Air pollution, traffic noise, mental health, and cognitive development: A multi-exposure longitudinal study of London adolescents in the SCAMP cohort.

BACKGROUND: There is increasing evidence that air pollution and noise may have detrimental psychological impacts, but there are few studies evaluating adolescents, ground-level ozone exposure, multi-exposure models, or metrics beyond outdoor residential exposure. This study aimed to address these gaps. METHODS: Annual air pollution and traffic noise exposure at home and school were modelled for adolescents in the Greater London SCAMP cohort (N=7555). Indoor, outdoor and hybrid environments were modelled for air pollution. Cognitive and mental health measures were self-completed at two timepoints (baseline aged 11-12 and follow-up aged 13-15). Associations were modelled using multi-level multivariate linear or ordinal logistic regression. RESULTS: This is the first study to investigate ground-level ozone exposure in relation to adolescent executive functioning, finding that a 1 interquartile range increase in outdoor ozone corresponded to -0.06 (p < 0.001) z-score between baseline and follow-up, 38 % less improvement than average (median development + 0.16). Exposure to nitrogen dioxide (NO2), 24-hour traffic noise, and particulate matter < 10 µg/m3 (PM10) were also significantly associated with slower executive functioning development when adjusting for ozone. In two-pollutant models, particulate matter and ozone were associated with increased externalising problems. Daytime and evening noise were associated with higher anxiety symptoms, and 24-hour noise with worse speech-in-noise perception (auditory processing). Adjusting for air pollutants, 24-hour noise was also associated with higher anxiety symptoms and slower fluid intelligence development. CONCLUSIONS: Ozone's potentially detrimental effects on adolescent cognition have been overlooked in the literature. Our findings also suggest harmful impacts of other air pollutants and noise on mental health. Further research should attempt to replicate these findings and use mechanistic enquiry to enhance causal inference. Policy makers should carefully consider how to manage the public health impacts of ozone, as efforts to reduce other air pollutants such as NO2 can increase ozone levels, as will the progression of climate change.

The effects of radiofrequency exposure on male fertility: A systematic review of human observational studies with dose-response meta-analysis.

BACKGROUND: The World Health Organization (WHO) is bringing together evidence on radiofrequency electromagnetic field (RF-EMF) exposure in relation to health outcomes, previously identified as priorities for research and evaluation by experts in the field, to inform exposure guidelines. A suite of systematic reviews have been undertaken by a network of topic experts and methodologists to collect, assess and synthesise data relevant to these guidelines. Following the WHO handbook for guideline development and the COSTER conduct guidelines, we systematically reviewed the evidence on the potential effects of RF-EMF exposure on male fertility in human observational studies. METHODS: We conducted a broad and sensitive search for potentially relevant records within the following bibliographic databases: MEDLINE; Embase; Web of Science and EMF Portal. We also conducted searches of grey literature through relevant databases including OpenGrey, and organisational websites and consulted RF-EMF experts. We hand searched reference lists of included study records and for citations of these studies. We included quantitative human observational studies on the effect of RF-EMF exposure in adult male participants on infertility: sperm concentration; sperm morphology; sperm total motility; sperm progressive motility; total sperm count; and time to pregnancy. Titles and abstracts followed by full texts were screened in blinded duplicate against pre-set eligibility criteria with consensus input from a third reviewer as required. Data extraction from included studies was completed by two reviewers, as was risk of bias assessment using the Office of Health Assessment and Translation (OHAT) tool. We conducted a dose-response meta-analysis as possible and appropriate. Certainty of the evidence was assessed by two reviewers using the OHAT GRADE tool with input from a third reviewer as required. RESULTS: We identified nine studies in this review; seven were general public studies (with the general public as the population of interest) and two were occupational studies (with specific workers/workforces as the population of interest). General public studies. Duration of phone use: The evidence is very uncertain surrounding the effects of RF-EMF on sperm concentration (10/6 mL) (MD (mean difference) per hour of daily phone use 1.6 106/mL, 95 % CI -1.7 to 4.9; 3 studies), sperm morphology (MD 0.15 percentage points of deviation of normal forms per hour, 95 % CI -0.21 to 0.51; 3 studies), sperm progressive motility (MD -0.46 percentage points per hour, 95 % CI -1.04 to 0.13; 2 studies) and total sperm count (MD per hour -0.44 106/ejaculate, 95 % CI -2.59 to 1.7; 2 studies) due to very low-certainty evidence. Four additional studies reported on the effect of mobile phone use on sperm motility but were unsuitable for pooling; only one of these studies identified a statistically significant effect. All four studies were at risk of exposure characterisation and selection bias; two of confounding, selective reporting and attrition bias; three of outcome assessment bias and one used an inappropriate statistical method. Position of phone: There may be no or little effect of carrying a mobile phone in the front pocket on sperm concentration, total count, morphology, progressive motility or on time to pregnancy. Of three studies reporting on the effect of mobile phone location on sperm total motility and, or, total motile count, one showed a statistically significant effect. All three studies were at risk of exposure characterisation and selection bias; two of confounding, selective reporting and attrition bias; three of outcome assessment bias and one used inappropriate statistical method. RF-EMF Source: One study indicates there may be little or no effect of computer or other electric device use on sperm concentration, total motility or total count. This study is at probably high risk of exposure characterisation bias and outcome assessment bias. Occupational studies. With only two studies of occupational exposure to RF-EMF and heterogeneity in the population and exposure source (technicians exposed to microwaves or seamen exposed to radar equipment), it was not plausible to statistically pool findings. One study was at probably or definitely high risk of bias across all domains, the other across domains for exposure characterisation bias, outcome assessment bias and confounding. DISCUSSION: The majority of evidence identified was assessing localised RF-EMF exposure from mobile phone use on male fertility with few studies assessing the impact of phone position. Overall, the evidence identified is very uncertain about the effect of RF-EMF exposure from mobile phones on sperm outcomes. One study assessed the impact of other RF-EMF sources on male fertility amongst the general public and two studies assessed the impact of RF-EMF exposure in occupational cohorts from different sources (radar or microwave) on male fertility. Further prospective studies conducted with greater rigour (in particular, improved accuracy of exposure measurement and appropriate statistical method use) would build the existing evidence base and are required to have greater certainty in any potential effects of RF-EMF on male reproductive outcomes. Prospero Registration: CRD42021265401 (SR3A).

