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4.
  • Angelopoulus, M., et al. (author)
  • Physical properties of sea ice cores from site MCS_FYI measured on legs 1 to 3 of the MOSAiC expedition.
  • 2022
  • In: PANGAEA.
  • Other publication (other academic/artistic)abstract
    • We present sea ice temperature and salinity data from first-year ice (FYI) and second-year ice (SYI) relevant to the temporal development of sea ice permeability and brine drainage efficiency from the early growth phase in October 2019 to the onset of spring warming in May 2020. Our dataset was collected in the central Arctic Ocean during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) Expedition in 2019 to 2020. MOSAiC was an international transpolar drift expedition in which the German icebreaker RV Polarstern anchored into an ice floe to gain new insights into Arctic climate over a full annual cycle. In October 2019, RV Polarstern moored to an ice floe in the Siberian sector of the Arctic at 85 degrees north and 137 degrees east to begin the drift towards the North Pole and the Fram Strait via the Transpolar Drift Stream. The data presented here were collected during the first three legs of the expedition, so all the coring activities took place on the same floe. The end dates of legs 1, 2, and 3 were 13 December, 24 February, and 4 June, respectively. The dataset contributed to a baseline study entitled, Deciphering the properties of different Arctic ice types during the growth phase of the MOSAiC floes: Implications for future studies. The study highlights downward directed gas pathways in FYI and SYI by inferring sea ice permeability and potential brine release from several time series of temperature and salinity measurements. The physical properties presented in this paper lay the foundation for subsequent analyses on actual gas contents measured in the ice cores, as well as air-ice and ice-ocean gas fluxes. Sea ice cores were collected with a Kovacs Mark II 9 cm diameter corer. To measure ice temperatures, about 4.5 cm deep holes were drilled into the core (intervals varied by site and leg) . The temperatures were measured by a digital thermometer within minutes after the cores were retrieved. The ice cores were placed into pre-labelled plastic sleeves sealed at the bottom end. The ice cores were transported to RV Polarstern and stored in a -20 degrees Celsius freezer. Each of the cores was sub-sampled, melted at room temperature, and processed for salinity within one or two days. The practical salinity was estimated by measuring the electrical conductivity and temperature of the melted samples using a WTW Cond 3151 salinometer equipped with a Tetra-Con 325 four-electrode conductivity cell. The practical salinity represents the the salinity estimated from the electrical conductivity of the solution. The dataset also contains derived variables, including sea ice density, brine volume fraction, and the Rayleigh number.
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5.
  • Angelopoulus, M., et al. (author)
  • Physical properties of sea ice cores from site MCS-SYI measured on legs 1 to 3 of the MOSAiC expedition
  • 2022
  • In: PANGAEA.
  • Other publication (other academic/artistic)abstract
    • We present sea ice temperature and salinity data from first-year ice (FYI) and second-year ice (SYI) relevant to the temporal development of sea ice permeability and brine drainage efficiency from the early growth phase in October 2019 to the onset of spring warming in May 2020. Our dataset was collected in the central Arctic Ocean during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) Expedition in 2019 to 2020. MOSAiC was an international transpolar drift expedition in which the German icebreaker RV Polarstern anchored into an ice floe to gain new insights into Arctic climate over a full annual cycle. In October 2019, RV Polarstern moored to an ice floe in the Siberian sector of the Arctic at 85 degrees north and 137 degrees east to begin the drift towards the North Pole and the Fram Strait via the Transpolar Drift Stream. The data presented here were collected during the first three legs of the expedition, so all the coring activities took place on the same floe. The end dates of legs 1, 2, and 3 were 13 December, 24 February, and 4 June, respectively. The dataset contributed to a baseline study entitled, Deciphering the properties of different Arctic ice types during the growth phase of the MOSAiC floes: Implications for future studies. The study highlights downward directed gas pathways in FYI and SYI by inferring sea ice permeability and potential brine release from several time series of temperature and salinity measurements. The physical properties presented in this paper lay the foundation for subsequent analyses on actual gas contents measured in the ice cores, as well as air-ice and ice-ocean gas fluxes. Sea ice cores were collected with a Kovacs Mark II 9 cm diameter corer. To measure ice temperatures, about 4.5 cm deep holes were drilled into the core (intervals varied by site and leg) . The temperatures were measured by a digital thermometer within minutes after the cores were retrieved. The ice cores were placed into pre-labelled plastic sleeves sealed at the bottom end. The ice cores were transported to RV Polarstern and stored in a -20 degrees Celsius freezer. Each of the cores was sub-sampled, melted at room temperature, and processed for salinity within one or two days. The practical salinity was estimated by measuring the electrical conductivity and temperature of the melted samples using a WTW Cond 3151 salinometer equipped with a Tetra-Con 325 four-electrode conductivity cell. The practical salinity represents the the salinity estimated from the electrical conductivity of the solution. The dataset also contains derived variables, including sea ice density, brine volume fraction, and the Rayleigh number.
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  • Benavent, N., et al. (author)
  • Substantial contribution of iodine to Arctic ozone destruction
  • 2022
  • In: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 15, s. 770-773
  • Journal article (peer-reviewed)abstract
    • Unlike bromine, the effect of iodine chemistry on the Arctic surface ozone budget is poorly constrained. We present ship-based measurements of halogen oxides in the high Arctic boundary layer from the sunlit period of March to October 2020 and show that iodine enhances springtime tropospheric ozone depletion. We find that chemical reactions between iodine and ozone are the second highest contributor to ozone loss over the study period, after ozone photolysis-initiated loss and ahead of bromine.
