Nationwide population-based cohort study of psychiatric disorders in individuals with Ehlers-Danlos syndrome or hypermobility syndrome and their siblings

Background: To assess the risk of psychiatric disorders in Ehlers-Danlos syndrome (EDS) and hypermobility syndrome. Methods: Nationwide population-based matched cohort study. EDS, hypermobility syndrome and psychiatric disorders were identified through Swedish national registries. Individuals with EDS (n = 1,771) were matched with comparison individuals (n = 17,710). Further, siblings to individuals with EDS who did not have an EDS diagnosis themselves were compared with matched comparison siblings. Using conditional logistic regression, risk of autism spectrum disorder (ASD), bipolar disorder, attention deficit hyperactivity disorder (ADHD), depression, attempted suicide, suicide and schizophrenia were estimated. The same analyses were conducted in individuals with hypermobility syndrome (n = 10,019) and their siblings. Results: EDS was associated with ASD: risk ratio (RR) 7.4, 95 % confidence interval (95 % CI) 5.2–10.7; bipolar disorder: RR 2.7, CI 1.5–4.7; ADHD: RR 5.6, CI 4.2–7.4; depression: RR 3.4, 95 % CI 2.9–4.1; and attempted suicide: RR 2.1, 95 % CI 1. 7–2.7, but not with suicide or schizophrenia. EDS siblings were at increased risk of ADHD: RR 2.1, 95 % CI 1.4–3.3; depression: RR 1.5, 95 % CI 1.1–1.8; and suicide attempt: RR 1.8, 95 % CI 1.4–2.3. Similar results were observed for individuals with hypermobility syndrome and their siblings. Conclusions: Individuals with EDS and hypermobility syndrome are at increased risks of being diagnosed with psychiatric disorders. These risk increases may have a genetic and/or early environmental background as suggested by evidence showing that siblings to patients have elevated risks of certain psychiatric disorders.NonePublishe

Cohort profile : Swedish Twin Study on Prediction and Prevention of Asthma (STOPPA)

Asthma is a common childhood disease and several risk factors have been identified, however the impact of genes and environment is not fully understood. The aim of the Swedish Twin study On Prediction and Prevention of Asthma (STOPPA) is to identify environmental (birth characteristics and early life) and genetic (including epigenetic) factors as determinants for asthmatic disease. Based on the Child and Adolescent Twin Study in Sweden (parental interview at 9 or 12 years, N~23,900) and an asthma and/or wheezing algorithm, we identified a sample of monozygotic (MZ) and dizygotic (DZ) same-sexed twin pairs. The twin pairs were identified as asthma concordant (ACC), asthma discordant (ADC) and healthy concordant (HCC). A sample of 9- to 14-year-old twins and their parents were invited to participate in a clinical examination. Background characteristics were collected in questionnaires and obtained from the National Health Registers. A clinical examination was performed to test lung function and capacity (spirometry with reversibility test and exhaled nitric oxide) and collect blood (serology and DNA), urine (metabolites), feces (microbiota) and saliva (cortisol). In total, 376 twin pairs (752 individual twins) completed the study, response rate 52%. All participating twins answered the questionnaire and >90% participated in lung function testing, blood and saliva sampling. This article describes the design, recruitment, data collection, measures, background characteristics as well as ongoing and planned analyses in STOPPA. Potential gains of the study include the identification of biomarkers, the emergence of candidates for drug development and new leads for prevention of asthma and allergic disease.NonePublishe

Patterns of Nonrandom Mating Within and Across 11 Major Psychiatric Disorders

Psychiatric disorders are heritable, polygenic traits, which often share risk alleles and for which nonrandom mating has been suggested. However, despite the potential etiological implications, the scale of nonrandom mating within and across major psychiatric conditions remains unclear

Early-Life Adversity Due to Bereavement and Inflammatory Diseases in the Next Generation: A Population Study in Transgenerational Stress Exposure

Emerging evidence suggests that trauma experienced in childhood has negative transgenerational implications for offspring mental and physical health. We aimed to investigate whether early-life adversity experienced as bereavement is associated with chronic inflammatory health in offspring. The study population included 3 generations of Swedish families with a base population of 453,516 children (generation 3) born in 2001-2012. Exposure was defined as the middle generation's (generation 2) experiencing bereavement in childhood due to the death of a parent (generation 1). Outcomes in generation 3 included 2 diagnoses of inflammatory diseases, including asthma, allergic diseases, eczema, and autoimmune diseases. Survival analysis was used to identify causal pathways, including investigation of mediation by generation 2 mood disorders and socioeconomic status (SES). We found that early-life bereavement experienced by women was associated with early-onset offspring asthma (hazard ratio = 1.15, 95% confidence interval: 1.08, 1.23); mediation analysis revealed that 28%-33% of the association may be mediated by SES and 9%-20% by mood disorders. Early-life bereavement experienced by men was associated with autoimmune diseases in offspring (hazard ratio = 1.31, 95% confidence interval: 1.06, 1.62), with no evidence of mediation. In conclusion, adversity experienced early in life may contribute to an increased risk of inflammatory diseases which is partly mediated by mood disorders and SES

