| 1. |
- Fletcher, Kevin, et al.
(författare)
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Glucocorticoid response to both predictable and unpredictable challenges detected as corticosterone metabolites in collared flycatcher droppings
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- In most vertebrate animals, glucocorticoid hormones are the chief mediators of homeostasis in response to ecological conditions and as they progress through their lifecycle. In addition, glucocorticoids are a major part of the stress response and stress induced elevations of the hormone can make it difficult to assess glucocorticoid secretion in response to changes in life-stage and current environmental conditions in wild animals. Particularly when quantifying circulating levels of glucocorticoids in the blood which fluctuate rapidly in response to stress. An alternative method of quantifying glucocorticoids is as hormone metabolites in faeces or urine giving a historical sample related to the gut passage time and urinary tract that is less sensitive to stressful events which cause spikes in the circulating hormone level. Although the concentration of glucocorticoid metabolites are influenced by faecal mass thereby potentially affecting any differences in hormone metabolites detected amongst samples. In the present study, we aimed to detect changes in levels of corticosterone, the primary bird glucocorticoid, in relation to the phase of reproduction, in a breeding population of collared flycatchers by sampling corticosterone metabolites in droppings. We also tested how corticosterone metabolite concentrations were affected by ambient temperature and related to body condition in adult birds. Our results indicate that the upregulation of corticosterone between incubation and nestling feeding in female birds is crucial for successful reproduction in this species. Also, females appear to downregulate corticosterone during incubation in response to lower ambient temperature and poorer body condition. Our results did not indicate a relationship between dropping mass and corticosterone metabolite concentrations, which suggests that our findings were linked to the regulation of corticosterone in response to predictable and unpredictable challenges.
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| 2. |
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| 3. |
- Tinetti, G., et al.
(författare)
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A chemical survey of exoplanets with ARIEL
- 2018
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Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 46:1, s. 135-209
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Tidskriftsartikel (refereegranskat)abstract
- Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.
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| 4. |
- Arridge, Christopher S., et al.
(författare)
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Uranus Pathfinder : exploring the origins and evolution of Ice Giant planets
- 2012
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 33:2-3, s. 753-791
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Tidskriftsartikel (refereegranskat)abstract
- The "Ice Giants" Uranus and Neptune are a different class of planet compared to Jupiter and Saturn. Studying these objects is important for furthering our understanding of the formation and evolution of the planets, and unravelling the fundamental physical and chemical processes in the Solar System. The importance of filling these gaps in our knowledge of the Solar System is particularly acute when trying to apply our understanding to the numerous planetary systems that have been discovered around other stars. The Uranus Pathfinder (UP) mission thus represents the quintessential aspects of the objectives of the European planetary community as expressed in ESA's Cosmic Vision 2015-2025. UP was proposed to the European Space Agency's M3 call for medium-class missions in 2010 and proposed to be the first orbiter of an Ice Giant planet. As the most accessible Ice Giant within the M-class mission envelope Uranus was identified as the mission target. Although not selected for this call the UP mission concept provides a baseline framework for the exploration of Uranus with existing low-cost platforms and underlines the need to develop power sources suitable for the outer Solar System. The UP science case is based around exploring the origins, evolution, and processes at work in Ice Giant planetary systems. Three broad themes were identified: (1) Uranus as an Ice Giant, (2) An Ice Giant planetary system, and (3) An asymmetric magnetosphere. Due to the long interplanetary transfer from Earth to Uranus a significant cruise-phase science theme was also developed. The UP mission concept calls for the use of a Mars Express/Rosetta-type platform to launch on a Soyuz-Fregat in 2021 and entering into an eccentric polar orbit around Uranus in the 2036-2037 timeframe. The science payload has a strong heritage in Europe and beyond and requires no significant technology developments.
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| 5. |
- Barnaby, Jonathan, 1965-, et al.
