| 1. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 2. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 3. |
- Amiel, Joshua Johnstone, et al.
(författare)
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Egg incubation effects generate positive correlations between size, speed and learning ability in young lizards
- 2014
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Ingår i: Animal Cognition. - : Springer Berlin/Heidelberg. - 1435-9448 .- 1435-9456. ; 17:2, s. 337-347
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have suggested that body size and locomotor performance are targets of Darwinian selection in reptiles. However, much of the variation in these traits may derive from phenotypically plastic responses to incubation temperature, rather than from underlying genetic variation. Intriguingly, incubation temperature may also influence cognitive traits such as learning ability. Therefore, we might expect correlations between a reptiles size, locomotor speed and learning ability either due to selection on all of these traits or due to environmental effects during egg incubation. In the present study, we incubated lizard eggs (Scincidae: Bassiana duperreyi) under hot and cold thermal regimes and then assessed differences in hatchling body size, running speed and learning ability. We measured learning ability using a Y-maze and a food reward. We found high correlations between size, speed and learning ability, using two different metrics to quantify learning (time to solution, and directness of route), and showed that environmental effects (incubation temperature) cause these correlations. If widespread, such correlations challenge any simple interpretation of fitness advantages due to body size or speed within a population; for example, survivors may be larger and faster than nonsurvivors because of differences in learning ability, not because of their size or speed.
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| 4. |
- Carré, Helena, et al.
(författare)
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Asking about condom use : a key to individualized care when screening for chlamydia
- 2011
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Ingår i: International Journal of STD and AIDS (London). - : Sage Publications. - 0956-4624 .- 1758-1052. ; 22:8, s. 436-441
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Tidskriftsartikel (refereegranskat)abstract
- Chlamydia trachomatis (CT) infection has been a target for both selective and national screening programmes, and Sweden has an opportunistic approach. A national plan of action states that risk groups should be identified and offered risk reduction counselling. Patients attending a drop-in sexually transmitted infection (STI) clinic reception at the University Hospital, Umeå, Sweden, were invited to complete a questionnaire regarding sociodemographic characteristics, symptoms and sexual risk behaviour; all had a CT test taken. A total of 1305 patients were included, 58% men, mean age 27.8 years. CT prevalence was 11%; 51% of those with CT were ≥ 25 years old. Only 5% used a condom during the entire sexual intercourse with their last new/temporary partner. Sexually active inconsistent condom users comprised 62% of the study population and contributed to 81% of the chlamydia infections. Asking whether a condom was used could quickly triage patients into groups with a 'higher risk' (none or inconsistent use of condoms and at least one new/temporary partners), and 'lower risk' (with more consistent condom use, although not always accurate) allowing for individualized care and counselling when screening for chlamydia. Evaluating whether a condom was used throughout the sexual intercourse did not add any useful information.
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| 5. |
- Carré, Helena, 1979-, et al.
(författare)
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High prevalence of anxiety and hazardous alcohol consumption among patients attending an STI-clinic in northern Sweden
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Depression and hazardous alcohol consumption is associated to high-risk sexual behaviours among adolescents and young adults. Is the same true among grownups? The impact of anxiety on sexual risk behaviour is not thoroughly investigated. Our aim was to evaluate the correlation between hazardous alcohol consumption, depression and anxiety to sexual risk taking including Chlamydia infections, among patients attending an STI reception. Method: Patients attending an urban STI reception in Sweden were consecutively included and received questionnaires; screening- and demographic information, Alcohol Use Disorder Identification Test (AUDIT) and Hospital Anxiety and Depression scale (HAD). All patients also had a test for Chlamydia trachomatis taken. Results: 539 patients were included in the study, mean age 28 years. 152 (30%) had signs of anxiety and 37 (7%) of depression, of which 30 had also anxiety. Neither anxiety nor depression was correlated to sexual risk behaviour. >50% had hazardous alcohol consumption and it was independently linked to sexual risk behaviours and anxiety. Conclusion: Depression is not associated to sexual risk behaviours among adult STI-patients. Health care staff and must consider the high frequency of anxiety and hazardous alcohol consumption at their treatment of STI-clinic patients and in the preventive work. The society must work with lowering the stigmatization that still seems to be connected to STIs.
