| 1. |
- Docherty, Anna R, et al.
(författare)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
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Tidskriftsartikel (refereegranskat)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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| 2. |
- Mullins, Niamh, et al.
(författare)
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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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| 3. |
- Anthony, Kenneth R. N., et al.
(författare)
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Operationalizing resilience for adaptive coral reef management under global environmental change
- 2015
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 21:1, s. 48-61
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Forskningsöversikt (refereegranskat)abstract
- Cumulative pressures from global climate and ocean change combined with multiple regional and local-scale stressors pose fundamental challenges to coral reef managers worldwide. Understanding how cumulative stressors affect coral reef vulnerability is critical for successful reef conservation now and in the future. In this review, we present the case that strategically managing for increased ecological resilience (capacity for stress resistance and recovery) can reduce coral reef vulnerability (risk of net decline) up to a point. Specifically, we propose an operational framework for identifying effective management levers to enhance resilience and support management decisions that reduce reef vulnerability. Building on a system understanding of biological and ecological processes that drive resilience of coral reefs in different environmental and socio-economic settings, we present an Adaptive Resilience-Based management (ARBM) framework and suggest a set of guidelines for how and where resilience can be enhanced via management interventions. We argue that press-type stressors (pollution, sedimentation, overfishing, ocean warming and acidification) are key threats to coral reef resilience by affecting processes underpinning resistance and recovery, while pulse-type (acute) stressors (e.g. storms, bleaching events, crown-of-thorns starfish outbreaks) increase the demand for resilience. We apply the framework to a set of example problems for Caribbean and Indo-Pacific reefs. A combined strategy of active risk reduction and resilience support is needed, informed by key management objectives, knowledge of reef ecosystem processes and consideration of environmental and social drivers. As climate change and ocean acidification erode the resilience and increase the vulnerability of coral reefs globally, successful adaptive management of coral reefs will become increasingly difficult. Given limited resources, on-the-ground solutions are likely to focus increasingly on actions that support resilience at finer spatial scales, and that are tightly linked to ecosystem goods and services.
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| 4. |
- Mcleod, Elizabeth, et al.
(författare)
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The future of resilience-based management in coral reef ecosystems
- 2019
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Ingår i: Journal of Environmental Management. - : Elsevier BV. - 0301-4797 .- 1095-8630. ; 233, s. 291-301
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Forskningsöversikt (refereegranskat)abstract
- Resilience underpins the sustainability of both ecological and social systems. Extensive loss of reef corals following recent mass bleaching events have challenged the notion that support of system resilience is a viable reef management strategy. While resilience-based management (RBM) cannot prevent the damaging effects of major disturbances, such as mass bleaching events, it can support natural processes that promote resistance and recovery. Here, we review the potential of RBM to help sustain coral reefs in the 21st century. We explore the scope for supporting resilience through existing management approaches and emerging technologies and discuss their opportunities and limitations in a changing climate. We argue that for RBM to be effective in a changing world, reef management strategies need to involve both existing and new interventions that together reduce stress, support the fitness of populations and species, and help people and economies to adapt to a highly altered ecosystem.
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| 5. |
- Williams, David J., et al.
(författare)
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Comparability : Manufacturing, characterization and controls, report of a UK Regenerative Medicine Platform Pluripotent Stem Cell Platform Workshop, Trinity Hall, Cambridge, 14-15 September 2015
- 2016
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Ingår i: Regenerative Medicine. - : Future Medicine Ltd. - 1746-0751 .- 1746-076X. ; 11:5, s. 483-492
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Tidskriftsartikel (refereegranskat)abstract
- This paper summarizes the proceedings of a workshop held at Trinity Hall, Cambridge to discuss comparability and includes additional information and references to related information added subsequently to the workshop. Comparability is the need to demonstrate equivalence of product after a process change; a recent publication states that this 'may be difficult for cell-based medicinal products'. Therefore a well-managed change process is required which needs access to good science and regulatory advice and developers are encouraged to seek help early. The workshop shared current thinking and best practice and allowed the definition of key research questions. The intent of this report is to summarize the key issues and the consensus reached on each of these by the expert delegates.
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| 6. |
- Axelsson, Rebecca, et al.
(författare)
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Simultaneous digital breast tomosynthesis and mechanical imaging in women recalled from screening - A preliminary analysis
- 2022
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Ingår i: 16th International Workshop on Breast Imaging, IWBI 2022. - : SPIE. - 0277-786X .- 1996-756X. - 9781510655843 ; 12286
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Konferensbidrag (refereegranskat)abstract
- We have developed a method for simultaneous tomosynthesis and mechanical imaging, called DBTMI. Mechanical imaging measures the stress distribution over the compressed breast surface. Malignant tissue is usually stiffer than benign, which results in higher stress on the compressed breast and enables to distinguish malignant from benign findings. By combining tomosynthesis and mechanical imaging, we could improve cancer detection accuracy by reducing the number of false positive findings. In this study we have analysed clinical DBTMI data, collected from 52 women from an ongoing pilot study at the Skåne University Hospital, Malmö, Sweden. We measured the range of the average stress over the breast surface, the range of average stress over the location of suspected lesions, and the normalized stress over the lesion location. Preliminary results show that the range of stress over the breast surface was 1.23-5.84 kPa, the range over the lesion location 2.10-10.10 kPa, and the normalized stress 1.12-2.44 over the lesion location. Overall, the local stress over malignant lesions was higher than the average stress over the entire breast surface. This is the first step investigating criteria to distinguish between malignant and benign findings based upon clinical DBTMI data.
