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Exposure Measurement Error in Air Pollution Epidemiology and its Determinants: Results from the MELONS Study
No full textIntroduction
In air pollution epidemiology, measured or modelled surrogate exposure estimates, prone to measurement error (ME), are used to investigate the health effects of exposure to pollution of outdoor origin, potentially leading to biased effect estimates. We predicted annual personal exposure from outdoor sources using personal measurements, compared it with concentrations from surrogate metrics and quantified ME magnitude, type and determinants.
Methods
We used measurements from four panel studies in London, UK, and predicted personal exposures to fine particulate matter (PM2.5), nitrogen dioxide (NO2), ozone (O3) and black carbon (BC). We compared those with surrogate exposures, including measurements from fixed-site monitors, modelled ambient concentrations or hybrid methods accounting for people’s mobility. We estimated the exposure ME magnitude, correlations and variance ratios between surrogate measures and personal exposure and the percentages of classical/Berkson in the errors. Individual- and area-level characteristics, such as age, sex, socioeconomic status and time spent outdoors were assessed as potential error determinants.
Results
Predicted annual personal exposures to PM2.5, NO2, O3 and BC from outdoor sources were overestimated by surrogate metrics, with mean differences up to 10.1 μg/m3, 40.0 μg/m3, 61.7 μg/m3 and 2.6 μg/m3, respectively. Variance ratios and Pearson correlation coefficients between surrogate and predicted personal exposures ranged from 0.03 to 165.02 and -0.24 to 0.25. Time-activity adjustment reduced errors substantially. Berkson type dominated ME for PM2.5 and BC (43-81% and 26-98%, respectively), whilst classical error characterised gases (>94% for both NO2 and O3). Time spent outdoors, house type and deprivation were associated with exposure error.
Conclusions
The use of surrogate exposures to investigate the health effects of long-term exposure to air pollution from outdoor sources may bias the epidemiological estimates due to ME. Information about the error structures and its determinants can be used for correction and the identification of the true exposure-response functions
Abnormal expression of miRNA-21 and other miRNAs involved in polycystic ovary syndrome and the implications for public health especially in low- and middle-income countries
No full textBackground: MicroRNAs are small non-coding RNA molecules crucial in regulating gene expression. In Polycystic Ovary Syndrome (PCOS), a common endocrine disorder in women of reproductive age, miRNA-21 and other miRNAs have been consistently reported as dysregulated, contributing to its pathophysiology. In PCOS, these are commonly altered (either raised or lowered) in ovarian cells and blood and this alteration can lead to the abnormal development of follicles, inflammation and hormone imbalance, which are major issues in PCOS. As a result, a potential biomarker for this condition that is associated with considerable morbidity. The development of potential biomarkers is important in developing countries such as Pakistan with high prevalence rates of up to 52% in Pakistani women of reproductive age as well as high co-payments impacting on seeking care. This is a key public health consideration in developing countries where multiple visits may be needed before a diagnosis of PCOS is made. Consequently, there is a need to consolidate current evidence to provide future direction. Method: A systematic review including studies showing that miRNA-21 and other miRNAs are involved in dysregulation in women with PCOS, including studies analyzing ovarian tissue and blood samples, and providing public health guidance building on co-author experience. Results: 52 studies were involved in the review. The dysregulation of miRNA-21 in PCOS is associated with altered hormonal levels, particularly elevated androgens, and insulin resistance. The overexpression of miRNA-21 is believed to contribute to metabolic disturbances commonly observed in PCOS patients. Overall, miRNAs have emerged as potential biomarkers for diagnosing PCOS due to their significant role in associate metabolic and hormonal alterations. Conclusion: The findings from provide valuable insights into the mechanisms of PCOS and the potential for miRNA-21as a biomarker and therapeutic target. This is crucial in developing countries such as Pakistan to address the challenges associated with diagnosing and managing PCOS. Other approaches are also needed to improve the mental health, and reduce morbidity, in this vulnerable group
Mechanoregulation of lymphatic valve morphogenesis and lymphedema via Plexin D1
No full textLymphatic valves are essential for maintaining tissue fluid homeostasis and their dysfunction leads to lymphedema, a morbid and disfiguring disease without a cure. Mechanical forces due to lymph flow are required for proper lymphatic valve development, yet it remains unclear how lymphatic endothelial cells (LECs) sense and decode mechanical signals. In this study, we identify the cell guidance semaphorin receptor Plexin D1 (PLXND1) as a lymphatic mechanosensor required for lymphatic valve morphogenesis. Conditional genetic ablation of plxnd1 in LECs causes major defects in lymphatic valve development in two different lymphatic vascular beds. Mechanistically, PLXND1 acts as a mechanosensor within a lymphatic mechanocomplex, initiating distinct mechanical signals and activating the lymphatic valve transcriptional program through an unconventional pathway. Screening of primary lymphoedema patients identified PLXND1 missense variants and functional analysis establishes two pathogenic variants that selectively disrupt the ligand vs mechanosensing functions of this receptor. Variants associated with lymphoedema in members of the mechanocomplex disrupt its formation, underscoring the central role of this complex in lymphatic valve biology. Our work uncovers a novel mechanosensing mechanism guiding lymphatic valve development, with profound implications for the understanding and treatment of primary lymphoedema in humans
Challenges regarding the provision of antibiotics via the informal sector across low- and middle-income countries and potential ways forward
No full textLeveraging census data to design and implement an area-based deprivation index to assess health inequalities in Ecuador
No full textIntroduction: Deprivation measures have been used in research to assess within-country health inequalities globally. Most of these indices are created using data from national census, given their availability and nationwide coverage.
Objectives: This study aims to create a census-based deprivation index in Ecuador, the Ecuadorian Deprivation Index (EDI), that reflects the country specific context using national census data for four geographical units (census sector, parish, canton and province). It will be compared to two traditional small area indices (Townsend and Carstairs) to assess the most appropriate and context specific index for Ecuador. Finally, the performance of the three indices will be assessed by examining the association and extent of inequalities with teenage pregnancy as this has been shown to be socially patterned in other countries.
Methods: This study uses the 2010 Ecuadorian census and follows the stages and recommendations for developing small-area deprivation indices. The Townsend and Carstairs are firstly replicated. For the EDI, Principal Component Analysis is used to select the most appropriate indicators. Summary measures for higher-level geographical areas were developed following the techniques used in the English Index of Multiple Deprivation. Inequalities in teenage pregnancy is measured using the Slope index of inequality and the Relative index of inequality.
Results: The three indices exhibit a good match in urban areas and can describe pattern of inequalities in teenage pregnancy. However, the EDI Index captures rural deprivation more appropriately and that includes the Coast and Amazon geographical regions.
Conclusions: Traditional deprivation measures may not adequately identify deprivation in Ecuador, given the country’s unique specific contextual factors. The wider scope of the EDI will inform policy-makers towards developing tailored programs to alleviate deprivation and health inequalities in Ecuador
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