| 1. |
- Hess, Timo, et al.
(författare)
-
Dissecting the genetic heterogeneity of gastric cancer
- 2023
-
Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
|
|
| 2. |
- Bertl, Kristina, et al.
(författare)
-
Prevalence and severity of periodontal disease in a historical Austrian population.
- 2020
-
Ingår i: Journal of Periodontal Research. - : John Wiley & Sons. - 0022-3484 .- 1600-0765. ; 55:6, s. 931-945
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the prevalence and severity of periodontitis based on different diagnostic methods in a historical Austrian population from the early middle ages.Background: The description of the oral health status of archaeological material can provide interesting insights into prevalence, severity, and extent of oral diseases. Herein, the periodontal health status of the skeletal remains of medieval Avars (700-800 AD), which were considered as one of the earliest Avarian settlements in Austria, was investigated.Methods: The skeletal remains of 128 Avars were examined; age and gender were estimated by standard forensic methods and tooth loss and root caries were recorded. Periodontitis was assessed by (a) measurement of the alveolar bone levels (ABL) and (b) evaluation of the interdental septa.Results: A mean ABL of 4.8 mm was determined, root caries tended to accumulate in teeth with a higher alveolar bone loss, and on average, 6.2 teeth were lost antemortem. Independent of the diagnostic method >90% of the subjects were judged as periodontally diseased, and age and tooth type were significant predictors. However, on the tooth level the presence of periodontitis varied considerably depending on the diagnostic method; that is, 7.6% versus 47.2% of the teeth were judged as healthy based on ABL or interdental septa, respectively.Conclusion: The periodontal status of the skeletal remains of medieval Avars revealed a considerable high prevalence of periodontitis (ie, >90% of this population displayed periodontal tissue breakdown). However, the diagnostic method, disease definition, and data presentation should be considered when comparing results of archaeological material.
|
|
| 3. |
- Budreviciute, Aida, et al.
(författare)
-
Management and Prevention Strategies for Non-communicable Diseases (NCDs) and Their Risk Factors
- 2020
-
Ingår i: Frontiers In Public Health. - : Frontiers Media SA. - 2296-2565. ; 8
-
Forskningsöversikt (refereegranskat)abstract
- Non-communicable diseases (NCDs) are of increasing concern for society and national governments, as well as globally due to their high mortality rate. The main risk factors of NCDs can be classified into the categories of self-management, genetic factors, environmental factors, factors of medical conditions, and socio-demographic factors. The main focus is on the elements of self-management and to reach a consensus about the influence of food on risk management and actions toward the prevention of NCDs at all stages of life. Nutrition interventions are essential in managing the risk of NCDs. As they are of the utmost importance, this review highlights NCDs and their risk factors and outlines several common prevention strategies. We foresee that the best prevention management strategy will include individual (lifestyle management), societal (awareness management), national (health policy decisions), and global (health strategy) elements, with target actions, such as multi-sectoral partnership, knowledge and information management, and innovations. The most effective preventative strategy is the one that leads to changes in lifestyle with respect to diet, physical activities, cessation of smoking, and the control of metabolic disorders.
|
|
| 4. |
- Höijer, Carl Johan, et al.
(författare)
-
Single chamber atrial pacing: A realistic option in sinus node disease: A long-term follow-up study of 213 patients
- 2007
-
Ingår i: PACE. - : Wiley. - 1540-8159. ; 30:6, s. 740-747
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Despite several decades of experience with atrial pacing, many centers do not apply this mode to any greater extent, mainly because of concerns for the development of future atrioventricular (AV) block or atrial fibrillation. Recent studies have emphasized possible negative effects of right ventricular stimulation, even when AV-synchrony is preserved, and have thus given rise to renewed interest in single chamber atrial pacing for sinus node disease. Methods: This study presents the results of up to 19 years' follow-up of 213 patients with sinus node disease treated with atrial pacing with respect to survival and causes of death, development of atrial fibrillation and AV block, and total mode survival. Patients were divided into two groups: with or without associated atrial tachyarrhythmias at the time of implant. Results are given for all patients and for the two groups separately. Results: The mean follow-up time was 10.1 years. The survival of the entire group was lower after 10 years than that of an age and gender-matched general Swedish population. This was caused by patients with the brady-tachy syndrome (BT) having a significantly higher mortality rate than controls, whereas those with bradycardia only (B) had survival comparable to the general population. Permanent atrial fibrillation (AF) developed in 20% of patients and was significantly more common in patients with BT. The majority of patients with AF (78%) no longer needed any pacing, i.e., did not require ventricular stimulation due to slow ventricular rate. The annual incidence of high grade AV block was 1.8%. If patients with preexisting bundle branch block were excluded, the incidence was 1.6%. No fatal episode of AV block was seen. The overall mode survival at the end of follow-up was 75%, with 155 patients still with atrial pacemakers. Conclusion: Atrial pacing is a safe and reliable mode of pacing in patients with sinus node disease, even in the very long-term.
