Here we describe the development of the London Hybrid Exposure Model (LHEM), which calculates exposure of the Greater London population to outdoor air pollution sources, in-buildings, in-vehicles, ...and outdoors, using survey data of when and where people spend their time. For comparison and to estimate exposure misclassification we compared Londoners LHEM exposure with exposure at the residential address, a commonly used exposure metric in epidemiological research. In 2011, the mean annual LHEM exposure to outdoor sources was estimated to be 37% lower for PM2.5 and 63% lower for NO2 than at the residential address. These decreased estimates reflect the effects of reduced exposure indoors, the amount of time spent indoors (∼95%), and the mode and duration of travel in London. We find that an individual’s exposure to PM2.5 and NO2 outside their residential address is highly correlated (Pearson’s R of 0.9). In contrast, LHEM exposure estimates for PM2.5 and NO2 suggest that the degree of correlation is influenced by their exposure in different transport modes. Further development of the LHEM has the potential to increase the understanding of exposure error and bias in time-series and cohort studies and thus better distinguish the independent effects of NO2 and PM2.5.
Low emission zones (LEZ) are an increasingly common, but unevaluated, intervention aimed at improving urban air quality and public health. We investigated the impact of London's LEZ on air quality ...and children's respiratory health.
We did a sequential annual cross-sectional study of 2164 children aged 8–9 years attending primary schools between 2009–10 and 2013–14 in central London, UK, following the introduction of London's LEZ in February, 2008. We examined the association between modelled pollutant exposures of nitrogen oxides (including nitrogen dioxide NO2) and particulate matter with a diameter of less than 2·5 μm (PM2·5) and less than 10 μm (PM10) and lung function: postbronchodilator forced expiratory volume in 1 s (FEV1, primary outcome), forced vital capacity (FVC), and respiratory or allergic symptoms. We assigned annual exposures by each child's home and school address, as well as spatially resolved estimates for the 3 h (0600–0900 h), 24 h, and 7 days before each child's assessment, to isolate long-term from short-term effects.
The percentage of children living at addresses exceeding the EU limit value for annual NO2 (40 μg/m3) fell from 99% (444/450) in 2009 to 34% (150/441) in 2013. Over this period, we identified a reduction in NO2 at both roadside (median −1·35 μg/m3 per year; 95% CI −2·09 to −0·61; p=0·0004) and background locations (−0·97; −1·56 to −0·38; p=0·0013), but not for PM10. The effect on PM2·5 was equivocal. We found no association between postbronchodilator FEV1 and annual residential pollutant attributions. By contrast, FVC was inversely correlated with annual NO2 (−0·0023 L/μg per m3; −0·0044 to −0·0002; p=0·033) and PM10 (−0·0090 L/μg per m3; −0·0175 to −0·0005; p=0·038).
Within London's LEZ, a smaller lung volume in children was associated with higher annual air pollutant exposures. We found no evidence of a reduction in the proportion of children with small lungs over this period, despite small improvements in air quality in highly polluted urban areas during the implementation of London's LEZ. Interventions that deliver larger reductions in emissions might yield improvements in children's health.
National Institute for Health Research Biomedical Research Centre at Guy's and St Thomas' National Health Service (NHS) Foundation Trust and King's College London, NHS Hackney, Lee Him donation, and Felicity Wilde Charitable Trust.
Short telomeres are associated with chronic disease and early mortality. Recent studies in adults suggest an association between telomere length and exposure to particulate matter, and that ethnicity ...may modify the relationship. However associations in children are unknown.
We examined associations between air pollution and telomere length in an ethnically diverse group of children exposed to high levels of traffic derived pollutants, particularly diesel exhaust, and to environmental tobacco smoke.
Oral DNA from 333 children (8–9years) participating in a study on air quality and respiratory health in 23 inner city London schools was analysed for relative telomere length using monochrome multiplex qPCR. Annual, weekly and daily exposures to nitrogen oxides and particulate matter were obtained from urban dispersion models (2008–10) and tobacco smoke by urinary cotinine. Ethnicity was assessed by self-report and continental ancestry by analysis of 28 random genomic markers. We used linear mixed effects models to examine associations with telomere length.