(författare)
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Development of a suit of microsatellite markers for the southern anteater-chat Myrmecocichla formicivora.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We tested the cross amplification of 37 microsatellite markers for their suitability in genotyping the southern anteater-chat Myrmecocichla formicivora, an opportunistic cooperatively breeding passerine bird endemic to southern Africa. Fourteen microsatellite markers were identified as having suitable characteristics, with minor deviation from Hardy-Weinberg equilibrium and little evidence of null alleles. These 14 Primer pairs were combined in 4 multiplexes and run on 183 individual samples from our study population of southern anteater-chat on Benfontein Nature Reserve, near Kimberley in central South Africa. The loci ranged from 3-34 alleles per locus, and observed heterozygosity ranged from 0.45 -0.93. We then tested these 14 microsatellites for their use in examining paternity in a population of southern anteater-chat being studied on Benfontein Nature Reserve, near Kimberley in South Africa. Of the population of 183 individuals (the 2011 population) 93% of the offspring could be allocated a mother, 97% a father, and 87% a parent pair with 95% confidence. The remainder could be allocated at the 80% confidence level. Where mothers could be assigned from observations this was in 100% agreement with the microsatellite results, giving us good support for the accurate assignment of parentage in our population.
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| 6. |
- Barnaby, Jonathan, 1965-, et al.
(författare)
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Group-living in the southern anteater-chat Myrmecocichla formicivora.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Group-living sets the scene for complex social behaviours such as cooperative breeding, and exploring the factors that shape group-living is crucial in understanding these behaviours. Here we describe some aspects of the ecology of a population of the facultative cooperative breeding southern anteater-chat (Myrmecocichla formicivora), a group living bird species endemic to southern Africa. We used data from a four year study of individually marked birds, with pedigrees completed using microsatellite genotyping. Southern anteater-chats live in groups of 2-5 individuals - a breeding pair and up to three additional none-breeders. These auxiliary birds were either retained offspring or unrelated individuals, and all birds in a group assisted by feeding at the nest. Our population had a skewed sex ratio of approximately 58% males to 42% females, yet the sex ratio of fledglings was equal, suggesting sex-biased mortality. Helpers were predominantly retained male offspring; however 21% of helpers were unrelated to either of the breeding pair. Southern anteater-chats appear to be non-territorial, with an apparent lack of aggression both within and between groups. Our study confirms that the southern anteater-chat is a facultative cooperative breeder, with both pair breeders and groups with helpers capable of fledging youngsters. We provide evidence suggesting that the breeding system of the southern anteater-chat is based on prompt female dispersal, and male philopatry due to an apparent shortage of mates, potential benefits of the natal site and possible high costs of floating. It appears that ecological constraints promoting delayed dispersal are reinforced by benefits gained from remaining philopatric.
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| 7. |
- Fletcher, Kevin
(författare)
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Causes and consequences of life-history variation : The effects of parasites, glucocorticoids, and environmental conditions in the collared flycatcher (Ficedula albicollis)
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Life-history is the study of all the different stages of life that affect reproductive success and survival between the birth and death of an organism. The reproductive output of an organism is constrained by many things including time, resource, disease agents and environmental conditions. In addition, lineage-specific traits and the limitations of the physiological systems can limit how an organism responds to ecological processes, and thus constrains the variation of life histories represented in nature. Central to the theory of life history are the trade-offs that organisms make during their lifetime to maximise their reproductive potential. In this thesis, I focus on the effect of haemosporidian blood parasites on host life history, in relation to the glucocorticoid response and environmental conditions. The host study species is a population of collared flycatchers (Ficedula albicollis), a species that provides bi-parental care, located in the south of Gotland. We show that nestling condition predicts parasite infection and that parasite-mediated selection can start early on in the birds’ life. We also found a link between Lower levels of glucocorticoids and parasite infection, which might indicate a trade-off between immunity and reproductive effort. Adult birds’ upregulated glucocorticoids in response to an increase in reproductive effort and a predictable change in energy demand during reproduction. I also show that glucocorticoids respond to changing environmental conditions. These results together accentuate the importance of the plasticity of the glucocorticoid response to reproductive success. Moreover, higher levels of hormone during reproduction predicted survival to the next breeding season. In nestlings, glucocorticoid levels increased as a consequence of parent infection status and an increase in reproductive effort. Overall, our results indicate that the glucocorticoid response is context dependent. Finally, female collared flycatchers might pay a fitness cost as a consequence of parasite infection, but can still reproduce successfully suggesting that they can tolerate the parasite. To further our understanding of costs related to parasite infection, we must understand better the mechanisms that enable the host to tolerate infection. This study indicates that glucocorticoids provide a useful tool to detect how wild birds respond to predictable and unpredictable challenges.
