| 11. |
- Dreilich, M., et al.
(författare)
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High-risk human papilloma virus (HPV) and survival in patients with esophageal carcinoma : a pilot study
- 2006
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 6, s. 94-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Human papilloma virus (HPV) in patients with esophageal carcinoma has previously been studied with an average detection rate of 15%, but the role of HPV in relation to survival is less clear. In cervical cancer, lung cancer and tonsil cancer HPV viral load is a predictive factor for survival and outcome of treatment. The primary aim was to study the spectrum of high-risk HPV types in esophageal tumors. Secondary, as a pilot study we investigated the association between HPV status and the survival rates. METHODS: We compared both the presence and the viral load of high-risk HPV types 16, 18, 31, 33, 39, 45, 52, 58, and 67 in relation to clinical data from patients with esophageal carcinoma. Survival data and tumor samples were retrieved from 100 patients receiving treatment at the Department of Oncology, Uppsala Hospital, Uppsala, Sweden. The tumor samples were investigated for HPV viral load using real-time PCR. RESULTS: HPV 16 was detected in 16% of the patients; no other HPV type was detected. HPV 16 infection had no significant effect on survival (p = 0.72). Also, HPV 16 did not improve survival after treatment (radiotherapy or chemotherapy). CONCLUSION: Only HPV 16 was detected among the patients. HPV 16 in esophageal carcinoma patients did not influence survival or improve therapy response. However, given the size of the study there is a need to examine a larger cohort in order to understand in more detail the effect of high risk HPV types in esophageal carcinoma.
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| 12. |
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| 13. |
- Malmström, Per-Uno, et al.
(författare)
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AdCD40L immunogene therapy for bladder carcinoma--the first phase I/IIa trial
- 2010
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Ingår i: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 16:12, s. 3279-3287
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Immunotherapy with Bacillus Calmette-Guerin (BCG) instillation is recommended for high-risk, non-muscle invasive bladder cancer. Bacillus Calmette-Guerin is not effective in advanced tumors, and better alternatives are warranted. Immunostimulating gene therapy with adenoviral vectors expressing CD40 ligand (AdCD40L) has shown efficacy in tumor models. CD40 ligand stimulates systemic immunity and may be effective in local and invasive human disease.EXPERIMENTAL DESIGN: Patients with invasive bladder cancer scheduled for cystectomy or patients with T(a) tumors were enrolled in a phase I/IIa trial. Patients were treated with three cycles of intrabladder Clorpactin WCS-90 prewash, followed by AdCD40L instillation 1 week apart. Safety, gene transfer, immune effects, and antitumor responses were monitored.RESULTS: All eight recruited patients were treated as scheduled, and therapy was well tolerated. The main adverse effect was transient local pain during prewash. Postoperatively, urinary tract infections and one case of late septicemia with elevated potassium were reported. No adverse events were ascribed to vector therapy. Gene transfer was detected in biopsies, and bladders were heavily infiltrated with T cells. The effector marker IFN-gamma increased in biopsies, whereas levels of circulating T regulatory cells were reduced. Histologic evaluation indicated that AdCD40L therapy reduced the load of malignant cells.CONCLUSIONS: To our knowledge, this is the first report on immunogene therapy in bladder cancer and the first using AdCD40L in vivo. Local AdCD40L gene therapy was safe, boosted immune activation, and should be further evaluated as a single or an adjuvant therapy for urothelial malignancies.
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| 14. |
- Perry, J. J., et al.
(författare)
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Hysteresis in broad-line regions of active galactic nuclei
- 1994
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Ingår i: Monthly notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 271:3, s. 561-572572
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Tidskriftsartikel (refereegranskat)abstract
- The response of emission-line luminosities to changes in the observed continuum in active galaxies is commonly used for reverberation mapping (RM) of the emission-line region. The method assumes regularity in the continuum source and linearity in the line response to the continuum, and that the phase-space distribution of the line-emitting gas is constant in time. The wealth of information contained in the detailed line profiles is under-utilized in current methods of RM. The authors propose a new method to improve this situation. The authors define normalized profiles and show how their use enables one to explore details of the emission-line region that have hitherto eluded detection. Furthermore, the authors investigate the possibility of testing the validity of the assumptions as used in the standard application of RM. The authors present new methods, the hysteresis test and the Q concept - also based on the line profiles - to test the basic assumptions of RM. The test fails when applied to NGC 4151. The authors show that there is good evidence either for significantly extended and complex emission-line regions, or for changes in the mass distribution over time-scales of months or more - i.e. on time-scales comparable to the length of typical observing campaigns
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| 15. |
- Ronnback, J., et al.
