| 1. |
- Niemi, MEK, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 2. |
- Kanai, M, et al.
(författare)
-
- 2023
-
swepub:Mat__t
|
|
| 3. |
- Bryois, J., et al.
(författare)
-
Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
- 2020
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:5, s. 482-493
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Eijsbouts, C., et al.
(författare)
-
Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders
- 2021
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53:11, s. 1543-1552
-
Tidskriftsartikel (refereegranskat)abstract
- Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS. © 2021, The Author(s).
|
|
| 9. |
|
|
| 10. |
- Brennan, Seán J., 1995-, et al.
(författare)
-
Spectroscopic observations of progenitor activity 100 days before a Type Ibn supernova
- 2024
-
Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 684
-
Tidskriftsartikel (refereegranskat)abstract
- Obtaining spectroscopic observations of the progenitors of core-collapse supernovae is often unfeasible, due to an inherent lack of knowledge as to what stars experience supernovae and when they will explode. In this Letter we present photometric and spectroscopic observations of the progenitor activity of SN 2023fyq before the He-rich progenitor explodes as a Type Ibn supernova. The progenitor of SN 2023fyq shows an exponential rise in flux prior to core collapse. Complex He I emission line features are observed in the progenitor spectra, with a P Cygni-like profile, as well as an evolving broad base with velocities of the order of 10 000 km s−1. The luminosity and evolution of SN 2023fyq is consistent with a Type Ibn, reaching a peak r-band magnitude of −18.8 mag, although there is some uncertainty regarding the distance to the host, NGC 4388, which is located in the Virgo cluster. We present additional evidence of asymmetric He-rich material being present both prior to and after the explosion of SN 2023fyq, which suggests that this material survived the ejecta interaction. Broad [O I], C I, and the Ca II triplet lines are observed at late phases, confirming that SN 2023fyq was a genuine supernova, rather than a non-terminal interacting transient. SN 2023fyq provides insight into the final moments of a massive star’s life, demonstrating that the progenitor is likely highly unstable before core collapse.
|
|
| 11. |
|
|
| 12. |
- Dunham, I, et al.
(författare)
-
The DNA sequence of human chromosome 22
- 1999
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 402:6761, s. 489-495
-
Tidskriftsartikel (refereegranskat)
|
|
| 13. |
- Frazier-Wood, Alexis C., et al.
(författare)
-
Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
-
Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
-
Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
|
|
| 14. |
- Smith, Jennifer A, et al.
(författare)
-
Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
-
Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
-
Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
|
|
| 15. |
|
|
| 16. |
- Bender, R., et al.
(författare)
-
Corrosion challenges towards a sustainable society
- 2022
-
Ingår i: Materials and corrosion - Werkstoffe und Korrosion. - : Wiley. - 0947-5117 .- 1521-4176. ; 73:11, s. 1730-1751
-
Tidskriftsartikel (refereegranskat)abstract
- A global transition towards more sustainable, affordable and reliable energy systems is being stimulated by the Paris Agreement and the United Nation's 2030 Agenda for Sustainable Development. This poses a challenge for the corrosion industry, as building climate-resilient energy systems and infrastructures brings with it a long-term direction, so as a result the long-term behaviour of structural materials (mainly metals and alloys) becomes a major prospect. With this in mind “Corrosion Challenges Towards a Sustainable Society” presents a series of cases showing the importance of corrosion protection of metals and alloys in the development of energy production to further understand the science of corrosion, and bring the need for research and the consequences of corrosion into public and political focus. This includes emphasis on the limitation of greenhouse gas emissions, on the lifetime of infrastructures, implants, cultural heritage artefacts, and a variety of other topics.
|
|
| 17. |
- Chen, Z. H., et al.
