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Julia Lichtnekert, Hans-Joachim Anders, Maciej Lech Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, München, GermanyCorrespondence: Maciej Lech, Medizinische Klinik und Poliklinik IV Klinikum der Universität München, Goethestr. 31, München, D-80336, Germany, Tel +49-89-218075842, Fax +49-89-218075860, Email Maciej.Lech@med.uni-muenchen.deAbstract: Lupus nephritis is a severe organ manifestation of systemic lupus erythematosus, and its pathogenesis involves complex etiology and mechanisms. Despite significant knowledge gains and extensive efforts put into understanding the development and relapsing disease activity, lupus nephritis remains a substantial cause of morbidity and mortality in lupus patients. Current therapies retain a significant unmet medical need regarding rates of complete response, preventing relapse of lupus nephritis, progression of chronic kidney disease to kidney failure, drug toxicity, and pill burden-related drug non-adherence. Connected to progression of chronic kidney disease are the associated risks for disabling or even lethal cardiovascular events, as well as chronic kidney disease-related secondary immunodeficiency and serious infections. In this regard, biomarkers are needed that can predict treatment response to specific drugs to enable personalized precision medicine. A series of clinical trials with innovative immunomodulatory drugs are ongoing and raise expectations for improvements in the management of lupus nephritis. Here, we review how new developments in pathogenesis connect with current and future perspectives for the management of lupus nephritis.Keywords: systemic lupus erythematosus, glomerulonephritis, proteinuria, autoimmunity, steroids

Abstract Hydrogen could play an important role in reducing the climate impact of the transport sector. This study explores the possibility of using existing biomethane infrastructure to enable the accelerated roll‐out of hydrogen as a transport fuel in a Swedish context. The concept of multifuel filling stations for hydrogen and biomethane are examined based on four cases, where the hydrogen is produced either via electrolysis or biomethane reforming, at a smaller or larger scale, and through either centralised or decentralised production. The cases are compared using established life cycle assessment (LCA) methodology to establish their respective impact from a greenhouse gas (GHG) emission mitigation potential. The LCA results show generally good GHG performance for all production paths being studied with a range from −7 g CO2 eq./MJ hydrogen for hydrogen production based on biomethane via steam reformation (SMR) compared to +19 g CO2 eq. for production based on Swedish National Grid Mix via electrolyser. The SMR is the more efficient technology in mitigating GHG emissions, especially if system expansion is applied. In addition, sensitivity analyses also show that electrolyses production based on renewable wind power will decrease the impact significantly and vice versa that a European Average Electricity Grid Mix (EU – 28) would increase the impact significantly. The findings of this study underline the potential of the gradual introduction of hydrogen as a fuel for transport without the need for large investments in a dedicated fuel‐specific distribution system. The concept could contribute to overcoming the current chicken‐and‐egg catch of achieving both scalable and profitable supply of hydrogen for transport as well as the vehicles using it as fuel.

Abstract Background Child health and development can be promoted by strengthening and supporting parents. Research on parental support programs based on positive psychology and a health-promoting approach aimed at all parents, and in particular parents of infants is limited. All Children in Focus (ACF) is a parental support program that has been evaluated in a randomized trial in parents of children 3–12 years. The ACF is based on health promotion aiming to increase parents’ confidence and child’s well-being. In the current study, we will study the effects of a revised version of the ACF called Little ACF adapted to parents with children aged 1–2 years. Methods The study includes a randomized controlled trial (RCT) taking place at several Child Health Centers (CHCs) in Sweden. The RCT will evaluate the efficacy of Little ACF (intervention) in comparison with four digital lectures about child development and parenting (active control). Parents are recruited at the 10-, 12-, or 18-month visits to CHC by CHC-nurses. Data to assess changes in parental competencies and child socio-emotional development are collected through online questionnaires completed by parents at five time points: baseline, post-intervention, after 6 and 12 months, and when the child is 3 years old. Discussion The paper describes a study protocol of a randomized controlled trial evaluating the effects of a parental support program during infancy. Several issues related to the methodology and implementation are discussed. Trial registration ClinicalTrials.gov NCT05445141. Registered on 6 July 2022.

Abstract Background Pleural mesothelioma (PM) is typically diagnosed late during the disease. Earlier detection can increase the chance of effective therapy. Recurrent pleural effusions are the earliest symptoms displaying an array of cytomorphological changes from reactive atypia to malignancy. Diagnosis is possible on effusion cytology by applying molecular and immunocytochemical markers, the main difficulty being when to suspect PM and to differentiate PM from metastatic adenocarcinoma and reactive mesothelial proliferations. Methods We evaluated the diagnostic performance of two immunocytochemical dual stains (BerEp4/Calretinin and Desmin/Epithelial Membrane Antigen (EMA)) on 149 ethanol‐fixed cytospin preparation as an initial step to solve the mentioned diagnostic difficulty. The immunocytochemical reactivity pattern was evaluated by two independent investigators. The final diagnosis corresponded to PM (n = 20), metastatic adenocarcinoma (n = 83), and mesotheliosis (n = 46) in these cases. Results Calretinin had 99% specificity and 98% sensitivity for indicating a mesothelial phenotype, while BerEp4 distinguished the adenocarcinoma cases with 98% specificity and 99% sensitivity. EMA displayed 96% specificity and 99% sensitivity in malignant cases, while Desmin without EMA present showed 99% specificity and 96% sensitivity for indicating benign mesothelial proliferation. Conclusions Interpretation of the four immunoreactions is improved when performed as dual stains. The dual staining is a useful tool in the initial handling of atypical effusions and guides the subsequent choice of antibody panels for more detailed subclassification of malignant effusions.

Abstract Physiological properties and function of the lymphatic system is still somewhat of a mystery. We report the current knowledge about human lymphatic vessel contractility and capability of adaptation. A literature search in PubMed identified studies published January 2000–September 2022. Inclusion criteria were studies investigating parameters related to contraction frequency, fluid velocity, and lymphatic pressure in vivo and ex vivo in human lymphatic vessels. The search returned 2885 papers of which 28 met the inclusion criteria. In vivo vessels revealed baseline contraction frequencies between 0.2 ± 0.2 and 1.8 ± 0.1 min1, velocities between 0.008 ± 0.002 and 2.3 ± 0.3 cm/s, and pressures between 4.5 (range 0.5–9.2) and 60.3 ± 2.8 mm Hg. Gravitational forces, hyperthermia, and treatment with nifedipine caused increases in contraction frequency. Ex vivo lymphatic vessels displayed contraction frequencies between 1.2 ± 0.1 and 5.5 ± 1.2 min−1. Exposure to agents affecting cation and anion channels, adrenoceptors, HCN channels, and changes in diameter‐tension properties all resulted in changes in functional parameters as known from the blood vascular system. We find that the lymphatic system is dynamic and adaptable. Different investigative methods yields alternating results. Systematic approaches, consensus on investigative methods, and larger studies are needed to fully understand lymphatic transport and apply this in a clinical context.

To computationally support hydrogen and helium plasma discharges in the early stages of tokamak operation and to support the commissioning of the neutron detectors during these operational phases, creation of a realistic neutron and gamma ray particle source for Monte Carlo simulations will be needed. One of the most important parts of creating the particle source is calculating the reaction rates of the particle-emitting reactions to determine the emission profile in the plasma and the energy spectra of the emitted particles. In this paper the analysis and evaluation of cross sections for important neutron-emitting reactions, namely, ^9 Be(p,n γ ) ^9 B, ^9 Be( ^3 He,n γ ) ^11 C, and charged-particle emission reactions ^9 Be(p,d)2 α and ^9 Be(p, α ) ^6 Li that cause neutron emission in the next step of interactions are presented. The reaction cross sections were evaluated based on experimental measurements and empirical models describing the interaction of two charged particles. Evaluation of the associated uncertainties was also performed. The main goal of the work is to propose the newly evaluated cross sections for inclusion in the FENDL nuclear data library, thus making the cross section available to other researchers studying the above listed reactions.

