| 1. |
- Blizard, David A., et al.
(författare)
-
Blood pressure and heart rate QTL in mice of the B6/D2 lineage sex differences and environmental influences
- 2009
-
Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 36:3, s. 158-166
-
Tidskriftsartikel (refereegranskat)abstract
- A quantitative trait locus (QTL) approach was used to define the genetic architecture underlying variation in systolic blood pressure (SBP) and heart rate (HR), measured indirectly on seven occasions by the tail cuff procedure. The tests were conducted in 395 F(2) adult mice (197 males, 198 females) derived from a cross of the C57BL/6J (B6) and DBA/2J (D2) strains and in 22 BXD recombinant-inbred (RI) strains. Interval mapping of F(2) data for the first 5 days of measurement nominated one statistically significant and one suggestive QTL for SBP on chromosomes (Chr) 4 and 14, respectively, and two statistically significant QTL for HR on Chr 1 (which was specific to female mice) and Chr 5. New suggestive QTL emerged for SBP on Chr 3 (female-specific) and 8 and for HR on Chr 11 for measurements recorded several weeks after mice had undergone stressful blood sampling procedures. The two statistically significant HR QTL were confirmed by analyses of BXD RI strain means. Male and female F(2) mice did not differ in SBP or HR but RI strain analyses showed pronounced strain-by-sex interactions and a negative genetic correlation between the two measures in both sexes. Evidence for a role for mitochondrial DNA was found for both HR and SBP. QTL for HR and SBP may differ in males and females and may be sensitive to different environmental contexts.
|
|
| 2. |
- Gear, Jonathan I., et al.
(författare)
-
EANM practical guidance on uncertainty analysis for molecular radiotherapy absorbed dose calculations
- 2018
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 45:13, s. 2456-2474
-
Tidskriftsartikel (refereegranskat)abstract
- A framework is proposed for modelling the uncertainty in the measurement processes constituting the dosimetry chain that are involved in internal absorbed dose calculations. The starting point is the basic model for absorbed dose in a site of interest as the product of the cumulated activity and a dose factor. In turn, the cumulated activity is given by the area under a time–activity curve derived from a time sequence of activity values. Each activity value is obtained in terms of a count rate, a calibration factor and a recovery coefficient (a correction for partial volume effects). The method to determine the recovery coefficient and the dose factor, both of which are dependent on the size of the volume of interest (VOI), are described. Consideration is given to propagating estimates of the quantities concerned and their associated uncertainties through the dosimetry chain to obtain an estimate of mean absorbed dose in the VOI and its associated uncertainty. This approach is demonstrated in a clinical example.
|
|
| 3. |
- Hindorf, Cecilia, et al.
(författare)
-
EANM Dosimetry Committee guidelines for bone marrow and whole-body dosimetry
- 2010
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 37:6, s. 1238-1250
-
Tidskriftsartikel (refereegranskat)abstract
- The level of administered activity in radionuclide therapy is often limited by haematological toxicity resulting from the absorbed dose delivered to the bone marrow. The purpose of these EANM guidelines is to provide advice to scientists and clinicians on data acquisition and data analysis related to bone-marrow and whole-body dosimetry. The guidelines are divided into sections "Data acquisition" and "Data analysis". The Data acquisition section provides advice on the measurements required for accurate dosimetry including blood samples, quantitative imaging and/or whole-body measurements with a single probe. Issues specific to given radiopharmaceuticals are considered. The Data analysis section provides advice on the calculation of absorbed doses to the whole body and the bone marrow. The total absorbed dose to the bone marrow consists of contributions from activity in the bone marrow itself (self-absorbed dose) and the cross-absorbed dose to the bone marrow from activity in bone, larger organs and the remainder of the body. As radionuclide therapy enters an era where patient-specific dosimetry is used to guide treatments, accurate bone-marrow and whole-body dosimetry will become an essential element of treatment planning. We hope that these guidelines will provide a basis for the optimization and standardization of the treatment of cancer with radiopharmaceuticals, which will facilitate single- and multi-centre radionuclide therapy studies.
|
|
| 4. |
- Johansson, Linda, 1975-
(författare)
-
The Role of Cognitive Processes in Eating Pathology
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Researchers have recently combined clinical and cognitive areas of research in order to investigate the role of cognitive factors in explaining how emotional disorders are developed and maintained. It is believed that biased cognitive processing of emotionally relevant information can greatly affect emotional responses and behaviour where insights into such cognitive processes can have invaluable clinical implications.The present thesis investigates the role of cognitive biases for information related to food and body appearance in individuals with eating disorders (ED) and those with non-clinically eating disorder-related concerns (NED). Are ED characterised by cognitive biases toward such information related to their specific concerns? Are such cognitive biases specific to clinical ED or present also in NED samples? Are cognitive biases operating at both conscious and unconscious levels of cognitive processing?The tasks used to pursue these questions were: the emotional Stroop task, an Internet version of the emotional Stroop, Jacoby’s white noise paradigm and a recognition task. The influence of priming on the emotional Stroop task was also investigated in order to test whether the use of this task could be extended to more complex investigations than selective attention.Results provide support for that cognitive processing of information related to eating and body appearance is biased in individuals with ED. It is, however, unclear whether such biased processing is specific to clinical ED. Findings further suggest that cognitive biases occur primarily at unconscious levels of cognitive processing. Support was also obtained for that the emotional Stroop task is sensitive to priming where initial body perception may be one factor influencing cognitive responses toward negative self referent words following exposure to thin ideal images. Results further suggest that the emotional Stroop task successfully can be administered via the Internet where manipulating task delivery and response mode may increase the sensitivity of this task. Some of the advantages of administering the emotional Stroop task via Internet over traditional methods are access to more heterogeneous samples, more ecologically valid situations, reduced costs and minimisation of demand characteristics.
|
|
| 5. |
- 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.
|
|
| 6. |
- Miloff, Alexander, et al.
