| 1. |
- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 2. |
- Abazov, V. M., et al.
(författare)
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The upgraded DO detector
- 2006
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 565:2, s. 463-537
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Tidskriftsartikel (refereegranskat)abstract
- The DO experiment enjoyed a very successful data-collection run at the Fermilab Tevatron collider between 1992 and 1996. Since then, the detector has been upgraded to take advantage of improvements to the Tevatron and to enhance its physics capabilities. We describe the new elements of the detector, including the silicon microstrip tracker, central fiber tracker, solenoidal magnet, preshower detectors, forward muon detector, and forward proton detector. The uranium/liquid -argon calorimeters and central muon detector, remaining from Run 1, are discussed briefly. We also present the associated electronics, triggering, and data acquisition systems, along with the design and implementation of software specific to DO.
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| 3. |
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| 4. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 5. |
- Fynbo, J. P. U., et al.
(författare)
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Low-resolution Spectroscopy of Gamma-ray Burst Optical Afterglows : Biases in the Swift Sample and Characterization of the Absorbers
- 2009
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 185:2, s. 526-573
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Tidskriftsartikel (refereegranskat)abstract
- We present a sample of 77 optical afterglows (OAs) of Swift detected gamma-ray bursts (GRBs) for which spectroscopic follow-up observations have been secured. Our first objective is to measure the redshifts of the bursts. For the majority (90%) of the afterglows, the redshifts have been determined from the spectra. We provide line lists and equivalent widths (EWs) for all detected lines redward of Lyα covered by the spectra. In addition to the GRB absorption systems, these lists include line strengths for a total of 33 intervening absorption systems. We discuss to what extent the current sample of Swift bursts with OA spectroscopy is a biased subsample of all Swift detected GRBs. For that purpose we define an X-ray-selected statistical sample of Swift bursts with optimal conditions for ground-based follow-up from the period 2005 March to 2008 September; 146 bursts fulfill our sample criteria. We derive the redshift distribution for the statistical (X-ray selected) sample and conclude that less than 18% of Swift bursts can be at z > 7. We compare the high-energy properties (e.g., γ-ray (15-350 keV) fluence and duration, X-ray flux, and excess absorption) for three subsamples of bursts in the statistical sample: (1) bursts with redshifts measured from OA spectroscopy; (2) bursts with detected optical and/or near-IR afterglow, but no afterglow-based redshift; and (3) bursts with no detection of the OA. The bursts in group (1) have slightly higher γ-ray fluences and higher X-ray fluxes and significantly less excess X-ray absorption than bursts in the other two groups. In addition, the fractions of dark bursts, defined as bursts with an optical to X-ray slope βOX < 0.5, is 14% in group (1), 38% in group (2), and >39% in group (3). For the full sample, the dark burst fraction is constrained to be in the range 25%-42%. From this we conclude that the sample of GRBs with OA spectroscopy is not representative for all Swift bursts, most likely due to a bias against the most dusty sight lines. This should be taken into account when determining, e.g., the redshift or metallicity distribution of GRBs and when using GRBs as a probe of star formation. Finally, we characterize GRB absorption systems as a class and compare them to QSO absorption systems, in particular the damped Lyα absorbers (DLAs). On average GRB absorbers are characterized by significantly stronger EWs for H I as well as for both low and high ionization metal lines than what is seen in intervening QSO absorbers. However, the distribution of line strengths is very broad and several GRB absorbers have lines with EWs well within the range spanned by QSO-DLAs. Based on the 33 z > 2 bursts in the sample, we place a 95% confidence upper limit of 7.5% on the mean escape fraction of ionizing photons from star-forming galaxies. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere, Chile, under programs 275.D-5022 (PI: Chincarini), 075.D-0270 (PI: Fynbo), 077.D-0661 (PI: Vreeswijk), 077.D-0805 (PI: Tagliaferri), 177.A-0591 (PI: Hjorth), 078.D-0416 (PI: Vreeswijk), 079.D-0429 (PI: Vreeswijk), 080.D-0526 (PI: Vreeswijk), 081.A-0135 (PI: Greiner), 281.D-5002 (PI: Della Valle), and 081.A-0856 (PI: Vreeswijk). Also based on observations made with the Nordic Optical Telescope, operated on the island of La Palma jointly by Denmark, Finland, Iceland, Norway, and Sweden, in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias. Some of the data obtained herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck foundation.
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| 6. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Forskningsöversikt (refereegranskat)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
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| 7. |
- Graham, Nicholas A. J., et al.
(författare)
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Climate Warming, Marine Protected Areas and the Ocean-Scale Integrity of Coral Reef Ecosystems
- 2008
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:8, s. e3039-
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Tidskriftsartikel (refereegranskat)abstract
- Coral reefs have emerged as one of the ecosystems most vulnerable to climate variation and change. While the contribution of a warming climate to the loss of live coral cover has been well documented across large spatial and temporal scales, the associated effects on fish have not. Here, we respond to recent and repeated calls to assess the importance of local management in conserving coral reefs in the context of global climate change. Such information is important, as coral reef fish assemblages are the most species dense vertebrate communities on earth, contributing critical ecosystem functions and providing crucial ecosystem services to human societies in tropical countries. Our assessment of the impacts of the 1998 mass bleaching event on coral cover, reef structural complexity, and reef associated fishes spans 7 countries, 66 sites and 26 degrees of latitude in the Indian Ocean. Using Bayesian meta-analysis we show that changes in the size structure, diversity and trophic composition of the reef fish community have followed coral declines. Although the ocean scale integrity of these coral reef ecosystems has been lost, it is positive to see the effects are spatially variable at multiple scales, with impacts and vulnerability affected by geography but not management regime. Existing no-take marine protected areas still support high biomass of fish, however they had no positive affect on the ecosystem response to large-scale disturbance. This suggests a need for future conservation and management efforts to identify and protect regional refugia, which should be integrated into existing management frameworks and combined with policies to improve system-wide resilience to climate variation and change.
