Test, test, test for COVID-19 antibodies:the importance of sensitivity, specificity and predictive powers

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests of varying specificity and sensitivity are now available. For informing individuals whether they have had coronavirus disease 2019 (COVID-19), they need to be very accurate. For measuring population prevalence of past infection, the numbers of false positives and negatives need to be roughly equal. With a series of worked examples for a notional population of 100,000 people, we show that even test systems with a high specificity can yield a large number of false positive results, especially where the population prevalence is low. For example, at a true population prevalence of 5%, using a test with 99% sensitivity and specificity, 16% of positive results will be false and thus 950 people will be incorrectly informed they have had the infection. Further confirmatory testing may be needed. Giving false reassurance on which personal or societal decisions might be based could be harmful for individuals, undermine public confidence and foster further outbreaks

Neonatal mortality rates, characteristics, and risk factors for neonatal deaths in Ghana:analyses of data from two health and demographic surveillance systems

BACKGROUND: Reducing neonatal mortality rates (NMR) in developing countries is a key global health goal, but weak registration systems in the region stifle public health efforts. OBJECTIVE: To calculate NMRs, investigate modifiable risk factors, and explore neonatal deaths by place of birth and death, and cause of death in two administrative areas in Ghana. METHODS: Data on livebirths were extracted from the health and demographic surveillance systems in Navrongo (2004-2012) and Kintampo (2005-2010). Cause of death was determined from neonatal verbal autopsy forms. Univariable and multivariable logistic regression were used to analyse factors associated with neonatal death. Multiple imputations were used to address missing data. RESULTS: The overall NMR was 18.8 in Navrongo (17,016 live births, 320 deaths) and 12.5 in Kintampo (11,207 live births, 140 deaths). The annual NMR declined in both areas. 54.7% of the births occurred in health facilities. 70.9% of deaths occurred in the first week. The main causes of death were infection (NMR 4.3), asphyxia (NMR 3.7) and prematurity (NMR 2.2). The risk of death was higher among hospital births than home births: Navrongo (adjusted OR 1.14, 95% CI: 1.03-1.25, p = 0.01); Kintampo (adjusted OR 1.76, 95% CI: 1.55-2.00, p < 0.01). However, a majority of deaths occurred at home (Navrongo 61.3%; Kintampo 50.7%). Among hospital births dying in hospital, the leading cause of death was asphyxia; among hospital and home births dying at home, it was infection. CONCLUSION: The NMR in these two areas of Ghana reduced over time. Preventing deaths by asphyxia and infection should be prioritised, centred respectively on improving post-delivery care in health facilities and subsequent post-natal care at home

Smoking and Ischemic Heart Disease Disparities Between Studies, Genders, Times, and Socioeconomic Strata

Large, unexplained, but possibly related disparities exist between heart disease risks observed in differing genders, educational levels, times, and studies. Such heart disease disparities might be related to cumulative tobacco smoke damage (smoke load) disparities that are overlooked in standard assessments of point smoking status. So, I reviewed possible relationships between smoke load and heart disease levels across genders, educational strata, years, and leading studies. Smoker heart disease risk assessments in the Nurses Health Study (Nurses), Cancer Prevention Study-II (CPS-II), and British Doctors studies were compared and related to their likely selection and misclassification biases. Relationships between smoke loads and United States (US) education- and gender-related heart disease mortality disparities were qualitatively assessed using lung cancer rates as a smoke load proxy. The high heart disease mortality risks observed in smoking Nurses in 1980–2004 and in less educated US women in 2001 were qualitatively associated with their higher smoke loads and lower selection and exposure misclassification biases than in the CPS-II and Doctors studies. Smoking-attributable heart disease death tolls and disparities extrapolated from mortality ratios from the CPS-II and Doctors studies may be substantial underestimates. Such studies appear to have compared convenience samples of light smokers to lighter smokers instead of comparing representative smokers to the unexposed. Further efforts to minimize smoke exposures and better quantify cumulative smoking-attributable burdens are needed

Menstrual Product Insecurity Resulting From COVID-19‒Related Income Loss, United States, 2020.