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  • Dellenmark-Blom, Michaela, 1983, et al. (author)
  • Establishment of a condition-specific quality-of-life questionnaire for children born with esophageal atresia aged 2-7 across 14 countries
  • 2023
  • In: Frontiers in Pediatrics. - 2296-2360. ; 11
  • Journal article (peer-reviewed)abstract
    • BackgroundEsophageal atresia (EA) is a rare congenital anomaly characterized by a discontinuity of the esophagus. Following surgical repair, survival rates have improved dramatically the past decenniums and today exceed 90%, but the children commonly present with esophageal and respiratory morbidity. In 2018, a condition-specific quality-of-life questionnaire for children with esophageal atresia (EA) aged 2-7 in Sweden-Germany was finalized (The EA-QOL questionnaire). The study aim was to describe the evaluation of the new translations across 12 new countries in Europe, Asia, Africa, Central-and North America.MethodsFollowing forward-backward translation into the new languages, the 17-item EA-QOL questionnaire was tested in cognitive debriefing interviews with parents of children with EA aged 2-7. Parents rated if each item was easy to understand (clarity) and sensitive to answer (interference with personal integrity). They could skip responding to a non-applicable/problematic item and give open comments. Predefined psychometric criteria were used; item clarity >= 80%/item sensitive to answer <= 20%/item feasibility <= 5% missing item responses. The decision to modify the translation was based on native expert, patient stakeholder, and instrument developer review, and the need for harmonization between translations.ResultsSimilar to findings in the Swedish-German cognitive debriefing, the cross-cultural analysis of input from 116 parents from 12 new countries (4-14 parents, median 9 parents/country) showed that all items in the EA-QOL questionnaire fulfilled the criteria for item clarity >= 80% and sensitive to answer (ranging from 1%-4.5%), although results varied between countries. Four items had missing responses between 5.2% and 13.4%, three within the same domain and were in line with parents' explanations. Poor translations and feasibility were improved.ConclusionsBased on parent input, the collaboration between native experts, patient stakeholders, and instrument developers, a linguistic version of the EA-QOL questionnaire for children aged 2-7 for use in and across 14 countries has been established. These efforts have set the conditions for a cross-cultural field test of the EA-QOL questionnaire and will open the doors for a new chapter in outcome research, registries, and clinical practice concerning children with EA. In the long-term, this will help increase knowledge of the disease's burden, promote patient-centeredness, exchange of information between nations, and strengthen evidence-based treatments for children born with EA.
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9.
  • Fantini, R, et al. (author)
  • EU FP7 INFSO-ICT-317669 METIS, D3.2 First performance results for multi-node/multi-antenna transmission technologies
  • 2014
  • Reports (other academic/artistic)abstract
    • This deliverable describes the current results of the multi-node/multi-antenna technologies investigated within METIS and analyses the interactions within and outside Work Package 3. Furthermore, it identifies the most promising technologies based on the current state of obtained results. This document provides a brief overview of the results in its first part. The second part, namely the Appendix, further details the results, describes the simulation alignment efforts conducted in the Work Package and the interaction of the Test Cases. The results described here show that the investigations conducted in Work Package 3 are maturing resulting in valuable innovative solutions for future 5G systems.
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  • Carvalho, E. de, et al. (author)
  • EU FP7 INFSO-ICT-317669 METIS, D3.1 Positioning of multi-node/multi-antenna technologies
  • 2013
  • Reports (other academic/artistic)abstract
    • This document describes the research activity in multi-node/multi-antenna technologies within METIS and positions it with respect to the state-of-the-art in the academic literature and in the standardization bodies. Based on the state-of-the-art and as well as on the METIS objectives,we set the research objectives and we group the different activities (or technology components) into research clusters with similar research objectives. The technologycomponents and the research objectives have been set to achieve an ambidextrous purpose. On one side we aim at providing the METIS system with those technological components that are a natural but non-trivial evolution of 4G. On the other side, we aim at seeking for disruptivetechnologies that could radically change 5G with respect to 4G. Moreover, we mapped the different technology components to METIS’ other activities and to the overall goals of theproject.
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  • Le Roch, Sarah, et al. (author)
  • European survey on criteria of aesthetics for periodontal evaluation: The ESCAPE study
  • 2019
  • In: Journal of Clinical Periodontology. - : Wiley. - 0303-6979 .- 1600-051X. ; 46:11, s. 1116-1123
  • Journal article (peer-reviewed)abstract
    • © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Objective: The ESCAPE multicentre survey was designed to (a) compare the agreement of three relevant aesthetic scoring systems among different centres, and (b) evaluate the reproducibility of each question of the questionnaires. Materials and Methods: EFP centres (n=14) were involved in an e-survey. Forty-two participants (28 teachers, 14 postgraduate students) were asked to score the one-year aesthetic outcomes of photographs using the Before–After Scoring System (BASS), the Pink Esthetic Score (PES) and the Root coverage Esthetic Score (RES). Mean values of kappa statistics performed on each question were provided to resume global agreement of each method. Results: Between teachers, a difference of kappa≥0.41 (p=.01) was found for BASS (75%) and PES (57%). Similarly, RES (84%) and PES (57%) were different (p<.001). No difference was found between BASS (75%) and RES (84%). No difference was found between students, whatever the scoring system. Questions of each scoring system showed differences in their reproducibility. Conclusions: The outcomes of this study indicate that BASS and RES scoring systems are reproducible tools to evaluate aesthetic after root coverage therapies between different centres. Among the various variables, lack of scar, degree of root coverage, colour match and gingival margin that follows the CEJ show the best reliability.
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  • Aapro, M, et al. (author)
  • Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel
  • 2008
  • In: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 19:3, s. 420-432
  • Journal article (peer-reviewed)abstract
    • Bisphosphonates (BP) prevent, reduce, and delay cancer-related skeletal complications in patients, and have substantially decreased the prevalence of such events since their introduction. Today, a broad range of BP with differences in potency, efficacy, dosing, and administration as well as approved indications is available. In addition, results of clinical trials investigating the efficacy of BP in cancer treatment-induced bone loss (CTIBL) have been recently published. The purpose of this paper is to review the current evidence on the use of BP in solid tumours and provide clinical recommendations. An interdisciplinary expert panel of clinical oncologists and of specialists in metabolic bone diseases assessed the widespread evidence and information on the efficacy of BP in the metastatic and nonmetastatic setting, as well as ongoing research on the adjuvant use of BP. Based on available evidence, the panel recommends amino-bisphosphonates for patients with metastatic bone disease from breast cancer and zoledronic acid for patients with other solid tumours as primary disease. Dosing of BP should follow approved indications with adjustments if necessary. While i.v. administration is most often preferable, oral administration (clodronate, IBA) may be considered for breast cancer patients who cannot or do not need to attend regular hospital care. Early-stage cancer patients at risk of developing CTIBL should be considered for preventative BP treatment. The strongest evidence in this setting is now available for ZOL. Overall, BP are well-tolerated, and most common adverse events are influenza-like syndrome, arthralgia, and when used orally, gastrointestinal symptoms. The dose of BP may need to be adapted to renal function and initial creatinine clearance calculation is mandatory according to the panel for use of any BP. Subsequent monitoring is recommended for ZOL and PAM, as described by the regulatory authority guidelines. Patients scheduled to receive BP (mainly every 3-4 weeks i.v.) should have a dental examination and be advised on appropriate measures for reducing the risk of jaw osteonecrosis. BP are well established as supportive therapy to reduce the frequency and severity of skeletal complications in patients with bone metastases from different cancers.