A Multi-Phase Transport model for nuclear collisions at RHIC

To study heavy ion collisions at energies available from the Relativistic Heavy Ion Collider, we have developed a multi-phase transport model that includes both initial partonic and final hadronic interactions. Specifically, the parton cascade model ZPC, which uses as input the parton distribution from the HIJING model, is extended to include the quark-gluon to hadronic matter transition and also final-state hadronic interactions based on the ART model. Predictions of the model for central Au on Au collisions at RHIC are reported.Comment: 7 pages, 4 figure

Correlation of computed tomography with carotid plaque transcriptomes associates calcification with lesion-stabilization

Background and aims: Unstable carotid atherosclerosis causes stroke, but methods to identify patients and lesions at risk are lacking. We recently found enrichment of genes associated with calcification in carotid plaques from asymptomatic patients. Here, we hypothesized that calcification represents a stabilising feature of plaques and investigated how macro-calcification, as estimated by computed tomography (CT), correlates with gene expression profiles in lesions. Methods: Plaque calcification was measured in pre-operative CT angiographies. Plaques were sorted into high- and lowcalcified, profiled with microarrays, followed by bioinformatic analyses. Immunohistochemistry and qPCR were performed to evaluate the findings in plaques and arteries with medial calcification from chronic kidney disease patients. Results: Smooth muscle cell (SMC) markers were upregulated in high-calcified plaques and calcified plaques from symptomatic patients, whereas macrophage markers were downregulated. The most enriched processes in high-calcified plaques were related to SMCs and extracellular matrix (ECM) organization, while inflammation, lipid transport and chemokine signaling were repressed. These findings were confirmed in arteries with high medial calcification. Proteoglycan 4 (PRG4) was identified as the most upregulated gene in association with plaque calcification and found in the ECM, SMA+ and CD68+/TRAP + cells. Conclusions: Macro-calcification in carotid lesions correlated with a transcriptional profile typical for stable plaques, with altered SMC phenotype and ECM composition and repressed inflammation. PRG4, previously not described in atherosclerosis, was enriched in the calcified ECM and localized to activated macrophages and smooth muscle-like cells. This study strengthens the notion that assessment of calcification may aid evaluation of plaque phenotype and stroke risk.The European Union’s Horizon 2020/Marie Sklodowska-Curie grant agreement No 722609 (INTRICARE);Swedish Heart and Lung FoundationSwedish Research Council (K2009-65X-2233-01-3, K2013- 65X-06816-30-4, 349-2007-8703)Uppdrag Besegra Stroke (P581/ 2011-123)Stockholm County Council (ALF2011-0260, ALF-2011- 0279)Swedish Society for Medical ResearchTore Nilsson’s FoundationMagnus Bergvall’s FoundationKarolinska Institutet FoundationEuropean Commission (722609)Publishe

Study of in-medium ω\omega meson properties in Ap, pA and AA collisions

We propose to investigate the in-medium properties of vector $\omega$ mesons at the normal nuclear density in Ap(pA) collisions and at higher density in AA collisions at the ITEP accelerator facility TWAC. Using of the inverse Ap kinematics will permit us to study the $\omega$ meson production in a wide momentum interval included the not yet explored range of small meson momenta relative to the projectile nuclei where the mass modification effect in nuclear matter is expected to be the strongest. Momentum dependence of the in-medium $\omega$ meson width will be studied in the traditional pA kinematics. We intend to use the electromagnetic calorimeter for reconstruction of the $\omega$ meson invariant mass by detecting photons from the $\omega \to \pi^{0}\gamma \to 3\gamma$ decay. The model calculations and simulations with RQMD generator show feasibility of the proposed experiment. Available now intensity of the ion beams provides a possibility to collect large statistics and make decisive conclusion about the $\omega$ meson properties at density of normal nuclei. At the second stage of the investigation the $\omega$ meson properties will be studied in AA collisions at higher density. Interpretation of these measurements will be based on the results obtained in Ap(pA) interactions. Further investigation of the in-medium properties of light unflavored and charmed mesons can be performed at ITEP and at GSI(FAIR) where higher ion energies will be accessible in near future.Comment: 26 pages, 10 figures, 2 table

Physical and cognitive fitness in young adulthood and risk of amyotrophic lateral sclerosis at early age

