Search

Sports participation, physical activity, and friendship quality are theorized to have protective effects on the developmental emergence of substance use and self-harm behavior in adolescence, but existing research has been mixed. This ambiguity could reflect, in part, the potential for confounding of observed associations by genetic and environmental factors, which previous research has been unable to rigorously rule out. We used data from the prospective, population-based Child and Adolescent Twin Study in Sweden ( n = 18,234 born 1994-2001) and applied a co-twin control design to account for potential genetic and environmental confounding of sports participation, physical activity, and friendship quality (assessed at age 15) as presumed protective factors for adolescent substance use and self-harm behavior (assessed at age 18). While confidence intervals widened to include the null in numerous co-twin control analyses adjusting for childhood psychopathology, parent-reported sports participation and twin-reported positive friendship quality were associated with increased odds of alcohol problems and nicotine use. However, parent-reported sports participation, twin-reported physical activity, and twin-reported friendship quality were associated with decreased odds of self-harm behavior. The findings provide a more nuanced understanding of the risks and benefits of putative protective factors for risky behaviors that emerge during adolescence.

Background: An outdoor pig herd was affected by severe respiratory disease in one out of three pastures. At necropsy, Mycoplasma hyopneumoniae and Pasteurella multocida were detected in the lungs, as well as the lung worm Metastrongylus apri. The life cycle of Metastrongylus spp. includes earthworms as intermediate hosts, and since domestic pigs mainly are reared indoors, lungworm infections have not been diagnosed in domestic pigs in Sweden for decades, not even in pigs reared outdoors. Therefore, this disease outbreak was scrutinised from the view of validating the impact of Metastrongylus spp., Results: At the time of the disease outbreak, neither eggs of Metastrongylus spp., Trichuris suis nor Ascaris suum were detected in faeces of pigs aged ten weeks. In contrast, five-months-old pigs at the pasture with respiratory disease shed up to 3800 eggs per gram (Epg) of Ascaris suum and up to 1100 Epg of Trichuris suis, whereas eggs of these parasites were not demonstrated in healthy pigs aged six months at another pasture. Low numbers of eggs from Metastrongylus spp. (< 150 Epg) were seen in faecal samples from both these age categories. At slaughter, seven weeks later, ten normal weighted pigs in the preceding healthy batch were compared with ten normal weighted and five small pigs from the affected batch. Healing Mycoplasma-like pneumonic lesions were seen in all groups. All small pigs shed eggs of Ascaris suum in the faeces, compared to around 50% of the larger pigs. Metastrongylus spp. were demonstrated in 13 of the 25 pigs (52%), representing all groups included., Conclusion: As Metastrongylus spp. were demonstrated regardless of health status, and also in another healthy outdoor herd, the impact of Metastrongylus spp. on the outbreak of respiratory disease was depreciated. Instead, a possible association with a high burden of Ascaris suum was suggested to have preceded the severe outbreak with respiratory disease in the affected herd. Further, it was concluded that Metastrongylus spp. will escape detection at routine meat inspections made at slaughterhouses, and as they appeared to generally not induce clinical signs of respiratory disease Metastrongylus spp. may be more common in outdoor production than previously believed., (© 2022. The Author(s).)

Purpose: To examine the trajectory of psychological distress from 1 to 2 years after esophageal cancer surgery, and whether dispositional optimism could predict the risk of postoperative psychological distress., Methods: This Swedish nationwide longitudinal study included 192 patients who had survived for 1 year after esophageal cancer surgery. We measured dispositional optimism with the Life Orientation Test-Revised (LOT-R) 1 year post-surgery and psychological distress with the Hospital Anxiety and Depression Scale 1, 1.5, and 2 years post-surgery. Latent growth curve models were used to assess the trajectory of postoperative psychological distress and to examine the predictive validity of dispositional optimism., Results: One year after surgery, 11.5% (22 of 192) patients reported clinically significant psychological distress, and the proportion increased to 18.8% at 1.5 years and to 25.0% at 2 years post-surgery. Higher dispositional optimism predicted a lower probability of self-reported psychological distress at 1, 1.5, and 2 years after esophageal cancer surgery. For each point increase in the LOT-R sum score, the odds of psychological distress decreased by 44% (OR, 0.56; 95% CI, 0.40 to 0.79)., Conclusion: The high prevalence and longitudinal increase of self-reported psychological distress after esophageal cancer surgery indicate the unmet demands for timely psychological screening and interventions. Measuring dispositional optimism may help identify patients at higher risk of developing psychological distress, thereby contributing to the prevention of postoperative psychological distress., (© 2021. The Author(s).)

Purpose: To assess whether higher dispositional optimism could predict better health-related quality of life (HRQL) after esophageal cancer surgery., Methods: This Swedish nationwide longitudinal study included 192 patients who underwent esophagectomy for cancer. The exposure was dispositional optimism measured by the Life Orientation Test-Revised (LOT-R) at 1 year post-surgery. Patients were categorized into four subgroups (very low, moderately low, moderately high, and very high dispositional optimism) based on the quartile of the LOT-R sum score. The outcome was HRQL assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and Quality of Life Questionnaire-Esophago-Gastric module 25 (QLQ-OG25) at 1, 1.5, and 2 years post-surgery. Linear mixed-effects models, adjusted for potential confounders, were used to examine the mean score difference (MSD) with 95% confidence interval of HRQL among the four patient subgroups., Results: Patients with very high dispositional optimism reported clinically relevantly better global quality of life, emotional function, and social function (MSD range 10-16) and less severe symptoms in pain, dyspnea, diarrhea, eating difficulty, anxiety, dry mouth, trouble with taste, worry about weight loss, and self-doubt about body image (MSD range - 9 to - 22) than patients with lower dispositional optimism. Patients with moderately high dispositional optimism reported clinically and statistically significantly better global quality of life (MSD 10) and less severe diarrhea (MSD - 9) than patients with lower dispositional optimism. Adjusted MSDs were constant over the three time points in all aspects except for eating difficulty., Conclusions: Measuring dispositional optimism could help identify patients at higher risk of poor HRQL recovery after esophageal cancer surgery., (© 2021. The Author(s).)

Purpose: The aim of the study was to investigate the magnitude of an independent association between bullying victimization and self-harm and suicide attempt in adolescence after adjusting for unmeasured and measured confounding factors., Methods: Using the Child and Adolescent Twin Study in Sweden, we examined twins born between 1994 and 1999 (n = 13,852). Twins self-reported bullying victimization at age 15 years and self-harm and suicide attempt at age 18 years. We created a factor score of 13 bullying items, on which self-harm and suicide attempt items were regressed in three models: (1) among unrelated individuals; (2) among co-twins, in which a twin exposed to more bullying was compared with his/her co-twin who was exposed to less; and (3) among co-twins while adjusting for indicators of childhood psychopathology., Results: Among unrelated individuals, a one standard deviation increase in bullying victimization was associated with increased odds for self-harm (odds ratio [OR], 1.29 [95% confidence interval, 1.23-1.36]) and suicide attempt (OR, 1.68 [1.53-1.85]). Among co-twins, the odds attenuated for self-harm (OR, 1.19 [1.09-1.30]) and suicide attempt (OR, 1.39 [1.17-1.66]). Finally, when accounting for childhood psychopathology, there was a 14% (1.04-1.25) and 25% (1.03-1.52) relative increase in odds of self-harm and suicide attempt, respectively., Conclusions: The results suggest that bullying victimization was uniquely associated with self-harm and suicide attempt over and above the confounding because of unmeasured and measured factors (i.e., familial vulnerability and pre-existing psychopathy). However, magnitudes were small, suggesting that additional interventions and screenings are needed to address suicidality apart from bullying interventions., (Copyright © 2020 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Participation in daily activities is expressed as a human right. Full participation of children with disabilities in daily activities creates optimal opportunities for learning and development. Previous studies have focused primarily on proxy ratings of participation of children with intellectual disabilities in daily activities. However, little is known about how the children rate barriers and facilitators to their participation in everyday activities., Objectives: To identify barriers to and facilitators for everyday activities as experienced by children with intellectual disabilities from low- and middle-income countries and high-income countries. The research questions were as follows: 'what barriers to participation do children with disabilities experience in everyday activities?' and 'what facilitators to participation do children with disabilities experience in everyday activities?', Method: A qualitative content analyses was used in this study, and individual interviews were conducted with 49 children with intellectual disabilities. The interviews were performed using pictures. The children also selected the most important activities and described in their own words the facilitators and barriers relevant to being able to perform the activities., Results: The most important activities were organised leisure activities, formal learning at school, taking care of other family members and family mealtimes. Self-reported barriers identified were personal functioning, social exclusion and lack of resources. The identified facilitators included satisfaction, personal capability, being included and having access to resources., Conclusion: These findings provide important knowledge about the factors to consider in the development of interventions, aimed at improving the participation of children with intellectual disabilities., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2021. The Authors.)

