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Sökning: WFRF:(Specht L)

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  • Forner, L. E., et al. (författare)
  • Hyperbaric oxygen treatment of mandibular osteoradionecrosis: Combined data from the two randomized clinical trials DAHANCA-21 and NWHHT2009-1
  • 2022
  • Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140. ; 166, s. 137-144
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Osteoradionecrosis (ORN) of the mandible is a serious complication of head and neck radiotherapy. This study aims to investigate the effect of hyperbaric oxygen (HBO) treatment on ORN in two randomized, controlled multicentre trials. Methods and materials: Patients with ORN with indication for surgical treatment were randomised to either group 1: surgical removal of necrotic mandibular bone supplemented by 30 pre- and 10 postoperative HBO exposures at 243 kPa for 90 min each, or group 2: surgical removal of necrotic bone only. Primary outcome was healing of ORN one year after surgery evaluated by a clinically adjusted version of the Common Toxicity Criteria of Adverse Events (CTCAE) v 3.0. Secondary outcomes included xerostomia, unstimulated and stimulated whole salivation rates, trismus, dysphagia, pain, Activities of Daily Living (ADL) and quality of life according to EORTC. Data were combined from two separate trials. Ninety-seven were enrolled and 65 were eligible for the intent-to-treat analysis. The 33% drop-out was equally distributed between groups. Results: In group 1, 70% (21/30) healed compared to 51% (18/35) in group 2. HBO was associated with an increased chance of healing independent of baseline ORN grade or smoking status as well as improved xerostomia, unstimulated whole salivary flow rate, and dysphagia. Due to insufficient recruitment, none of the endpoints reached a statistically significant difference between groups. ADL data could only be obtained from 50 patients. Conclusion: Hyperbaric oxygen did not significantly improve the healing outcome of osteoradionecrosis after surgical removal of necrotic bone as compared to standard care (70% vs. 51%). This effect is not statistically significant due to the fact that the study was underpowered and is therefore prone to type II error. © 2021 The Authors
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  • Baron, J. S., et al. (författare)
  • Synthesis Centers as Critical Research Infrastructure
  • 2017
  • Ingår i: Bioscience. - : Oxford University Press (OUP). - 0006-3568 .- 1525-3244. ; 67:8, s. 750-759
  • Tidskriftsartikel (refereegranskat)abstract
    • Synthesis centers offer a unique amalgam of culture, infrastructure, leadership, and support that facilitates creative discovery on issues crucial to science and society. The combination of logistical support, postdoctoral or senior fellowships, complex data management, informatics and computing capability or expertise, and most of all, opportunity for group discussion and reflection lowers the "activation energy" necessary to promote creativity and the cross-fertilization of ideas. Synthesis centers are explicitly created and operated as community-oriented infrastructure, with scholarly directions driven by the ever-changing interests and needs of an open and inclusive scientific community. The last decade has seen a rise in the number of synthesis centers globally but also the end of core federal funding for several, challenging the sustainability of the infrastructure for this key research strategy. Here, we present the history and rationale for supporting synthesis centers, integrate insights arising from two decades of experience, and explore the challenges and opportunities for long-term sustainability.
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  • Christensen, P S, et al. (författare)
  • Environmental cadmium and lead exposure and anti-Müllerian hormone in pregnant women
  • 2016
  • Ingår i: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238. ; 61, s. 114-119
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Anti-Müllerian Hormone (AMH) has been suggested as a marker for ovarian function. Cadmium and lead have been suggested to reduce female fecundity. In this study we aimed to investigate whether environmental exposure to cadmium and lead was associated with alterations in serum-AMH.MATERIALS AND METHOD: The associations between serum-AMH and whole blood cadmium or lead were investigated by general linear models in a population-based sample of 117 pregnant women.RESULTS: The mean concentrations of blood cadmium and lead were 0.71μg/L and 17.4μg/L, respectively. The mean serum-AMH was 17.3pmol/L. No association between lead and AMH was detected. In the cadmium analysis the adjusted mean AMH level (95% CI) in the highest exposure tertile was 12.4 (6.4;23.8) compared to 5.6 (2.7;11.4) in the lowest exposure tertile (p=0.06).CONCLUSION: The study provides suggestive evidence that environmental exposure to cadmium, but not lead, may alter the level of AMH.