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| 7. |
- Ba, Alexandre, et al.
(författare)
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Inter-laboratory comparison of channelized hotelling observer computation
- 2018
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Ingår i: Medical Physics. - : Wiley. - 0094-2405 .- 2473-4209. ; 45:7, s. 3019-3030
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The task-based assessment of image quality using model observers is increasingly used for the assessment of different imaging modalities. However, the performance computation of model observers needs standardization as well as a well-established trust in its implementation methodology and uncertainty estimation. The purpose of this work was to determine the degree of equivalence of the channelized Hotelling observer performance and uncertainty estimation using an intercomparison exercise. Materials and Methods: Image samples to estimate model observer performance for detection tasks were generated from two-dimensional CT image slices of a uniform water phantom. A common set of images was sent to participating laboratories to perform and document the following tasks: (a) estimate the detectability index of a well-defined CHO and its uncertainty in three conditions involving different sized targets all at the same dose, and (b) apply this CHO to an image set where ground truth was unknown to participants (lower image dose). In addition, and on an optional basis, we asked the participating laboratories to (c) estimate the performance of real human observers from a psychophysical experiment of their choice. Each of the 13 participating laboratories was confidentially assigned a participant number and image sets could be downloaded through a secure server. Results were distributed with each participant recognizable by its number and then each laboratory was able to modify their results with justification as model observer calculation are not yet a routine and potentially error prone. Results: Detectability index increased with signal size for all participants and was very consistent for 6 mm sized target while showing higher variability for 8 and 10 mm sized target. There was one order of magnitude between the lowest and the largest uncertainty estimation. Conclusions: This intercomparison helped define the state of the art of model observer performance computation and with thirteen participants, reflects openness and trust within the medical imaging community. The performance of a CHO with explicitly defined channels and a relatively large number of test images was consistently estimated by all participants. In contrast, the paper demonstrates that there is no agreement on estimating the variance of detectability in the training and testing setting.
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| 8. |
- Bakic, Predrag R., et al.
(författare)
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Evaluation of a flat fielding method for simultaneous DBT and MI acquisition
- 2020
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Ingår i: 15th International Workshop on Breast Imaging, IWBI 2020. - : SPIE. - 1996-756X .- 0277-786X. - 9781510638310 ; 11513
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Konferensbidrag (refereegranskat)abstract
- We are developing a prototype system for simultaneous digital breast tomosynthesis (DBT) and mechanical imaging (MI). MI maps the local pressure distribution during clinical exams, to distinguish breast abnormalities from the normal tissue. Both DBT alone, and MI when combined with digital mammography, have demonstrated the ability to reduce false positives; however, the benefit of combining DBT with MI has not been investigated. A practical limitation in simultaneous DBT and MI is the presence of the MI sensor in DBT images. Metallic elements of the sensor generate noticeable artifacts, which may interfere with clinical analysis. Previously, we shown that the sensor artifacts can be reduced by flat fielding, which combines projections of the sensor acquired with and without the breast. In this paper we evaluate the flat fielding by assessing artifact reduction and visibility of breast abnormalities. Images of a physical anthropomorphic breast phantom were acquired using a clinical wide-angle DBT system. Visual evaluation was performed by experienced medical physicists. Image quality descriptors were calculated in images with and without flat fielding. To evaluate the visibility of abnormalities we estimated the full width at half maximum (FWHM) for calcifications modeled in the phantom. Our preliminary results suggest a substantial reduction of artifacts by flat fielding (on average 83%). Few noticeable artifacts remain near the breast edge, in the reconstructed image with the sensor in focus. We observed a 17% reduction in the FWHM. Future work would include a detailed assessment, and method optimization using virtual trials as a design aid.
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| 9. |
- Bejnö, Anna, et al.
(författare)
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Artificial intelligence together with mechanical imaging in mammography
- 2020
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Ingår i: 15th International Workshop on Breast Imaging, IWBI 2020. - : SPIE. - 0277-786X .- 1996-756X. - 9781510638310 ; 11513
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Konferensbidrag (refereegranskat)abstract
- Artificial intelligence (AI) applications are increasingly seeing use in breast imaging, particularly to assist in or automate the reading of mammograms. Another novel technique is mechanical imaging (MI) which estimates the relative stiffness of suspicious breast abnormalities by measuring the distribution of pressure on the compressed breast. This study investigates the feasibility of combining AI and MI information in breast imaging to provide further diagnostic information. Forty-six women recalled from screening were included in the analysis. Mammograms with findings scored on a suspiciousness scale by an AI tool, and corresponding pressure distributions were collected for each woman. The cases were divided into three groups by diagnosis; biopsy-proven cancer, biopsy-proven benign and non-biopsied, very likely benign. For all three groups, the relative increase of pressure at the location of the finding marked most suspicious by the AI software was recorded. A significant correlation between the relative pressure increase at the AI finding and the AI score was established in the group with cancer (p=0.043), but neither group of healthy women showed such a correlation. This study suggests that AI and MI indicate independent markers for breast cancer. The combination of these two methods has the potential to increase the accuracy of mammography screening, but further research is needed.
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| 10. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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