| 1. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 2. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 3. |
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| 4. |
- Ankarcrona, Victoria, et al.
(författare)
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Obstetric anal sphincter injury after episiotomy in vacuum extraction: an epidemiological study using an emulated randomized trial approach
- 2021
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Ingår i: BJOG : an international journal of obstetrics and gynaecology. - : Wiley. - 1471-0528 .- 1470-0328. ; 128:10, s. 1663-1671
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Tidskriftsartikel (refereegranskat)abstract
- To emulate a randomized controlled trial investigating if lateral or mediolateral episiotomy compared to no episiotomy reduces the prevalence of obstetric anal sphincter injury (OASIS) in nulliparous women delivered with vacuum extraction.A population-based observational study.Sweden.63 654 nulliparous women delivered with vacuum extraction derived from the Swedish Medical Birth Register 2000-2011, with a live singleton baby without known malformations in cephalic presentation in gestational week ≥34+0, and subject to lateral or mediolateral episiotomy or no episiotomy.The effect of episiotomy was calculated using a causal doubly robust estimation method based on propensity scores. Results are presented as the average treatment effect and numbers needed to treat (NNT).OASIS (third- and fourth-degree perineal injury) in nulliparous women delivered with vacuum extraction.Episiotomy was associated with a reduction in OASIS from 15.5% to 11.8%, average treatment effect -3.66% (95% CI -4.31 to -3.01) and NNT 27. Third-degree perineal injuries were reduced from 14.0% to 10.9% (-3.08, 95% CI -3.71 to -2.42) with NNT 32. Fourth-degree perineal injuries were reduced from 1.6% to 1.0 % (-0.58%, 95% CI -0.79 to -0.37) with NNT 172.Lateral or mediolateral episiotomy reduced the prevalence of OASIS in nulliparous women delivered with vacuum extraction, compared to women with no episiotomy.
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| 5. |
- Axelsson, Rebecca, et al.
(författare)
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Computer model of mechanical imaging acquisition for virtual clinical trials
- 2021
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Ingår i: Medical Imaging 2021 : Physics of Medical Imaging - Physics of Medical Imaging. - : SPIE. - 1605-7422. - 9781510640191 ; 11595, s. 1-115950
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Konferensbidrag (refereegranskat)abstract
- Malignant breast tumours can be distinguished from benign lesions and normal tissue based on their mechanical properties. Our pilot studies have demonstrated the potential of using Mechanical Imaging (MI) combined with mammography to reduce recalls and false positives in breast cancer screening by more accurately identifying benign lesions. To enable further optimization of MI we propose a computer simulation of the MI acquisition, for use in a Virtual Clinical Trial (VCT) framework. VCTs are computer simulated clinical trials used to efficiently evaluate clinical imaging systems. A linear elastic finite element (FE) model of the breast under dynamic compression was implemented using an open-source FE solver. A spherical tumour (15 mm in diameter) was inserted into the simulated predominantly adipose breast. The location and stiffness of the tumour was varied. The average stress on the compressed breast surface was calculated and compared with the local average stress at the tumour location and the Relative Mean Pressure over lesion Area (RMPA) was calculated. Preliminary results were within a realistic range with an average stress on the breast (tumour) of 5.9-16.6 kPa which is in agreement with published values between 1.0 - 22.5 kPa. This corresponds to RMPA values of 0.96-2.15 depending on stiffness and location of the tumour. This can lead to more detailed validation of various MI acquisition schemes through VCTs before their use in clinical studies.
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| 6. |
- C. Manchaiah, Vinaya K., 1983-, et al.
(författare)
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The role of communication partners in the audiological enablement/rehabilitation of a person with hearing impairment : An overview
- 2012
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Ingår i: Audiological Medicine. - 1651-386X .- 1651-3835. ; 10:1, s. 21-30
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Hearing impairment is known to have various effects upon both the person with hearing impairment (PHI) and their communication partners (CPs). In addition, CPs are reported to play an important role in making the decision to seek a consultation and the acceptance of intervention by the PHI. The overall aim of this paper is to provide a comprehensive overview of the role of the CP in the audiological enablement/rehabilitation of the PHI keeping clinical practice in focus. Method: A literature review was conducted using a number of resources including electronic databases, books and websites. Results: An overview of the literature was presented in the following sections: 1) Factors influencing the audiological enablement/rehabilitation of the PHI; 2) Effect of the PHI's hearing impairment on their CPs; 3) CPs’ influence on their PHI's audiological enablement/rehabilitation; 4) Positive experiences reported by CPs of the PHI; 5) Models to represent CPs within the social network context of the PHI; and 6) CP involvement in the audiological enablement/rehabilitation. This paper also identifies gaps in the literature and provides recommendations for further research. Conclusion: It is clear that involvement of the CP in the audiological enablement/rehabilitation can result in mutual advantages for both the PHI and their CPs.
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| 7. |
- Gravelsins, Laura, et al.
