| 1. |
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| 2. |
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| 3. |
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| 4. |
- Fantini, R, et al.
(författare)
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EU FP7 INFSO-ICT-317669 METIS, D3.2 First performance results for multi-node/multi-antenna transmission technologies
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)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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| 5. |
- Carvalho, E. de, et al.
(författare)
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EU FP7 INFSO-ICT-317669 METIS, D3.1 Positioning of multi-node/multi-antenna technologies
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)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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| 6. |
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| 7. |
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| 8. |
- Abrahamsson, B., et al.
(författare)
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Six years of progress in the oral biopharmaceutics area - A summary from the IMI OrBiTo project
- 2020
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : ELSEVIER. - 0939-6411 .- 1873-3441. ; 152, s. 236-247
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Tidskriftsartikel (refereegranskat)abstract
- OrBiTo was a precompetitive collaboration focused on the development of the next generation of Oral Biopharmaceutics Tools. The consortium included world leading scientists from nine universities, one regulatory agency, one non-profit research organisation, three small/medium sized specialist technology companies together with thirteen pharmaceutical companies. The goal of the OrBiTo project was to deliver a framework for rational application of predictive biopharmaceutics tools for oral drug delivery. This goal was achieved through novel prospective investigations to define new methodologies or refinement of existing tools. Extensive validation has been performed of novel and existing biopharmaceutics tools using historical datasets supplied by industry partners as well as laboratory ring studies. A combination of high quality in vitro and in vivo characterizations of active drugs and formulations have been integrated into physiologically based in silico biopharmaceutics models capturing the full complexity of gastrointestinal drug absorption and some of the best practices has been highlighted. This approach has given an unparalleled opportunity to deliver transformational change in European industrial research and development towards model based pharmaceutical product development in accordance with the vision of model-informed drug development.
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| 9. |
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| 10. |
- Lennernäs, Hans, et al.
(författare)
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Oral biopharmaceutics tools - Time for a new initiative - An introduction to the IMI project OrBiTo
- 2014
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 57:SI, s. 292-299
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Forskningsöversikt (refereegranskat)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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| 11. |
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| 12. |
- Ziska, F., et al.
(författare)
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Global sea-to-air flux climatology for bromoform, dibromomethane and methyl iodide
- 2013
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 13:17, s. 8915-8934
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Tidskriftsartikel (refereegranskat)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.
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| 13. |
- Aapro, M, et al.
(författare)
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Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel
- 2008
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 19:3, s. 420-432
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Tidskriftsartikel (refereegranskat)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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| 14. |
- Abbatt, J. P. D., et al.
(författare)
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Halogen activation via interactions with environmental ice and snow in the polar lower troposphere and other regions
- 2012
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 12:14, s. 6237-6271
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Tidskriftsartikel (refereegranskat)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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| 15. |
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| 16. |
- Christensson, A, et al.
(författare)
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Serum prostate specific antigen complexed to alpha 1-antichymotrypsin as an indicator of prostate cancer
- 1993
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Ingår i: Journal of Urology. - 1527-3792. ; 150:1, s. 100-105
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Tidskriftsartikel (refereegranskat)abstract
- Prostate specific antigen (PSA) in serum has recently been shown to occur in complex with alpha 1-antichymotrypsin and as an approximately 30 kDa. noncomplexed molecular form. We characterized PSA by 3 different assays in samples from 144 patients with benign prostatic hyperplasia (BPH) and 121 with carcinoma of the prostate. One of these noncompetitive assays measured total PSA by detecting PSA complexed to serine proteinase inhibitors and the noncomplexed molecular form, a second measured only PSA in complex with alpha 1-antichymotrypsin, whereas a third detected the noncomplexed form. PSA in complex with alpha 1-antichymotrypsin was the predominant form in all patient sera. Noncomplexed PSA constituted a minor fraction that was significantly smaller in patients with untreated prostate cancer than in those with BPH (p < 0.0001). The proportion of noncomplexed PSA does not correlate to the serum concentration of PSA or that of alpha 1-antichymotrypsin. In men with a serum PSA concentration of less than 10 micrograms./l. the combination of assays measuring total PSA immunoreactivity, the noncomplexed molecular form and PSA in complex with alpha 1-antichymotrypsin may facilitate discrimination between prostate cancer and BPH.
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| 17. |
- Le Roch, Sarah, et al.
(författare)
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European survey on criteria of aesthetics for periodontal evaluation: The ESCAPE study
- 2019
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Ingår i: Journal of Clinical Periodontology. - : Wiley. - 0303-6979 .- 1600-051X. ; 46:11, s. 1116-1123
-
Tidskriftsartikel (refereegranskat)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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| 18. |
- Lennernäs, Hans, et al.
(författare)
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In Vivo Predictive Dissolution (IPD) and Biopharmaceutical Modeling and Simulation : Future Use of Modern Approaches and Methodologies in a Regulatory Context
- 2017
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 14:4, s. 1307-1314
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Tidskriftsartikel (refereegranskat)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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| 19. |
- Polli, James E, et al.
