| 1. |
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| 2. |
- Ederle, Joerg, et al.
(author)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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In: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Journal article (peer-reviewed)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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| 3. |
- Grieser, M., et al.
(author)
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Storage ring at HIE-ISOLDE Technical design report
- 2012
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In: The European Physical Journal Special Topics. - : Springer Science and Business Media LLC. - 1951-6355 .- 1951-6401. ; 207:1, s. 1-117
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Research review (peer-reviewed)abstract
- We propose to install a storage ring at an ISOL-type radioactive beam facility for the first time. Specifically, we intend to setup the heavy-ion, low-energy ring TSR at the HIE-ISOLDE facility in CERN, Geneva. Such a facility will provide a capability for experiments with stored secondary beams that is unique in the world. The envisaged physics programme is rich and varied, spanning from investigations of nuclear ground-state properties and reaction studies of astrophysical relevance, to investigations with highly-charged ions and pure isomeric beams. The TSR might also be employed for removal of isobaric contaminants from stored ion beams and for systematic studies within the neutrino beam programme. In addition to experiments performed using beams recirculating within the ring, cooled beams can also be extracted and exploited by external spectrometers for high-precision measurements. The existing TSR, which is presently in operation at the Max-Planck Institute for Nuclear Physics in Heidelberg, is well-suited and can be employed for this purpose. The physics cases as well as technical details of the existing ring facility and of the beam and infrastructure requirements at HIE-ISOLDE are discussed in the present technical design report.
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| 4. |
- Grieser, M., et al.
(author)
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Storage ring at HIE-ISOLDE
- 2012
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In: European Physical Journal: Special Topics. - : Springer Science and Business Media LLC. - 1951-6401 .- 1951-6355. ; 207:1, s. 1-117
-
Journal article (peer-reviewed)abstract
- We propose to install a storage ring at an ISOL-type radioactive beam facility for the first time. Specifically, we intend to setup the heavy-ion, low-energy ring TSR at the HIE-ISOLDE facility in CERN, Geneva. Such a facility will provide a capability for experiments with stored secondary beams that is unique in the world. The envisaged physics programme is rich and varied, spanning from investigations of nuclear ground-state properties and reaction studies of astrophysical relevance, to investigations with highly-charged ions and pure isomeric beams. The TSR might also be employed for removal of isobaric contaminants from stored ion beams and for systematic studies within the neutrino beam programme. In addition to experiments performed using beams recirculating within the ring, cooled beams can also be extracted and exploited by external spectrometers for high-precision measurements. The existing TSR, which is presently in operation at the Max-Planck Institute for Nuclear Physics in Heidelberg, is well-suited and can be employed for this purpose. The physics cases as well as technical details of the existing ring facility and of the beam and infrastructure requirements at HIE-ISOLDE are discussed in the present technical design report.
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| 5. |
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| 6. |
- Ho, Joshua W. K., et al.
(author)
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Comparative analysis of metazoan chromatin organization
- 2014
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 512:7515, s. 449-U507
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Journal article (peer-reviewed)abstract
- Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms(1-3). Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths(4,5). To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.
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| 7. |
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| 8. |
- Barrett, Jennifer H., et al.
(author)
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Genome-wide association study identifies three new melanoma susceptibility loci
- 2011
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1108-1113
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Journal article (peer-reviewed)abstract
- We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 x 10(-9)), an SNP in MX2 (rs45430, P = 2.9 x 10-9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 x 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 x 10(-7) under a fixed-effects model and P = 1.2 x 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.
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| 9. |
- Demenais, F, et al.
(author)
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Association of MC1R Variants and Host Phenotypes With Melanoma Risk in CDKN2A Mutation Carriers: A GenoMEL Study.
- 2010
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 102, s. 1568-1583
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Journal article (peer-reviewed)abstract
- Background Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited. Methods We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, ≥2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided. Results Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10(-6) ≤ P ≤ .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; P(trend) = 1.86 × 10(-8)). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 ≤ P ≤ .04), hair color (.006 ≤ P ≤ .06), and number of nevi (6.9 × 10(-6) ≤ P ≤ .02). Conclusion Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings.