To identify key effects of the pandemic and its economic consequences on menstrual product insecurity with implications for public health practice and policy. Study participants (n = 1496) were a subset of individuals enrolled in a national (US) prospective cohort study. Three survey waves were included (March‒October 2020). Menstrual product insecurity outcomes were explored with bivariate associations and logistic regression models to examine the associations between outcomes and income loss. Income loss was associated with most aspects of menstrual product insecurity (adjusted odds ratios from 1.34 to 3.64). The odds of not being able to afford products for those who experienced income loss was 3.64 times (95% confidence interval [CI] = 2.14, 6.19) that of those who had no income loss and 3.95 times (95% CI = 1.78, 8.79) the odds for lower-income participants compared with higher-income participants. Pandemic-related income loss was a strong predictor of menstrual product insecurity, particularly for populations with lower income and educational attainment. Provision of free or subsidized menstrual products is needed by vulnerable populations and those most impacted by pandemic-related income loss.( 2022;112(4):675-684. (https://doi.org/10.2105/AJPH.2021.306674)

The impact of life tables adjusted for smoking on the socio-economic difference in net survival for laryngeal and lung cancer.

BACKGROUND: Net survival is a key measure in cancer control, but estimates for cancers that are strongly associated with smoking may be biased. General population life tables represent background mortality in net survival, but may not adequately reflect the higher mortality experienced by smokers. METHODS: Life tables adjusted for smoking were developed, and their impact on net survival and inequalities in net survival for laryngeal and lung cancers was examined. RESULTS: The 5-year net survival estimated with smoking-adjusted life tables was consistently higher than the survival estimated with unadjusted life tables: 7% higher for laryngeal cancer and 1.5% higher for lung cancer. The impact of using smoking-adjusted life tables was more pronounced in affluent patients; the deprivation gap in 5-year net survival for laryngeal cancer widened by 3%, from 11% to 14%. CONCLUSIONS: Using smoking-adjusted life tables to estimate net survival has only a small impact on the deprivation gap in survival, even when inequalities are substantial. Adjusting for the higher, smoking-related background mortality did increase the estimates of net survival for all deprivation groups, and may be more important when measuring the public health impact of differences or changes in survival, such as avoidable deaths or crude probabilities of death

Set points, settling points and some alternative models: theoretical options to understand how genes and environments combine to regulate body adiposity

The close correspondence between energy intake and expenditure over prolonged time periods, coupled with an apparent protection of the level of body adiposity in the face of perturbations of energy balance, has led to the idea that body fatness is regulated via mechanisms that control intake and energy expenditure. Two models have dominated the discussion of how this regulation might take place. The set point model is rooted in physiology, genetics and molecular biology, and suggests that there is an active feedback mechanism linking adipose tissue (stored energy) to intake and expenditure via a set point, presumably encoded in the brain. This model is consistent with many of the biological aspects of energy balance, but struggles to explain the many significant environmental and social influences on obesity, food intake and physical activity. More importantly, the set point model does not effectively explain the &lsquo;obesity epidemic' - the large increase in body weight and adiposity of a large proportion of individuals in many countries since the 1980s. An alternative model, called the settling point model, is based on the idea that there is passive feedback between the size of the body stores and aspects of expenditure. This model accommodates many of the social and environmental characteristics of energy balance, but struggles to explain some of the biological and genetic aspects. The shortcomings of these two models reflect their failure to address the gene-by-environment interactions that dominate the regulation of body weight. We discuss two additional models - the general intake model and the dual intervention point model - that address this issue and might offer better ways to understand how body fatness is controlled

Arabidopsis thaliana encodes a bacterial-type heterodimeric isopropylmalate isomerase involved in both Leu biosynthesis and the Met chain elongation pathway of glucosinolate formation