Background: Research has demonstrated that individuals who identify as a sexual minority (e.g., gay/lesbian, bisexual) are at increased risk for suicidality-related outcomes. However, previous research is primarily limited by the lack of adjustment for unmeasured (i.e., genetic and environmental) confounding factors and previous psychopathology., Methods: Using the Child and Adolescent Twin Study in Sweden, we employed a co-twin control design to examine the extent to which the association between sexual orientation and adolescent suicide attempt and self-harm (SA/SH) was independent of genetic and environmental factors shared by twins, as well as measured symptoms of childhood psychopathology., Results: Adolescents who identified as a sexual minority (i.e., gay/lesbian, bisexual, or other sexual orientation) were at two-fold increased odds for SA/SH (OR, 2.01 [95% confidence interval, 1.63-2.49) compared to heterosexual adolescents. When adjusting for all genetic and shared environmental factors that make twins similar and for measured childhood psychopathology, the association remained positive but attenuated to OR, 1.55 (1.11-2.16)., Conclusions: Identifying as a sexual minority was associated with approximately 50% increased odds of SA/SH in adolescence after adjusting for unmeasured genetic and environmental factors shared by twins and for childhood psychopathology. The results support that environmental factors specifically associated with identifying as a sexual minority likely increase risk for SA/SH. Our findings highlight the need to monitor suicidality risk among this group., (© 2020 Association for Child and Adolescent Mental Health.)

Anthelmintic efficacy was investigated in nine sow herds that had been identified with high faecal egg counts in a prevalence study. Faecal samples were collected from a total of 104 individual sows, and analysed using a centrifugal flotation McMaster technique. Samples positive for strongyle eggs were cultured to third stage larvae (L3) for genus identification and then further identified to Oesophagostomum species by sequencing. Following the initial sample collection, the sows were treated with either fenbendazole (FBZ, n = 5 farms) or ivermectin (IVM, n = 4 farms) at the recommended dosing and sampled again 14 days post treatment. Faecal Egg Count Reduction (FECR) was used to determine the treatment efficacy. With respect to Ascaris suum, the anthelmintic treatment was successful (FECR >90%) on the five farms where this parasite was detected, regardless of what drug had been used. In contrast, 4/9 farms were positive for Oesophagostomum spp. post treatment, out of which three had a FECR of <90%. These three herds had all been treated with injectable IVM. Out of the six farms where treatment showed good efficacy (FECR 95-100%), five herds had used FBZ and one herd IVM. This study is the first to recognise reduced efficacy to IVM on Oesophagostomum spp. in Swedish pigs. Sequencing of the Oesophagostomum L3 showed that both O. dentatum and O. quadrispinulatum were present on 5/9 farms pre-treatment and on 2/9 farms post-treatment, unrelated to what anthelmintic had been used. Given these findings we could not correlate the reduced efficacy by the species of Oesophagostomum present in the herd. Prolonged usage of only one class of anthelmintic may predispose selection of resistance and has been suspected as a cause of treatment failure of porcine Oesophagostomum spp. in other studies. On all three farms showing reduced efficacy, IVM had been used as the sole anthelmintic drug for several years, and two of the farms also used IVM twice or more per year to control sarcoptic mange. A reduced efficacy to the available anthelmintic drugs used in the control of Oesophagostomum spp., may result in a subsequent surge of the possible negative effects caused by this parasite., (Copyright © 2021. Published by Elsevier B.V.)

The global pig production has undergone major changes over the past 30 years with larger farms, more intensified production as well as improved hygiene and biosecurity practices. To investigate whether these changes, along with expanded pig welfare, have had an impact on parasite occurrence, a cross-sectional study was conducted in Sweden on farms where the pigs are always loose-housed, floors are solid and bedding material is provided. A total of 1615 faecal samples were collected on 42 conventional indoor farms from a) post-weaning piglets (n = 337); b) growers (n = 345); c) fatteners (n = 308); d) dry sows (n = 277) and e) pre-partum sows (n = 348). Samples were analysed using centrifugal flotation with a saturated glucose-salt solution and a modified McMaster technique, with a lower detection limit of 50 eggs or oocysts per gram. Samples positive for strongyle-type eggs were cultured to third stage larvae for genus identification. Farms also responded to a questionnaire regarding biosecurity, hygienic measures, and other management routines. Risk factors for parasite occurrence were assessed using mixed-effects logistical regression to account for farm-level clustering of samples. Interestingly, the prevalence of Ascaris suum was reduced compared to a similar investigation in the 1980s. In the present study A. suum was detected only in 43 % of the herds, with the highest prevalence in pre-partum sows (37 %) followed by fatteners (25 %). Small sized farms were associated with higher odds of being positive, compared to large sized farms (OR = 159.1, P = 0.010). Oesophagostomum spp. were detected in 64 % of the herds and again mainly in pre-partum sows (63 %). Trichuris suis was detected in 10 % of the herds but only in <1% of the samples. Moreover, Cystoisospora suis and Eimeria spp. were detected on 60 % and 64 % the farms, with the highest prevalence in post-weaning piglets and sows, respectively. Anthelmintic drugs (ivermectin or fenbendazole) were commonly used and administered mainly to pre-partum sows on 93 % of the farms. Toltrazuril against neonatal coccidiosis was administered to piglets on 14 % of the farms. The use of antiparasitic drugs did not significantly affect parasite prevalence. Overall, it appears that the altered farming routines with focus on improved pig welfare have not solely resulted in a higher occurrence of parasites, most likely due to the adequate biosecurity and hygiene practices instituted. Thus, there seems to be no conflict between implementing measures to promote pig welfare and adequately control the more pathogenic and economically important parasites., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Internal parasites are common in pigs worldwide and may induce clinical disease or subclinical infections with negative effects such as poor weight gain and reduced welfare, which in turn affect productivity. Effective parasite control to reduce the negative impact of parasitic infections demands a combination of antiparasitic drugs as well as various hygiene and biosecurity practices. The aim of this study was to obtain information on current management practices and parasite control routines used on Swedish pig farms using an online questionnaire., Results: Antiparasitic drugs were used on 69% of the farms routinely and were mainly administered to sows just prior to farrowing. Less than 5% of the herds conducted faecal analysis for parasites. Batchwise, age segregated rearing was common and overall, it was practiced for piglets, growers, and fatteners on 88, 80 and 75% of the farms, respectively. Large and medium sized farms appeared to apply stricter hygiene and biosecurity measures to the growing pigs compared to small farms. Dry sows were mainly housed in groups on deep litter straw beds and cleaning, as well as disinfection, between each group was less common compared to what was practiced for growing pigs. Outdoor access was rare and only occurred on organic and small farms. Most of the farms, 54, 74 and 82% of small, medium, and large sized herds respectively, reported to have less than 5% white spot lesions, caused by migrating A. suum larvae, registered at slaughter., Conclusion: Several risk factors for parasite infections, such as bedding material, group housing and solid floors, are mandatory requirements by national law. However, it was evident from this study that although strategic hygiene and biosecurity practices appeared common, they were not practiced in all herds and less so for dry sows. Antiparasitic drugs were used frequently and mainly through routine prophylactic treatments without prior testing for parasites. A holistic approach is necessary when designing efficient parasite control programs, and it is essential that management factors and routine monitoring of parasites are given attention. This to achieve efficient parasite control and reduce the risk of unnecessary use of antiparasitic drugs.

