| 1. |
- Djoussé, L, et al.
(author)
-
Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease.
- 2003
-
In: American Journal of Medical Genetics. Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 119A:3, s. 279-82
-
Journal article (peer-reviewed)abstract
- Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. Past studies have shown that the size of expanded CAG repeat is inversely associated with age at onset (AO) of HD. It is not known whether the normal Huntington allele size influences the relation between the expanded repeat and AO of HD. Data collected from two independent cohorts were used to test the hypothesis that the unexpanded CAG repeat interacts with the expanded CAG repeat to influence AO of HD. In the New England Huntington Disease Center Without Walls (NEHD) cohort of 221 HD affected persons and in the HD-MAPS cohort of 533 HD affected persons, we found evidence supporting an interaction between the expanded and unexpanded CAG repeat sizes which influences AO of HD (P = 0.08 and 0.07, respectively). The association was statistically significant when both cohorts were combined (P = 0.012). The estimated heritability of the AO residual was 0.56 after adjustment for normal and expanded repeats and their interaction. An analysis of tertiles of repeats sizes revealed that the effect of the normal allele is seen among persons with large HD repeat sizes (47-83). These findings suggest that an increase in the size of the normal repeat may mitigate the expression of the disease among HD affected persons with large expanded CAG repeats.
|
|
| 2. |
- Claesson, Åsa, et al.
(author)
-
Novel Er:Yb phosphate glass fiber laser pumped by a 946 nm Nd:YAG laser
- 2001
-
In: Technical Digest. Summaries of papers presented at the Conference on Lasers and Electro-Optics. Postconference Technical Digest (IEEE Cat. No.01CH37170).
-
Conference paper (peer-reviewed)abstract
- Summary form only given. Recently, Kigre introduced a new family of rare-earth doped fibers (Wu et al, 2000), based on phosphate laser glass. Due to their phonon energy, erbium-doped phosphate glasses exhibit lower up-conversion losses than silica glass. This, and the high solubility for rare-earth ions, makes phosphate glasses promising candidates for high-gain erbium devices. High doping concentrations enable short devices, and fiber lasers or amplifiers with only a few centimeters of active fiber can be realized. This is to be compared to standard EDFAs that normally contain tens of meters of erbium-doped silica fibers. We have demonstrated a short fiber-laser based on a single-mode Er:Yb codoped phosphate fiber, pumped by a 946 nm Nd:YAG laser.
|
|
| 3. |
- Jenkins, S. R., et al.
(author)
-
Population dynamics of the intertidal barnacle Semibalanus balanoides at three European locations: spatial scales of variability
- 2001
-
In: Marine Ecology Progress Series. - : Inter-Research Science Center. - 0171-8630 .- 1616-1599. ; 217, s. 207-217
-
Journal article (peer-reviewed)abstract
- Spatial variability in the population dynamics of the intertidal acorn barnacle Semibalanus balanoides was investigated using a hierarchical sampling programme. Variability in a number of population parameters (size distribution, density, % cover, absolute growth and instantaneous mortality) was determined separately for new recruits and adults over 3 spatial scales. Three locations, SW Ireland, the Isle of Man and the west coast of Sweden, which cover a large part of the European range of this species, were selected to investigate variability over a large spatial scale (100s of kilometres). Two smaller scales, shore (1000s of metres) and site (10s of metres) nested within each location were also used. In addition, temporal variation over two 6 mo periods was also examined in the Isle of Man and Ireland. Most variability for all population parameters occurred over the largest spatial scale (location). This was a direct result of differences between Sweden and the other 2 locations, the Isle of Man and Ireland, which showed highly similar levels of all population parameters. The population of S, balanoides at the Swedish location was characterised by high growth rates, large size, high levels of mortality and a large turnover of bare space. At the spatial scale 'shore', only 1 population parameter, the growth rate of recruits, showed variability. At the smallest scale of 'site', all parameters showed significant variability except growth rate of adults. Calculation of variance components showed that differences between replicates (spatial scale: <0.5 m) accounted for little of the overall variability, in general less than the scales of site and shore. Examination of temporal variability over two 6 mo periods revealed no difference between time periods and no significant interaction between temporal and spatial scales, Thus, there was consistency of spatial variability over time. The potential causes of variability in population parameters of S, balanoides at different spatial scales and the implications for future studies are discussed.
|
|
| 4. |
- Jenkins, S. R., et al.
(author)
-
Spatial and temporal variation in settlement and recruitment of the intertidal barnacle Semibalanus balanoides (L.) (Crustacea : Cirripedia) over a European scale
- 2000
-
In: Journal of Experimental Marine Biology and Ecology. - 0022-0981. ; 243:2, s. 209-225
-
Journal article (peer-reviewed)abstract
- Variation in the level of settlement and recruitment in the intertidal barnacle Semibalanus balanoides was studied using a hierarchical sampling programme. The effect of three spatial scales, 10s of metres (sites), 1000s of metres (shores) and 100s of kilometres (locations), was determined. The largest spatial scale represented the distance between four widely separated locations, Sweden, the Isle of Man, SW Ireland and SW England, covering a. large part of the range of S. balanoides in Europe. Temporal variation was determined by comparison between two years, 1997 and 1998. The settlement period of S. balanoides varied in length and timing, being earlier and shorter at the most northerly location, Sweden. The duration of settlement showed little difference among shores within locations, but the pattern of settlement did vary. Estimates of total settlement throughout the settlement period and of recruitment at the end of this period both showed substantial variation among locations which was dependent on the year of study. There was little consistency in the ranking of locations between the two years. Recruitment showed significant variation I the lower spatial scales of shore and site. In addition, examination of variance components showed a high degree of variation between replicates within sites in 1997. There was a significant relationship between settlement and recruitment at three of the four locations. Across all locations variation in settlement explained between 29 and 99% of variation in recruitment. However, locations showed distinct differences in the level of post-settlement survival. (C) 2000 Elsevier Science B.V. All rights reserved.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Djoussé, Luc, et al.