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| 8. |
- Gateva, Vesela, et al.
(författare)
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A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:11, s. 1228-1233
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have recently identified at least 15 susceptibility loci for systemic lupus erythematosus (SLE). To confirm additional risk loci, we selected SNPs from 2,466 regions that showed nominal evidence of association to SLE (P < 0.05) in a genome-wide study and genotyped them in an independent sample of 1,963 cases and 4,329 controls. This replication effort identified five new SLE susceptibility loci (P < 5 x 10(-8)): TNIP1 (odds ratio (OR) = 1.27), PRDM1 (OR = 1.20), JAZF1 (OR = 1.20), UHRF1BP1 (OR = 1.17) and IL10 (OR = 1.19). We identified 21 additional candidate loci with P< or = 1 x 10(-5). A candidate screen of alleles previously associated with other autoimmune diseases suggested five loci (P < 1 x 10(-3)) that may contribute to SLE: IFIH1, CFB, CLEC16A, IL12B and SH2B3. These results expand the number of confirmed and candidate SLE susceptibility loci and implicate several key immunologic pathways in SLE pathogenesis.
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| 9. |
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| 10. |
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| 11. |
- Agüero, Juan C., et al.
(författare)
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Fundamental Limitations on the Accuracy of MIMO Linear Models Obtained by PEM for Systems Operating in Open Loop
- 2009
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Ingår i: Proceedings of the Joint 48th IEEE Conference on Decision and Control (CDC’09) and 28th Chinese Control Conference (CCC’09). - 9781424438716 ; , s. 482-487
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Konferensbidrag (refereegranskat)abstract
- In this paper we show that the variance of estimated parametric models for open loopMultiple-Input Multiple-Output (MIMO) systems obtained by the prediction error method (PEM) satisfies a fundamental integral limitation. The fundamental limitation gives rise to a multivariable 'water-bed' effect.
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Cox, David G, et al.
(författare)
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Haplotypes of the estrogen receptor beta gene and breast cancer risk
- 2008
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 122:2, s. 387-392
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to exogenous (oral contraceptives, postmenopausal hormone therapy) and endogenous (number of ovulatory cycles, adiposity) steroid hormones is associated with breast cancer risk. Breast cancer risk associated with these exposures could hypothetically be modified by genes in the steroid hormone synthesis, metabolism and signaling pathways. Estrogen receptors are the first step along the path of signaling cell growth and development upon stimulation with estrogens. The National Cancer Institute Breast and Prostate Cancer Cohort Consortium has systematically selected haplotype tagging SNPs in genes along the steroid hormone synthesis, metabolism and binding pathways, including the estrogen receptor beta (ESR2) gene. Four htSNPs tag the 6 major (>5% frequency) haplotypes of the ESR2 gene. These polymorphisms have been genotyped in 5,789 breast cancer cases and 7,761 controls nested within the American Cancer Society Cancer Prevention Study II, European Prospective Investigation into Cancer and Nutrition, Multiethnic Cohort, Nurses' Health Study and Women's Health Study cohorts. None of the SNPs were independently associated with breast cancer risk. One haplotype of the ESR2 gene was associated with breast cancer risk before correction for multiple testing (OR 1.17, 95% CI 1.07-1.28, p = 0.0007). This haplotype remained associated with breast cancer risk after adjustment for multiple testing using a permutation procedure. There was no statistically significant heterogeneity in SNP or haplotype odds ratios across cohorts. These data suggest that inherited variants in ESR2 (while possibly conferring a small increased risk of breast cancer) are not associated with appreciable (OR > 1.2) changes in breast cancer risk among Caucasian women.
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| 16. |
- Figaji, Anthony A., et al.
(författare)
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Pressure autoregulation, intracranial pressure, and brain tissue oxygenation in children with severe traumatic brain injury
- 2009
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Ingår i: Journal of Neurosurgery: Pediatrics. - 1933-0715. ; 4:5, s. 420-428
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Tidskriftsartikel (refereegranskat)abstract
- Object. Cerebral pressure autoregulation is an important neuroprotective mechanism that stabilizes cerebral blood flow when blood pressure (BP) changes In this study the authors examined the association between autoregulation and clinical factors. BR. intracranial pressure (ICP), brain tissue oxygen tension (PbtO(2)), and outcome after pediatric severe traumatic brain injury (TBI). In particular we examined how the Status 01: autoregulation influenced the effect of BP changes on ICP and PbtO(2) Methods In this prospective observational study. 52 autoregulation tests were performed in 24 patients with severe. TBI. The patients had a mean age of 6.3 +/- 3.2 years. and a postresuscitation Glasgow Coma Scale score of 6 (range 3-8). All patients underwent continuous ICP and MID, monitoring. and transcranial Doppler ultrasonography was, used to examine the autoregulatory index (ARI) based on blood flow velocity of the middle cerebral artery after increasing mean arterial pressure by 20% of the baseline value Impaired autoregulation was defined as an ARI < 0 4 and intact autoregulation as an ART >= 0 4 The relationships between autoregulation (measured as both a Continuous and dichotomous variable), outcome, and clinical and physiological variables were examined using Multiple logistic regression analysis Results. Autoregulation was impaired (ART < 0 4) in 29% of patients (7 patients). The initial Glasgow Coma Scale score was significantly associated with the ARI (p = 0.02, r = 0.32) but no other clinical factors were associated with autoregulation Status. Baseline values at the time of testing for ICP, PbtO(2), the ratio PbtO(2)/PaO2, mean arterial pressure, and middle cerebral artery blood flow velocity were similar in the patients with impaired or intact autoregulation. There was an inverse relationship between ART (continuous and dichotomous) with a chancle in ICP (continuous ARI, p 0.005, dichotomous ARI, p = 0 02): that is. ICP increased with the BP increase when ARI was low (weak autoregulation) The ART (continuous and dichotomous) was also inversely associated with a change in PbtO(2). (continuous ART. p 0.002. dichotomous ARI, p = 0 02). The PbtO(2) increased when BP was increased in most patients, even when the ARI was relatively high (stronger autoregulation). but the magnitude of this response was still associated with the ART. There was no relationship between the ART and Outcome Conclusion. These data demonstrate the influence of the strength of autoregulation on the response of ICP and MO. to BP changes and the variability of this response between individuals The findings suggest that autoregulation testing may assist clinical decision-making in pediatric severe TBI and help better define optimal BP or cerebral perfusion pressure targets for individual patients. (DOI: 10.3171/2009.6.PEDS096)
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| 17. |
- Goodwin, Graham C., et al.