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  • Deans, Andrew R, et al. (författare)
  • Finding Our Way through Phenotypes.
  • 2015
  • Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.
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  • Ek, M., et al. (författare)
  • Probing Catalyst Surfaces at the Atomic-scale
  • 2023
  • Ingår i: Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada. - 1435-8115. ; 29:1, s. 1291-1291
  • Tidskriftsartikel (refereegranskat)
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  • Lastras-Martí­nez, L. F., et al. (författare)
  • Reflectance difference spectroscopy of GaAs asymmetric surface quantum wells above the fundamental gap
  • 1998
  • Ingår i: Physica status solidi. A, Applied research. - 0031-8965 .- 1521-396X. ; 170:2, s. 317-321
  • Tidskriftsartikel (refereegranskat)abstract
    • We report Reflectance Difference (RD) measurement on (001) GaAs surface quantum wells (QW) under Ultra High Vacuum (UHV) conditions from 1.7 to 5.0eV. The QW is embedded between an arsenic-rich reconstructed GaAs surface and an AlAs barrier. The samples, grown by MBE with a protective arsenic cap layer, were heated to 320 and 430°C to desorb the As layer and form c(4 x 4) and (2 x 4) surface reconstructions, respectively. By modifying the surface reconstructure, we are able to separate the contributions to the optical anisotropy from the surface region (mainly associated with the As dimers) from those originating below the surface.
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  • Loures, Flávio V, et al. (författare)
  • Recognition of Aspergillus fumigatus Hyphae by Human Plasmacytoid Dendritic Cells Is Mediated by Dectin-2 and Results in Formation of Extracellular Traps
  • 2015
  • Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 11:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Plasmacytoid dendritic cells (pDCs) were initially considered as critical for innate immunity to viruses. However, our group has shown that pDCs bind to and inhibit the growth of Aspergillus fumigatus hyphae and that depletion of pDCs renders mice hypersusceptible to experimental aspergillosis. In this study, we examined pDC receptors contributing to hyphal recognition and downstream events in pDCs stimulated by A. fumigatus hyphae. Our data show that Dectin-2, but not Dectin-1, participates in A. fumigatus hyphal recognition, TNF-α and IFN-α release, and antifungal activity. Moreover, Dectin-2 acts in cooperation with the FcRγ chain to trigger signaling responses. In addition, using confocal and electron microscopy we demonstrated that the interaction between pDCs and A. fumigatus induced the formation of pDC extracellular traps (pETs) containing DNA and citrullinated histone H3. These structures closely resembled those of neutrophil extracellular traps (NETs). The microarray analysis of the pDC transcriptome upon A. fumigatus infection also demonstrated up-regulated expression of genes associated with apoptosis as well as type I interferon-induced genes. Thus, human pDCs directly recognize A. fumigatus hyphae via Dectin-2; this interaction results in cytokine release and antifungal activity. Moreover, hyphal stimulation of pDCs triggers a distinct pattern of pDC gene expression and leads to pET formation.
