| 41. |
- Stevens, A., et al.
(författare)
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Gene expression signatures predict response to therapy with growth hormone
- 2021
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Ingår i: Pharmacogenomics Journal. - : Springer Science and Business Media LLC. - 1470-269X .- 1473-1150. ; 21, s. 594-607
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Tidskriftsartikel (refereegranskat)abstract
- Recombinant human growth hormone (r-hGH) is used as a therapeutic agent for disorders of growth including growth hormone deficiency (GHD) and Turner syndrome (TS). Treatment is costly and current methods to model response are inexact. GHD (n = 71) and TS patients (n = 43) were recruited to study response to r-hGH over 5 years. Analysis was performed using 1219 genetic markers and baseline (pre-treatment) blood transcriptome. Random forest was used to determine predictive value of transcriptomic data associated with growth response. No genetic marker passed the stringency criteria for prediction. However, we identified an identical set of genes in both GHD and TS whose expression could be used to classify therapeutic response to r-hGH with a high accuracy (AUC > 0.9). Combining transcriptomic markers with clinical phenotype was shown to significantly reduce predictive error. This work could be translated into a single genomic test linked to a prediction algorithm to improve clinical management. Trial registration numbers: NCT00256126 and NCT00699855.
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| 42. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Growth Hormone Research Society perspective on biomarkers of GH action in children and adults
- 2018
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Ingår i: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The Growth Hormone Research Society (GRS) convened a Workshop in 2017 to evaluate clinical endpoints, surrogate endpoints and biomarkers during GH treatment of children and adults and in patients with acromegaly. Participants: GRS invited 34 international experts including clinicians, basic scientists, a regulatory scientist and physicians from the pharmaceutical industry. Evidence: Current literature was reviewed and expert opinion was utilized to establish the state of the art and identify current gaps and unmet needs. Consensus process: Following plenary presentations, breakout groups discussed questions framed by the planning committee. The attendees re-convened after each breakout session to share the group reports. A writing team compiled the breakout session reports into a document that was subsequently discussed and revised by participants. This was edited further and circulated for final review after the meeting. Participants from pharmaceutical companies were not part of the writing process. Conclusions: The clinical endpoint in paediatric GH treatment is adult height with height velocity as a surrogate endpoint. Increased life expectancy is the ideal but unfeasible clinical endpoint of GH treatment in adult GH-deficient patients (GHDA) and in patients with acromegaly. The pragmatic clinical endpoints in GHDA include normalization of body composition and quality of life, whereas symptom relief and reversal of comorbidities are used in acromegaly. Serum IGF-I is widely used as a biomarker, even though it correlates weakly with clinical endpoints in GH treatment, whereas in acromegaly, normalization of IGF-I may be related to improvement in mortality. There is an unmet need for novel biomarkers that capture the pleiotropic actions of GH in relation to GH treatment and in patients with acromegaly.
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| 43. |
- Clayton, Geoffrey C., et al.
(författare)
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THE CIRCUMSTELLAR ENVIRONMENT OF R CORONAE BOREALIS : WHITE DWARF MERGER OR FINAL-HELIUM-SHELL FLASH?
- 2011
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 743:1, s. 44-
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Tidskriftsartikel (refereegranskat)abstract
- In 2007, R Coronae Borealis (R CrB) went into a historically deep and long decline. In this state, the dust acts like a natural coronagraph at visible wavelengths, allowing faint nebulosity around the star to be seen. Imaging has been obtained from 0.5 to 500 mu m with Gemini/GMOS, Hubble Space Telescope/WFPC2, Spitzer/MIPS, and Herschel/SPIRE. Several of the structures around R CrB are cometary globules caused by wind from the star streaming past dense blobs. The estimated dust mass of the knots is consistent with their being responsible for the R CrB declines if they form along the line of sight to the star. In addition, there is a large diffuse shell extending up to 4 pc away from the star containing cool 25 K dust that is detected all the way out to 500 mu m. The spectral energy distribution of R CrB can be well fitted by a 150 AU disk surrounded by a very large diffuse envelope which corresponds to the size of the observed nebulosity. The total masses of the disk and envelope are 10(-4) and 2M(circle dot), respectively, assuming a gas-to-dust ratio of 100. The evidence pointing toward a white dwarf merger or a final-helium-shell flash origin for R CrB is contradictory. The shell and the cometary knots are consistent with a fossil planetary nebula. Along with the fact that R CrB shows significant lithium in its atmosphere, this supports the final-helium-shell flash. However, the relatively high inferred mass of R CrB and its high fluorine abundance support a white dwarf merger.
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| 44. |
- Maghnie, M., et al.
