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The use of ionising radiation (IR) for medical diagnosis and treatment procedures has had a major impact on the survival of paediatric patients. Although the benefits of these techniques lead to efficient health care, evaluation of potential associated long-term health effects is required. HARMONIC aims to better understand the increased risk of cancer and non-cancer effects after exposure to medical IR in children with cancer treated with modern external beam radiotherapy (EBRT) – radiation energy in MeV range – and in children with cardiac defects diagnosed and treated with cardiac fluoroscopy procedures (CFP) – radiation energy in keV range. The project investigates, among survivors of paediatric cancer, potential endocrine dysfunction, cardiovascular and neurovascular damage, health-related quality of life and second (and subsequent) primary cancer (SPC). The cardiac component builds a pooled cohort of approximately 90 000 paediatric patients who underwent CFP during childhood and adolescence to investigate cancer risk following exposure to IR and explore the potential effects of conditions predisposing to cancer. HARMONIC develops software tools to allow dose reconstruction in both EBRT and CFP to enable epidemiological investigations and future optimisation of treatments. With the creation of a biobank of blood and saliva samples, HARMONIC aims to provide a mechanistic understanding of radiation-induced adverse health effects and identify potential biomarkers that can predict these effects.

Background: The current demographic transition has resulted in the growth of the older population in India, a population group which has a higher chance of being affected by multimorbidity and its subsequent healthcare and economic consequences. However, little attention has been paid to the dual effect of mental health conditions and physical multimorbidity in India. The present study, therefore, aimed to analyse the moderating effects of mental health and health insurance ownership in the association between physical multimorbidity and healthcare utilisation and catastrophic health expenditure (CHE)., Methods: We analysed the Longitudinal Aging Study in India, wave 1 (2017-2018). We determined physical multimorbidity by assessing the number of physical conditions. We built multivariable logistic regression models to determine the moderating effect of mental health and health insurance ownership in the association between the number of physical conditions and healthcare utilisation and CHE. Wald tests were used to evaluate if the estimated effects differ across groups defined by the moderating variables., Results: Overall, around one-quarter of adults aged 45 and above had physical multimorbidity, one-third had a mental health condition and 20.5% owned health insurance. Irrespective of having a mental condition and health insurance, physical multimorbidity was associated with increased utilisation of healthcare and CHE. Having an additional mental condition strengthened the adverse effect of physical multimorbidity on increased inpatient service use and experience of CHE. Having health insurance, on the other hand, attenuated the effect of experiencing CHE, indicating a protective effect., Conclusions: The coexistence of mental health conditions in people with physical multimorbidity increases the demands of healthcare service utilisation and can lead to CHE. The findings point to the need for multidisciplinary interventions for individuals with physical multimorbidity, ensuring their mental health needs are also addressed. Our results urge enhancing health insurance schemes for individuals with mental and physical multimorbidity., (© 2024. The Author(s).)