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  • Mocevic, Emina, et al. (författare)
  • Environmental mercury exposure, semen quality and reproductive hormones in Greenlandic Inuit and European men: a cross-sectional study
  • 2013
  • Ingår i: Asian Journal of Andrology. - : Medknow. - 1008-682X .- 1745-7262. ; 15:1, s. 97-104
  • Tidskriftsartikel (refereegranskat)abstract
    • Several animal studies indicate that mercury is a male reproductive toxicant, but human studies are few and contradictory. We examined semen characteristics and serum levels of reproductive hormones in relation to environmental exposure to mercury. Blood and semen samples were collected from 529 male partners of pregnant women living in Greenland, Poland and Ukraine between May 2002 and February 2004. The median concentration of the total content of mercury in whole blood was 9.2 ng ml(-1) in Greenland (0.2-385.8 ng ml(-1)), 1.0 ng ml(-1) in Poland (0.2-6.4 ng ml(-1)) and 1.0 ng ml(-1) in Ukraine (0.2-4.9 ng ml(-1)). We found a significantly positive association between the blood levels of mercury and serum concentration of inhibin B in men from Greenland (beta=0.074, 95% confidence interval (CI)=0.021 to 0.126) and in an analysis including men from all three regions (beta=0.067, 95% CI=0.024 to 0.110). The association may be due to beneficial effects of polyunsaturated fatty acids (PUFAs), which are contained in seafood and fish. No significant association (P>0.05) was found between blood concentrations of mercury and any of the other measured semen characteristics (semen volume, total sperm count, sperm concentration, morphology and motility) and reproductive hormones (free androgen index (FAI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone and LHxtestosterone) in any region. In conclusion, the findings do not provide evidence that environmental mercury exposure in Greenlandic and European men with median whole blood concentration up to 10 ng ml(-1) has adverse effects on biomarkers of male reproductive health. Asian Journal of Andrology (2013) 15, 97-104; doi:10.1038/aja.2012.121; published online 10 December 2012
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  • Tsakonas, G, et al. (författare)
  • Randomized Phase II Study with Cetuximab in Combination with 5-FU and Cisplatin or Carboplatin vs. Cetuximab in Combination with Paclitaxel and Carboplatin for Treatment of Patients with Relapsed or Metastatic Squamous Cell Carcinoma of the Head and Neck (CETMET Trial)
  • 2020
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Platinum-based chemotherapy with cetuximab is the standard of care for relapsed or metastatic squamous cell carcinoma of the head and neck (SCCHN). The aim of this trial was to investigate whether cetuximab and paclitaxel/carboplatin can achieve similar progression-free survival (PFS) with standard cetuximab and 5-FU/platinum-based chemotherapy. Standard chemotherapy treatment for SCCHN is related to severe toxicity and new, less toxic regimens are needed. Methods: In this multicentre, randomized, controlled, phase 2 trial, 85 patients with relapsed or metastatic SCCHN were randomized in a 1:1 ratio to cetuximab and 5-FU/cisplatin or carboplatin (arm A) vs. cetuximab and paclitaxel/carboplatin (arm B). Eligibility criteria included age ≥18 years, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–1, and adequate organ functions. The primary endpoint was to investigate whether PFS in arm B is significantly worse than PFS in arm A. Results: Median PFS in arm A was 4.37 months (95% CI: 2.9–5.9 m) and 6.5 months (95% CI: 4.8–8.2 m) in arm B, (p = 0.064). Median overall survival (OS) was 8.4 months (95% CI: 5.3–11.5 m) in arm A and 10.2 months (95% CI: 5.4–15 m) in arm B, (HR = 0.71; 95% CI: 0.43–1.16). PFS HR for arm B was not significantly worse than arm A (HR = 0.65; 95% CI: 0.41–1.03). Adverse events ≥ grade 3 were more frequent in arm A than arm B (60% vs. 40%; p = 0.034). Conclusion: Cetuximab and paclitaxel/carboplatin was found to have similar efficacy and less toxicity compared to cetuximab and 5-FU/cisplatin or carboplatin. The experimental arm is easier to administer rendering it a favorable alternative to standard therapy.
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  • Wortman, J. R., et al. (författare)
  • The 2008 update of the Aspergillus nidulans genome annotation: A community effort
  • 2009
  • Ingår i: Fungal Genetics and Biology. - : Elsevier BV. - 1096-0937 .- 1087-1845. ; 46, s. S2-S13
  • Tidskriftsartikel (refereegranskat)abstract
    • The identification and annotation of protein-coding genes is one of the primary goals of whole-genome sequencing projects, and the accuracy of predicting the primary protein products of gene expression is vital to the interpretation of the available data and the design of downstream functional applications. Nevertheless, the comprehensive annotation of eukaryotic genomes remains a considerable challenge. Many genomes submitted to public databases, including those of major model organisms, contain significant numbers of wrong and incomplete gene predictions. We present a community-based reannotation of the Aspergillus nidulans genome with the primary goal of increasing the number and quality of protein functional assignments through the careful review of experts in the field of fungal biology. (C) 2009 Elsevier Inc. All rights reserved.
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