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  • Lennernäs, Hans, et al. (author)
  • Oral biopharmaceutics tools - Time for a new initiative - An introduction to the IMI project OrBiTo
  • 2014
  • In: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 57:SI, s. 292-299
  • Research review (peer-reviewed)abstract
    • OrBiTo is a new European project within the IMI programme in the area of oral biopharmaceutics tools that includes world leading scientists from nine European universities, one regulatory agency, one non-profit research organization, four SMEs together with scientists from twelve pharmaceutical companies. The OrBiTo project will address key gaps in our knowledge of gastrointestinal (GI) drug absorption and deliver a framework for rational application of predictive biopharmaceutics tools for oral drug delivery. This will be achieved through novel prospective investigations to define new methodologies as well as refinement of existing tools. Extensive validation of novel and existing biopharmaceutics tools will be performed using active pharmaceutical ingredient (API), formulations and supporting datasets from industry partners. A combination of high quality in vitro or in silico characterizations of API and formulations will be integrated into physiologically based in silica biopharmaceutics models capturing the full complexity of GI drug absorption. This approach gives an unparalleled opportunity to initiate a transformational change in industrial research and development to achieve model-based pharmaceutical product development in accordance with the Quality by Design concept. Benefits include an accelerated and more efficient drug candidate selection, formulation development process, particularly for challenging projects such as low solubility molecules (BCS II and IV), enhanced and modified-release formulations, as well as allowing optimization of clinical product performance for patient benefit. In addition, the tools emerging from OrBiTo are expected to significantly reduce demand for animal experiments in the future as well as reducing the number of human bioequivalence studies required to bridge formulations after manufacturing or composition changes.
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  • Modvig, S, et al. (author)
  • Value of flow cytometry for MRD-based relapse prediction in B-cell precursor ALL in a multicenter setting.
  • 2021
  • In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 35, s. 1894-1906
  • Journal article (peer-reviewed)abstract
    • PCR of TCR/Ig gene rearrangements is considered the method of choice for minimal residual disease (MRD) quantification in BCP-ALL, but flow cytometry analysis of leukemia-associated immunophenotypes (FCM-MRD) is faster and biologically more informative. FCM-MRD performed in 18 laboratories across seven countries was used for risk stratification of 1487 patients with BCP-ALL enrolled in the NOPHO ALL2008 protocol. When no informative FCM-marker was available, risk stratification was based on real-time quantitative PCR. An informative FCM-marker was found in 96.2% and only two patients (0.14%) had non-informative FCM and non-informative PCR-markers. The overall 5-year event-free survival was 86.1% with a cumulative incidence of relapse (CIR5y) of 9.5%. FCM-MRD levels on days 15 (HzR 4.0, p<0.0001), 29 (HzR 2.7, p<0.0001), and 79 (HzR 3.5, p<0.0001) associated with hazard of relapse adjusted for age, cytogenetics, and WBC. The early (day 15) response associated with CIR5y adjusted for day 29 FCM-MRD, with higher levels in adults (median 2.4×10-2 versus 5.2×10-3, p<0.0001). Undetectable FCM- and/or PCR-MRD on day 29 identified patients with a very good outcome (CIR5y=3.2%). For patients who did not undergo transplantation, day 79 FCM-MRD>10-4 associated with a CIR5y=22.1%. In conclusion, FCM-MRD performed in a multicenter setting is a clinically useful method for MRD-based treatment stratification in BCP-ALL.
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20.
  • Angelopoulos, M., et al. (author)
  • Physical properties of sea ice cores from site BGC2 measured on legs 1 to 3 of the MOSAiC expedition
  • 2022
  • In: PANGAEA.
  • Other publication (other academic/artistic)abstract
    • We present sea ice temperature and salinity data from first-year ice (FYI) and second-year ice (SYI) relevant to the temporal development of sea ice permeability and brine drainage efficiency from the early growth phase in October 2019 to the onset of spring warming in May 2020. Our dataset was collected in the central Arctic Ocean during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) Expedition in 2019 to 2020. MOSAiC was an international transpolar drift expedition in which the German icebreaker RV Polarstern anchored into an ice floe to gain new insights into Arctic climate over a full annual cycle. In October 2019, RV Polarstern moored to an ice floe in the Siberian sector of the Arctic at 85 degrees north and 137 degrees east to begin the drift towards the North Pole and the Fram Strait via the Transpolar Drift Stream. The data presented here were collected during the first three legs of the expedition, so all the coring activities took place on the same floe. The end dates of legs 1, 2, and 3 were 13 December, 24 February, and 4 June, respectively. The dataset contributed to a baseline study entitled, Deciphering the properties of different Arctic ice types during the growth phase of the MOSAiC floes: Implications for future studies. The study highlights downward directed gas pathways in FYI and SYI by inferring sea ice permeability and potential brine release from several time series of temperature and salinity measurements. The physical properties presented in this paper lay the foundation for subsequent analyses on actual gas contents measured in the ice cores, as well as air-ice and ice-ocean gas fluxes. Sea ice cores were collected with a Kovacs Mark II 9 cm diameter corer. To measure ice temperatures, about 4.5 cm deep holes were drilled into the core (intervals varied by site and leg) . The temperatures were measured by a digital thermometer within minutes after the cores were retrieved. The ice cores were placed into pre-labelled plastic sleeves sealed at the bottom end. The ice cores were transported to RV Polarstern and stored in a -20 degrees Celsius freezer. Each of the cores was sub-sampled, melted at room temperature, and processed for salinity within one or two days. The practical salinity was estimated by measuring the electrical conductivity and temperature of the melted samples using a WTW Cond 3151 salinometer equipped with a Tetra-Con 325 four-electrode conductivity cell. The practical salinity represents the the salinity estimated from the electrical conductivity of the solution. The dataset also contains derived variables, including sea ice density, brine volume fraction, and the Rayleigh number.