(författare)
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Host galaxies of intermediate redshift radio-loud and radio-quiet quasars
- 1996
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Ingår i: Monthly notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 283:1, s. 282-296296
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Tidskriftsartikel (refereegranskat)abstract
- In a search for host galaxies associated with quasars, the authors present results from deep CCD imaging using the European Southern Observatory 3.5-m New Technology Telescope. Altogether 21 targets, 12 radio-loud and nine radio-quiet quasars, were observed in R, and additional V and Gunn i images were collected for a subgroup of these. The quasar redshifts are between 0.4 and 0.8, a range largely unexplored in previous studies. At these redshifts the R band corresponds to a rest-frame wavelength between 4600 and 3600 Aring. Thus, the authors are primarily probing the light from young stellar components of the presumed host galaxies. To separate out the light originating from the host object the authors remove the quasar contribution by scaling the point spread function (PSF). The PSF is a combination of an empirical PSF model, derived from stars lying in the same field as the quasars (used for the core of the PSF), and an analytical model for the wings of the PSF. After PSF subtraction of the QSO image the authors identify extended residual objects in 17 targets (nine in radio-loud and eight in radio-quiet quasars), of which a few are only marginal detections. These objects are large and luminous and their colours are relatively blue. Their V-R colours are consistent with a stellar population typical of late-type spirals and irregular galaxies. The blue colours could be caused by recent star formation events or by scattering of the QSO light
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| 16. |
- van Groningen, E., et al.
(författare)
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An algorithm for the relative scaling of spectra
- 1992
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 104:678, s. 700-703703
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Tidskriftsartikel (refereegranskat)abstract
- A method is described for the automatic relative scaling of spectra in which one or more lines with constant flux are present. The algorithm takes into account differences in spectral resolution, flux factors, and spectral shifts. It was developed for the relative calibration of series of optical spectra obtained in variability studies of active galactic nuclei but it also can be used for other purposes, e.g., the subtraction of an underlying stellar continuum in AGN with a template spectrum. Tests show that a high degree of accuracy is obtained, and that the method is superior to scaling the spectra by eye or measuring narrow-band fluxes
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| 17. |
- van Kuilenburg, Andre B. P., et al.
(författare)
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Glutaminase Deficiency Caused by Short Tandem Repeat Expansion in GLS
- 2019
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 380:15, s. 1433-1441
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Tidskriftsartikel (refereegranskat)abstract
- We report an inborn error of metabolism caused by an expansion of a GCA-repeat tract in the 5′ untranslated region of the gene encoding glutaminase (GLS) that was identified through detailed clinical and biochemical phenotyping, combined with whole-genome sequencing. The expansion was observed in three unrelated patients who presented with an early-onset delay in overall development, progressive ataxia, and elevated levels of glutamine. In addition to ataxia, one patient also showed cerebellar atrophy. The expansion was associated with a relative deficiency of GLS messenger RNA transcribed from the expanded allele, which probably resulted from repeat-mediated chromatin changes upstream of the GLS repeat. Our discovery underscores the importance of careful examination of regions of the genome that are typically excluded from or poorly captured by exome sequencing.
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| 18. |
- Van Loon, Anne F., et al.
