| 11. |
- Hin, Harold, et al.
(författare)
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Clinical relevance of low serum vitamin B12 concentrations in older people : the Banbury B12 study
- 2006
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Ingår i: Age and Ageing. - London : Oxford University Press. - 0002-0729 .- 1468-2834. ; 35:4, s. 416-422
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Tidskriftsartikel (refereegranskat)abstract
- Background: low vitamin B12 concentrations are common in older people, but the clinical relevance of biochemical evidence of vitamin B12 deficiency in the absence of anaemia is uncertain. Objective: to examine associations of cognitive impairment, depression and neuropathy with blood measurements of vitamin B12 and folate status in older people. Design: cross-sectional study in general practice in Banbury, England. Participants: a total of 1,000 individuals aged 75 years or older living in the community. Results: low vitamin B12 concentrations were identified in 13% of older people and were associated with memory impairment and depression. After adjustment for age, sex and smoking, individuals with vitamin B12 or holotranscobalamin (holoTC) in the bottom compared with top quartiles had a 2-fold risk (OR = 2.17; 95% CI 1.11-4.27) and a 3-fold risk (OR = 3.02; 95% CI 1.31-6.98) of cognitive impairment, respectively. Low vitamin B12 status was also associated with missing ankle tendon jerks but not with depression. Treatment with vitamin B12 for 3 months corrected the biochemical abnormalities but had no effect on any of the clinical measurements. Conclusions: low vitamin B12 concentrations are associated with cognitive impairment and missing ankle tendon jerks in older people in the absence of anaemia. Large-scale trials of vitamin B12 supplementation are required to assess the clinical significance of these associations.
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| 12. |
- Hirani, Bhavna, et al.
(författare)
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Cyclometallated iridium and platinum complexes with noninnocent ligands
- 2007
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 1520-510X .- 0020-1669. ; 46:10, s. 3865-3875
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Tidskriftsartikel (refereegranskat)abstract
- The electronic properties of the cyclometalated ((CN)-N-and) complexes of iridium and platinum metals with a catechol ligand have been studied experimentally and computationally. The synthesis and characterization of (p-tolylpyridine)Ir(3,5-di-tert-butylcatechol) (abbreviated Ir-sq) and (2,4-diflorophenylpyridine)Pt(3,5-di-tert-butylcatechol) (abbreviated Pt-sq) are reported along with their structural, spectral, and electrochemical properties. Reaction of the 3,5-di-tert-butylcatechol (DTBCat) ligand with the prepared cyclometalated metal complex was carried out in air in the presence of a base. The resulting complexes are air stable and are paramagnetic with the unpaired electron residing mainly on the catechol ligand. The bond lengths obtained from X-ray structure analysis and the theoretical results suggest the semiquinone form of the catechol ligand. Low-energy, intense (similar to 10(3) M-1 cm(-1)) transitions are observed in the visible to near-infrared region (600-700 nm) of the absorption spectra of the metal complexes. Electrochemically, the complexes exhibit a reversible reduction of the semiquinone form to the catechol form of the ligand and an irreversible oxidation to the unstable quinone form of the ligand. The noninnocent catechol ligand plays a significant role in the electronic properties of the metal complexes. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations on the two open-shell molecules provide the ground-state and excited-state energies of the molecular orbitals involved in the observed low-energy transitions. The spin density in the two complexes resides mainly on the catechol ligand. The intense transition arises from excitation of the beta electron from a HOMO-n (n = 1 or 2 here) to the LUMO, rather than from the excitation of the unpaired alpha electron.
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| 13. |
- Hsiao, Ya-Wen, et al.
(författare)
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EXAFS structure refinement supplemented by computational chemistry
- 2006
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Ingår i: Physical Review B (Condensed Matter and Materials Physics). - 1098-0121. ; 74:21
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Tidskriftsartikel (refereegranskat)abstract
- We present a method that combines structure determination using extended x-ray absorption fine structure (EXAFS) measurements and computational chemistry (CC) calculations, EXAFS/CC. Using such an approach, it is possible to obtain a full structure of model complexes or protein metal active sites, although the EXAFS data primarily give radial distance information about the metal ion's nearest neighbors. In essence, CC provides a formalism within which chemical knowledge can be introduced to EXAFS modeling. In this sense, the method is analogous to the use of molecular mechanics in standard crystallographic or NMR structure refinement. In addition, the method provides structures that are a compromise between EXAFS data and the CC calculations. Therefore, they can be used directly to obtain energies or study reaction mechanisms. The method is implemented for both density functional theory and molecular mechanics calculations. It is applied to five Ni(II) (both low- and high-spin) and Cu(I/II) complexes with known crystal structures and it is shown to perform well. We also show that the method can be successfully combined with the calculation of ab initio Debye-Waller factors for all paths using the equation-of-motion method and force constants obtained from the CC calculations.