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Greiner, J., et al.
(author)
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GRIPS - Gamma-Ray Imaging, Polarimetry and Spectroscopy
- 2012
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In: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 34:2, s. 551-582
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Journal article (peer-reviewed)abstract
- We propose to perform a continuously scanning all-sky survey from 200 keV to 80 MeV achieving a sensitivity which is better by a factor of 40 or more compared to the previous missions in this energy range (COMPTEL, INTEGRAL; see Fig. 1). These gamma-ray observations will be complemented by observations in the soft X-ray and (near-)infrared region with the corresponding telescopes placed on a separate satellite. The Gamma-Ray Imaging, Polarimetry and Spectroscopy ("GRIPS") mission with its three instruments Gamma-Ray Monitor (GRM), X-Ray Monitor (XRM) and InfraRed Telescope (IRT) addresses fundamental questions in ESA's Cosmic Vision plan. Among the major themes of the strategic plan, GRIPS has its focus on the evolving, violent Universe, exploring a unique energy window. We propose to investigate γ-ray bursts and blazars, the mechanisms behind supernova explosions, nucleosynthesis and spallation, the enigmatic origin of positrons in our Galaxy, and the nature of radiation processes and particle acceleration in extreme cosmic sources including pulsars and magnetars. The natural energy scale for these non-thermal processes is of the order of MeV. Although they can be partially and indirectly studied using other methods, only the proposed GRIPS measurements will provide direct access to their primary photons. GRIPS will be a driver for the study of transient sources in the era of neutrino and gravitational wave observatories such as IceCUBE and LISA, establishing a new type of diagnostics in relativistic and nuclear astrophysics. This will support extrapolations to investigate star formation, galaxy evolution, and black hole formation at high redshifts.
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| 14. |
- Iles, Mark M., et al.
(author)
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A variant in FTO shows association with melanoma risk not due to BMI
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:4, s. 428-432
-
Journal article (peer-reviewed)abstract
- We report the results of an association study of melanoma that is based on the genome-wide imputation of the genotypes of 1,353 cases and 3,566 controls of European origin conducted by the GenoMEL consortium. This revealed an association between several SNPs in intron 8 of the FTO gene, including rs16953002, which replicated using 12,313 cases and 55,667 controls of European ancestry from Europe, the USA and Australia (combined P = 3.6 x 10(-12), per-allele odds ratio for allele A = 1.16). In addition to identifying a new melanomasusceptibility locus, this is to our knowledge the first study to identify and replicate an association with SNPs in FTO not related to body mass index (BMI). These SNPs are not in intron 1 (the BMI-related region) and exhibit no association with BMI. This suggests FTO's function may be broader than the existing paradigm that FTO variants influence multiple traits only through their associations with BMI and obesity.
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| 15. |
- Rothman, Nathaniel, et al.
(author)
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A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 978-984
-
Journal article (peer-reviewed)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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| 16. |
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| 17. |
- Eardley, S., et al.
(author)
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A pilot feasibility study of a questionnaire to determine European union-wide CAM use
- 2012
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In: Forschende Komplementarmedizin. - : S. Karger AG. - 1661-4119. ; 19:6, s. 302-310
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Journal article (peer-reviewed)abstract
- Background: No questionnaire specifically measuring the core components of complementary and alternative medicine (CAM) use has been validated for use across European Union (EU) countries. We aimed to determine the face validity, acceptability and the participants' comprehension of a pre-existing questionnaire designed to measure 'CAM use', to provide a comparative, standardised questionnaire for use by health care providers, policy makers and purchasers throughout Europe. Methods: Established procedures were employed to translate the questionnaire into 4 EU languages. The translated questionnaires were piloted on 50 healthy adults from each country who may never have used CAM. 10 participants per country also took part in audio-recorded think aloud interviews about the questionnaire. The interviews were transcribed and analysed in the language in which they were conducted; findings were summarised in English. Questionnaire data were pooled across countries, and patterns of completion and missing data were analysed. Results: The questionnaire was translated into Italian, Spanish, Dutch and Romanian. The mean age of the participants was 43.6 years. 34% were male, 87.4% were either light or heavy CAM users, and 12.6% were non-users. Qualitative analysis identified common problems across countries including a 'hard-to-read' layout, misunderstood terminology and uncertainty in choosing response options. Quantitative analysis confirmed that a substantial minority of respondents failed to follow questionnaire instructions and that some questions had substantial rates of missing data. Conclusions: The I-CAM-Q has low face validity and low acceptability, and is likely to produce biased estimates of CAM use if applied in England, Romania, Italy, The Netherlands or Spain. Further work is required to develop the layout, terms, some response options and instructions for completion before it can be used across the EU. © 2012 S. Karger AG, Basel.