|
|
| 5. |
|
|
| 6. |
- Letcher, Susan G., et al.
(författare)
-
Environmental gradients and the evolution of successional habitat specialization : a test case with 14 Neotropical forest sites
- 2015
-
Ingår i: Journal of Ecology. - : Wiley. - 0022-0477 .- 1365-2745. ; 103:5
-
Tidskriftsartikel (refereegranskat)abstract
- * Successional gradients are ubiquitous in nature, yet few studies have systematically examined the evolutionary origins of taxa that specialize at different successional stages. Here we quantify successional habitat specialization in Neotropical forest trees and evaluate its evolutionary lability along a precipitation gradient. Theoretically, successional habitat specialization should be more evolutionarily conserved in wet forests than in dry forests due to more extreme microenvironmental differentiation between early and late-successional stages in wet forest. * We applied a robust multinomial classification model to samples of primary and secondary forest trees from 14 Neotropical lowland forest sites spanning a precipitation gradient from 788 to 4000 mm annual rainfall, identifying species that are old-growth specialists and secondary forest specialists in each site. We constructed phylogenies for the classified taxa at each site and for the entire set of classified taxa and tested whether successional habitat specialization is phylogenetically conserved. We further investigated differences in the functional traits of species specializing in secondary vs. old-growth forest along the precipitation gradient, expecting different trait associations with secondary forest specialists in wet vs. dry forests since water availability is more limiting in dry forests and light availability more limiting in wet forests. * Successional habitat specialization is non-randomly distributed in the angiosperm phylogeny, with a tendency towards phylogenetic conservatism overall and a trend towards stronger conservatism in wet forests than in dry forests. However, the specialists come from all the major branches of the angiosperm phylogeny, and very few functional traits showed any consistent relationships with successional habitat specialization in either wet or dry forests. * Synthesis. The niche conservatism evident in the habitat specialization of Neotropical trees suggests a role for radiation into different successional habitats in the evolution of species-rich genera, though the diversity of functional traits that lead to success in different successional habitats complicates analyses at the community scale. Examining the distribution of particular lineages with respect to successional gradients may provide more insight into the role of successional habitat specialization in the evolution of species-rich taxa.
|
|
| 7. |
- Lundstedt-Enkel, Katrin, et al.