BACKGROUND AND PURPOSE: There is a clinical impression that patients with amyotrophic lateral sclerosis (ALS) have a higher level of physical fitness and lower body mass index (BMI) than average. However, there is a lack of literature examining the relationship between cognitive fitness and ALS risk. In this study we explored the associations of both physical and cognitive fitness with future risk of ALS. METHODS: Data on physical fitness, BMI, intelligence quotient (IQ) and stress resilience were collected from 1 838 376 Swedish men aged 17-20 years at conscription during 1968-2010. Their subsequent ALS diagnoses were identified through the Swedish Patient Register. Hazard ratios (HRs) and 95% CIs from flexible parametric models were used to assess age-specific associations of physical fitness, BMI, IQ and stress resilience with ALS. RESULTS: We identified 439 incident ALS cases during follow-up (mean age at diagnosis: 48 years). Individuals with physical fitness above the highest tertile tended to have a higher risk of ALS before the age of 45 years (range of HRs: 1.42-1.75; statistically significant associations at age 41-43 years) compared with others. Individuals with BMI >/= 25 tended to have a lower risk of ALS at all ages (range of HRs: 0.42-0.80; statistically significant associations at age 42-48 years) compared with those with BMI < 25. Individuals with IQ above the highest tertile had a statistically significantly increased risk of ALS at an age of 56 years and above (range of HRs: 1.33-1.81), whereas individuals with stress resilience above the highest tertile had a lower risk of ALS at an age of 55 years and below (range of HRs: 0.47-0.73). CONCLUSIONS: Physical fitness, BMI, IQ and stress resilience in young adulthood might be associated with the development of ALS at an early age.NoneAccepte

Overweight in relation to allergic disease in childhood and adolescence

The prevalences of childhood overweight and allergic diseases have increased in parallel during the last decades. The overall aim of this thesis was to investigate the associations between overweight (maternal and childhood) and allergic diseases, as well as lung function, throughout childhood up to adolescence. In addition, we investigated the validity of self-reported height, weight and corresponding body mass index (BMI) among Swedish adolescents. All studies were based on the BAMSE study, a population-based birth cohort of 4,089 children followed until age 16 years. Maternal BMI was obtained from the Swedish medical birth register, while childhood BMI was measured at clinical investigations, collected from child and school health care records and self-reported. Allergic diseases were assessed by repeated questionnaires regarding symptoms and medications, while allergic sensitization to inhalant allergens was defined by the presence of specific immunoglobulin E (IgE)-antibodies in blood. Lung function was measured by spirometry at 8 and 16 years and by impulse oscillometry (IOS) at 16 years. The results of Study I showed that maternal BMI in early pregnancy was associated with asthma, but not rhinitis, eczema or allergic sensitization in the offspring up to 16 years. The association was strongest for persistent asthma, while no increased risk was observed for transient asthma. Categorization of maternal BMI showed that maternal obesity, but not overweight, was significantly associated with childhood asthma. However, the child’s own weight status could partly explain the observed association between maternal BMI and asthma in the offspring. In Study II, we found that girls with persistent asthma had a higher BMI and an increased risk of overweight throughout childhood, compared to girls without asthma. Girls with transient asthma had an increased risk of overweight at ages 4-7.9 years, whereas girls with late-onset asthma had a tendency towards an increased risk of overweight at age ≥15 years. In boys, the difference in BMI between children with and without asthma was smaller, and no consistent association was observed between asthma phenotypes and overweight. In Study III, we observed that overweight and obesity at age 8 years were associated with increased forced vital capacity (FVC) and to some extent forced expiratory volume in one second (FEV1), but reduced FEV1/FVC ratios at 8 and 16 years. The strongest association with FEV1/FVC was observed for persistent overweight at both 8 and 16 years, whereas no significant association was found for transient overweight. Cross-sectional analyses of IOS showed that overweight and obesity were associated with higher peripheral airway resistance and reactance at 16 years. The result of Study IV showed that self-reported and measured height and weight were highly correlated at 16 years (r=0.98 for height, r=0.96 for weight). On average, self-reported weight was underreported by 1.1 kg and height was overreported by 0.5 cm, leading to an underestimation of BMI by 0.5 kg/m2. The accuracy of self-reported BMI was somewhat lower among girls and among overweight and obese participants, compared to normal weight participants. Our results suggest that maternal and childhood overweight and obesity are associated with asthma and evidence of airway obstruction in children and adolescents. The association between maternal BMI and asthma may, to some extent, be mediated through childhood overweight and seems to be explained by non-allergic mechanisms. In addition, we conclude that web-based self-reported BMI can be used as a valid, quick and cost-effective alternative to measured BMI among Swedish adolescents. The accuracy however declines with increasing BMI, and is somewhat lower among girls compared to boys

Heavy Meson Production in Proton-Nucleus Reactions with Empirical Spectral Functions

We study the production of $K^+, \rho, \omega$ and $\phi$ mesons in $p + ^{12}C$ reactions on the basis of empirical spectral functions. The high momentum, high removal energy part of the spectral function is found to be negligible in all cases close to the absolute threshold. Furthermore, the two-step process ($pN \rightarrow \pi N N; \pi N \rightarrow N + K^+, \rho, \omega, \phi$) dominates the cross section at threshold energies in line with earlier calculations based on the folding model.Comment: 18 pages, LaTeX, plus 14 postscript figures, submitted to Z. Phys.