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| 18. |
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| 19. |
- Kharchenko, Peter V, et al.
(author)
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Comprehensive analysis of the chromatin landscape in Drosophila melanogaster
- 2011
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 471:7339, s. 480-485
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Journal article (peer-reviewed)abstract
- Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melanogaster based on eighteen histone modifications, summarized by nine prevalent combinatorial patterns. Integrative analysis with other data (non-histone chromatin proteins, DNase I hypersensitivity, GRO-Seq reads produced by engaged polymerase, short/long RNA products) reveals discrete characteristics of chromosomes, genes, regulatory elements and other functional domains. We find that active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions and genomic contexts. We also demonstrate a diversity of signatures among Polycomb targets that include a subset with paused polymerase. This systematic profiling and integrative analysis of chromatin signatures provides insights into how genomic elements are regulated, and will serve as a resource for future experimental investigations of genome structure and function.
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| 20. |
- Lall, Gurdeep K., et al.
(author)
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Amplified fragment length polymorphism (AFLP) analysis of closely related wild and captive tsetse fly (Glossina morsitans morsitans) populations
- 2010
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In: Parasites & Vectors. - : Springer Science and Business Media LLC. - 1756-3305. ; 3, s. 47-
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Journal article (peer-reviewed)abstract
- Background: Tsetse flies (Diptera: Glossinidae) are vectors of trypanosomes that cause sleeping sickness in humans and nagana in livestock across sub-Saharan Africa. Tsetse control strategies rely on a detailed understanding of the epidemiology and ecology of tsetse together with genetic variation within and among populations. High-resolution nuclear genetic markers are useful tools for elucidation of the genetic basis of phenotypic traits. In this study amplified fragment length polymorphism (AFLP) markers were developed to analyze genetic variation in Glossina morsitans morsitans from laboratory and field-collected populations from Zimbabwe. Results: A total of seven hundred and fifty one loci from laboratory and field populations of G. m. morsitans from Zimbabwe were genotyped using AFLP with seven primer combinations. Analysis identified 335 polymorphic loci. The two populations could be distinguished by cluster and principal components analysis (PCA) analysis, indicating that AFLP markers can be used to separate genetically similar populations; at the same time differences observed between laboratory and field populations were not very great. Among the techniques investigated, the use of acetone was the most reliable method of preservation of tsetse for subsequent extraction of high molecular weight DNA. An interesting finding was that AFLP also enabled robust within-population discrimination of male and female tsetse flies due to their different X chromosome DNA complements. Conclusions: AFLP represents a useful additional tool to add to the suite of techniques currently available for the genetic analysis of tsetse populations and represents a useful resource for identification of the genetic basis of important phenotypic traits.
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| 21. |
- Litvinov, Yu.A., et al.
(author)
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Nuclear physics experiments with ion storage rings
- 2013
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In: Nuclear Instruments and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms. - : Elsevier BV. - 0168-583X. ; 317:PART B, s. 603-616
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Journal article (peer-reviewed)abstract
- In the last two decades a number of nuclear structure and astrophysics experiments were performed at heavy-ion storage rings employing unique experimental conditions offered by such machines. Furthermore, building on the experience gained at the two facilities presently in operation, several new storage ring projects were launched worldwide. This contribution is intended to provide a brief review of the fast growing field of nuclear structure and astrophysics research at storage rings.