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  • Lennernäs, Hans, et al. (author)
  • In Vivo Predictive Dissolution (IPD) and Biopharmaceutical Modeling and Simulation : Future Use of Modern Approaches and Methodologies in a Regulatory Context
  • 2017
  • In: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 14:4, s. 1307-1314
  • Journal article (peer-reviewed)abstract
    • The overall objective of OrBiTo, a project within Innovative Medicines Initiative (IMI), is to streamline and optimize the development of orally administered drug products through the creation and efficient application of biopharmaceutics tools. This toolkit will include both experimental and computational Models developed on improved understanding of the highly dynamic gastrointestinal (GI) physiology relevant to the GI absorption of drug products in both fasted and fed states. A part of the annual OrBiTo meeting in 2015 was dedicated: to the presentation of the most recent progress in the development of the regulatory use of PBPK in silk() modeling, in vivo predictive dissolution (IPD) tests, and their application to biowaivers. There are still several areas for improvement of in vitro dissolution testing by means of generating results relevant for the intraluminal conditions in the GI tract. The major opportunity is probably in combining IPD testing and physiologically based in silico models where the in vitro data provide input to the absorption predictions. The OrBiTo project and other current research projects include-definition of test media representative for the more distal parts of the GI tract, models capturing supersaturation and precipitation phenomena, and influence of motility waves on shear and other forces of hydrodynamic origin, addressing the inter individual variability in composition and characteristics of GI fluids, food effects, definition of biorelevant buffer systems, and intestinal water volumes. In conclusion, there is currently a mismatch between the extensive industrial usage of modern in vivo predictive tools and very limited inclusion of such data in regulatory files. However, there is a great interest among all stakeholders to introduce recent progresses in prediction of in vivo GI drug absorption into regulatory context.
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24.
  • Modvig, S, et al. (author)
  • Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia
  • 2019
  • In: Leukemia. - : Nature Publishing Group. - 0887-6924 .- 1476-5551. ; 33:6, s. 1324-1336
  • Journal article (peer-reviewed)abstract
    • Minimal residual disease (MRD) measured by PCR of clonal IgH/TCR rearrangements predicts relapse in T-cell acute lymphoblastic leukemia (T-ALL) and serves as risk stratification tool. Since 10% of patients have no suitable PCR-marker, we evaluated flowcytometry (FCM)-based MRD for risk stratification. We included 274 T-ALL patients treated in the NOPHO-ALL2008 protocol. MRD was measured by six-color FCM and real-time quantitative PCR. Day 29 PCR-MRD (cut-off 10-3) was used for risk stratification. At diagnosis, 93% had an FCM-marker for MRD monitoring, 84% a PCR-marker, and 99.3% (272/274) had a marker when combining the two. Adjusted for age and WBC, the hazard ratio for relapse was 3.55 (95% CI 1.4-9.0, p = 0.008) for day 29 FCM-MRD ≥ 10-3 and 5.6 (95% CI 2.0-16, p = 0.001) for PCR-MRD ≥ 10-3 compared with MRD < 10-3. Patients stratified to intermediate-risk therapy on day 29 with MRD 10-4-<10-3 had a 5-year event-free survival similar to intermediate-risk patients with MRD < 10-4 or undetectable, regardless of method for monitoring. Patients with day 15 FCM-MRD < 10-4 had a cumulative incidence of relapse of 2.3% (95% CI 0-6.8, n = 59). Thus, FCM-MRD allows early identification of patients eligible for reduced intensity therapy, but this needs further studies. In conclusion, FCM-MRD provides reliable risk prediction for T-ALL and can be used for stratification when no PCR-marker is available.
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25.
  • Polli, James E, et al. (author)
  • Summary workshop report : bioequivalence, biopharmaceutics classification system, and beyond
  • 2008
  • In: AAPS Journal. - : Springer Science and Business Media LLC. - 1550-7416. ; 10:2, s. 373-379
  • Journal article (peer-reviewed)abstract
    • The workshop "Bioequivalence, Biopharmaceutics Classification System, and Beyond" was held May 21-23, 2007 in North Bethesda, MD, USA. This workshop provided an opportunity for pharmaceutical scientists to discuss the FDA guidance on the Biopharmaceutics Classification System (BCS), bioequivalence of oral products, and related FDA initiatives such as the FDA Critical Path Initiative. The objective of this Summary Workshop Report is to document the main points from this workshop. Key highlights of the workshop were (a) the described granting of over a dozen BCS-based biowaivers by the FDA for Class I drugs whose formulations exhibit rapid dissolution, (b) continued scientific support for biowaivers for Class III compounds whose formulations exhibit very rapid dissolution, (c) scientific support for a number of permeability methodologies to assess BCS permeability class, (d) utilization of BCS in pharmaceutical research and development, and (e) scientific progress in in vitro dissolution methods to predict dosage form performance.
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26.
  • Quist-Paulsen, P., et al. (author)
  • T-cell acute lymphoblastic leukemia in patients 1-45 years treated with the pediatric NOPHO ALL2008 protocol
  • 2020
  • In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 34:2, s. 347-357
  • Journal article (peer-reviewed)abstract
    • The NOPHO ALL2008 is a population-based study using an unmodified pediatric protocol in patients 1-45 years of age with acute lymphoblastic leukemia. Patients with T-ALL were given a traditional pediatric scheme if fast responding (minimal residual disease (MRD) < 0.1% day 29), or intensive block-based chemotherapy if slow responding (MRD > 0.1% day 29). Both treatment arms included pediatric doses of high-dose methotrexate and asparaginase. If MRD >= 5% on day 29 or >= 0.1% after consolidation, patients were assigned to allogeneic hematopoietic stem cell transplantation. The 5-year overall survival of the 278 T-ALL patients was 0.75 (95% CI 0.69-0.81), being 0.82 (0.74-0.88) for patients 1.0-9.9 years, 0.76 (0.66-0.86) for those 10.0-17.9 years, and 0.65 (0.55-0.75) for the older patients. The risk of death in first remission was significantly higher in adults (12%) compared with the 1-9 years group (4%). The MRD responses in the three age groups were similar, and only a nonsignificant increase in relapse risk was found in adults. In conclusion, an unmodified pediatric protocol in patients 1-45 years is effective in all age groups. The traditional pediatric treatment schedule was safe for all patients, but the intensive block therapy led to a high toxic death rate in adults.
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28.