(författare)
-
The Hydrogen-poor Superluminous Supernovae from the Zwicky Transient Facility Phase I Survey. I. Light Curves and Measurements
- 2023
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 943:1
-
Tidskriftsartikel (refereegranskat)abstract
- During the Zwicky Transient Facility (ZTF) Phase I operations, 78 hydrogen-poor superluminous supernovae (SLSNe-I) were discovered in less than 3 yr, constituting the largest sample from a single survey. This paper (Paper I) presents the data, including the optical/UV light curves and classification spectra, while Paper II in this series will focus on the detailed analysis of the light curves and modeling. Our photometry is primarily taken by ZTF in the g, r, and i bands, and with additional data from other ground-based facilities and Swift. The events of our sample cover a redshift range of z = 0.06 − 0.67, with a median and 1σ error (16% and 84% percentiles) of zmed=0.265. The peak luminosity covers −22.8 mag ≤ Mg,peak ≤ −19.8 mag, with a median value of -21.48. The light curves evolve slowly with a mean rest-frame rise time of trise = 41.9 ± 17.8 days. The luminosity and timescale distributions suggest that low-luminosity SLSNe-I with a peak luminosity ∼−20 mag or extremely fast-rising events (<10 days) exist, but are rare. We confirm previous findings that slowly rising SLSNe-I also tend to fade slowly. The rest-frame color and temperature evolution show large scatters, suggesting that the SLSN-I population may have diverse spectral energy distributions. The peak rest-frame color shows a moderate correlation with the peak absolute magnitude, i.e., brighter SLSNe-I tend to have bluer colors. With optical and UV photometry, we construct the bolometric luminosity and derive a bolometric correction relation that is generally applicable for converting g, r-band photometry to the bolometric luminosity for SLSNe-I.
|
|
| 18. |
|
|
| 19. |
- DeWitt, Douglas S., et al.
(författare)
-
Pre-clinical testing of therapies for traumatic brain injury
- 2018
-
Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 35:23, s. 2737-2754
-
Tidskriftsartikel (refereegranskat)abstract
- Despite the large number of promising neuroprotective agents identified in experimental traumatic brain injury (TBI) studies, none has yet shown meaningful improvements in long-term outcome in clinical trials. To develop recommendations and guidelines for pre-clinical testing of pharmacological or biological therapies for TBI, the Moody Project for Translational Traumatic Brain Injury Research hosted a symposium attended by investigators with extensive experience in pre-clinical TBI testing. The symposium participants discussed issues related to pre-clinical TBI testing including experimental models, therapy and outcome selection, study design, data analysis, and dissemination. Consensus recommendations included the creation of a manual of standard operating procedures with sufficiently detailed descriptions of modeling and outcome measurement procedures to permit replication. The importance of the selection of clinically relevant outcome variables, especially related to behavior testing, was noted. Considering the heterogeneous nature of human TBI, evidence of therapeutic efficacy in multiple, diverse (e.g., diffuse vs. focused) rodent models and a species with a gyrencephalic brain prior to clinical testing was encouraged. Basing drug doses, times, and routes of administration on pharmacokinetic and pharmacodynamic data in the test species was recommended. Symposium participants agreed that the publication of negative results would reduce costly and unnecessary duplication of unsuccessful experiments. Although some of the recommendations are more relevant to multi-center, multi-investigator collaborations, most are applicable to pre-clinical therapy testing in general. The goal of these consensus guidelines is to increase the likelihood that therapies that improve outcomes in pre-clinical studies will also improve outcomes in TBI patients.
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
- Chen, Z. H., et al.