(författare)
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Summary workshop report : bioequivalence, biopharmaceutics classification system, and beyond
- 2008
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Ingår i: AAPS Journal. - : Springer Science and Business Media LLC. - 1550-7416. ; 10:2, s. 373-379
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Tidskriftsartikel (refereegranskat)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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| 20. |
- Ziegler, P., et al.
(författare)
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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
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Ingår i: Plos Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 17:4
-
Tidskriftsartikel (refereegranskat)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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| 21. |
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| 22. |
- Derks, Jan, 1977, et al.
(författare)
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Reconstructive surgical therapy of peri-implantitis: A multicenter randomized controlled clinical trial
- 2022
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Ingår i: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 33:9, s. 921-944
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate the potential benefit of the use of a bone substitute material in the reconstructive surgical therapy of peri-implantitis. Methods In this multicenter randomized clinical trial, 138 patients (147 implants) with peri-implantitis were treated surgically, randomized by coin toss to either a control (access flap surgery) or a test group (reconstructive surgery using bone substitute material). Clinical assessments, including probing pocket depth (PPD), bleeding and suppuration on probing (BOP & SOP) as well as soft tissue recession (REC), were recorded at baseline, 6 and 12 months. Marginal bone levels (MBL), measured on intra-oral radiographs, and patient-reported outcomes (PROs) were recorded at baseline and 12 months. No blinding to group allocation was performed. The primary outcome at 12 months was a composite measure including (i) implant not lost, (ii) absence of BOP/SOP at all aspects, (iii) PPD <= 5 mm at all aspects and (iv) <= 1 mm recession of mucosal margin on the buccal aspect of the implant. Secondary outcomes included (i) changes of MBL, (ii) changes of PPD, BOP%, and buccal KM, (iii) buccal REC and (iv) patient-reported outcomes. Results During follow-up, four implants (one in the test group, three in the control group) in four patients were removed due to disease progression. At 12 months, a total of 69 implants in the test and 68 implants in the control group were examined. Thus, 16.4% and 13.5% of implants in the test and control group, respectively, met all predefined criteria of the composite outcome. PPD reduction and MBL gain were 3.7 mm and about 1.0 mm in both groups. Reduction in mean BOP% varied between 45% (test) and 50% (control), without significant differences between groups. Buccal REC was less pronounced in the test group (M = 0.7, SD = 0.9 mm) when compared to controls (M = 1.1, SD = 1.5 mm). PROs were favorable in both groups without significant differences. One case of allergic reaction to the antibiotic therapy was recorded. No other adverse events were noted. Conclusions Surgical therapy of peri-implantitis effectively improved the clinical and radiographic status at 12 months. While the use of a bone substitute material did not improve reductions of PPD and BOP, buccal REC was less pronounced in the test group. Patient satisfaction was high in both groups.
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| 23. |
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| 24. |
- Frost, B.-M., et al.
(författare)
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Vincristine in childhood leukaemia : No pharmacokinetic rationale for dose reduction in adolescents
- 2003
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Ingår i: Acta Paediatrica. - 0803-5253 .- 1651-2227. ; 92:5, s. 551-557
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To investigate whether there is any pharmacokinetic rationale for the common practice of administering vincristine to adolescents at relatively lower doses than those to younger children. Methods: A total of 98 children, aged 1.3-17.3 y, with acute lymphoblastic leukaemia (ALL) were studied on day 1 of induction therapy. Plasma samples were drawn before and 10, 30, 360 and 1380 min after injection of vincristine 2.0 mg/m2 (maximum dose 2.0 mg) and analysed by high-performance liquid chromatography. Results: The median value (and range) for distribution half-life was 6.4 min (0.8-11.8), elimination half-life 1014 min (258-2570), volume of distribution 445 L/m 2 (137-1241) and total body clearance 362 ml/min/m2 (134-2553). No correlation was found between age and any of these pharmacokinetic parameters. The area under the concentration time curve (AUC) was significantly correlated to age (p = 0.002, ?-0.31), as expected from the dosage of vincristine. The lower AUC in children with a body surface area > 1 m2, which is reached at 8-9 y of age, indicates that they received a less intense treatment because of the capping of the vincristine dose at 2.0 mg. Conclusions: Vincristine pharmacokinetics were not age dependent in this paediatric population. Thus, we found no pharmacokinetic rationale for dose reduction in adolescents. The common practice of limiting the vincristine dose to 2.0 mg should be carefully reconsidered.
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| 25. |
- Gray, Victor, 1988, et al.
(författare)
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CdS/ZnS core-shell nanocrystal photosensitizers for visible to UV upconversion
- 2017
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Ingår i: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6539 .- 2041-6520. ; 8:8, s. 5488-5496
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Tidskriftsartikel (refereegranskat)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.
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| 26. |
- Gulje, F. L., et al.
(författare)
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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
-
Ingår i: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 32:1, s. 15-22
-
Tidskriftsartikel (refereegranskat)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.
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| 27. |
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| 28. |
- Ichioka, Yuki, et al.