The importance of the social environment and social inequalities in disease etiology is well-known due to the profound research and conceptual framework on social determinants of health. For a long period, in exposome research with its classical orientation towards detrimental health effects of biological, chemical, and physical exposures, this knowledge remained underrepresented. But currently it gains great awareness and calls for innovations in rethinking the role of social environmental health determinants. To fill this gap that exists in terms of the social domain within exposome research, we propose a novel conceptual framework of the Social Exposome, to integrate the social environment in conjunction with the physical environment into the exposome concept. The iterative development process of the Social Exposome was based on a systematic compilation of social exposures in order to achieve a holistic portrayal of the human social environment - including social, psychosocial, socioeconomic, sociodemographic, local, regional, and cultural aspects, at individual and contextual levels. In order to move the Social Exposome beyond a mere compilation of exposures, three core principles are emphasized that underly the interplay of the multitude of exposures: Multidimensionality, Reciprocity, and Timing and continuity. The key focus of the conceptual framework of the Social Exposome is on understanding the underlying mechanisms that translate social exposures into health outcomes. In particular, insights from research on health equity and environmental justice have been incorporated to uncover how social inequalities in health emerge, are maintained, and systematically drive health outcomes. Three transmission pathways are presented: Embodiment, Resilience and Susceptibility or Vulnerability, and Empowerment. The Social Exposome conceptual framework may serve as a strategic map for, both, research and intervention planning, aiming to further explore the impact of the complex social environment and to alter transmission pathways to minimize health risks and health inequalities and to foster equity in health., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Inappropriate ventilator settings, non-adherence to a lung-protective ventilation strategy, and inadequate patient monitoring during mechanical ventilation can potentially expose critically ill children to additional risks. We set out to improve team theoretical knowledge and practical skills regarding pediatric mechanical ventilation and to increase compliance with treatment goals., Methods: An educational initiative was conducted from August 2019 to July 2021 in a neonatal and pediatric intensive care unit of the University Children's Hospital, Hamburg-Eppendorf, Germany. We tested baseline theoretical knowledge using a multiple choice theory test (TT) and practical skills using a practical skill test (PST), consisting of four sequential Objective Structured Clinical Examinations of physicians and nurses. We then implemented an educational bundle that included video self-training, checklists, pocket cards, and reevaluated team performance. Ventilators and monitor settings were randomly checked in all ventilated patients. We used a process control chart and a mixed-effects model to analyze the primary outcome., Results: A total of 47 nurses and 20 physicians underwent assessment both before and after the implementation of the initiative using TT. Additionally, 34 nurses and 20 physicians were evaluated using the PST component of the initiative. The findings revealed a significant improvement in staff performance for both TT and PST (TT: 80% [confidence interval (CI): 77.2-82.9] vs. 86% [CI: 83.1-88.0]; PST: 73% [CI: 69.7-75.5] vs. 95% [CI: 93.8-97.1]). Additionally, there was a notable increase in self-confidence among participants, and compliance with mechanical ventilation treatment goals also saw a substantial rise, increasing from 87.8% to 94.5%., Discussion: Implementing a pediatric mechanical ventilation education bundle improved theoretical knowledge and practical skills among interprofessional pediatric intensive care staff and increased treatment goal compliance in ventilated children., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Severe nuclear accidents may lead to a release of radioactivity, including radioactive iodine, into the environment. The thyroid gland in the human body needs natural or stable iodine to function properly and this iodine is normally absorbed in small quantities from food. Following a release of radioactive iodine from a nuclear or radiological accident, the body will absorb and accumulate the radioactive iodine in the thyroid gland. This increases the risk of thyroid cancer, especially in children. Since the thyroid gland cannot distinguish between radioactive and stable iodine, stable iodine can be taken to prevent the absorption of radioiodine by the thyroid in the event of a nuclear emergency. This is referred to as Iodine Thyroid Blocking (ITB). In 2017, the World Health Organization published revised guidelines entitled 'Iodine Thyroid Blocking: guidelines for use in planning for and responding to radiological and nuclear emergencies'. The purpose of these guidelines is to support Member States in planning for and implementation of ITB before and during a radiation emergency. To enable the monitoring and measurement of the impact of a specific recommended intervention, a baseline should be established against which the impact will be measured over a certain period of time. With that in mind, a global WHO survey of national policies on ITB was carried out in 2016-2017. Here, an overview of some core findings of this survey is provided., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Ltd.)

Objective: To obtain insights into the perceptions of barriers and facilitators to implementation of the WHO Framework Convention on Tobacco Control (FCTC) among smokeless tobacco (SLT) supply chain actors in the Khyber Pakhtunkhwa province of Pakistan., Methods: We conducted a qualitative study to investigate the perceptions about SLT control policy formulation and implementation among exclusive Naswar sellers and point of sale vendors. We conducted five focus group discussions in three districts of Khyber Pakhtunkhwa using combined deductive-inductive thematic analyses., Results: We identified three central themes that potentially impact policy formulation, its implementation and application. The first theme examines the role of children in the Naswar business: as potential customers, and as potential heirs to a Naswar-selling business. A second theme targets the 'business of Naswar', which includes a specific identity of Naswar sellers, its potential to generate profits and the special case of Naswar regulation as a socially accepted and culturally rooted product. The third theme addresses the unusual ingredients of Naswar and its production process, making Naswar a health risk for consumers and producers. We also report conflicting views regarding SLT control among the supply chain actors., Conclusions: This study provides insights into the perceptions of important SLT supply-side stakeholders regarding various SLT control policy options based on the FCTC. While there is some opposition to policy approaches like taxation and switching of business, implementing a ban on selling SLT to minors may be a viable option for policymakers in the short term., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The HARMONIC project (Health Effects of Cardiac Fluoroscopy and Modern Radiotherapy in Paediatrics) is a European study aiming to improve our understanding of the long-term health risks from radiation exposures in childhood and early adulthood. Here, we present the study design for the cardiac fluoroscopy component of HARMONIC. A pooled cohort of approximately 100 000 patients who underwent cardiac fluoroscopy procedures in Belgium, France, Germany, Italy, Norway, Spain or the UK, while aged under 22 years, will be established from hospital records and/or insurance claims data. Doses to individual organs will be estimated from dose indicators recorded at the time of examination, using a lookup-table-based dosimetry system produced using Monte Carlo radiation transport simulations and anatomically realistic computational phantom models. Information on beam geometry and x-ray energy spectra will be obtained from a representative sample of radiation dose structured reports. Uncertainties in dose estimates will be modelled using 2D Monte Carlo methods. The cohort will be followed up using national registries and insurance records to determine vital status and cancer incidence. Information on organ transplantation (a major risk factor for cancer development in this patient group) and/or other conditions predisposing to cancer will be obtained from national or local registries and health insurance data, depending on country. The relationship between estimated radiation dose and cancer risk will be investigated using regression modelling. Results will improve information for patients and parents and aid clinicians in managing and implementing changes to reduce radiation risks without compromising medical benefits., (Creative Commons Attribution license.)