  • Ziegler, P., et al. (author)
  • A primary nasopharyngeal three-dimensional air-liquid interface cell culture model of the pseudostratified epithelium reveals differential donor- and cell type-specific susceptibility to Epstein-Barr virus infection
  • 2021
  • In: Plos Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 17:4
  • Journal article (peer-reviewed)abstract
    • Epstein-Barr virus (EBV) is a ubiquitous gamma-herpesvirus with latent and lytic cycles. EBV replicates in the stratified epithelium but the nasopharynx is also composed of pseudostratified epithelium with distinct cell types. Latent infection is associated with nasopharyngeal carcinoma (NPC). Here, we show with nasopharyngeal conditionally reprogrammed cells cultured at the air-liquid interface that pseudostratified epithelial cells are susceptible to EBV infection. Donors varied in susceptibility to de novo EBV infection, but susceptible cultures also displayed differences with respect to pathogenesis. The cultures from one donor yielded lytic infection but cells from two other donors were positive for EBV-encoded EBERs and negative for other lytic infection markers. All cultures stained positive for the pseudostratified markers CK7, MUC5AC, alpha-tubulin in cilia, and the EBV epithelial cell receptor Ephrin receptor A2. To define EBV transcriptional programs by cell type and to elucidate latent/lytic infection-differential changes, we performed single cell RNA-sequencing on one EBV-infected culture that resulted in alignment with many EBV transcripts. EBV transcripts represented a small portion of the total transcriptome (similar to 0.17%). All cell types in the pseudostratified epithelium had detectable EBV transcripts with suprabasal cells showing the highest number of reads aligning to many EBV genes. Several restriction factors (IRF1, MX1, STAT1, C18orf25) known to limit lytic infection were expressed at lower levels in the lytic subcluster. A third of the differentially-expressed genes in NPC tumors compared to an uninfected pseudostratified ALI culture overlapped with the differentially-expressed genes in the latent subcluster. A third of these commonly perturbed genes were specific to EBV infection and changed in the same direction. Collectively, these findings suggest that the pseudostratified epithelium could harbor EBV infection and that the pseudostratified infection model mirrors many of the transcriptional changes imposed by EBV infection in NPC. Author summary It has been known for over 50 years that EBV latent infection is associated with NPC. Despite many advances from studies in 2-dimensional cell culture, many aspects of EBV molecular pathogenesis in the nasopharynx remain undefined because the cell types and the biology of the nasopharyngeal epithelium can only be faithfully captured in 3-dimensional cell culture. In the stratified epithelium, cellular differentiation triggers lytic infection but it is not clear to what degree the pseudostratified epithelium is involved. The pseudostratified epithelium is abundant in the lateral wall where the lymphoid-rich fossa of Rosenmuller is located and is a site where NPC tumors most often arises. While the oral epithelium is a site of EBV replication, whether the nasopharyngeal epithelium is a major source of EBV shedding in the nasopharynx is not well defined. Here, we present a 3-dimensional organoid model of the nasopharyngeal pseudostratified epithelium showing that such cells can be infected with EBV in some donor cultures, with examples of both latent and lytic infection. We propose that the cell types of the pseudostratified epithelium should be considered a component of EBV pathogenesis in the nasopharynx and that the difference in donor susceptibility and latent/lytic infection could influence EBV's fitness in the nasopharynx.
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29.
  • Ziska, F., et al. (author)
  • Global sea-to-air flux climatology for bromoform, dibromomethane and methyl iodide
  • 2013
  • In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 13:17, s. 8915-8934
  • Journal article (peer-reviewed)abstract
    • Volatile halogenated organic compounds containing bromine and iodine, which are naturally produced in the ocean, are involved in ozone depletion in both the troposphere and stratosphere. Three prominent compounds transporting large amounts of marine halogens into the atmosphere are bromoform (CHBr3), dibromomethane (CH2Br2) and methyl iodide (CH3I). The input of marine halogens to the stratosphere has been estimated from observations and modelling studies using low-resolution oceanic emission scenarios derived from top-down approaches. In order to improve emission inventory estimates, we calculate data-based high resolution global sea-to-air flux estimates of these compounds from surface observations within the HalOcAt (Halocarbons in the Ocean and Atmosphere) database (https://halocat.geomar.de/). Global maps of marine and atmospheric surface concentrations are derived from the data which are divided into coastal, shelf and open ocean regions. Considering physical and biogeochemical characteristics of ocean and atmosphere, the open ocean water and atmosphere data are classified into 21 regions. The available data are interpolated onto a 1 degrees x 1 degrees grid while missing grid values are interpolated with latitudinal and longitudinal dependent regression techniques reflecting the compounds' distributions. With the generated surface concentration climatologies for the ocean and atmosphere, global sea-to-air concentration gradients and sea-to-air fluxes are calculated. Based on these calculations we estimate a total global flux of 1.5/2.5 Gmol Br yr(-1) for CHBr3, 0.78/0.98 Gmol Br yr(-1) for CH2Br2 and 1.24/1.45 Gmol Br yr(-1) for CH3I (robust fit/ordinary least squares regression techniques). Contrary to recent studies, negative fluxes occur in each sea-to-air flux climatology, mainly in the Arctic and Antarctic regions. "Hot spots" for global polybromomethane emissions are located in the equatorial region, whereas methyl iodide emissions are enhanced in the subtropical gyre regions. Inter-annual and seasonal variation is contained within our flux calculations for all three compounds. Compared to earlier studies, our global fluxes are at the lower end of estimates, especially for bromoform. An under-representation of coastal emissions and of extreme events in our estimate might explain the mismatch between our bottom-up emission estimate and top-down approaches.
  •  
30.
  • Abrahamsson, M. L. A., et al. (author)
  • Ruthenium-manganese complexes for artificial photosynthesis : Factors controlling intramolecular electron transfer and excited-state quenching reactions
  • 2002
  • In: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 41:6, s. 1534-1544
  • Journal article (peer-reviewed)abstract
    • Continuing our work toward a system mimicking the electron-transfer steps from manganese to P-680(+) in photosystem II (PS II), we report a series of ruthenium(II)-manganese(II) complexes that display intramolecular electron transfer from manganese(II) to photooxidized ruthenium(III). The electron-transfer rate constant (k(ET)) values span a large range, 1 X 10(5)-2 x 10(7) s(-1), and we have investigated different factors that are responsible for the variation. The reorganization energies determined experimentally (lambda = 1.5-2.0 eV) are larger than expected for solvent reorganization in complexes of similar size in polar solvents (typically lambda approximate to 1.0 eV). This result indicates that the inner reorganization energy is relatively large and, consequently, that at moderate driving force values manganese complexes are not fast donors. Both the type of manganese ligand and the link between the two metals are shown to be of great importance to the electron-transfer rate. In contrast, we show that the quenching of the excited state of the ruthenium(II) moiety by manganese(II) in this series of complexes mainly depends on the distance between the metals. However, by synthetically modifying the sensitizer so that the lowest metal-to-ligand charge transfer state was localized on the nonbridging ruthenium(II) ligands, we could reduce the quenching rate constant in one complex by a factor of 700 without changing the bridging ligand. Still, the manganese(II)-ruthenium (III) electrontransfer rate constant was not reduced. Consequently, the modification resulted in a complex with very favorable properties.
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31.
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32.