Background: Although attention-deficit hyperactivity disorder (ADHD) is classified as a neurodevelopmental disorder in the latest diagnostic manuals, it shows phenotypic and genetic associations of similar magnitudes across neurodevelopmental, externalising and internalising disorders., Aims: To investigate if ADHD is aetiologically more closely related to neurodevelopmental than externalising or internalising disorder clusters, after accounting for a general psychopathology factor., Method: Full and maternal half-sibling pairs (N = 774 416), born between 1980 and 1995, were identified from the Swedish Medical Birth and Multi-Generation Registers, and ICD diagnoses were obtained from the Swedish National Patient Register. A higher-order confirmatory factor analytic model was fitted to examine associations between ADHD and a general psychopathology factor, as well as a neurodevelopmental, externalising and internalising subfactor. Quantitative genetic modelling was performed to estimate the extent to which genetic, shared and non-shared environmental effects influenced the associations with ADHD., Results: ADHD was significantly and strongly associated with all three factors (r = 0.67-0.75). However, after controlling for a general psychopathology factor, only the association between ADHD and the neurodevelopmental-specific factor remained moderately strong (r = 0.43, 95% CI = 0.42-0.45) and was almost entirely influenced by genetic effects. In contrast, the association between ADHD and the externalising-specific factor was smaller (r = 0.25, 95% CI = 0.24-0.27), and largely influenced by non-shared environmental effects. There remained no internalising-specific factor after accounting for a general factor., Conclusions: Findings suggest that ADHD comorbidity is largely explained by genetically influenced general psychopathology, but the strong link between ADHD and other neurodevelopmental disorders is also substantially driven by unique genetic influences.

Understanding the dynamics of the human proteome is crucial for developing biomarkers to be used as measurable indicators for disease severity and progression, patient stratification, and drug development. The Proximity Extension Assay (PEA) is a technology that translates protein information into actionable knowledge by linking protein-specific antibodies to DNA-encoded tags. In this report we demonstrate how we have combined the unique PEA technology with an innovative and automated sample preparation and high-throughput sequencing readout enabling parallel measurement of nearly 1500 proteins in 96 samples generating close to 150,000 data points per run. This advancement will have a major impact on the discovery of new biomarkers for disease prediction and prognosis and contribute to the development of the rapidly evolving fields of wellness monitoring and precision medicine., Competing Interests: Conflict of interest All authors are employees of Olink Proteomics AB commercializing the described method. An author may or may not be named as an inventor on current patents owned and controlled by Olink Proteomics AB, https://www.olink.com/patents/, as amended from time to time. All authors have financial interest in Olink Holding AB., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Top-down volitional command of eye movements may serve as a candidate endophenotype of ADHD, an important function underlying goal-directed action in everyday life. In this twin study, we examined the relation between performance on a response inhibition eye-tracking paradigm and parent-rated ADHD traits in a population-based twin sample. We hypothesized that altered eye movement control is associated with the severity of ADHD traits and that this association is attributable to genetic factors., Methods: A total of 640 twins (320 pairs, 50% monozygotic) aged 9-14 years) from the Child and Adolescent Twin Study in Sweden (CATSS) participated. Twins performed the antisaccade task indexing inhibitory alterations as either direction errors (following exogenous cues rather than instructions) or premature anticipatory eye movements (failure to wait for cues). We calculated the associations of eye movement control and ADHD traits using linear regression mixed-effects models and genetic and environmental influences with multivariate twin models., Results: Premature anticipatory eye movements were positively associated with inattentive traits (β = .17; 95% CI: 0.04, 0.31), while controlling for hyperactive behaviors and other covariates. Both premature anticipatory eye movements and inattention were heritable (h 2  = 0.40, 95% CI: 0.22, 0.56; h 2  = 0.55; 95% CI: 0.42, 0.65; respectively), and their genetic correlation was small but statistically significant (r = .19, 95% CI: 0.02, 0.36). However, the genetic correlation did not remain significant after adjusting for covariates (age, sex, hyperactivity traits, IQ). No link was found between direction errors and ADHD traits., Conclusions: This study indicates that there is a specific, genetically influenced, relation between top-down eye movement control and the inattentive traits typical of ADHD., (© 2020 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

This study investigated the association between the ability to maintain prolonged (2-minute) fixation on a visual target and ADHD traits in a sample consisting of 120 monozygotic and 120 dizygotic twin pairs, aged 9 to 14 years. More intrusive saccades during the task was associated with higher level of parent-reported ADHD traits. Both intrusive saccades and ADHD symptoms had high heritability estimates, and there was a moderate genetic correlation between number of intrusive saccades and ADHD. This study suggests that inability to maintain ocular fixation for longer times is etiologically linked to ADHD traits in the general population., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

The beneficial effects of protons are primarily based on reduction of low to intermediate radiation dose bath to normal tissue surrounding the radiotherapy target volume. Despite promise for reduced long-term toxicity, the percentage of cancer patients treated with proton therapy remains low. This is probably caused by technical improvements in planning and delivery of photon therapy, and by high cost, low availability and lack of high-level evidence on proton therapy. A number of proton treatment facilities are under construction or have recently opened; there are now two operational Scandinavian proton centres and two more are under construction, thereby eliminating the availability hurdle. Even with the advantageous physical properties of protons, there is still substantial ambiguity and no established criteria related to which patients should receive proton therapy. This topic was discussed in a session at the Nordic Collaborative Workshop on Particle Therapy, held in Uppsala 14-15 November 2019. This paper resumes the Nordic-Baltic perspective on proton therapy indications and discusses strategies to identify patients for proton therapy. As for indications, neoplastic entities, target volume localisation, size, internal motion, age, second cancer predisposition, dose escalation and treatment plan comparison based on the as low as reasonably achievable (ALARA) principle or normal tissue complication probability (NTCP) models were discussed. Importantly, the patient selection process should be integrated into the radiotherapy community and emphasis on collaboration across medical specialties, involvement of key decision makers and knowledge dissemination in general are important factors. An active Nordic-Baltic proton therapy organisation would also serve this purpose.

Common genetic risk variants have been implicated in the etiology of clinical attention-deficit/hyperactivity disorder (ADHD) diagnoses and symptoms in the general population. However, given the extensive comorbidity across ADHD and other psychiatric conditions, the extent to which genetic variants associated with ADHD also influence broader psychopathology dimensions remains unclear. The aim of this study was to evaluate the associations between ADHD polygenic risk scores (PRS) and a broad range of childhood psychiatric symptoms, and to quantify the extent to which such associations can be attributed to a general factor of childhood psychopathology. We derived ADHD PRS for 13,457 children aged 9 or 12 from the Child and Adolescent Twin Study in Sweden, using results from an independent meta-analysis of genome-wide association studies of ADHD diagnosis and symptoms. We estimated associations between ADHD PRS, a general psychopathology factor, and several dimensions of neurodevelopmental, externalizing, and internalizing symptoms, using structural equation modeling. Higher ADHD PRS were statistically significantly associated with elevated neurodevelopmental, externalizing, and depressive symptoms (R 2  = 0.26-1.69%), but not with anxiety. After accounting for a general psychopathology factor, on which all symptoms loaded positively (mean loading = 0.50, range = 0.09-0.91), an association with specific hyperactivity/impulsivity remained significant. ADHD PRS explained ~ 1% (p value < 0.0001) of the variance in the general psychopathology factor and ~ 0.50% (p value < 0.0001) in specific hyperactivity/impulsivity. Our results suggest that common genetic risk variants associated with ADHD, and captured by PRS, also influence a general genetic liability towards broad childhood psychopathology in the general population, in addition to a specific association with hyperactivity/impulsivity symptoms.