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| 14. |
- Joura, Elmar A., et al.
(författare)
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HPV antibody levels and clinical efficacy following administration of a prophylactic quadrivalent HPV vaccine
- 2008
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 26:52, s. 6844-6851
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Tidskriftsartikel (refereegranskat)abstract
- The efficacy of the quadrivalent Human Papillomavirus (HPV) vaccine is thought to be mediated by humoral immunity. We evaluated the correlation between quadrivalent HPV vaccine-induced serum anti-HPV responses and efficacy. 17,622 women were vaccinated at day 1, and months 2 and 6. At day I and at 6-12 months intervals for up to 48 months, subjects underwent Papanicolaou and genital HPV testing. No immune correlate of protection could be found due to low number of cases. Although 40% of vaccine subjects were anti-HPV 18 seronegative at end-of-study, efficacy against HPV 18-related disease remained high (98.4%; 95% CI: 90.5-100.0) despite high attack rates in the placebo group. These results suggest vaccine-induced protection via immune memory, or lower than detectable HPV 18 antibody titers. (C) 2008 Elsevier Ltd. All rights reserved.
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| 15. |
- Kathiresan, Sekar, et al.
(författare)
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Common variants at 30 loci contribute to polygenic dyslipidemia
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 56-65
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Tidskriftsartikel (refereegranskat)abstract
- Blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels are risk factors for cardiovascular disease. To dissect the polygenic basis of these traits, we conducted genome-wide association screens in 19,840 individuals and replication in up to 20,623 individuals. We identified 30 distinct loci associated with lipoprotein concentrations (each with P < 5 x 10(-8)), including 11 loci that reached genome-wide significance for the first time. The 11 newly defined loci include common variants associated with LDL cholesterol near ABCG8, MAFB, HNF1A and TIMD4; with HDL cholesterol near ANGPTL4, FADS1-FADS2-FADS3, HNF4A, LCAT, PLTP and TTC39B; and with triglycerides near AMAC1L2, FADS1-FADS2-FADS3 and PLTP. The proportion of individuals exceeding clinical cut points for high LDL cholesterol, low HDL cholesterol and high triglycerides varied according to an allelic dosage score (P < 10(-15) for each trend). These results suggest that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia.
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| 16. |
- Leonard, Jennifer A, et al.
(författare)
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A rapid loss of stripes : the evolutionary history of the extinct quagga.
- 2005
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Ingår i: Biol Lett. - 1744-9561. ; 1:3, s. 291-5
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Tidskriftsartikel (refereegranskat)abstract
- Twenty years ago, the field of ancient DNA was launched with the publication of two short mitochondrial (mt) DNA sequences from a single quagga (Equus quagga) museum skin, an extinct South African equid (Higuchi et al. 1984 Nature312, 282-284). This was the first extinct species from which genetic information was retrieved. The DNA sequences of the quagga showed that it was more closely related to zebras than to horses. However, quagga evolutionary history is far from clear. We have isolated DNA from eight quaggas and a plains zebra (subspecies or phenotype Equus burchelli burchelli). We show that the quagga displayed little genetic diversity and very recently diverged from the plains zebra, probably during the penultimate glacial maximum. This emphasizes the importance of Pleistocene climate changes for phylogeographic patterns in African as well as Holarctic fauna.
