| 1. |
- Blokland, G. A. M., et al.
(författare)
-
Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
-
Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
|
|
| 2. |
- Jones, Gregory T., et al.
(författare)
-
Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
- 2017
-
Ingår i: Circulation Research. - 0009-7330 .- 1524-4571. ; 120:2, s. 341-
-
Tidskriftsartikel (refereegranskat)abstract
- Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
|
|
| 3. |
- Noz, Marilyn E., et al.
(författare)
-
Modus Operandi for a Picture Archiving and Communication System (PACS)
- 1984
-
Ingår i: Radiology. - : Radiological Society of North America. - 0033-8419 .- 1527-1315. ; 152:1, s. 221-223
-
Tidskriftsartikel (refereegranskat)abstract
- The authors describe their 18 month experience operating an all digital nuclear medicine department, which led to the development of a system that allows multiple users to access patient reports and images through terminals located in various parts of the hospital. All user interactions are mediated through protocols that automatically acquire, process, display, and archive data. This approach offers distinct advantages over film and paper methods and is applicable in theory to any digital image format.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Erdman, William A., et al.
(författare)
-
Development of a Digital Nuclear-Medicine System
- 1983
-
Ingår i: Proceedings of the Society of Photo-Optical Instrumentation Engineers. - : Society of Photo-Optical Instrumentation Engineers. - 0361-0748. ; 418, s. 100-102
-
Tidskriftsartikel (refereegranskat)
|
|
| 8. |
|
|
| 9. |
- Ivanics, Tommy, et al.
(författare)
-
Dynamic risk profiling of HCC recurrence after curative intent liver resection
- 2022
-
Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 76:5, s. 1291-1301
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Aim: Following liver resection (LR) for HCC, the likelihood of survival is dynamic, in that multiple recurrences and/or metastases are possible, each having variable impacts on outcomes. We sought to evaluate the natural progression, pattern, and timing of various disease states after LR for HCC using multistate modeling and to create a practical calculator to provide prognostic information for patients and clinicians.Approach and Results: Adult patients undergoing LR for HCC between January 2000 and December 2018 were retrospectively identified at a single center. Multistate analysis modeled post-LR tumor progression by describing transitions between distinct disease states. In this model, the states included surgery, intrahepatic recurrence (first, second, third, fourth, fifth), distant metastasis with or without intrahepatic recurrence, and death. Of the 486 patients included, 169 (34.8%) remained recurrence-free, 205 (42.2%) developed intrahepatic recurrence, 80 (16.5%) developed distant metastasis, and 32 (7%) died. For an average patient having undergone LR, there was a 33.1% chance of remaining disease-free, a 31.0% chance of at least one intrahepatic recurrence, a 16.3% chance of distant metastasis, and a 19.8% chance of death within the first 60 months post-LR. The transition probability from surgery to first intrahepatic recurrence, without a subsequent state transition, increased from 3% (3 months) to 17.4% (30 months) and 17.2% (60 months). Factors that could modify these probabilities included tumor size, satellite lesions, and microvascular invasion. The online multistate model calculator can be found on https://multistatehcc.shinyapps.io/home/.Conclusions: In contrast to standard single time-to-event estimates, multistate modeling provides more realistic prognostication of outcomes after LR for HCC by taking into account many postoperative disease states and transitions between them. Our multistate modeling calculator can provide meaningful data to guide the management of patients undergoing postoperative surveillance and therapy.
|
|
| 10. |
- Ivanics, Tommy, et al.
(författare)
-
Machine learning-based mortality prediction models using national liver transplantation registries are feasible but have limited utility across countries
- 2023
-
Ingår i: American Journal of Transplantation. - : ELSEVIER SCIENCE INC. - 1600-6135 .- 1600-6143. ; 23:1, s. 64-71
-
Tidskriftsartikel (refereegranskat)abstract
- Many countries curate national registries of liver transplant (LT) data. These registries are often used to generate predictive models; however, potential performance and transferability of these models remain unclear. We data from 3 national registries and developed machine learning algorithm (MLA)-based models to predict 90 post-LT mortality within and across countries. Predictive performance and external validity of each model assessed. Prospectively collected data of adult patients (aged >= 18 years) who underwent primary LTs between January 2008 and December 2018 from the Canadian Organ Replacement Registry (Canada), National Service Blood and Transplantation (United Kingdom), and United Network for Organ Sharing (United were used to develop MLA models to predict 90-day post-LT mortality. Models were developed using each registry individually (based on variables inherent to the individual databases) and using all 3 registries combined iables in common between the registries [harmonized]). The model performance was evaluated using area the receiver operating characteristic (AUROC) curve. The number of patients included was as follows: Canada, = 1214; the United Kingdom, n = 5287; and the United States, n = 59,558. The best performing MLA-based model was ridge regression across both individual registries and harmonized data sets. Model performance diminished from individualized to the harmonized registries, especially in Canada (individualized ridge: AUROC, 0.74; range, 0.73-0.74; harmonized: AUROC, 0.68; range, 0.50-0.73) and US (individualized ridge: AUROC, range, 0.70-0.71; harmonized: AUROC, 0.66; range, 0.66-0.66) data sets. External model performance countries was poor overall. MLA-based models yield a fair discriminatory potential when used within individual databases. However, the external validity of these models is poor when applied across countries. Standardization of registry-based variables could facilitate the added value of MLA-based models in informing decision making future LTs.
|
|
