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Träfflista för sökning "WFRF:(Silverman J M) srt2:(2005-2009)"

Sökning: WFRF:(Silverman J M) > (2005-2009)

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1.
  • Ng, M Y M, et al. (författare)
  • Meta-analysis of 32 genome-wide linkage studies of schizophrenia
  • 2009
  • Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 14:8, s. 774-785
  • Tidskriftsartikel (refereegranskat)abstract
    • A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (P(SR)) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for 'aggregate' genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies.
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2.
  • Iacopetta, B, et al. (författare)
  • Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.
  • 2006
  • Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. - : Elsevier BV. - 0923-7534. ; 17:5, s. 842-7
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified according to functional status for transactivation. RESULTS: Inactive TP53 mutations were found in 29% of all CRCs and were more frequent in rectal (32%) than proximal colon (22%) tumours (P < 0.001). Higher frequencies of inactive TP53 mutations were also seen in advanced stage tumours (P = 0.0003) and in tumours with the poor prognostic features of vascular (P = 0.006) and lymphatic invasion (P = 0.002). Inactive TP53 mutations were associated with significantly worse outcome only in patients with Dukes' stage D tumours (RR = 1.71, 95%CI 1.25-2.33, P < 0.001). Patients with Dukes' C stage tumours appeared to gain a survival benefit from 5-fluorouracil-based chemotherapy regardless of TP53 functional status for transactivation ability. CONCLUSIONS: Mutations that inactivate the transactivational ability of TP53 are more frequent in advanced CRC and are associated with worse prognosis in this stage of disease.
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3.
  • Brand, P L P, et al. (författare)
  • Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach.
  • 2008
  • Ingår i: The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. - : European Respiratory Society (ERS). - 1399-3003. ; 32:4, s. 1096-110
  • Forskningsöversikt (refereegranskat)abstract
    • There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.
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4.
  • Szatmari, Peter, et al. (författare)
  • Mapping autism risk loci using genetic linkage and chromosomal rearrangements.
  • 2007
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 319-328
  • Tidskriftsartikel (refereegranskat)abstract
    • Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
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5.
  • Foley, R. J., et al. (författare)
  • Spectroscopy of High-Redshift Supernovae from the Essence Project : The First Four Years
  • 2009
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 137, s. 3731-3742
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results of spectroscopic observations from the ESSENCE high-redshift supernova (SN) survey during its first four years of operation. This sample includes spectra of all SNe Ia whose light curves were presented by Miknaitis et al. and used in the cosmological analyses of Davis et al. and Wood-Vasey et al. The sample represents 273 hr of spectroscopic observations with 6.5-10 m class telescopes of objects detected and selected for spectroscopy by the ESSENCE team. We present 184 spectra of 156 objects. Combining this sample with that of Matheson et al., we have a total sample of 329 spectra of 274 objects. From this, we are able to spectroscopically classify 118 Type Ia SNe. As the survey has matured, the efficiency of classifying SNe Ia has remained constant while we have observed both higher-redshift SNe Ia and SNe Ia farther from maximum brightness. Examining the subsample of SNe Ia with host-galaxy redshifts shows that redshifts derived from only the SN Ia spectra are consistent with redshifts found from host-galaxy spectra. Moreover, the phases derived from only the SN Ia spectra are consistent with those derived from light-curve fits. By comparing our spectra to local templates, we find that the rate of objects similar to the overluminous SN 1991T and the underluminous SN 1991bg in our sample are consistent with that of the local sample. We do note, however, that we detect no object spectroscopically or photometrically similar to SN 1991bg. Although systematic effects could reduce the high-redshift rate we expect based on the low-redshift surveys, it is possible that SN 1991bg-like SNe Ia are less prevalent at high redshift.
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7.
  • Ruperto, N., et al. (författare)
  • A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis
  • 2007
  • Ingår i: Arthritis Rheum. - : Wiley. - 0004-3591. ; 56:9, s. 3096-3106
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To evaluate the safety and efficacy of infliximab in the treatment of juvenile rheumatoid arthritis (JRA). METHODS: This was an international, multicenter, randomized, placebo-controlled, double-blind study. One hundred twenty-two children with persistent polyarticular JRA despite prior methotrexate (MTX) therapy were randomized to receive infliximab or placebo for 14 weeks, after which all children received infliximab through week 44. Patients received MTX plus infliximab 3 mg/kg through week 44, or MTX plus placebo for 14 weeks followed by MTX plus infliximab 6 mg/kg through week 44. RESULTS: Although a higher proportion of patients in the 3 mg/kg infliximab group than in the placebo group had achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) criteria for improvement at week 14 (63.8% and 49.2%, respectively), the between-group difference in this primary efficacy end point was not statistically significant (P = 0.12). By week 16, after the crossover from placebo to infliximab 6 mg/kg when all patients were receiving infliximab, an ACR Pedi 30 response was achieved in 73.2% of all patients. By week 52, ACR Pedi 50 and ACR Pedi 70 responses had been reached in 69.6% and 51.8%, respectively, of patients. Infliximab was generally well tolerated, but the safety profile of infliximab 3 mg/kg appeared less favorable than that of infliximab 6 mg/kg, with more frequent occurrences of serious adverse events, infusion reactions, antibodies to infliximab, and newly induced antinuclear antibodies and antibodies to double-stranded DNA observed with the 3 mg/kg dose. CONCLUSION: While infliximab at 3 mg/kg and 6 mg/kg showed durable efficacy at 1 year, achievement of the primary efficacy end point at 3 months did not differ significantly between infliximab-treated and placebo-treated patients. Safety data indicated that the 6-mg/kg dose may provide a more favorable risk/benefit profile. These results warrant further investigation in children with JRA.