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| 17. |
- Lorenz, Henning, 1972-
(författare)
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Eurasian Arctic Tectonics: Geology of Severnaya Zemlya (North Kara Terrane) and Relationships to the Timanide Margin of Baltica
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The North Kara Terrane (NKT), with Severnaya Zemlya as its main outcrop area, constitutes the Palaeozoic and older rocks of the northern part of the Kara Shelf. Potential field data suggest a continuation into the eastern Barents Shelf. Several lines of evidence imply that the NKT was a part of Baltica at least during the latter part of the Neoproterozoic, and probably was influenced by Timanian orogeny.The Timanide type area is characterised by metaturbidites from the pre-Timanian passive margin of the East European Craton (EEC). Regional amphibolite facies metamorphism, as exposed on Kanin Peninsula, was probably followed by near-isothermal decompression. It is inferred that these conditions were reached by depression beneath the accreted outboard terranes. Subsequently, the metaturbidites were thrust into their present position onto the EEC’s pericratonic unmetamorphosed shelf sediments. The thrusting was accompanied by rapid exhumation. About 560 Ma late-orogenic granites intrude the Timanian accreted terranes.On Severnaya Zemlya, Neoproterozoic turbidites, containing ca. 560 Ma zircons, are overlain by shelf deposits, which dominate the Palaeozoic until the end of the Silurian. The succession is interrupted by the regional Kan’on (canyon) River Unconformity and probably by a late Neoproterozoic unconformity. New U-Th-Pb ion-microprobe isotope-ages on volcanics and faunal evidence imply that the Kan'on River Unconformity developed in a short time span around the Cambrian-Ordovician boundary. Other isotope-ages demonstrate that intense igneous activity, which has been inferred to be related to rifting within the NKT, extended into the Arenig and was contemporaneous with the development of Baltica’s northeastern passive margin. Zircon xenocrysts (ca. 540 - 580 Ma) in these igneous rocks indicate a Timanian component in the crust below the Severnaya Zemlya Archipelago. In the latest Silurian, Old Red Sandstone facies sedimentation began with the migration of an inferred Caledonian foreland basin into the area of Severnaya Zemlya. The Caledonian deformation front overrode the area in the latest Devonian or earliest Carboniferous.The inferred late Caledonian deformation terminated, according to biostratigraphy and new isotope-ages from Bol'shevik Island granites, before the end of the Visean (ca. 345 Ma). Thus, the Uralian collision between the NKT and Siberia (ca. 300 Ma) apparently did not affect the Severnaya Zemlya Archipelago.
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| 18. |
- McGrath, Patrick J., et al.
(författare)
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Core outcome domains and measures for pediatric acute and chronic/recurrent pain clinical trials : PedIMMPACT recommendations
- 2008
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Ingår i: Journal of Pain. - : Elsevier BV. - 1526-5900 .- 1528-8447. ; 9:9, s. 771-83
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Tidskriftsartikel (refereegranskat)abstract
- Under the auspices of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), 26 professionals from academia, governmental agencies, and the pharmaceutical industry participated in a 2-stage Delphi poll and a consensus meeting that identified core outcome domains and measures that should be considered in clinical trials of treatments for acute and chronic pain in children and adolescents. Consensus was refined by consultation with the international pediatric pain community through announcement of our recommendations on the Pediatric Pain List and inviting and incorporating comments from external sources. There was consensus that investigators conducting pediatric acute pain clinical trials should consider assessing outcomes in pain intensity; global judgment of satisfaction with treatment; symptoms and adverse events; physical recovery; emotional response; and economic factors. There was also agreement that investigators conducting pediatric clinical trials in chronic and recurrent pain should consider assessing outcomes in pain intensity; physical functioning; emotional functioning; role functioning; symptoms and adverse events; global judgment of satisfaction with treatment; sleep; and economic factors. Specific measures or measurement strategies were recommended for different age groups for each domain. PERSPECTIVE: Based on systematic review and consensus of experts, core domains and measures for clinical trials to treat pain in children and adolescents were defined. This will assist in comparison and pooling of data and promote evidence-based treatment, encourage complete reporting of outcomes, simplify the review of proposals and manuscripts, and facilitate clinicians making informed decisions regarding treatment.
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| 19. |
- Menzies, Scott W, et al.
(författare)
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Dermoscopic evaluation of amelanotic and hypomelanotic melanoma.
- 2008
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Ingår i: Archives of dermatology. - : American Medical Association (AMA). - 1538-3652 .- 0003-987X. ; 144:9, s. 1120-7
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Tidskriftsartikel (refereegranskat)abstract
- To determine the predictive dermoscopic features of amelanotic and hypomelanotic melanoma.
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| 20. |
- Mikkelsen, Tarjei, et al.
(författare)
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Initial sequence of the chimpanzee genome and comparison with the human genome
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 437:7055, s. 69-87
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Tidskriftsartikel (refereegranskat)abstract
- Here we present a draft genome sequence of the common chimpanzee (Pan troglodytes). Through comparison with the human genome, we have generated a largely complete catalogue of the genetic differences that have accumulated since the human and chimpanzee species diverged from our common ancestor, constituting approximately thirty-five million single-nucleotide changes, five million insertion/deletion events, and various chromosomal rearrangements. We use this catalogue to explore the magnitude and regional variation of mutational forces shaping these two genomes, and the strength of positive and negative selection acting on their genes. In particular, we find that the patterns of evolution in human and chimpanzee protein-coding genes are highly correlated and dominated by the fixation of neutral and slightly deleterious alleles. We also use the chimpanzee genome as an outgroup to investigate human population genetics and identify signatures of selective sweeps in recent human evolution.
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