Telomere length increased with increasing annual exposure to NOx (model coefficient 0.003, 0.001, 0.005, p<0.001), NO2 (0.009 0.004, 0.015, p<0.001), PM2.5 (0.041, 0.020, 0.063, p<0.001) and PM10 (0.096, 0.044, 0.149, p<0.001). There was no association with environmental tobacco smoke. Telomere length was increased in children reporting black ethnicity (22% 95% CI 10%, 36%, p<0.001)
Pollution exposure is associated with longer telomeres in children and genetic ancestry is an important determinant of telomere length. Further studies should investigate both short and long-term associations between pollutant exposure and telomeres in childhood and assess underlying mechanisms.
•This is the first study on air pollution and telomere length in children.•Genetic ancestry is a major determinant of telomere length in children.•Continuous exposure to pollution is associated with telomere elongation.•Future research should investigate longitudinal effects on telomeres.
Here we describe the development of the London Hybrid Exposure Model (LHEM), which calculates exposure of the Greater London population to outdoor air pollution sources, in-buildings, in-vehicles, ...and outdoors, using survey data of when and where people spend their time. For comparison and to estimate exposure misclassification we compared Londoners LHEM exposure with exposure at the residential address, a commonly used exposure metric in epidemiological research. In 2011, the mean annual LHEM exposure to outdoor sources was estimated to be 37% lower for PM
and 63% lower for NO
than at the residential address. These decreased estimates reflect the effects of reduced exposure indoors, the amount of time spent indoors (∼95%), and the mode and duration of travel in London. We find that an individual's exposure to PM
and NO
outside their residential address is highly correlated (Pearson's R of 0.9). In contrast, LHEM exposure estimates for PM
and NO
suggest that the degree of correlation is influenced by their exposure in different transport modes. Further development of the LHEM has the potential to increase the understanding of exposure error and bias in time-series and cohort studies and thus better distinguish the independent effects of NO
and PM
.
Here we describe the development of the London Hybrid Exposure Model (LHEM), which calculates exposure of the Greater London population to outdoor air pollution sources, in-buildings, in-vehicles, ...and outdoors, using survey data of when and where people spend their time. For comparison and to estimate exposure misclassification we compared Londoners LHEM exposure with exposure at the residential address, a commonly used exposure metric in epidemiological research. In 2011, the mean annual LHEM exposure to outdoor sources was estimated to be 37% lower for PM^sub 2.5^ and 63% lower for NO^sub 2^ than at the residential address. These decreased estimates reflect the effects of reduced exposure indoors, the amount of time spent indoors (~95%), and the mode and duration of travel in London. We find that an individual's exposure to PM^sub 2.5^ and NO^sub 2^ outside their residential address is highly correlated (Pearson's R of 0.9). In contrast, LHEM exposure estimates for PM^sub 2.5^ and NO^sub 2^ suggest that the degree of correlation is influenced by their exposure in different transport modes. Further development of the LHEM has the potential to increase the understanding of exposure error and bias in time-series and cohort studies and thus better distinguish the independent effects of NO^sub 2^ and PM^sub 2.5^.
Here we describe the development of the London Hybrid Exposure Model (LHEM), which calculates exposure of the Greater London population to outdoor air pollution sources, in-buildings, in-vehicles, ...and outdoors, using survey data of when and where people spend their time. For comparison and to estimate exposure misclassification we compared Londoners LHEM exposure with exposure at the residential address, a commonly used exposure metric in epidemiological research. In 2011, the mean annual LHEM exposure to outdoor sources was estimated to be 37% lower for PM sub( 2.5) and 63% lower for NO sub( 2) than at the residential address. These decreased estimates reflect the effects of reduced exposure indoors, the amount of time spent indoors (~95%), and the mode and duration of travel in London. We find that an individual's exposure to PM sub( 2.5) and NO sub( 2) outside their residential address is highly correlated (Pearson's R of 0.9). In contrast, LHEM exposure estimates for PM sub( 2.5) and NO sub( 2) suggest that the degree of correlation is influenced by their exposure in different transport modes. Further development of the LHEM has the potential to increase the understanding of exposure error and bias in time-series and cohort studies and thus better distinguish the independent effects of NO sub( 2) and PM sub( 2.5).