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| 22. |
- MacGregor, Stuart, et al.
(author)
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Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3
- 2011
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1114-1118
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Journal article (peer-reviewed)abstract
- We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 x 10(-11), OR in combined replication cohorts of 0.89 (95% CI 0.85-0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 x 10(-8)). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1. Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density.
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| 23. |
- Moon, J. C., et al.
(author)
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Different initiatives across Europe to enhance losartan utilization post generics: impact and implications
- 2014
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In: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 5
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Journal article (peer-reviewed)abstract
- Introduction: There is an urgent need for health authorities across Europe to fully realize potential savings from increased use of generics to sustain their healthcare systems. A variety of strategies were used across Europe following the availability of generic losartan, the first angiotensin receptor blocker (ARB) to be approved and marketed, to enhance its prescribing vs. single-sourced drugs in the class. Demand-side strategies ranged from 100% co-payment for single-sourced ARBs in Denmark to no specific measures. We hypothesized this heterogeneity of approaches would provide opportunities to explore prescribing in a class following patent expiry. Objective: Contrast the impact of the different approaches among European countries and regions to the availability of generic losartan to provide future guidance. Methodology: Retrospective segmented regression analyses applying linear random coefficient models with country specific intercepts and slopes were used to assess the impact of the various initiatives across Europe following the availability of generic losartan. Utilization measured in defined daily doses (DDDs). Price reductions for generic losartan were also measured. Results: Utilization of losartan was over 90% of all ARBs in Denmark by the study end. Multiple measures in Sweden and one English primary care group also appreciably enhanced losartan utilization. Losartan utilization actually fell in some countries with no specific demand-side measures. Considerable differences were seen in the prices of generic losartan. Conclusion: De listing single-sourced ARBs produced the greatest increase in losartan utilization. Overall, multiple demand-side measures are needed to change physician prescribing habits to fully realize savings from generics. There is no apparent "spill over" effect from one class to another to influence future prescribing patterns even if these are closely related.
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| 24. |
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| 25. |
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| 26. |
- Amos, Christopher I, et al.
(author)
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Genome-wide association study identifies novel loci predisposing to cutaneous melanoma
- 2011
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:24, s. 23-5012
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Journal article (peer-reviewed)abstract
- We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.3 (MC1R) regions that reached genome-wide significance within this study and also found strong evidence for genetic effects on susceptibility to melanoma from markers on chromosome 9p21.3 in the p16/ARF region and on chromosome 1q21.3 (ARNT/LASS2/ANXA9 region). The most significant single-nucleotide polymorphisms (SNPs) in the 15q13.1 locus (rs1129038 and rs12913832) lie within a genomic region that has profound effects on eye and skin color; notably, 50% of variability in eye color is associated with variation in the SNP rs12913832. Because eye and skin colors vary across European populations, we further evaluated the associations of the significant SNPs after carefully adjusting for European substructure. We also evaluated the top 10 most significant SNPs by using data from three other genome-wide scans. Additional in silico data provided replication of the findings from the most significant region on chromosome 1q21.3 rs7412746 (P = 6 × 10(-10)). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma.
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| 27. |
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| 28. |
- Bradley, KA, et al.
