| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Ip, H. F., et al.
(författare)
-
Genetic association study of childhood aggression across raters, instruments, and age
- 2021
-
Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association metaanalysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE= 0.0038). We found no genome-wide significant SNPs for AGG(overall). The gene-based analysis returned three significant genes: ST3GAL3 (P= 1.6E-06), PCDH7 (P= 2.0E-06), and IPO13 (P= 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from r(g)= 0.46 between self- and teacher-assessment to r(g)d= 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range r(g): 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r(g)=-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |r(g)| : 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
|
|
| 5. |
- Jami, E. S., et al.
(författare)
-
Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms
- 2022
-
Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567 .- 1527-5418. ; 61:7, s. 934-945
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. Results: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, n(effective) = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (vertical bar r(g)vertical bar > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range vertical bar r(g)vertical bar = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.
|
|
| 6. |
- Lewis, M. C., et al.
(författare)
-
Decay of a 19(-) isomeric state in Lu-156
- 2018
-
Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 98:2
-
Tidskriftsartikel (refereegranskat)abstract
- A multiparticle spin-trap isomeric state having a half-life of 179(4) ns and lying 2601 keV above the yrast 10(+) state in Lu-156 has been discovered. The Lu-156 nuclei were produced by bombarding isotopically enriched Cd-106 targets with beams of Ni-58 ions, separated in flight using the gas-filled separator RITU and their decays were measured using the GREAT spectrometer. Analysis of the main decay path that populates yrast states observed previously suggests a spin-parity assignment of 19(-) for the isomeric state, which is consistent with isomeric states identified in the N = 85 isotones. Comparison with other decay paths in Lu-156 indicates that the [pi h(11/)(2)(-1) circle times nu h(9/2)]10(+) state at the bottom of the yrast sequence is likely to be the a-decaying isomeric state, with the [pi h(11/)(2)(-1) circle times nu f(7/2)]9(+) state lying 62 keV above it. The relative ordering of the lowest-lying 9(+) and 10(+) states is inverted in Lu-156 compared with its odd-odd isotones.
|
|
| 7. |
- Parr, E., et al.
(författare)
-
Fine structure in the alpha decay of high-spin isomers in Lu-155 and Hf-156
- 2018
-
Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 98:2
-
Tidskriftsartikel (refereegranskat)abstract
- Fine structure in the a decay of high-spin isomers in Lu-155( 25/2(-)) and Hf-156(8(+))has been studied for the first time using alpha gamma- coincidence analysis. Three new a decays from Lu-155(25/2(-)) and two from Hf-156(8(+)) have been identified, populating seniority s > 1 states in the N = 82 nuclei Tm-151 and Yb-152, respectively. The reduced hindrance factors of the a decays support the previous configuration assignments of the populated states. This is the first observation of states with excitation energy greater than 1.5 MeV being populated following a decay in nuclei outside of the Pb-208 region.
|
|
| 8. |
- Parr, E., et al.
(författare)
-
Single-particle states and parity doublets in odd- Z Ac 221 and Pa 225 from α -decay spectroscopy
- 2022
-
Ingår i: Physical Review C. - 2469-9985. ; 105:3
-
Tidskriftsartikel (refereegranskat)abstract
- Low-lying states in the odd-Z isotopes Ac13289221 and Pa13491225 have been studied using α-particle and αγ-coincidence spectroscopy in the Pa225→Ac221→Fr217 decay chain. Ground-state spin and parity assignments of Iπ = 5/2- are proposed for both Ac221 and Pa225, with the odd proton occupying the ω = 5/2 orbital of the quadrupole-octupole deformed shell model in both nuclei. In Ac221, excited states in the bands based on the ω = 5/2 and ω = 3/2 orbitals have been identified, including proposed parity-doublet states. The results suggest that reflection-asymmetric deformation of the ground state persists in the odd-A members of the isotope chains down to N = 132 for Ac and N = 134 for Pa, before reaching the transitional region at N = 130.
|
|
| 9. |
- Parr, E., et al.
(författare)
-
Identification of the J(pi)=1(-) state in Ra-218 populated via alpha decay of Th-222
- 2016
-
Ingår i: PHYSICAL REVIEW C. - 2469-9985. ; 94:1
-
Tidskriftsartikel (refereegranskat)abstract
- The alpha decay of Th-222 populating the low-lying J(pi) = 3(-) state, and also a proposed 1(-) state, in Ra-218 has been observed. The observations suggest an excitation energy of 853 keV for the 1(-) state, which is 60 keV above the 3(-) state. The hindrance factors of these alpha decays give a possible boundary to the region of ground-state octupole deformation in the light-actinide nuclei. The relative positions of the J(pi) = 1(-) and 3(-) states suggest they are produced by an octupole-vibrational mechanism, as opposed to alpha clustering or rotations of a reflection-asymmetric octupole-deformed shape.
|
|
| 10. |
- Gordon, C., et al.
(författare)
-
EULAR points to consider for conducting clinical trials in systemic lupus erythematosus
- 2009
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 68:4, s. 470-476
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Systemic lupus erythematosus (SLE) is a complex multi-organ disease, characterised by relapses and remissions. Designing a high-quality randomised controlled trial poses many challenges. We have developed evidenced-based recommendations for points to consider in conducting clinical trials in patients with SLE. Methods: The EULAR Task Force on SLE comprised 19 specialists and a clinical epidemiologist. Initially, the evidence for clinical trial end-points in SLE was evaluated and this has been reported separately. A consensus approach was developed by the SLE Task Force in formulating recommendations for points to consider when conducting clinical trials in SLE. Results: The literature review revealed that most outcome measures used in phase 2/3 trials in SLE have not actually been validated in clinical trials, although other forms of validation have been undertaken. The final recommendations for points to consider for conducting clinical trials in SLE address the following areas: study design, eligibility criteria, outcome measures including adverse events, concomitant therapies for SLE and its complications. Conclusions: Recommendations for points to consider when conducting clinical trials in SLE were developed using an evidence-based approach followed by expert consensus. The recommendations should be disseminated, implemented and then reviewed in detail and revised using an evidence-based approach in about 5 years, by which time there will be further evidence to consider from current clinical trials.
|
|