Objectives: To determine cancer mortality compared with the general population and to examine dose-response relationships between cumulative occupational radiation dose and specific cancer outcomes in the German aircrew cohort., Methods: For a cohort of 26 846 aircrew personnel, standardised mortality ratios (SMR) were calculated. Dose-response analyses were carried out using Poisson regression to assess dose-related cancer risks for the period 1960-2014. Exposure assessment comprises recently available dose register data for all cohort members and newly estimated retrospective cabin crew doses for 1960-2003., Results: SMR for all-cause, specific cancer groups and most individual cancers were reduced in all aircrew groups. The only increases were seen for brain cancer in pilots (n=23, SMR 2.01, 95% CI 1.15 to 3.28) and for malignant melanoma (n=10, SMR 1.88, 95% CI 0.78 to 3.85). Breast cancer mortality among female cabin crew was similar to the general population (n=71, SMR 1.06, 95% CI 0.77 to 1.44). Overall median cumulative effective dose was 34.2 mSv (max: 116 mSv) for 1960-2014. No dose-response associations were seen in any of the models. For brain cancer, relative risks were elevated across dose categories. An indicative negative trend with increasing dose category was seen for large intestine cancer in female cabin crew (n=23)., Conclusions: There was no evidence for significant dose-response patterns for the considered cancer types. Interpretation of results remains difficult as cumulative dose is closely related to age. Future work should focus on investigating radiation jointly with other risk factors that may contribute to risks for specific cancers among aircrew., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Ambient air pollution is a long-standing and significant public health issue. The aim of this review is to systematically examine the peer-reviewed evidence on social inequalities and ambient air pollution in the World Health Organization European Region. Articles published between 2010 and 2017 were analyzed in the review. In total 31 articles were included in the review. There is good evidence from ecological studies that higher deprivation indices and low economic position are usually linked with higher levels of pollutants such as particulate matter (particulate matter under 2.5 and 10 microns in diameter, PM 2.5 , PM 10 ) and oxides of nitrogen (e.g., NO 2 , and NO x ). There is also evidence that ethnic minorities experience a mixed exposure in comparison to the majority population being sometimes higher and sometimes lower depending on the ethnic minority under consideration. The studies using data at the individual level in this review are mainly focused on pregnant women or new mothers, in these studies deprivation and ethnicity are more likely to be linked to higher exposures of poor air quality. Therefore, there is evidence in this review that the burden of higher pollutants falls disproportionally on different social groups.

Residential green and blue spaces and their potential health benefits have received increasing attention in the context of environmental health inequalities, because an unequal social distribution of these resources may contribute to inequalities in health outcomes. This systematic review synthesised evidence of environmental inequalities, focusing on availability and accessibility measures of green and blue spaces. Studies in the World Health Organisation (WHO) European Region published between 2010 and 2017 were considered for the review. In total, 14 studies were identified, where most of them ( n = 12) analysed inequalities of green spaces. The majority had an ecological study design that mostly applied deprivation indices on the small area level, whereas cross-sectional studies on the individual level mostly applied single social measures. Ecological studies consistently showed that deprived areas had lower green space availability than more affluent areas, whereas mixed associations were found for single social dimensions in cross-sectional studies on the individual level. In order to gain more insights into how various social dimensions are linked to the distribution of environmental resources within the WHO European Region, more studies are needed that apply comparable methods and study designs for analysing social inequalities in environmental resources.

Environmental noise is an important public health problem, being among the top environmental risks to health. The burden of noise exposure seems to be unequally distributed in societies. Up to now there is fragmentary evidence regarding which social groups are most affected. The aim of this review was to systematically assess published evidence on social inequalities in environmental noise exposure in the WHO European Region, taking different sociodemographic and socioeconomic dimensions as well as subjective and objective measures of environmental noise exposure into account. Articles published in English in a peer reviewed journal between 2010 and 2017 were included in the review. Eight studies were finally included in the review, four of them analysed aggregated data and four analysed individual data. Though results of social inequalities in noise exposures were mixed between and within studies, there was a trend that studies using indicators of material deprivation and deprivation indices showed higher environmental noise exposures in groups with lower socioeconomic position. More research on the social distribution of environmental noise exposure on a small spatial scale is needed, taking into account aspects of vulnerability and procedural justice.