(författare)
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Factors influencing outcomes of surgical therapy of peri-implantitis: A secondary analysis of 1-year results from a randomized clinical study
- 2023
-
Ingår i: JOURNAL OF CLINICAL PERIODONTOLOGY. - 0303-6979. ; 50:10, s. 1282-1304
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: To identify predictors of treatment outcomes following surgical therapy of peri-implantitis.Materials and Methods: We performed a secondary analysis of data from a randomized controlled trial (RCT) comparing access flap with or without bone replacement graft. Outcomes at 12 months were probing pocket depth (PPD), bleeding on probing (BOP), soft-tissue recession (REC) and marginal bone level (MBL) change. Multilevel regression analyses were used to identify predictors. We also built an explanatory model for residual signs of inflammation.Results: Baseline PPD was the most relevant predictor, showing positive associations with final PPD, REC and MBL gain, and negative association with probability of pocket closure. Smokers presented higher residual PPD. Absence of keratinized mucosa at baseline increased the probability of BOP but was otherwise not indicative of outcomes. Plaque at 6 weeks was detrimental in terms of residual PPD and BOP. Treatment allocation had an effect on REC. Final BOP was explained by residual PPD & GE;6 mm and plaque at more than two sites.Conclusions: Baseline PPD was the most relevant predictor of the outcomes of surgical therapy of peri-implantitis. Pocket closure should be a primary goal of treatment. Bone replacement grafts may be indicated in aesthetically demanding cases to reduce soft-tissue recession. The importance of smoking cessation and patient-performed plaque control is also underlined.
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| 29. |
- Laurell, M, et al.
(författare)
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Protein C inhibitor in human body fluids. Seminal plasma is rich in inhibitor antigen deriving from cells throughout the male reproductive system
- 1992
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 89:4, s. 101-1094
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Tidskriftsartikel (refereegranskat)abstract
- An assay was developed for the measurement of human protein C inhibitor antigen (PCI) in blood plasma and other biological fluids. Both native PCI, modified inhibitor, and complexes of inhibitor with activated protein C or plasma kallikrein could be measured with the assay. Inhibitor antigen concentrations were found to be very high in seminal plasma (greater than 200 mg/liter), more than 40 times the concentration of PCI found in blood plasma. The inhibitor in seminal plasma was unable to form complexes with activated protein C. Gel filtration and immunoblotting findings indicated that the inhibitor in seminal plasma is present in a high molecular mass complex or cleaved to its modified form. As PCI antigen was absent from seminal plasma of patients with dysfunctional seminal vesicles, the seminal vesicle glands would appear to be the major source of seminal plasma PCI, a conclusion supported by immunohistochemical demonstration of the presence of PCI epitopes in the secretory epithelium of the seminal vesicles. Specific PCI immunoreactivity was also shown to be present in the testes, the epididymis glands, and the prostate, suggesting the inhibitor to have a complex or multiple function in the male reproductive system. Conclusive evidence of a local synthesis of PCI in the four male sex glands was provided by Northern blot analysis of RNA from these organs.
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| 30. |
- Marcinkiewicz, Katarzyna, et al.
(författare)
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The androgen receptor and stem cell pathways in prostate and bladder cancers (review).
- 2012
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Ingår i: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 40:1, s. 5-12
-
Tidskriftsartikel (refereegranskat)abstract
- Bladder cancer is three times more common in men than in women. However, the physiological basis of the male predominance of bladder cancer remains poorly understood. A higher than expected association of prostate and bladder cancers has also been reported which may indicate a common mechanism of carcinogenesis. Consistent with this, androgens and the androgen receptor (AR) play essential roles in prostate carcinogenesis and are believed to play a role in bladder carcinogenesis. There is also evidence implicating cancer stem cells in prostate and bladder cancers. Indeed putative prostate and bladder cancer stem cells share some common molecular features. We highlight key proteins (CD49f, CD133, PTEN, CD44) which are implicated in both prostate and bladder cancers and are enriched in putative prostate and bladder cancer stem cells. We examine published chromatin immuno-precipitation studies analyzing the genome-wide distribution of the AR to identify AR association with, and by inference potential AR-regulation of, these loci. We discuss recent evidence indicating a role for the AR in the splicing of the key urological stem cell protein CD44. We propose a model whereby aberrant AR regulation of these putative stem cell proteins contributes to malignant transformation of prostate and bladder cells. For these reasons we propose that the relationship between androgens and cancer stem cell associated proteins warrants further investigation.
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| 31. |
- Martin, William P., et al.