The effects of radiofrequency exposure on adverse female reproductive outcomes: A systematic review of human observational studies with dose-response meta-analysis.

BACKGROUND: To inform radiofrequency electromagnetic field (RF-EMF) exposure guidelines the World Health Organization (WHO) is bringing together evidence on RF-EMF in relation to health outcomes prioritised for evaluation by experts in this field. Given this, a network of topic experts and methodologists have conducted a series of systematic reviews collecting, assessing, and synthesising data of relevance to these guidelines. Here we present a systematic review of the effect of RF-EMF exposure on adverse pregnancy outcomes in human observational studies which follows the WHO handbook for guideline development and the COSTER conduct guidelines. METHODS: We conducted a broad, sensitive search for potentially relevant records within the following bibliographic databases: MEDLINE; Embase; and the EMF Portal. Grey literature searches were also conducted through relevant databases (including OpenGrey), organisational websites and via consultation of RF-EMF experts. We included quantitative human observational studies on the effect of RF-EMF exposure in adults' preconception or pregnant women on pre-term birth, small for gestational age (SGA; associated with intrauterine growth restriction), miscarriage, stillbirth, low birth weight (LBW) and congenital anomalies. In blinded duplicate, titles and abstracts then full texts were screened against eligibility criteria. A third reviewer gave input when consensus was not reached. Citation chaining of included studies was completed. Two reviewers' data extracted and assessed included studies for risk of bias using the Office of Health Assessment and Translation (OHAT) tool. Random effects meta-analyses of the highest versus the lowest exposures and dose-response meta-analysis were conducted as appropriate and plausible. Two reviewers assessed the certainty in each body of evidence using the OHAT GRADE tool. RESULTS: We identified 18 studies in this review; eight were general public studies (with the general public as the population of interest) and 10 were occupational studies (with the population of interest specific workers/workforces). General public studies. From pairwise meta-analyses of general public studies, the evidence is very uncertain about the effects of RF-EMF from mobile phone exposure on preterm birth risk (relative risk (RR) 1.14, 95% confidence interval (CI): 0.97-1.34, 95% prediction interval (PI): 0.83-1.57; 4 studies), LBW (RR 1.14, 95% CI: 0.96-1.36, 95% PI: 0.84-1.57; 4 studies) or SGA (RR 1.13, 95% CI: 1.02-1.24, 95% PI: 0.99-1.28; 2 studies) due to very low-certainty evidence. It was not feasible to meta-analyse studies reporting on the effect of RF-EMF from mobile phone exposure on congenital anomalies or miscarriage risk. The reported effects from the studies assessing these outcomes varied and the studies were at some risk of bias. No studies of the general public assessed the impact of RF-EMF exposure on stillbirth. Occupational studies. In occupational studies, based on dose-response meta-analyses, the evidence is very uncertain about the effects of RF-EMF amongst female physiotherapists using shortwave diathermy on miscarriage due to very low-certainty evidence (OR 1.02 95% CI 0.94-1.1; 2 studies). Amongst offspring of female physiotherapists using shortwave diathermy, the evidence is very uncertain about the effects of RF-EMF on the risk of congenital malformations due to very low-certainty evidence (OR 1.4, 95% CI 0.85 to 2.32; 2 studies). From pairwise meta-analyses, the evidence is very uncertain about the effects of RF-EMF on the risk of miscarriage (RR 1.06, 95% CI 0.96 to 1.18; very low-certainty evidence), pre-term births (RR 1.19, 95% CI 0.32 to 4.37; 3 studies; very low-certainty evidence), and low birth weight (RR 2.90, 95% CI: 0.69 to 12.23; 3 studies; very low-certainty evidence). Results for stillbirth and SGA could not be pooled in meta-analyses. The results from the studies reporting these outcomes were inconsistent and the studies were at some risk of bias. DISCUSSION: Most of the evidence identified in this review was from general public studies assessing localised RF-EMF exposure from mobile phone use on female reproductive outcomes. In occupational settings, each study was of heterogenous whole-body RF-EMF exposure from radar, short or microwave diathermy, surveillance and welding equipment and its effect on female reproductive outcomes. Overall, the body of evidence is very uncertain about the effect of RF-EMF exposure on female reproductive outcomes. Further prospective studies conducted with greater rigour (particularly improved accuracy of exposure measurement and using appropriate statistical methods) are required to identify any potential effects of RF-EMF exposure on female reproductive outcomes of interest.

