Trends and country-level variation in age at first sex in sub-Saharan Africa among birth cohorts entering adulthood between 1985 and 2020

Background: Debuting sexual intercourse marks exposure to pregnancy or fatherhood and sexually transmitted infections (STIs), including HIV. In sub-Saharan Africa (SSA), sexual debut varies according to cultural, religious, and economic factors, and encouraging delay has been a longstanding component of behavioural HIV prevention strategies. Age at first sex (AFS) is routinely collected in national household surveys, but data are affected by reporting biases, limiting utility to monitor trends and guide sexual health interventions. Methods: We collated individual-level data from nationally-representative household surveys to analyse timing and national trends in AFS in 42 SSA countries. We used a log-skew-logistic distribution to characterize the time to AFS in a Bayesian spatio-temporal model, providing estimates of the sexual debut rate by sex, age, time, and country. We statistically adjusted for reporting biases by comparing AFS reported by the same birth cohorts in multiple survey rounds, allowing different reporting biases by sex and country. Results: Median AFS in 2015 ranged from 15.8 among Angolan women to 25.3 among men in Niger. AFS was younger for women than men in 37/40 countries. The gap was largest for Sahel region countries and minimal in southern African countries. The distribution of female AFS was asymmetric with half debuting sex in an age range of 3.9 years [IQR 3.4–5.0 across countries]. Median AFS increased slightly between 1985 and 2020, ranging 0.84 years [IQR 0.11–1.55] and 0.79 [IQR -0.23–1.98] for females and males, respectively. The gender gap changed little over time in most countries. Female teens often reported higher AFS compared to when asked in their late twenties while male teens reported lower AFS; both sexes recalled a higher AFS in older ages compared to their thirties. Conclusions: AFS increased slightly in most SSA countries, but changes were modest relative to large and persistent variation between countries and sexes, indicating relatively entrenched socio-cultural practices around sexual debut. Sexual health, family planning, and HIV/STI prevention services should adapt to local practices rather than focusing interventions to change AFS. These estimates for rates of sexual debut provide data to guide programmatic prioritization and implementation of sexual health services

Microfluidic impedance biosensors for monitoring a single and multiple cancer cells in anticancer drug treatments

In this work, we present a novel microfluidic impedance biosensor chip for trapping both a single and multiple cancer cells and monitoring their response to the anti-cancer drug treatment. By designing different sizes of working microelectrodes together with the V-shaped cell capture structures, a single or multiple cells are trapped on the microelectrodes surfaces. In addition, by utilizing the passive pumping method, cells can be trapped and positioned inside the microchannels without the need of using the outer micro pump or syringe. The impedance change induced by the response of cells to the anticancer drug Cisplatin treatment was successfully recorded. The proposed biosensor chip has a great potential for applications in cancer cell research, drug screening, and quantification of cancer cells from various tumor stages. The results of this study open potential research collaborations about development of cost-effective devices and lab-on-chips for early disease detection, studies of cancerous cells and their response to anti-cancer drugs to optimize cancer treatments, characterisation of mechanical properties of cells, new drug delivery mechanisms, and micro and nano manufacturing

How acceptable are antiretrovirals for the prevention of sexually transmitted HIV? A review of research on the acceptability of oral pre-exposure prophylaxis and treatment as prevention

Recent research has demonstrated how antiretrovirals (ARVs) could be effective in the prevention of sexually transmitted HIV. We review research on the acceptability of oral pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) for HIV prevention amongst potential users. We consider with whom, where and in what context this research has been conducted, how acceptability has been approached, and what research gaps remain. Findings from 33 studies show a lack of TasP research, PrEP studies which have focused largely on men who have sex with men (MSM) in a US context, and varied measures of acceptability. In order to identify when, where and for whom PrEP and TasP would be most appropriate and effective, research is needed in five areas: acceptability of TasP to people living with HIV; motivation for PrEP use and adherence; current perceptions and management of risk; the impact of broader social and structural factors; and consistent definition and operationalisation of acceptability which moves beyond adherence

Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits

Autism spectrum disorder (ASD) defines a group of common, complex neurodevelopmental disorders. Although the aetiology of ASD has a strong genetic component, there is considerable monozygotic (MZ) twin discordance indicating a role for non-genetic factors. Because MZ twins share an identical DNA sequence, disease-discordant MZ twin pairs provide an ideal model for examining the contribution of environmentally driven epigenetic factors in disease. We performed a genome-wide analysis of DNA methylation in a sample of 50 MZ twin pairs (100 individuals) sampled from a representative population cohort that included twins discordant and concordant for ASD, ASD-associated traits and no autistic phenotype. Within-twin and between-group analyses identified numerous differentially methylated regions associated with ASD. In addition, we report significant correlations between DNA methylation and quantitatively measured autistic trait scores across our sample cohort. This study represents the first systematic epigenomic analyses of MZ twins discordant for ASD and implicates a role for altered DNA methylation in autism

Dissecting complex transcriptional responses using pathway-level scores based on prior information

<p>Abstract</p> <p>Background</p> <p>The genomewide pattern of changes in mRNA expression measured using DNA microarrays is typically a complex superposition of the response of multiple regulatory pathways to changes in the environment of the cells. The use of prior information, either about the function of the protein encoded by each gene, or about the physical interactions between regulatory factors and the sequences controlling its expression, has emerged as a powerful approach for dissecting complex transcriptional responses.</p> <p>Results</p> <p>We review two different approaches for combining the noisy expression levels of multiple individual genes into robust pathway-level differential expression scores. The first is based on a comparison between the distribution of expression levels of genes within a predefined gene set and those of all other genes in the genome. The second starts from an estimate of the strength of genomewide regulatory network connectivities based on sequence information or direct measurements of protein-DNA interactions, and uses regression analysis to estimate the activity of gene regulatory pathways. The statistical methods used are explained in detail.</p> <p>Conclusion</p> <p>By avoiding the thresholding of individual genes, pathway-level analysis of differential expression based on prior information can be considerably more sensitive to subtle changes in gene expression than gene-level analysis. The methods are technically straightforward and yield results that are easily interpretable, both biologically and statistically.</p

Identification of Type 1 Diabetes-Associated DNA Methylation Variable Positions That Precede Disease Diagnosis

Monozygotic (MZ) twin pair discordance for childhood-onset Type 1 Diabetes (T1D) is similar to 50%, implicating roles for genetic and non-genetic factors in the aetiology of this complex autoimmune disease. Although significant progress has been made in elucidating the genetics of T1D in recent years, the non-genetic component has remained poorly defined. We hypothesized that epigenetic variation could underlie some of the non-genetic component of T1D aetiology and, thus, performed an epigenome-wide association study (EWAS) for this disease. We generated genome-wide DNA methylation profiles of purified CD14(+) monocytes (an immune effector cell type relevant to T1D pathogenesis) from 15 T1D-discordant MZ twin pairs. This identified 132 different CpG sites at which the direction of the intra-MZ pair DNA methylation difference significantly correlated with the diabetic state, i.e. T1D-associated methylation variable positions (T1D-MVPs). We confirmed these T1D-MVPs display statistically significant intra-MZ pair DNA methylation differences in the expected direction in an independent set of T1D-discordant MZ pairs (P = 0.035). Then, to establish the temporal origins of the T1D-MVPs, we generated two further genome-wide datasets and established that, when compared with controls, T1D-MVPs are enriched in singletons both before (P = 0.001) and at (P = 0.015) disease diagnosis, and also in singletons positive for diabetes-associated autoantibodies but disease-free even after 12 years follow-up (P = 0.0023). Combined, these results suggest that T1D-MVPs arise very early in the etiological process that leads to overt T1D. Our EWAS of T1D represents an important contribution toward understanding the etiological role of epigenetic variation in type 1 diabetes, and it is also the first systematic analysis of the temporal origins of disease-associated epigenetic variation for any human complex disease

Complete genome characterization of two wild-type measles viruses from Vietnamese infants during the 2014 outbreak

A large measles virus outbreak occurred across Vietnam in 2014. We identified and obtained complete measles virus genomes in stool samples collected from two diarrheal pediatric patients in Dong Thap Province. These are the first complete genome sequences of circulating measles viruses in Vietnam during the 2014 measles outbreak