(författare)
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Robust Identification of Process Models from Plant Data
- 2008
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Ingår i: Journal of Process Control. - : Elsevier. - 0959-1524. ; 18:9, s. 810-820
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Tidskriftsartikel (refereegranskat)abstract
- A precursor to any advanced control solution is the step of obtaining an accurate model of the process. Suitable models can be obtained from phenomenological reasoning, analysis of plant data or a combination of both. Here, we will focus on the problem of estimating (or calibrating) models from plant data. A key goal is to achieve robust identification. By robust we mean that small errors in the hypotheses should lead to small errors in the estimated models. We argue that, in some circumstances, it is essential that special precautions, including discarding some part of the data, be taken to ensure that robustness is preserved. We present several practical case studies to illustrate the results.
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| 18. |
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| 19. |
- Graham, R. Robert, et al.
(författare)
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Three functional variants of IFN regulatory factor 5 (IRF5) define risk and protective haplotypes for human lupus
- 2007
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 104:16, s. 6758-6763
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Tidskriftsartikel (refereegranskat)abstract
- Systematic genome-wide studies to map genomic regions associated with human diseases are becoming more practical. Increasingly, efforts will be focused on the identification of the specific functional variants responsible for the disease. The challenges of identifying causal variants include the need for complete ascertainment of genetic variants and the need to consider the possibility of multiple causal alleles. We recently reported that risk of systemic lupus erythematosus (SLE) is strongly associated with a common SNP in IFN regulatory factor 5 (IRF5), and that this variant altered spicing in a way that might provide a functional explanation for the reproducible association to SLE risk. Here, by resequencing and genotyping in patients with SLE, we find evidence for three functional alleles of IRF5: the previously described exon 1B splice site variant, a 30-bp in-frame insertion/deletion variant of exon 6 that alters a proline-, glutamic acid-, serine- and threonine-rich domain region, and a variant in a conserved polyA+ signal sequence that alters the length of the 3' UTR and stability of IRF5 mRNAs. Haplotypes of these three variants define at least three distinct levels of risk to SLE. Understanding how combinations of variants influence IRF5 function may offer etiological and therapeutic insights in SLE; more generally, IRF5 and SLE illustrates how multiple common variants of the same gene can together influence risk of common disease.
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| 20. |
- Kennedy, L J, et al.
(författare)
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Association of canine hypothyroidism with a common major histocompatibility complex DLA class II allele.
- 2006
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Ingår i: Tissue Antigens. - : Wiley. - 0001-2815 .- 1399-0039. ; 68:1, s. 82-6
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Tidskriftsartikel (refereegranskat)abstract
- Dogs exhibit a range of immune-mediated conditions including a lymphocytic thyroiditis which has many similarities to Hashimoto's thyroiditis in man. We have recently reported an association in Doberman Pinschers between canine hypothyroidism and a rare DLA class II haplotype that contains the DLA-DQA1*00101 allele. We now report a further series of 173 hypothyroid dogs in a range of breeds where a significant association with DLA-DQA1*00101 is shown.
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| 21. |
- Leachman, Sancy A., et al.
(författare)
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Selection criteria for genetic assessment of patients with familial melanoma
- 2009
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Ingår i: Journal of American Academy of Dermatology. - : Elsevier BV. - 0190-9622. ; 61:4, s. 677-684
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Forskningsöversikt (refereegranskat)abstract
- Approximately 5% to 10% of melanoma may be hereditary in nature, and about 2% of melanoma can be specifically attributed to pathogenic germline mutations in cyclin-dependent kinase inhibitor 2A (CDKN2A). To appropriately identify the small proportion of patients Who benefit most from referral to a genetics specialist for consideration of genetic testing for CDKN2A, We have reviewed available published studies of CDKN2A mutation analysis in cohorts with invasive, cutaneous melanoma and found variability in the rate of CDKN2A mutations based on geography, ethnicity, and the type of study and eligibility criteria used. Except in regions of high melanoma incidence, such as Australia, we found higher rates of CDKN2A positivity in individuals with 3 or more primary invasive melanomas and/or families with at least one invasive melanoma and two or more other diagnoses of invasive melanoma and/or pancreatic cancer among first- or second-degree relatives on the same side of the family. The Work summarized in this review should help identify individuals who are appropriate candidates for referral for genetic consultation and possible testing. (J Am Acad Dermatol 2009;61:677-84.)
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| 22. |
- Lee, Jung Eun, et al.