(författare)
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Dietary restriction and medical therapy drive PPARα-regulated improvements in early diabetic kidney disease in male rats
- 2022
-
Ingår i: Clinical science (London, England : 1979). - 1470-8736. ; 136:21, s. 1485-1511
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Tidskriftsartikel (refereegranskat)abstract
- The attenuation of diabetic kidney disease (DKD) by metabolic surgery is enhanced by pharmacotherapy promoting renal fatty acid oxidation (FAO). Using the Zucker Diabetic Fatty and Zucker Diabetic Sprague Dawley rat models of DKD, we conducted studies to determine if these effects could be replicated with a non-invasive bariatric mimetic intervention. Metabolic control and renal injury were compared in rats undergoing a dietary restriction plus medical therapy protocol (DMT; fenofibrate, liraglutide, metformin, ramipril, and rosuvastatin) and ad libitum-fed controls. The global renal cortical transcriptome and urinary 1H-NMR metabolomic profiles were also compared. Kidney cell type-specific and medication-specific transcriptomic responses were explored through in silico deconvolution. Transcriptomic and metabolomic correlates of improvements in kidney structure were defined using a molecular morphometric approach. The DMT protocol led to ∼20% weight loss, normalized metabolic parameters and was associated with reductions in indices of glomerular and proximal tubular injury. The transcriptomic response to DMT was dominated by changes in fenofibrate- and peroxisome proliferator-activated receptor-α (PPARα)-governed peroxisomal and mitochondrial FAO transcripts localizing to the proximal tubule. DMT induced urinary excretion of PPARα-regulated metabolites involved in nicotinamide metabolism and reversed DKD-associated changes in the urinary excretion of tricarboxylic acid (TCA) cycle intermediates. FAO transcripts and urinary nicotinamide and TCA cycle metabolites were moderately to strongly correlated with improvements in glomerular and proximal tubular injury. Weight loss plus pharmacological PPARα agonism is a promising means of attenuating DKD.
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| 32. |
- Stratmann, Svea, 1989-, et al.
(författare)
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Genomic characterization of relapsed acute myeloid leukemia reveals novel putative therapeutic targets
- 2021
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 5:3, s. 900-912
-
Tidskriftsartikel (refereegranskat)abstract
- Relapse is the leading cause of death of adult and pediatric patients with acute myeloid leukemia (AML). Numerous studies have helped to elucidate the complex mutational landscape at diagnosis of AML, leading to improved risk stratification and new therapeutic options. However, multi-whole-genome studies of adult and pediatric AML at relapse are necessary for further advances. To this end, we performed whole-genome and whole-exome sequencing analyses of longitudinal diagnosis, relapse, and/or primary resistant specimens from 48 adult and 25 pediatric patients with AML. We identified mutations recurrently gained at relapse in ARID1A and CSF1R, both of which represent potentially actionable therapeutic alternatives. Further, we report specific differences in the mutational spectrum between adult vs pediatric relapsed AML, with MGA and H3F3A p.Lys28Met mutations recurrently found at relapse in adults, whereas internal tandem duplications in UBTF were identified solely in children. Finally, our study revealed recurrent mutations in IKZF1, KANSL1, and NIPBL at relapse. All of the mentioned genes have either never been reported at diagnosis in de novo AML or have been reported at low frequency, suggesting important roles for these alterations predominantly in disease progression and/or resistance to therapy. Our findings shed further light on the complexity of relapsed AML and identified previously unappreciated alterations that may lead to improved outcomes through personalized medicine.
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| 33. |
- Stratmann, Svea, 1989-, et al.
(författare)
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Transcriptomic analysis reveals proinflammatory signatures associated with acute myeloid leukemia progression
- 2022
-
Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 6:1, s. 152-164
-
Tidskriftsartikel (refereegranskat)abstract
- Numerous studies have been performed over the last decade to exploit the complexity of genomic and transcriptomic lesions driving the initiation of acute myeloid leukemia (AML). These studies have helped improve risk classification and treatment options. Detailed molecular characterization of longitudinal AML samples is sparse, however; meanwhile, relapse and therapy resistance represent the main challenges in AML care. To this end, we performed transcriptome-wide RNA sequencing of longitudinal diagnosis, relapse, and/or primary resistant samples from 47 adult and 23 pediatric AML patients with known mutational background. Gene expression analysis revealed the association of short event-free survival with overexpression of GLI2 and IL1R1, as well as downregulation of ST18. Moreover, CR1 downregulation and DPEP1 upregulation were associated with AML relapse both in adults and children. Finally, machine learning–based and network-based analysis identified overexpressed CD6 and downregulated INSR as highly copredictive genes depicting important relapse-associated characteristics among adult patients with AML. Our findings highlight the importance of a tumor-promoting inflammatory environment in leukemia progression, as indicated by several of the herein identified differentially expressed genes. Together, this knowledge provides the foundation for novel personalized drug targets and has the potential to maximize the benefit of current treatments to improve cure rates in AML. ß 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
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| 34. |
- Abrahamsson, Katarina, 1957, et al.
