| 1. |
- Castaman, G., et al.
(författare)
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Hemorrhagic symptoms and bleeding risk in obligatory carriers of type 3 von Willebrand disease: an international, multicenter study
- 2006
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 4:10, s. 2164-2169
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We undertook an international, multicenter study to describe the clinical picture and to estimate the bleeding risk in a group of obligatory carriers of type 3 von Willebrand disease (VWD). Patients and methods: Obligatory carriers (OC) of type 3 VWD were identified by the presence of offspring with type 3 VWD or by being an offspring of a type 3 patient. Normal controls were age- and sex-matched with the obligatory carriers. A physician-administered standardized questionnaire was used to evaluate hemorrhagic symptoms at presentation. A score system ranging from 0 (no symptom) to 3 (hospitalization, replacement therapy, blood transfusion) was used to quantitate bleeding manifestations. Odds ratios were computed for each symptom. Results: Ten centers participated to the study, enrolling a total of 35 type 3 VWD families, with 70 OC. A total of 215 normal controls and 42 OC for type 1 VWD were also included. About 40% of type 3 OC had at least one bleeding symptom compared to 23% of normal controls and 81.8% of type 1 OC (P < 0.0001 by chi-squared test), showing that type 3 OC clearly represent a distinct population from type 1 OC. The clinical situations associated with an increase of bleeding risk in type 3 OC were epistaxis [odds ratio 3.6; 90% confidence intervals (CI) 1.84-21.5], cutaneous bleeding (odds ratio 5.5; 90% CI 2.5-14.1) and postsurgical bleeding (odds ratio 16.3; 90% CI 4.5-59). The severity of bleeding score correlated with the degree of factor (F) VIII reduction in plasma. Conclusions: OC for type 3 VWD represent a distinctive population from type 1 OC. These patients, however, present with more frequent bleeding symptoms in comparison to normal controls, especially in case of significantly low FVIII. Desmopressin and/or tranexamic acid might be useful to prevent or treat bleeding in these cases.
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| 2. |
- Castaman, G., et al.
(författare)
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Validation of a rapid test (VWF-LIA) for the quantitative determination of von Willebrand factor antigen in type 1 von Willebrand disease diagnosis within the European multicenter study MCMDM-1VWD
- 2010
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Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 126:3, s. 227-231
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Tidskriftsartikel (refereegranskat)abstract
- Background: Accurate measurement of von Willebrand factor (VWF) is a critical requirement for the diagnosis of von Willebrand disease (VWD). Aim of the study: To evaluate the diagnostic efficiency of a rapid quantitative test for the measurement of VWF antigen (VWF:Ag) in type 1 VWD. Patients and methods: VWF: Ag was measured with an ELISA in a robotic instrument, as a reference method, and with a fully automated latex-immunoassay (LIA) on an ACL 9000 analyser in 1,716 subjects enrolled within the Molecular and Clinical Markers for Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD) Study. Among these subjects, 1,049 were healthy controls, 281 healthy family members and 386 affected members from 127 European families with type 1 VWD. Results: The assay linearity range was 10-125 IU/dL for LIA (R-2 = 0.99) and 5-133 IU/dL for ELISA (R-2 = 0.99). The inter-assay CV for low VWF levels (similar to 30 IU/dL) was 2% for the LIA test and 8.7 % for ELISA. The sensitivity for detection of type 1 VWD affected members was 86% and the specificity 91% for LIA, 87% and 90% for ELISA. A receiver-operator (ROC) analysis disclosed only a marginal difference between the two tests, LIA having a slightly greater area under the curve (0.94 vs. 0.93, p = 0.03). Conclusion: VWF: Ag LIA compared well to standard ELISA in this large population of patients and controls, showing better CV. However the lower detection limit for the VWF: Ag LIA compared to the VWF: Ag ELISA means that the LIA assay is less good at discriminating between type 3 VWD and moderate type 1 VWD. (C) 2010 Elsevier Ltd. All rights reserved.
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| 3. |
- Spolaor, A., et al.