(författare)
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Fat, Protein, and Meat Consumption and Renal Cell Cancer Risk : A Pooled Analysis of 13 Prospective Studies
- 2008
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Ingår i: Journal of the National Cancer Institute. - : OXFORD UNIV PRESS INC. - 0027-8874 .- 1460-2105. ; 100:23, s. 1695-1706
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Tidskriftsartikel (refereegranskat)abstract
- Results of several case-control studies suggest that high consumption of meat (all meat, red meat, or processed meat) is associated with an increased risk of renal cell cancer, but only a few prospective studies have examined the associations of intakes of meat, fat, and protein with renal cell cancer. We conducted a pooled analysis of 13 prospective studies that included 530 469 women and 244 483 men and had follow-up times of up to 7-20 years to examine associations between meat, fat, and protein intakes and the risk of renal cell cancer. All participants had completed a validated food frequency questionnaire at study entry. Using the primary data from each study, we calculated the study-specific relative risks (RRs) for renal cell cancer by using Cox proportional hazards models and then pooled these RRs by using a random-effects model. All statistical tests were two-sided. A total of 1478 incident cases of renal cell cancer were identified (709 in women and 769 in men). We observed statistically significant positive associations or trends in pooled age-adjusted models for intakes of total fat, saturated fat, monounsaturated fat, polyunsaturated fat, cholesterol, total protein, and animal protein. However, these associations were attenuated and no longer statistically significant after adjusting for body mass index, fruit and vegetable intake, and alcohol intake. For example, the pooled age-adjusted RR of renal cell cancer for the highest vs the lowest quintile of intake for total fat was 1.30 (95% confidence interval [CI] = 1.08 to 1.56; P-trend = .001) and for total protein was 1.17 (95% CI = 0.99 to 1.38; P-trend = .02). By comparison, the pooled multivariable RR for the highest vs the lowest quintile of total fat intake was 1.10 (95% CI = 0.92 to 1.32; P-trend = .31) and of total protein intake was 1.06 (95% CI = 0.89 to 1.26; P-trend = .37). Intakes of red meat, processed meat, poultry, or seafood were not associated with the risk of renal cell cancer. Intakes of fat and protein or their subtypes, red meat, processed meat, poultry, and seafood are not associated with risk of renal cell cancer.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Rojas, Cristian R., et al.
(författare)
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On the Equivalence of Least Costly and Traditional Experiment Design for Control
- 2008
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Ingår i: Automatica. - : Elsevier BV. - 0005-1098 .- 1873-2836. ; 44:11, s. 2706-2715
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we establish the equivalence between least costly and traditional experiment design for control. We consider experiment design problems for both open and closed loop systems. In open loop, equivalence is established for three specific cases, relating to different parametrisations of the covariance expression (i.e. finite and high order approximations) and model structure (i.e. dependent and independently parameterised plant and noise models). In the closed loop setting, we consider only finite order covariance expressions. H(infinity) performance specifications for control are used to determine the bounds on the covariance expression for both the open and closed loop cases.
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| 27. |
- Shin, J. H., et al.
(författare)
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IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5
- 2007
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Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 503-12
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Tidskriftsartikel (refereegranskat)abstract
- In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.
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| 28. |
- Smith-Warner, Stephanie A., et al.
(författare)
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Methods for pooling results of epidemiologic studies - The pooling project of prospective studies of diet and cancer
- 2006
-
Ingår i: American Journal of Epidemiology. - Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. NCI, Nutr Epidemiol Branch, Bethesda, MD USA. Loma Linda Univ, Sch Med, Ctr Hlth Res, Loma Linda, CA 92350 USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA USA. Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. NCI, Epidemiol Unit, Milan, Italy. Maastricht Univ, Fac Hlth Sci, Dept Epidemiol, Maastricht, Netherlands. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Ctr Canc Prevent, Boston, MA USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY USA. TNO Qual Life, Dept Epidemiol, Zeist, Netherlands. No Calif Canc Ctr, Fremont, CA USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA. Amer Canc Soc, Epidemiol & Surveilliance Res, Atlanta, GA USA. Univ Toronto, Fac Med, Dept Publ Hlth Sci, Toronto, ON, Canada. Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY USA. NYU, Sch Med, Dept Environm Med, New York, NY USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. Natl Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden. : OXFORD UNIV PRESS INC. - 0002-9262 .- 1476-6256. ; 163:11, s. 1053-1064
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Tidskriftsartikel (refereegranskat)abstract
- With the growing number of epidemiologic publications on the relation between dietary factors and cancer risk, pooled analyses that summarize results from multiple studies are becoming more common. Here, the authors describe the methods being used to summarize data on diet-cancer associations within the ongoing Pooling Project of Prospective Studies of Diet and Cancer, begun in 1991. In the Pooling Project, the primary data from prospective cohort studies meeting prespecified inclusion criteria are analyzed using standardized criteria for modeling of exposure, confounding, and outcome variables. In addition to evaluating main exposure-disease associations, analyses are also conducted to evaluate whether exposure-disease associations are modified by other dietary and nondietary factors or vary among population subgroups or particular cancer subtypes. Study-specific relative risks are calculated using the Cox proportional hazards model and then pooled using a random- or mixed-effects model. The study-specific estimates are weighted by the inverse of their variances in forming summary estimates. Most of the methods used in the Pooling Project may be adapted for examining associations with dietary and nondietary factors in pooled analyses of case-control studies or case-control and cohort studies combined.
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| 29. |
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| 30. |
- Agarwal, A., et al.