An exploration of having social media influencers deliver a first-line digital intervention to improve body image among adolescent girls: A qualitative study.

Social media influencers are popular among adolescents and could offer a unique way to reach young people at scale with body image interventions. This study explored girls' and influencers' views on having influencers deliver body image interventions through vlogs (video blogs) and to gain insight into their preferred format, content, and views on factors that encourage engagement with vlogs. Twenty-one UK based participants were recruited. Three online focus groups were conducted with adolescent girls (n = 16) aged 14-18 years and one with influencers (n = 5) aged 24-33 years, who had a collective following of over 1.5 million subscribers across social media platforms. Data were analysed using reflexive thematic analysis and four themes were generated: Choosing an influencer whose messages and core values are aligned with the topic of body image; the importance of influencer authenticity and personal experience; collaborating on content creation with mental health professionals; and the need for long-form (i.e., 10-20 min) content to address serious topics. Findings suggest having influencers deliver body image interventions to young people could be a useful approach. Results highlight the need to engage with end users from the outset of intervention development to increase the likelihood of intervention effectiveness and engagement.

A UK framework for the assessment and integration of different scientific evidence streams in chemical risk assessment.

BACKGROUND: Few methods are available for transparently combining different evidence streams for chemical risk assessment to reach an integrated conclusion on the probability of causation. Hence, the UK Committees on Toxicity (COT) and on Carcinogenicity (COC) have reviewed current practice and developed guidance on how to achieve this in a transparent manner, using graphical visualisation. METHODS/APPROACH: All lines of evidence, including toxicological, epidemiological, new approach methodologies, and mode of action should be considered, taking account of their strengths/weaknesses in their relative weighting towards a conclusion on the probability of causation. A qualitative estimate of the probability of causation is plotted for each line of evidence and a combined estimate provided. DISCUSSION/CONCLUSIONS: Guidance is provided on integration of multiple lines of evidence for causation, based on current best practice. Qualitative estimates of probability for each line of evidence are plotted graphically. This ensures a deliberative, consensus conclusion on likelihood of causation is reached. It also ensures clear communication of the influence of the different lines of evidence on the overall conclusion on causality. Issues on which advice from the respective Committees is sought varies considerably, hence the guidance is designed to be sufficiently flexible to meet this need.

Regression calibration of self-reported mobile phone use to optimize quantitative risk estimation in the COSMOS study.

The Cohort Study of Mobile Phone Use and Health (COSMOS) has repeatedly collected self-reported and operator-recorded data on mobile phone use. Assessing health effects using self-reported information is prone to measurement error, but operator data were available prospectively for only part of the study population and did not cover past mobile phone use. To optimize the available data and reduce bias, we evaluated different statistical approaches for constructing mobile phone exposure histories within COSMOS. We evaluated and compared the performance of 4 regression calibration (RC) methods (simple, direct, inverse, and generalized additive model for location, shape, and scale), complete-case analysis, and multiple imputation in a simulation study with a binary health outcome. We used self-reported and operator-recorded mobile phone call data collected at baseline (2007-2012) from participants in Denmark, Finland, the Netherlands, Sweden, and the United Kingdom. Parameter estimates obtained using simple, direct, and inverse RC methods were associated with less bias and lower mean squared error than those obtained with complete-case analysis or multiple imputation. We showed that RC methods resulted in more accurate estimation of the relationship between mobile phone use and health outcomes by combining self-reported data with objective operator-recorded data available for a subset of participants.

Change, Adversity, and Adaptation: Young People's Experience of the COVID-19 Pandemic Expressed through Artwork and Semi-Structured Interviews.