(author)
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Alcohol Screening and Risk of Postoperative Complications on Male VA Patients Undergoing Major Non-cardiac Surgery
- 2011
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In: Journal of General Internal Medicine. - : Springer Science and Business Media LLC. - 0884-8734 .- 1525-1497. ; 26:2, s. 162-169
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Journal article (peer-reviewed)abstract
- BACKGROUND: Patients who misuse alcohol are at increased risk for surgical complications. Four weeks of preoperative abstinence decreases the risk of complications, but practical approaches for early preoperative identification of alcohol misuse are needed. OBJECTIVE: To evaluate whether results of alcohol screening with the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) questionnaire—up to a year before surgery—were associated with the risk of postoperative complications. DESIGN: This is a cohort study. SETTING AND PARTICIPANTS: Male Veterans Affairs (VA) patients were eligible if they had major noncardiac surgery assessed by the VA’s Surgical Quality Improvement Program (VASQIP) in fiscal years 2004-2006, and completed the AUDIT-C alcohol screening questionnaire (0-12 points) on a mailed survey within 1 year before surgery. MAIN OUTCOME MEASURE: One or more postoperative complication(s) within 30 days of surgery based on VASQIP nurse medical record reviews. RESULTS Among 9,176 eligible men, 16.3% screened positive for alcohol misuse with AUDIT-C scores ≥ 5, and 7.8% had postoperative complications. Patients with AUDIT-C scores ≥ 5 were at significantly increased risk for postoperative complications, compared to patients who drank less. In analyses adjusted for age, smoking, and days from screening to surgery, the estimated prevalence of postoperative complications increased from 5.6% (95% CI 4.8–6.6%) in patients with AUDIT-C scores 1–4, to 7.9% (6.3–9.7%) in patients with AUDIT-Cs 5–8, 9.7% (6.6–14.1%) in patients with AUDIT-Cs 9–10 and 14.0% (8.9–21.3%) in patients with AUDIT-Cs 11–12. In fully-adjusted analyses that included preoperative covariates potentially in the causal pathway between alcohol misuse and complications, the estimated prevalence of postoperative complications increased significantly from 4.8% (4.1–5.7%) in patients with AUDIT-C scores 1–4, to 6.9% (5.5–8.7%) in patients with AUDIT-Cs 5-8 and 7.5% (5.0–11.3%) among those with AUDIT-Cs 9–10. CONCLUSIONS: AUDIT-C scores of 5 or more up to a year before surgery were associated with increased postoperative complications.
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| 29. |
- Byström, Jonas, et al.
(author)
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Inducible CYP2J2 and its product 11,12-EET promotes bacterial phagocytosis : a role for CYP2J2 deficiency in the pathogenesis of Crohn's disease?
- 2013
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:9
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Journal article (peer-reviewed)abstract
- The epoxygenase CYP2J2 has an emerging role in inflammation and vascular biology. The role of CYP2J2 in phagocytosis is not known and its regulation in human inflammatory diseases is poorly understood. Here we investigated the role of CYP2J2 in bacterial phagocytosis and its expression in monocytes from healthy controls and Crohns disease patients. CYP2J2 is anti-inflammatory in human peripheral blood monocytes. Bacterial LPS induced CYP2J2 mRNA and protein. The CYP2J2 arachidonic acid products 11,12-EET and 14,15-EET inhibited LPS induced TNFα release. THP-1 monocytes were transformed into macrophages by 48h incubation with phorbol 12-myristate 13-acetate. Epoxygenase inhibition using a non-selective inhibitor SKF525A or a selective CYP2J2 inhibitor Compound 4, inhibited E. coli particle phagocytosis, which could be specifically reversed by 11,12-EET. Moreover, epoxygenase inhibition reduced the expression of phagocytosis receptors CD11b and CD68. CD11b also mediates L. monocytogenes phagocytosis. Similar, to E. coli bioparticle phagocytosis, epoxygenase inhibition also reduced intracellular levels of L. monocytogenes, which could be reversed by co-incubation with 11,12-EET. Disrupted bacterial clearance is a hallmark of Crohn's disease. Unlike macrophages from control donors, macrophages from Crohn's disease patients showed no induction of CYP2J2 in response to E. coli. These results demonstrate that CYP2J2 mediates bacterial phagocytosis in macrophages, and implicates a defect in the CYP2J2 pathway may regulate bacterial clearance in Crohn's disease.