(författare)
-
A ray tracing approach to calculate acoustic shielding by the silent aircraft airframe
- 2006
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Ingår i: Collection of Technical Papers - 12th AIAA/CEAS Aeroacoustics Conference. - 1563478099 - 9781563478093 ; , s. 2799-2818
-
Konferensbidrag (refereegranskat)abstract
- The Silent Aircraft is in the form of a flying wing with a large wing planform and a propulsion system that is embedded in the rear of the airframe with intakes on the upper surface of the wing. Thus a large part of the forward-propagating noise from the intake ducts is expected to be shielded from observers on the ground by the wing. Acoustic shielding effects can be calculated by solving an external acoustic scattering problem for a moving aircraft. In this paper, acoustic shielding effects of the Silent Aircraft airframe are quantified by a ray-tracing method. The dominant frequencies from the noise spectrum of the engines are sufficiently high for ray theory to yield accurate results. It is shown that for low-Mach number homentropic flows, a condition satisfied approximately by the Silent Aircraft during take-off and approach, the acoustic rays propagate in straight lines. Thus, from Fermat's principle it is clear that classical Geometrical Optics and Geometrical Theory of Diffraction solutions are applicable to this moving-body problem as well. The total amount of acoustic shielding at an observer located in the shadow region is calculated by adding the contributions from all the diffracted rays (edge-diffracted and creeping rays) and then subtracting the result from the incident field without the airframe. Experiments on a model-scale geometry have been conducted in an anechoic chamber to test the applicability of the ray-tracing technique. The three-dimensional ray-tracing solver is validated by comparing the numerical solution with analytical high-frequency asymptotic solutions for canonical shapes.
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| 31. |
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| 32. |
- Bannister, R., et al.
(författare)
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Afuni, a novel transforming growth factor-β gene is involved in arm regeneration by the brittle star Amphiura filiformis
- 2005
-
Ingår i: Development Genes and Evolution. - : Springer Science and Business Media LLC. - 0949-944X .- 1432-041X. ; 215:8, s. 393-401
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Tidskriftsartikel (refereegranskat)abstract
- The bone morphogenetic proteins (BMPs) are a family of the transforming growth factor-beta (TGF-beta) superfamily that perform multiple roles during vertebrate and invertebrate development. Here, we report the molecular cloning of a novel BMP from regenerating arms of the ophiuroid Amphiura filiformis. The theoretically translated amino acid sequence of this novel BMP has high similarity to that of the sea urchin BMP univin. This novel BMP has been named afuni. Whole-mount in situ hybridisation implicates afuni in arm regeneration. Expression occurs in distinct proximal and distal regions of late regenerates (3- and 5-week postablation). These sites are at different stages of regeneration, suggesting multiple roles for this gene in adult arm development. Cellular expression of this gene occurs in migratory cells within the radial water canal (RWC) of regenerating and nonregenerating arms. These migrating coelomocytes suggest a key role for the coelomic RWC as a source of the cellular material for use in arm regeneration by A. filiformis
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| 33. |
- Bannister, R., et al.
(författare)
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Coelomic expression of a novel bone morphogenetic protein in regenerating arms of the brittle star Amphiura filiformis
- 2008
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Ingår i: Development Genes and Evolution. - 0949-944X. ; 218:1, s. 33-38
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Tidskriftsartikel (refereegranskat)abstract
- The bone morphogenetic proteins (BMPs) are a family of signalling molecules involved in numerous developmental processes including cell fate determination in embryonic ectoderm of vertebrate and invertebrate species. Recently, published evidence has indicated that BMPs are involved in echinoderm adult tissue regeneration. We have cloned a novel member of the BMP2/4 subfamily from the ophiuroid echinoderm Amphiura filiformis, which we have named afBMP2/4. Whole-mount in-situ hybridisation performed on non-regenerating brittle star arms revealed that expression of afBMP2/4 is localised to the radial water canal (RWC) and that this expression is upregulated at segmental intervals along the arm. This observed expression pattern suggests a putative active role for this echinoderm BMP transcript in somatic growth and maintenance of the brittle star arm. Expression of this factor has also been observed in regenerating arms 2 weeks post-ablation, implicating the RWC as a source of cells for ophiuroid arm regeneration.
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| 34. |
- Bekris, LM, et al.
(författare)
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Glutamate cysteine ligase catalytic subunit promoter polymorphisms and associations with type 1 diabetes age-at-onset and GAD65 autoantibody levels.
- 2007
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Ingår i: Exp Clin Endocrinol Diabetes. - : Georg Thieme Verlag KG. ; 115:4, s. 221-228
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to test the hypothesis that glutamate cysteine ligase catalytic subunit (GCLC) promoter polymorphisms are susceptibility factors for type 1 diabetes (T1D), T1D age-at-onset and T1D autoantibodies. T1D patients and control subjects from the Swedish Childhood Diabetes Registry and the Swedish Diabetes Incidence Study registry were genotyped for two GCLC promoter polymorphisms; the GCLC -129 C to T single nucleotide polymorphism (GCLC -129 SNP) and the GCLC GAG trinucleotide repeat polymorphism (GCLC TNR). Glutamate decarboxylase antibody (GAD65Ab) positive T1D patients with the GCLC -129 SNP C/T genotype have increased GAD65Ab levels (p-value, <0.05) compared to the GCLC -129 SNP C/C genotype. T1D patients with an age-at-onset of 14-35 years who possess the GCLC -129 SNP T/T genotype have a higher GAD65Ab index than T1D patients with the GCLC -129 SNP C/C genotype (p-value <0.05). In addition, T1D patients with an age-at-onset of 14-35 years possess the GCLC TNR 7/8 genotype at a lower frequency than the control subjects (OR, 0.33, 95% CI, 0.13-0.82). The GCLC -129 SNP and GCLC TNR appear to be in linkage disequilibrium (p-value<0.0001). These results suggest that GCLC promoter polymorphisms may influence GAD65Ab levels and may influence the age at which T1D is diagnosed.
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| 35. |
- Bishop, D. Timothy, et al.