(author)
-
Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16.
- 2004
-
In: Neurogenetics. - : Springer Science and Business Media LLC. - 1364-6745 .- 1364-6753. ; 5:2, s. 109-14
-
Journal article (peer-reviewed)abstract
- Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. A recent genome scan for genetic modifiers of age at onset of motor symptoms (AO) in HD suggests that one modifier may reside in the region close to the HD gene itself. We used data from 535 HD participants of the New England Huntington cohort and the HD MAPS cohort to assess whether AO was influenced by any of the three markers in the 4p16 region: MSX1 (Drosophila homeo box homologue 1, formerly known as homeo box 7, HOX7), Delta2642 (within the HD coding sequence), and BJ56 ( D4S127). Suggestive evidence for an association was seen between MSX1 alleles and AO, after adjustment for normal CAG repeat, expanded repeat, and their product term (model P value 0.079). Of the variance of AO that was not accounted for by HD and normal CAG repeats, 0.8% could be attributed to the MSX1 genotype. Individuals with MSX1 genotype 3/3 tended to have younger AO. No association was found between Delta2642 (P=0.44) and BJ56 (P=0.73) and AO. This study supports previous studies suggesting that there may be a significant genetic modifier for AO in HD in the 4p16 region. Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the MSX1 marker.
|
|
| 8. |
- Li, Jian-Liang, et al.
(author)
-
A genome scan for modifiers of age at onset in Huntington disease : The HD MAPS study.
- 2003
-
In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 73:3, s. 682-7
-
Journal article (peer-reviewed)abstract
- Huntington disease (HD) is caused by the expansion of a CAG repeat within the coding region of a novel gene on 4p16.3. Although the variation in age at onset is partly explained by the size of the expanded repeat, the unexplained variation in age at onset is strongly heritable (h2=0.56), which suggests that other genes modify the age at onset of HD. To identify these modifier loci, we performed a 10-cM density genomewide scan in 629 affected sibling pairs (295 pedigrees and 695 individuals), using ages at onset adjusted for the expanded and normal CAG repeat sizes. Because all those studied were HD affected, estimates of allele sharing identical by descent at and around the HD locus were adjusted by a positionally weighted method to correct for the increased allele sharing at 4p. Suggestive evidence for linkage was found at 4p16 (LOD=1.93), 6p21-23 (LOD=2.29), and 6q24-26 (LOD=2.28), which may be useful for investigation of genes that modify age at onset of HD.
|
|
| 9. |
- Piepoli, MF, et al.
(author)
-
Exercise training meta-analysis of trials in patients with chronic heart failure (ExTraMATCH)
- 2004
-
In: BMJ: British Medical Journal. - 1756-1833. ; 328:7433, s. 189-192
-
Journal article (peer-reviewed)abstract
- Objective To determine the effect of exercise training on survival in patients with heart failure due to left ventricular systolic dysfunction. Design Collaborative meta-analysis. Inclusion criteria Randomised parallel group controlled trials of exercise training, for at least eight weeks with individual patient data on survival for at least three months. Studies reviewed Nine datasets, totalling 801 patients: 395 received exercise training and 406 were controls. Main outcome measure Death from all causes. Results During a mean (SD) follow up of 705 (729) days there were 88 (22%) deaths in the exercise arm and 105 (26%) in the control arm. Exercise training significantly reduced mortality (hazard ratio 0.65, 95% confidence interval, 0.46 to 0.92; log rank chi(2) = 5.9; P = 0.015). The secondary end point of death or admission to hospital was also reduced (0.72, 0.56 to 0.93; log rank chi(2) = 6.4; P = 0.011). No statistically significant subgroup specific treatment effect was observed. Conclusion Meta-analysis of randomised trials to date gives no evidence that properly supervised medical training programmes for patients with heart failure might be dangerous, and indeed there is clear evidence of an overall reduction in mortality. Further research should focus on optimising exercise programmes and identifying appropriate patient groups to target.
|
|
| 10. |
- Shubayev, V. I., et al.
(author)
-
Titanium implants induce expression of matrix metalloproteinases in bone during osseointegration
- 2004
-
In: J Rehabil Res Dev. - 0748-7711. ; 41:6A, s. 757-66
-
Journal article (peer-reviewed)abstract
- Implanted pure titanium fixtures are able to completely integrate with bone, in part because of the formation of a strong extracellular matrix (ECM) bond at the titanium-bone interface. In this study, we used a rodent femur model of intramedullary osseointegration to analyze the changes in immunoreactivity of ECM-controlling matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinase-3 (TIMP-3), and tumor necrosis factor alpha (TNF-alpha) during osseointegration. We observed dramatic increases in MMP-2, MMP-9, MMP-7, TIMP-3, and TNF-alpha in osteocytes, osteoclasts, haversian canals, and the interface matrix in bone ipsilateral to the titanium implant. An increase in TIMP-3, MMP-9, and MMP-7 in hypertrophied chondrocytes and the vascular component of the epiphysial growth plate was also observed in experimental bone. These findings were not seen in contralateral or sham-operated bone, where the titanium fixtures were threaded into the femur and immediately removed. Our data link titanium-induced bone remodeling to changes in expression and distribution of MMPs.
|
|
