Nevin Manimala

J Infect Dis. 2021 Nov 23;224(Supplement_5):S475-S483. doi: 10.1093/infdis/jiab187.

ABSTRACT

BACKGROUND: Typhoid fever remains a major public health problem in India. Recently, the Surveillance for Enteric Fever in India program completed a multisite surveillance study. However, data on subnational variation in typhoid fever are needed to guide the introduction of the new typhoid conjugate vaccine in India.

METHODS: We applied a geospatial statistical model to estimate typhoid fever incidence across India, using data from 4 cohort studies and 6 hybrid surveillance sites from October 2017 to March 2020. We collected geocoded data from the Demographic and Health Survey in India as predictors of typhoid fever incidence. We used a log linear regression model to predict a primary outcome of typhoid incidence.

RESULTS: We estimated a national incidence of typhoid fever in India of 360 cases (95% confidence interval [CI], 297-494) per 100 000 person-years, with an annual estimate of 4.5 million cases (95% CI, 3.7-6.1 million) and 8930 deaths (95% CI, 7360-12 260), assuming a 0.2% case-fatality rate. We found substantial geographic variation of typhoid incidence across the country, with higher incidence in southwestern states and urban centers in the north.

CONCLUSIONS: There is a large burden of typhoid fever in India with substantial heterogeneity across the country, with higher burden in urban centers.

PMID:35238365 | DOI:10.1093/infdis/jiab187

Hum Reprod. 2022 Mar 3:deac036. doi: 10.1093/humrep/deac036. Online ahead of print.

ABSTRACT

STUDY QUESTION: What are the intentions of men and women of reproductive age in the UK regarding reproduction and family building?

SUMMARY ANSWER: We identified six main categories of people; Avoiders, Betweeners, Completers, Desirers, Expectants and Flexers, for whom reproduction education strategies should be tailored differently to suit intentions.

WHAT IS KNOWN ALREADY: Several studies have highlighted poor fertility awareness across men and women of reproductive age. As the average age of first-time parents continues to rise, there has been a concerted effort from educators, healthcare professionals, charities, reproductive health groups and government policymakers, to improve fertility awareness. In order to ensure that these messages are effective and to deploy the best strategies, it is important to understand people’s reproductive health needs. This study therefore aimed to explore different reproductive intentions to aid tailoring of information to help individuals and couples achieve their family building desires.

STUDY DESIGN, SIZE, DURATION: We conducted a mixed-method study via a UK-wide cross-sectional survey with 1082 participants and semi-structured interviews of 20 women and 15 men who agreed to follow-up interviews. Interviews lasted an hour on average. Ethics approval from UCL Research Ethics Committee.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Survey participants were recruited nationwide via online newspaper and social media adverts. Interviewees were purposely sampled to include men and women from the reproductive age range (18-45 years), varying ethnicity and education background. Survey data were analysed using the Minitab statistical software package. Interview data were transcribed and analysed using the framework method.

MAIN RESULTS AND THE ROLE OF CHANCE: From the survey and interviews, we identified six key categories of people, grouped alphabetically, in a user-friendly manner to highlight a spectrum of reproductive intentions: Avoiders describes respondents who have no children and do not want to have children in the future; Betweeners describes those who already have child(ren) and want more in the future but are not actively trying to conceive; Completers describes those who have child(ren) but do not want more; Desirers describes those who are actively trying to conceive or plan to have child(ren) in the future; Expectants describes those who were pregnant at the time of the study; and Flexers describes those who may or may not already have and are unsure but or open to having child(ren) in the future. Analysis of survey data identified the following proportions in our study: Avoiders, 4.7%; Betweeners, 11.3%; Completers, 13.6%; Desirers, 36.9%; Expectants, 4.1%; and Flexers 28.4% and 2.4% preferring not to answer. There was one ‘other’ group from qualitative analysis, who would like to have children in the future but were unsure whether they could or had changing views. We recommend classifying as ‘Desirers’ or ‘Flexers’ for the purposes of fertility education. A majority of the survey population were trying to get pregnant; were pregnant; or planning to have a child in the future-whether actively, passively or simply open to the idea, with interviews providing deep insights into their family building decision-making.