Objective: In Germany, there is a lack of information on the correlation between tobacco use by adolescents and their utilization of medical care. The aim of this article is to identify possible early consequences of adolescent smoking., Methods: We conducted a re-analysis of cross-sectional data of the baseline wave (2003-2006) of the German Health Survey for Children and Adolescents (KiGGS). To examine the association between current smoking status and utilization of medical care during the 12 months before the interview, prevalence of selected diseases was calculated, and stratified by smoking status. Besides, the proportion of adolescents who consulted a physician at least once and the total number of medical consultations were estimated. For the inpatient setting, information about the number of nights spent in a hospital was analyzed. In a multiple logistic regression, the association of smoking behavior with utilization of outpatient medical care was assessed, further adjusting for sociodemographic variables and comorbidities., Results: The study population included 3 679 adolescents aged between 14 and 17 years. 49.1% were female and 31.7% were current smokers. Among smokers, there was an increased prevalence of cystitis (+87.0%) and bronchitis (+50.0%). Tobacco users consulted a general practitioner more frequently than non-smokers (+30.8%). As far as medical specialists are concerned, there were more consultations with psychiatrists (+171.4%) and psychologists (+94.4%), but there was no increase in the total number of visits. Additionally, smoking adolescents were more frequently hospitalized (+26.5%) and the stays were of longer duration (+19.7%). There was a statistically significant association between current tobacco use and a greater utilization of medical care (OR=1.20; 95%-CI: 1.02-1.40)., Conclusions: Tobacco use among adolescents was associated with increased prevalence of certain diseases and a greater utilization of medical care. Nevertheless, whether there is a causal connection is still debatable. The KiGGS cohort study will provide opportunities to further clarify the observed association., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: With an annual increase of 16000 new cases each year, oral cancer is the second most common cancer in Pakistan. There is conflicting evidence regarding the carcinogenicity of different forms of smokeless tobacco (SLT) from different countries. This difference in evidence may be attributed to the varied composition of SLT products used around the world, necessitating the establishment of individual risks related to each SLT product., Methods: An electronic search in relevant databases yielded 119 publications, out of which six were included in this review. Effect estimates (odds ratios (ORs)) were abstracted or calculated from the given data. A fixed effects meta-analysis was performed to assess the risk of oral cancer with the use of Naswar. Population attributable fractions (PAF) were also calculated., Results: The Meta Odds Ratio (mOR) for oral cancer associated with the "ever use" of Naswar compared to "never use" was 11.8 (95% CI = 8.4-16.4), I2 = 67%. The pooled estimate for oral cancer in "Ever-users" of Naswar compared to "Never-users," in the Khyber Pakhtunkhwa province was 18.3 (95% CI = 8.7-38.5), I2 = 0%. The PAF for oral cancer associated with the use of Naswar in Pakistan was 44% (95% CI = 35-53)., Discussion: This review highlights a strong relationship between oral cancer incidence and the use of Naswar in Pakistan and adds to the evidence base on the carcinogenicity of SLT products in humans. Although the synthesized evidence may not be of a high quality, it represents the "best available evidence" which can be used to inform policy., Implications: The carcinogenicity of Naswar, a form of smokeless tobacco used extensively in Pakistan, Afghanistan, and Central Asia, has yet to be recognized by the International Agency for Research on Cancer (IARC), partly due to the lack of evidence on the association of Naswar use and cancer. Additionally, Naswar is yet un-regulated in Pakistan and evades the tax net, resulting in it being freely available to both adults and children at very cheap prices compared to cigarettes, which has been the main focus of tobacco control in Pakistan. This review provides ample evidence for the IARC to declare Naswar as carcinogenic, as well as the Government of Pakistan to regulate the production and sale of Naswar.

Perceived annoyance due to traffic noise and lack of urban green space is mostly determined using data from self-administered questionnaires. However, there is still no clear evidence to what extent such perceived measures are related to objectively assessed environmental data and whether socioeconomic dimensions modify such relationships. In a cross-sectional study in Dortmund, Germany, georeferenced home addresses from parents with preschool aged children were used to analyse relations between exposures to objectively measured green space and traffic noise and subjective annoyance due to noise and lack of green space with the additional consideration of socioeconomic characteristics as effect modifiers. Higher perceived annoyance correlated with higher objectively measured traffic noise and lower objectively measured green, respectively. Stratified logistic regression models indicated a modifying role of socioeconomic characteristics. The strengths of associations between objectively measured environmental exposures and perceived annoyance differed by socioeconomic strata. Especially for noise, odds ratios were higher in low socioeconomic strata than in high socioeconomic strata. Therefore, using objective measures of the built environment as a proxy for individual perception should be made with caution as negative relations between objectively assessed built environments and health could be underestimated when considering individual socioeconomic position only as a confounder.