Abstract Background To study the association of maternal age upon arrival and length of residence in Sweden with the 4-year caries increment in their children between ages 3 and 7 years in relation to the human development index (HDI) of the maternal country of origin. Method This registry-based cohort study included all children born in 2000–2003 who resided in Stockholm County, Sweden, at age 3 years and who were followed up at age 7 (n = 63,931). Negative binomial regressions were used to analyze different models adjusted for sociodemographic factors. Results Children of foreign-born mothers, regardless of the HDI of the maternal country of origin, had a higher risk of caries increment between ages 3 and 7 years than children of Swedish-born mothers. Furthermore, children of mothers who had arrived from a low or medium HDI country had a lower caries increment if their mothers arrived before age 7 compared with after age 7. Nearly half (44%) of the children whose mothers arrived in Sweden at age ≥ 20 years from a low HDI country had a caries increment compared to 22% of the children whose mothers had arrived in Sweden before 7 years of age. Furthermore, children whose mothers were born in a low HDI country and had resided in Sweden ≤ 19 years had approximately 1.5 times higher risk of caries increment compared to children of mothers who had resided in Sweden for more than 20 years. Conclusions Caries increment in the children of foreign-born mothers was associated with the age of their mother when she arrived in Sweden and was lower when the mother had arrived before age 7 years. This indicates an intergenerational effect that carries over to the children and is greater the longer the mother has participated in Swedish dental healthcare.

Abstract Background Undocumented migrants face many hardships in their everyday life such as poor living conditions, discrimination, and lack of access to healthcare. Previous studies have demonstrated considerable health care needs for psychiatric disorders as well as physical diseases. The aim of this paper was to find out the main barriers that undocumented migrants experience in accessing the Swedish healthcare system and to explore their relation with socioeconomic factors. Methods A cross-sectional study with adult undocumented migrants was performed in the three largest cities of Sweden in 2014–2016. Sampling was done via informal networks. A socioeconomic questionnaire was constructed including 22 barriers to health care. Trained field workers conducted the interviews. A principal component analysis was conducted of all barriers to reveal central components. Then, Pearson’s chi-squared test was used to explore the characteristics of undocumented migrants experiencing barriers to care. Results Two main components/barriers were extracted: “Fear of being taken by police/authorities”, which was related to fear of disclosure by or in relation to seeking health care, and “Structural and psychosocial factors” which was related to practical obstacles or shame of being ill. Lower age (74.1 % vs 56.0 %), lower level of education (75.0 % vs. 45.1 %), and having no children (70.3 % vs. 48.1 %) were significantly related to a higher likelihood of experiencing a barrier. Conclusion Fear of deportation and practical and psychosocial factors constitute hinderance of access to healthcare for undocumented migrants in Sweden. This highlights the importance of clear instructions, both to undocumented migrants and health professionals about the right to health care according to the international law on human rights as well as the law of confidentiality.

Abstract Background To analyse the impact of austerity measures taken by European governments as a response to the 2008 economic and financial crisis on social determinants on child health (SDCH), and child health outcomes (CHO). Methods A systematic literature review was carried out in Medline (Ovid), Embase, Web of Science, PsycInfo, and Sociological abstracts in the last 5 years from European countries. Studies aimed at analysing the Great Recession, governments’ responses to the crisis, and its impact on SDCH were included. A narrative synthesis of the results was carried out. The risk of bias was assessed using the STROBE and EPICURE tools. Results Fourteen studies were included, most of them with a low to intermediate risk of bias (average score 72.1%). Government responses to the crisis varied, although there was general agreement that Greece, Spain, Ireland and the United Kingdom applied higher levels of austerity. High austerity periods, compared to pre-austerity periods were associated with increased material deprivation, child poverty rates, and low birth weight. Increasing child poverty subsequent to austerity measures was associated with deterioration of child health. High austerity was also related to poorer access and quality of services provided to disabled children. An annual reduction of 1% on public health expenditure was associated to 0.5% reduction on Measles-Mumps-Rubella vaccination coverage in Italy. Conclusions Countries that applied high level of austerity showed worse trends on SDCH and CHO, demonstrating the importance that economic policy may have for equity in child health and development. European governments must act urgently and reverse these austerity policy measures that are detrimental to family benefits and child protection.

Abstract Background Fathers may affect expectant mothers’ daily living situations, which in turn might influence pregnancy outcomes. We investigated the association between paternal violent criminality and risk of preterm birth (≤36 weeks). Methods We conducted a register-based study with all live singleton births in the Swedish Medical Birth Register from 1992 to 2012, linked with records of paternal violent crime convictions from the National Crime Register from 1973 to 2012. Results Paternal violent criminality was associated with increased risk of preterm birth and lower gestational age. The association was especially pronounced among infants of reoffenders: men convicted of three or more violent crimes (adjusted odds ratio [aOR] 1.23 [95% CI 1.17, 1.29]). Maternal half sibling-comparisons, an analytic approach controlling for maternal factors stable across pregnancies, also suggested increased risk of preterm birth and lower gestational age when exposed to a violently reoffending father compared to a father without violent criminal convictions (aOR 1.30 [0.99, 1.72], adjusted mean difference − 1.07 [− 1.78, − 0.36]). Conclusions Persistent paternal violent criminality was associated with increased risk of preterm birth, even after controlling for maternal characteristics that did not change between pregnancies.

BackgroundDue to the circumstances of their early lives, young refugees are at risk of experiencing adverse labour market and health outcomes. The post-settlement environment is thought to play a decisive role in determining how this vulnerability plays out. This study compared trends in labour market marginalisation in young refugees and their majority peers during early adulthood in two national contexts, Denmark and Sweden, and explored the mediating role of common mental disorders and secondary school completions.MethodsUsing registry data, 13,390/45,687 refugees were included in Denmark/Sweden and 1:5 matched to majority peers. Inequalities in labour market marginalisation were investigated during 2012-2015 in each country using linear probability models and mediation analysis. Country trends were standardised to account for differences in observed population characteristics.ResultsThe risk of marginalisation was 2.1-2.3 times higher among young refugees compared with their majority peers, but the risk decreased with age in Sweden and increased in Denmark for refugees. Birth-cohort differences drove the increase in Denmark, while trends were consistent across birth-cohorts in Sweden. Differences in population characteristics did not contribute to country differences. Common mental disorders did not mediate the inequality in either country, but secondary school completions did (77-85% of associations eliminated).ConclusionsThe findings document both the vulnerability of young refugees to labour market marginalisation and the variability in this vulnerability across post-settlement contexts. While the contrast in policy climates in Denmark and Sweden sharpened over time, the risk of marginalisation appeared more similar in younger cohorts, pointing to the importance of factors other than national immigration and integration policies. Institutional efforts to assist young refugees through secondary education are likely to have long-lasting consequences for their socio-economic trajectories.

Background In the context of containment measures against the COVID-19 pandemic, the aims were to examine the impact of lockdown and school closures on childs’ and adolescents’ health and well-being and social inequalities in health.Methods Literature review by searching five databases until November 2020. We included quantitative peer-reviewed studies reporting health and well-being outcomes in children (0–18 years) related to closure measures' impact due to COVID-19. A pair of authors assessed the risk of bias of included studies. A descriptive and narrative synthesis was carried out.Findings Twenty-two studies, including high-income, middle-income and low-income countries, fulfilled our search criteria and were judged not to have an increased risk of bias. Studies from Australia, Spain and China showed an increase in depressive symptoms and decrease in life satisfaction. A decrease in physical activity and increase in unhealthy food consumption were shown in studies from two countries. There was a decrease in the number of visits to the emergency department in four countries, an increase in child mortality in Cameroon and a decrease by over 50% of immunisations administered in Pakistan. A significant drop of 39% in child protection medical examination referrals during 2020 compared with the previous years was found in the UK, a decrease in allegations of child abuse and neglect by almost one-third due to school closures in Florida, and an increase in the number of children with physical child abuse trauma was found in one centre in the USA.Interpretation From available reports, pandemic school closure and lockdown have adverse effects on child health and well-being in the short and probably long term. We urge governments to take the negative public health consequences into account before adopting restrictive measures in childhood.