LIMITATIONS, REASONS FOR CAUTION: Due to the online recruitment method, there may be a bias towards more educated respondents.

WIDER IMPLICATIONS OF THE FINDINGS: We developed a user-friendly, alphabetical categorization of reproductive intentions, which may be used by individuals, healthcare professionals, educators, special interest groups, charities and policymakers to support and enable individuals and couples in making informed choices to achieve their desired intentions, if and when they choose to start a family.

STUDY FUNDING/COMPETING INTEREST(S): There was no external funding for this study. The authors report no competing interests.

TRIAL REGISTRATION NUMBER: N/A.

PMID:35238351 | DOI:10.1093/humrep/deac036

Cereb Cortex. 2022 Mar 3:bhac077. doi: 10.1093/cercor/bhac077. Online ahead of print.

ABSTRACT

Goal-directed behavior is dependent upon the ability to detect errors and implement appropriate posterror adjustments. Accordingly, several studies have explored the neural activity underlying error-monitoring processes, identifying the insula cortex as crucial for error awareness and reporting mixed findings with respect to the anterior cingulate cortex (ACC). Variable patterns of activation have previously been attributed to insufficient statistical power. We therefore sought to clarify the neural correlates of error awareness in a large event-related functional magnetic resonance imaging (fMRI) study. Four hundred and two healthy participants undertook the error awareness task, a motor Go/No-Go response inhibition paradigm in which participants were required to indicate their awareness of commission errors. Compared to unaware errors, aware errors were accompanied by significantly greater activity in a network of regions, including the insula cortex, supramarginal gyrus (SMG), and midline structures, such as the ACC and supplementary motor area (SMA). Error awareness activity was related to indices of task performance and dimensional measures of psychopathology in selected regions, including the insula, SMG, and SMA. Taken together, we identified a robust and reliable neural network associated with error awareness.

PMID:35238340 | DOI:10.1093/cercor/bhac077

J AOAC Int. 2022 Mar 3:qsac029. doi: 10.1093/jaoacint/qsac029. Online ahead of print.

ABSTRACT

BACKGROUND: PathogenDx family of assays use microarray technology to simultaneously detect the presence of bacterial and fungal pathogens in food products, environmental surfaces and cannabis products.

OBJECTIVE: The Detectx Combined assay, was validated for the detection of Aspergillus, (Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger and Aspergillus terreus), Salmonella, and a broad range of STEC (stx1 and/or 2) species. The validation consisted of two matrix studies in dried hemp flower and dried cannabis flower (> 0.3% delta-9 tetrahydrocannabinol) flower, product consistency, stability, robustness and inclusivity and exclusivity for two targets: Aspergillus and STEC.

METHODS: The PathogenDx Detectx Combined assay was evaluated with 30 replicates in each matrix and confirmed according to the instructions outlined in this study.

RESULTS: Results of the validation study met the requirements of AOAC SMPR 2020.002 and 2020.012. In the inclusivity and exclusivity study, all target isolates (Aspergillus and STEC) were correctly detected. For the exclusivity study, 26 out of 30 Aspergillus and 30 out of 30 STEC non-target strains were correctly excluded. In the matrix study, the PathogenDx Detectx Combined assay showed no significant statistical differences between confirmed results for dried hemp and cannabis flower. Robustness testing indicated small changes to the method parameters did not impact the performance of the assay. Stability and consistency studies verified the assay’s shelf-life claims were appropriate and manufacturing of the assay was consistent.

CONCLUSIONS: The validation study indicated that the PathogenDx Detectx Combined assay was successful in detection of the new target analytes (Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger and Aspergillus terreus, and STEC containing stx1 and/or 2) and could successfully recover these organisms and Salmonella from dried hemp flower and dried cannabis flower (> 0.3% delta-9 tetrahydrocannabinol).