Background: Cryptosporidium is a genus of apicomplexan parasites that cause enteric disease in vertebrates. In pigs, infections are most often asymptomatic, but may result in diarrhoea and poor growth. The most common species detected in pigs are C. suis and C. scrofarum with low zoonotic potential. C. parvum, with higher zoonotic potential, may also be found. As previous knowledge on the occurrence of Cryptosporidium in Swedish pigs is scarce, this was investigated in our study. Faecal samples from 13 pig herds were collected and a total of 222 pooled pen samples, from suckling piglets (n = 48), growers, aged 6-12 weeks (n = 57), fatteners, aged 13-24 weeks (n = 67) and adult animals (n = 50) were included. Samples were analysed using microscopy and positive samples were further analysed using polymerase chain reaction and sequencing of the 18S rRNA gene and the 28S rRNA gene to determine species., Results: Cryptosporidium spp. were detected in all sampled herds and in 25% (56/222) of the individual pen samples. Infections were most common in growers and fatteners with 51% (29/57) and 35% (20/67) positive samples in each group, respectively. The piglets had 8% (4/48) positive samples and adults had 6% (3/50). Species determination showed C. suis and C. scrofarum in piglets and growers, C. scrofarum in the fatteners, and C. suis and C. parvum in the adults. Although no mixed infections could be confirmed we saw signs of double peaks in the 28S rRNA gene chromatograms, possibly indicating more than one species present per sample., Conclusion: Cryptosporidium spp. were detected on every sampled farm and in 25% of the individual pen samples in our study. We therefore conclude that Cryptosporidium spp. are present and likely common in Swedish pig herds, where pigs are loose and reared on solid floors. However, none of the farms reported any problems with poor weight gain, diarrhoea, or reduced appetite in their pig herds. The pig adapted C. suis and C. scrofarum were the predominant species identified. Two samples were positive for the more zoonotic C. parvum, and pigs should hence not be disregarded as a possible source of zoonotic cryptosporidiosis.

Background: We examined whether childhood conduct problems predicted a wide range of adverse outcomes in emerging adulthood and whether the association with internalizing problems remained after adjusting for general comorbidity and externalizing problems., Methods: Participants were 18,649 twins from the Child and Adolescent Twin Study in Sweden. At age 9/12, parents rated their children on eight conduct problems. Adverse outcomes were retrieved from national registers in emerging adulthood (median follow-up time = 9.2 years), including diagnoses of six psychiatric disorders, prescriptions of antidepressants, suicide attempts, criminality, high school ineligibility, and social welfare recipiency. We estimated risk for the separate outcomes and examined if conduct problems predicted an internalizing factor above and beyond a general comorbidity and an externalizing factor. We used twin analyses to estimate genetic and environmental contributions to these associations., Results: On the average, each additional conduct symptom in childhood was associated with a 32% increased risk of the adverse outcomes in emerging adulthood (mean hazard ratio = 1.32; range = 1.16, 1.56). A latent childhood conduct problems factor predicted the internalizing factor in emerging adulthood (β boys  = .24, standard error, SE = 0.03; β girls  = .17, SE = 0.03), above and beyond its association with the externalizing (β boys  = 0.21, SE = 0.04; β girls  = 0.17, SE = 0.05) and general factors (β boys  = 0.45, SE = 0.03; β girls  = 0.34, SE = 0.04). These associations were differentially influenced by genetic and environmental factors., Conclusions: It is important to monitor boys and girls with conduct problems not only for future externalizing problems, but also for future internalizing problems. Prevention of specific outcomes, however, might require interventions at different levels., (© 2019 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

In recent years, there has been a surge of interest in the general factor of psychopathology ("p"), which is intended to summarize broad psychiat-ric comorbidity into a single index. In this study, rather than attempting to validate this model using statistical techniques, we compared the magnitude (as indicated by the variance explained in the respective indicators) and the predictive validity of the "p" factor with those of the gen-eral factor of intelligence ("g"). To compare the magnitude, for "g", we analyzed fifteen Wechsler Adult Intelligence Scale subtests (N=1,200). For "p", we analyzed fourteen psychiatric diagnoses in Swedish adults (N=909,699), eight self- and parent-rated psychopathology scales in Swedish adolescents (N=2,069), and sixteen parent-rated psychopathology scales in Swedish children (N=14,589). To compare the predictive validity, we analyzed Swedish male military conscripts (N=414,595, mean age: 18.3 years) with measures on both "g" and "p" (derived from eight psychiatric diagnoses). We then examined their unique associations with three intelligence-related outcomes (annual income, highest education, and university entrance exam scores), and sixteen adverse outcomes (e.g., suicidal behavior, psychotropic medication prescription, and criminality) retrieved from registers (mean age at follow-up = 29.2 years). Results indicated that the magnitudes of "g" and "p" were very similar. Controlling for "p", "g" significantly predicted later education (standardized beta, β=0.38, SE=0.01) and university entrance exam scores (β=0.48, SE=0.01). Controlling for "g", "p" significantly predicted all adverse outcomes (mean β=0.32; range: 0.15 to 0.47). These findings support the notion that psychopathology indicators can be combined into a single score, similar to how intelligence subtests are combined into a general intelligence score. This "p" score might supplement specific diagnoses when formulating a management plan and predicting prognosis., (© 2020 World Psychiatric Association.)

Visual disengagement has been hypothesized as an endophenotype for autism. In this study we used twin modelling to assess the role of genetics in basic measures of visual disengagement, and tested their putative association to autistic traits in the general population. We used the Gap Overlap task in a sample of 492 twins. Results showed that most of the covariance among eye movement latencies across conditions was shared and primarily genetic. Further, there were unique genetic contributions to the Gap condition, but not to the Overlap condition-i.e. the one theorized to capture visual disengagement. We found no phenotypic association between autistic traits and disengagement, thus not supporting the hypothesis of visual disengagement as an endophenotype for autistic traits.