Exposure to ionizing radiation of cosmic origin is an occupational risk factor in commercial aircrew. In a historic cohort of 26,774 German aircrew, radiation exposure was previously estimated only for cockpit crew using a job-exposure matrix (JEM). Here, a new method for retrospectively estimating cabin crew dose is developed. The German Federal Radiation Registry (SSR) documents individual monthly effective doses for all aircrew. SSR-provided doses on 12,941 aircrew from 2004 to 2015 were used to model cabin crew dose as a function of age, sex, job category, solar activity, and male pilots' dose; the mean annual effective dose was 2.25 mSv (range 0.01-6.39 mSv). In addition to an inverse association with solar activity, exposure followed age- and sex-dependent patterns related to individual career development and life phases. JEM-derived annual cockpit crew doses agreed with SSR-provided doses for 2004 (correlation 0.90, 0.40 mSv root mean squared error), while the estimated average annual effective dose for cabin crew had a prediction error of 0.16 mSv, equaling 7.2% of average annual dose. Past average annual cabin crew dose can be modeled by exploiting systematic external influences as well as individual behavioral determinants of radiation exposure, thereby enabling future dose-response analyses of the full aircrew cohort including measurement error information.

In the wake of smokeless tobacco (SLT) being advocated as a mean of tobacco harm reduction, it is pertinent to establish individual health risks associated with each SLT product. This case-control study was aimed at assessing the risk of oral cancer associated with a smokeless tobacco product (Naswar). The study was conducted from September 2014 till May 2015 in Khyber Pakhtunkhwa, Pakistan. Exposure and covariate information was collected through a structured questionnaire. Conditional logistic regression was used to calculate odds ratios (OR) along with their 95% confidence intervals (CI). 84 oral cancer cases (62% males) and 174 age- and sex-matched controls were recruited. Ever users of Naswar had more than a 20-fold higher risk of oral cancer compared to never-users (OR 21.2, 95% CI 8.4-53.8). Females had a higher risk of oral cancer with the use of Naswar (OR 29.0, 95% CI 5.4-153.9) as compared to males (OR 21.0, 95% CI 6.1-72.1). Based on this result, 68% (men) and 38% (women) of the oral cancer burden in Pakistan is attributable to Naswar. The risk estimates observed in this study are comparable to risk estimates reported by previous studies on other forms of SLT use and the risk of oral cancer in Pakistan. The exposure-response relationship also supports a strong role of Naswar in the etiology of oral cancer in Pakistan. Although still requiring further validation through independent studies, these findings may be used for smokeless tobacco control in countries where Naswar use is common.

Computed tomography (CT) is an essential tool in modern medicine and is frequently used to diagnose a wide range of conditions, particularly in industrial countries, such as Japan and Germany. However, markedly higher doses of ionizing radiation are delivered during CT imaging than during conventional X-ray examinations. To assess pediatric CT practice patterns, data from three university hospital databases (two in Japan and one in Germany) were analyzed. Anonymized data for patients aged 0 to 14 years who had undergone CT examinations between 2008 and 2010 were extracted. To assess CT practice, an interdisciplinary classification scheme for CT indications, which incorporated the most common examination types and radiosensitive tissues, was developed. The frequency of CT examinations was determined according to sex, age at examination, and indications. A total of 5182 CT examinations were performed in 2955 children. Overall, the frequency of CT examinations at the Japanese university hospitals did not differ significantly from that at the German hospital. However, differences were detected in the age distribution of the patients who underwent CT examinations (the proportion of patients <5 years of age was significantly higher in Japan than in Germany) and in the indications for CT. Substantial practice differences regarding the use of CT in pediatric health care were detected between the three hospitals. The results of this study point towards a need for approaches such as clinical guidelines to reduce unwarranted medical radiation exposures, particularly abdominal and head CT, in the Japanese health system., (© The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: In 2001, calculations in models based on atomic bomb survivors indicated that children exposed to ionizing radiation by computed tomography (CT) would be expected to have an increased risk of cancer. This led to the issuance of new recommendations in Germany concerning CT in children., Methods: We analyzed data from the German pediatric CT cohort study together with data on children from a large general statutory health insurance provider (AOK) in order to characterize the secular trend in the use of CT in Germany. We used information from the Picture Archiving and Communication System (PACS) to estimate individual organ doses per scan and their development over time., Results: The number of CT scans performed on children in Germany each year declined by 29% from 2006 to 2012. Over the same period, younger children were exposed to lower organ doses during CT scanning, although some organ doses were higher in neonates than in older children. The highest organ doses were in the 7.6 to 12.5-year-old age group and affected the brain (37.12 mGy ± 19.68 mGy) and the lenses (41.24 mGy ± 20.08 mGy). In every age group, the organ doses declined from year to year. With approximately 21 000 children aged 0-13 undergoing CT each year (extrapolated from insurance data of 2008), one can expect 2.3 [-1.7; 6.3] additional new cases of leukemia and 1 [-2.3; 4.0] additional new tumor of the central nervous system to arise each year., Conclusion: In view of the risks, children should undergo CT only for the indications listed by the German Commission on Radiological Protection (Strahlenschutzkommission). Further epidemiological studies are needed for estimation of the risk associated with the use of newer CT technology.