PMID:35238337 | DOI:10.1093/jaoacint/qsac029

Am J Epidemiol. 2022 Mar 3:kwac040. doi: 10.1093/aje/kwac040. Online ahead of print.

ABSTRACT

Dietary copper intake may be associated with cognitive decline and dementia. We used data from 10,269 participants of the Atherosclerosis Risks in Communities Study to study the associations of dietary copper intake with 20-year cognitive decline and incident dementia. Dietary copper intake from food and supplements was quantified using food frequency questionnaires. Cognition was assessed using three cognitive tests at study visits; dementia was ascertained at study visits and via surveillance. Multiple imputation by chained equations was applied to account for the missing information of cognitive function during follow-up. Survival analysis with parametric models and mixed-effect models were used to estimate the associations for incident dementia and cognitive decline, respectively. During 20 years of follow-up (1996-1998 to 2016-2017), 1,862 incident cases of dementia occurred. Higher intake of dietary copper from food was associated with higher risk of incident dementia among those with high intake of saturated fat (hazards ratio: 1.49, 95% confidence interval (CI): 1.04, 1.95). Higher intake of dietary copper from food was associated with greater decline in language overall (beta: -0.12, 95% CI: -0.23, -0.02). Therefore, a diet high in copper, particularly when combined with a diet high in saturated fat, may increase the risk of cognitive impairment.

PMID:35238336 | DOI:10.1093/aje/kwac040

Am J Epidemiol. 2022 Mar 3:kwac043. doi: 10.1093/aje/kwac043. Online ahead of print.

ABSTRACT

The inverse probability of treatment weighting (IPTW) approach is popular for evaluating causal effects in observational studies, but extreme propensity scores could bias the estimator and induce excessive variance. Recently, the overlap weighting approach has been proposed to alleviate this problem, which smoothly down-weights the subjects with extreme propensity scores. Although advantages of overlap weighting have been extensively demonstrated in literature with continuous and binary outcomes, research on its performance with time-to-event or survival outcomes is limited. In this article, we propose estimators that combine propensity score weighting and inverse probability of censoring weighting to estimate the counterfactual survival functions. These estimators are applicable to the general class of balancing weights, which includes IPTW, trimming, and overlap weighting as special cases. We conduct simulations to examine the empirical performance of these estimators with different propensity score weighting schemes in terms of bias, variance, and 95% confidence interval coverage, under various degree of covariate overlap between treatment groups and censoring rate. We demonstrate that overlap weighting consistently outperforms IPTW and associated trimming methods in bias, variance, and coverage for time-to-event outcomes, and the advantages increase as the degree of covariate overlap between the treatment groups decreases.

PMID:35238335 | DOI:10.1093/aje/kwac043

Bioinformatics. 2022 Mar 3:btac132. doi: 10.1093/bioinformatics/btac132. Online ahead of print.

ABSTRACT

MOTIVATION: Batch effects in omics datasets are usually a source of technical noise that masks the biological signal and hampers data analysis. Batch effect removal has been widely addressed for individual omics technologies. However, multi-omic datasets may combine data obtained in different batches where omics type and batch are often confounded. Moreover, systematic biases may be introduced without notice during data acquisition, which creates a hidden batch effect. Current methods fail to address batch effect correction in these cases.

RESULTS: In this paper we introduce the MultiBaC R package, a tool for batch effect removal in multi-omics and hidden batch effect scenarios. The package includes a diversity of graphical outputs for model validation and assessment of the batch effect correction.

AVAILABILITY: MultiBaC package is available on Bioconductor (https://www.bioconductor.org/packages/release/bioc/html/MultiBaC.html) and GitHub (https://github.com/ConesaLab/MultiBaC.git).

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:35238331 | DOI:10.1093/bioinformatics/btac132

Bioinformatics. 2022 Mar 3:btac134. doi: 10.1093/bioinformatics/btac134. Online ahead of print.