Few quantitative behavior genetic studies have examined why psychopathology is associated with suicide attempt (SA) and self-harm (SH) in adolescence. The present study analyzed data from the Child and Adolescent Twin Study in Sweden to examine the extent to which genetic and environmental factors explain SA/SH and its association with psychopathology in childhood, an often-cited risk factor of subsequent SA/SH. When children were 9 or 12 years old ( n = 30,444), parents completed the Autism-Tics, AD/HD and other Comorbidities Inventory (Larson et al., 2010) regarding their children's psychiatric problems as part of an ongoing, longitudinal study. At age 18 years ( n = 10,269), adolescents completed self-report questionnaires, including SA/SH assessments. In a bifactor model of childhood psychopathology, a general factor of psychopathology was a statistically significant predictor of adolescent SA/SH at a higher magnitude (β, 0.25, 95% confidence interval [CI; 0.15, 0.34] for suicide attempt), as compared with specific factors of inattention, impulsivity, oppositional behavior, and anxiety/emotion symptoms. Quantitative genetic modeling indicated that the additive genetic influences on the general factor accounted for the association with each outcome (β, 0.24, 95% CI [0.13, 0.34] for suicide attempt). The results remained virtually identical when we fit a higher order factors model. Two additional outcomes demonstrated comparable results. The results extend current literature by revealing the shared genetic overlap between general psychopathology during childhood and adolescent SA/SH. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background: Traits of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are strongly associated in children and adolescents, largely due to genetic factors. Less is known about the phenotypic and aetiological overlap between ADHD and ASD traits in adults., Methods: We studied 6866 individuals aged 20-28 years from the Swedish Study of Young Adult Twins. Inattention (IA) and hyperactivity/impulsivity (HI) were assessed using the WHO Adult ADHD Self-Report Scale-V1.1. Repetitive and restricted behaviours (RRB) and social interaction and communication (SIC) were assessed using the Autism-Tics, ADHD, and other Comorbidities inventory. We used structural equation modelling to decompose covariance between these ADHD and ASD trait dimensions into genetic and shared/non-shared environmental components., Results: At the phenotypic level, IA was similarly correlated with RRB (r = 0.33; 95% Confidence Interval (CI) 0.31-0.36) and with SIC (r = 0.32; 95% CI 0.29-0.34), whereas HI was more strongly associated with RRB (r = 0.38; 95% CI 0.35-0.40) than with SIC (r = 0.24; 95% CI 0.21-0.26). Genetic and non-shared environmental effects accounted for similar proportions of the phenotypic correlations, whereas shared environmental effects were of minimal importance. The highest genetic correlation was between HI and RRB (r = 0.56; 95% 0.46-0.65), and the lowest was between HI and SIC (r = 0.33; 95% CI 0.23-0.43)., Conclusions: We found evidence for dimension-specific phenotypic and aetiological overlap between ADHD and ASD traits in adults. Future studies investigating mechanisms underlying comorbidity between ADHD and ASD may benefit from exploring several symptom-dimensions, rather than considering only broad diagnostic categories.

Background: Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders., Methods: We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia., Results: Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50., Conclusions: Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.

Importance: It is unclear if the associations between fetal growth and later mental health conditions remain after controlling for familial factors and psychiatric comorbidity., Objective: To examine the associations between fetal growth and general and specific mental health conditions, controlling for familial factors., Design, Setting, and Participants: This register-based study conducted in Sweden analyzed 546 894 pairs of full siblings born between January 1, 1973, and December 31, 1998. Sibling pairs were followed up through December 31, 2013. First, population-based and within-sibling pair associations (which controlled for time-invariant familial confounders) between fetal growth and the outcomes were estimated. Second, exploratory factor analysis was applied to the outcomes to derive 1 general factor and 4 specific and independent factors. Third, the general and specific factors were regressed on fetal growth. Statistical analysis was performed from March 27, 2017, to October 27, 2018., Main Outcome and Measures: The outcomes were 11 psychiatric diagnoses (depression, anxiety, obsessive-compulsive disorder, posttraumatic stress disorder, bipolar disorder, alcohol abuse, drug use, attention-deficit/hyperactivity disorder, autism, schizophrenia, and schizoaffective disorder) and court convictions of violent crimes. Birth weight (in kilograms) statistically adjusted for gestational age was the exposure., Results: The mean (SD) age of the 1 093 788 participants was 27.2 (6.8) years (range, 15.1-40.9 years) and 51.5% were male. Nine outcomes were significantly associated with birth weight in the population at large: depression (odds ratio [OR], 0.96; 95% CI, 0.95-0.98), anxiety (OR, 0.94; 95% CI, 0.92-0.95), posttraumatic stress disorder (OR, 0.91; 95% CI, 0.89-0.93), bipolar disorder (OR, 0.94; 95% CI, 0.89-1.00), alcohol abuse (OR, 0.89; 95% CI, 0.87-0.91), drug use (OR, 0.83; 95% CI, 0.80-0.85), violent crimes (OR, 0.85; 95% CI, 0.83-0.86), attention-deficit/hyperactivity disorder (OR, 0.88; 95% CI, 0.86-0.90), and autism (OR, 0.95; 95% CI, 0.92-0.97). Only depression (OR, 0.95; 95% CI 0.92-0.98), obsessive-compulsive disorder (OR, 0.93; 95% CI, 0.87-0.99), attention-deficit/hyperactivity disorder (OR, 0.86; 95% CI, 0.82-0.89), and autism (OR, 0.72; 95% CI, 0.69-0.76) remained significantly associated within sibling pairs. An exploratory factor analysis indicated that 1 general and 4 specific factors (capturing anxiety, externalizing, neurodevelopmental, and psychotic conditions) fit the outcomes well. Across almost all sensitivity analyses, an increase in birth weight by 1 kg significantly reduced the general (β, -0.047; 95% CI, -0.071 to -0.023) and the specific neurodevelopmental factors (β, -0.159; 95% CI, -0.190 to -0.128) within sibling pairs., Conclusions and Relevance: Controlling for familial confounders, reduced fetal growth was associated with a small but significant increase in the general factor of psychopathology and a moderate increase in a specific neurodevelopmental factor.

Background and Purpose: Metal artefacts in computed tomography (CT) images impairs structure delineation. These artefacts can potentially be reduced with dual-energy CT (DECT) with or without using metal artefact reduction (MAR). The purpose was to investigate how structure delineation in DECT with or without MAR and single-energy CT (SECT) images were affected by metals., Materials and Methods: A phantom with known irregular structures was developed. Reference structures were determined from a low-noise scan without metal. Bilateral hip prostheses were simulated with steel or titanium inserts. The phantom was scanned with SECT and fast-kV switching DECT with optional MAR. Four radiation oncologists delineated the structures in two phantom set-ups. Delineated structures were evaluated with Dice similarity coefficient (DSC) and Hausdorff distance relative to the reference structures., Results: With titanium inserts, more structures were detected for non-MAR DECT compared to SECT while the same or less were detected with steel inserts. MAR improved delineation in DECT images. For steel inserts, three structures in the region of artefacts, were delineated by at least two oncologists with MAR-DECT compared to none with non-MAR DECT or SECT. The highest values of DSC for MAR-DECT were 0.69, 0.81 and 0.77 for those structures., Conclusions: Delineation was improved with non-MAR DECT compared to SECT, especially for titanium inserts. A larger improvement was seen with the use of MAR for both steel and titanium inserts. The improvement was dependent on the location of the structure relative to the inserts, and the structure contrast relative to the background., (© 2019 The Authors.)

Background: Piglet diarrhoea is considered a worldwide problem resulting in animal welfare problems and financial losses for pig farmers. Porcine rotavirus and the coccidian parasite Cystoisospora suis ( C. suis ) are considered two important pathogens associated with diarrhoea in piglets during the suckling and early post weaning periods. To obtain an overview on the prevalence of porcine rotavirus and C. suis in piglet producing herds with solid floors and age segregated rearing, faecal sampling of 791 litters in 81 farms was performed., Results: For porcine rotavirus, faecal samples were analysed using a sandwich ELISA. The overall prevalence of rotavirus in the examined herds was 11.4 ± 17.7% at 2 weeks, 56.8 ± 30.7% at 4 weeks and 71.1 ± 29.1% at 6 weeks of age and the accumulated prevalence was 49, 97 and 100%. To detect C. suis, faecal samples were analysed using sedimentation. The overall prevalence of C. suis in the examined herds was 11.9 ± 15.1% at 2 weeks of age, 10.7 ± 16.7% at 4 weeks and 8.7 ± 15.3% at 6 weeks of age and the accumulated prevalence was 56, 76 and 85%. The number of empty days between farrowing batches did influence the shedding of rotavirus at 2 weeks of age but not later. Regarding C. suis , no difference in prevalence was correlated to the number of days between consecutive farrowing batches., Conclusions: Our study confirmed that rotavirus should be regarded as an ubiquitous virus that can be expected to be present in almost every pig herd in Sweden. The study also demonstrated that the number of infected litters increased from birth to 6 weeks of age. Secondly, it showed that C. suis frequently occurred in pig herds and that the number of infected litters was rather stable from two to 6 weeks of age. Consequently, both rotavirus and C. suis may play a role in intestinal disturbances in piglets during the suckling and post weaning periods despite age segregated rearing, at least in systems with solid floors. However, as this study was carried out in herds without reported problems with diarrhoea or poor weight gain, the role of these pathogens should not be overestimated., Competing Interests: Not applicable.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Hot flushes are common and troublesome symptoms of menopause. The neuropeptide calcitonin gene-related peptide (CGRP) is increased in plasma during hot flushes but it has not been clear if CGRP is causally involved in the mechanism underpinning the flushes. Here, we examined the effect of interventions with CGRP in a mouse model of hot flushes based on flush-like temperature increases triggered by forced physical activity in ovariectomized mice. Compared to normal mice, ovariectomized mice reacted with an exaggerated, flush-like, temperature increase after physical exercise. This increase was completely blocked by the non-peptide CGRP-antagonist MK-8825 (-0.41 degrees Celsius, 95% CI: -0,83 to 0,012, p < 0.0001) at a dose that had no obvious effects on locomotor activity (50 mg/kg). Further, the flush-like temperature increases were strongly attenuated in ovariectomized mice lacking αCGRP due to a genetic modification. Collectively, our findings suggest that CGRP is an important mediator of experimentally induced hot flushes and they identify CGRP antagonists as promising treatment candidates for women and possibly also men with hot flushes.