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8.
  • Simon, Joshua D., et al. (författare)
  • Variable Sodium Absorption in a Low-extinction Type Ia Supernova
  • 2009
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 702, s. 1157-1170
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent observations have revealed that some Type Ia supernovae exhibit narrow, time-variable Na I D absorption features. The origin of the absorbing material is controversial, but it may suggest the presence of circumstellar gas in the progenitor system prior to the explosion, with significant implications for the nature of the supernova (SN) progenitors. We present the third detection of such variable absorption, based on six epochs of high-resolution spectroscopy of the Type Ia supernova SN 2007le from the Keck I Telescope and the Hobby-Eberly Telescope. The data span a time frame of approximately three months, from 5 days before maximum light to 90 days after maximum. We find that one component of the Na I D absorption lines strengthened significantly with time, indicating a total column density increase of ~2.5 × 1012 cm-2. The data limit the typical timescale for the variability to be more than 2 days but less than 10 days. The changes appear to be most prominent after maximum light rather than at earlier times when the ultraviolet flux from the SN peaks. As with SN 2006X, we detect no change in the Ca II H and K absorption lines over the same time period, rendering line-of-sight effects improbable and suggesting a circumstellar origin for the absorbing material. Unlike the previous two supernovae exhibiting variable absorption, SN 2007le is not highly reddened (E B - V = 0.27 mag), also pointing toward circumstellar rather than interstellar absorption. Photoionization calculations show that the data are consistent with a dense (107 cm-3) cloud or clouds of gas located ~0.1 pc (3 × 1017 cm) from the explosion. These results broadly support the single-degenerate scenario previously proposed to explain the variable absorption, with mass loss from a nondegenerate companion star responsible for providing the circumstellar gas. We also present possible evidence for narrow Hα emission associated with the SN, which will require deep imaging and spectroscopy at late times to confirm. Some of the data presented 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 NASA. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation. Based in part on observations obtained with the Hobby-Eberly Telescope, which is a joint project of the University of Texas at Austin, the Pennsylvania State University, Stanford University, Ludwig-Maximilians-Universität München, and Georg-August-Universität Göttingen.
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10.
  • Kotak, R., et al. (författare)
  • Dust and The Type II-Plateau Supernova 2004et
  • 2009
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 704:1, s. 306-323
  • Tidskriftsartikel (refereegranskat)abstract
    • We present mid-infrared (MIR) observations of the Type II-plateau supernova (SN) 2004et, obtained with the Spitzer Space Telescope between 64 and 1406 days past explosion. Late-time optical spectra are also presented. For the period 300-795 days past explosion, we argue that the spectral energy distribution (SED) of SN 2004et comprises (1) a hot component due to emission from optically thick gas, as well as free-bound radiation; (2) a warm component due to newly formed, radioactively heated dust in the ejecta; and (3) a cold component due to an IR echo from the interstellar-medium dust of the host galaxy, NGC 6946. There may also have been a small contribution to the IR SED due to free-free emission from ionized gas in the ejecta. We reveal the first-ever spectroscopic evidence for silicate dust formed in the ejecta of a supernova. This is supported by our detection of a large, but progressively declining, mass of SiO. However, we conclude that the mass of directly detected ejecta dust grew to no more than a few times 10-4 M sun. We also provide evidence that the ejecta dust formed in comoving clumps of fixed size. We argue that, after about two years past explosion, the appearance of wide, box-shaped optical line profiles was due to the impact of the ejecta on the progenitor circumstellar medium and that the subsequent formation of a cool, dense shell was responsible for a later rise in the MIR flux. This study demonstrates the rich, multifaceted ways in which a typical core-collapse supernova and its progenitor can produce and/or interact with dust grains. The work presented here adds to the growing number of studies that do not support the contention that SNe are responsible for the large mass of observed dust in high-redshift galaxies.
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