This study explores how young people's mental health was affected by the COVID-19 pandemic using artwork and semi-structured interviews. The mental health impacts of the pandemic are important to understand so that policy and practice professionals can support those affected, prepare and respond to future crises, and support young people who are isolated and restricted in other contexts. Co-designed participatory art workshops and interviews were conducted with 16-18-year-olds (n = 21, 62% female) from the London-based Longitudinal cohort Study of Cognition, Adolescents and Mobile Phones (SCAMP). Artworks and interview transcripts were qualitatively co-and analysed with young people. From interviews, six themes were identified: adaptation, restriction, change, challenges, overcoming adversity, and lockdown life. From the artwork, four themes were identified: trapped, negative mental wellbeing, positive emotions, and technology. Everyday factors such as home environment, social support, hobbies, habits, and online education were key determinants of how challenged and restricted participants felt, and their capacity to overcome this. This demonstrates the importance of wider (social and environmental) determinants and supports a systems-level public health approach to young people's mental health. For example, young people's mental health services should collaborate with other sectors to address such determinants in a holistic way. Clearer guidance and support with occupation, relationships, environment, routine and activities could mitigate the negative mental health impacts of major environmental changes on young people.

Childhood adversities characterize the heterogeneity in the brain pattern of individuals during neurodevelopment.

BACKGROUND: Several factors shape the neurodevelopmental trajectory. A key area of focus in neurodevelopmental research is to estimate the factors that have maximal influence on the brain and can tip the balance from typical to atypical development. METHODS: Utilizing a dissimilarity maximization algorithm on the dynamic mode decomposition (DMD) of the resting state functional MRI data, we classified subjects from the cVEDA neurodevelopmental cohort (n = 987, aged 6-23 years) into homogeneously patterned DMD (representing typical development in 809 subjects) and heterogeneously patterned DMD (indicative of atypical development in 178 subjects). RESULTS: Significant DMD differences were primarily identified in the default mode network (DMN) regions across these groups (p < 0.05, Bonferroni corrected). While the groups were comparable in cognitive performance, the atypical group had more frequent exposure to adversities and faced higher abuses (p < 0.05, Bonferroni corrected). Upon evaluating brain-behavior correlations, we found that correlation patterns between adversity and DMN dynamic modes exhibited age-dependent variations for atypical subjects, hinting at differential utilization of the DMN due to chronic adversities. CONCLUSION: Adversities (particularly abuse) maximally influence the DMN during neurodevelopment and lead to the failure in the development of a coherent DMN system. While DMN's integrity is preserved in typical development, the age-dependent variability in atypically developing individuals is contrasting. The flexibility of DMN might be a compensatory mechanism to protect an individual in an abusive environment. However, such adaptability might deprive the neural system of the faculties of normal functioning and may incur long-term effects on the psyche.

Mobile phone use and brain tumour risk - COSMOS, a prospective cohort study.

BACKGROUND: Each new generation of mobile phone technology has triggered discussions about potential carcinogenicity from exposure to radiofrequency electromagnetic fields (RF-EMF). Available evidence has been insufficient to conclude about long-term and heavy mobile phone use, limited by differential recall and selection bias, or crude exposure assessment. The Cohort Study on Mobile Phones and Health (COSMOS) was specifically designed to overcome these shortcomings. METHODS: We recruited participants in Denmark, Finland, the Netherlands, Sweden, and the UK 2007-2012. The baseline questionnaire assessed lifetime history of mobile phone use. Participants were followed through population-based cancer registers to identify glioma, meningioma, and acoustic neuroma cases during follow-up. Non-differential exposure misclassification was reduced by adjusting estimates of mobile phone call-time through regression calibration methods based on self-reported data and objective operator-recorded information at baseline. Hazard ratios (HR) and 95% confidence intervals (CI) for glioma, meningioma, and acoustic neuroma in relation to lifetime history of mobile phone use were estimated with Cox regression models with attained age as the underlying time-scale, adjusted for country, sex, educational level, and marital status. RESULTS: 264,574 participants accrued 1,836,479 person-years. During a median follow-up of 7.12 years, 149 glioma, 89 meningioma, and 29 incident cases of acoustic neuroma were diagnosed. The adjusted HR per 100 regression-calibrated cumulative hours of mobile phone call-time was 1.00 (95 % CI 0.98-1.02) for glioma, 1.01 (95 % CI 0.96-1.06) for meningioma, and 1.02 (95 % CI 0.99-1.06) for acoustic neuroma. For glioma, the HR for ≥ 1908 regression-calibrated cumulative hours (90th percentile cut-point) was 1.07 (95 % CI 0.62-1.86). Over 15 years of mobile phone use was not associated with an increased tumour risk; for glioma the HR was 0.97 (95 % CI 0.62-1.52). CONCLUSIONS: Our findings suggest that the cumulative amount of mobile phone use is not associated with the risk of developing glioma, meningioma, or acoustic neuroma.

Depression and Anxiety in Adolescents During the COVID-19 Pandemic in Relation to the Use of Digital Technologies: Longitudinal Cohort Study.

