The application of a new method to the multivariate analysis of incomplete data sets is described. The new method, called maximum likelihood principal component analysis (MLPCA), is analogous to ...conventional principal component analysis (PCA), but incorporates measurement error variance information in the decomposition of multivariate data. Missing measurements can be handled in a reliable and simple manner by assigning large measurement uncertainties to them. The problem of missing data is pervasive in chemistry, and MLPCA is applied to three sets of experimental data to illustrate its utility. For exploratory data analysis, a data set from the analysis of archeological artifacts is used to show that the principal components extracted by MLPCA retain much of the original information even when a significant number of measurements are missing. Maximum likelihood projections of censored data can often preserve original clusters among the samples and can, through the propagation of error, indicate which samples are likely to be projected erroneously. To demonstrate its utility in modeling applications, MLPCA is also applied in the development of a model for chromatographic retention based on a data set which is only 80% complete. MLPCA can predict missing values and assign error estimates to these points. Finally, the problem of calibration transfer between instruments can be regarded as a missing data problem in which entire spectra are missing on the ‘slave’ instrument. Using NIR spectra obtained from two instruments, it is shown that spectra on the slave instrument can be predicted from a small subset of calibration transfer samples even if a different wavelength range is employed. Concentration prediction errors obtained by this approach were comparable to cross-validation errors obtained for the slave instrument when all spectra were available.
Regression and principal components analysis (PCA) are two of the most widely used techniques in chemometrics. In this paper, these methods are compared by considering their application to linear, ...two-dimensional data sets with a zero intercept. The need for accommodating measurement errors with these methods is addressed and various techniques to accomplish this are considered. Seven methods are examined: ordinary least squares (OLS), weighted least squares (WLS), the effective variance method (EVM), multiply weighted regression (MWR), unweighted PCA (UPCA), and two forms of weighted PCA. Additionally, five error structures in
x and
y are considered: homoscedastic equal, homoscedastic unequal, proportional equal, proportional unequal, and random. It is shown that for certain error structures, several of the methods are mathematically equivalent. Furthermore, it is demonstrated that all of the methods can be unified under the principle of maximum likelihood estimation, embodied in the general case by MWR. Extensive simulations show that MWR produces the most reliable parameter estimates in terms of bias and mean-squared error. Finally, implications for modeling in higher dimensions are considered.
Connexins Harris, Andrew L; Locke, Darren
2008, 2008-12-02
eBook
Connexins: A Guide is a practical and valuable reference and text covering a wide scope of information about the connexin family of membrane channel proteins. The editors and contributing authors ...intend for this cutting-edge work to be informative to scientists wishing to learn about the field, as well as to those who are active researchers in this area. Connexins: A Guide masterfully addresses specific needs of the scientific community; it is a comprehensive and comprehensible narrative of the uncommonly diverse connexin field, making previously hard-to-find information easily accessible, while also presenting intelligible insights into the extensive experimental methods and conceptual frameworks necessary to appreciate and understand the important roles that connexin channel proteins play in health and disease.
Typhoid fevers are infections caused by the bacteria Salmonella enterica serovar Typhi (Salmonella Typhi) and Paratyphi A, B and C (Salmonella Paratyphi). Approximately 17.8 million incident cases of ...typhoid fever occur annually, and incidence is highest in children. The accuracy of current diagnostic tests of typhoid fever is poorly understood. We aimed to determine the comparative accuracy of available tests for the pediatric population.
We first conducted a systematic literature review to identify studies that compared diagnostic tests for typhoid fever in children (aged ≤15 years) to blood culture results. We applied a Bayesian latent-class extension to a network meta-analysis model. We modelled known diagnostic properties of bone marrow culture and the relationship between bone marrow and blood culture as informative priors in a Bayesian framework. We tested sensitivities for the proportion of negative blood samples that were false as well as bone marrow sensitivity and specificity.
We found 510 comparisons from 196 studies and 57 specific to the pediatric population. IgM-based tests outperformed their IgG-based counterparts for ELISA and Typhidot tests. The lateral flow IgG test performed comparatively well with 92% sensitivity (72% to 98% across scenario analyses) and 94% specificity. The most sensitive test of those investigated for the South Asian pediatric population was the Reverse Passive Hemagglutination Assay with 99% sensitivity (98% - 100% across scenario analyses). Adding a Widal slide test to other typhoid diagnostics did not substantially improve diagnostic performance beyond the single test alone, however, a lateral flow-based IgG rapid test combined with the typhoid/paratyphoid (TPT) assay yielded improvements in sensitivity without substantial declines in specificity and was the best performing combination test in this setting.
In the pediatric population, lateral-flow IgG, TPT and Reverse Passive Hemagglutination tests had high diagnostic accuracy compared to other diagnostics. Combinations of tests may provide a feasible option to increase diagnostic sensitivity. South Asia has the most informed set of data on typhoid diagnostic testing accuracy, and the evidence base in other important regions needs to be expanded.