Background: Nature and extent of welfare regimes and social policies are important determinants of health and health inequalities. This study examines the association of gender and mental wellbeing in European countries and investigates whether type of welfare regime plays a role in this association., Method: Data of 19 366 women and 14 338 men of the third round of the European Quality of Life Survey (2011-12) was used to analyse mental wellbeing, assessed by the World Health Organization 5-Mental Wellbeing Index. Multilevel logistic regression analyses were performed to analyse the association between gender and good mental wellbeing first at country-level, and secondly the between country variation was analysed and welfare regimes were included as explanatory variables., Results: We observed cross-national variation in good mental wellbeing. At country levels gender inequalities in good mental wellbeing were observed in 7 out of 26 countries. In analyses considering all countries together gender inequalities in good mental wellbeing were identified independent of further individual socio-demographic variables and independent of the welfare regimes that people lived in [women vs. men: OR = 0.76; (95% CI = 0.71-0.81)]. Gender inequalities in good mental wellbeing were not modified by welfare regimes., Conclusion: There are cross-national differences in good mental wellbeing between European countries. Gender inequalities with a lower prevalence of good mental wellbeing among women are common in European countries. This study suggests that welfare regimes do not modify these gender inequalities in mental wellbeing., (© The Author 2016. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Background: Conflicting findings were observed in recent studies assessing the association between patients' area-level socio-economic status and the received number of computed tomography (CT) examinations in children. The aim was to investigate the association between area-level socio-economic status and variation in CT examination practice for pediatric patients in Germany., Methods: Data from Radiology Information Systems for children aged 0 to < 15 years without cancer who had at least one CT examination between 2001 and 2010 were extracted in 20 hospitals across Germany. The small-area German Index of Multiple Deprivation (GIMD) was used to assess regional deprivation. The GIMD scores were classified into least, medium and most deprived areas and linked with the patient's last known postal code. A multinomial logistic regression model was used to assess the association between patients' CT numbers and regional deprivation adjusting for age, sex, and location of residence (urban/rural)., Results: A total of 37,810 pediatric patients received 59,571 CT scans during the study period. 27,287 (72%) children received only one CT, while n = 885 (2.3%) received six or more. Increasing numbers of CT examinations in non-cancer patients were significantly associated with higher regional deprivation, which increased, although CI overlap, for higher CT categories: '2-3 CT' odds ratio (OR) = 1.45, 95%CI: 1.40-1.50; '4-5 CT' OR = 1.48, 95%CI: 1.38-1.59; '6+CT' OR = 1.54, 95%CI: 1.41-1.69. In addition, male sex, higher age categories, and specific body regions were positively associated with increased numbers of CT examinations., Conclusion: We observed a positive association between regional deprivation and CT numbers in non-cancer pediatric patients. Limitations of the ecological approach and the lack of differentiation of CT details have to be acknowledged. More information on CT indications is necessary for a full assessment of this finding. In addition, further work on ways to assess socio-economic status more accurately may be required.