BACKGROUND: Adolescents are susceptible to mental illness and have experienced substantial disruption owing to the COVID-19 pandemic. The digital environment is increasingly important in the context of a pandemic when in-person social connection is restricted. OBJECTIVE: This study aims to estimate whether depression and anxiety had worsened compared with the prepandemic period and examine potential associations with sociodemographic characteristics and behavioral factors, particularly digital behaviors. METHODS: We analyzed cross-sectional and longitudinal data from a large, representative Greater London adolescent cohort study: the Study of Cognition, Adolescents and Mobile Phones (SCAMP). Participants completed surveys at T1 between November 2016 and July 2018 (N=4978; aged 13 to 15 years) and at T2 between July 2020 and June 2021 (N=1328; aged 16 to 18 years). Depression and anxiety were measured using the Patient Health Questionnaire and Generalized Anxiety Disorder scale, respectively. Information on the duration of total mobile phone use, social network site use, and video gaming was also collected using questionnaires. Multivariable logistic regression was used to assess the cross-sectional and longitudinal associations of sociodemographic characteristics, digital technology use, and sleep duration with clinically significant depression and anxiety. RESULTS: The proportion of adolescents who had clinical depression and anxiety significantly increased at T2 (depression: 140/421, 33.3%; anxiety: 125/425, 29.4%) compared with the proportion of adolescents at T1 (depression: 57/421, 13.5%; anxiety: 58/425, 13.6%; P for 2-proportion z test <.001 for both depression and anxiety). Depression and anxiety levels were similar between the summer holiday, school opening, and school closures. Female participants had higher odds of new incident depression (odds ratio [OR] 2.5, 95% CI 1.5-4.18) and anxiety (OR 2.11, 95% CI 1.23-3.61) at T2. A high level of total mobile phone use at T1 was associated with developing depression at T2 (OR 1.89, 95% CI 1.02-3.49). Social network site use was associated with depression and anxiety cross-sectionally at T1 and T2 but did not appear to be associated with developing depression or anxiety longitudinally. Insufficient sleep at T1 was associated with developing depression at T2 (OR 2.26, 95% CI 1.31-3.91). CONCLUSIONS: The mental health of this large sample of adolescents from London deteriorated during the pandemic without noticeable variations relating to public health measures. The deterioration was exacerbated in girls, those with preexisting high total mobile phone use, and those with preexisting disrupted sleep. Our findings suggest the necessity for allocating resources to address these modifiable factors and target high-risk groups.

Cholangiocarcinoma across England: Temporal changes in incidence, survival and routes to diagnosis by region and level of socioeconomic deprivation.

Background & Aims: While cholangiocarcinoma (CCA) incidence and mortality rates are increasing globally, whether there are regional/temporal variations in these rates for different biliary tract cancer (BTC) subtypes, or whether they differ by sex, socioeconomic status, or route to diagnosis (RtD) remains unknown. In this work, we aimed to perform an in-depth analysis of data on the incidence, mortality, survival and RtD of CCA and other BTCs. Methods: Data on all BTCs diagnosed in England between 2001 and 2018 were extracted from NHS Digital's National Cancer Registration Dataset. Age-standardised incidence rates (ASRs), mortality rates (ASMRs) and net survival rates were calculated, and Kaplan-Meier overall survival estimates and RtD trends were analysed. Analyses were stratified by sex, socioeconomic deprivation, tumour subtype and region. Results: The ASR for CCA rose from 2.9 in 2001-2003 to 4.6 in 2016-2018 and from 1.0 to 1.8 for gallbladder cancers (GBCs). ASMR trends mirror those of incidence, with most deaths due to iCCA. Over 20% of patients with CCA were under 65 years old. The ASRs and ASMRs were consistently higher in the most socioeconomically deprived group for CCA and GBC. The most common RtD was the emergency route (CCA 49.6%, GBC 46.2% and ampulla of Vater cancer 43.0%). The least deprived patients with CCA and ampulla of Vater cancer had better overall survival (p <0.001). Net survival rates rose for all BTCs, with 3-year net survival for CCA increasing from 9.2% in 2001 to 12.6% in 2016-2018. There was notable geographical variation in ASRs, ASMRs and net survival for all BTCs. Conclusions: BTC incidence and mortality rates are increasing, with differences observed between tumour types, socioeconomic deprivation groups, RtDs and geographical regions. This highlights the need for targeted interventions, earlier diagnosis and better awareness of this condition amongst the public and healthcare professionals. Impact and implications: Cholangiocarcinoma (CCA) incidence and mortality rates are rising globally, particularly for intrahepatic CCA. However, it has not previously been reported if, within a single country, there are temporal and regional differences in incidence, mortality and survival rates for different biliary tract subtypes, and whether these differ by sex, socioeconomic status, or route of diagnosis. In this study we show that mortality rates for patients with CCA continue to rise and are almost 40% higher in the most socioeconomically deprived compared to the least; additionally, we observed regional variation within England in incidence, mortality and survival. This study is relevant to researchers and policy makers as it highlights regional variation and inequality, as well as emphasising the need for earlier diagnosis and better awareness of this condition amongst the public and healthcare professionals.