(författare)
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Diurnal cycle of iodine, bromine, and mercury concentrations in Svalbard surface snow
- 2019
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 19:20, s. 13325-13339
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Tidskriftsartikel (refereegranskat)abstract
- Sunlit snow is highly photochemically active and plays a key role in the exchange of gas phase species between the cryosphere and the atmosphere. Here, we investigate the behaviour of two selected species in surface snow: mercury (Hg) and iodine (I). Hg can deposit year-round and accumulate in the snowpack. However, photo-induced re-emission of gas phase Hg from the surface has been widely reported. Iodine is active in atmospheric new particle formation, especially in the marine boundary layer, and in the destruction of atmospheric ozone. It can also undergo photochemical re-emission. Although previous studies indicate possible post-depositional processes, little is known about the diurnal behaviour of these two species and their interaction in surface snow. The mechanisms are still poorly constrained, and no field experiments have been performed in different seasons to investigate the magnitude of re-emission processes Three sampling campaigns conducted at an hourly resolution for 3 d each were carried out near Ny-Alesund (Svalbard) to study the behaviour of mercury and iodine in surface snow under different sunlight and environmental conditions (24 h darkness, 24 h sunlight and day-night cycles). Our results indicate a different behaviour of mercury and iodine in surface snow during the different campaigns. The day-night experiments demonstrate the existence of a diurnal cycle in surface snow for Hg and iodine, indicating that these species are indeed influenced by the daily solar radiation cycle. Differently, bromine did not show any diurnal cycle. The diurnal cycle also disappeared for Hg and iodine during the 24 h sunlight period and during 24 h darkness experiments supporting the idea of the occurrence (absence) of a continuous recycling or exchange at the snow-air interface. These results demonstrate that this surface snow recycling is seasonally dependent, through sunlight. They also highlight the non-negligible role that snowpack emissions have on ambient air concentrations and potentially on iodine-induced atmospheric nucleation processes.
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| 4. |
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| 5. |
- Humphries, Matthew P., et al.
(författare)
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A case-matched gender comparison transcriptomic screen identifies eIF4E and eIF5 as potential prognostic markers in male breast cancer
- 2017
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 23:10, s. 2575-2583
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Breast cancer affects both genders, but is understudied in men. Although still rare, male breast cancer (MBC) is being diagnosed more frequently. Treatments are wholly informed by clinical studies conducted in women, based on assumptions that underlying biology is similar. Experimental Design: A transcriptomic investigation of male and female breast cancer was performed, confirming transcriptomic data in silico. Biomarkers were immunohistochemically assessed in 697 MBCs (n = 477, training; n = 220, validation set) and quantified in pre- and posttreatment samples from an MBC patient receiving everolimus and PI3K/mTOR inhibitor. Results: Gender-specific gene expression patterns were identified. eIF transcripts were upregulated in MBC. eIF4E and eIF5 were negatively prognostic for overall survival alone (log-rank P = 0.013; HR = 1.77, 1.12-2.8 and P = 0.035; HR = 1.68, 1.03-2.74, respectively), or when coexpressed (P = 0.01; HR = 2.66, 1.26-5.63), confirmed in the validation set. This remained upon multivariate Cox regression analysis [eIF4E P = 0.016; HR = 2.38 (1.18-4.8), eIF5 P = 0.022; HR = 2.55 (1.14-5.7); coexpression P = 0.001; HR = 7.04 (2.22-22.26)]. Marked reduction in eIF4E and eIF5 expression was seen post BEZ235/everolimus, with extended survival. Conclusions: Translational initiation pathway inhibition could be of clinical utility in MBC patients overexpressing eIF4E and eIF5. With mTOR inhibitors that target this pathway now in the clinic, these biomarkers may represent new targets for therapeutic intervention, although further independent validation is required.
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| 6. |
- Rodeghiero, F, et al.
(författare)
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The discriminant power of bleeding history for the diagnosis of type 1 von Willebrand disease: an international, multicenter study
- 2005
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 3:12, s. 2619-2626
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was the validation of the criteria defining a significant mucocutaneous-bleeding history in type 1 von Willebrand disease (VWD). Subjects and methods: To avoid selection bias, 42 obligatory carriers (OC) of type 1 VWD were identified from a panel of 42 families with type 1 VWD enrolled by 10 expert centers. OC were identified by the presence of an offspring and another first degree relative with type 1 VWD (affected subjects, AFF). A standardized questionnaire was administered to evaluate hemorrhagic symptoms at the time of first examination, using a bleeding score ranging from 0 (no symptom) to 3 (hospitalization, replacement therapy, blood transfusion). Sensitivity, specificity, diagnostic likelihood ratios, positive and negative predictive values for the diagnosis of type 1 VWD were calculated from the data collected in OC and in 215 controls. Results: Having at least three hemorrhagic symptoms or a bleeding score of 3 in males and 5 in females was very specific (98.6%) for the bleeding history of type 1 VWD, although less sensitive (69.1%). None of the misclassified OC had life-threatening bleeding episodes after diagnosis. Conclusions: We suggest that the use of a standardized questionnaire and bleeding score may be useful for the identification of subjects requiring laboratory evaluation for VWD.