(författare)
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Variations of biochemical parameters along a transect in the Southern Ocean, with special emphasis on volatile halogenated organic compounds
- 2004
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Ingår i: Deep-sea research. Part II, Topical studies in oceanography. - : Elsevier BV. - 0967-0645. ; 51:22-24, s. 2745-2756
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Tidskriftsartikel (refereegranskat)abstract
- A number of parameters of biogeochemical interest were monitored along a north-southerly transect (S 43-S 63degrees) in the Atlantic Sector of the Southern Ocean from the 8th to the 20th of December 1997. Changes in total dissolved inorganic carbon (C-T) and total alkalinity (A(T)) were mostly dependent on temperature and salinity until the ice edge was reached. After this point only a weak correlation was seen between these. Highest mean values of C-T and A(T) were observed in the Winter Ice Edge (WIE) (2195 and 2319 mumol kg(-1), respectively). Lowest mean AT (2277 mumol kg(-1)) was observed in the Sub-Antarctic Front (SAF), whereas lowest mean CT concentration (2068 mumol kg(-1)) was associated with the Sub-Tropical Front (STF). The pH in situ varied between 8.060 and 8.156 where the highest values were observed in the southern part of the Antarctic Polar Front (APF) and in the Summer Ice Edge (SIE) Region. These peaks were associated with areas of high chlorophyll a (chl a) and tribromomethane values. In the other areas the pH in situ was mainly dependent on hydrography. Bacterial abundance decreased more than one order of magnitude when going from north to south. The decrease appeared to be strongly related to water temperature and there were no elevated abundances at frontal zones. Microphytoplankton dominated in the SAF and APF, whereas the nano- and picoplankton dominated outside these regions. Volatile halogenated compounds were found to vary both with regions, and with daylight. For the iodinated compounds, the highest concentrations were found north of the STF. Brominated hydrocarbons had high concentrations in the STF, but elevated concentrations were also found in the APF and SIE regions. No obvious correlation could be found between the occurrence of individual halocarbons and chl a. On some occasions trichloroethene and tribromomethane related to the presence of nano- and microplankton, respectively.
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| 35. |
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| 36. |
- Abrahamsson, Per-Anders, et al.
(författare)
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Calcitonin and calcitonin gene-related peptide in the human prostate gland
- 2000
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Ingår i: The Prostate. - 0270-4137. ; 44:3, s. 181-186
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Calcitonin-related peptides have been found in the human prostate, and calcitonin (CT) and calcitonin gene-related peptide (CGRP) have been demonstrated in subpopulations of neuroendocrine (NE) cells. The purpose of this study was to determine the concentrations of CT and CGRP as well as the densities of NE cells in normal prostates, benign prostatic hyperplasia (BPH), and carcinoma of the prostate (CAP). METHODS: In 42 specimens of radical prostatectomy, the number of CT- and CGRP-immunoreactive NE cells in areas of normal and BPH tissue was determined, and compared with CAP tissue using immunocytochemistry. In addition, by radioimmunoassay (RIA), tissue levels of CT and CGRP were analyzed in extracts from areas of normal, BPH, and CAP tissue, as verified by adjacent histologic sections. RESULTS: A significant decrease in CT-immunoreactive NE cells was observed in hyperplastic nodules of BPH in comparison to normal tissue. These findings were in parallel with a significant reduction in tissue CT level in BPH compared to normal tissue. There was also a marked, but statistically nonsignificant, reduction in CT levels in CAP tissue. In contrast, levels of CGRP in BPH and CAP tissue did not show any significant differences compared to normal tissue. CONCLUSIONS: CT and CGRP are present in NE cells of the human prostate. Calcitonin levels are significantly reduced in BPH, in parallel with a decreased number of CT-immunoreactive NE cells, whereas no significant changes in tissue levels of CGRP were observed. The functional significance of these findings is discussed.
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| 37. |
- Abrahamsson, P. ‐A, et al.
(författare)
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Immunohistochemical distribution of the three predominant secretory proteins in the parenchyma of hyperplastic and neoplastic prostate glands
- 1988
-
Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 12:1, s. 39-46
-
Tidskriftsartikel (refereegranskat)abstract
- Prostatic acid phosphatase (PAP), prostate‐specific antigen (PSA), and β‐microseminoprotein (β‐MSP) were regularly localized immunohistochemically to the epithelium of the acini and that of the ducts in the nodules of 24 cases of benign prostatic hyperplasia. The immunohistochemical distribution of these three prostatic‐secreted proteins was also examined, with monoclonal antisera against PAP and PSA and with polyclonal antisera against PAP, PSA, and β‐MSP, in a series of 40 cases of prostatic adenocarcinomas graded according to the WHO classification. Highly differentiated (grade I) carcinomas showed a high incidence of PAP‐, PSA‐, and β‐MSP‐immunoreactive cells. As in the normal and hyperplastic prostate parenchyma, highly differentiated (grade I) carcinomas were found to contain an almost equal number of PAP‐, PSA‐, and β‐MSP‐immunoreactive cells. When semiquantitatively assessed, the incidence of PAP‐, PSA‐, and β‐MSP‐immunoreactive cells was found to be lower in the moderately and poorly differentiated (grades II and III) tumors than in the highly differentiated ones; they also showed greater staining variability. Tumor cells immunoreactive with a monoclonal antiserum raised against PAP in carcinomas of grades II and III were less frequent than tumor cells immunoreactive with antisera against PSA, β‐MSP, and a polyclonal antiserum against PAP. The almost identical distribution of PSA and β‐MSP in carcinomas of grades II and III suggests that PSA and β‐MSP are not less sensitive tumor markers than PAP for the monitoring of the course and the treatment of prostatic carcinomas.
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| 38. |
- Abrahamsson, P. A., et al.