(författare)
-
The Hydrogen-poor Superluminous Supernovae from the Zwicky Transient Facility Phase I Survey. II. Light-curve Modeling and Characterization of Undulations
- 2023
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 943:1, s. 42-
-
Tidskriftsartikel (refereegranskat)abstract
- We present analysis of the light curves (LCs) of 77 hydrogen-poor superluminous supernovae (SLSNe I) discovered during the Zwicky Transient Facility Phase I operation. We find that the majority (67%) of the sample can be fit equally well by both magnetar and ejecta-circumstellar medium (CSM) interaction plus 56Ni decay models. This implies that LCs alone cannot unambiguously constrain the physical power sources for an SLSN I. However, 23% of the sample show inverted V-shape, steep-declining LCs or features of long rise and fast post-peak decay, which are better described by the CSM+Ni model. The remaining 10% of the sample favors the magnetar model. Moreover, our analysis shows that the LC undulations are quite common, with a fraction of 18%-44% in our gold sample. Among those strongly undulating events, about 62% of them are found to be CSM-favored, implying that the undulations tend to occur in the CSM-favored events. Undulations show a wide range in energy and duration, with median values (and 1σ errors) being as 1.7 % − 0.7 % + 1.5 % E rad , total and 28.8 − 9.1 + 14.4 days, respectively. Our analysis of the undulation timescales suggests that intrinsic temporal variations of the central engine can explain half of the undulating events, while CSM interaction (CSI) can account for the majority of the sample. Finally, all of the well-observed He-rich SLSNe Ib either have strongly undulating LCs or the LCs are much better fit by the CSM+Ni model. These observations imply that their progenitor stars have not had enough time to lose all of the He-envelopes before supernova explosions, and H-poor CSM are likely to present in these events.
|
|
| 23. |
|
|
| 24. |
- Sharma, Yashvi, et al.
(författare)
-
Dramatic Rebrightening of the Type-changing Stripped-envelope Supernova SN 2023aew
- 2024
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 966:2
-
Tidskriftsartikel (refereegranskat)abstract
- Multipeaked supernovae with precursors, dramatic light-curve rebrightenings, and spectral transformation are rare, but are being discovered in increasing numbers by modern night-sky transient surveys like the Zwicky Transient Facility. Here, we present the observations and analysis of SN 2023aew, which showed a dramatic increase in brightness following an initial luminous (−17.4 mag) and long (∼100 days) unusual first peak (possibly precursor). SN 2023aew was classified as a Type IIb supernova during the first peak but changed its type to resemble a stripped-envelope supernova (SESN) after the marked rebrightening. We present comparisons of SN 2023aew's spectral evolution with SESN subtypes and argue that it is similar to SNe Ibc during its main peak. P-Cygni Balmer lines are present during the first peak, but vanish during the second peak's photospheric phase, before Hα resurfaces again during the nebular phase. The nebular lines ([O i], [Ca ii], Mg i], Hα) exhibit a double-peaked structure that hints toward a clumpy or nonspherical ejecta. We analyze the second peak in the light curve of SN 2023aew and find it to be broader than that of normal SESNe as well as requiring a very high 56Ni mass to power the peak luminosity. We discuss the possible origins of SN 2023aew including an eruption scenario where a part of the envelope is ejected during the first peak and also powers the second peak of the light curve through interaction of the SN with the circumstellar medium.
|
|
| 25. |
- Zheng, Hou-Feng, et al.
(författare)
-
Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112-
-
Tidskriftsartikel (refereegranskat)abstract
- The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
- Lunetta, Kathryn L., et al.
(författare)
-
Rare coding variants and X-linked loci associated with age at menarche
- 2015
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only similar to 3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency proteincoding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P<5 x 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P = 9.4 x 10(-13)) and FAAH2 (rs5914101, P = 4.9 x 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P = 2.8 x 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain similar to 0.5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait.
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
- Robinson, James B., et al.
(författare)
-
Identifying Defects in Li-Ion Cells Using Ultrasound Acoustic Measurements
- 2020
-
Ingår i: Journal of the Electrochemical Society. - : The Electrochemical Society. - 0013-4651 .- 1945-7111. ; 167:12
-
Tidskriftsartikel (refereegranskat)abstract
- Identification of the state-of-health (SoH) of Li-ion cells is a vital tool to protect operating battery packs against accelerated degradation and failure. This is becoming increasingly important as the energy and power densities demanded by batteries and the economic costs of packs increase. Here, ultrasonic time-of-flight analysis is performed to demonstrate the technique as a tool for the identification of a range of defects and SoH in Li-ion cells. Analysis of large, purpose-built defects across multiple length scales is performed in pouch cells. The technique is then demonstrated to detect a microscale defect in a commercial cell, which is validated by examining the acoustic transmission signal through the cell. The location and scale of the defects are confirmed using X-ray computed tomography, which also provides information pertaining to the layered structure of the cells. The demonstration of this technique as a methodology for obtaining direct, non-destructive, depth-resolved measurements of the condition of electrode layers highlights the potential application of acoustic methods in real-time diagnostics for SoH monitoring and manufacturing processes.