Background Parental separation has been associated with adverse child mental health outcomes in the literature. For school-aged children, joint physical custody (JPC), that is, spending equal time in both parents’ homes after a divorce, has been associated with better health and well-being than single care arrangements. Preschool children’s well-being in JPC is less studied. The aim of this study was to investigate the association of living arrangements and coparenting quality with mental health in preschool children after parental separation.Methods This cross-sectional population-based study includes 12 845 three-year-old children in Sweden. Mental health was measured by parental reports of the Strength and Difficulties Questionnaire and coparenting quality with a four-item scale. The living arrangements of the 642 children in non-intact families were categorised into JPC, living mostly with one parent and living only with one parent.Results Linear regression models, adjusted for sociodemographic confounders, showed an association between increased mental health problems and living mostly and only with one parent (B=1.18; 95% CI 0.37 to 2.00, and B=1.20; 95% CI 0.40 to 2.00, respectively), while children in intact families vs JPC did not differ significantly (B=−0.11; 95% CI −0.58 to 0.36). After adjusting the analyses for coparenting quality, differences in child mental health between the post divorce living arrangements were, however, minimal while children in intact families had more mental health problems compared with JPC (B=0.70; 95% CI 0.24 to 1.15). Factorial analysis of covariance revealed that low coparenting quality was more strongly related to mental health problems for children in intact families and JPC compared with children living mostly or only with one parent.Conclusions This study suggests that coparenting quality is a key determinant of mental health in preschool children and thus should be targeted in preventive interventions.

Introduction Sweden has long been praised for a generous parental leave policy oriented towards facilitating a gender-equitable approach to work and parenting. Yet certain aspects of Swedish parental leave could also be responsible for the maintenance of (or even the increase in) health inequalities. Using a ‘Health in All Policies’ lens, this research project aims to assess the unintended health consequences of various components of Sweden’s parental leave policy, including eligibility for and uptake of earnings based benefits.Methods and analysis We will use individual-level data from multiple Swedish registers. Sociodemographic information, including parental leave use, will be retrieved from the total population register, Longitudinal Integration Database for Health Insurance and Labour Market Studies and Social Insurance Agency registers. Health information for parents and children will be retrieved from the patient, prescribed drug, cause of death, medical birth and children’s health registers. We will evaluate parents’ mental, mothers’ reproductive and children’s general health outcomes in relation to several policy reforms aiming to protect parental leave benefits in short birth spacing (the speed premium) and to promote father’s uptake (the father’s quota) and sharing of parental leave days (the double days reform). We will also examine effects of increases in basic parental leave benefit levels. Using quasi-experimental designs, we will compare health outcomes across these reforms and eligibility thresholds with interrupted time series, difference-in-difference and regression discontinuity approaches to reduce the risk of health selection and assess causality in the link between parental leave use and health.Ethics and dissemination This project has been granted all necessary ethical permissions from the Stockholm Regional Ethical Review Board (Dnr 2019-04913) for accessing and analysing deidentified data. The final outputs will primarily be disseminated as scientific articles published in open-access, high-impact peer-reviewed international journals, as well as press releases and policy briefs.

This paper introduces a new teaching design called Takeaway Teaching. The design consists of pre-designed generic themes and activities that support the development of study strategies in higher education. These themes and activities are easily redesigned by the teacher and integrated into the academic curriculum. The purpose of the design is twofold. It supports the didactic reflection and development of the teacher and the development of the students’ study competence. This paper presents the theoretical framework of the design, based on a theoretical approach of metacognition and second-order teaching and learning, and an example of a redesign of one of the generic themes; Literature Search.

Abstract Background Herd immunity levels of vaccine uptake are still not reached in some high-income countries, usually in countries with persisting social inequities in uptake. Previous studies have focused on factors within one health care system. This study takes a broader health care systems approach by reviewing the socioeconomic distribution of vaccination coverage on the national level in light of structural and organizational differences of primary care for children. Methods A systematic literature review of socio-economic patterns of uptake of Measles-Mumps-Rubella (MMR) and/or Diphteria-Tetanus-Pertusis (DTP) in population based studies of children 0–5 years of age living in the 30 European Economic Area (EEA) or European Free Trade Association (EFTA) countries and Australia, was carried out using the PRISMA guidelines. The health care system in the countries in the study were categorized by degree of freedom of the primary care provider (hierarchical or non-hierarchical) and whether preventive services were provided in a separate organization (well-baby clinics). Results The review identified 15 studies from 10 European countries and Australia that fulfilled the criteria. Although the heterogeneity of the socio-economic indicators did not allow for a conclusive meta-analysis, the study pointed towards lower levels of inequities in primary care models with well-baby clinics. In non-hierarchical primary care organizations that also lacked well-baby clinics, socioeconomic gaps in uptake were often found to be large. Conclusion This review indicates that structural and organizational aspects of health care systems for young children are important for equity in vaccine uptake.

Background: Isolated limb perfusion (ILP) is a treatment option for malignancies localized to an extremity and is performed by surgical isolation of the limb which is connected to an extracorporeal circulation system. A high concentration of a chemotherapeutic agent is perfused through the limb, while systemic toxicity is avoided. Currently, the use of packed red blood cells in the priming solution is the norm during ILP. The aim of this study was to investigate the possibility to replace an erythrocyte-based prime solution with a crystalloid-based prime solution while maintaining the regional metabolic oxygen demand during ILP. Methods: In a single-center, randomized controlled, non-blinded, non-inferiority clinical trial, 21 patients scheduled for treatment with ILP were included and randomized 1:1 to either an erythrocyte-based prime solution (control) or a crystalloid-based prime solution (intervention). Results: There was a significant difference in lactate level (mmol/L) during the perfusion between the intervention group and the control group (1.6 ± 0.4 vs. 3.6 ± 0.7, p = .001). No significant differences in oxygen extraction (%) (22 ± 11 vs. 14 ± 4, p = .06), oxygen delivery (ml/min) (90 ± 49 vs. 108 ± 38, p = .39), oxygen consumption (ml/min) (14 ± 2 vs. 14 ± 5, p = .85), regional central venous saturation (%) (83 ± 10 vs. 91 ± 4, p = .07) or INVOS (%) (76 ± 14 vs. 81 ± 11, p = .42) were found between the intervention group and the control group. Conclusion: This study showed no significant improvement with the addition of packed red blood cells into the prime solution in ensuring the metabolic oxygen demand in the treated extremity during ILP, and we, therefore, recommend that a crystalloid-based prime solution should be used.