(författare)
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Safety and Efficacy of Pediatric Growth Hormone Therapy: Results From the Full KIGS Cohort
- 2022
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 107:12, s. 3287-3301
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Tidskriftsartikel (refereegranskat)abstract
- Context The Kabi/Pfizer International Growth Database (KIGS) is a large, international database (1987-2012) of children treated with recombinant human growth hormone (rhGH) in real-world settings. Objective This work aimed to evaluate the safety and efficacy of rhGH from the full KIGS cohort. Methods Data were collected by investigators from children with growth disorders treated with rhGH (Genotropin [somatropin]; Pfizer). Safety was evaluated in all treated patients, and efficacy in those treated for 1 year or more. A subgroup included patients treated for 5 years or more (>= 2 years prepubertal) who had reached near-adult height (NAH). Main outcomes included adverse events (AEs), serious AEs (SAEs), and height growth. Results The full KIGS cohort (N = 83 803 [58% male]) was treated for idiopathic GH deficiency (IGHD; 46.9%), organic GHD (10.0%), small for gestational age (SGA; 9.5%), Turner syndrome (TS; 9.2%), idiopathic short stature (ISS; 8.2%), and others (16.2%). Median rhGH treatment duration was 2.7 years and observation 3.1 years. SAEs occurred in 3.7% of patients and death in 0.4%. The most common SAEs were recurrence of craniopharyngioma (n = 151), neoplasm (n = 99), and cancer (n = 91); and scoliosis (n = 91). Median first-year delta height-SD score (SDS) (Prader) in prepubertal patients was 0.66 (IGHD), 0.55 (ISS), 0.58 (TS), and 0.71 (SGA). Median gains in NAH-SDS were 1.79 (IGHD), 1.37 (ISS), and 1.34 (SGA) for boys, and 2.07 (IGHD), 1.62 (ISS), 1.07 (TS), and 1.57 (SGA) for girls. Conclusion Data from KIGS, the largest and longest running international database of rhGH-treated children, show that rhGH is safe and increases short-term height gain and adult height across GHD and non-GHD conditions.
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| 45. |
- Meixner, Margaret, et al.
(författare)
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Herschel and ALMA measurements of dust and molecules in supernova 1987A
- 2013
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Ingår i: Proceedings of Science. - 1824-8039. ; Part F113823
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Konferensbidrag (refereegranskat)abstract
- Dust production by supernovae is important in the dust life cycle of a galaxy. The explosion of SN 1987A was the nearest SN detected in the last 400 years, allowing us detailed studies of contemporary evolution of a supernova for the first time. In 2011, Matsuura et al. reported 0.4-0.7 M of dust in SN 1987A based on Herschel HERITAGE survey data, which is surprisingly large compared to prior measurements of supernovae. In this paper, we present our follow-up studies of this important discovery about SN 1987A using the Herschel Space Observatory and the Atacama Large Millimeter Array (ALMA). We highlight two important results, the detection of cold molecular gas and dust in the ejected material of SN 1987A. Our results suggest that SNe are significant producers of dust and molecules, as well as heavy elements, driving chemical evolution of galaxies.
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| 46. |
- Morales, E, et al.
(författare)
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Combined impact of healthy lifestyle factors on risk of asthma, rhinoconjunctivitis and eczema in school children: ISAAC phase III
- 2019
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Ingår i: Thorax. - : BMJ. - 1468-3296 .- 0040-6376. ; 74:6, s. 531-538
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Tidskriftsartikel (refereegranskat)abstract
- Asthma is not the key focus of prevention strategies. A Healthy Lifestyle Index (HLI) was developed to examine the combined effect of modifiable lifestyle factors on asthma, rhinoconjunctivitis and eczema using data from the International Study of Asthma and Allergies in Childhood (ISAAC) phase III.MethodsInformation on symptoms of asthma, rhinoconjunctivitis, eczema and several lifestyle factors was obtained from children aged 6–7 years through written questionnaires. The HLI combined five lifestyle factors: no parental smoking, child’s adherence to Mediterranean diet, child’s healthy body mass index, high physical activity and non-sedentary behaviour. The association between the HLI and risk of asthma, rhinoconjunctivitis and eczema was evaluated using multilevel mixed-effects logistic regression models.FindingsData of 70 795 children from 37 centres in 19 countries were analysed. Each additional healthy lifestyle factor was associated with a reduced risk of current wheeze (OR 0.87, 95% CI 0.84 to 0.89), asthma ever (OR 0.89, 95% CI 0.87 to 0.92), current symptoms of rhinoconjunctivitis (OR 0.95, 95% CI 0.92 to 0.97) and current symptoms of eczema (OR 0.92, 95% CI 0.92 to 0.98). Theoretically, if associations were causal, a combination of four or five healthy lifestyle factors would result into a reduction up to 16% of asthma cases (ranging from 2.7% to 26.3 % according to region of the world).ConclusionsThese findings should be interpreted with caution given the limitations to infer causality from cross-sectional observational data. Efficacy of interventions to improve multiple modifiable lifestyle factors to reduce the burden asthma and allergy in childhood should be assessed.