Background: Autism spectrum disorder (ASD), Attention-deficit/Hyperactivity disorder (ADHD), and other related neurodevelopmental disorders (NDDs) have, in some previous studies, been shown to increase the risk of being sexually victimized. However, no studies have examined whether the association is driven by a general NDD phenotype versus specific diagnoses, nor the etiology of the association., Method: Using a genetically informative, prospective design, we examined the association between ASD and ADHD in childhood and coercive sexual victimization up to age 18. A total of 4,500 children participating in the Child and Adolescent Twin Study in Sweden (CATSS) were rated by their parents on NDDs at age 9 or 12 years, and self-reported at age 18 on lifetime experiences of coercive sexual touching and/or coercive sex. First, we regressed sexual victimization on the NDDs. Second, we regressed sexual victimization on general and specific NDD symptoms identified via a bifactor model. Third, we decomposed the observed associations into genetic and environmental parts., Results: In females, ASD was associated with an almost threefolded increased risk of coercive sexual victimization, and ADHD with a doubled risk. In males, the risk associated with ASD and ADHD was of the same magnitude but not significant. When controlling for overall NDD symptom load ASD or ADHD, no longer uniquely predicted coercive sexual victimization. The association between the NDD general factor and coercive sexual victimization was due to shared genetics., Conclusions: General NDD symptom load, rather than specific ASD or ADHD symptoms, seems to be a moderate vulnerability factor for coercive sexual victimization. We speculate that an evocative gene-environment correlation might account for this observation, such that sexual perpetrators actively target NDD individuals., (© 2018 Association for Child and Adolescent Mental Health.)

Objective: We examined whether a parent-rated general factor of psychopathology in childhood would predict independently measured, severe adverse mental health outcomes in adolescence., Method: We used the Child and Adolescent Twin Study in Sweden, which targets all twin children in Sweden. Parents rated their children (N = 16,806) on 43 symptoms of inattention, hyperactivity/impulsivity, conduct problems, and anxiety/emotionality when the twins turned 9 or 12 years of age. Adverse mental health outcomes in adolescence were retrieved from national registers, and included psychiatric diagnoses, prescription of anxiolytic or antidepressant medication, court convictions of crimes, and failure to achieve eligibility for high school., Results: Parent-rated inattention, hyperactivity/impulsivity, conduct problems, and anxiety/emotionality in childhood predicted all adverse mental health outcomes in adolescence (mean odds ratio = 1.76; range = 1.41-2.18; all p < .05). However, several of these associations were nonsignificant in a multiple regression framework, suggesting the influence of common variance. A general factor of psychopathology uniquely predicted all outcomes (mean odds ratio = 1.58; range = 1.34-1.84; all p < .05), whereas the specific factors predicted only a subset of the outcomes., Conclusion: Mental health problems in childhood are associated with a host of adverse outcomes in adolescence, and, to a considerable extent, these associations are driven by a general factor of psychopathology. The general factor may therefore be important to clinical prognosis, which informs clinical decision making for children., (Copyright © 2018 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.

Autism spectrum disorder (ASD) has been associated with gastrointestinal (GI) problems, but the nature of this association is unclear. Parents to siblings, concordant or discordant for ASD (N = 217), participated in a web survey covering mother's weight gain during pregnancy, maternal viral/bacterial infection and use of antibiotics, duration of breastfeeding, mode of delivery, birth weight and child GI problems. ASD was associated with GI problems and perinatal environmental risk, based on a summation of maternal infection and antibiotic use during pregnancy and/or the breastfeeding period. The association between GI problems and ASD remained within the sibling pairs (β = 1.23; p < .001) in the adjusted model. Our results indicate non-shared environmental effects on the ASD/GI association, but none of the factors examined explained the link.

Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of problematic alcohol and other substance use in adolescence. This study used data from an ongoing, prospective, population-based twin study of Swedish children and adolescents to evaluate the extent to which the association between ADHD symptoms and alcohol problems reflects a unique source of genetic or environmental risk related to ADHD versus a broader predisposition to youth externalizing behavior. We used all available data from same-sex monozygotic (MZ) and dizygotic (DZ) twins on ADHD symptoms in childhood (age 9/12; N = 15,549) and alcohol problems in late adolescence (age 18; N = 2,564). Consistent with prior longitudinal studies, the phenotypic association between hyperactive/impulsive ADHD symptoms and alcohol problems was small in magnitude, whereas the association for inattentive symptoms was even weaker. Additive genetic influences explained 99.8% of the association between hyperactive/impulsive symptoms and alcohol problems. Furthermore, we found that the genetic risk specifically associated with hyperactive/impulsive symptoms was attenuated when estimated in the context of externalizing behavior liability during childhood, of which ADHD symptoms were specific expressions. In sensitivity analyses exploring hyperactivity in mid-adolescence, we found a similar pattern of genetic associations. These results are consistent with previous findings of genetically driven overlap in the etiology of ADHD and problematic alcohol use. At least some of this co-occurrence may result from a general predisposition to externalizing behaviors in youth. © 2015 Wiley Periodicals, Inc., Competing Interests: Henrik Larsson has served as a speaker for Eli-Lilly and Shire and has received a research grant from Shire, all outside the submitted work., (© 2015 Wiley Periodicals, Inc.)

Recent studies have shown that different mental-health problems appear to be partly influenced by the same set of genes, which can be summarized by a general genetic factor. To date, such studies have relied on surveys of community-based samples, which could introduce potential biases. The goal of this study was to examine whether a general genetic factor would still emerge when based on a different ascertainment method with different biases from previous studies. We targeted all adults in Sweden (n=3 475 112) using national registers and identified those who had received one or more psychiatric diagnoses after seeking or being forced into mental health care. In order to examine the genetic versus environmental etiology of the general factor, we examined whether participants' full- or half-siblings had also received diagnoses. We focused on eight major psychiatric disorders based on the International Classification of Diseases, including schizophrenia, schizoaffective disorder, bipolar disorder, depression, anxiety, attention-deficit/hyperactivity disorder, alcohol use disorder and drug abuse. In addition, we included convictions of violent crimes. Multivariate analyses demonstrated that a general genetic factor influenced all disorders and convictions of violent crimes, accounting for between 10% (attention-deficit/hyperactivity disorder) and 36% (drug abuse) of the variance of the conditions. Thus, a general genetic factor of psychopathology emerges when based on both surveys as well as national registers, indicating that a set of pleiotropic genes influence a variety of psychiatric disorders.