Background: Environmental noise is considered a threat to public health as 20% of the EU population is exposed to health influencing noise levels. An association of noise and mental health problems in children has been suggested by some studies, but results are not consistent and there are no longitudinal studies of this association. Our aim was to investigate the influence of different environmental noise sources at children's homes on incident mental health problems in school-aged children., Method: A cohort study of children from first (t0) to fourth grade (t1) of primary school was conducted. Different environmental noise sources (day/night separately) at children's home were assessed via parental annoyance reports. Increased noise exposure between t0 and t1 was the exposure variable. Incident mental health problems were assessed with the parental version of the Strengths and Difficulties Questionnaire (SDQ). RRs and 95% CIs were analysed to investigate the association between different noise sources and incident mental health problems., Results: The study population consisted of 583 boys and 602 girls. The most common increase in noise exposure between t0 and t1 was road traffic noise day (26.38%). After adjusting for covariates exposure to road traffic night was significantly associated with the total difficulties score (RR=2.06; 95% CI=1.25-3.40), emotional symptoms (RR=1.69, 95% CI=1.04-2.72), and conduct problems (RR=1.57, 95% CI=1.04-2.38). Noise by neighbours during the day was associated with conduct problems (RR=1.62, 95% CI=1.11-2.40) and hyperactivity (RR=1.69, 95% CI=1.08-2.65). Aircraft noise day and construction work day were not associated with any of the SDQ categories at a significant level., Conclusion: Environmental noise is an important public health problem. This is the first study to investigate the association of a broad range of noise sources and incident mental health problems in children in a cohort study. Our results suggest that exposure to noise at children's home is associated with mental health problems such as emotional symptoms, conduct problems and hyperactivity., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: One of the most efficient radiation protection methods to reduce the risk of adverse health outcomes in case of accidental radioactive iodine release is the administration of potassium iodine (KI). Although KI administration is recommended by WHO's guidelines for iodine prophylaxis following nuclear accidents and is also widely implemented in most national guidelines, the scientific evidence for the guidelines lacks as the guidelines are mostly based on expert opinions and recommendations. Therefore, this study will provide evidence by systematically reviewing the effects of KI administration in case of accidental radioactive iodine release on thyroid cancer, hypothyroidism, and benign nodules., Methods: We will apply standard systematic review methodology for the identification of eligible studies, data extraction, assessment of risk of biases, heterogeneity, and data synthesis. The electronic database search will be conducted in MEDLINE (via PubMed) and EMBASE, and covers three search blocks with terms related to the health condition, intervention, and occurrence/location. We have no date or language restrictions, but restrictions to humans only. We will include studies comparing the effects of KI administration on thyroid cancer, hypothyroidism, and benign thyroid nodules in a population exposed to radioactive iodine release. The quality of the studies will be graded. If feasible, a meta-analysis will be conducted., Discussion: This proposed systematic review will update the existing WHO guideline from 1999. New evidence on the efficacy of KI administration to reduce thyroid cancer, hypothyroidism, and benign thyroid nodules in the event of an accidental release of radioactive iodine to the environment will provide the basis for an update of the WHO guideline for iodine prophylaxis following nuclear accidents., Systematic Review Registration: PROSPERO CRD42015024340.

Background: Exposure to medical ionizing radiation has been increasing over the past decades and constitutes the largest contributor to overall radiation exposure in the general population. While occupational exposures are generally monitored by national radiation protection agencies, individual data on medical radiation exposure for the general public are not regularly collected. The aim of this study was to determine the feasibility of assessing lifetime medical ionizing radiation exposure from diagnostic and therapeutic procedures retrospectively and prospectively within the framework of the German National Cohort study., Methods: Retrospective assessment of individual medical radiation exposure was done using an interviewer-based questionnaire among 199 participants (87 men and 112 women) aged 20-69 randomly drawn from the general population at two recruitment locations in Germany. X-ray cards were distributed to 97 participants at one recruitment center to prospectively collect medical radiation exposure over a 6-month period. The Wilcoxon-Mann-Whitney test was used to test differences in self-reported median examination frequencies for the variables age, sex, and recruitment center. To evaluate the self-reported information on radiological procedures, agreement was assessed using health insurance data as gold standard for the time period 2005 to 2010 from 8 participants., Results: Participants reported a median of 7 lifetime X-ray examinations (interquartile range 4-13), and 42% (n = 83) reported having had a CT scan (2, IQR = 1-3). Women reported statistically significant more X-ray examinations than men. Individual frequencies above the 75th percentile (≥15 X-ray examinations) were predominantly observed among women and in individuals >50 years of age. The prospective exposure assessment yielded a 60% return-rate of X-ray cards (n = 58). 16 (28%) of the returned cards reported radiological examinations conducted during the 6-month period but generally lacked more detailed exposure information. X-ray examinations reported for the period for which health insurance data were available provided a moderately valid measure of individual medical radiation exposure., Conclusions: The assessment of more recent medical examinations seems in the German National Cohort study feasible, whereas lifetime medical radiation exposure appears difficult to assess via self-reports. Health insurance data may be a potentially useful tool for the assessment of individual data on medical radiation exposure both retrospectively and prospectively.