(författare)
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Molecular forms of serum prostate-specific antigen : The clinical value of percent free prostate-specific antigen
- 1997
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Ingår i: Urologic Clinics of North America. - 0094-0143. ; 24:2, s. 353-365
-
Tidskriftsartikel (refereegranskat)abstract
- The concept of measuring the proportions of various forms of PSA in serum, particularly the proportion of free to total PSA, represents a new and exciting method of detecting early curable prostate cancers and avoiding unnecessary prostate biopsies in men who have BPH only. Compared with other methods of improving diagnostic specificity, it does not require transrectal ultrasound for determination of prostate volume, as does the use of PSA density, and it does not require multiple blood sampling over a sufficiently long period, as does PSA velocity. Recent findings suggest determination of the proportion of free to total PSA, rather than that of complexed to total PSA, to be the optimal discriminator between patients with prostate cancer and those with BPH in the PSA reflex range of 2.5 or 3 ng/mL to 10 ng/mL, and to improve the clinical accuracy of the PSA test substantially. If the total PSA value is normal, percent free PSA improves the sensitivity (increases cancer detection) of the PSA test; if the total PSA value is slightly elevated, percent free PSA enhances the specificity (eliminates unnecessary negative prostate biopsies) of the PSA test. Both of these outcomes are clinically desirable in attempting to diagnose early, curable prostate cancers in a cost-effective manner among men who also have varying degrees of BPH. Figure 5 contains a diagnostic algorithm for the detection of clinically significant prostate cancers at a curable stage, employing the concept of percent free PSA. As more is learned about percent free PSA, however, it may be necessary to make modifications in how this concept is used clinically.
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| 39. |
- Abrahamsson, P. ‐A, et al.
(författare)
-
Partial characterization of a thyroid‐stimulating hormone‐like peptide in neuroendocrine cells of the human prostate gland
- 1989
-
Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 14:1, s. 71-81
-
Tidskriftsartikel (refereegranskat)abstract
- Immunohistochemical identification of the most prevalent type of neuroendocrine (NE) cells in the human prostate gland can be made with polyclonal antisera against human thyroid‐stimulating hormone (TSH). A TSH‐like peptide was characterized by analysis of prostatic tissue homogenates with sodium dodecyl sulfate‐polyacrylamide gel (SDS‐PAGE) electrophoresis followed by immunoblotting. A single protein band, with an apparent mass of about 32 kDa after reduction, was identified both with polyclonal antisera against human TSH and with a polyclonal antiserum raised against a synthetic peptide corresponding to the carboxyterminal part of the β‐subunit of human TSH. The TSH‐like prostatic peptide identified here is, on the basis of its molecular mass and absence of immunoreactivity with an antiserum raised against a synthetic peptide representing the mid‐portion of the β‐subunit of TSH, not identical with the pituitary β‐subunit of TSH. On the other hand, this 32 kDa prostatic peptide may have certain structural elements in common with the pituitary β‐subunit of TSH, since it is recognized both with polyclonal antisera against TSH and with an antiserum against the carboxyterminal part of the β‐subunit of TSH.
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| 40. |
- Abrahamsson, P. ‐A, et al.
(författare)
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Three predominant prostatic proteins : Drei vorherrschende Prostataproteine
- 1990
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Ingår i: Andrologia. - : Hindawi Limited. - 0303-4569 .- 1439-0272. ; 22:1 S, s. 122-131
-
Tidskriftsartikel (refereegranskat)abstract
- Summary Prostatic acid phosphatase (PAP), prostate‐specific antigen (PSA; or γ‐seminoprotein), and β‐microseminoprotein (β‐MSP; PSP94 or β‐inhibin) are the three predominant proteins secreted by the normal human prostate gland. In the epithelium of normal and hyperplastic prostatic acini and ducts PAP, PSA and β‐MSP have an identical immunohistochemical localization. Highly differentiated (grade I) carcinomas contain an almost equal number of PAP‐, PSA‐ and β‐MSP‐immunoreactive cells; the incidence of these cells is lower and they display a greater staining variability in the moderately and poorly (grade II‐III) differentiated tumours. Especially in poorly differentiated tumours PSA seems to be a more sensitive immunohistochemical marker than PAP or prostatic carcinomas. Moreover, the use of PAP as a marker for prostatic carcinomas is complicated by the reported structural similarities between the prostatic secreted acid phosphatase and lysosomal acid phosphatase occurring in all tissues. The use of β‐MSP as a marker for prostatic carcinomas may be limited by indications of non‐prostatic production of this protein.
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| 41. |
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| 42. |
- Ampatzoglou, Areti, et al.
(författare)
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The Perception of Technical Debt in the Embedded Systems Domain: An Industrial Case Study
- 2016
-
Ingår i: 8th IEEE International Workshop on Managing Technical Debt (MTD). - 2377-8571. - 9781509038541 ; , s. 9-16
-
Konferensbidrag (refereegranskat)abstract
- Technical Debt Management (TDM) has drawn the attention of software industries during the last years, including embedded systems. However, we currently lack an overview of how practitioners from this application domain perceive technical debt. To this end, we conducted a multiple case study in the embedded systems industry, to investigate: (a) the expected lifetime of components that have TD, (b) the most frequently occurring types of TD in them, and (c) the significance of TD against run-time quality attributes. The case study was performed on seven embedded systems industries (telecommunications, printing, smart manufacturing, sensors, etc.) from five countries (Greece, Netherlands, Sweden, Austria, and Finland). The results of the case study suggest that: (a) maintainability is more seriously considered when the expected lifetime of components is larger than ten years; (b) the most frequent types of debt are test, architectural, and code debt; and (c) in embedded systems the run-time qualities are prioritized compared to design-time qualities that are usually associated with TD. The obtained results can be useful for both researchers and practitioners: the former can focus their research on the most industrially-relevant aspects of TD, whereas the latter can be informed about the most common types of TD and how to focus their TDM processes.