Abstract Background Undocumented migrants (UMs) in Europe constitute a heterogeneous group. They are typically in a vulnerable and marginalised situation, since most of them have exhausted their options for gaining asylum and protection from war and persecution, many are traumatised and fear disclosure and deportation, and they typically lack basic social security. The present study investigates living conditions, access to human rights and mental health of UMs living in Sweden. Methods A cross-sectional study with adult UMs was performed in the three largest cities in Sweden in 2014–2016. Sampling was done via informal networks. A socioeconomic questionnaire was constructed, and psychiatric symptoms were screened for using Beck’s Depression Inventory II, Beck’s Anxiety Inventory and the PTSD Checklist (PCL) for civilians. Trained field workers conducted the interviews. Descriptive statistics, chi-square tests and logistic regression models were used. Results A total number of 104 individuals participated. Preliminary findings show that 68% of respondents were suffering from either moderate or severe anxiety, 71% from either moderate or severe depression and 58% from PTSD. No statistically significant gender differences occurred, but age was statistically significant in relation to anxiety and depression. The majority feared returning to their country of origin, for political reasons, due to war in progress there and/or because they belonged to a minority and feared harassment. Almost all had an unstable housing situation and were often forced to move. Fifty-seven percent experienced food insecurity. Conclusion The psychosocial situation among UMs in Sweden, in addition to insecure living conditions without a guarantee of basic needs being met is stressful, and many UMs live in constant fear of disclosure and deportation, all of which has a detrimental effect of the mental health. It is important to understand both associated risk factors for ill-health and coping strategies in this vulnerable population in order try to reduce ongoing stress.

This study aims to examine whether disparities in gestational age outcomes between foreign and Swedish-born mothers are contingent on the measure used to estimate gestational age and, if so, to identify which maternal factors are associated with the discrepancy. Using population register data, we studied all singleton live births in Sweden from 1992-2012 (n = 1,317,265). Multinomial logistic regression was performed to compare gestational age outcomes classified into very (

Background: Non-European international adoptees in Sweden were shown to have a three-to fourfold higher risk of suicidal behaviour in youth during 1986–1995 compared with the general population. The aim of this study was to investigate whether this high risk persists beyond youth and in later cohorts. Methods: A register study of Swedish national cohorts born 1972–86 including 20 625 non-European international adoptees, and comparison populations of 10 915 non-European immigrants and 1 435 167 Swedish born was performed. The study population was followed from age 18 between 1991 and 2016, with suicide and hospital admissions due to suicide attempt as outcomes. Poisson regression models of person time in the study, adjusted for gender and household income at age 17, were fitted to calculate relative risks (RR). Findings: Adjusted RR for suicide in non-European international adoptees was high at age 18–22, 2·74 (95% C.I. 1·95–3·86), but decreased gradually to age 33–43 when the risk was similar to Swedish-born. Adjusted RR for suicide attempts in international adoptees was 2·33 (2·15–2·52) at age 18–22, decreased slightly with older age, but remained higher than Swedish born in all age-classes. Risks for both outcomes were greatest, around three times higher compared with the Swedish-born in the oldest birth cohorts of non-European international adoptees, born 1972–76. Risks for both suicidal outcomes increased with higher age at adoption. Interpretation: The risk of suicidal behaviour in non-European international adoptees in Sweden decreases with age and is lower in later birth cohorts and in infant adoptions.

Background Europe has experienced a marked increase in the number of children on the move. The evidence on the health risks and needs of migrant children is primarily from North America and Australia.Objective To summarise the literature and identify the major knowledge gaps on the health risks and needs of asylum seeking, refugee and undocumented children in Europe in the early period after arrival, and the ways in which European health policies respond to these risks and needs.Design Literature searches were undertaken in PubMed and EMBASE for studies on migrant child health in Europe from 1 January 2007 to 8 August 2017. The database searches were complemented by hand searches for peer-reviewed papers and grey literature reports.Results The health needs of children on the move in Europe are highly heterogeneous and depend on the conditions before travel, during the journey and after arrival in the country of destination. Although the bulk of the recent evidence from Europe is on communicable diseases, the major health risks for this group are in the domain of mental health, where evidence regarding effective interventions is scarce. Health policies across EU and EES member states vary widely, and children on the move in Europe continue to face structural, financial, language and cultural barriers in access to care that affect child healthcare and outcomes.Conclusions Asylum seeking, refugee and undocumented children in Europe have significant health risks and needs that differ from children in the local population. Major knowledge gaps were identified regarding interventions and policies to treat and to promote the health and well-being of children on the move.

Background More than 800 000 asylum-seeking children were registered in Europe during 2015–2017. Many of them arrived with accumulated needs of healthcare. In this study, we examined the legislation for health examinations on arrival for migrant children in the EU/EAA area.Methods We did a survey to child health professionals within the EU-funded MOCHA project, supplemented by desktop research of official documents.Results In all but three surveyed countries in the EU/EEA, there were systematic health examinations of newly settled migrant children. In most eastern European countries and Germany, this health examination was mandatory; while in the rest of western and northern Europe it was mostly voluntary. All countries that had a mandatory policy of health examinations screened for communicable diseases to protect the host population. Almost all countries with a voluntary policy also aimed to assess a child’s individual healthcare needs, but this was rarely the case in countries with a mandatory policy.Conclusion Systematic health examinations of migrant children are routinely performed in most countries in the EU/EEA; but in many countries, it could be improved considerably by extending the focus from screening for communicable diseases to assessing and addressing individual needs of healthcare.

Abstract Background Child psychiatric treatment facilities vary greatly worldwide and are virtually non-existent in many low-income countries. One of the most common psychiatric disorders in childhood is ADHD, with an estimated prevalence of 3–5% in Sweden. Previous studies have shown a similar prevalence of ADHD in minority and majority children in Sweden and the UK. However, clinical studies demonstrated that children from immigrant families living in Sweden received less psychiatric care than those of native-born parents. We tested the hypothesis that the consumption of child psychiatric care in immigrant families would be determined by the availability of such treatment in the parents’ country of origin. Patterns of medication for attention-deficit hyperactivity disorder (ADHD) were studied as a proxy for child psychiatric care. Methods This was a register study of dispensed stimulant medication during 2013–2014 in Swedish national birth cohorts from 1995–2009. The study population, consisting of nearly 1.4 million children, was divided by national income of the parental country of origin and whether the parents were native Swedes, European immigrants, non-European immigrants or a mixture. Logistic regression was used to calculate the odds ratios of having been dispensed at least one ADHD drug during 2013, with adjustments for gender, family status indicating whether the child is living with both parents, household income and area of residence. Results Having parents born in low-income (OR [95% confidence interval] 0.27 [0.24–0.29]) or middle-income (European: OR 0.23 [0.20–0.26], non-European: OR 0.39 [0.34–0.41]) countries was associated with lower ADHD treatment levels than having parents born in high-income countries (European: OR 0.60 [0.54–0.66], non-European: OR 0.68 [0.59–0.79]), when compared to children of parents born in Sweden. In families with a background in low or middle income countries, there was no significant association between household income and ADHD medication, while in children with Swedish and mixed backgrounds high level of disposable income was associated with lower levels of ADHD medication. Conclusion The use of child psychiatric care by immigrant families in Sweden was largely associated with the income level of the country of origin.

Abstract Background Fetal alcohol spectrum disorders (FASD) is an umbrella term covering several conditions for which alcohol consumption during pregnancy is taken to play a causal role. The benefit of individuals being identified with a condition within FASD remains controversial. The objective of the present study was to identify ethical aspects and consequences of diagnostics, interventions, and family support in relation to FASD. Methods Ethical aspects relating to diagnostics, interventions, and family support regarding FASD were compiled and discussed, drawing on a series of discussions with experts in the field, published literature, and medical ethicists. Results Several advantages and disadvantages in regards of obtaining a diagnosis or description of the condition were identified. For instance, it provides an explanation and potential preparedness for not yet encountered difficulties, which may play an essential role in acquiring much needed help and support from health care, school, and the social services. There are no interventions specifically evaluated for FASD conditions, but training programs and family support for conditions with symptoms overlapping with FASD, e.g. ADHD, autism, and intellectual disability, are likely to be relevant. Stigmatization, blame, and guilt are potential downsides. There might also be unfortunate prioritization if individuals with equal needs are treated differently depending on whether or not they meet the criteria for a specific condition. Conclusions The value for the concerned individuals of obtaining a FASD-related description of their condition – for instance, in terms of wellbeing – is not established. Nor is it established that allocating resources based on whether individuals fulfil FASD-related criteria is justified, compared to allocations directed to the most prominent specific needs.