Abstract
STUDY QUESTION
We aim to develop, disseminate and implement a minimum data set, known as a core outcome set, for future male infertility research.
WHAT IS KNOWN ALREADY
Research into male ...infertility can be challenging to design, conduct and report. Evidence from randomized trials can be difficult to interpret and of limited ability to inform clinical practice for numerous reasons. These may include complex issues, such as variation in outcome measures and outcome reporting bias, as well as failure to consider the perspectives of men and their partners with lived experience of fertility problems. Previously, the Core Outcome Measure for Infertility Trials (COMMIT) initiative, an international consortium of researchers, healthcare professionals and people with fertility problems, has developed a core outcome set for general infertility research. Now, a bespoke core outcome set for male infertility is required to address the unique challenges pertinent to male infertility research.
STUDY DESIGN, SIZE, DURATION
Stakeholders, including healthcare professionals, allied healthcare professionals, scientists, researchers and people with fertility problems, will be invited to participate. Formal consensus science methods will be used, including the modified Delphi method, modified Nominal Group Technique and the National Institutes of Health’s consensus development conference.
PARTICIPANTS/MATERIALS, SETTING, METHODS
An international steering group, including the relevant stakeholders outlined above, has been established to guide the development of this core outcome set. Possible core outcomes will be identified by undertaking a systematic review of randomized controlled trials evaluating potential treatments for male factor infertility. These outcomes will be entered into a modified Delphi method. Repeated reflection and re-scoring should promote convergence towards consensus outcomes, which will be prioritized during a consensus development meeting to identify a final core outcome set. We will establish standardized definitions and recommend high-quality measurement instruments for individual core outcomes.
STUDY FUNDING/COMPETING INTEREST(S)
This work has been supported by the Urology Foundation small project award, 2021. C.L.R.B. is the recipient of a BMGF grant and received consultancy fees from Exscentia and Exceed sperm testing, paid to the University of Dundee and speaking fees or honoraria paid personally by Ferring, Copper Surgical and RBMO. S.B. received royalties from Cambridge University Press, Speaker honoraria for Obstetrical and Gynaecological Society of Singapore, Merk SMART Masterclass and Merk FERRING Forum, paid to the University of Aberdeen. Payment for leadership roles within NHS Grampian, previously paid to self, now paid to University of Aberdeen. An Honorarium is received as Editor in Chief of Human Reproduction Open. M.L.E. is an advisor to the companies Hannah and Ro. B.W.M. received an investigator grant from the NHMRC, No: GNT1176437 is a paid consultant for ObsEva and has received research funding from Ferring and Merck. R.R.H. received royalties from Elsevier for a book, consultancy fees from Glyciome, and presentation fees from GryNumber Health and Aytu Bioscience. Aytu Bioscience also funded MiOXYS systems and sensors. Attendance at Fertility 2020 and Roadshow South Africa by Ralf Henkel was funded by LogixX Pharma Ltd. R.R.H. is also Editor in Chief of Andrologia and has been an employee of LogixX Pharma Ltd. since 2020. M.S.K. is an associate editor with Human Reproduction Open. K.Mc.E. received an honoraria for lectures from Bayer and Pharmasure in 2019 and payment for an ESHRE grant review in 2019. His attendance at ESHRE 2019 and AUA 2019 was sponsored by Pharmasure and Bayer, respectively. The remaining authors declare no competing interests.
