| 1. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
- Conde, Lucia, et al.
(författare)
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Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:8, s. 661-664
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, combined P = 2.00 x 10(-19); r(2) = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 x 10(-9)).
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| 3. |
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| 4. |
- Behrendt, Christian-Alexander, et al.
(författare)
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Editor's Choice - Recommendations for Registry Data Collection for Revascularisations of Acute Limb Ischaemia : A Delphi Consensus from the International Consortium of Vascular Registries
- 2019
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : W B SAUNDERS CO LTD. - 1078-5884 .- 1532-2165. ; 57:6, s. 816-821
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To develop a minimum core data set for evaluation of acute limb ischaemia (ALI) revascularisation treatment and outcomes that would enable collaboration among international registries. Methods: A modified Delphi approach was used to achieve consensus among international multidisciplinary vascular specialists and registry members of the International Consortium of Vascular Registries (ICVR). Variables identified in the literature or suggested by the expert panel, and variables, including definitions, currently used in 15 countries in the ICVR, were assessed to define both a minimum core and an optimum data set to register ALI treatment. Clinical relevance and practicability were both assessed, and consensus was defined as >= 80% agreement among participants. Results: Of 40 invited experts, 37 completed a preliminary survey and 31 completed the two subsequent Delphi rounds via internet exchange and face to face discussions. In total, 117 different items were generated from the various registry data forms, an extensive review of the literature, and additional suggestions from the experts, for potential inclusion in the data set. Ultimately, 35 items were recommended for inclusion in the minimum core data set, including 23 core items important for all registries, and an additional 12 more specific items for registries capable of capturing more detail. These 35 items supplement previous data elements recommended for registering chronic peripheral arterial occlusive disease treatment. Conclusion: A modified Delphi study allowed 37 international vascular registry experts to achieve a consensus recommendation for a minimum core and an optimum data set for registries covering patients who undergo ALI revascularisation. Continued global harmonisation of registry infrastructure and definition of items allows international comparisons and global quality improvement. Furthermore, it can help to define and monitor standards of care and enable international research collaboration.
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| 5. |
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| 6. |
- Boyle, Mark, et al.
(författare)
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Excitation dynamics of Rydberg states in C60
- 2005
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Ingår i: European Physical Journal D. - : Springer Science and Business Media LLC. - 1434-6060 .- 1434-6079. ; 36, s. 339-351
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Tidskriftsartikel (refereegranskat)abstract
- The electron and nuclear dynamics of C60 fullerenes irradiated with femtosecond laser pulses are investigated with photoelectron and photoion spectroscopy. The focus of this work is the detailed exploration of the population mechanism of Rydberg levels within the excitation process of neutral C60. The effect of excitation wavelength, intensity, chirp, and polarization on the kinetic energy distribution of photoelectrons in single-pulse experiments gives first insight into the underlying processes. In combination with time-resolved two-color pump-probe spectroscopy depending on either pump, or probe pulse intensity, a more complete picture of the interaction can be drawn. The results point towards a very interesting but nevertheless complex behavior including four steps: (i) non-adiabatic multielectron excitation of the HOMO (hu) → LUMO+1 (t1g) transition; (ii) thermalization within the hot electron cloud on a time scale below 100fs, followed by a coupling of energy to vibrational modes of the molecule via doorway state(s); (iii) population of electronically excited Rydberg states by multiphoton absorption, and (iv) single photon ionization from the excited Rydberg states. This excitation process results in a characteristic sequence of photoelectron lines in the photoemission spectra. The comparison of the experimental results with recent theoretical work gives convincing evidence that non-adiabatic multielectron dynamics (NMED) plays a key role for the understanding of the response of C60 to short-pulse laser radiation.
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| 7. |
- Boyle, Mark, et al.
(författare)
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Two colour pump-probe study and internal energy dependence of Rydberg state excitation
- 2004
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Ingår i: Physical Review A. - 1050-2947. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- Excitation of Rydberg states in isolated C60 is studied by time-resolved photoelectron spectroscopy in a femtosecond two-color pump-probe experiment. The relaxation time for electron-electron interaction is determined to be approximately 100 fs with the t1g(LUMO + 1) orbital being considered to define the doorway state in a nonadiabatic multielectron excitation process. The internal energy stored in vibrational modes of the C60 at 770 K is found to support the excitation process very efficiently while in "cold" C60 (80 K), no significant Rydberg population is detected.
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| 8. |
- Dixon-Suen, Suzanne C, et al.
(författare)
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Physical activity, sedentary time and breast cancer risk : a Mendelian randomisation study
- 2022
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Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 56:20, s. 1157-1170
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.METHODS: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.RESULTS: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).CONCLUSION: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.
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| 9. |
- Frazier-Wood, Alexis C., et al.
(författare)
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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
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Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
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Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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| 10. |
- Lassesson, Andreas, 1976, et al.
(författare)
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A femtosecond laser study of the endoral fullerenes Li@C60 and La@C82
- 2005
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Ingår i: Eur. Phys. J. D. - : Springer Science and Business Media LLC. - 1434-6060. ; 34, s. 205-209
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Tidskriftsartikel (refereegranskat)abstract
- The endohedral fullerenes La@C82 and Li@C60 have been studied in the gas phase with femtosecond laser excitation. The two molecules show qualitatively the same behaviour with respect to ion yield vs. pulse energy, but markedly different fragmentation patterns, with La@C82 fragmenting via the shrink-wrap mechanism and Li@C60 predominantly losing the metal atom in the first fragmentation step. The ion yields and electron energy distributions of La@C82 agree well with a recently developed model for fs laser ionisation of C60.