ABSTRACT

MOTIVATION: A key process in anti-viral adaptive immunity is that the Human Leukocyte Antigen system (HLA) presents epitopes as Major Histocompatibility Complex I (MHC I) protein-peptide complexes on cell surfaces and in this way alerts CD8+ cytotoxic T-Lymphocytes (CTLs). This pathway exerts strong selection pressure on viruses, favoring viral mutants that escape recognition by the HLA/CTL system. Naturally, such immune escape mutations often emerge in highly variable viruses, e.g. HIV or HBV, as HLA-associated mutations (HAMs), specific to the hosts MHC I proteins. The reliable identification of HAMs is not only important for understanding viral genomes and their evolution, but it also impacts the development of broadly effective anti-viral treatments and vaccines against variable viruses. By their very nature, HAMs are amenable to detection by statistical methods in paired sequence/HLA data. However, HLA alleles are very polymorphic in the human host population which makes the available data relatively sparse and noisy. Under these circumstances, one way to optimize HAM detection is to integrate all relevant information in a coherent model. Bayesian inference offers a principled approach to achieve this.

RESULTS: We present a new Bayesian regression model for the detection of HAMs that integrates a sparsity-inducing prior, epitope predictions, and phylogenetic bias assessment, and that yields easily interpretable quantitative information on HAM candidates. The model predicts experimentally confirmed HAMs as having high posterior probabilities, and it performs well in comparison to state-of-the-art models for several data sets from individuals infected with HBV, HDV, and HIV.

AVAILABILITY: The source code of this software is available at https://github.com/HAMdetector/Escape.jl under a permissive MIT license.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:35238330 | DOI:10.1093/bioinformatics/btac134

Genet Mol Biol. 2022 Feb 28;45(1):e20200480. doi: 10.1590/1678-4685-GMB-2020-0480. eCollection 2022.

ABSTRACT

Runs of homozygosity (ROH) in the human genome may be clinically relevant. The aim of this study was to report the frequency of increased ROH of the autosomal genome in individuals with neurodevelopmental delay/intellectual disability and/or multiple congenital anomalies, and to compare these data with a control group. Data consisted of calls of homozygosity from 265 patients and 289 controls. In total, 7.2% (19/265) of the patients showed multiple ROH exceeding 1% of autosomal genome, compared to 1.4% (4/289) in the control group (p=0.0006). Homozygosity ranged from 1.38% to 22.12% among patients, and from 1.53 to 2.40% in the control group. In turn, 1.9% (5/265) of patients presented ROH ≥10Mb in a single chromosome, compared to 0.3% (1/289) of individuals from the control group (p=0.0801). By excluding cases with reported consanguineous parents (15/24), the frequency of increased ROH was 3.4% (9/250) among patients and 1.7% (5/289) in the control group, considering multiple ROH exceeding 1% of the autosome genome and ROH ≥10Mb in a single chromosome together, although not statistically significant (p=0.1873). These results reinforce the importance of investigating ROH, which with complementary diagnostic tests can improve the diagnostic yield for patients with such conditions.

PMID:35238326 | DOI:10.1590/1678-4685-GMB-2020-0480

Adv Sci (Weinh). 2022 Mar 3:e2103729. doi: 10.1002/advs.202103729. Online ahead of print.

ABSTRACT

Studying the compositional instability of mixed ion perovskites under light illumination is important to understand the mechanisms underlying their efficiency and stability. However, current techniques are limited in resolution and are unable to deconvolute minor ion migration phenomena. Here, a method that enables ion migration to be studied allowing different segregation mechanisms to be elucidated is described. Statistical analysis is applied to cathodoluminescence data to generate compositional distribution histograms. Using these histograms, two different ion migration phenomena, horizontal ion migration (HIM) and vertical ion migration (VIM), are identified in different perovskite films. It is found that most passivating agents inhibit HIM, but not VIM. However, VIM can be reduced by deposition of imidazolium iodide on the perovskite surface. This method can be used to study perovskite-based devices efficiency and stability by providing molecular level mechanistic understanding of passivation approaches leading to performance improvement of perovskite solar cells via rational design.

PMID:35238172 | DOI:10.1002/advs.202103729