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
- Wightman, D. P., et al.
(författare)
-
A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease
- 2021
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:9, s. 1276-1282
-
Tidskriftsartikel (refereegranskat)abstract
- Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology.
|
|
| 39. |
- Zhang, G., et al.
(författare)
-
Genetic Associations with Gestational Duration and Spontaneous Preterm Birth
- 2017
-
Ingår i: New England Journal of Medicine. - 0028-4793. ; 377:12, s. 1156-1167
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Despite evidence that genetic factors contribute to the duration of gestation and the risk of preterm birth, robust associations with genetic variants have not been identified. We used large data sets that included the gestational duration to determine possible genetic associations. We performed a genomewide association study in a discovery set of samples obtained from 43,568 women of European ancestry using gestational duration as a continuous trait and term or preterm (< 37 weeks) birth as a dichotomous outcome. We used samples from three Nordic data sets (involving a total of 8643 women) to test for replication of genomic loci that had significant genomewide association (P< 5.0x10(-8)) or an association with suggestive significance (P< 1.0x10(-6)) in the discovery set. In the discovery and replication data sets, four loci (EBF1, EEFSEC, AGTR2, and WNT4) were significantly associated with gestational duration. Functional analysis showed that an implicated variant in WNT4 alters the binding of the estrogen receptor. The association between variants in ADCY5 and RAP2C and gestational duration had suggestive significance in the discovery set and significant evidence of association in the replication sets; these variants also showed genomewide significance in a joint analysis. Common variants in EBF1, EEFSEC, and AGTR2 showed association with preterm birth with genomewide significance. An analysis of mother-infant dyads suggested that these variants act at the level of the maternal genome. In this genomewide association study, we found that variants at the EBF1, EEFSEC, AGTR2, WNT4, ADCY5, and RAP2C loci were associated with gestational duration and variants at the EBF1, EEFSEC, and AGTR2 loci with preterm birth. Previously established roles of these genes in uterine development, maternal nutrition, and vascular control support their mechanistic involvement.
|
|
| 40. |
- Bilderbeck, Amy C., et al.
(författare)
-
Psychoeducation and online mood tracking for patients with bipolar disorder : A randomised controlled trial
- 2016
-
Ingår i: Journal of Affective Disorders. - : ELSEVIER SCIENCE BV. - 0165-0327 .- 1573-2517. ; 205, s. 245-251
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Psychoeducation is an effective adjunct to medications in bipolar disorder (BD). Brief psychoeducational approaches have been shown to improve early identification of relapse. However, the optimal method of delivery of psychoeducation remains uncertain. Here, our objective was to compare a short therapist-facilitated vs. self-directed psychoeducational intervention for BD. Methods: BD outpatients who were receiving medication-based treatment were randomly assigned to 5 psychoeducation sessions administered by a therapist (Facilitated Integrated Mood Management; FIMM; n=60), or self-administered psychoeducation (Manualized Integrated Mood Management; MIMM; n=61). Follow-up was based on patients' weekly responses to an electronic mood monitoring programme over 12 months. Results: Over follow-up, there were no group differences in weekly self-rated depression symptoms or relapse/readmission rates. However, knowledge of BD (assessed with the Oxford Bipolar Knowledge questionnaire (OBQ)) was greater in the FIMM than the MIMM group at 3 months. Greater illness knowledge at 3 months was related to a higher proportion of weeks well over 12 months. Limitations: Features of the trial may have reduced the sensitivity to our psychoeducation approach, including that BD participants had been previously engaged in self-monitoring. Conclusions: Improved OBQ score, while accelerated by a short course of therapist-administered psychoeducation (FIMM), was seen after both treatments. It was associated with better outcome assessed as weeks well. When developing and testing a new psychosocial intervention, studies should consider proximal outcomes (e.g., acquired knowledge) and their short-term impact on illness course in bipolar disorder. (C) 2016 Elsevier B.V. All rights reserved.
|
|
| 41. |
- Ferreira, Manuel A R, et al.