Abstract Background Infant mortality rates are commonly used to compare the health of populations. Observed differences are often attributed to variation in child health care quality. However, any differences are at least partly explained by variation in the prevalence of risk factors at birth, such as low birth weight. This distinction is important for designing interventions to reduce infant mortality. We suggest a simple method for decomposing inter-country differences in crude infant mortality rates into two metrics representing risk factors operating before and after birth. Methods We used data from 7 European countries participating in the EURO-PERISTAT project in 2010. We calculated crude and birth weight-standardised stillbirth and infant mortality rates using Norway as the standard population. We decomposed between-country differences in crude stillbirth and infant mortality rates into the within-country difference in crude and birth weight-standardised stillbirth and infant mortality rates (metric 1), reflecting prenatal risk factors, and the between-country difference in birth weight-standardised stillbirth and infant mortality rates (metric 2), reflecting risk factors operating after birth. We also calculated birth weight-specific mortality. Results Using our metrics, we showed that for England, Wales and Scotland risk factors before and after birth contributed equally to the differences in crude stillbirth and infant mortality rates relative to Norway. In Austria, Czech Republic and Switzerland the differences were driven primarily by metric 1, reflecting high rate of low birth weight. The highest values of metric 2 observed in Poland partially reflected high rates of congenital anomalies. Conclusions Our suggested metrics can be used to guide policy decisions on preventing infant deaths through reducing risk factors at birth or improving the care of babies after birth. Aggregate data tabulated by birth weight/gestational age should be routinely collected and published in high-income countries where birth weight is reported on birth certificates.

Abstract Background The cell-surface heparan sulfate proteoglycan syndecan-1 is important for tumor cell proliferation, migration, and cell cycle regulation in a broad spectrum of malignancies. Syndecan-1, however, also translocates to the cell nucleus, where it might regulate various molecular functions. Results We used a fibrosarcoma model to dissect the functions of syndecan-1 related to the nucleus and separate them from functions related to the cell-surface. Nuclear translocation of syndecan-1 hampered the proliferation of fibrosarcoma cells compared to the mutant lacking nuclear localization signal. The growth inhibitory effect of nuclear syndecan-1 was accompanied by significant accumulation of cells in the G0/G1 phase, which indicated a possible G1/S phase arrest. We implemented multiple, unsupervised global transcriptome and proteome profiling approaches and combined them with functional assays to disclose the molecular mechanisms that governed nuclear translocation and its related functions. We identified genes and pathways related to the nuclear compartment with network enrichment analysis of the transcriptome and proteome. The TGF-β pathway was activated by nuclear syndecan-1, and three genes were significantly altered with the deletion of nuclear localization signal: EGR-1 (early growth response 1), NEK11 (never-in-mitosis gene a-related kinase 11), and DOCK8 (dedicator of cytokinesis 8). These candidate genes were coupled to growth and cell-cycle regulation. Nuclear translocation of syndecan-1 influenced the activity of several other transcription factors, including E2F, NFκβ, and OCT-1. The transcripts and proteins affected by syndecan-1 showed a striking overlap in their corresponding biological processes. These processes were dominated by protein phosphorylation and post-translation modifications, indicative of alterations in intracellular signaling. In addition, we identified molecules involved in the known functions of syndecan-1, including extracellular matrix organization and transmembrane transport. Conclusion Collectively, abrogation of nuclear translocation of syndecan-1 resulted in a set of changes clustering in distinct patterns, which highlighted the functional importance of nuclear syndecan-1 in hampering cell proliferation and the cell cycle. This study emphasizes the importance of the localization of syndecan-1 when considering its effects on tumor cell fate.

Extracellular vesicles (EVs), comprising exosomes, microvesicles, and apoptotic bodies, are released by all cells into the extracellular matrix and body fluids, where they play important roles in intercellular communication and matrix remodeling in various pathological conditions. Malignant pleural mesothelioma (MPM) is a primary tumor of mesothelial origin, predominantly related to asbestos exposure. The detection of MPM at an early stage and distinguishing it from benign conditions and metastatic adenocarcinomas (AD) is sometimes challenging. Pleural effusion is often the first available biological material and an ideal source for characterizing diagnostic and prognostic factors. Specific proteins have previously been identified as diagnostic markers in effusion, but it is not currently known whether these are associated with vesicles or released in soluble form. Here, we study and characterize tumor heterogeneity and extracellular vesicle diversity in pleural effusion as diagnostic or prognostic markers for MPM. We analyzed extracellular vesicles and soluble proteins from 27 pleural effusions, which were collected and processed at the department of pathology and cytology at Karolinska University Hospital, representing three different patient groups, MPM (n = 9), benign (n = 6), and AD (n = 12). The vesicles were fractionated into apoptotic bodies, microvesicles, and exosomes by differential centrifugation and characterized by nanoparticle tracking analysis and Western blotting. Multiplex bead-based flow cytometry analysis showed that exosomal markers were expressed differently on EVs present in different fractions. Further characterization of exosomes by a multiplex immunoassay (Luminex) showed that all soluble proteins studied were also present in exosomes, though the ratio of protein concentration present in supernatant versus exosomes varied. The proportion of Angiopoietin-1 present in exosomes was generally higher in benign compared to malignant samples. The corresponding ratios of Mesothelin, Galectin-1, Osteopontin, and VEGF were higher in MPM effusions compared to those in the benign group. These findings demonstrate that relevant diagnostic markers can be recovered from exosomes.

OBJECTIVE: The detection of high titers of antibodies against small nuclear ribonucleoproteins (snRNP) is a diagnostic finding in patients in whom systemic lupus erythematosus (SLE) is suspected. Endogenous RNA molecules within snRNP trigger Toll-like receptor 7 (TLR-7) activation in B cells and dendritic cells, leading to anti-snRNP antibody production, which is associated with the development of immune complex nephritis in SLE. The purpose of this study was to investigate the role of TLR-7 in anti-snRNP antibody production and renal disease in SLE induced by an exogenous factor in the absence of genetic predisposition, using the pristane-induced murine lupus model. METHODS: Serum autoantibodies, IgG isotypes, and cytokine levels in pristane-treated wild-type and TLR-7-deficient mice were analyzed by enzyme-linked immunosorbent assay. Histopathologic changes in mouse kidneys were determined by light immunofluorescence microscopy. Cell subsets in splenocytes and peritoneal lavage cells from the mice were examined by flow cytometry. RESULTS: We found that anti-snRNP antibody production induced by pristane treatment was entirely dependent on the expression of TLR-7, whereas anti-double-stranded DNA antibody production was not affected by a lack of TLR-7. Impaired anti-snRNP antibody production in TLR-7-deficient mice was paralleled by lower levels of glomerular IgG and complement deposits, as well as less severe glomerulonephritis. CONCLUSION: TLR-7 is specifically required for the production of RNA-reactive autoantibodies and the development of glomerulonephritis in pristane-induced murine lupus, a model of environmentally triggered SLE in the absence of genetic susceptibility to autoimmunity. Specific interference with TLR-7 activation by endogenous TLR-7 ligands may therefore be a promising novel strategy for the treatment of SLE. [ABSTRACT FROM AUTHOR]

This study investigated mental health in schoolchildren in different living arrangements after parental separation. The study population included 31,519 children from the Danish National Birth Cohort, followed-up at age 11 in 2010–2014. Child mental health was measured with a maternal report of the Strength and Difficulties Questionnaire (SDQ). Associations between living arrangements and mental health were analyzed using logistic and linear regression models, taking into account early childhood indicators of the parents’ relations, income, education and psychiatric care. At age 11, children living in a nuclear family had the lowest rate of total SDQ score, 8.9%. Of the children who had experienced parental separation, children in joint physical custody had the lowest adjusted odds ratio (OR)1.25 (95%-CI 1.09–1.44), for a high SDQ score relative to children living in a nuclear family, with adjusted ORs of 1.63 (1.42–1.86) and OR 1.72 (1.52–1.95) for sole physical custody arrangements with and without a new partner. An analysis of change in SDQ scores between ages 7 and 11 in children showed a similar pattern. This study indicates that joint physical custody is associated with slightly more favorable mental health in schoolchildren after parental separation than sole physical custody arrangements.