TRIAL REGISTRATION NUMBER
Core Outcome Measures in Effectiveness Trials (COMET) initiative registration No: 1586. Available at www.comet-initiative.org/Studies/Details/1586.
TRIAL REGISTRATION DATE
N/A.
DATE OF FIRST PATIENT’S ENROLMENT
N/A.
The ZIC2 transcription factor is one of the genes most commonly mutated in Holoprosencephaly (HPE) probands. Studies in cultured cell lines and mice have shown a loss of ZIC2 function is the ...pathogenic mechanism but the molecular details of this ZIC2 requirement remain elusive. HPE arises when signals that direct morphological and fate changes in the developing brain and facial primordia are not sent or received. One critical signal is sent from the prechordal plate (PrCP) which develops beneath the ventral forebrain. An intact NODAL signal transduction pathway and functional ZIC2 are both required for PrCP establishment. We now show that ZIC2 acts downstream of the NODAL signal during PrCP development. ZIC2 physically interacts with SMAD2 and SMAD3, the receptor activated proteins that control transcription in a NODAL dependent manner. Together SMAD3 and ZIC2 regulate FOXA2 transcription in cultured cells and Zic2 also controls the foxA2 expression during Xenopus development. Variant forms of the ZIC2 protein, associated with HPE in man or mouse, are deficient in their ability to influence SMAD-dependent transcription. These findings reveal a new mechanism of NODAL signal transduction in the mammalian node and provide the first molecular explanation of how ZIC2 loss-of-function precipitates HPE.
Beijing, as a representative megacity in China, is experiencing some of the most severe air pollution episodes in the world, and its fast urbanization has led to substantial urban and peri-urban ...disparities in both health status and air quality. Uncertainties remain regarding the possible causal links between individual air pollutants and health outcomes, with spatial comparative investigations of these links lacking, particularly in developing megacities. In light of this challenge, Effects of AIR pollution on cardiopuLmonary disEaSe in urban and peri-urban reSidents in Beijing (AIRLESS) was initiated, with the aim of addressing the complex issue of relating multi-pollutant exposure to cardiopulmonary outcomes. This paper presents the novel methodological framework employed in the project, namely (1) the deployment of two panel studies from established cohorts in urban and peri-urban Beijing, with different exposure settings regarding pollution levels and diverse sources; (2) the collection of detailed measurements and biomarkers of participants from a nested case (hypertensive) and control (healthy) study setting; (3) the assessment of indoor and personal exposure to multiple gaseous pollutants and particulate matter at unprecedented spatial and temporal resolution with validated novel sensor technologies; (4) the assessment of ambient air pollution levels in a large-scale field campaign, particularly the chemical composition of particulate matter. Preliminary results showed that there is a large difference between ambient and personal air pollution levels, and the differences varied between seasons and locations. These large differences were reflected on the different health responses between the two panels.
Less than 20% of cancer patients meet the recommended physical activity (PA) guidelines, partially due to poor knowledge and enforcement/encouragement amongst health-care professionals (HCPs). The ...primary aim of this study was to explore the perceptions of exercise practitioners on the role of PA and the physiological and psychological benefits to recovering cancer patients; the secondary aim was to understand the barriers and facilitators of promoting PA to cancer survivors. The third aim was to, seek the perspectives on the effectiveness of referral systems between the hospitals and PA structures. A purposive sample of five exercise practitioners' (four male and one female) with experience with cancer patients participated in a semi-structured interview (45-60 min). Interviews addressed five key topics: intervention procedures, patient well-being, patient education on PA, effectiveness of referrals from hospitals, and post-intervention PA. Interviews were transcribed verbatim and analysed via thematic analysis. The participants believed that recovering cancer patients possess a knowledge of the physiological benefits of PA, yet psychological understanding remains unknown. Social environments are key to participation in PA and most HCPs lacked knowledge/awareness of the benefits of engaging in PA. There is a need to improve HCPs knowledge of the benefits of PA, whilst providing standardised training on how PA can improve cancer patients' outcomes.
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