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| 11. |
- Smedby, Karin E., et al.
(författare)
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GWAS of Follicular Lymphoma Reveals Allelic Heterogeneity at 6p21.32 and Suggests Shared Genetic Susceptibility with Diffuse Large B-cell Lymphoma
- 2011
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:4, s. e1001378-
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Tidskriftsartikel (refereegranskat)abstract
- Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA) class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL-associated locus on 6p21.32, rs2647012 (ORcombined = 0.64, P-combined= 2x10(-21)) located 962 bp away from rs10484561 (r(2)< 0.1 in controls). After mutual adjustment, the associations at the two SNPs remained genome-wide significant (rs2647012: ORadjusted = 0.70, P-adjusted= 4x10(-12); rs10484561: ORadjusted = 1.64, P-adjusted= 5x10(-15)). Haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct haplotype from that of rs10484561 and tags a novel allele with an opposite (protective) effect on FL risk. Moreover, in a follow-up analysis of the top 6 FL-associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma (ORcombined = 1.36, P-combined = 1.4x10(-7)). Our results reveal the presence of allelic heterogeneity within the HLA class II region influencing FL susceptibility and indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA class II region plays a complex yet important role in NHL.
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| 12. |
- Smith, Jennifer A, et al.
(författare)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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| 13. |
- Sullivan, Richard, et al.
(författare)
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Delivering affordable cancer care in high-income countries
- 2011
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Ingår i: The Lancet Oncology. - London : Lancet Oncology. - 1470-2045 .- 1474-5488. ; 12:10, s. 933-980
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Tidskriftsartikel (refereegranskat)abstract
- The burden of cancer is growing, and the disease is becoming a major economic expenditure for all developed countries. In 2008, the worldwide cost of cancer due to premature death and disability (not including direct medical costs) was estimated to be US$895 billion. This is not simply due to an increase in absolute numbers, but also the rate of increase of expenditure on cancer. What are the drivers and solutions to the so-called cancer-cost curve in developed countries? How are we going to afford to deliver high quality and equitable care? Here, expert opinion from health-care professionals, policy makers, and cancer survivors has been gathered to address the barriers and solutions to delivering affordable cancer care. Although many of the drivers and themes are specific to a particular field-eg, the huge development costs for cancer medicines-there is strong concordance running through each contribution. Several drivers of cost, such as over-use, rapid expansion, and shortening life cycles of cancer technologies (such as medicines and imaging modalities), and the lack of suitable clinical research and integrated health economic studies, have converged with more defensive medical practice, a less informed regulatory system, a lack of evidence-based sociopolitical debate, and a declining degree of fairness for all patients with cancer. Urgent solutions range from re-engineering of the macroeconomic basis of cancer costs (eg, value-based approaches to bend the cost curve and allow cost-saving technologies), greater education of policy makers, and an informed and transparent regulatory system. A radical shift in cancer policy is also required. Political toleration of unfairness in access to affordable cancer treatment is unacceptable. The cancer profession and industry should take responsibility and not accept a substandard evidence base and an ethos of very small benefit at whatever cost; rather, we need delivery of fair prices and real value from new technologies.
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| 14. |
- Tobias, Deirdre K, et al.
(författare)
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
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Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
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Forskningsöversikt (refereegranskat)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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| 15. |
- Wanhainen, Anders, et al.
(författare)
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European Society for Vascular Surgery (ESVS) 2024 Clinical Practice Guidelines on the Management of Abdominal Aorto-Iliac Artery Aneurysms
- 2024
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier. - 1078-5884 .- 1532-2165. ; 67:2, s. 192-331
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThe European Society for Vascular Surgery (ESVS) has developed clinical practice guidelines for the care of patients with aneurysms of the abdominal aorta and iliac arteries in succession to the 2011 and 2019 versions, with the aim of assisting physicians and patients in selecting the best management strategy.MethodsThe guideline is based on scientific evidence completed with expert opinion on the matter. By summarising and evaluating the best available evidence, recommendations for the evaluation and treatment of patients have been formulated. The recommendations are graded according to a modified European Society of Cardiology grading system, where the strength (class) of each recommendation is graded from I to III and the letters A to C mark the level of evidence.ResultsA total of 160 recommendations have been issued on the following topics: Service standards, including surgical volume and training; Epidemiology, diagnosis, and screening; Management of patients with small abdominal aortic aneurysm (AAA), including surveillance, cardiovascular risk reduction, and indication for repair; Elective AAA repair, including operative risk assessment, open and endovascular repair, and early complications; Ruptured and symptomatic AAA, including peri-operative management, such as permissive hypotension and use of aortic occlusion balloon, open and endovascular repair, and early complications, such as abdominal compartment syndrome and colonic ischaemia; Long term outcome and follow up after AAA repair, including graft infection, endoleaks and follow up routines; Management of complex AAA, including open and endovascular repair; Management of iliac artery aneurysm, including indication for repair and open and endovascular repair; and Miscellaneous aortic problems, including mycotic, inflammatory, and saccular aortic aneurysm. In addition, Shared decision making is being addressed, with supporting information for patients, and Unresolved issues are discussed.ConclusionThe ESVS Clinical Practice Guidelines provide the most comprehensive, up to date, and unbiased advice to clinicians and patients on the management of abdominal aorto-iliac artery aneurysms.
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