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| 6. |
- Chen, Hongjie, et al.
(författare)
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Large-scale cross-cancer fine-mapping of the 5p15.33 region reveals multiple independent signals
- 2021
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Ingår i: Human Genetics and Genomics Advances. - : Cell Press. - 2666-2477. ; 2:3
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) have identified thousands of cancer risk loci revealing many risk regions shared across multiple cancers. Characterizing the cross-cancer shared genetic basis can increase our understanding of global mechanisms of cancer development. In this study, we collected GWAS summary statistics based on up to 375,468 cancer cases and 530,521 controls for fourteen types of cancer, including breast (overall, estrogen receptor [ER]-positive, and ER-negative), colorectal, endometrial, esophageal, glioma, head/neck, lung, melanoma, ovarian, pancreatic, prostate, and renal cancer, to characterize the shared genetic basis of cancer risk. We identified thirteen pairs of cancers with statistically significant local genetic correlations across eight distinct genomic regions. Specifically, the 5p15.33 region, harboring the TERT and CLPTM1L genes, showed statistically significant local genetic correlations for multiple cancer pairs. We conducted a cross-cancer fine-mapping of the 5p15.33 region based on eight cancers that showed genome-wide significant associations in this region (ER-negative breast, colorectal, glioma, lung, melanoma, ovarian, pancreatic, and prostate cancer). We used an iterative analysis pipeline implementing a subset-based meta-analysis approach based on cancer-specific conditional analyses and identified ten independent cross-cancer associations within this region. For each signal, we conducted cross-cancer fine-mapping to prioritize the most plausible causal variants. Our findings provide a more in-depth understanding of the shared inherited basis across human cancers and expand our knowledge of the 5p15.33 region in carcinogenesis.
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| 7. |
- Dahlgren Lindström, Adam, 1993-
(författare)
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Learning, reasoning, and compositional generalisation in multimodal language models
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- We humans learn language and how to interact with the world through our different senses, grounding our language in what we can see, touch, hear, and smell. We call these streams of information different modalities, and our efficient processing and synthesis of the interactions between different modalities is a cornerstone of our intelligence. Therefore, it is important to study how we can build multimodal language models, where machine learning models learn from more than just text. This is particularly important in the era of large language models (LLMs), where their general capabilities are unclear and unreliable. This thesis investigates learning and reasoning in multimodal language models, and their capabilities to compositionally generalise in visual question answering tasks. Compositional generalisation is the process in which we produce and understand novel sentences, by systematically combining words and sentences to uncover the meaning in language, and has proven a challenge for neural networks. Previously, the literature has focused on compositional generalisation in text-only language models. One of the main contributions of this work is the extensive investigation of text-image language models. The experiments in this thesis compare three neural network-based models, and one neuro-symbolic method, and operationalise language grounding as the ability to reason with relevant functions over object affordances.In order to better understand the capabilities of multimodal models, this thesis introduces CLEVR-Math as a synthetic benchmark of visual mathematical reasoning. The CLEVR-Math dataset involve tasks such as adding and removing objects from 3D scenes based on textual instructions, such as \emph{Remove all blue cubes. How many objects are left?}, and is given as a curriculum of tasks of increasing complexity. The evaluation set of CLEVR-Math includes extensive testing of different functional and object attribute generalisations. We open up the internal representations of these models using a technique called probing, where linear classifiers are trained to recover concepts such as colours or named entities from the internal embeddings of input data. The results show that while models are fairly good at generalisation with attributes (i.e.~solving tasks involving never before seen objects), it is a big challenge to generalise over functions and to learn abstractions such as categories. The results also show that complexity in the training data is a driver of generalisation, where an extended curriculum improves the general performance across tasks and generalisation tests. Furthermore, it is shown that training from scratch versus transfer learning has significant effects on compositional generalisation in models.The results identify several aspects of how current methods can be improved in the future, and highlight general challenges in multimodal language models. A thorough investigation of compositional generalisation suggests that the pre-training of models allow models access to inductive biases that can be useful to solve new tasks. Contrastingly, models trained from scratch show much lower overall performance on the synthetic tasks at hand, but show lower relative generalisation gaps. In the conclusions and outlook, we discuss the implications of these results as well as future research directions.