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| 7. |
- Spolaor, A., et al.
(författare)
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Source, timing and dynamics of ionic species mobility in the Svalbard annual snowpack
- 2021
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 751
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Tidskriftsartikel (refereegranskat)abstract
- Nearly all ice core archives from the Arctic and middle latitudes (such as the Alps), apart from some very high elevation sites in Greenland and the North Pacific, are strongly influenced by melting processes. The increases in the average Arctic temperature has enhanced surface snow melting even of higher elevation ice caps, especially on the Svalbard Archipelago. The increase of the frequency and altitude of winter "rain on snow" events as well as the increase of the length of the melting season have had a direct impact on the chemical composition of the seasonal and permanent snow layers due to different migration processes of water-soluble species, such as inorganic ions. This re-allocation along the snowpack of ionic species could significantly modify the original chemical signal present in the annual snow. This paper aims to give a picture of the evolution of the seasonal snow strata with a daily time resolution to better understand: a) the processes that can influence deposition b) the distribution of ions in annual snow c) the impact of the presence of liquid water on chemical re-distribution within the annual snow pack. Specifically, the chemical composition of the first 100 cm of seasonal snow on the Austre Broggerbreen Glacier (Spitsbergen, Svalbard Islands, Norway) was monitored daily from the 27th of March to the 31st of May 2015. The experimental period covered almost the entire Arctic spring until the melting season. This unique dataset gives us a daily picture of the snow pack composition, and helps us to understand the behaviour of cations (K+, Ca2+, Na+, Mg2+) and anions (Br-, I-, SO42-, NO3-, Cl-, MSA) in the Svalbard snow pack. We demonstrate that biologically related depositions occur only at the end of the snow season and that rain and melting events have different impacts on the snowpack chemistry. (C) 2020 Elsevier B.V. All rights reserved.
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| 8. |
- Barbaro, E., et al.
(författare)
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Free amino acids in the Arctic snow and ice core samples: Potential markers for paleoclimatic studies
- 2017
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 607, s. 454-462
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Tidskriftsartikel (refereegranskat)abstract
- The role of oceanic primary production on climate variability has long been debated. Defining changes in past oceanic primary production can help understanding of the important role that marine algae have in climate variability. In ice core research methanesulfonic acid is the chemical marker commonly used for assessing changes in past primary production. However, other organic compounds such as amino acids, can be produced and emitted into the atmosphere during a phytoplankton bloom. These species can be transported and deposited onto the ice cap in polar regions. Here we investigate the correlation between the concentration of chlorophyll-a, marker of marine primary production, and amino acids present in an ice core. For the first time, free L- and D-amino acids in Arctic snow and firn samples were determined by a sensitive and selective analytical method based on liquid chromatography coupled with tandem mass spectrometry. The new method for the determination of free amino acids concentrations was applied to firn core samples collected on April 2015 from the summit of the Holtedahlfonna glacier, Svalbard (N 79'08.424, E 13'23.639, 1120 m a.s.l.). The main results of this work are summarized as follows: (1) glycine, alanine and proline, were detected and quantified in the firn core samples; (2) their concentration profiles, compared with that of the stable isotope delta O-18 ratio, show a seasonal cycling with the highest concentrations during the spring and summer time; (3) back-trajectories and Greenland Sea chlorophyll-a concentrations obtained by satellite measurements were compared with the amino acids profile obtained from ice core samples, this provided further insights into the present results. This study suggests that the amino acid concentrations in the ice samples collected from the Holtedahlfonna glaciers could reflect changes in oceanic phytoplankton abundance.
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| 9. |
- Spolaor, A., et al.
(författare)
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Evolution of the Svalbard annual snow layer during the melting phase
- 2016
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Ingår i: Rendiconti Lincei-Scienze Fisiche E Naturali. - : Springer Science and Business Media LLC. - 2037-4631. ; 27:Supplement 1, s. 147-154
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Tidskriftsartikel (refereegranskat)abstract
- Understanding and monitoring the evolution of annual snow is an important aspect of cryosphere research. Changes in physical proprieties such as hardness, presence of melt layers, or the shape and size of crystals can completely modify the robustness, propriety and quality of the snow. Evaluating these changes can inform the study and prediction of avalanches. The annual snow layer is also a sink for several compounds and elements. In the polar environment, many compounds can be accumulated during winter depositions, especially during the polar night. During the spring, the combination of solar radiation and the melting of annual snow can release these compounds and elements into the atmosphere and groundwater. An in-depth investigation of the evolution of the first meter of the annual snow layer was conducted in the glacier of Austre Broggerbreen, Svalbard, between the 27th of March and the 31st of May, in concomitance with the start of the melting phase. The present monitoring study mainly aimed to evaluate changes in the thermal profile and water content during the formation of a new ice layer as well as the re-allocation of the total dissolved salts in the different snow layers.