(författare)
-
Eleven loci with new reproducible genetic associations with allergic disease risk.
- 2019
-
Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 143:2, s. 691-699
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A recent genome-wide association study (GWAS) identified 99 loci that contain genetic risk variants shared between asthma, hay fever, and eczema. Many more risk loci shared between these common allergic diseases remain to be discovered, which could point to new therapeutic opportunities.OBJECTIVE: We sought to identify novel risk loci shared between asthma, hay fever, and eczema by applying a gene-based test of association to results from a published GWAS that included data from 360,838 subjects.METHODS: We used approximate conditional analysis to adjust the results from the published GWAS for the effects of the top risk variants identified in that study. We then analyzed the adjusted GWAS results with the EUGENE gene-based approach, which combines evidence for association with disease risk across regulatory variants identified in different tissues. Novel gene-based associations were followed up in an independent sample of 233,898 subjects from the UK Biobank study.RESULTS: Of the 19,432 genes tested, 30 had a significant gene-based association at a Bonferroni-corrected P value of 2.5 × 10-6. Of these, 20 were also significantly associated (P < .05/30 = .0016) with disease risk in the replication sample, including 19 that were located in 11 loci not reported to contain allergy risk variants in previous GWASs. Among these were 9 genes with a known function that is directly relevant to allergic disease: FOSL2, VPRBP, IPCEF1, PRR5L, NCF4, APOBR, IL27, ATXN2L, and LAT. For 4 genes (eg, ATXN2L), a genetically determined decrease in gene expression was associated with decreased allergy risk, and therefore drugs that inhibit gene expression or function are predicted to ameliorate disease symptoms. The opposite directional effect was observed for 14 genes, including IL27, a cytokine known to suppress TH2 responses.CONCLUSION: Using a gene-based approach, we identified 11 risk loci for allergic disease that were not reported in previous GWASs. Functional studies that investigate the contribution of the 19 associated genes to the pathophysiology of allergic disease and assess their therapeutic potential are warranted.
|
|
| 42. |
- Finegan, Donal P, et al.
(författare)
-
Quantifying Bulk Electrode Strain and Material Displacement within Lithium Batteries via High-Speed Operando Tomography and Digital Volume Correlation
- 2015
-
Ingår i: Advanced Science. - : Wiley. - 2198-3844.
-
Tidskriftsartikel (refereegranskat)abstract
- Tracking the dynamic morphology of active materials during operation of lithium batteries is essential for identifying causes of performance loss. Digital volume correlation (DVC) is applied to high-speed operando synchrotron X-ray computed tomography of a commercial Li/MnO2 primary battery during discharge. Real-time electrode material displacement is captured in 3D allowing degradation mechanisms such as delamination of the electrode from the current collector and electrode crack formation to be identified. Continuum DVC of consecutive images during discharge is used to quantify local displacements and strains in 3D throughout discharge, facilitating tracking of the progression of swelling due to lithiation within the electrode material in a commercial, spiral-wound battery during normal operation. Displacement of the rigid current collector and cell materials contribute to severe electrode detachment and crack formation during discharge, which is monitored by a separate DVC approach. Use of time-lapse X-ray computed tomography coupled with DVC is thus demonstrated as an effective diagnostic technique to identify causes of performance loss within commercial lithium batteries; this novel approach is expected to guide the development of more effective commercial cell designs.
|
|
| 43. |
- Goobar, Ariel, 1962-, et al.