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| 8. |
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| 9. |
- Fletcher, Kevin, et al.
(författare)
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Importance of infection of haemosporidia blood parasites during different life history stages for long-term reproductive fitness of collared flycatchers
- 2019
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Ingår i: Journal of Avian Biology. - : John Wiley & Sons. - 0908-8857 .- 1600-048X. ; 50:8
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Tidskriftsartikel (refereegranskat)abstract
- The interaction between birds and haemosporidia blood parasites is a well-used system in the study of parasite biology. However, where, when and how parasites are transmitted is often unclear and defining parasite transmission dynamics is essential because of how they influence parasite-mediated costs to the host. In this study, we used cross-sectional and longitudinal data taken from a collared flycatcher Ficedula albicollis population to investigate the temporal dynamics of haemosporidia parasite infection and parasite-mediated costs to host fitness. We investigated host-parasite interactions starting at the nestling stage of the bird's life-cycle and then followed their progress over three breeding attempts to quantify their fitness - measured as the number of offspring they produced that recruited back into the breeding population. We found that the majority of haemosporidia blood parasite infections occurred within the first year of life and that the most common parasite lineages that infected the breeding population also infected juvenile birds in the natal environment. Moreover, our findings suggest that collared flycatcher nestlings in poorer condition could be at a higher risk of haemosporidia blood parasite infection. In this study, only female and not male bird fitness was adversely affected by parasite infection and the cost of infection on female fitness depended on the timing of transmission. In conclusion, our study indicates that in collared flycatchers, early-life is potentially important for many of the interactions with haemosporidia parasite lineages, and evidence of parasite-mediated costs to fitness suggest that these parasites may have influenced the host population dynamics.
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| 10. |
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Freedman, Kevin J., et al.
(författare)
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Nonequilibrium Capture Rates Induce Protein Accumulation and Enhanced Adsorption to Solid-State Nanopores
- 2014
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 8:12, s. 12238-12249
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Tidskriftsartikel (refereegranskat)abstract
- Single molecule capturing of analytes using an electrically biased nanopore is the fundamental mechanism in which nearly all nanopore experiments are conducted. With pore dimensions being on the order of a single molecule, the spatial zone of sensing only contains approximately a zeptoliter of volume. As a result, nanopores offer high precision sensing within the pore but provide little to no information about the analytes outside the pore. In this study, we use capture frequency and rate balance theory to predict and study the accumulation of proteins at the entrance to the pore. Protein accumulation is found to have positive attributes such as capture rate enhancement over time but can additionally lead to negative effects such as long-term blockages typically attributed to protein adsorption on the surface of the pore. Working with the folded and unfolded states of the protein domain PDZ2 from SAP97, we show that applying short (e.g., 3-25 s in duration) positive voltage pulses, rather than a constant voltage, can prevent long-term current blockades (i.e., adsorption events). By showing that the concentration of proteins around the pore can be controlled in real time using modified voltage protocols, new experiments can be explored which study the role of concentration on single molecular kinetics including protein aggregation, folding, and protein binding.
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| 15. |
- Grant, Michael C., et al.