  • Andresen Bergström, Moa, 1978, et al. (author)
  • Rethinking Drug Analysis in Health Care: High-Throughput Analysis of 71 Drugs of Abuse in Oral Fluid Using Ion Mobility-High-Resolution Mass Spectrometry
  • 2022
  • In: Journal of Analytical Toxicology. - : Oxford University Press (OUP). - 0146-4760 .- 1945-2403. ; 46:7, s. 765-775
  • Journal article (peer-reviewed)abstract
    • We have identified a clinical need for a sensitive, specific, flexible, comprehensive and affordable analytical technology to efficiently detect polydrug use. In addition, the current standard practice of surveilled urine sampling is uncomfortable for the patient; hence, more patient-friendly sample collection methods are requested. To fill these needs, we have developed and validated a high-throughput liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method for the analysis of drugs of abuse (DoA) in oral fluid (OF). The method covers a panel of 71 substances including traditional DoA, prescription narcotics and new psychoactive substances (NPS), with a guaranteed limit of identification of <3 mu g/L for 87% of the analytes. Method validation showed high accuracy (>99.7%), sensitivity (>99.7%) and specificity (100%). Most analytes had a high process efficiency during the salting-out liquid-liquid extraction sample preparation and no or only a minor matrix effect during the analysis. We have implemented this method in clinical routine and present data from 18,579 OF samples collected during routine patient treatment in mainly psychiatric and addiction clinics in West Sweden between September 2020 and June 2021. Seventy-one percent of the samples were positive and a total of 41,472 DoA findings were detected. Amphetamine (27%), buprenorphine (25%), nordiazepam (18%) and alprazolam (16%) were most prevalent. New psychoactive substances were detected in 189 samples (1.0%). The occurrence of polydrug use was common; 34% of the positive samples contained three analytes or more and 12% six or more. To the best of our knowledge, this is the first method for comprehensive analysis of DoA in OF using LC-HRMS and the largest dataset published on the detection of DoA in OF. With the current complex and variable drug use pattern, this broad, cost-effective and reliable method has largely replaced immunoassay screening in urine in our laboratory.
  •  
33.
  • Benetton, M., et al. (author)
  • Molecular Measurable Residual Disease Assessment before Hematopoietic Stem Cell Transplantation in Pediatric Acute Myeloid Leukemia Patients: A Retrospective Study by the I-BFM Study Group
  • 2022
  • In: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:7
  • Journal article (peer-reviewed)abstract
    • Hematopoietic stem cell transplantation (HSCT) is a curative post-remission treatment in patients with acute myeloid leukemia (AML), but relapse after transplant is still a challenging event. In recent year, several studies have investigated the molecular minimal residual disease (qPCR-MRD) as a predictor of relapse, but the lack of standardized protocols, cut-offs, and timepoints, especially in the pediatric setting, has prevented its use in several settings, including before HSCT. Here, we propose the first collaborative retrospective I-BFM-AML study assessing qPCR-MRD values in pretransplant bone marrow samples of 112 patients with a diagnosis of AML harboring t(8;21)(q22; q22)RUNX1::RUNX1T1, or inv(16)(p13q22)CBFB::MYH11, or t(9;11)(p21;q23)KMT2A::MLLT3, or FLT3-ITD genetic markers. We calculated an ROC cut-off of 2.1 x 10(-4) that revealed significantly increased OS (83.7% versus 57.1%) and EFS (80.2% versus 52.9%) for those patients with lower qPCR-MRD values. Then, we partitioned patients into three qPCR-MRD groups by combining two different thresholds, 2.1 x 10(-4) and one lower cut-off of 1 x 10(-2), and stratified patients into low-, intermediate-, and high-risk groups. We found that the 5-year OS (83.7%, 68.6%, and 39.2%, respectively) and relapse-free survival (89.2%, 73.9%, and 67.9%, respectively) were significantly different independent of the genetic lesion, conditioning regimen, donor, and stem cell source. These data support the PCR-based approach playing a clinical relevance in AML transplant management.
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34.
  • Berg, K. E., et al. (author)
  • Covalently linked ruthenium(II)-manganese(II) complexes : Distance dependence of quenching and electron transfer
  • 2001
  • In: European Journal of Inorganic Chemistry. - 1434-1948 .- 1099-1948. ; 2001:4, s. 1019-1029
  • Journal article (peer-reviewed)abstract
    • Continuing our development of artificial models for photosystem II in green plants, a series of compounds have been prepared in which a RU(bpy)(3)(2+) photosensitizer is covalently Linked to a manganese(II) electron donor. In addition to a trispicolylamine Ligand, two other manganese Ligands, dipicolylamine and aminodiacetic acid, have been introduced in order to study Ligands that are appropriate for the construction of manganese dimers with open coordination sites for the binding of water. Coordination equilibria of the manganese ions were monitored by EPR. The interactions between the ruthenium and manganese moieties were probed by flash photolysis, cyclic voltammetry and steady-state and time-resolved emission measurements. The quenching of the Ru-II excited state by Mn-II was found to be rapid in complexes with short Ru-Mn distances. Nevertheless, each Run species could be photo-oxidized by bimolecular quenching with methylviologen, and the subsequent electron transfer from Mn-II to Ru-III could be monitored.
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35.
  • Brunner, M, et al. (author)
  • Ambient networks management challenges and approaches
  • 2004
  • In: MOBILITY AWARE TECHNOLOGIES AND APPLICATIONS, PROCEEDINGS. - BERLIN : SPRINGER. - 3540234233 ; , s. 196-216
  • Conference paper (peer-reviewed)abstract
    • System management addresses the provision of functions required for controlling, planning, allocating, monitoring, and deploying the resources of a network and of its services in order to optimize its efficiency and productivity and to safeguard its operation. It is also an enabler for the creation and sustenance of new business models and value chains, reflecting the different roles the service providers and users of a network can assume. Ambient Network represents a new networking approach and it aims to enable the cooperation of heterogeneous networks, on demand and transparently, to the potential users, without the need for pre-configuration or offline negotiation between network operators. To achieve these goals, ambient network management systems have to become dynamic, adaptive, autonomic and responsive to the network and its ambience. This paper discusses relationships between the concepts of autonomous and self-manageability and those of ambient networking, and the challenges and benefits that arise from their employment.
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36.
  • Brunner, M, et al. (author)
  • Towards Ambient Networks Management
  • 2005
  • In: MOBILITY AWARE TECHNOLOGIES AND APPLICATIONS, PROCEEDINGS. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 3540294104 ; , s. 215-229
  • Conference paper (peer-reviewed)abstract
    • Ambient Networks (AN) are under development and they are based on novel networking concepts and systems that will enable a wide range of user and business communication scenarios beyond today's fixed, 3(rd) generation mobile and IP standards. Central to this project is the concept of Ambient Control Space (ACS) and the Domain Manager control function, which manages the underlying data transfer capabilities and presents a set of interfaces towards the supported services and applications. Network Management Systems of Ambient Networks must work in an environment where heterogeneous networks compose and cooperate, on demand and transparently, without the need for manual (pre or re)-configuration or offline negotiations between network operators. To achieve these goals, ambient network management systems must become dynamic, distributed, self-managing and responsive to the network and its ambience. This paper describes the different management research challenges and four complementary solution approaches (i.e. Pattern-based Management, Peer-to-Peer Management, (Un)PnP Management, Traffic Engineering Management Application Approaches) that enable efficient management of ambient networks, and the relationships between them, and presents the main results achieved so far.