(författare)
-
Uncovering a population of gravitational lens galaxies with magnified standard candle SN Zwicky
- 2023
-
Ingår i: Nature Astronomy. - 2397-3366. ; 7:9, s. 1098-1107
-
Tidskriftsartikel (refereegranskat)abstract
- Detecting gravitationally lensed supernovae is among the biggest challenges in astronomy. It involves a combination of two very rare phenomena: catching the transient signal of a stellar explosion in a distant galaxy and observing it through a nearly perfectly aligned foreground galaxy that deflects light towards the observer. Here we describe how high-cadence optical observations with the Zwicky Transient Facility, with its unparalleled large field of view, led to the detection of a multiply imaged type Ia supernova, SN Zwicky, also known as SN 2022qmx. Magnified nearly 25-fold, the system was found thanks to the standard candle nature of type Ia supernovae. High-spatial-resolution imaging with the Keck telescope resolved four images of the supernova with very small angular separation, corresponding to an Einstein radius of only θE = 0.167″ and almost identical arrival times. The small θE and faintness of the lensing galaxy are very unusual, highlighting the importance of supernovae to fully characterize the properties of galaxy-scale gravitational lenses, including the impact of galaxy substructures.
|
|
| 44. |
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
- Huusko, Johanna M, et al.
(författare)
-
Whole exome sequencing reveals HSPA1L as a genetic risk factor for spontaneous preterm birth.
- 2018
-
Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 14:7
-
Tidskriftsartikel (refereegranskat)abstract
- Preterm birth is a leading cause of morbidity and mortality in infants. Genetic and environmental factors play a role in the susceptibility to preterm birth, but despite many investigations, the genetic basis for preterm birth remain largely unknown. Our objective was to identify rare, possibly damaging, nucleotide variants in mothers from families with recurrent spontaneous preterm births (SPTB). DNA samples from 17 Finnish mothers who delivered at least one infant preterm were subjected to whole exome sequencing. All mothers were of northern Finnish origin and were from seven multiplex families. Additional replication samples of European origin consisted of 93 Danish sister pairs (and two sister triads), all with a history of a preterm delivery. Rare exonic variants (frequency <1%) were analyzed to identify genes and pathways likely to affect SPTB susceptibility. We identified rare, possibly damaging, variants in genes that were common to multiple affected individuals. The glucocorticoid receptor signaling pathway was the most significant (p<1.7e-8) with genes containing these variants in a subgroup of ten Finnish mothers, each having had 2-4 SPTBs. This pathway was replicated among the Danish sister pairs. A gene in this pathway, heat shock protein family A (Hsp70) member 1 like (HSPA1L), contains two likely damaging missense alleles that were found in four different Finnish families. One of the variants (rs34620296) had a higher frequency in cases compared to controls (0.0025 vs. 0.0010, p = 0.002) in a large preterm birth genome-wide association study (GWAS) consisting of mothers of general European ancestry. Sister pairs in replication samples also shared rare, likely damaging HSPA1L variants. Furthermore, in silico analysis predicted an additional phosphorylation site generated by rs34620296 that could potentially affect chaperone activity or HSPA1L protein stability. Finally, in vitro functional experiment showed a link between HSPA1L activity and decidualization. In conclusion, rare, likely damaging, variants in HSPA1L were observed in multiple families with recurrent SPTB.
|
|
| 49. |
- Morris, John A, et al.
(författare)
-
An atlas of genetic influences on osteoporosis in humans and mice.
- 2019
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 51, s. 258-266
-
Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis is a common aging-related disease diagnosed primarily using bone mineral density (BMD). We assessed genetic determinants of BMD as estimated by heel quantitative ultrasound in 426,824 individuals, identifying 518 genome-wide significant loci (301 novel), explaining 20% of its variance. We identified 13 bone fracture loci, all associated with estimated BMD (eBMD), in ~1.2 million individuals. We then identified target genes enriched for genes known to influence bone density and strength (maximum odds ratio (OR)=58, P=1 × 10-75) from cell-specific features, including chromatin conformation and accessible chromatin sites. We next performed rapid-throughput skeletal phenotyping of 126 knockout mice with disruptions in predicted target genes and found an increased abnormal skeletal phenotype frequency compared to 526 unselected lines (P<0.0001). In-depth analysis of one gene, DAAM2, showed a disproportionate decrease in bone strength relative to mineralization. This genetic atlas provides evidence linking associated SNPs to causal genes, offers new insight into osteoporosis pathophysiology, and highlights opportunities for drug development.
|
|
| 50. |
|
|