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| 43. |
- Artibani, Walter, et al.
(författare)
-
EAU Policy on Live Surgery Events.
- 2014
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 66:1, s. 87-97
-
Forskningsöversikt (refereegranskat)abstract
- Live surgery is an important part of surgical education, with an increase in the number of live surgery events (LSEs) at meetings despite controversy about their real educational value, risks to patient safety, and conflicts of interest.
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| 44. |
- Aumüller, G., et al.
(författare)
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Species‐ and organ‐specificity of secretory proteins derived from human prostate and seminal vesicles
- 1990
-
Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 17:1, s. 31-40
-
Tidskriftsartikel (refereegranskat)abstract
- Polyclonal antibodies against semenogelin (SG) isolated from human seminal vesicle secretion and acid phosphatase (PAP), β‐microseminoprotein (β‐MSP), and Prostate‐Specific Antigen (PSA) derived from human prostatic fluid, as well as a monoclonal antibody against β‐MSP were used for immunocytochemical detection of the respective antigens in different organs from different species. SG immunoreactivity was detected in the epithelium of the pubertal and adult human and in monkey seminal vesicle, ampulla of the vas deferens, and ejaculatory duct. PAP, β‐MSP, and PSA immunoreactivities were detected in the pubertal and adult human prostate and the cranial and caudal monkey prostate. With the exception of a weak PSA immunoreactivity in the proximal portions of the ejaculatory duct, none of the latter antisera reacted with seminal vesicle, ampullary, and ejaculatory duct epithelium. Among the non‐primate species studied (dog, bull, rat, guinea pig) only the canine prostatic epithelium displayed a definite immunoreactivity with the PAP antibody and a moderate reaction with the PSA antibody. No immunoreaction was seen in bull and rat seminal vesicle and canine ampulla of the vas deferens with the SG antibody. The same was true for the (ventral) prostate of rat, bull, and dog for β‐MSP. The epithelium of the rat dorsal prostate showed a slight cross‐reactivity with the monoclonal antibody against β‐MSP and one polyclonal antibody against PSA. The findings indicate a rather strict species‐dependent expression of human seminal proteins which show some similarities in primates, but only marginal relationship to species with different physiology of seminal fluid.
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| 45. |
- Benetton, M., et al.
(författare)
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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
-
Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:7
-
Tidskriftsartikel (refereegranskat)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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| 46. |
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| 47. |
- Brewick, P., et al.
(författare)
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Hybrid Time/Frequency Domain Identification of Real Base-Isolated Structure
- 2016
-
Ingår i: Conference Proceedings of the Society for Experimental Mechanics Series. - Cham : Springer International Publishing. - 2191-5644 .- 2191-5652. - 9783319297514 ; 2, s. 303-311
-
Konferensbidrag (refereegranskat)abstract
- This paper presents a case study using hybrid time-and frequency-domain identifications in a synergistic manner to develop models of a full-scale experimental base-isolated structure. This four-story reinforced-concrete building on an isolation layer (of rubber bearings, elastic sliding bearings, passive metallic yielding dampers, and controllable oil dampers) was designed and constructed at the large-scale Japanese NIED E-Defense earthquake engineering laboratory. A variety of sensors, including accelerometers, were mounted within the structure to measure building response to shake table excitations. While the building was ultimately subjected to historical and synthetic ground motions, the recorded table and building accelerations during a number of random excitation tests are used to identify the structure's natural frequencies, damping ratios and mode shapes. The substantial damping provided by the isolation layer necessitates adopting a hybrid time-and frequency-domain approach for identification. The modes of the structure are separated by frequency content wherein lower frequency modes are identified using time domain approaches from the subspace identification family of methods and higher frequency modes are identified using frequency response functions. Individually, neither approach is able to successfully identify all of the desired modes but, through their combination, the modal properties of the structure are successfully characterized.
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| 48. |
- Burlen, J., et al.