(författare)
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Perioperative Care in Cardiac Surgery : A Joint Consensus Statement by the Enhanced Recovery After Surgery (ERAS) Cardiac Society, ERAS International Society, and The Society of Thoracic Surgeons (STS)
- 2024
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Ingår i: Annals of Thoracic Surgery. - : Elsevier. - 0003-4975 .- 1552-6259. ; 117:4, s. 669-689
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Tidskriftsartikel (refereegranskat)abstract
- Enhanced Recovery After Surgery (ERAS) programs have been shown to lessen surgical insult, promote recovery, and improve postoperative clinical outcomes across a number of specialty operations. A core tenet of ERAS involves the provision of protocolized evidence-based perioperative interventions. Given both the growing enthusiasm for applying ERAS principles to cardiac surgery and the broad scope of relevant interventions, an international, multidisciplinary expert panel was assembled to derive a list of potential program elements, review the literature, and provide a statement regarding clinical practice for each topic area. This article summarizes those consensus statements and their accompanying evidence. These results provide the foundation for best practice for the management of the adult patient undergoing cardiac surgery.
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| 16. |
- Griesser, Michael, et al.
(författare)
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Experience buffers extrinsic mortality in a group-living bird species
- 2017
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Ingår i: Oikos. - : Wiley. - 0030-1299 .- 1600-0706. ; 126:9, s. 1258-1268
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Tidskriftsartikel (refereegranskat)abstract
- Extrinsic mortality has a strong impact on the evolution of life-histories, prey morphology and behavioural adaptations, but for many animals the causes of mortality are poorly understood. Predation is an important driver of extrinsic mortality and mobile animals form groups in response to increased predation risk. Furthermore, in many species juveniles suffer higher mortality than older individuals, which may reflect a lower phenotypic quality, lower competitiveness, or a lack of antipredator or foraging skills. Here we assessed the causes of mortality for 371 radio tagged Siberian jays. This sedentary bird species lives in family groups that contain a breeding pair as well as related and unrelated non-breeders. Ninety-five percent of death were due to predation (n = 59 out of 62 individuals) and most individuals were killed by Accipiter hawks. Multivariate Cox proportional hazards models showed that non-breeders had a lower survival than breeders, but only in territories in managed forest with little visual cover. Examining breeders, only sex influenced survival with males having a lower survival than females. For non-breeders, juveniles had lower survival than older non-breeders, and those on managed territories had lower survival than those on unmanaged territories. Additionally, a low feather quality reduced the survival probability of non-breeders only. Thus, living on managed territories and having a low feature quality affected only non-breeders, particularly juveniles. These findings add to previous research demonstrating that juvenile Siberian jays acquire critical antipredator skills from experienced group members. Thus, experience can buffer extrinsic mortality, highlighting that group living not only provides safety in numbers, but also provide social opportunities to learn critical life-skills.
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| 17. |
- Johansson, Mattias, et al.
(författare)
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The influence of obesity-related factors in the etiology of renal cell carcinoma—A mendelian randomization study
- 2019
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation.Methods and findings: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44–1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40–1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44–1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30–2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11–1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84–1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.Conclusions: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.
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| 18. |
- Laskar, Ruhina S, et al.
(författare)
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Sex specific associations in genome wide association analysis of renal cell carcinoma.
- 2019
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 27:10, s. 1589-1598
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Tidskriftsartikel (refereegranskat)abstract
- Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (ORmale) = 0.83 [95% CI = 0.78-0.89], Pmale = 1.71 × 10-8 compared with female odds ratio (ORfemale) = 0.98 [95% CI = 0.90-1.07], Pfemale = 0.68) and 12q23.3 (intergenic, ORmale = 0.75 [95% CI = 0.68-0.83], Pmale = 1.59 × 10-8 compared with ORfemale = 0.93 [95% CI = 0.82-1.06], Pfemale = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC.
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| 19. |
- Machiela, Mitchell J, et al.
(författare)
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Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma.
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 72:5, s. 747-754
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings.OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations.DESIGN, SETTING, AND PARTICIPANTS: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis.RESULTS AND LIMITATIONS: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p<0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R2>0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13).CONCLUSIONS: Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk.PATIENT SUMMARY: Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma.
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| 20. |
- Rothman, Nathaniel, et al.
(författare)
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A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 978-984
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis.
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| 21. |
- Scelo, Ghislaine, et al.
(författare)
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Genome-wide association study identifies multiple risk loci for renal cell carcinoma.
