zero unmet need for modern contraceptive choices and 95% coverage of MH services by 2030 in select Small Island Developing States. METHODS: Five Pacific (Kiribati, Samoa, Solomon Islands, Tonga and Vanuatu) and four Caribbean (Barbados, Guyana, Jamaica and Saint Lucia) countries were considered based on population survey data availability. For each country, the Lives Saved Tool was used to model costs, health outcomes and economic benefits for two scenarios: business-as-usual (BAU) (coverage maintained) and coverage-targets-achieved, which scaled linearly from 2022 (following COVID-19 disruptions) coverage of evidence-based family planning and MH interventions to reach United Nations targets, including modern contraceptive methods and access to complete antenatal, delivery and emergency care. Unintended pregnancies, maternal deaths, stillbirths and newborn deaths averted by the coverage-targets-achieved scenario were converted to workforce, education and social economic benefits; and benefit-cost ratios were calculated. RESULTS: The coverage-targets-achieved scenario required an additional US$12.6M (US$10.8M-US$15.9M) over 2020-2030 for the five Pacific countries (15$82.4M to maintain BAU). This additional investment was estimated to avert 126 000 (40%) unintended pregnancies, 2200 (28%) stillbirths and 121 (29%) maternal deaths and lead to a 15-fold economic benefit of US$190.6M (US$67.0M-US$304.5M) by 2050. For the four Caribbean countries, an additional US$17.8M (US$15.3M-US$22.4M) was needed to reach the targets (4% more than US$405.4M to maintain BAU). This was estimated to avert 127 000 (23$426.2M (US$138.6M-US$745.7M) by 2050. CONCLUSION: Achieving full coverage of contraceptive and MH services in the Pacific and Caribbean is likely to have a high return on investment

Molecular evolution of HoxA13 and the multiple origins of limbless morphologies in amphibians and reptiles

Developmental processes and their results, morphological characters, are inherited through transmission of genes regulating development. While there is ample evidence that cis-regulatory elements tend to be modular, with sequence segments dedicated to different roles, the situation for proteins is less clear, being particularly complex for transcription factors with multiple functions. Some motifs mediating protein-protein interactions may be exclusive to particular developmental roles, but it is also possible that motifs are mostly shared among different processes. Here we focus on HoxA13, a protein essential for limb development. We asked whether the HoxA13 amino acid sequence evolved similarly in three limbless clades: Gymnophiona, Amphisbaenia and Serpentes. We explored variation in ω (dN/dS) using a maximum-likelihood framework and HoxA13sequences from 47 species. Comparisons of evolutionary models provided low ω global values and no evidence that HoxA13 experienced relaxed selection in limbless clades. Branch-site models failed to detect evidence for positive selection acting on any site along branches of Amphisbaena and Gymnophiona, while three sites were identified in Serpentes. Examination of alignments did not reveal consistent sequence differences between limbed and limbless species. We conclude that HoxA13 has no modules exclusive to limb development, which may be explained by its involvement in multiple developmental processes

Recent acquisition of Helicobacter pylori by Baka Pygmies

Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and most divergent population, hpAfrica2, evolved within San hunter-gatherers, who represent one of the deepest branches of the human population tree. Anticipating the presence of ancient H. pylori lineages within all hunter-gatherer populations, we investigated the prevalence and population structure of H. pylori within Baka Pygmies in Cameroon. Gastric biopsies were obtained by esophagogastroduodenoscopy from 77 Baka from two geographically separated populations, and from 101 non-Baka individuals from neighboring agriculturalist populations, and subsequently cultured for H. pylori. Unexpectedly, Baka Pygmies showed a significantly lower H. pylori infection rate (20.8%) than non-Baka (80.2%). We generated multilocus haplotypes for each H. pylori isolate by DNA sequencing, but were not able to identify Baka-specific lineages, and most isolates in our sample were assigned to hpNEAfrica or hpAfrica1. The population hpNEAfrica, a marker for the expansion of the Nilo-Saharan language family, was divided into East African and Central West African subpopulations. Similarly, a new hpAfrica1 subpopulation, identified mainly among Cameroonians, supports eastern and western expansions of Bantu languages. An age-structured transmission model shows that the low H. pylori prevalence among Baka Pygmies is achievable within the timeframe of a few hundred years and suggests that demographic factors such as small population size and unusually low life expectancy can lead to the eradication of H. pylori from individual human populations. The Baka were thus either H. pylori-free or lost their ancient lineages during past demographic fluctuations. Using coalescent simulations and phylogenetic inference, we show that Baka almost certainly acquired their extant H. pylori through secondary contact with their agriculturalist neighbors

Revealing Nanomechanical Domains and Their Transient Behavior in Mixed‐Halide Perovskite Films

Abstract: Halide perovskites are a versatile class of semiconductors employed for high performance emerging optoelectronic devices, including flexoelectric systems, yet the influence of their ionic nature on their mechanical behavior is still to be understood. Here, a combination of atomic‐force, optical, and compositional X‐ray microscopy techniques is employed to shed light on the mechanical properties of halide perovskite films at the nanoscale. Mechanical domains within and between morphological grains, enclosed by mechanical boundaries of higher Young's Modulus (YM) than the bulk parent material, are revealed. These mechanical boundaries are associated with the presence of bromide‐rich clusters as visualized by nano‐X‐ray fluorescence mapping. Stiffer regions are specifically selectively modified upon light soaking the sample, resulting in an overall homogenization of the mechanical properties toward the bulk YM. This behavior is attributed to light‐induced ion migration processes that homogenize the local chemical distribution, which is accompanied by photobrightening of the photoluminescence within the same region. This work highlights critical links between mechanical, chemical, and optoelectronic characteristics in this family of perovskites, and demonstrates the potential of combinational imaging studies to understand and design halide perovskite films for emerging applications such as photoflexoelectricity