(författare)
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Efficacy of Gastric Electrical Stimulation for Gastroparesis: US/European Comparison
- 2018
-
Ingår i: Gastroenterology Research. - : Elmer Press, Inc.. - 1918-2805 .- 1918-2813. ; 11:5, s. 349-354
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gastric electrical stimulation (GES) is used in both the US and Europe, but little research has investigated the demographics of gastroparesis patients receiving GES by geographic location. Methods: We compared data from 380 patients, 296 female and 84 males, mean age 42 years, 246 idiopathic (ID), 107 diabetic (DM), and 27 post-surgical (PS). The statistical significance was calculated by Chi-square test and a P-value obtained for ID, DM, and PS. The statistical significance was calculated by Fischer exact test and a P-value obtained comparing male vs. female. Results: European centers had 61 GES patients compared to 319 from the US. In Europe, 100% of patients had gastric emptying test (GET) values available; in the US, it was 75% of patients. European centers had more DM patients (59%) than the US (22%), and a smaller proportion of ID patients (25%) than the US (72%). There was a statistical difference between the causes of gastroparesis in the patients receiving GES (P-value < 0.00001). There was also significant difference in the gender of the patients receiving GES, with a greater proportion of women in the US (P value = 0.0023). Conclusions: Comparing GES in US vs. Europe demonstrated significant differences in gastroparesis demographics and percentage of patients with GET data. After analyzing the previously discussed results and reviewing recent updates in evidence-based medicine guidelines, the discrepancy and variance in patient populations in the US and Europe emphasizes the need for a database that allows better analysis and treatment of gastroparesis patients worldwide including stimulation therapies.
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| 49. |
- Dellenmark-Blom, Michaela, 1983, et al.
(författare)
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Schooling experiences in children with long-gap esophageal atresia compared with children with esophageal atresia and primary anastomosis: a Swedish study
- 2023
-
Ingår i: Orphanet Journal of Rare Diseases. - : BioMed Central (BMC). - 1750-1172. ; 18:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundChildren with long-gap esophageal atresia (LGEA) risk living with aerodigestive morbidity and mental health difficulties. No previous study has investigated their experiences of schooling, despite the importance of schools in children's development, learning and social relationships. We aimed to describe experiences of schooling in children with LGEA in Sweden in comparison with children with EA who had primary anastomosis.MethodChildren with LGEA aged 3-17 were recruited nationwide in Sweden. One parent completed a survey on their child's school-based supports (according to definitions from the Swedish National Agency for Education), school absence, school satisfaction, school functioning (PedsQL 4.0), mental health (Strength and Difficulties Questionnaire) and current symptomatology. School data were compared between 26 children with LGEA to that from 95 children with EA who had PA, a hypothesized milder affected group. Mental health level was determined using validated norms; abnormal & GE; 90 percentile. Data were analyzed using descriptives, correlation and Mann-Whitney-U test. Significance level was p < 0.05.ResultsFormal school-based support was reported in 17 (65.4%) children with LGEA and concerned support with nutritional intake (60%), education (50%) and medical/special health needs (35%). The prevalence of school-based support was significantly higher compared to children with PA overall (36.8%, p = 0.013) and regarding nutritional intake support (20%, p < 0.001). In children with LGEA, school-based support was related to low birth weight (p = 0.036), young child age (p = 0.014), height & LE; -2SD for age/sex (p = 0.024) and an increased number of aerodigestive symptoms (p < 0.05). All children with LGEA who had abnormal mental health scores had school-based support, except for one child. Nine children with LGEA (36%) had school absence & GE; 1times/month the past year, more frequently because of colds/airway infections (p = 0.045) and GI-specific problems compared to PA (p = 0.003). School functioning scores were not significantly different from children with PA (p = 0.34) but correlated negatively with school-based support (< 0.001) and school absence (p = 0.002). One parent out of 26 reported their child's school satisfaction as "not good".ConclusionsChildren with LGEA commonly receive school-based support, reflecting multifaceted daily needs and disease severity. School absence is frequent and related to poorer school functioning. Future research focusing on academic achievement in children with EA is needed.
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| 50. |
- Dickinson, Paul A, et al.
(författare)
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Clinical relevance of dissolution testing in quality by design
- 2008
-
Ingår i: AAPS Journal. - : Springer Science and Business Media LLC. - 1550-7416. ; 10:2, s. 380-390
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Forskningsöversikt (refereegranskat)abstract
- Quality by design (QbD) has recently been introduced in pharmaceutical product development in a regulatory context and the process of implementing such concepts in the drug approval process is presently on-going. This has the potential to allow for a more flexible regulatory approach based on understanding and optimisation of how design of a product and its manufacturing process may affect product quality. Thus, adding restrictions to manufacturing beyond what can be motivated by clinical quality brings no benefits but only additional costs. This leads to a challenge for biopharmaceutical scientists to link clinical product performance to critical manufacturing attributes. In vitro dissolution testing is clearly a key tool for this purpose and the present bioequivalence guidelines and biopharmaceutical classification system (BCS) provides a platform for regulatory applications of in vitro dissolution as a marker for consistency in clinical outcomes. However, the application of these concepts might need to be further developed in the context of QbD to take advantage of the higher level of understanding that is implied and displayed in regulatory documentation utilising QbD concepts. Aspects that should be considered include identification of rate limiting steps in the absorption process that can be linked to pharmacokinetic variables and used for prediction of bioavailability variables, in vivo relevance of in vitro dissolution test conditions and performance/interpretation of specific bioavailability studies on critical formulation/process variables. This article will give some examples and suggestions how clinical relevance of dissolution testing can be achieved in the context of QbD derived from a specific case study for a BCS II compound.
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