The last steps of the Leu biosynthetic pathway and the Met chain elongation cycle for glucosinolate formation share identical reaction types suggesting a close evolutionary relationship of these pathways. Both pathways involve the condensation of acetyl-CoA and a 2-oxo acid, isomerization of the resulting 2-malate derivative to form a 3-malate derivative, the oxidation-decarboxylation of the 3-malate derivative to give an elongated 2-oxo acid, and transamination to generate the corresponding amino acid. We have now analyzed the genes encoding the isomerization reaction, the second step of this sequence, in Arabidopsis thaliana. One gene encodes the large subunit and three encode small subunits of this enzyme, referred to as isopropylmalate isomerase (IPMI) with respect to the Leu pathway. Metabolic profiling of large subunit mutants revealed accumulation of intermediates of both Leu biosynthesis and Met chain elongation, and an altered composition of aliphatic glucosinolates demonstrating the function of this gene in both pathways. In contrast, the small subunits appear to be specialized to either Leu biosynthesis or Met chain elongation. Green fluorescent protein tagging experiments confirms the import of one of the IPMI small subunits into the chloroplast, the localization of the Met chain elongation pathway in these organelles. These results suggest the presence of different heterodimeric IPMIs in Arabidopsis chloroplasts with distinct substrate specificities for Leu or glucosinolate metabolism determined by the nature of the different small subunit

Aconitase B Is Required for Optimal Growth of Xanthomonas campestris pv. vesicatoria in Pepper Plants

The aerobic plant pathogenic bacterium Xanthomonas campestris pv. vesicatoria (Xcv) colonizes the intercellular spaces of pepper and tomato. One enzyme that might contribute to the successful proliferation of Xcv in the host is the iron-sulfur protein aconitase, which catalyzes the conversion of citrate to isocitrate in the tricarboxylic acid (TCA) cycle and might also sense reactive oxygen species (ROS) and changes in cellular iron levels. Xcv contains three putative aconitases, two of which, acnA and acnB, are encoded by a single chromosomal locus. The focus of this study is aconitase B (AcnB). acnB is co-transcribed with two genes, XCV1925 and XCV1926, encoding putative nucleic acid-binding proteins. In vitro growth of acnB mutants was like wild type, whereas in planta growth and symptom formation in pepper plants were impaired. While acnA, XCV1925 or XCV1926 mutants showed a wild-type phenotype with respect to bacterial growth and in planta symptom formation, proliferation of the acnB mutant in susceptible pepper plants was significantly impaired. Furthermore, the deletion of acnB led to reduced HR induction in resistant pepper plants and an increased susceptibility to the superoxide-generating compound menadione. As AcnB complemented the growth deficiency of an Escherichia coli aconitase mutant, it is likely to be an active aconitase. We therefore propose that optimal growth and survival of Xcv in pepper plants depends on AcnB, which might be required for the utilization of citrate as carbon source and could also help protect the bacterium against oxidative stress

Formal specification of multi-agent systems by using EUSMs

The behavior of e-commerce agents can be defined at different levels of abstraction. A formalism allowing to define them in terms of their economic activities, Utility State Machines, has been proposed. Due to its high level of abstraction, this formalism focuses on describing the economic goals rather on how they are achieved. Though this approach is suitable to specify the objectives of e-commerce agents, as well as to construct formal analysis methodologies, this framework is not suitable to define the strategic behavior of agents. In this paper we develop a new formalism to explicitly define the strategic behavior of agents in a modular way. In particular, we reinterpret the role of utility functions, already used in USMs in a more restrictive manner, so that they define strategic preferences and activities of agents. We apply the formalism to define the agents in a benchmark e-commerce agent environment, the Supply Chain Management Game. Since the strategic behavior of agents is located in a specific part of the formalism, different strategies can be easily considered, which enhances the reusability of the proposed specification