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| 30. |
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| 31. |
- Hytteborn, Julia, 1976-
(author)
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Water Quality in Swedish Lakes and Watercourses : Modeling the Intra-Annual Variability
- 2014
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Doctoral thesis (other academic/artistic)abstract
- Water quality is of great importance for ecosystems and society. This thesis characterized and modeled the variation in several key constituents of Swedish surface waters, with particular consideration given to intra-annual variability and sensitivity to climate change. Cyanobacterial data from 29 lakes and basins as well as total organic carbon (TOC) from 215 watercourses were used. Extensive data on catchment characteristics, morphometry, discharge, temperature and other water chemistry data were also analyzed. Models characterizing the seasonality in cyanobacterial concentration and relative cyanobacterial abundance were developed with common lake variables. Concentrations of TOC, iron and absorbance were simulated using discharge, seasonality and long-term trend terms in the Fluxmaster modeling system. Spatial patterns in these model terms were investigated, and the sensitivity of cyanobacteria and TOC to future climate was explored.Nutrients were the major control on cyanobacterial concentration seasonality, while temperature was more important for relative cyanobacterial abundance. No cyanobacterial blooms occurred below a total phosphorus threshold of 20 µg l-1. Discharge and seasonality explained much of the intra-annual variability in TOC, but catchment characteristics could only explain a limited amount of the spatial patterns in the sensitivity to these influences. North of Limes Norrlandicus the discharge term had a larger impact on the TOC concentration in large catchments than in small catchments, while south of Limes Norrlandicus the seasonality had a larger impact in small catchments than in larger catchments. According to the climate change scenarios, both TOC and cyanobacterial concentrations will be higher in the future. The cyanobacterial dominance will start earlier and persist longer. The spring TOC concentration peak will come earlier. The changes in TOC loads are more uncertain due to predicted declines in discharge.Parsimonious statistical regression models could explain observed variability in cyanobacteria and TOC. For predictions, these models assume that future aquatic ecosystems will exhibit the same sensitivity to major drivers as in the past. If this proves not to be the case, the modeling can serve as a sentinel for changing catchment function as indicated by degradation in model performance when calibrations on older data are used to model later observations.
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| 32. |
- Laurent, C Matthew, et al.
(author)
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A Practical Approach to Monitoring Recovery: Development of a Perceived Recovery Status Scale
- 2011
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In: Journal of Strength and Conditioning Research. - 1064-8011 .- 1533-4287. ; 25:3, s. 620-628
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Journal article (peer-reviewed)abstract
- A practical approach to monitoring recovery: development of a perceived recovery status scale. J Strength Cond Res 24(x): 000-000, 2010-The aim of this study was to develop and test the practical utility of a perceived recovery status (PRS) scale. Sixteen volunteers (8 men, 8 women) performed 4 bouts of high-intensity intermittent sprint exercise. After completion of the baseline trial, in a repeated-measures design, subjects were given variable counterbalanced recovery periods of 24, 48, and 72 hours whereupon they repeated an identical intermittent exercise protocol. After a warm-up period, but before beginning each subsequent bout of intermittent sprinting, each individual provided their perceived level of recovery with a newly developed PRS scale. Similar to perceived exertion during exercise, PRS was based on subjective feelings. The utility of the PRS scale was assessed by measuring the level of agreement of an individual's perceived recovery relative to their performance during the exercise bout. Perceived recovery status and change (both positive and negative) in sprint performance during multiple bouts of repeated sprint exercise were moderately negative correlated (r = -0.63). Additionally, subjects were able to accurately assess level of recovery using the PRS scale indicated by correspondence with negative and positive changes in total sprint time relative to their previous session. The ability to detect changes in performance using a noninvasive psychobiological tool to identify differences in performance was independent of other psychological and physiological markers measured during testing, because there were no differences (p > 0.05) among ratings of perceived exertion (RPE), heart rate, blood lactate concentration, or session RPE values among any of the performance trials. Although further study is needed, current results indicate a subjective approach may be an effective means for assessing recovery from day to day, at least under similar conditions.
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| 33. |
- Laurent, C M, et al.