(författare)
-
A Statistical Resampling Method To Calculate Biomagnification Factors Exemplified with Organochlorine Data from Herring (Clupea harengus) Muscle and Guillemot (Uria aalge) Egg from the Baltic Sea
- 2005
-
Ingår i: ENVIRONMENTAL SCIENCE & TECHNOLOGY. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 39:21, s. 8395-8402
-
Tidskriftsartikel (refereegranskat)abstract
- A novel method for calculating biomagnification factors is presented and demonstrated using contaminant concentration data from the Swedish national monitoring program regarding organochlorine contaminants (OCs) in herring (Clupea harengus) muscle and guillemot (Uria aalge) egg, sampled from 1996 to 1999 from the Baltic Sea. With this randomly sampled ratios (RSR) method, biomagnification factors (BMFRSR) were generated and denoted with standard deviation (0) as a measure of the variation. The BMFRSR were calculated by randomly selecting one guillemot egg out of a total of 29 and one herring out of a total of 74, and the ratio was determined between the concentration of a given OC in that egg and the concentration of the same OC in that herring. With the resampling technique, this was performed 50 000 times for any given OC, and from this new distribution of ratios, BMFRSR for each OC were calculated and given as geometric mean (GM) with GM standard deviation (GMSD) range, arithmetic mean (AM) with AMSD range, and minimum (BMFMIN) as well as maximum (BMFMAX) biomagnification factors. The 14 analyzed OCs were p,p'DDT and its metabolites p,p'DDE and p,p'DDD, polychlorinated biphenyls (PCB congeners: CB28, CB52, CB101, CB118, CB138, CB153, and CB180), hexachlorocyclohexane isomers (alpha-, beta-, and gamma HCH), and hexachlorobenzene (HCB). Multivariate data analysis (MVDA) methods, including principal components analysis (PCA), partial least squares regression (PLS), and PLS discriminant analyses (PLS-DA), were first used to extract information from the complex biological and chemical data generated from each individual animal. MVDA were used to model similarities/dissimilarities regarding species (PCA, PLS-DA), sample years (PLS), and sample location (PLS-DA) to give a deeper understanding of the data that the BMF modeling was based upon. Contaminants that biomagnify, that had BMFRSR significantly higher than one, were p,p'DDE, CB118, HCB, CB138, CB180, CB153, beta HCH, and CB28. The contaminants that did not biomagnify were p,p'DDT, p,p'DDD, alpha HCH, CB101, and CB52. Eventual biomagnification for gamma HCH could not be determined. The BMFRSR for OCs present in herring muscle and guillemot egg showed a broad span with large variations for each contaminant. To be able to make reliable calculations of BMFs for different contaminants, we emphasize the importance of using data based upon large numbers of, as well as well-defined, individuals.
|
|
| 8. |
|
|
| 9. |
- Mansouri, Masoumeh, 1985-, et al.
(författare)
-
Combining Task and Motion Planning : Challenges and Guidelines
- 2021
-
Ingår i: Frontiers in Robotics and AI. - : Frontiers Media S.A.. - 2296-9144. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Combined Task and Motion Planning (TAMP) is an area where no one-fits-all solution can exist. Many aspects of the domain, as well as operational requirements, have an effect on how algorithms and representations are designed. Frequently, trade-offs have to be madet o build a system that is effective. We propose five research questions that we believe need to be answered to solve real-world problems that involve combined TAMP. We show which decisions and trade-offs should be made with respect to these research questions, and illustrate these on examples of existing application domains. By doing so, this article aims to provide a guideline for designing combined TAMP solutions that are adequate and effective in the target scenario.
|
|
| 10. |
- Pokorny, Florian B., et al.
(författare)
-
Earlier Identification of Children with Autism Spectrum Disorder : An Automatic Vocalisation-based Approach
- 2017
-
Ingår i: 18Th Annual Conference Of The International Speech Communication Association (INTERSPEECH 2017), Vols 1-6. - 9781510848764 ; , s. 309-313
-
Konferensbidrag (refereegranskat)abstract
- Autism spectrum disorder (ASD) is a neurodevelopmental disorder usually diagnosed in or beyond toddlerhood. ASD is defined by repetitive and restricted behaviours, and deficits in social communication. The early speech-language development of individuals with ASD has been characterised as delayed. However, little is known about ASD-related characteristics of pre-linguistic vocalisations at the feature level. In this study. we examined pre-linguistic vocalisations of 10-month-old individuals later diagnosed with ASD and a matched control group of typically developing individuals (N = 20). We segmented 684 vocalisations from parent-child interaction recordings. All vocalisations were annotated and signal-analytically decomposed. We analysed ASD-related vocalisation specificities on the basis of a standardised set (eGeMAPS) of 88 acoustic features selected for clinical speech analysis applications. 54 features showed evidence for a differentiation between vocalisations of individuals later diagnosed with ASD and controls. In addition, we evaluated the feasibility of automated, vocalisation-based identification of individuals later diagnosed with ASD. We compared linear kernel support vector machines and a 1-layer bidirectional long short-term memory neural network. Both classification approaches achieved an accuracy of 75% for subject-wise identification in a subject-independent 3-fold cross-validation scheme. Our promising results may be an important contribution en-route to facilitate earlier identification of ASD.
|
|