Tumor cells undergoing epithelial-mesenchymal transition (EMT) lose cell surface adhesion molecules and gain invasive and metastatic properties. EMT is a plastic process and tumor cells may shift between different epithelial-mesenchymal states during metastasis. However, how this is regulated is not fully understood. Syndecan-1 (SDC1) is the major cell surface proteoglycan in epithelial cells and has been shown to regulate carcinoma progression and EMT. Recently, it was discovered that SDC1 translocates into the cell nucleus in certain tumor cells. Nuclear SDC1 inhibits cell proliferation, but whether nuclear SDC1 contributes to the regulation of EMT is not clear. Here, we report that loss of nuclear SDC1 is associated with cellular elongation and an E-cadherin-to-N-cadherin switch during TGF-β1-induced EMT in human A549 lung adenocarcinoma cells. Further studies showed that nuclear translocation of SDC1 contributed to the repression of mesenchymal and invasive properties of human B6FS fibrosarcoma cells. The results demonstrate that nuclear translocation contributes to the capacity of SDC1 to regulate epithelial-mesenchymal plasticity in human tumor cells and opens up to mechanistic studies to elucidate the mechanisms involved.

Abstract Background Psychological distress and lack of family support may explain the mental health problems that are consistently found in young unaccompanied refugees in Western countries. Given the strong relationship between poor mental health and alcohol misuse, this study investigated hospital admissions due to alcohol related disorders among accompanied and unaccompanied young refugees who settled in Sweden as teenagers. Methods The dataset used in this study was derived from a combination of different registers. Cox regression models were used to estimate the risks of hospital care due to alcohol related disorders in 15,834 accompanied and 4376 unaccompanied young refugees (2005–2012), aged 13 to 19 years old when settling in Sweden and 19 to 32 years old in December 2004. These young refugees were divided into regions with largely similar attitudes toward alcohol: the former Yugoslavian republics, Somalia, and the Middle East. The findings were compared with one million peers in the native Swedish population. Results Compared to native Swedes, hospital admissions due to alcohol related disorders were less common in young refugees, with a hazard ratio (HR) of 0.65 and 95% confidence interval (CI) between 0.56 and 0.77. These risks were particularly lower among young female refugees. However, there were some differences across the refugee population. For example, the risks were higher in unaccompanied (male) refugees than accompanied ones (HR = 1.49, 95% CI = 1.00–2.19), also when adjusted for age, domicile and income. While the risks were lower in young refugees from Former Yugoslavia and the Middle East relative to native Swedes, independent of their length of residence in Sweden, refugees from Somalia who had lived in Sweden for more than ten years showed increased risks (HR = 2.54, 95% CI = 1.71–3.76), after adjustments of age and domicile. These risks decreased considerably when income was adjusted for. Conclusion Young refugees have lower risks of alcohol disorders compared with native Swedes. The risks were higher in unaccompanied young (male) refugees compared to the accompanied ones. Moreover, Somalian refugees who had lived in Sweden for more than ten years seems to be particularly vulnerable to alcohol related disorders.

A growing corpus of evidence reveals that smoking patterns of migrant women tend to converge with that of the host population over time (‘acculturation paradox’). In this paper we aim to adopt a health equity perspective by studying the extent to which this pattern reflects a convergence with the group of natives who are more socioeconomically disadvantaged. Using population-based registers, we study 1,194,296 women who gave birth in Sweden between 1991 and 2012. Using logistic regression, we estimated odds ratios to assess the effect of duration of residence on the association between smoking during pregnancy and women's origin (classified according to inequality-adjusted Human Development Index (iHDI) of the country of birth). Sibling information and multilevel models were used to assess the extent to which our results might be affected by the cross-sectional nature of the data. Smoking during pregnancy increases with duration of residence among migrants from all levels of iHDI to such an extent that they tend to converge or increase in relation to the levels of the Swedish population with low education and low income, leaving behind the native population with high education and income. The results are robust to possible selection bias related to the cross-sectional nature of the data. Our findings indicate the need of a health equity perspective and suggest the use of ‘unequal assimilation’ rather than ‘acculturation paradox’ as a more suitable framework to interpret these findings. Keywords: Assimilation paradox, Acculturation paradox, Tobacco, Migration, Social determinants, Unequal assimilation

Joint physical custody (JPC) refers to a practice where children with separated parents share their time between the parents' respective homes. Studies on parents' views of JPC for young children are scarce. The aim of this interview study was to explore parents' perceptions on how they experience and practice equally shared JPC for their 1-4 year-olds in Sweden. Forty-six parents (18 fathers and 28 mothers) of 50 children (31 boys and 19 girls) under 5 years of age were interviewed. Parents were recruited through information in the media and represented a broad range of socioeconomic backgrounds, as well as both voluntary and court-ordered custody arrangements. The interviews were semi-structured and analyzed using systematic text condensation. Two themes emerged regarding the research question. In the first theme, Always free, never free, parents described their striving to coparent without a love relationship. While they appreciated the freedom of being a "half-time parent", doing things one's own way, they felt constrained by the long-term commitment to live close to and keep discussing child rearing issues with the ex-partner. Good communication was key and lessened parent's feelings of being cut-off from half of the child's life. When JPC was ordered by court or conflicts were intense, parents tried to have less contact and worried when the children were in the other home. The second theme, Is it right, is it good?, included descriptions of how the parents monitored the child's responses to the living arrangement and made changes to optimize their adjustment. Adaptations included visits for the child with the other parent mid-week, shared meals or adapting schedules. In conclusion, these parents worked hard to make JPC work and cause minimal damage to their children. Most parents were pleased with the arrangements with the notable exception of couples experiencing ongoing conflict.

Background Migrants' socioeconomic adversity has been linked to schizophrenia. Aims To investigate whether the more favourable socioeconomic situation of adoptees prevents them from the high risk of schizophrenia found in other migrants. Method Register study in a cohort of refugees and inter-country adoptees aged 16–40 years, born in East Africa (n=8389), Latin America (n=11 572) and 1.2 million native Swedes. Cox-regression models estimated hazard ratios (HRs) of schizophrenia in data from psychiatric care. Results Despite diverse income levels, HRs for schizophrenia were similar for refugees and adoptees, with East Africans having the highest HRs: 5.83 (3.30–10.27) and 5.80 (5.03–6.70), followed by Latin Americans: HRs 3.09 (2.49–3.83) and 2.31 (1.79–2.97), compared with native Swedes. Adjustment for income decreased these risks slightly for refugees, but not for adoptees. Conclusions This study suggests that risk factors associated with origin are more important determinants of schizophrenia than socioeconomic adversity in the country of settlement.

