44 research outputs found

    Lung transplantation after allogeneic stem cell transplantation : a pan-European experience

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    Late-onset noninfectious pulmonary complications (LONIPCs) affect 6% of allogeneic stem cell transplantation (SCT) recipients within 5 years, conferring subsequent 5-year survival of 50%. Lung transplantation is rarely performed in this setting due to concomitant extrapulmonary morbidity, excessive immunosuppression and concerns about recurring malignancy being considered contraindications. This study assesses survival in highly selected patients undergoing lung transplantation for LONIPCs after SCT. SCT patients undergoing lung transplantation at 20 European centres between 1996 and 2014 were included. Clinical data pre- and post-lung transplantation were reviewed. Propensity score-matched controls were generated from the Eurotransplant and Scandiatransplant registries. Kaplan-Meier survival analysis and Cox proportional hazard regression models evaluating predictors of graft loss were performed. Graft survival at 1, 3 and 5 years of 84%, 72% and 67%, respectively, among the 105 SCT patients proved comparable to controls (p=0.75). Sepsis accounted for 15 out of 37 deaths (41%), with prior mechanical ventilation (HR 6.9, 95% CI 1.0-46.7; p Lung transplantation outcomes following SCT were comparable to other end-stage diseases. Lung transplantation should be considered feasible in selected candidates. No SCT-specific factors influencing outcome were identified within this carefully selected patient cohort.Peer reviewe

    Pan-Eurasian Experiment (PEEX) Program : An Overview of the First 5 Years in Operation and Future Prospects

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    The Pan-Eurasian Experiment (PEEX) program was initiated as a bottom-up approach by the researchers coming from Finland and Russia in October 2012. The PEEX China kick off meeting was held in November 2013. During its five years in operation, the program has established a governance structure and delivered a science plan for the Northern Eurasian region. PEEX has also introduced a concept design for a modelling platform and ground-based in situ observation systems for detecting land-atmosphere and ocean-atmosphere interactions. Today, PEEX has an extensive researcher’s network representing research communities coming from the Nordic countries, Russia and China. PEEX is currently carrying out its research activities on a project basis, but is looking for more coordinated funding bases, especially in Russia and in China. The near-future challenge in implementing the PEEX research agenda is to achieve a successful integration and identification of the methodological approaches of the socio-economic research to environmental sciences. Here we give insight into these issues and provide an overview on the main tasks for the upcoming years.The Pan-Eurasian Experiment (PEEX) program was initiated as a bottom-up approach by the researchers coming from Finland and Russia in October 2012. The PEEX China kick off meeting was held in November 2013. During its five years in operation, the program has established a governance structure and delivered a science plan for the Northern Eurasian region. PEEX has also introduced a concept design for a modelling platform and ground-based in situ observation systems for detecting land-atmosphere and ocean-atmosphere interactions. Today, PEEX has an extensive researcher’s network representing research communities coming from the Nordic countries, Russia and China. PEEX is currently carrying out its research activities on a project basis, but is looking for more coordinated funding bases, especially in Russia and in China. The near-future challenge in implementing the PEEX research agenda is to achieve a successful integration and identification of the methodological approaches of the socio-economic research to environmental sciences. Here we give insight into these issues and provide an overview on the main tasks for the upcoming years.The Pan-Eurasian Experiment (PEEX) program was initiated as a bottom-up approach by the researchers coming from Finland and Russia in October 2012. The PEEX China kick off meeting was held in November 2013. During its five years in operation, the program has established a governance structure and delivered a science plan for the Northern Eurasian region. PEEX has also introduced a concept design for a modelling platform and ground-based in situ observation systems for detecting land-atmosphere and ocean-atmosphere interactions. Today, PEEX has an extensive researcher’s network representing research communities coming from the Nordic countries, Russia and China. PEEX is currently carrying out its research activities on a project basis, but is looking for more coordinated funding bases, especially in Russia and in China. The near-future challenge in implementing the PEEX research agenda is to achieve a successful integration and identification of the methodological approaches of the socio-economic research to environmental sciences. Here we give insight into these issues and provide an overview on the main tasks for the upcoming years.Peer reviewe

    Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma.

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    Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide association studies (GWAS). This meta-analysis combines 11 GWAS (5 previously unpublished) and a further three stage 2 data sets, totaling 15,990 CMM cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P < 5 × 10(-8)), as did 2 previously reported but unreplicated loci and all 13 established loci. Newly associated SNPs fall within putative melanocyte regulatory elements, and bioinformatic and expression quantitative trait locus (eQTL) data highlight candidate genes in the associated regions, including one involved in telomere biology.[Please see the Supplementary Note for acknowledgments.]This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.337

    Particulate matter exposure during pregnancy is associated with birth weight, but not gestational age, 1962-1992: a cohort study