(författare)
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Drought in a human-modified world : reframing drought definitions, understanding, and analysis approaches
- 2016
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Ingår i: Hydrology and Earth System Sciences. - : Copernicus GmbH. - 1027-5606 .- 1607-7938. ; 20:9, s. 3631-3650
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Tidskriftsartikel (refereegranskat)abstract
- In the current human-modified world, or Anthropocene, the state of water stores and fluxes has become dependent on human as well as natural processes. Water deficits (or droughts) are the result of a complex interaction between meteorological anomalies, land surface processes, and human inflows, outflows, and storage changes. Our current inability to adequately analyse and manage drought in many places points to gaps in our understanding and to inadequate data and tools. The Anthropocene requires a new framework for drought definitions and research. Drought definitions need to be revisited to explicitly include human processes driving and modifying soil moisture drought and hydrological drought development. We give recommendations for robust drought definitions to clarify timescales of drought and prevent confusion with related terms such as water scarcity and overexploitation. Additionally, our understanding and analysis of drought need to move from single driver to multiple drivers and from uni-directional to multi-directional. We identify research gaps and propose analysis approaches on (1) drivers, (2) modifiers, (3) impacts, (4) feedbacks, and (5) changing the baseline of drought in the Anthropocene. The most pressing research questions are related to the attribution of drought to its causes, to linking drought impacts to drought characteristics, and to societal adaptation and responses to drought. Example questions include (i) What are the dominant drivers of drought in different parts of the world? (ii) How do human modifications of drought enhance or alleviate drought severity? (iii) How do impacts of drought depend on the physical characteristics of drought vs. the vulnerability of people or the environment? (iv) To what extent are physical and human drought processes coupled, and can feedback loops be identified and altered to lessen or mitigate drought? (v) How should we adapt our drought analysis to accommodate changes in the normal situation (i.e. what are considered normal or reference conditions) over time? Answering these questions requires exploration of qualitative and quantitative data as well as mixed modelling approaches. The challenges related to drought research and management in the Anthropocene are not unique to drought, but do require urgent attention. We give recommendations drawn from the fields of flood research, ecology, water management, and water resources studies. The framework presented here provides a holistic view on drought in the Anthropocene, which will help improve management strategies for mitigating the severity and reducing the impacts of droughts in future.
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| 19. |
- Wanders, A., et al.
(författare)
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Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis : a randomized clinical trial
- 2005
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Ingår i: Arthritis Rheum. ; 52:6, s. 1756-65
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: A 2-year randomized controlled trial was performed to test the hypothesis that long-term, continuous treatment with nonsteroidal antiinflammatory drugs (NSAIDs), in comparison with NSAID treatment on demand only, influences radiographic progression in patients with ankylosing spondylitis (AS). METHODS: Patients with AS (n = 215), who had previously participated in a 6-week, randomized, double-blind clinical trial that compared celecoxib, ketoprofen, and placebo, were randomly allocated to receive either continuous treatment with NSAIDs or on-demand treatment with NSAIDs for a period of 2 years. All patients began treatment with celecoxib, at a starting dosage of 100 mg twice daily; patients could increase this dosage to 200 mg twice daily or could switch to another NSAID while maintaining the same treatment strategy. Structural changes were assessed by radiographs of the lumbar and cervical spine and scored according to the modified Stoke Ankylosing Spondylitis Spine Score by one observer who was blinded to the treatment strategy and temporal order of the radiographs. Statistical analyses included a between-group comparison of 1) radiographic progression scores (by Mann-Whitney U test), 2) time-averaged values of variables reflecting signs and symptoms of AS (by linear regression analysis), and 3) the frequency of reported site-specific adverse events (by chi-square test or Fisher's exact test, as appropriate). RESULTS: Complete sets of radiographs were available for 76 of the 111 patients in the continuous-treatment group and for 74 of the 104 patients in the on-demand group. The mean +/- SD scores for radiographic progression were 0.4 +/- 1.7 in the continuous-treatment group and 1.5 +/- 2.5 in the on-demand treatment group (P = 0.002). Parameters reflecting signs and symptoms were not statistically significantly different between groups. The between-group difference in radiographic progression did not disappear after adjusting for baseline values of radiographic damage or disease activity variables and for time-averaged values of disease activity variables, nor after input of missing data. Relevant adverse events tended to occur more frequently in the continuous-treatment group than in the on-demand group (for hypertension, 9% versus 3%; for abdominal pain, 11% versus 6%; for dyspepsia, 41% versus 38%), but the differences were not statistically significant. CONCLUSION: A strategy of continuous use of NSAIDs reduces radiographic progression in symptomatic patients with AS, without increasing toxicity substantially.
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| 20. |
- WANDERS, I
(författare)
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EVOLUTION OF THE BROAD-LINE REGION IN NGC-5548
- 1995
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Ingår i: ASTRONOMY AND ASTROPHYSICS. - : SPRINGER VERLAG. - 0004-6361. ; 296:2, s. 332-338
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this paper I show that the broad-line region (BLR) of the Seyfert-1 galaxy NGC 5548 is an evolving entity on its dynamical time scale of a few years. The total observed H beta reprocessing of the BLR decreased by about 5% per year during four consecuti
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