Syndecan-1 (SDC1) is a cell surface heparan sulfate proteoglycan (HSPG), which regulates various signaling pathways controlling the proliferation and migration of malignant mesothelioma and other types of cancer. We have previously shown that SDC1 can translocate to the nucleus in mesothelioma cells through a tubulin-dependent transport mechanism. However, the role of nuclear SDC1 is largely unknown. Here, we performed co-immunoprecipitation (Co-IP) of SDC1 in a mesothelioma cell line to identify SDC1 interacting proteins. The precipitates contained a large number of proteins, indicating the recovery of protein networks. Proteomic analysis with a focus on nuclear proteins revealed an association with pathways related to cell proliferation and RNA synthesis, splicing and transport. In support of this, the top RNA splicing candidates were verified to interact with SDC1 by Co-IP and subsequent Western blot analysis. Further loss- and gain-of-function experiments showed that SDC1 influences RNA levels in mesothelioma cells. The results identify a proteomic map of SDC1 nuclear interactors in a mesothelioma cell line and suggest a previously unknown role for SDC1 in RNA biogenesis. The results should serve as a fundament for further studies to discover the role of nuclear SDC1 in normal and cancer cells of different origin.

Malignant pleural mesothelioma (MPM) is a highly aggressive and therapy resistant pleural malignancy that is caused by asbestos exposure. MPM is associated with poor prognosis and a short patient survival. The survival time is strongly influenced by the subtype of the tumor. Dyspnea and accumulation of pleural effusion in the pleural cavity are common symptoms of MPM. The diagnostic distinction from other malignancies and reactive conditions is done using histopathology or cytopathology, always supported by immunohistochemistry, and sometimes also by analyses of soluble biomarkers in effusion supernatant. We evaluated the soluble angiogenesis related molecules as possible prognostic and diagnostic biomarkers for MPM by Luminex multiplex assay. Pleural effusion from 42 patients with malignant pleural mesothelioma (MPM), 36 patients with adenocarcinoma (AD) and 40 benign (BE) effusions were analyzed for 10 different analytes that, in previous studies, were associated with angiogenesis, consisting of Angiopoietin-1, HGF, MMP-7, Osteopontin, TIMP-1, Galectin, Mesothelin, NRG1-b1, Syndecan-1 (SDC-1) and VEGF by a Human Premixed Multi-Analyte Luminex kit. We found that shed SDC-1 and MMP-7 levels were significantly lower, whereas Mesothelin and Galectin-1 levels were significantly higher in malignant mesothelioma effusions, compared to adenocarcinoma. Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1, NRG1-β1, VEGF and TIMP-1 were significantly higher in malignant pleural mesothelioma effusions compared to benign samples. Moreover, there is a negative correlation between Mesothelin and shed SDC-1 and positive correlation between VEGF, Angiopoietin-1 and shed SDC-1 level in the pleural effusion from malignant cases. Shed SDC-1 and VEGF have a prognostic value in malignant mesothelioma patients. Collectively, our data suggest that MMP-7, shed SDC-1, Mesothelin and Galectin-1 can be diagnostic and VEGF and SDC-1 prognostic markers in MPM patients. Additionally, Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1 and TIMP-1 can be diagnostic for malignant cases.

Objective Our aim was to investigate whether the risk of depression in adulthood in children raised by substitute parents from an early age differ by care arrangements.Methods Register study in Swedish national cohorts born 1972–1981, with three study groups of children raised in adoptive or foster homes with care starting before the age of 2 years and a comparison majority population group. Cox regression estimated HRs of prescribed antidepressive medication and specialised psychiatric care with a diagnosis of depression in adulthood during 2006–2012.Results Compared with the general population, long-term foster care carried the highest age-adjusted and sex-adjusted HR for both antidepressive medication, 2.07 (95% CI 1.87 to 2.28), and psychiatric care for depression, 2.85 (95% CI 2.42 to 3.35), in adulthood. Adults raised by adoptive parents were far more similar to the general population with HR of 1.19 (95% CI 1.00 to 1.43) for domestic and 1.13 (95% CI 1.08 to 1.18) for international adoption for antidepressive medication. Adjusting the analysis for school marks and income attenuated these risks more in the long-term foster care group.Conclusion The study demonstrates the benefits of early adoption when substitute parents are provided for young children, and underlines the importance of improved educational support for children in foster care.

Introduction Child mortality is nearly twice as high in England as in Sweden. A comparison of mortality from potentially preventable causes could inform health system responses. This study focused on respiratory tract infection (RTI)-related deaths, amenable to healthcare interventions, and sudden unexpected deaths in infancy (SUDI), amenable to public health interventions. Objectives and Approach We developed nationally-representative birth cohorts of singleton live births in 2003-2012 using a hospital admissions database in England and the Medical Birth Register in Sweden. Children were followed-up from 31st day of life until their fifth birthday via linkage to hospital admission and mortality records. We compared child mortality using Cox proportional hazards models to estimate hazard ratios (HR) for England versus Sweden for RTI-related mortality at 31-364 days and 1-4 years, and for SUDI mortality at 31-364 days. Models were adjusted for birth characteristics (gestational age, birthweight, sex, congenital anomalies), and socio-economic factors (maternal age and socio-economic status). Results Of 3,928,483 children in England, there were 807 RTI-related deaths at 31-364 days (17% of all deaths in the age range), 691 deaths at 1-4 years (31%), and 1,166 SUDIs (24%) in England. Corresponding figures for 1,012,682 children in Sweden were 136 (18%), 118 (25%) and 189 (24%). Unadjusted HRs for RTI-related deaths in England versus Sweden were 1.50 (95% confidence interval: 1.25-1.80) at 31-364 days. Adjustment for birth characteristics reduced the HR to 1.16 (0.97-1.39), and for socio-economic factors to 1.11 (0.92-1.33). Corresponding figures for RTI-related mortality at 1-4 years were 1.58 (1.30-1.92), 1.32 (1.09-1.61) and 1.30 (1.07-1.59), respectively. Unadjusted HRs for SUDIs reduced from 1.59 (1.36-1.85) to 1.40 (1.20-1.63) after adjusting for birth characteristics, and to 1.19 (1.02-1.39) after adjusting for socio-economic factors. Conclusion/Implications Higher prevalence of adverse birth characteristics (such as prematurity, low birthweight, congenital anomalies) contributed to increased risks of RTI-related and SUDI mortality in England relative to Sweden. Therefore, preventive strategies should focus on maternal health and socio-economic circumstances before and during pregnancy to reduce RTI-related and SUDI mortality in England.

Introduction Separation from one’s child can have significant consequences for parental health and well-being. Objectives and Approach We aimed to investigate whether parents whose children were placed in care had higher rates of avoidable (amenable and preventable) mortality. Data were obtained from the Swedish national registers. Mortality rates among parents whose children were placed in care between 1990 and 2012 (17 505 mothers, 18 286 fathers) were compared with a 5:1 matched cohort of parents whose children were not placed. We computed rate differences and hazard ratios of all-cause and avoidable mortality. Results When compared with parents who did not have a child placed in care, there were an additional 21 avoidable deaths per 10 000-person years among mothers and an additional 27 avoidable deaths per 10 000-person years among fathers whose children were placed in care. Among mothers, death due to preventable causes were 3·83 times greater (95% CI 2·82-5·21) and deaths due to amenable causes were 3·12 times greater (95% CI 2·07-4·69) for those whose children were placed in care. Among fathers, death due to preventable causes was 1·75 times greater (95% CI 1·41-2·16) and deaths due to amenable causes were 1·52 times greater (95% CI 1·08- 2·13) for those whose children were placed in care. Avoidable mortality rates were higher among mothers whose children were young when placed in care and parents whose children were all placed in care. Conclusion/Implications Mothers who had a young child placed and parents whose children were all placed in care are at much higher risk of avoidable mortality than parents whose children were not placed in care. Targeted public health interventions and more attentive health care could reduce risk of avoidable mortality in this group of parents.