Headache in the international cohort study of mobile phone use and health (COSMOS) in the Netherlands and the United Kingdom.

Headache is a common condition with a substantial burden of disease worldwide. Concerns have been raised over the potential impact of long-term mobile phone use on headache due to radiofrequency electromagnetic fields (RF-EMFs). We explored prospectively the association between mobile phone use at baseline (2009-2012) and headache at follow-up (2015-2018) by analysing pooled data consisting of the Dutch and UK cohorts of the Cohort Study of Mobile Phone Use and Health (COSMOS) (N = 78,437). Frequency of headache, migraine, and information on mobile phone use, including use of hands-free devices and frequency of texting, were self-reported. We collected objective operator data to obtain regression calibrated estimates of voice call duration. In the model mutually adjusted for call-time and text messaging, participants in the high category of call-time showed an adjusted odds ratio (OR) of 1.04 (95 % CI: 0.94-1.15), with no clear trend of reporting headache with increasing call-time. However, we found an increased risk of weekly headache (OR = 1.40, 95 % CI: 1.25-1.56) in the high category of text messaging, with a clear increase in reporting headache with increasing texting. Due to the negligible exposure to RF-EMFs from texting, our results suggest that mechanisms other than RF-EMFs are responsible for the increased risk of headache that we found among mobile phone users.

Salivary androgens in adolescence and their value as a marker of puberty: results from the SCAMP cohort.

Context: Salivary androgens represent non-invasive biomarkers of puberty that may have utility in clinical and population studies. Objective: To understand normal age-related variation in salivary sex steroids and demonstrate their correlation to pubertal development in young adolescents. Design, setting and participants: School-based cohort study of 1495 adolescents at two time points for collecting saliva samples approximately 2 years apart. Outcome measures: The saliva samples were analyzed for five androgens (testosterone, androstenedione (A4), 17-hydroxyprogesterone, 11-ketotestosterone and 11ß-hydroxyandrostenedione) using liquid chromatography-mass spectrometry; in addition, salivary dehydroepiandrosterone (DHEA) and oestradiol (OE2) were analysed by ELISA. The pubertal staging was self-reported using the Pubertal Development Scale (PDS). Results: In 1236 saliva samples from 903 boys aged between 11 and 16 years, salivary androgens except DHEA exhibited an increasing trend with an advancing age (ANOVA, P < 0.001), with salivary testosterone and A4 concentration showing the strongest correlation (r = 0.55, P < 0.001 and r = 0.48, P < 0.001, respectively). In a subgroup analysis of 155 and 63 saliva samples in boys and girls, respectively, morning salivary testosterone concentrations showed the highest correlation with composite PDS scores and voice-breaking category from PDS self-report in boys (r = 0.75, r = 0.67, respectively). In girls, salivary DHEA and OE2 had negligible correlations with age or composite PDS scores. Conclusion: In boys aged 11-16 years, an increase in salivary testosterone and A4 is associated with self-reported pubertal progress and represents valid non-invasive biomarkers of puberty in boys.

Ambient temperature and mental health: a systematic review and meta-analysis.

BACKGROUND: Increasing evidence indicates that ambient outdoor temperature could affect mental health, which is especially concerning in the context of climate change. We aimed to comprehensively analyse the current evidence regarding the associations between ambient temperature and mental health outcomes. METHODS: We did a systematic review and meta-analysis of the evidence regarding associations between ambient outdoor temperature and changes in mental health outcomes. We searched WebOfScience, Embase, PsychINFO, and PubMed for articles published from database origin up to April 7, 2022. Eligible articles were epidemiological, observational studies in humans of all ages, which evaluated real-world responses to ambient outdoor temperature, and had mental health as a documented outcome; studies of manipulated or controlled temperature or those with only physical health outcomes were excluded. All eligible studies were synthesised qualitatively. If three or more studies reported the same or equivalent effect statistics and if they had equivalent exposure, outcome, and metrics, the studies were pooled in a random-effects meta-analysis. The risk of bias for individual studies was assessed using the Newcastle-Ottawa Scale. The quality of evidence across studies was assessed using the Office of Health Assessment and Translation (OHAT) approach. FINDINGS: 114 studies were included in the systematic review, of which 19 were suitable for meta-analysis. Three meta-analyses were conducted for suicide outcomes: a 1°C increase in mean monthly temperature was associated with an increase in incidence of 1·5% (95% CI 0·8-2·2, p<0·001; n=1 563 109, seven effects pooled from three studies); a 1°C increase in mean daily temperature was associated with an increase in incidence of 1·7% (0·3-3·0, p=0·014; n=113 523, five effects pooled from five studies); and a 1°C increase in mean monthly temperature was associated with a risk ratio of 1·01 (95% CI 1·00-1·01, p<0·001; n=111 794, six effects pooled from three studies). Three meta-analyses were conducted for hospital attendance or admission for mental illness: heatwaves versus non-heatwave periods were associated with an increase in incidence of 9·7% (95% CI 7·6-11·9, p<0·001; n=362 086, three studies); the risk ratio at the 99th percentile of daily mean temperature compared with the 50th percentile was 1·02 (95% CI 1·01-1·03, p=0·006; n=532 296, three studies); and no significant association was found between a 10°C increase in daily mean temperature and hospital attendance. In a qualitative narrative synthesis, we found that ambient outdoor temperature (including absolute temperatures, temperature variability, and heatwaves) was positively associated with attempted and completed suicides (86 studies), hospital attendance or admission for mental illness (43 studies), and worse outcomes for community mental health and wellbeing (19 studies), but much of the evidence was of low certainty with high heterogeneity. INTERPRETATION: Increased temperature and temperature variability could be associated with increased cases of suicide and suicidal behaviour, hospital attendance or admission for mental illness, and poor community health and wellbeing. Climate change is likely to increase temperature anomalies, variability, and heatwaves as well as average temperatures; as such, health system leaders and policy makers must be adequately prepared and should develop adaptation strategies. More high-quality, standardised research is required to improve our understanding of these effects. FUNDING: None.