Studies suggest associations between childhood autistic traits and adolescent psychotic experiences. However, recent research suggests that a general neuropsychiatric problems factor predicts adverse outcomes better than specific diagnostic entities. To examine if the alleged association between autistic traits and psychotic experiences could rather be explained by a general neuropsychiatric problems factor comprising symptoms of ADHD, tic disorder, developmental coordination disorder, and learning disorder, we conducted a prospective cohort study based on the Child and Adolescent Twin Study in Sweden. In addition, we examined the genetic and environmental influences on the associations. A total of 9,282 twins with data on childhood autistic traits and other neuropsychiatric problems, and follow-up data on psychotic experiences at ages 15 and/or 18 years were included. First, psychotic experiences were regressed on autistic traits and second, the general neuropsychiatric problems factor was added to the model. Auditory hallucinations were analyzed separately from the other psychotic experiences. Finally, twin analyses were employed to disentangle genetic from environmental influences in the observed associations. Replicating prior research, significant associations were found between autistic traits in childhood and auditory hallucinations at ages 15 and 18. However, after controlling for the general neuropsychiatric problems factor, the associations between autistic traits and auditory hallucinations disappeared, whereas the association between the general neuropsychiatric problems factor and auditory hallucinations persisted after controlling for autistic traits. Twin analyses revealed that the association between the general neuropsychiatric problems factor and auditory hallucinations was driven by shared genetic influences. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.

Background: Smoke from combustion of biomass fuels is a major risk factor for respiratory disease, but the underlying mechanisms are poorly understood. The aim of this study was to determine whether exposure to wood smoke from incomplete combustion would elicit airway inflammation in humans., Methods: Fourteen healthy subjects underwent controlled exposures on two separate occasions to filtered air and wood smoke from incomplete combustion with PM1 concentration at 314 μg/m(3) for 3 h in a chamber. Bronchoscopy with bronchial wash (BW), bronchoalveolar lavage (BAL) and endobronchial mucosal biopsies was performed after 24 h. Differential cell counts and soluble components were analyzed, with biopsies stained for inflammatory markers using immunohistochemistry. In parallel experiments, the toxicity of the particulate matter (PM) generated during the chamber exposures was investigated in vitro using the RAW264.7 macrophage cell line., Results: Significant reductions in macrophage, neutrophil and lymphocyte numbers were observed in BW (p < 0.01, <0.05, <0.05, respectively) following the wood smoke exposure, with a reduction in lymphocytes numbers in BAL fluid (<0.01. This unexpected cellular response was accompanied by decreased levels of sICAM-1, MPO and MMP-9 (p < 0.05, <0.05 and <0.01). In contrast, significant increases in submucosal and epithelial CD3+ cells, epithelial CD8+ cells and submucosal mast cells (p < 0.01, <0.05, <0.05 and <0.05, respectively), were observed after wood smoke exposure. The in vitro data demonstrated that wood smoke particles generated under these incomplete combustion conditions induced cell death and DNA damage, with only minor inflammatory responses., Conclusions: Short-term exposure to sooty PAH rich wood smoke did not induce an acute neutrophilic inflammation, a classic hallmark of air pollution exposure in humans. While minor proinflammatory lymphocytic and mast cells effects were observed in the bronchial biopsies, significant reductions in BW and BAL cells and soluble components were noted. This unexpected observation, combined with the in vitro data, suggests that wood smoke particles from incomplete combustion could be potentially cytotoxic. Additional research is required to establish the mechanism of this dramatic reduction in airway leukocytes and to clarify how this acute response contributes to the adverse health effects attributed to wood smoke exposure., Trial Registration: NCT01488500.

Bully victimization is a common problem among children with neurodevelopmental disorders, including attention deficit/hyperactivity disorder and autism spectrum disorder. Previous research was mostly cross-sectional and seldom accounted for co-morbid psychopathology, which makes it difficult to draw conclusions about causality and specificity of any association. Using a genetically informative prospective design, we investigated the association between various neurodevelopmental problems (NDPs) in childhood and bully victimization in adolescence, and the relative contributions of genetic and environmental factors to this association. We obtained parent-reports of NDPs at age 9/12 years and self-reported bully victimization at age 15 for 3,921 children participating in the The Child and Adolescent Twin Study in Sweden (CATSS). Structural equation modelling was used to control for NDP co-morbidity and bully victimization at baseline. Cholesky decomposition was used to analyse genetic and environmental contributions to observed associations. Because most of the NDPs were associated to later bully victimization, a common effect of all NDPs was summarized into a general NDP factor. Controlling for this general factor, only problems with social interaction and motor control uniquely predicted subsequent bully victimization in girls. General and unique associations were influenced by both genetic and unique environmental factors. NDPs in general and social interaction and motor problems in particular predicted later bully victimization. The longitudinal design and twin analyses indicated that these associations might be causal. Knowledge of these vulnerabilities may be important when designing risk assessment and prevention strategies.

Background: Respiratory tract deposition of air pollution particles is a key to their adverse health effects. This study was aimed to determine the size-resolved deposition fraction (DF) of sooty wood smoke particles in the lungs of healthy subjects. The type of wood smoke investigated is typical for household air pollution from solid fuels, which is among the largest environmental health problems globally., Methods: Twelve healthy volunteers inhaled diluted wood smoke from incomplete soot-rich combustion in a common wood stove. The DF of smoke particles (10-500 nm) was measured during three 15-min exposures in each subject during spontaneous breathing. Lung function was measured using standard spirometry., Results: The total DFs by particle number concentration were 0.34±0.08. This can be compared with DFs of 0.21-0.23 in healthy subjects during previous experiments with wood pellet combustion. For particle mass, the total DFs found in this study were 0.22±0.06. DF and breathing frequency were negatively correlated as expected from model calculations (p<0.01)., Conclusions: The DF of the investigated sooty wood smoke particles was higher than for previously investigated particles generated during more efficient combustion of biomass. Together with toxicological studies, which have indicated that incomplete biomass combustion particles rich in soot and polycyclic aromatic hydrocarbons (PAHs) are especially harmful, these data highlight the health risks of inadequate wood combustion.

Importance: Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases)., Objectives: To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD., Design, Setting, and Participants: Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014., Main Outcomes and Measures: Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts., Results: A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10-12 < P < .05) and MDD (4.02 × 10-9 < P < .05) in the 2 other cohorts., Conclusions and Relevance: This study identifies a novel locus for neuroticism. The variant is located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies. In addition, the study shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants. These genetic variants also influence MDD. Future studies should confirm the role of the MAGI1 locus for neuroticism and further investigate the association of MAGI1 and the polygenic association to a range of other psychiatric disorders that are phenotypically correlated with neuroticism.

Background: Studies have found an association between low birth weight and ADHD, but the nature of this relation is unclear. First, it is uncertain whether birth weight is associated with both of the ADHD dimensions, inattentiveness and hyperactivity-impulsivity. Second, it remains uncertain whether the association between birth weight and ADHD symptom severity is confounded by familial factors., Method: Parents of all Swedish 9- and 12-year-old twins born between 1992 and 2000 were interviewed for DSM-IV inattentive and hyperactive-impulsive ADHD symptoms by the Autism - Tics, AD/HD and other Comorbidities (A-TAC) inventory (N = 21,775 twins). Birth weight was collected prospectively through the Medical Birth Registry. We used a within-twin pair design to control for genetic and shared environmental factors., Results: Reduced birth weight was significantly associated with a mean increase in total ADHD (β = -.42; 95% CI: -.53, -.30), inattentive (β = -.26; 95% CI: -.33, -.19), and hyperactive-impulsive (β = -.16; 95% CI: -.22, -.10) symptom severity. These results imply that a change of one kilogram of birth weight corresponded to parents rating their child nearly one unit higher (going from "no" to "yes, to some extent" on a given symptom) on the total ADHD scale. These associations remained within pairs of MZ and DZ twins, and were also present when restricting the analyses to full term births., Conclusions: There is an independent association between low birth weight and all forms of ADHD symptoms, even after controlling for all environmental and genetic confounds shared within twin pairs. These results indicate that fetal growth restriction (as reflected in birth weight differences within twin pairs) and/or the environmental factors which influence it is in the casual pathway leading to ADHD., (© 2014 Association for Child and Adolescent Mental Health.)