Introduction Children born to teenage mothers have greater healthcare needs than those born to mothers in their 20s and older, including higher rates of childhood hospitalisations. We performed a direct cross-country comparison of maternal age-related inequalities in infant outcomes in England, Scotland, Sweden, New South Wales (NSW; Australia) and Ontario (Canada). Objectives and Approach We used administrative hospital data capturing 3,002,749 singleton births surviving to discharge between 2010-2014 (2008-2012 for Sweden). We derived risk ratios and risk differences to compare rates of preterm birth (24-37 weeks of gestation), unplanned hospital admissions, emergency department (ED) visits, and mortality within 12 months of postnatal discharge, for infants born to mothers aged 15-19, 20-24, 25-29 and 30-34 years. Results Infants born to teenage mothers experienced higher rates of preterm birth, unplanned admissions, ED visits, and mortality compared with older mothers in all countries. Despite variation in the distribution of maternal characteristics between countries, inequalities according to maternal age were similar. Infants of teenage mothers were between 1.37 (95% CI for risk ratio 1.28-1.47, Sweden) and 1.56 (95% CI 1.49-1.64, NSW) times more likely to have ≥1 unplanned hospital admission and between 2.25 (95% CI 1.92-2.64, England) and 3.87 (95% CI 2.07-7.36, Sweden) times more likely to die, compared with those born to mothers aged 30-34. Conclusion/Implications A similar excess of adverse outcomes was observed for teenage mothers in all five countries, despite different prevalence rates and support for young families. Public health strategies are needed to address these inequalities, which may be due to social risk factors associated with both young motherhood and adverse infant outcomes.

Linkage of population-based administrative data is a valuable tool for combining detailed individual-level information from different sources for research. While not a substitute for classical studies based on primary data collection, analyses of linked administrative data can answer questions that require large sample sizes or detailed data on hard-to-reach populations, and generate evidence with a high level of external validity and applicability for policy making. There are unique challenges in the appropriate research use of linked administrative data, for example with respect to bias from linkage errors where records cannot be linked or are linked together incorrectly. For confidentiality and other reasons, the separation of data linkage processes and analysis of linked data is generally regarded as best practice. However, the ‘black box’ of data linkage can make it difficult for researchers to judge the reliability of the resulting linked data for their required purposes. This article aims to provide an overview of challenges in linking administrative data for research. We aim to increase understanding of the implications of (i) the data linkage environment and privacy preservation; (ii) the linkage process itself (including data preparation, and deterministic and probabilistic linkage methods) and (iii) linkage quality and potential bias in linked data. We draw on examples from a number of countries to illustrate a range of approaches for data linkage in different contexts.

ABSTRACT Objectives England has one of the highest child mortality rates in Western Europe, while Sweden has one of the lowest. These differences suggest that improvements in early life mortality should be achievable in England. However, policy makers need to know when in the life course to target interventions to prevent the largest number of deaths in early life, e.g. by addressing the prevalence of risk factors at birth (such as preterm birth or low birthweight), or improving the care of babies after birth. This study aims to compare child mortality in England and in Sweden using whole country birth cohorts based on linked administrative health databases in order to determine whether the disparities are driven by risk factors operating before or after birth. Approach We created birth cohorts from a national birth register (Sweden) and a hospital admission database (England). These were linked to longitudinal hospital data and death registration data. All singleton live births for 2003-2012 were included and followed from birth up to five years. We compared mortality in England and in Sweden using Cox proportional hazard model with characteristics at birth (gestation, birthweight, gender, maternal age, congenital malformations), socio-economic status and country as covariates. Results The study cohort comprised 1,047,192 children in Sweden and 6,117,693 children in England. 2,820 of cohort children died in Sweden (0.3%) and 28,434 in England (0.5%). Preliminary results showed that under-5 mortality was almost twice as high in England as in Sweden (5.1 deaths per 1000 live births, 95% confidence interval (CI): 5.0/1000-5.2/1000 vs 3.0/1000, 95% CI: 2.9/1000-3.2/1000). Mortality rates were 45% higher in England during infancy, but only 15% higher in early-childhood (1-4 years). Children with congenital malformations were at similar risk of death in England (33.9/1000, 95% CI: 32.9/1000-34.8/1000) as in Sweden (32.7/1000, 95% CI: 29.5/1000-35.8/1000). The prevalence of congenital malformations, however, was twice as high in England (5.1% vs 2.6%). Conclusions Our preliminary results suggest that the disparities in early-childhood mortality were partly driven by increased prevalence of congenital malformations in England relative to Sweden, as mortality rates within this group were comparable. Individual-level data from birth cohorts constructed using linked administrative health databases enable comparing mortality among children with the same combinations of risk factors at birth. Such analyses can inform policy makers whether resources to prevent early-life mortality are most effectively targeted at improving the health of pregnant women, neonatal care, or supporting families with young children.

The aim of this paper is to estimate the cumulative effect of childhood household dysfunction (CHD) on alcohol related illness and death later in life and to test the interaction between CHD and socioeconomic background. The study utilised Swedish national registers including data of a Swedish national cohort born 1973-82 (n = 872,912), which was followed from age 18 to 29-40 years. Cox regression analyses were used to calculate hazard ratios (HR) for alcohol related illness or death in young adulthood. The CHD measure consisted of seven indicators: parental alcohol/drug misuse, mental health problems, criminality, death, divorce, social assistance, and child welfare interventions. Childhood socioeconomic position (SEP) was indicated by parental occupational status. Outcomes were alcohol related inpatient hospital care, specialised outpatient care or deaths. Using the highest socioeconomic group without CHD experience as a reference, those in the same socioeconomic group with one indicator of CHD had HRs of 2.1 [95% CI: 1.7-2.5], two CHD indicators 5.6 [4.4-7.1], three or more indicators 9.4 [7.1-12.4] for retrieving inpatient care. Socioeconomic disadvantage further increased the risks-those with low socioeconomic background and three CHD indicators or more had a HR of 12.5 [10.9-14.3]. Testing for interaction suggests that the combined HRs deviates from additivity [Synergy index: 1.6, 95% CI: 1.4-1.9]. The results for outpatient care were similar, but not as pronounced. In conclusion, this Swedish national cohort study shows that childhood household dysfunction is strongly and cumulatively associated to alcohol related illness later in life and that it interacts with socioeconomic disadvantage.

High rates of mental health problems have been described in young refugees, but few studies have been conducted on substance misuse. This study aimed to investigate the patterns of hospital care and criminality associated with substance misuse in refugees who settled in Sweden as teenagers.Gender stratified Cox regression models were used to estimate the risks of criminal convictions and hospital care associated with substance misuse from national Swedish data for 2005-2012. We focused on 22,992 accompanied and 5,686 unaccompanied refugees who were aged 13-19 years when they settled in Sweden and compared them with 1 million native Swedish youths from the same birth cohort.The risks of criminal conviction associated with substance misuse increased with the length of residency in male refugees, after adjustment for age and domicile. The hazard ratios (HRs) were 5.21 (4.39-6.19) for unaccompanied and 3.85 (3.42-4.18) for accompanied refugees after more than 10 years of residency, compared with the native population. The risks were slightly lower for hospital care, at 2.88 (2.18-3.79) and 2.52(2.01-3.01) respectively. Risks were particularly pronounced for male refugees from the Horn of Africa and Iran. The risks for all male refugees decreased substantially when income was adjusted for. Young female refugees had similar risks to the general population.The risks of criminality and hospital care associated with substance misuse in young male refugees increased with time of residency in Sweden and were associated with a low level of income compared with the native Swedish population. Risks were similar in accompanied and unaccompanied refugees.

Herpes simplex encephalitis (HSE) is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats) with the asymptomatic infection of BN (Brown Norway). Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains), displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus) named Hse6 towards the end of chromosome 4 (160.89-174Mb) containing the Vwf (von Willebrand factor) gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism). Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008) after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.