Regional variation in routes to diagnosis of cholangiocarcinoma in England from 2006 to 2017.

BACKGROUND: Incidence of cholangiocarcinoma (CCA) is rising, with overall prognosis re-maining very poor. Reasons for the high mortality of CCA include its late presentation in most patients, when curative options are no longer feasible, and poor response to systemic therapies for advanced disease. Late presentation presents a large barrier to improving outcomes and is often associated with diagnosis via mergency presentation (EP). Earlier diagnoses may be made by Two Week Wait (TWW) referrals through General practitioner (GP). We hypothesise that TWW referrals and EP routes to diagnosis differ across regions in England. AIM: To investigate routes to diagnosis of CCA over time, regional variation and influencing factors. METHODS: We linked patient records from the National Cancer Registration Dataset to Hospital Episode Statistics, Cancer Waiting Times and Cancer Screening Programme datasets to define routes to diagnosis and certain patient characteristics for patients diagnosed 2006-2017 in England. We used linear probability models to investigate geographic variation by assessing the proportions of patients diagnosed via TWW referral or EP across Cancer Alliances in England, adjusting for potential confounders. Correlation between the proportion of people diagnosed by TWW referral and EP was investigated with Spearman's correlation coefficient. RESULTS: Of 23632 patients diagnosed between 2006-2017 in England, the most common route to diagnosis was EP (49.6%). Non-TWW GP referrals accounted for 20.5% of diagnosis routes, 13.8% were diagnosed by TWW referral, and the remainder 16.2% were diagnosed via an 'other' or Unknown route. The proportion diagnosed via a TWW referral doubled between 2006-2017 rising from 9.9% to 19.8%, conversely EP diagnosis route declined, falling from 51.3% to 46.0%. Statistically significant variation in both the TWW referral and EP proportions was found across Cancer Alliances. Age, presence of comorbidity and underlying liver disease were independently associated with both a lower proportion of patients diagnosed via TWW referral, and a higher proportion diagnosed by EP after adjusting for other potential confounders. CONCLUSION: There is significant geographic and socio-demographic variation in routes to diagnosis of CCA in England. Knowledge sharing of best practice may improve diagnostic pathways and reduce unwarranted variation.

Neurocognitive Analysis of Low-level Arsenic Exposure and Executive Function Mediated by Brain Anomalies Among Children, Adolescents, and Young Adults in India.

Importance: Arsenic, a contaminant of groundwater and irrigated crops, is a global public health hazard. Exposure to low levels of arsenic through food extends well beyond the areas with high arsenic content in water. Objective: To identify cognitive impairments following commonly prevalent low-level arsenic exposure and characterize their underlying brain mechanisms. Design, Setting, and Participants: This multicenter population-based cohort study analyzed cross-sectional data of the Indian Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA) cohort, recruited between November 4, 2016, and May 4, 2019. Participants aged 6 to 23 years were characterized using deep phenotyping measures of behavior, neuropsychology, psychopathology, brain neuroimaging, and exposure to developmental adversities and environmental neurotoxins. All analyses were performed between June 1, 2020, and December 31, 2021. Exposure: Arsenic levels were measured in urine as an index of exposure. Main Outcomes and Measures: Executive function measured using the cVEDA neuropsychological battery, gray matter volume (GMV) from T1-weighted magnetic resonance imaging, and functional network connectivity measures from resting state functional magnetic resonance imaging. Results: A total of 1014 participants aged 6 to 23 years (589 male [58.1%]; mean [SD] age, 14.86 [4.79] years) were included from 5 geographic locations. Sparse-partial least squares analysis was used to describe a negative association of arsenic exposure with executive function (r = -0.12 [P = 5.4 × 10-4]), brain structure (r = -0.20 [P = 1.8 × 10-8]), and functional connectivity (within network, r = -0.12 [P = 7.5 × 10-4]; between network, r = -0.23 [P = 1.8 × 10-10]). Alterations in executive function were partially mediated by GMV (b = -0.004 [95% CI, -0.007 to -0.002]) and within-network functional connectivity (b = -0.004 [95% CI, -0.008 to -0.002]). Socioeconomic status and body mass index moderated the association between arsenic and GMV, such that the association was strongest in participants with lower socioeconomic status and body mass index. Conclusions and Relevance: The findings of this cross-sectional study suggest that low-level arsenic exposure was associated with alterations in executive functioning and underlying brain correlates. These results indicate potential detrimental consequences of arsenic exposure that are below the currently recommended guidelines and may extend beyond endemic risk areas. Precision medicine approaches to study global mental health vulnerabilities highlight widespread but potentially modifiable risk factors and a mechanistic understanding of the impact of low-level arsenic exposure on brain development.