A second is that small sections of the population usually remain out of reach of chemotherapy programmes, subgroups that frequently have a disproportionately heavy burden of infection, thereby ...serving as a reservoir for reinfection. ...longer-term effectiveness of chemotherapy in interrupting transmission is dependent on maintenance of regular retreatment. Other issues that are not yet resolved with regards to chemotherapy include potential teratogenic effects of benzimidazole drugs and associations with eczema in children following maternal chemotherapy during pregnancy 24. ...whilst chemotherapy is necessary to rapidly reduce the burden and morbidity of helminth infections, we argue that by itself it is an unsustainable strategy for helminth control and for reaching control and elimination targets.
sulfinamides, sulfonamides, and sulfonimidamides are in-demand motifs in medicinal chemistry, yet methods for the synthesis of alkyl variants that start from simple, readily available feedstocks are ...scarce. In addition, bespoke syntheses of each class of molecules are usually needed. In this report, we detail the synthesis of these three distinct sulfur functional groups, using readily available and structurally diverse alkyl carboxylic acids as the starting materials. The method harnesses alkyl radical generation from carboxylic acids using acridine photocatalysts and 400 nm light with subsequent radical addition to sulfinylamine reagents, delivering sulfinamide products. Using the N-alkoxy sulfinylamine reagent t-BuO-NSO as the radical trap provides common N-alkoxy sulfinamide intermediates, which can be converted in a divergent manner to either sulfonamides or sulfonimidamides, by treatment with sodium hydroxide, or an amine, respectively. The reactions are scalable, tolerate a broad range of functional groups, and can be used for the diversification of complex biologically active compounds.
Soil-transmitted helminths (STH) have acute and chronic manifestations, and can result in lifetime morbidity. Disease burden is difficult to quantify, yet quantitative evidence is required to justify ...large-scale deworming programmes. A recent Cochrane systematic review, which influences Global Burden of Disease (GBD) estimates for STH, has again called into question the evidence for deworming benefit on morbidity due to STH. In this narrative review, we investigate in detail what the shortfalls in evidence are.
We systematically reviewed recent literature that used direct measures to investigate morbidity from STH and we critically appraised systematic reviews, particularly the most recent Cochrane systematic review investigating deworming impact on morbidity. We included six systematic reviews and meta-analyses, 36 literature reviews, 44 experimental or observational studies, and five case series. We highlight where evidence is insufficient and where research needs to be directed to strengthen morbidity evidence, ideally to prove benefits of deworming.
Overall, the Cochrane systematic review and recent studies indicate major shortfalls in evidence for direct morbidity. However, it is questionable whether the systematic review methodology should be applied to STH due to heterogeneity of the prevalence of different species in each setting. Urgent investment in studies powered to detect direct morbidity effects due to STH is required.
No investigations have been undertaken of risk factors for intensity of soil-transmitted helminth (STH) infection in Timor-Leste. This study provides the first analysis of risk factors for intensity ...of STH infection, as determined by quantitative PCR (qPCR), examining a broad range of water, sanitation and hygiene (WASH) and environmental factors, among communities in Manufahi District, Timor-Leste.
A baseline cross-sectional survey of 18 communities was undertaken as part of a cluster randomised controlled trial, with additional identically-collected data from six other communities. qPCR was used to assess STH infection from stool samples, and questionnaires administered to collect WASH, demographic, and socioeconomic data. Environmental information was obtained from open-access sources and linked to infection outcomes. Mixed-effects multinomial logistic regression was undertaken to assess risk factors for intensity of Necator americanus and Ascaris infection.
2152 participants provided stool and questionnaire information for this analysis. In adjusted models incorporating WASH, demographic and environmental variables, environmental variables were generally associated with infection intensity for both N. americanus and Ascaris spp. Precipitation (in centimetres) was associated with increased risk of moderate-intensity (adjusted relative risk ARR 6.1; 95% confidence interval CI 1.9-19.3) and heavy-intensity (ARR 6.6; 95% CI 3.1-14.1) N. americanus infection, as was sandy-loam soil around households (moderate-intensity ARR 2.1; 95% CI 1.0-4.3; heavy-intensity ARR 2.7; 95% CI 1.6-4.5; compared to no infection). For Ascaris, alkaline soil around the household was associated with reduced risk of moderate-intensity infection (ARR 0.21; 95% CI 0.09-0.51), and heavy-intensity infection (ARR 0.04; 95% CI 0.01-0.25). Few WASH risk factors were significant.
In this high-prevalence setting, strong risk associations with environmental factors indicate that anthelmintic treatment alone will be insufficient to interrupt STH transmission, as conditions are favourable for ongoing environmental transmission. Integrated STH control strategies should be explored as a priority.