(författare)
-
Automated virtual reality exposure therapy for spider phobia vs. in-vivo one-session treatment : A randomized non-inferiority trial
- 2019
-
Ingår i: Behaviour Research and Therapy. - : Elsevier BV. - 0005-7967 .- 1873-622X. ; 118, s. 130-140
-
Tidskriftsartikel (refereegranskat)abstract
- This study compared the efficacy of a technician-assisted single-session virtual reality exposure therapy (VRET) for the treatment of spider phobia featuring low-cost consumer-available hardware and novel automated software to gold-standard in-vivo one-session treatment (OST), using a parallel group randomized non-inferiority design. Method Participants (N = 100) were randomized to VRET and OST arms. Assessors blinded to treatment allocation evaluated participants at pre- and post-treatment as well follow-up (3 and 12 months) using a behavioral approach test (BAT) and self-rated fear of spider, anxiety, depression and quality-of-life scales. A maximum post-treatment difference of 2-points on the BAT qualified as non-inferiority margin. Results Linear mixed models noted large, significant reductions in behavioral avoidance and self-reported fear in both groups at post-treatment, with VRET approaching the strong treatment benefits of OST over time. Non-inferiority was identified at 3- and 12- months follow-up but was significantly worse until 12-months. There was no significant difference on a questionnaire measuring negative effects. Conclusions Automated VRET efficaciously reduced spider phobia symptoms in the short-term and was non-inferior to in-vivo exposure therapy in the long-term. VRET effectiveness trials are warranted to evaluate real-world benefits and non-specific therapeutic factors accruing from the presence of a technician during treatment. ClinicalTrials.gov (NCT02533310).
|
|
| 7. |
|
|
| 8. |
- Nead, Kevin T., et al.
(författare)
-
Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity : a systematic review and meta-analysis with evidence from up to 331 175 individuals
- 2015
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:12, s. 3582-3594
-
Tidskriftsartikel (refereegranskat)abstract
- Polymorphisms rs6232 and rs6234/rs6235 in PCSK1 have been associated with extreme obesity [e.g. body mass index (BMI) a parts per thousand yen 40 kg/m(2)], but their contribution to common obesity (BMI a parts per thousand yen 30 kg/m(2)) and BMI variation in a multi-ethnic context is unclear. To fill this gap, we collected phenotypic and genetic data in up to 331 175 individuals from diverse ethnic groups. This process involved a systematic review of the literature in PubMed, Web of Science, Embase and the NIH GWAS catalog complemented by data extraction from pre-existing GWAS or custom-arrays in consortia and single studies. We employed recently developed global meta-analytic random-effects methods to calculate summary odds ratios (OR) and 95% confidence intervals (CIs) or beta estimates and standard errors (SE) for the obesity status and BMI analyses, respectively. Significant associations were found with binary obesity status for rs6232 (OR = 1.15, 95% CI 1.06-1.24, P = 6.08 x 10(-6)) and rs6234/rs6235 (OR = 1.07, 95% CI 1.04-1.10, P = 3.00 x 10(-7)). Similarly, significant associations were found with continuous BMI for rs6232 (beta = 0.03, 95% CI 0.00-0.07; P = 0.047) and rs6234/rs6235 (beta = 0.02, 95% CI 0.00-0.03; P = 5.57 x 10(-4)). Ethnicity, age and study ascertainment significantly modulated the association of PCSK1 polymorphisms with obesity. In summary, we demonstrate evidence that common gene variation in PCSK1 contributes to BMI variation and susceptibility to common obesity in the largest known meta-analysis published to date in genetic epidemiology.
|
|
| 9. |
- Nicolas, Aude, et al.
(författare)
-
Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
-
Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
-
Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
|
|
| 10. |
- Teo, Kevin, et al.
(författare)
-
rs641738C>T near MBOAT7 is associated with liver fat, ALT, and fibrosis in NAFLD: a meta-analysis.
- 2021
-
Ingår i: Journal of hepatology. - : Elsevier BV. - 1600-0641 .- 0168-8278. ; 74:1, s. 20-30
-
Tidskriftsartikel (refereegranskat)abstract
- A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in non-alcoholic fatty liver disease (NAFLD), however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and characterize its role in the regulation of related metabolic phenotypes through meta-analysis.We performed meta-analysis of studies with data on the association between rs641738C>T genotype and: liver fat, NAFLD histology, and serum ALT, lipids, or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed random effects meta-analysis using recessive, additive, and dominant genetic models.Data from 1,066,175 participants (9,688 with liver biopsies) across 42 studies were included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI: 0.02 - 0.05], pz=4.8x10-5) and diagnosis of NAFLD (OR 1.17 [95% CI 1.05 - 1.3], pz=0.003) in Caucasian adults. The variant was also positively associated with presence of advanced fibrosis (OR 1.22 [95% CI: 1.03 - 1.45], pz=0.021) in Caucasian adults using a recessive model of inheritance (CC+CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (pz=0.002) and lower serum triglycerides (pz=1.5x10-4). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD.Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent.
|
|