(författare)
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Hormonal contraception and cognition: Considering the influence of endogenous ovarian hormones and genes for clinical translation
- 2023
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Ingår i: Frontiers in Neuroendocrinology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0091-3022 .- 1095-6808. ; 70
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Forskningsöversikt (refereegranskat)abstract
- Despite the well-known influence of ovarian hormones on the brain and widespread use of hormonal contraception (HC) since the 1960s, our knowledge of HCs cognitive effects remains limited. To date, the cognitive findings have been inconsistent. In order to establish what might make HC studies more consistent, we surveyed the literature on HCs and cognition to determine whether studies considered HC formulation, phase, pharmacokinetics, duration, and gene interactions, and assessed whether oversight of these factors might contribute to variable findings. We found that synthetic HC hormones exert dose-dependent effects, the day of oral contraceptive (Pill) ingestion is critical for understanding cognitive changes, and gene-cognition relationships differ in women taking the Pill likely due to suppressed endogenous hormones. When these factors were overlooked, results were not consistent. We close with recommendations for research more likely to yield consistent findings and be therefore, translatable.
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| 8. |
- Orrú, Valeria, et al.
(författare)
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A loss-of-function variant of PTPN22 is associated with reduced risk of systemic lupus erythematosus
- 2009
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 18:3, s. 569-579
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Tidskriftsartikel (refereegranskat)abstract
- A gain-of-function R620W polymorphism in the PTPN22 gene, encoding the lymphoid tyrosine phosphatase LYP, has recently emerged as an important risk factor for human autoimmunity. Here we report that another missense substitution (R263Q) within the catalytic domain of LYP leads to reduced phosphatase activity. High-resolution structural analysis revealed the molecular basis for this loss of function. Furthermore, the Q263 variant conferred protection against human systemic lupus erythematosus, reinforcing the proposal that inhibition of LYP activity could be beneficial in human autoimmunity.
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| 9. |
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The Seventeenth Data Release of the Sloan Digital Sky Surveys : Complete Release of MaNGA, MaStar, and APOGEE-2 Data
- 2022
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Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics (IOP). - 0067-0049 .- 1538-4365. ; 259:2
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Tidskriftsartikel (refereegranskat)abstract
- This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys.
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| 10. |
- Tomic, Hanna, et al.
(författare)
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Assessment of a tumour growth model for virtual clinical trials of breast cancer screening
- 2021
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Ingår i: Medical Imaging 2021 : Physics of Medical Imaging - Physics of Medical Imaging. - : SPIE. - 1605-7422. - 9781510640191 ; 11595
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Konferensbidrag (refereegranskat)abstract
- Image-based analysis of breast tumour growth rate may help optimize breast cancer screening and diagnosis. It may improve the identification of aggressive tumours and suggest optimal screening intervals. Virtual clinical trial (VCT) is a simulation-based method used to evaluate and optimize medical imaging systems and design clinical trials. Our work is motivated by desire to simulate multiple screening rounds with growing tumours. We have developed a model to simulate tumours with various growth rates; this study aims at evaluating the model. We used clinical data on tumour volume doubling times (TVDT) from our previous study, to fit a probability distribution ("clinical fit"). Growing tumours were inserted into 30 virtual breasts ("simulated cohort"). Based on the clinical fit we simulated two successive screening rounds for each virtual breast. TVDT from clinical and simulated images were compared. Tumour size was measured from simulated mammograms by a radiologist in three repeated sessions, to estimate TVDT ("estimated TVDT"). Reproducibility of measured sizes decreased slightly for small tumours. The mean TVDT from the clinical fit was 297±169 days, whereas the simulated cohort had 322±217 days, and the average estimated TVDT 340 ± 287 days. The median difference between the simulated and estimated TVDT was 12 days (4% of the mean clinical TVDT). Comparisons between other data sets suggest no significant difference (p>0.5). The proposed tumour growth model suggested close agreement with clinical results, supporting potential use in VCTs of temporal breast imaging.
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| 11. |
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| 12. |
- Tomic, Hanna, et al.
(författare)
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Virtual clinical trial of simultaneous digital breast tomosynthesis and mechanical imaging: : model calibration and the effect of tumor depth
- 2022
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Ingår i: Medical Imaging 2022: : Physics of Medical Imaging - Physics of Medical Imaging. - : SPIE. ; 12031
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Konferensbidrag (refereegranskat)abstract
- Simultaneous Digital Breast Tomosynthesis (DBT) and mechanical imaging (MI), called DBTMI, is a novel breast imaging method aimed at improving sensitivity and specificity of breast cancer screening. DBTMI combines improved cancer detection by three-dimensional DBT imaging, with the analysis of local stress over the compressed breast by MI, which can reduce false positive findings. The MI signal is affected by various factors, e.g., breast size, composition, tumor depth, etc. Assessing the individual effect of those factors using clinical data is difficult, due to their interdependence. These open clinical questions can be addressed by virtual clinical trials. Our current work is focused on the effects of tumor depth on the DBTMI signal. We simulated the breast anatomy by a matrix of adipose and glandular tissue compartments. Spherical tumors were inserted at various depths. The MI sensor is modeled by a compound material of PMMA and Ag. We calculated the local stress on the compressed breast surface at the tumor location and simulated the MI sensor output. We also simulated the corresponding DBT images and calculated the signal-difference-to-noise ratio (SDNR) with and without pre-processing to analyze the reduction in artifacts. Our preliminary analysis of 24 simulated tumors has shown 16% reduction in the local stress, when increasing tumor depth by 15 mm (10-25 mm from the breast surface). The SDNR improvement was highest for tumors near the sensor and the effect of pre-processing decreased with increasing tumor depth.
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