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| 8. |
- Danielsson, Sverker, 1978-
(författare)
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Xylan Reactions in Kraft Cooking : Process and Product Considerations
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Xylan is the main hemicellulose in birch, eucalyptus, and most other hardwood species. During kraft pulping a series of chemical reactions and physical processes involving xylan takes place. The processes studied here are the following: dissolution, degradation, redeposition onto the fibres, side-group conversion, and cleavage of side groups off the xylan backbone. The side group in native xylan consists of methylglucuronic acid, which is partly converted into hexenuronic acid during kraft cooking. Hexenuronic acid affects the pulp in terms of increased brightness reversion and reduced bleachability. The kinetics of the side-group cleavage and conversion reactions were studied using various analytical tools. The study revealed that the most common methods for methylglucuronic acid quantifcation can be signifcantly improved in terms of accuracy. A modifcation and combination of two of the methods was suggested and evaluated. In order to minimise the hexenuronic acid content, a common suggestion involves the use of a high cooking temperature. The kinetic study found that the degree of substitution of pulp xylan is only slightly affected by temperature, and that the observed effects are likely to be more associated with the xylan content of the pulp than with the hexenuronic acid content of the xylan. For the dissolved xylan, however, the degree of substitution indicated a high temperature dependency for birch kraft cooking. By collecting black liquors at different stages in the cook, different molecular properties of the dissolved xylan was obtained. The liquors were charged at later parts of the cook, making the dissolved xylan to reattach to the fibres. Depending on the molecular properties of the added xylan, the tensile strength properties of the produced paper were improved. These improvements in paper properties were correlated to the molecular behaviour of the added xylan in solution.
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| 9. |
- Gamero, Anna, et al.
(författare)
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Tracking Progress Toward EU Biodiversity Strategy Targets : EU Policy Effects in Preserving its Common Farmland Birds
- 2017
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Ingår i: Conservation Letters. - : Wiley. - 1755-263X. ; 10:4, s. 395-402
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Tidskriftsartikel (refereegranskat)abstract
- Maximizing the area under biodiversity-related conservation measures is a main target of the European Union (EU) Biodiversity Strategy to 2020. We analyzed whether agrienvironmental schemes (AES) within EU common agricultural policy, special protected areas for birds (SPAs), and Annex I designation within EU Birds Directive had an effect on bird population changes using monitoring data from 39 farmland bird species from 1981 to 2012 at EU scale. Populations of resident and short-distance migrants were larger with increasing SPAs and AES coverage, while Annex I species had higher population growth rates with increasing SPAs, indicating that SPAs may contribute to the protection of mainly target species and species spending most of their life cycle in the EU. Because farmland birds are in decline and the negative relationship of agricultural intensification with their population growth rates was evident during the implementation of AES and SPAs, EU policies seem to generally attenuate the declines of farmland bird populations, but not to reverse them.
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| 10. |
- Gilleland, Eric, et al.
(författare)
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Spatial Forecast Verification: Image Warping
- 2010
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In response to a growing need for more informative forecast verification in the face of gridded verification sets, many new methods have been proposed. While widely varying in their approaches, the new methods generally fall into two ma- jor categories of filter and displacement, each of which can be further subdivided. One of the displacement approaches, a field deformation approach known as image warping, will be demonstrated here. Results for spatial verification of the spatial forecast verification Inter-Comparison Project test cases are shown. An initial look at space-time verification using the image warp is also discussed, with an applic- ation to NCAR and NCEP 4-km WRF models cases from the 2005 NSSL/SPC Spring Program. The approach is found to be very useful for obtaining guidance about forecast performance. Both diagnostic and summary score information can be gleaned. Initial findings for the space-time approach show that while the NCEP model has better initial scores, the NCAR models require drastically less deform- ation to achieve a much higher reduction in error. This is most likely a result of the NCEP model’s highly over forecasting low-intensity precipitation spatially.
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