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37.
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38.
  • Heuer, W. B., et al. (author)
  • New Dicarboxylic Acid Bipyridine Ligand for Ruthenium Polypyridyl Sensitization of TiO2
  • 2012
  • In: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 51:7, s. 3981-3988
  • Journal article (peer-reviewed)abstract
    • An ambidentate dicarboxylic acid bipyridine ligand, (4,5-diazafluoren-9-ylidene) malonic acid (dfm), was synthesized for coordination to Ru(II) and mesoporous nanocrystalline (anatase) TiO2 thin films. The dim ligand provides a conjugated pathway from the pyridyl rings to the carbonyl carbons of the carboxylic acid groups. X-ray crystal structures of [Ru(bpy)(2)(dfm)]Cl-2 and the corresponding diethyl ester compound, [Ru(bpy)(2)(defm)](PF6)(2), were obtained. The compounds displayed intense metal-to-ligand charge transfer (MLCT) absorption bands in the visible region (epsilon > 11,000 M-1 cm(-1) for [Ru(bpy)(2)(dfm)](PF6)(2) in acetonitrile). Significant room temperature photo-luminescence, PL, was absent in CH3CN but was observed at 77 K in a 4:1 EtOH:MeOH (v:v) glass. Cyclic voltammetry measurements revealed quasi-reversible Ru-III/(II) electrochemistry. Ligand reductions were quasi-reversible for the diethyl ester compound [Ru(bpy)(2)(defm)](2+), but were irreversible for [Ru(bpy)(2)(dfm)](2+). Both compounds were anchored to TiO2 thin films by overnight reactions in CH3CN to yield saturation surface coverages of 3 X 10(-8) mol/cm(2). Attenuated total reflection infrared measurements revealed that the [Ru(bpy)(2)(dfm)](2+) compound was present in the deprotonated carboxylate form when anchored to the TiO2 surface. The MLCT excited states of both compounds injected electrons into TiO2 with quantum yields of 0.70 in 0.1 M LiClO4 CH3CN. Micro- to milli- second charge recombination yielded ground state products. In regenerative solar cells with 0.5 M LiI/0.05 M I-2 in CH3CN, the Ru(bpy)(2)(dfm)/TiO2 displayed incident photon-to-current efficiencies of 0.7 at the absorption maximum. Under the same conditions, the diethylester compound was found to rapidly desorb from the TiO2 surface.
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39.
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40.
  • Nielsen, S. N., et al. (author)
  • Children with low-risk acute lymphoblastic leukemia are at highest risk of second cancers
  • 2017
  • In: Pediatr Blood Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 64:10
  • Journal article (peer-reviewed)abstract
    • BackgroundThe improved survival rates for childhood acute lymphoblastic leukemia (ALL) may be jeopardized by the development of a second cancer, which has been associated with thiopurine therapy. ProcedureWe retrospectively analyzed three sequential Nordic Society of Paediatric Haematology and Oncology's protocols characterized by increasing intensity of thiopurine-based maintenance therapy. We explored the risk of second cancer in relation to protocols, risk group, thiopurine methyltransferase (TPMT) activity, ALL high hyperdiploidy (HeH), and t(12;21)[ETV6/RUNX1]. ResultsAfter median 9.5 years (interquartile range, 5.4-15.3 yrs) of follow-up, 40 of 3,591 patients had developed a second cancer, of whom 38 had non-high-risk B-cell precursor ALL. Patients with standard-risk ALL, who received the longest maintenance therapy, had the highest adjusted hazard of second cancer (hazard ratio [HR], intermediate vs. standard risk: 0.16, 95% CI: 0.06-0.43, P < 0.001; HR, high vs. standard risk: 0.09, 95% CI: 0.02-0.49, P = 0.006); no significant effects of protocol, age, or white blood cell count at diagnosis, ALL HeH, or t(12;21)[ETV6/RUNX1] were observed. A subset analysis on the patients with standard-risk ALL did not show an increased hazard of second cancer from either HeH or t(12;21) (adjusted HR 2.02, 95% CI: 0.69-5.96, P = 0.20). The effect of low TPMT low activity was explored in patients reaching maintenance therapy in clinical remission (n = 3,368); no association with second cancer was observed (adjusted HR 1.43, 95% CI: 0.54-3.76, P = 0.47). ConclusionsThe rate of second cancer was generally highest in patients with low-risk ALL, but we could not identify a subset at higher risk than others.
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41.
  • Abbatt, J. P. D., et al. (author)
  • Halogen activation via interactions with environmental ice and snow in the polar lower troposphere and other regions
  • 2012
  • In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 12:14, s. 6237-6271
  • Journal article (peer-reviewed)abstract
    • The role of ice in the formation of chemically active halogens in the environment requires a full understanding because of its role in atmospheric chemistry, including controlling the regional atmospheric oxidizing capacity in specific situations. In particular, ice and snow are important for facilitating multiphase oxidative chemistry and as media upon which marine algae live. This paper reviews the nature of environmental ice substrates that participate in halogen chemistry, describes the reactions that occur on such substrates, presents the field evidence for ice-mediated halogen activation, summarizes our best understanding of ice-halogen activation mechanisms, and describes the current state of modeling these processes at different scales. Given the rapid pace of developments in the field, this paper largely addresses advances made in the past five years, with emphasis given to the polar boundary layer. The integrative nature of this field is highlighted in the presentation of work from the molecular to the regional scale, with a focus on understanding fundamental processes. This is essential for developing realistic parameterizations and descriptions of these processes for inclusion in larger scale models that are used to determine their regional and global impacts.
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42.
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43.
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44.