Conventional skin UV-sensitivity phototesting is based on semi-quantitative assessment of minimal erythema dose (MED). This study demonstrates a method for quantitative MED determination, using a lengthwise attenuating UVB-field combined with tissue viability imaging (TiVi). The study aim was to investigate the agreement between MED acquired by traditional phototest and by the new method. Forty-seven voluntary subjects underwent phototesting with a traditional phototest and with the new technique. Test reading, carried out after 24 h, showed moderate agreement between the methods when assessed with TiVi (Kappa value=0.46) and visually (Kappa value=0.48). For the new method, no systematic differences were seen between outcomes assessed with TiVi or visually (95% CI for the mean difference=-1.6-2.0). In conclusion, the results give promising support for the concept of achieving a more precise MED estimation by combining continuous attenuating UV fields with new available bioengineering technology.

Restriction enzymes that recognize specific sequences but cleave unknown sequence outside the recognition site are extensively utilized tools in molecular biology. Despite this, systematic functional categorization of cleavage performance has largely been lacking. We established a simple and automatable model system to assay cleavage distance variation (termed slippage) and the sequence dependence thereof. We coupled this to massively parallel sequencing in order to provide sensitive and accurate measurement. With this system 14 enzymes were assayed (AcuI, BbvI, BpmI, BpuEI, BseRI, BsgI, Eco57I, Eco57MI, EcoP15I, FauI, FokI, GsuI, MmeI and SmuI). We report significant variation of slippage ranging from 1-54%, variations in sequence context dependence, as well as variation between isoschizomers. We believe this largely overlooked property of enzymes with shifted cleavage would benefit from further large scale classification and engineering efforts seeking to improve performance. The gained insights of in-vitro performance may also aid the in-vivo understanding of these enzymes.

Background: Autistic-like traits (ALTs) are continuously distributed in the general population, with the autism spectrum disorder (ASD) at the upper extreme end. A genetic overlap has been shown between ALTs and ASD, indicating that common variation in ASD candidate genes may also influence ALTs. In our study, we have investigated the SNP rs4307059 that has been associated with both ALTs and ASD. In addition, we genotyped polymorphisms in a selection of genes involved in synaptic functioning, that is, SHANK3, RELN, and CNTNAP2, which repeatedly have been associated with ASD. The possible associations of these polymorphisms with ALTs, as well as genetic factors for neurodevelopmental problems (NDPs), were investigated in a large cohort from the general population: The Child and Adolescent Twin Study in Sweden. For analyses of ALTs and NDPs, 12,319 subjects (including 2,268 monozygotic (MZ) and 3,805 dizygotic (DZ) twin pairs) and 8,671 subjects (including 2,243 MZ and 2,044 DZ twin pairs), respectively, were included in the analyses., Findings: We could not replicate the previous association between rs4307059 and social communication impairment. Moreover, common variations in CNTNAP2 (rs7794745 and rs2710102), RELN (rs362691), and SHANK3 (rs9616915) were not significantly associated with ALTs in our study., Conclusions: Our results do not suggest that the investigated genes, which previously has been found associated with ASD diagnosis, have any major influence on ALTs in children from the general population.

Background: Empowerment is essential for gender equity and health. The city of Malmö, Sweden, has formulated a development plan for gender equity integration (GEIDP). A 'Policy Empowerment Index' (PEI) was previously developed to assess the empowerment potential of policies., Objectives: To pilot-evaluate the GEIDP's potential for empowerment and to test the PEI for future policy evaluations., Design: The GEIDP was analyzed and scored according to electronically retrieved evidence on constituent opinion, participation, capacity development, evaluation-adaptation, and impact., Results: The plan's PEI score was 64% (CI: 48-78) and was classified as 'enabling', ranging between 'enabling' and 'supportive'. The plan's strengths were: 1) constituent knowledge and concern; 2) peripheral implementation; 3) protection of vulnerable groups; and 4) evaluation/adaptation procedures. It scored average on: 1) policy agenda setting; 2) planning; 3) provisions for education; 4) network formation; 5) resource mobilization. The weakest point was regarding promotion of employment and entrepreneurship., Conclusions: The PEI evaluation highlighted the plan's potential of constituency empowerment and proposed how it could be augmented.

Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.

Although simple structure is often used as a theoretical guideline for rotation of exploratory factor structures, its empirical foundation is sometimes not investigated. We examined the degree of simple structure in 2 self-report inventories advocated for the description of personality pathology. The multivariate complexity of the inventories was compared against simulated factorial solutions with increasing degrees of simple structure. Results revealed a high degree of complexity in both inventories, regardless of whether focusing on a few broad or many narrow factors and whether items or scales were analyzed. It is concluded that Thurstone's (1934) simple structure criteria are rarely fulfilled in multivariate personality pathology solutions, and, therefore, that alternate rotations represent equally justifiable ways to operationalize the space. Furthermore, using iterative test development to impose simple structure where none originally existed increased standard errors around the factor scores in the interstitial areas between imposed simple structure dimensions. In both simulated and real data, multidimensional item response theory test information functions based on complex solutions demonstrated that test information was uniformly distributed across the space. In contrast, in simple structure solutions, information was weak in areas of the space where nonconforming items had been removed. Implications are discussed.

Time-resolved emissions of particulate polycyclic aromatic hydrocarbons (PAHs) and total organic particulate matter (OA) from a wood log stove and an adjusted pellet stove were investigated with high-resolution time-of-flight aerosol mass spectrometry (AMS). The highest OA emissions were found during the addition of log wood on glowing embers, that is, slow burning pyrolysis conditions. These emissions contained about 1% PAHs (of OA). The highest PAH emissions were found during fast burning under hot air starved combustion conditions, in both stoves. In the latter case, PAHs contributed up to 40% of OA, likely due to thermal degradation of other condensable species. The distribution of PAHs was also shifted toward larger molecules in these emissions. AMS signals attributed to PAHs were found at molecular weights up to 600 Da. The vacuum aerodynamic size distribution was found to be bimodal with a smaller mode (Dva ∼ 200 nm) dominating under hot air starved combustion and a larger sized mode dominating under slow burning pyrolysis (Dva ∼ 600 nm). Simultaneous reduction of PAHs, OA and total particulate matter from residential biomass combustion may prove to be a challenge for environmental legislation efforts as these classes of emissions are elevated at different combustion conditions.

In the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; American Psychiatric Association, 2013) personality disorder trait model, maladaptive behavior is located at one end of continuous scales. Widiger and colleagues, however, have argued that maladaptive behavior exists at both ends of trait continua. We propose that the role of evaluative variance differentiates these two perspectives and that once evaluation is isolated, maladaptive behaviors emerge at both ends of nonevaluative trait dimensions. In Study 1, we argue that evaluative variance is worthwhile to measure separately from descriptive content because it clusters items by valence regardless of content (e.g., lazy and workaholic; apathetic and anxious; gullible and paranoid; timid and hostile, etc.), which is unlikely to describe a consistent behavioral style. We isolate evaluation statistically (Study 2) and at the time of measurement (Study 3) to show that factors unrelated to valence evidence maladaptive behavior at both ends. We argue that nonevaluative factors, which display maladaptive behavior at both ends of continua, may better approximate ways in which individuals actually behave.