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10-10), 3p22.1 (rs67311347, P=2.5 × 10-8), 3q26.2 (rs10936602, P=8.8 × 10-9), 8p21.3 (rs2241261, P=5.8 × 10-9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10-8), 11q22.3 (rs74911261, P=2.1 × 10-10) and 14q24.2 (rs4903064, P=2.2 × 10-24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.
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| 22. |
- Tinetti, Giovanna, et al.
(författare)
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The EChO science case
- 2015
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 40:2-3, s. 329-391
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of almost two thousand exoplanets has revealed an unexpectedly diverse planet population. We see gas giants in few-day orbits, whole multi-planet systems within the orbit of Mercury, and new populations of planets with masses between that of the Earth and Neptune-all unknown in the Solar System. Observations to date have shown that our Solar System is certainly not representative of the general population of planets in our Milky Way. The key science questions that urgently need addressing are therefore: What are exoplanets made of? Why are planets as they are? How do planetary systems work and what causes the exceptional diversity observed as compared to the Solar System? The EChO (Exoplanet Characterisation Observatory) space mission was conceived to take up the challenge to explain this diversity in terms of formation, evolution, internal structure and planet and atmospheric composition. This requires in-depth spectroscopic knowledge of the atmospheres of a large and well-defined planet sample for which precise physical, chemical and dynamical information can be obtained. In order to fulfil this ambitious scientific program, EChO was designed as a dedicated survey mission for transit and eclipse spectroscopy capable of observing a large, diverse and well-defined planet sample within its 4-year mission lifetime. The transit and eclipse spectroscopy method, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allows us to measure atmospheric signals from the planet at levels of at least 10(-4) relative to the star. This can only be achieved in conjunction with a carefully designed stable payload and satellite platform. It is also necessary to provide broad instantaneous wavelength coverage to detect as many molecular species as possible, to probe the thermal structure of the planetary atmospheres and to correct for the contaminating effects of the stellar photosphere. This requires wavelength coverage of at least 0.55 to 11 mu m with a goal of covering from 0.4 to 16 mu m. Only modest spectral resolving power is needed, with R similar to 300 for wavelengths less than 5 mu m and R similar to 30 for wavelengths greater than this. The transit spectroscopy technique means that no spatial resolution is required. A telescope collecting area of about 1 m(2) is sufficiently large to achieve the necessary spectro-photometric precision: for the Phase A study a 1.13 m(2) telescope, diffraction limited at 3 mu m has been adopted. Placing the satellite at L2 provides a cold and stable thermal environment as well as a large field of regard to allow efficient time-critical observation of targets randomly distributed over the sky. EChO has been conceived to achieve a single goal: exoplanet spectroscopy. The spectral coverage and signal-to-noise to be achieved by EChO, thanks to its high stability and dedicated design, would be a game changer by allowing atmospheric composition to be measured with unparalleled exactness: at least a factor 10 more precise and a factor 10 to 1000 more accurate than current observations. This would enable the detection of molecular abundances three orders of magnitude lower than currently possible and a fourfold increase from the handful of molecules detected to date. Combining these data with estimates of planetary bulk compositions from accurate measurements of their radii and masses would allow degeneracies associated with planetary interior modelling to be broken, giving unique insight into the interior structure and elemental abundances of these alien worlds. EChO would allow scientists to study exoplanets both as a population and as individuals. The mission can target super-Earths, Neptune-like, and Jupiter-like planets, in the very hot to temperate zones (planet temperatures of 300-3000 K) of F to M-type host stars. The EChO core science would be delivered by a three-tier survey. The EChO Chemical Census: This is a broad survey of a few-hundred exoplanets, which allows us to explore the spectroscopic and chemical diversity of the exoplanet population as a whole. The EChO Origin: This is a deep survey of a subsample of tens of exoplanets for which significantly higher signal to noise and spectral resolution spectra can be obtained to explain the origin of the exoplanet diversity (such as formation mechanisms, chemical processes, atmospheric escape). The EChO Rosetta Stones: This is an ultra-high accuracy survey targeting a subsample of select exoplanets. These will be the bright "benchmark" cases for which a large number of measurements would be taken to explore temporal variations, and to obtain two and three dimensional spatial information on the atmospheric conditions through eclipse-mapping techniques. If EChO were launched today, the exoplanets currently observed are sufficient to provide a large and diverse sample. The Chemical Census survey would consist of > 160 exoplanets with a range of planetary sizes, temperatures, orbital parameters and stellar host properties. Additionally, over the next 10 years, several new ground- and space-based transit photometric surveys and missions will come on-line (e.g. NGTS, CHEOPS, TESS, PLATO), which will specifically focus on finding bright, nearby systems. The current rapid rate of discovery would allow the target list to be further optimised in the years prior to EChO's launch and enable the atmospheric characterisation of hundreds of planets.
