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- Berndt, Sonja, I, et al.
(författare)
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Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
- 2022
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Ingår i: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 36:12, s. 2835-2844
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Tidskriftsartikel (refereegranskat)abstract
- Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
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- Amano, Tatsuya, et al.
(författare)
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Transforming Practice : Checklists for Delivering Change
- 2022
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Ingår i: Transforming Conservation : A Practical Guide to Evidence and Decision Making - A Practical Guide to Evidence and Decision Making. - 9781800648562 - 9781800648586 ; , s. 367-386
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Bokkapitel (refereegranskat)abstract
- Delivering a revolution in evidence use requires a cultural change across society. For a wide range of groups (practitioners, knowledge brokers, organisations, organisational leaders, policy makers, funders, researchers, journal publishers, the wider conservation community, educators, writers, and journalists), options are described to facilitate a change in practice, and a series of downloadable checklists is provided.
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- Dudink, I., et al.
(författare)
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An Optimized and Detailed Step-by-Step Protocol for the Analysis of Neuronal Morphology in Golgi-Stained Fetal Sheep Brain
- 2022
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Ingår i: Developmental neuroscience. - : S. Karger AG. - 0378-5866 .- 1421-9859. ; 44:4-5, s. 344-362
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Tidskriftsartikel (refereegranskat)abstract
- Antenatal brain development during the final trimester of human pregnancy is a time when mature neurons become increasingly complex in morphology, through axonal and dendritic outgrowth, dendritic branching, and synaptogenesis, together with myelin production. Characterizing neuronal morphological development over time is of interest to developmental neuroscience and provides the framework to measure gray matter pathology in pregnancy compromise. Neuronal microstructure can be assessed with Golgi staining, which selectively stains a small percentage (1-3%) of neurons and their entire dendritic arbor. Advanced imaging processing and analysis tools can then be employed to quantitate neuronal cytoarchitecture. Traditional Golgi-staining protocols have been optimized, and commercial kits are readily available offering improved speed and sensitivity of Golgi staining to produce consistent results. Golgi-stained tissue is then visualized under light microscopy and image analysis may be completed with several software programs for morphological analysis of neurons, including freeware and commercial products. Each program requires optimization, whether semiautomated or automated, requiring different levels of investigator intervention and interpretation, which is a critical consideration for unbiased analysis. Detailed protocols for fetal ovine brain tissue are lacking, and therefore, we provide a step-by-step workflow of computer software analysis for morphometric quantification of Golgi-stained neurons. Here, we utilized the commonly applied FD Rapid GolgiStain kit (FD NeuroTechnologies) on ovine fetal brains collected at 127 days (0.85) of gestational age for the analysis of CA1 pyramidal neurons in the hippocampus. We describe the step-by-step protocol to retrieve neuronal morphometrics using Imaris imaging software to provide quantification of apical and basal dendrites for measures of dendrite length (mu m), branch number, branch order, and Sholl analysis (intersections over radius). We also detail software add-ons for data retrieval of dendritic spines including the number of spines, spine density, and spine classification, which are critical indicators of synaptic function. The assessment of neuronal morphology in the developing brain using Rapid-Golgi and Imaris software is labor-intensive, particularly during the optimization period. The methodology described in this step-by-step description is novel, detailed, and aims to provide a reproducible, working protocol to quantify neuronal cytoarchitecture with simple descriptions that will save time for the next users of these commonly used techniques.
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- Wallström, Sara, 1982, et al.
(författare)
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Distinguishing symptom patterns in adults newly diagnosed with cancer: a latent class analysis
- 2022
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Ingår i: Journal of Pain and Symptom Management. - : Elsevier BV. - 0885-3924. ; 64:2, s. 146-155
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Tidskriftsartikel (refereegranskat)abstract
- Context: Socio-demographic differences, including place of residence, socio-economic status, ethnicity, and gender, have been associated with various inequities in cancer care outcomes. Objectives: The aims were to distinguish subgroups of patients with different symptom patterns at the time of the initial oncology visit and determine which clinical and socio-demographic variables are associated the different symptom patterns. Method: Responses to the Edmonton Symptom Assessment Scale- revised and clinical and socio-demographic variables were obtained via the Ontario Cancer Registry and linked health data files. Latent class analyses were conducted to identify and compare the subgroups. Results: The cohort (n = 216,110) with a mean age of 64.5 years consisted of 54.1% women. The analyses identified six latent classes (proportions ranging from 0.09 to 0.31) with distinct symptom patterns, including: 1) many severe symptoms, 2) many less severe symptoms, 3) predominantly mild symptoms, 4) severe psychosocial symptoms, 5) severe somatic symptoms, 6) few symptoms. The subgroups were associated not only with clinical differences (diagnoses and functional status), but also with various socio-demographic (age, sex) and community characteristics (neighborhood income, proportion of foreign born, rurality). Conclusion: The results indicated that there were substantial differences in symptom patterns at the time of the initial oncology visit, which were associated with both clinical diagnoses and socio-demographic differences. These results point to the importance of taking the social situation of patients into account, and not just diagnosis, to better understand differences in symptom patterns of people living with cancer.
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