(författare)
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Genome-wide association study identifies three loci associated with melanoma risk
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:8, s. 920-925
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Tidskriftsartikel (refereegranskat)abstract
- We report a genome-wide association study of melanoma conducted by the GenoMEL consortium based on 317K tagging SNPs for 1,650 selected cases and 4,336 controls, with replication in an additional two cohorts (1,149 selected cases and 964 controls from GenoMEL, and a population-based case-control study in Leeds of 1,163 cases and 903 controls). The genome-wide screen identified five loci with genotyped or imputed SNPs reaching P < 5 x 10(-7). Three of these loci were replicated: 16q24 encompassing MC1R (combined P = 2.54 x 10(-27) for rs258322), 11q14-q21 encompassing TYR (P = 2.41 x 10(-14) for rs1393350) and 9p21 adjacent to MTAP and flanking CDKN2A (P = 4.03 x 10(-7) for rs7023329). MC1R and TYR are associated with pigmentation, freckling and cutaneous sun sensitivity, well-recognized melanoma risk factors. Common variants within the 9p21 locus have not previously been associated with melanoma. Despite wide variation in allele frequency, these genetic variants show notable homogeneity of effect across populations of European ancestry living at different latitudes and show independent association to disease risk.
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| 36. |
- Brus, Linda, 1977-
(författare)
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Nonlinear Identification and Control with Solar Energy Applications
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Nonlinear systems occur in industrial processes, economical systems, biotechnology and in many other areas. The thesis treats methods for system identification and control of such nonlinear systems, and applies the proposed methods to a solar heating/cooling plant. Two applications, an anaerobic digestion process and a domestic solar heating system are first used to illustrate properties of an existing nonlinear recursive prediction error identification algorithm. In both cases, the accuracy of the obtained nonlinear black-box models are comparable to the results of application specific grey-box models. Next a convergence analysis is performed, where conditions for convergence are formulated. The results, together with the examples, indicate the need of a method for providing initial parameters for the nonlinear prediction error algorithm. Such a method is then suggested and shown to increase the usefulness of the prediction error algorithm, significantly decreasing the risk for convergence to suboptimal minimum points. Next, the thesis treats model based control of systems with input signal dependent time delays. The approach taken is to develop a controller for systems with constant time delays, and embed it by input signal dependent resampling; the resampling acting as an interface between the system and the controller. Finally a solar collector field for combined cooling and heating of office buildings is used to illustrate the system identification and control strategies discussed earlier in the thesis, the control objective being to control the solar collector output temperature. The system has nonlinear dynamic behavior and large flow dependent time delays. The simulated evaluation using measured disturbances confirm that the controller works as intended. A significant reduction of the impact of variations in solar radiation on the collector outlet temperature is achieved, though the limited control range of the system itself prevents full exploitation of the proposed feedforward control. The methods and results contribute to a better utilization of solar power.
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| 37. |
- Cox, Angela, et al.
(författare)
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A common coding variant in CASP8 is associated with breast cancer risk
- 2007
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 352-358
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Tidskriftsartikel (refereegranskat)abstract
- The Breast Cancer Association Consortium (BCAC) has been established to conduct combined case-control analyses with augmented statistical power to try to confirm putative genetic associations with breast cancer. We genotyped nine SNPs for which there was some prior evidence of an association with breast cancer: CASP8 D302H (rs1045485), IGFBP3 -202 C --> A (rs2854744), SOD2 V16A (rs1799725), TGFB1 L10P (rs1982073), ATM S49C (rs1800054), ADH1B 3' UTR A --> G (rs1042026), CDKN1A S31R (rs1801270), ICAM5 V301I (rs1056538) and NUMA1 A794G (rs3750913). We included data from 9-15 studies, comprising 11,391-18,290 cases and 14,753-22,670 controls. We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85-0.94) and 0.74 (95% c.i.: 0.62-0.87) for heterozygotes and rare homozygotes, respectively, compared with common homozygotes; P(trend) = 1.1 x 10(-7)) and weaker evidence for TGFB1 L10P (OR = 1.07 (95% c.i.: 1.02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies.
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| 38. |
- Cox, David G., et al.
(författare)
-
A comprehensive analysis of the androgen receptor gene and risk of breast cancer: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)
- 2006
-
Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 8:5
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction Androgens have been hypothesised to influence risk of breast cancer through several possible mechanisms, including their conversion to estradiol or their binding to the oestrogen receptor and/ or androgen receptor ( AR) in the breast. Here, we report on the results of a large and comprehensive study of the association between genetic variation in the AR gene and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium ( BPC3). Methods The underlying genetic variation was determined by first sequencing the coding regions of the AR gene in a panel of 95 advanced breast cancer cases. Second, a dense set of markers from the public database was genotyped in a panel of 349 healthy women. The linkage disequilibrium relationships ( blocks) across the gene were then identified, and haplotypetagging single nucleotide polymorphisms ( htSNPs) were selected to capture the common genetic variation across the locus. The htSNPs were then genotyped in the nested breast cancer cases and controls from the Cancer Prevention Study II, European Prospective Investigation into Cancer and Nutrition, Multiethnic Cohort, Nurses' Health Study, and Women's Health Study cohorts ( 5,603 breast cancer cases and 7,480 controls). Results We found no association between any genetic variation ( SNP, haplotype, or the exon 1 CAG repeat) in the AR gene and risk of breast cancer, nor were any statistical interactions with known breast cancer risk factors observed. Conclusion Among postmenopausal Caucasian women, common variants of the AR gene are not associated with risk of breast cancer.
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| 39. |
- Daley, Allison C., 1980-, et al.
(författare)
-
The Burgess Shale Anomalocaridid Hurdia and Its Significance for Early Euarthropod Evolution
- 2009
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Ingår i: Science. - Washington, DC : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 323:5921, s. 1597-1600
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Tidskriftsartikel (refereegranskat)abstract
- As the largest predators of the Cambrian seas, the anomalocaridids had an important impact in structuring the first complex marine animal communities, but many aspects of anomalocaridid morphology, diversity, ecology, and affinity remain unclear owing to a paucity of specimens. Here we describe the anomalocaridid Hurdia, based on several hundred specimens from the Burgess Shale in Canada. Hurdia possesses a general body architecture similar to Anomalocaris and Laggania, including the presence of exceptionally well-preserved gills, but differs from those anomalocaridids by possessing a prominent anterior carapace structure. These features amplify and clarify the diversity of known anomalocaridid morphology and provide insight into the origins of important arthropod features, such as the head shield and respiratory exites.