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| 10. |
- Ciarelli, Giancarlo, et al.
(författare)
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Trends of inorganic and organic aerosols and precursor gases in Europe: Insights from the EURODELTA multi-model experiment over the 1990-2010 period
- 2019
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 12:12, s. 4923-4954
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Tidskriftsartikel (refereegranskat)abstract
- In the framework of the EURODELTA-Trends (EDT) modeling experiment, several chemical transport models (CTMs) were applied for the 1990-2010 period to investigate air quality changes in Europe as well as the capability of the models to reproduce observed long-term air quality trends. Five CTMs have provided modeled air quality data for 21 continuous years in Europe using emission scenarios prepared by the International Institute for Applied Systems Analysis/Greenhouse Gas - Air Pollution Interactions and Synergies (IIASA/GAINS) and corresponding year-by-year meteorology derived from ERA-Interim global reanalysis. For this study, long-term observations of particle sulfate (SO2 4-), total nitrate (TNO3), total ammonium (TNHx) as well as sulfur dioxide (SO2) and nitrogen dioxide (NO2) for multiple sites in Europe were used to evaluate the model results. The trend analysis was performed for the full 21 years (referred to as PT) but also for two 11-year subperiods: 1990-2000 (referred to as P1) and 2000-2010 (referred to as P2). The experiment revealed that the models were able to reproduce the faster decline in observed SO2 concentrations during the first decade, i.e., 1990-2000, with a 64%-76% mean relative reduction in SO2 concentrations indicated by the EDT experiment (range of all the models) versus an 82% mean relative reduction in observed concentrations. During the second decade (P2), the models estimated a mean relative reduction in SO2 concentrations of about 34%-54%, which was also in line with that observed (47%). Comparisons of observed and modeled NO2 trends revealed a mean relative decrease of 25% and between 19% and 23% (range of all the models) during the P1 period, and 12% and between 22% and 26% (range of all the models) during the P2 period, respectively. Comparisons of observed and modeled trends in SO4 2- concentrations during the P1 period indicated that the models were able to reproduce the observed trends at most of the sites, with a 42%-54% mean relative reduction indicated by the EDT experiment (range of all models) versus a 57% mean relative reduction in observed concentrations and with good performance also during the P2 and PT periods, even though all the models overpredicted the number of statistically significant decreasing trends during the P2 period. Moreover, especially during the P1 period, both modeled and observational data indicated smaller reductions in SO42- concentrations compared with their gas-phase precursor (i.e., SO2), which could be mainly attributed to increased oxidant levels and pH-dependent cloud chemistry. An analysis of the trends in TNO3 concentrations indicated a 28%-39% and 29% mean relative reduction in TNO3 concentrations for the full period for model data (range of all the models) and observations, respectively. Further analysis of the trends in modeled HNO3 and particle nitrate (NO-3 ) concentrations revealed that the relative reduction in HNO3 was larger than that for NO-3 during the P1 period, which was mainly attributed to an increased availability of "free ammonia". By contrast, trends in modeled HNO3 and NO-3 concentrations were more comparable during the P2 period. Also, trends of TNHx concentrations were, in general, underpredicted by all models, with worse performance for the P1 period than for P2. Trends in modeled anthropogenic and biogenic secondary organic aerosol (ASOA and BSOA) concentrations together with the trends in available emissions of biogenic volatile organic compounds (BVOCs) were also investigated. A strong decrease in ASOA was indicated by all the models, following the reduction in anthropogenic non-methane VOC (NMVOC) precursors. Biogenic emission data provided by the modeling teams indicated a few areas with statistically significant increase in isoprene emissions and monoterpene emissions during the 1990-2010 period over Fennoscandia and eastern European regions (i.e., around 14 %-27 %), which was mainly attributed to the increase of surface temperature. However, the modeled BSOA concentrations did not linearly follow the increase in biogenic emissions. Finally, a comprehensive evaluation against positive matrix factorization (PMF) data, available during the second period (P2) at various European sites, revealed a systematic underestimation of the modeled SOA fractions of a factor of 3 to 11, on average, most likely because of missing SOA precursors and formation pathways, with reduced biases for the models that accounted for chemical aging of semi-volatile SOA components in the atmosphere.
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