Objectives: To investigate the association between psychosocial, sociodemographic and material determinants of positive mental health in Europe., Design: Cross-sectional analysis of survey data., Setting: 34 European countries., Participants: Representative Europe-wide sample consisting of 21 066 men and 22 569 women aged 18 years and over, from 34 European countries participating in the third wave of the European Quality of Life Survey (2011-2012)., Outcome: Positive mental health as measured by the WHO-5-Mental Well-being Index, while the lowest 25% centile indicated poor positive mental health., Results: The prevalence of poor positive mental health was 30% in women and 24% in men. Material, as well as psychosocial, and sociodemographic factors were independently associated with poor positive mental health in a Europe-wide sample from 34 European countries. When studying all factors together, the highest OR for poor positive mental health was reported for social exclusion (men: OR=1.73, 95% CI 1.59 to 1.90; women: OR=1.69, 95% CI 1.57 to 1.81) among the psychosocial factors. Among the material factors, material deprivation had the highest impact (men: OR=1.96, 95% CI 1.78 to 2.15; women: OR=1.93, 95% CI 1.79 to 2.08)., Conclusions: This study gives the first overview on determinants of positive mental health at a European level and could be used as the basis for preventive policies in the field of positive mental health in Europe., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Integrin α9β1 is a receptor for ECM proteins, including Tenascin-C and the EDA domain of fibronectin, and has been shown to transduce TGFβ signalling. This study has examined the expression pattern of α9β1 in 141 frozen breast carcinoma samples and related expression to prognostic indices, molecular subtype and patient outcome. Effects of α9β1 on tumour cell migration and invasion were assessed using blocking antibody and gene transduction approaches. Integrin α9β1 localized to myoepithelial cells in normal ducts and acini, a pattern maintained in DCIS. A subset (17%) of invasive carcinomas exhibited tumour cell expression of α9β1, which related significantly to the basal-like phenotype, as defined by either CK5/6 or CK14 expression. Tumour expression of α9β1 showed a significant association with reduced overall patient survival (p < 0.0001; HR 5.94, 95%CI 3.26-10.82) and with reduced distant-metastasis-free survival (p < 0.0001; HR 6.37, CI 3.51-11.58). A series of breast cancer cell lines was screened for α9β1 with the highly invasive basal-like GI-101 cell line expressing significant levels. Both migration and invasion of this line were reduced significantly in the presence of α9-blocking antibody and following α9-knockdown with siRNA. Conversely, migratory and invasive behaviour of α9-negative MCF7 cells and α9-low MDA MB468 cells was enhanced significantly by over-expression of α9. Thus, α9β1 acts as a novel marker of the basal-like breast cancer subtype and expression is associated with reduced survival, while its ability to promote breast cancer cell migration and invasion suggests that it contributes to the aggressive clinical behaviour of this tumour subtype., (Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Glucosylation of RhoA, Rac1, and Cdc42 by Clostridium difficile toxin B from strain VPI 10463 (TcdB) results in actin reorganization (cytopathic effect) and apoptosis (cytotoxic effect). Toxin B from variant C. difficile strain 1470 serotype F (TcdBF) differs from TcdB with regard to substrate proteins, as it glucosylates Rac1 and R-Ras but not RhoA and Cdc42. In this study, we addressed the question of whether the cellular effects of the toxins depend on their protein substrate specificity. Rat basophilic leukemia (RBL) cells were synchronized using the thymidine double-block technique. We show that cells were most sensitive to the cytotoxic effect of TcdB in S phase, as analyzed in terms of phosphatidyl serine externalization, fragmentation of nuclei, and activation of caspase-3; in contrast, TcdBF induced only a marginal cytotoxic effect, suggesting that inactivation of RhoA (but not of Rac1) was required for the cytotoxic effect. The glucosylation of Rac1 was correlated to the cytopathic effect of either toxin, suggesting a close connection of the two effects. The cytotoxic effect of TcdB was executed by caspase-3, as it was responsive to inhibition by acetyl-Asp-Met-Gln-Asp-aldehyde (Ac-DMQD-CHO), an inhibitor of caspase-3. The viability of TcdB-treated RBL cells was reduced, whereas the viability of TcdBF-treated cells was unchanged, further confirming that inactivation of RhoA is required for the cytotoxic effect. In conclusion, the protein substrate specificity of the glucosylating toxins determines their biological activity.

This is a validation study of 2 commercially available enzyme linked immunosorbent assays (ELISA) for the detection of antibodies against Neospora caninum in bovine serum. The results of the reference sera (n = 30) and field sera from an infected beef herd (n = 150) were tested by both ELISAs and the results were compared statistically. When the immunoblotting results of the reference bovine sera were compared to the ELISA results, the same identity score (96.67%) and kappa values (K) (0.93) were obtained for both ELISAs. The sensitivity and specificity values for the IDEXX test were 100% and 93.33% respectively. For the Biovet test 93.33% and 100% were obtained. The corresponding positive (PV+) and negative predictive (PV-) values for the 2 assays were 93.75% and 100% (IDEXX), and 100% and 93.75% (Biovet). In the 2nd study, competitive inhibition ELISA (c-ELISA) results on bovine sera from an infected herd were compared to the 2 sets of ELISA results. The identity scores of the 2 ELISAs were 98% (IDEXX) and 97.33% (Biovet). The K values calculated were 0.96 (IDEXX) and 0.95 (Biovet). For the IDEXX test the sensitivity and specificity were 97.56% and 98.53%, whereas for the Biovet assay 95.12% and 100% were recorded, respectively. The corresponding PV+ and PV- values were 98.77% and 97.1% (IDEXX), and 100% and 94.44% (Biovet). Our validation results showed that the 2 ELISAs worked equally well and there was no statistically significant difference between the performance of the 2 tests. Both tests showed high reproducibility, repeatability and substantial agreement with results from 2 other laboratories. A quality assurance based on the requirement of the ISO/IEC 17025 standards has been adopted throughout this project for test validation procedures.