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| 40. |
- Davies, Simon J., et al.
(författare)
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Longitudinal relationships between fluid status, inflammation, urine volume and plasma metabolites of icodextrin in patients randomized to glucose or icodextrin for the long exchange
- 2008
-
Ingår i: NEPHROLOGY DIALYSIS TRANSPLANTATION. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 23:9, s. 2982-2988
-
Konferensbidrag (refereegranskat)abstract
- Background. Randomized trials have shown that icodextrin reduces the volume of extra-cellular fluid (ECFv) with variable effects on residual renal function. To explore this fluid shift and its possible mechanisms in more detail, prospectively collected data from one such trial, including measures of inflammation (C-reactive protein, tumor necrosis factor-a, albumin and low and high molecular weight hyaluronan) ANP (atrial naturetic peptide), an indirect marker of intra-vascular Volume, plasma concentrations of icodextrin metabolites and alpha-amylase activity were analysed. Methods. 50 patients were randomized to either 2,27% glucose or icodextrin (n = 28) ford long exchange following a month run in. Blood samples were obtained at - 1, 0, 3 and 6 months, coincident with measurements Of urine volume and fluid status. Results. In both randomized groups, a significant correlation between the fall in ECFv and the decline in urine Volume was observed (P = 0.001), although the relative drop in urine volume for patients randomized to icodextrin tended to be less. At baseline, ANP was higher in patients with proportionately more ECFv for a given body water or height. Icodextrin patients had non-significantly higher ANP levels at baseline, whereas by 3 (P = 0.026) and 6 months (P = 0.016) these differed between groups due to divergence. There was a correlation between increasing ANP and reduced ECF at 3 months, r = -0.46, P = 0.007. in patients randomized to icodextrin, but not glucose. There were no relationships between fluid Status and any inflammatory markers at any point of the Study, with the exception of albumin at baseline, r = -0.39, P = 0.007. Amylase activities at -1 month and baseline were highly correlated, r = 0.89, P < 0.0001. Within patients, concentrations of icodextrin metabolites were highly correlated: the only predictor of between-patient variability oil multivariate analysis was body weight. There was no relationship between plasma concentrations of icodextrin metabolites and any of the other clinical parameters, including change in daily Ultrafiltration, urine volume, fluid or inflammatory status. Conclusions. This analysis supports observational data that changes in fluid status are associated with changes ill urine volume. Icodextrin was not associated with a greater fall ill urine Output despite its larger effect on ECFv Changes ill fluid status Could not be explained or did not appeal to influence systemic inflammation. Nor call they be explained by individual variability in plasma concentrations of icodextrin that are in turn inversely proportional to the volume of distribution.
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| 41. |
- de Bakker, Paul I. W., et al.
(författare)
-
Transferability of tag SNPs in genetic association studies in multiple populations
- 2006
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 38:11, s. 1298-1303
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Tidskriftsartikel (refereegranskat)abstract
- A general question for linkage disequilibrium-based association studies is how power to detect an association is compromised when tag SNPs are chosen from data in one population sample and then deployed in another sample. Specifically, it is important to know how well tags picked from the HapMap DNA samples capture the variation in other samples. To address this, we collected dense data uniformly across the four HapMap population samples and eleven other population samples. We picked tag SNPs using genotype data we collected in the HapMap samples and then evaluated the effective coverage of these tags in comparison to the entire set of common variants observed in the other samples. We simulated case-control association studies in the non-HapMap samples under a disease model of modest risk, and we observed little loss in power. These results demonstrate that the HapMap DNA samples can be used to select tags for genome-wide association studies in many samples around the world.
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| 42. |
- Durakiewicz, T., et al.
(författare)
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Observation of a kink in the dispersion of f-electrons
- 2008
-
Ingår i: Europhysics letters. - : IOP Publishing. - 0295-5075 .- 1286-4854. ; 84:3, s. 37003-
-
Tidskriftsartikel (refereegranskat)abstract
- Strong interactions in correlated electron systems may result in the formation of heavy quasiparticles that exhibit kinks in their dispersion relation. Spectral weight is incoherently shifted away from the Fermi energy, but Luttinger's theorem requires the Fermi volume to remain constant. Our angle-resolved photoemission study of USb2 reveals a kink in a noncrossing 5f band, representing the first experimental observation of a kink structure in f-electron systems. The kink energy scale of 21 meV and the ultra-small peak width of 3 meV are observed. We propose the novel mechanism of renormalization of a point-like Fermi surface, and that Luttinger's theorem remains applicable.
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| 43. |
- Figaji, Anthony A., et al.
(författare)
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Transcranial Doppler pulsatility index is not a reliable indicator of intracranial pressure in children with severe traumatic brain injury
- 2009
-
Ingår i: Surgical Neurology. - : Elsevier BV. - 0090-3019. ; 72:4, s. 389-394
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The TCD-derived PI has been associated with ICP in adult studies but has not been well investigated in children. We examined the relationship between PI and ICP and CPP in children with severe TBI. Methods: Data were prospectively collected from consecutive TCD studies in children with severe TBI undergoing ICP monitoring. Ipsilateral ICP and CPP values were examined with Spearman correlation coefficient (mean values and raw observations), with a GEE, and as binary values (1 and 20 mm Hg, respectively). Results: Thirty-four children underwent 275 TCD studies. There was a weak relationship between mean values of ICP and PI (P = .04, r = 0.36), but not when raw observations (P = .54) or GEE (P = .23) were used. Pulsatility index was 0.76 when ICP was lower than 20 mm Hg and 0.86 when ICP was 20 mm Hg or higher. When PI was 1 or higher, ICP was lower than 20 mm Hg in 62.5% (25 of 40 studies), and when ICP was 20 mm Hg or higher, PI was lower than 1 in 75% (46 of 61 studies). The sensitivity and specificity of a PI threshold of 1 for examining the ICP threshold of 20 mm Hg were 25% and 88%, respectively. The relationship between CPP and PI was stronger (P = .001, r -0.41), but there were too few observations below 50 mm Hg to examine PI at this threshold. Conclusion: The absolute value of the PI is not a reliable noninvasive indicator of ICP in children with severe TBI. Further study is required to examine the relationship between PI and a CPP threshold of 50 mm Hg. (C) 2009 Elsevier Inc. All rights reserved.