(author)
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Effect of gender on fatigue and recovery following maximal intensity repeated sprint performance
- 2010
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In: Journal of Sports Medicine and Physical Fitness. - 0022-4707 .- 1827-1928. ; 50:3, s. 243-253
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Journal article (peer-reviewed)abstract
- Aim. This study investigated the effects of gender on repeated, maximal-intensity intermittent sprint exercise following variable day-to-day recovery periods.Methods. Sixteen volunteers (8 men, 8 women) performed four trials of high-intensity intermittent sprint exercise consisting of three bouts of eight 30 m sprints (total of 24 sprints). Following completion of the baseline trial, in repeated-measures design, participants were assigned, in counter-balanced order, variable recovery periods of 24, 48, and 72 h whereupon they repeated an identical exercise trial.Results. Results from a series of 4 (trial) x 3 (bout) repeated measures ANOVAs revealed men produced significantly (P < 0.01) faster times throughout all bouts and trials of repeated sprint exercise. Additionally, women exhibited significantly lower (P < 0.05) blood lactate concentration and significantly lower (P < 0.05) decrement in performance, indicating increased resistance to fatigue during repeated exercise sessions. There were no significant differences (P > 0.05) between genders for heart rate or rating of perceived exertion during or following trials. There were no significant differences for overall sprint performance within either gender among trials.Conclusions. These results indicate men, while able to produce higher absolute power outputs (i.e., lower sprint time), demonstrate higher decrement scores within a trial compared to women, thus suggesting women may recover faster and fatigue less. Also, gender differences affecting recovery within in a trial were observed to be diminished between trials (i.e., day-today recovery) of maximal intermittent sprint work evidenced by the observed stability of performance between trials following various recovery durations.
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| 34. |
- Laurent, C M, et al.
(author)
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Stability of RPE increase during repeated intermittent sprints
- 2010
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In: Journal of exercise science & fitness. - 1728-869X. ; 8:1, s. 1-10
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Journal article (peer-reviewed)abstract
- The current investigation examined the potential teleoanticipatory effect on perceptual response during repeated bouts of maximal sprint work. To determine the consistency of ratings of perceived exertion (RPE) increase during identical exercise bouts following variable recovery periods, 16 (8 men, 8 women) participants completed four separate trials of repeated maximal sprinting on 4 separate days utilizing different recovery periods. Following completion of the baseline trial, participants were given variable, counter-balanced recovery periods of 24, 48 and 72 hours, whereupon they repeated the intermittent exercise protocol. To determine the degree of similarity among trials, each individual's rate of RPE progression during each cycle of eight sprints throughout the recovery trials were compared to the rate of progression during the baseline exercise session. A series of 4 (trial) x 3 (cycle of sprints) repeated measures ANOVA were performed to identify significant main effects between trials and among cycles while session RPE was analyzed using one-way repeated measures ANOVA. Fisher's least significant difference post-hoc procedures were performed to identify where significant differences occurred when appropriate. Results revealed an inconsistency in the stability of RPE across repeated bouts of sprint exercise, with at least 50% of individuals having a substantial difference in RPE (i.e. +/- 1 unit change) in at least one subsequent trial. These variations in perceptual responses were observed despite a concomitant stability of physiological and performance responses between sessions. Results suggest that rate of RPE increase correspond more closely to increased or decreased physiologic strain than to an anticipatory, feed-forward mechanism following variable recovery durations.
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| 35. |
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| 36. |
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| 37. |
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| 38. |
- Nilsson Sköld, Helen, 1970, et al.
(author)
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The pattern of cell proliferation during budding in the colonial ascidian Diplosoma listerianum
- 2011
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In: Biological Bulletin.
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Journal article (peer-reviewed)abstract
- Many invertebrates reproduce asexually by budding, but morphogenesis and the role of cell proliferation in this diverse and non-conserved regeneration-like process are generally poorly understood and particularly little investigated in didemnid ascidians. We here analysed cell proliferation patterns and telomerase activity during budding in the colonial didemnid ascidian Diplosoma listerianum, with special focus on the thoracic bud where a new brain develops de novo. To help define developmental stages of the thoracic bud, the distribution of acetylated tubulin was also examined. We found extensive cell proliferation in both the thoracic and abdominal buds of D. listerianum as well as higher telomerase activity in bud tissue compared to adult tissues. In the parent adult, proliferation was found in various tissues, but was especially intense in the adult esophagus and epicardial structures that protrude into the proliferating and developing buds, confirming these tissues as the primary source of the cells that form the buds. The neural complex in the thoracic bud forms from a hollow tube that appears to separate into the neural gland and the cerebral ganglion. While most of the bud undergoes proliferation, including the hollow tube and the neural gland, the cerebral ganglion shows little or no proliferation. Pulse-chase labelling experiments indicate that the ganglion, as well as the myocardium, in adult zooids are instead composed of postmitotic cells.