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    <p>Abstract</p> <p>Background</p> <p>Exposure to air pollutants is suggested to adversely affect fetal growth, but the evidence remains inconsistent in relation to specific outcomes and exposure windows.</p> <p>Methods</p> <p>Using birth records from the two major maternity hospitals in Newcastle upon Tyne in northern England between 1961 and 1992, we constructed a database of all births to mothers resident within the city. Weekly black smoke exposure levels from routine data recorded at 20 air pollution monitoring stations were obtained and individual exposures were estimated via a two-stage modeling strategy, incorporating temporally and spatially varying covariates. Regression analyses, including 88,679 births, assessed potential associations between exposure to black smoke and birth weight, gestational age and birth weight standardized for gestational age and sex.</p> <p>Results</p> <p>Significant associations were seen between black smoke and both standardized and unstandardized birth weight, but not for gestational age when adjusted for potential confounders. Not all associations were linear. For an increase in whole pregnancy black smoke exposure, from the 1<sup>st </sup>(7.4 μg/m<sup>3</sup>) to the 25<sup>th </sup>(17.2 μg/m<sup>3</sup>), 50<sup>th </sup>(33.8 μg/m<sup>3</sup>), 75<sup>th </sup>(108.3 μg/m<sup>3</sup>), and 90<sup>th </sup>(180.8 μg/m<sup>3</sup>) percentiles, the adjusted estimated decreases in birth weight were 33 g (SE 1.05), 62 g (1.63), 98 g (2.26) and 109 g (2.44) respectively. A significant interaction was observed between socio-economic deprivation and black smoke on both standardized and unstandardized birth weight with increasing effects of black smoke in reducing birth weight seen with increasing socio-economic disadvantage.</p> <p>Conclusions</p> <p>The findings of this study progress the hypothesis that the association between black smoke and birth weight may be mediated through intrauterine growth restriction. The associations between black smoke and birth weight were of the same order of magnitude as those reported for passive smoking. These findings add to the growing evidence of the harmful effects of air pollution on birth outcomes.</p

    Acute Ultraviolet Radiation Perturbs Epithelialization but not the Biomechanical Strength of Full-thickness Cutaneous Wounds.

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    We hypothesized that priming of the skin with ultraviolet radiation (UVR) before being injured would enhance wound healing. Four groups, each comprising 20 immunocompetent hairless mice, were exposed to simulated solar irradiation in escalating UVR doses; 0 SED (standard erythema dose) = control, 1 SED, 3 SED and 5 SED. Twenty-four h after UV irradiation, inflammation was quantified by skin reflectance (erythema) and myeloperoxidase (MPO) tissue levels, and two 6-mm full-thickness excisional wounds and one 3-cm incisional wound were inflicted. Epidermal hyperplasia was assessed by quantitative histology. Five days after wounding, wound coverage by neoepithelium and wound width of the excisional wounds was quantified in hematoxylin-eosin sections, and breaking strength was measured in strips from incisional wounds. Erythema (P < 0.001), MPO levels (P < 0.0005) and epidermal cell layers (P < 0.001) increased dose-dependently by UV exposure of dorsal skin. In the excisional wounds, epithelial coverage decreased (P = 0.024) by increasing the UVR dose while there was no significant difference (P = 0.765) in wound MPO levels. Neither wound width (P = 0.850) nor breaking strength (P = 0.320) differed among the groups. Solar-simulated UVR 24 h before wounding impaired epithelialization but was not detrimental for surgical wound healing. This article is protected by copyright. All rights reserved

    Expression of TGF-beta isoforms, TGF-beta receptors, and SMAD molecules at different stages of human glioma

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    Human gliomas express TGF-beta but, so far the expression of downstream mediators has been investigated in only a few cell lines. We have examined tissue specimens of 23 gliomas: 3 astrocytomas grade II (AST), 8 anaplastic astrocytomas grade III (AAST), and 12 glioblastoma multiforme grade IV (GBM). We analyzed the mRNA expression of TGF-beta1, TGF-beta2, TGF-beta3, the TGF-beta receptors type I (TbetaR-I) and type II (TbetaR-II), Smad2, Smad3, and Smad4. mRNA expression of IL-10 and CD95 (FAS/APO-1) were also studied. We detected increased mRNA levels of the 3 TGF-beta isoforms, correlating with the degree of malignancy. TGF-beta3 mRNA was increased, particularly in AST and AAST, while TGF-beta1 and TGF-beta2 mRNAs were strongly expressed in GBM. TGF-beta normally up-regulates the TGF-beta receptors, and TbetaR-I and TbetaR-II showed stronger expression in all gliomas when compared to normal tissues. However, the mRNA expression of Smad2, Smad3, and Smad4 was decreased in GBM. IL-10 mRNA expression was detected in glioma tissues but not in glioma cell lines. No marked increase in the expression of soluble CD95 splicing variants was found in the gliomas compared with normal tissue. However, total CD95 mRNA was elevated among GBM tissues

    Lung transplantation after allogeneic stem cell transplantation: a pan-European experience

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    Late-onset noninfectious pulmonary complications (LONIPCs) affect 6% of allogeneic stem cell transplantation (SCT) recipients within 5 years, conferring subsequent 5-year survival of 50%. Lung transplantation is rarely performed in this setting due to concomitant extrapulmonary morbidity, excessive immunosuppression and concerns about recurring malignancy being considered contraindications. This study assesses survival in highly selected patients undergoing lung transplantation for LONIPCs after SCT.SCT patients undergoing lung transplantation at 20 European centres between 1996 and 2014 were included. Clinical data pre- and post-lung transplantation were reviewed. Propensity score-matched controls were generated from the Eurotransplant and Scandiatransplant registries. Kaplan-Meier survival analysis and Cox proportional hazard regression models evaluating predictors of graft loss were performed.Graft survival at 1, 3 and 5 years of 84%, 72% and 67%, respectively, among the 105 SCT patients proved comparable to controls (p=0.75). Sepsis accounted for 15 out of 37 deaths (41%), with prior mechanical ventilation (HR 6.9, 95% CI 1.0-46.7; p<0.001) the leading risk factor. No SCT-specific risk factors were identified. Recurring malignancy occurred in four patients (4%). Lung transplantation <2 years post-SCT increased all-cause 1-year mortality (HR 7.5, 95% CI 2.3-23.8; p=0.001).Lung transplantation outcomes following SCT were comparable to other end-stage diseases. Lung transplantation should be considered feasible in selected candidates. No SCT-specific factors influencing outcome were identified within this carefully selected patient cohort.status: publishe
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