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| 44. |
- Garcia-Closas, Montserrat, et al.
(författare)
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Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics
- 2008
-
Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 4:4, s. e1000054-
-
Tidskriftsartikel (refereegranskat)abstract
- A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
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| 45. |
- Goodwin, Graham C., et al.
(författare)
-
Good, Bad and Optimal Experiments for Identification
- 2006
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Ingår i: Forever Ljung in System Identification - Workshop on the occasion of Lennart Ljung’s 60th birthday. - Lund, Sweden : Studentlitteratur. - 9144020511
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 46. |
- Graham, C. R., et al.
(författare)
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Holographic formula for Q-curvature
- 2007
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Ingår i: Advances in Mathematics. - : Elsevier BV. - 0001-8708 .- 1090-2082. ; 216:2, s. 841-853
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Tidskriftsartikel (refereegranskat)
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| 47. |
- Graham, T. E., et al.
(författare)
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Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects
- 2006
-
Ingår i: N Engl J Med. - 1533-4406. ; 354:24, s. 2552-63
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Insulin resistance has a causal role in type 2 diabetes. Serum levels of retinol-binding protein 4 (RBP4), a protein secreted by adipocytes, are increased in insulin-resistant states. Experiments in mice suggest that elevated RBP4 levels cause insulin resistance. We sought to determine whether serum RBP4 levels correlate with insulin resistance and change after an intervention that improves insulin sensitivity. We also determined whether elevated serum RBP4 levels are associated with reduced expression of glucose transporter 4 (GLUT4) in adipocytes, an early pathological feature of insulin resistance. METHODS: We measured serum RBP4, insulin resistance, and components of the metabolic syndrome in three groups of subjects. Measurements were repeated after exercise training in one group. GLUT4 protein was measured in isolated adipocytes. RESULTS: Serum RBP4 levels correlated with the magnitude of insulin resistance in subjects with obesity, impaired glucose tolerance, or type 2 diabetes and in nonobese, nondiabetic subjects with a strong family history of type 2 diabetes. Elevated serum RBP4 was associated with components of the metabolic syndrome, including increased body-mass index, waist-to-hip ratio, serum triglyceride levels, and systolic blood pressure and decreased high-density lipoprotein cholesterol levels. Exercise training was associated with a reduction in serum RBP4 levels only in subjects in whom insulin resistance improved. Adipocyte GLUT4 protein and serum RBP4 levels were inversely correlated. CONCLUSIONS: RBP4 is an adipocyte-secreted molecule that is elevated in the serum before the development of frank diabetes and appears to identify insulin resistance and associated cardiovascular risk factors in subjects with varied clinical presentations. These findings provide a rationale for antidiabetic therapies aimed at lowering serum RBP4 levels.
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| 48. |
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| 49. |
- Hering, Bernhard J., et al.
(författare)
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Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates
- 2006
-
Ingår i: Nature Medicine. - : Nature Publishing Group. - 1078-8956 .- 1546-170X. ; 12:3, s. 301-303
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Tidskriftsartikel (refereegranskat)abstract
- Cell-based diabetes therapy requires an abundant cell source. Here, we report reversal of diabetes for more than 100 d in cynomolgus macaques after intraportal transplantation of cultured islets from genetically unmodified pigs without Gal-specific antibody manipulation. Immunotherapy with CD25-specific and CD154-specific monoclonal antibodies, FTY720 (or tacrolimus), everolimus and leflunomide suppressed indirect activation of T cells, elicitation of non-Gal pig-specific IgG antibody, intragraft expression of proinflammatory cytokines and invasion of infiltrating mononuclear cells into islets.
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| 50. |
- Hom, Geoffrey, et al.
(författare)
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Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX.
- 2008
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 358:9, s. 900-909
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease in which the risk of disease is influenced by complex genetic and environmental contributions. Alleles of HLA-DRB1, IRF5, and STAT4are established susceptibility genes; there is strong evidence for the existence of additional risk loci.METHODS: We genotyped more than 500,000 single-nucleotide polymorphisms (SNPs) in DNA samples from 1311 case subjects with SLE and 1783 control subjects; all subjects were North Americans of European descent. Genotypes from 1557 additional control subjects were obtained from public data repositories. We measured the association between the SNPs and SLE after applying strict quality-control filters to reduce technical artifacts and to correct for the presence of population stratification. Replication of the top loci was performed in 793 case subjects and 857 control subjects from Sweden.RESULTS: Genetic variation in the region upstream from the transcription initiation site of the gene encoding B lymphoid tyrosine kinase (BLK) and C8orf13 (chromosome 8p23.1) was associated with disease risk in both the U.S. and Swedish case–control series (rs13277113; odds ratio, 1.39; P=1×10−10) and also with altered levels of messenger RNA in B-cell lines. In addition, variants on chromosome 16p11.22, near the genes encoding integrin alpha M (ITGAM, or CD11b) and integrin alpha X (ITGAX), were associated with SLE in the combined sample (rs11574637; odds ratio, 1.33; P=3×10−11).
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