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| 39. |
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| 40. |
- Rubinsky, AD, et al.
(author)
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AUDIT-C Alcohol Screening Results and Postoperative Inpatient Health Care Use.
- 2012
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In: Journal of the American College of Surgeons. - : Ovid Technologies (Wolters Kluwer Health). - 1879-1190 .- 1072-7515. ; 214:3, s. 296-305
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Journal article (peer-reviewed)abstract
- BACKGROUND: Alcohol screening scores 5 on the Alcohol Use Disorders Identification Test–Consumption (AUDIT-C) up to a year before surgery have been associated with postoperative complications, but the association with postoperative health care use is unknown. This study evaluated whether AUDIT-C scores in the year before surgery were associated with postoperative hospital length of stay, total ICU days, return to the operating room, and hospital readmission. STUDY DESIGN: This cohort study included male Veterans Affairs patients who completed the AUDIT-C on mailed surveys (October 2003 through September 2006) and were hospitalized for nonemergent noncardiac major operations in the following year. Postoperative health care use was evaluated across 4 AUDIT-C risk groups (scores 0, 1 to 4, 5 to 8, and 9 to 12) using linear or logistic regression models adjusted for sociodemographics, smoking status, surgical category, relative value unit, and time from AUDIT-C to surgery. Patients with AUDIT-C scores indicating low-risk drinking (scores 1 to 4) were the referent group. RESULTS: Adjusted analyses revealed that among eligible surgical patients (n 5,171), those with the highest AUDIT-C scores (ie, 9 to 12) had longer postoperative hospital length of stay (5.8 [95% CI, 5.06.7] vs 5.0 [95% CI, 4.75.3] days), more ICU days (4.5 [95% CI, 3.25.8] vs 2.8 [95% CI, 2.63.1] days), and increased probability of return to the operating room (10% [95% CI, 613%] vs 5% [95% CI, 46%]) in the 30 days after surgery, but not increased hospital readmission within 30 days postdischarge, relative to the low-risk group. CONCLUSIONS: AUDIT-C screening results could be used to identify patients at risk for increased postoperative health care use who might benefit from preoperative alcohol interventions.
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| 41. |
- Sjökvist, Jesper, et al.
(author)
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Recovery from high-intensity training sessions in female soccer players
- 2011
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In: Journal of Strength and Conditioning Research. - 1064-8011 .- 1533-4287. ; 25:6, s. 1726-1735
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Journal article (peer-reviewed)abstract
- This study quantified the performance recovery time requirements after training sessions using high-intensity soccer drills with and without the ball in National Collegiate Athletic Association Division I female soccer players. Recovery time periods (24, 48, 72 hours of rest) from high-intensity soccer training sessions using drills with and without the ball were evaluated. Markers of recovery were each individual's performance relative to baseline performance in countermovement jump (CMJ) height, 5 bound jumps for distance (5BT), 20-m sprint (20SP), session rating of perceived effort (S-RPE), and heart rate (HR). Repeated-measures analysis of variance revealed a significant difference in CMJ performance (p < 0.04) and S-RPE (p < 0.02) after 24 hours of rest but not at 48 or 72 hours compared to baseline. There were no significant differences in 20SP, 5BT, or HR after 24, 48, or 72-hour recovery (p > 0.05). Therefore, high-intensity training drills produced a sufficient conditioning stimulus with little chance of underrecovery for the performance measures we tested. Countermovement jump and S-RPE may be more sensitive performance recovery indicators.
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