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| 23. |
- Tinetti, Giovanna, et al.
(författare)
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The science of EChO
- 2010
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Ingår i: Proceedings of the International Astronomical Union. - 1743-9213 .- 1743-9221. ; 6:S276, s. 359-370
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Tidskriftsartikel (refereegranskat)abstract
- The science of extra-solar planets is one of the most rapidly changing areas of astrophysics and since 1995 the number of planets known has increased by almost two orders of magnitude. A combination of ground-based surveys and dedicated space missions has resulted in 560-plus planets being detected, and over 1200 that await confirmation. NASA's Kepler mission has opened up the possibility of discovering Earth-like planets in the habitable zone around some of the 100,000 stars it is surveying during its 3 to 4-year lifetime. The new ESA's Gaia mission is expected to discover thousands of new planets around stars within 200 parsecs of the Sun. The key challenge now is moving on from discovery, important though that remains, to characterisation: what are these planets actually like, and why are they as they are In the past ten years, we have learned how to obtain the first spectra of exoplanets using transit transmission and emission spectroscopy. With the high stability of Spitzer, Hubble, and large ground-based telescopes the spectra of bright close-in massive planets can be obtained and species like water vapour, methane, carbon monoxide and dioxide have been detected. With transit science came the first tangible remote sensing of these planetary bodies and so one can start to extrapolate from what has been learnt from Solar System probes to what one might plan to learn about their faraway siblings. As we learn more about the atmospheres, surfaces and near-surfaces of these remote bodies, we will begin to build up a clearer picture of their construction, history and suitability for life. The Exoplanet Characterisation Observatory, EChO, will be the first dedicated mission to investigate the physics and chemistry of Exoplanetary Atmospheres. By characterising spectroscopically more bodies in different environments we will take detailed planetology out of the Solar System and into the Galaxy as a whole. EChO has now been selected by the European Space Agency to be assessed as one of four M3 mission candidates. © International Astronomical Union 2011.
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| 24. |
- Wu, Xifeng, et al.
(författare)
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A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:2, s. 456-462
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Tidskriftsartikel (refereegranskat)abstract
- Renal cell carcinoma (RCC) is the most lethal urologic cancer. Only two common susceptibility loci for RCC have been confirmed to date. To identify additional RCC common susceptibility loci, we conducted an independent genome- wide association study (GWAS). We analyzed 533 191 single nucleotide polymorphisms (SNPs) for association with RCC in 894 cases and 1516 controls of European descent recruited from MD Anderson Cancer Center in the primary scan, and validated the top 500 SNPs in silico in 3772 cases and 8505 controls of European descent involved in the only published GWAS of RCC. We identified two common variants in linkage disequilibrium, rs718314 and rs1049380 (r(2) = 0.64, D' = 0.84), in the inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) gene on 12p11.23 as novel susceptibility loci for RCC (P = 8.89 x 10(-10) and P = 6.07 x 10(-9), respectively, in meta-analysis) with an allelic odds ratio of 1.19 [95% confidence interval (CI): 1.13-1.26] for rs718314 and 1.18 (95% CI: 1.12-1.25) for rs1049380. It has been recently identified that rs718314 in ITPR2 is associated with waist-hip ratio (WHR) phenotype. To our knowledge, this is the first genetic locus associated with both cancer risk and WHR.
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