| 1. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 2. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 3. |
- Loza, M. J., et al.
(författare)
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Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study
- 2016
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Ingår i: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Methods: Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Results: Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Conclusions: Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies. Trial registration:NCT01274507(ADEPT), registered October 28, 2010 and NCT01982162(U-BIOPRED), registered October 30, 2013.
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| 4. |
- Pettersson, Anna, 1979-
(författare)
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Diet and Gastrointestinal Symptoms in Patients with Prostate Cancer Treated with Radiotherapy
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objective The main objective of this thesis was to explore the effects of diet on gastrointestinal symptoms in prostate cancer patients treated with local curative radiotherapy, by evaluating dietary intake prior to treatment (Study I), the psychometric properties of a new questionnaire on patient-reported gastrointestinal side effects (Study II), and the effect of a dietary intervention on acute and long-term gastrointestinal symptoms up to 2 years after radiotherapy completion (Study III-IV).Methods A total of 130 men with localized prostate cancer referred to dose-escalated radiotherapy (ED2 87-102 Gy, α/β=3 Gy) were recruited to a dietary intervention trial. Patients were randomized to receive either standard care plus the dietary intervention of a fibre- and lactose-restricted diet (intervention group, IG; n=64) or standard care alone (standard care group, SCG; n=66). Data on gastrointestinal symptoms and dietary intake were collected pre-treatment and at seven time points during a follow-up period of 26 months.Results Prior to treatment, grain products and milk products were major sources of energy. Unbalanced fatty acid intake and low intake of selenium were observed (Study I). Validation of the Gastrointestinal Side Effects Questionnaire (GISEQ) revealed satisfactory internal consistency, moderate concurrent validity and adequate responsiveness (Study II). There were no significant effects of the intervention on acute or long-term gastrointestinal symptoms, but a tendency towards lower prevalence and severity of bloating and diarrhoea in the IG compared to the SCG during radiotherapy. Gastrointestinal symptoms were predominantly mild, and the frequency of clinically relevant symptoms was merely a few percent. Dietary adherence in the IG was initially good, but tended to decline beyond 12 months post-radiotherapy (Study III-IV).Conclusions A fibre- and lactose-restricted diet was not superior to the habitual diet in reducing gastrointestinal symptoms in patients undergoing high-dose, small-volume radiotherapy for localized prostate cancer. The GISEQ enables assessment of patient-perceived change in symptoms, but further work is needed to strengthen its psychometric qualities. It is suggested that continued research in this area target patient categories referred to irradiation of larger pelvic volumes with a higher risk of gastrointestinal symptoms, and that dietary interventions incorporate established strategies to enhance adherence and effectiveness.
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| 5. |
- Rothenberg, Elisabet, et al.
(författare)
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Global Leadership Initiative on Malnutrition (GLIM) for the diagnosis of malnutrition : a framework for consistent dietetic practice
- 2024
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Ingår i: Clinical Nutrition ESPEN. - : Elsevier Ltd.. - 2405-4577. ; 60, s. 261-265
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Summary Malnutrition is an alarming and ongoing healthcare problem globally. Malnutrition has a negative impact on the individual patient, leading to poorer clinical outcomes and increased mortality, but also poses an economic burden on society. Proper identification and diagnostics are prerequisites for initiation of treatment. In 2019, the Global Leadership Initiative on Malnutrition, a consensus-based global framework to uniformly diagnose malnutrition across populations, healthcare settings, and countries was published. Identifying and treating malnutrition is an interdisciplinary team effort. Nonetheless, the nutrition and dietetics profession is specifically trained for diagnosing and treating nutrition(-related) conditions, and therefore has a key role in the interdisciplinary team in implementing the GLIM framework in clinical practice. For the nutrition and dietetics profession, GLIM offers a great opportunity for moving both the scientific and clinical knowledge of malnutrition management forward. While the GLIM framework has been extensively studied since its launch, various knowledge gaps still remain. For the nutrition and dietetics profession, these knowledge gaps mainly relate to the GLIM implementation process, to the role of GLIM in relation to the nutrition care process, and to treatment strategies for various nutrition-related conditions. In this opinion paper, we aimed to describe the rationale for implementing the GLIM framework in clinical dietetic practice, and propose a research agenda based on knowledge gaps regarding GLIM in relation to nutrition care from a dietetic point of view.
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