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| 47. |
- Denomme-Pichon, AS, et al.
(författare)
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Solve-RD: the ITHACA perspective
- 2022
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Ingår i: EUROPEAN JOURNAL OF HUMAN GENETICS. - 1018-4813. ; 30:SUPPL 1, s. 236-237
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 48. |
- Griffith, Simon C., et al.
(författare)
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Variation in reproductive success across captive populations: Methodological differences, potential biases and opportunities
- 2017
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Ingår i: Ethology. - : Wiley. - 1439-0310 .- 0179-1613. ; 123:1, s. 1-29
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Tidskriftsartikel (refereegranskat)abstract
- Our understanding of fundamental organismal biology has been disproportionately influenced by studies of a relatively small number of ‘model’ species extensively studied in captivity. Laboratory populations of model species are commonly subject to a number of forms of past and current selection that may affect experimental outcomes. Here, we examine these processes and their outcomes in one of the most widely used vertebrate species in the laboratory – the zebra finch (Taeniopygia guttata). This important model species is used for research across a broad range of fields, partly due to the ease with which it can be bred in captivity. However despite this perceived amenability, we demonstrate extensive variation in the success with which different laboratories and studies bred their subjects, and overall only 64% of all females that were given the opportunity, bred successfully in the laboratory. We identify and review several environmental, husbandry, life-history and behavioural factors that potentially contribute to this variation. The variation in reproductive success across individuals could lead to biases in experimental outcomes and drive some of the heterogeneity in research outcomes across studies. The zebra finch remains an excellent captive animal system and our aim is to sharpen the insight that future studies of this species can provide, both to our understanding of this species and also with respect to the reproduction of captive animals more widely. We hope to improve systematic reporting methods and that further investigation of the issues we raise will lead both to advances in our fundamental understanding of avian reproduction as well as to improvements in future welfare and experimental efficiency.
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| 49. |
- Matsuura, M., et al.
(författare)
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A STUBBORNLY LARGE MASS OF COLD DUST IN THE EJECTA OF SUPERNOVA 1987A
- 2015
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 800:1
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Tidskriftsartikel (refereegranskat)abstract
- We present new Herschel photometric and spectroscopic observations of Supernova 1987A, carried out in 2012. Our dedicated photometric measurements provide new 70 mu m data and improved imaging quality at 100 and 160 mu m compared to previous observations in 2010. Our Herschel spectra show only weak CO line emission, and provide an upper limit for the 63 mu m [O-I] line flux, eliminating the possibility that line contaminations distort the previously estimated dustmass. The far-infrared spectral energy distribution (SED) is well fitted by thermal emission from cold dust. The newly measured 70 mu m flux constrains the dust temperature, limiting it to nearly a single temperature. The far-infrared emission can be fitted by 0.5 +/- 0.1M(circle dot) of amorphous carbon, about a factor of two larger than the current nucleosynthetic mass prediction for carbon. The observation of SiO molecules at early and late phases suggests that silicates may also have formed and we could fit the SED with a combination of 0.3M(circle dot) of amorphous carbon and 0.5M(circle dot) of silicates, totalling 0.8M(circle dot) of dust. Our analysis thus supports the presence of a large dust reservoir in the ejecta of SN 1987A. The inferred dust mass suggests that supernovae can be an important source of dust in the interstellar medium, from local to high-redshift galaxies.
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| 50. |
- Pathan, M., et al.
(författare)
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A novel community driven software for functional enrichment analysis of extracellular vesicles data
- 2017
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Ingår i: Journal of Extracellular Vesicles. - : Wiley. - 2001-3078. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Bioinformatics tools are imperative for the in depth analysis of heterogeneous high-throughput data. Most of the software tools are developed by specific laboratories or groups or companies wherein they are designed to perform the required analysis for the group. However, such software tools may fail to capture "what the community needs in a tool". Here, we describe a novel community-driven approach to build a comprehensive functional enrichment analysis tool. Using the existing FunRich tool as a template, we invited researchers to request additional features and/or changes. Remarkably, with the enthusiastic participation of the community, we were able to implement 90% of the requested features. FunRich enables plugin for extracellular vesicles wherein users can download and analyse data from Vesiclepedia database. By involving researchers early through community needs software development, we believe that comprehensive analysis tools can be developed in various scientific disciplines.
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