Changes in life expectancy and house prices in London from 2002 to 2019: hyper-resolution spatiotemporal analysis of death registration and real estate data.

Background: London has outperformed smaller towns and rural areas in terms of life expectancy increase. Our aim was to investigate life expectancy change at very-small-area level, and its relationship with house prices and their change. Methods: We performed a hyper-resolution spatiotemporal analysis from 2002 to 2019 for 4835 London Lower-layer Super Output Areas (LSOAs). We used population and death counts in a Bayesian hierarchical model to estimate age- and sex-specific death rates for each LSOA, converted to life expectancy at birth using life table methods. We used data from the Land Registry via the real estate website Rightmove (www.rightmove.co.uk), with information on property size, type and land tenure in a hierarchical model to estimate house prices at LSOA level. We used linear regressions to summarise how much life expectancy changed in relation to the combination of house prices in 2002 and their change from 2002 to 2019. We calculated the correlation between change in price and change in sociodemographic characteristics of the resident population of LSOAs and population turnover. Findings: In 134 (2.8%) of London's LSOAs for women and 32 (0.7%) for men, life expectancy may have declined from 2002 to 2019, with a posterior probability of a decline >80% in 41 (0.8%, women) and 14 (0.3%, men) LSOAs. The life expectancy increase in other LSOAs ranged from <2 years in 537 (11.1%) LSOAs for women and 214 (4.4%) for men to >10 years in 220 (4.6%) for women and 211 (4.4%) for men. The 2.5th-97.5th-percentile life expectancy difference across LSOAs increased from 11.1 (10.7-11.5) years in 2002 to 19.1 (18.4-19.7) years for women in 2019, and from 11.6 (11.3-12.0) years to 17.2 (16.7-17.8) years for men. In the 20% (men) and 30% (women) of LSOAs where house prices had been lowest in 2002, mainly in east and outer west London, life expectancy increased only in proportion to the rise in house prices. In contrast, in the 30% (men) and 60% (women) most expensive LSOAs in 2002, life expectancy increased solely independently of price change. Except for the 20% of LSOAs that had been most expensive in 2002, LSOAs with larger house price increases experienced larger growth in their population, especially among people of working ages (30-69 years), had a larger share of households who had not lived there in 2002, and improved their rankings in education, poverty and employment. Interpretation: Large gains in area life expectancy in London occurred either where house prices were already high, or in areas where house prices grew the most. In the latter group, the increases in life expectancy may be driven, in part, by changing population demographics. Funding: Wellcome Trust; UKRI (MRC); Imperial College London; National Institutes of Health Research.

Growth trajectories for executive and social cognitive abilities in an Indian population sample: Impact of demographic and psychosocial determinants.

Cognitive abilities are markers of brain development and psychopathology. Abilities, across executive, and social domains need better characterization over development, including factors that influence developmental change. This study is based on the cVEDA [Consortium on Vulnerability to Externalizing Disorders and Addictions] study, an Indian population based developmental cohort. Verbal working memory, visuo-spatial working memory, response inhibition, set-shifting, and social cognition (faux pas recognition and emotion recognition) were cross-sectionally assessed in > 8000 individuals over the ages 6-23 years. There was adequate representation across sex, urban-rural background, psychosocial risk (psychopathology, childhood adversity and wealth index, i.e. socio-economic status). Quantile regression was used to model developmental change. Age-based trajectories were generated, along with examination of the impact of determinants (sex, childhood adversity, and wealth index). Development in both executive and social cognitive abilities continued into adulthood. Maturation and stabilization occurred in increasing order of complexity, from working memory to inhibitory control to cognitive flexibility. Age related change was more pronounced for low quantiles in response inhibition (ß∼4 versus  -1 versus -0.25 for lower quantiles). Wealth index had the largest influence on developmental change across cognitive abilities. Sex differences were prominent in response inhibition, set-shifting and emotion recognition. Childhood adversity had a negative influence on cognitive development. These findings add to the limited literature on patterns and determinants of cognitive development. They have implications for understanding developmental vulnerabilities in young persons, and the need for providing conducive socio-economic environments.