  • Gray, Victor, 1988, et al. (author)
  • CdS/ZnS core-shell nanocrystal photosensitizers for visible to UV upconversion
  • 2017
  • In: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6539 .- 2041-6520. ; 8:8, s. 5488-5496
  • Journal article (peer-reviewed)abstract
    • Herein we report the first example of nanocrystal (NC) sensitized triplet-triplet annihilation based photon upconversion from the visible to ultraviolet (vis-to-UV). Many photocatalyzed reactions, such as water splitting, require UV photons in order to function efficiently. Upconversion is one possible means of extending the usable range of photons into the visible. Vis-to-UV upconversion is achieved with CdS/ZnS core-shell NCs as the sensitizer and 2,5-diphenyloxazole (PPO) as annihilator and emitter. The ZnS shell was crucial in order to achieve any appreciable upconversion. From time resolved photoluminescence and transient absorption measurements we conclude that the ZnS shell affects the NC and triplet energy transfer (TET) from NC to PPO in two distinct ways. Upon ZnS growth the surface traps are passivated thus increasing the TET. The shell, however, also acts as a tunneling barrier for TET, reducing the efficiency. This leads to an optimal shell thickness where the upconversion quantum yield (Phi(UC)') is maximized. Here the maximum Phi(UC)' was determined to be 5.2 +/- 0.5% for 4 monolayers of ZnS shell on CdS NCs.
  •  
45.
  • Gulje, F. L., et al. (author)
  • Comparison of 6-mm and 11-mm dental implants in the posterior region supporting fixed dental prostheses: 5-year results of an open multicenter randomized controlled trial
  • 2021
  • In: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 32:1, s. 15-22
  • Journal article (peer-reviewed)abstract
    • Objective The aim of this multicenter, randomized controlled trial was to compare the clinical and radiographic outcomes of 6-mm or 11-mm implants, placed in the posterior maxilla and mandible, during a 5-year follow-up period. Materials and methods Ninety-five patients with adequate bone height for 11-mm implants, were randomly allocated to a 6-mm group (test group with short implants) or an 11-mm group (control group with standard-length implants). Two or three implants of the same length were placed in each patient and after 6 weeks loaded with a splinted provisional restoration. This was followed by definitive splinted restoration 6 months after implant placement. Clinical and radiographic parameters, including the occurrence of complications were recorded. Results A total of 49 patients were enrolled to receive 6-mm implants (n = 108) and 46 patients to receive 11-mm implants (n = 101). Three implants (two of 6 mm and one of 11 mm in length) were lost before loading and one 6-mm implant after 15 months of function, and one 11-mm implant was lost during the first year of function. The 5-year survival rates were 96.0% and 98.9% in the 6-mm and 11-mm group, respectively. The mean marginal bone level changes 5 years post-loading were 0.01 +/- 0.45 mm (bone gain) in the 6-mm group and -0.12 +/- 0.93 mm (bone loss) in the 11-mm group (p = .7670). Clinical parameters, including plaque, bleeding on probing and pocket probing depth were not significantly different between the groups, and also technical complications were low. Conclusion The clinical and radiographic outcomes of 6-mm short and 11-mm standard-length implants were not different during a 5-year evaluation period.
  •  
46.
  • Lie, S. O., et al. (author)
  • Long-term results in children with AML: NOPHO-AML Study Group--report of three consecutive trials
  • 2005
  • In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 19:12, s. 2090-100
  • Journal article (peer-reviewed)abstract
    • In all, 447 children with acute myeloid leukaemia (AML) have been treated on three consecutive NOPHO studies from July 1984 to December 2001. NOPHO-AML 84 was of moderate intensity with an induction of three courses of cytarabine, 6-thioguanine and doxorubicin followed by four consolidation courses with high-dose cytarabine. The 5-year event-free survival (EFS), disease free survival (DFS) and overall survival (OS) were 29, 37 and 38%. NOPHO-AML 88 was of high intensity with the addition of etoposide and mitoxantrone in selected courses during induction and consolidation. The interval between the induction courses should be as short as possible, that is, time intensity was introduced. The 5-year EFS, DFS and OS were 41, 48 and 46%. In NOPHO-AML 93, the treatment was stratified according to response to first induction course. The protocol utilised the same induction blocks as NOPHO-AML 88, but after the first block, children with a hypoplastic, nonleukaemic bone marrow were allowed to recover before the second block. Consolidation was identical with NOPHO-AML 88. The 5-year EFS, DFS and OS in NOPHO-AML 93 were 48, 52 and 65%. The new NOPHO-AML protocol has been based on experiences from previous protocols with stratification of patients with regard to in vivo response and specific cytogenetic aberrations.
  •  
47.
  •  
48.
  • Toft, N, et al. (author)
  • Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia.
  • 2018
  • In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 32, s. 606-615
  • Journal article (peer-reviewed)abstract
    • Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1-45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients were of age 1-9 years (A), 266 were 10-17 years (B) and 221 were 18-45 years (C). Sixteen patients (three adults) died during induction. All others achieved remission after induction or 1-3 intensive blocks. Subsequently, 45 patients (12 adults) died, 122 patients relapsed (32 adults) with a median time to relapse of 1.6 years and 13 (no adult) developed a second malignancy. Median follow-up time was 4.6 years. Among the three age groups, older patients more often had higher risk ALL due to T-ALL (32%/25%/9%, P<0.001), KMT2A rearrangements (6%/5%/3%, P<0.001) and higher day 29 residual leukemia for B-lineage (P<0.001), but not T-ALL (P=0.53). Event-free survival rates (pEFS5y) were 89±1% (A), 80±3% (B) and 74±4% (C) with significant differences only for non-high risk groups. Except for thrombosis, pancreatitis and osteonecrosis, the risk of 19 specified toxicities was not enhanced by age above 10 years. In conclusion, a pediatric-based protocol is tolerable and effective for young adults, despite their increased frequency of higher risk features.Leukemia advance online publication, 22 September 2017; doi:10.1038/leu.2017.265.
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49.
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50.
  • Johansson, A., et al. (author)
  • Synthesis and photophysics of one mononuclear Mn(III) and one dinuclear Mn(III,III) complex covalently linked to a ruthenium(II) tris(bipyridyl) complex
  • 2003
  • In: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 42, s. 7502-7511
  • Journal article (peer-reviewed)abstract
    • The preparation of donor (D)-photosensitizer (S) arrays, consisting of a manganese complex as D and a ruthenium tris(bipyridyl) complex as S has been pursued. Two new ruthenium complexes containing coordinating sites for one (2a) and two manganese ions (3a) were prepared in order to provide models for the donor side of photosystem II in green plants. The manganese coordinating site consists of bridging and terminal phenolate as well as terminal pyridyl ligands. The corresponding ruthenium-manganese complexes, a manganese monomer 2b and dimer 3b, were obtained. For the dimer 3b, our data suggest that intramolecular electron transfer from manganese to photogenerated ruthenium(III) is fast, k(ET) > 5 x 10(7) s(-1).
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