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Sökning: WFRF:(Finne P)

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1.
  • Mottola, Luca, et al. (författare)
  • MakeSense : Simplifying the Integration of Wireless Sensor Networks into Business Processes
  • 2019
  • Ingår i: IEEE Transactions on Software Engineering. - : Institute of Electrical and Electronics Engineers Inc.. - 0098-5589 .- 1939-3520. ; 45:6, s. 576-596
  • Tidskriftsartikel (refereegranskat)abstract
    • A wide gap exists between the state of the art in developing Wireless Sensor Network (WSN) software and current practices concerning the design, execution, and maintenance of business processes. WSN software is most often developed based on low-level OS abstractions, whereas business process development leverages high-level languages and tools. This state of affairs places WSNs at the fringe of industry. The makeSense system addresses this problem by simplifying the integration of WSNs into business processes. Developers use BPMN models extended with WSN-specific constructs to specify the application behavior across both traditional business process execution environments and the WSN itself, which is to be equipped with application-specific software. We compile these models into a high-level intermediate language-Also directly usable by WSN developers-And then into OS-specific deployment-ready binaries. Key to this process is the notion of meta-Abstraction, which we define to capture fundamental patterns of interaction with and within the WSN. The concrete realization of meta-Abstractions is application-specific; developers tailor the system configuration by selecting concrete abstractions out of the existing codebase or by providing their own. Our evaluation of makeSense shows that i) users perceive our approach as a significant advance over the state of the art, providing evidence of the increased developer productivity when using makeSense; ii) in large-scale simulations, our prototype exhibits an acceptable system overhead and good scaling properties, demonstrating the general applicability of makeSense; and, iii) our prototype-including the complete tool-chain and underlying system support-sustains a real-world deployment where estimates by domain specialists indicate the potential for drastic reductions in the total cost of ownership compared to wired and conventional WSN-based solutions.
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  • Finne, P, et al. (författare)
  • Algorithms based on prostate-specific antigen (PSA), free PSA, digital rectal examination and prostate volume reduce false-positive PSA results in prostate cancer screening.
  • 2004
  • Ingår i: Int J Cancer. - : Wiley. ; 111:2, s. 310-315
  • Tidskriftsartikel (refereegranskat)abstract
    • Our objective was to determine whether multivariate algorithms based on serum total PSA, the free proportion of PSA, age, digital rectal examination and prostate volume can reduce the rate of false-positive PSA results in prostate cancer screening more effectively than the proportion of free PSA alone at 95% sensitivity. A total of 1,775 consecutive 55- to 67-year-old men with a serum PSA of 4-10 g/l in the European Randomized Study of Screening for Prostate Cancer were included. To predict the presence of cancer, multivariate algorithms were constructed using logistic regression (LR) and a multilayer perceptron neural network with Bayesian regularization (BR-MLP). A prospective setting was simulated by dividing the data set chronologically into one set for training and validation (67%, n = 1,183) and one test set (33%, n = 592). The diagnostic models were calibrated using the training set to obtain 95% sensitivity. When applied to the test set, the LR model, the BR-MLP model and the proportion of free PSA reached 92%, 87% and 94% sensitivity and reduced 29%, 36% and 22% of the false-positive PSA results, respectively. At a fixed sensitivity of 95% in the test set, the LR model eliminated more false-positive PSA results (22%) than the proportion of free PSA alone (17%) (p < 0.001), whereas the BR-MLP model did not (19%) (p = 0.178). The area under the ROC curve was larger for the LR model (0.764, p = 0.030) and the BR-MLP model (0.760, p = 0.049) than for the proportion of free PSA (0.718). A multivariate algorithm can be used to reduce unnecessary prostate biopsies in screening more effectively than the proportion of free PSA alone, but the algorithms will require updating when clinical practice develops with time. © 2004 Wiley-Liss, Inc.
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  • Koopman, J J E, et al. (författare)
  • Senescence rates in patients with end-stage renal disease: a critical appraisal of the Gompertz model.
  • 2011
  • Ingår i: Aging Cell. - : Wiley. - 1474-9726 .- 1474-9718. ; Dec, s. 233-238
  • Tidskriftsartikel (refereegranskat)abstract
    • The most frequently used model to describe the exponential increase in mortality rate over age is the Gompertz equation. Logarithmically transformed, the equation conforms to a straight line, of which the slope has been interpreted as the rate of senescence. Earlier, we proposed the derivative function of the Gompertz equation as a superior descriptor of senescence rate. Here, we tested both measures of the rate of senescence in a population of patients with end-stage renal disease. It is clinical dogma that patients on dialysis experience accelerated senescence, whereas those with a functional kidney transplant have mortality rates comparable to the general population. Therefore, we calculated the age-specific mortality rates for European patients on dialysis (n=274,221; follow-up=594,767 person-years), for European patients with a functioning kidney transplant (n=61,286; follow-up=345,024 person-years), and for the general European population. We found higher mortality rates, but a smaller slope of logarithmical mortality curve for patients on dialysis compared to both patients with a functioning kidney transplant and the general population (p<0.001). A classical interpretation of the Gompertz model would imply that the rate of senescence in patients on dialysis is lower than in patients with a functioning transplant and lower than in the general population. In contrast, the derivative function of the Gompertz equation yielded highest senescence rates for patients on dialysis, whereas the rate was similar in patients with a functioning transplant and the general population. We conclude that the rate of senescence is better described by the derivative function of the Gompertz equation.
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  • Arvidson, K., et al. (författare)
  • Bone regeneration and stem cells
  • 2011
  • Ingår i: Journal of Cellular and Molecular Medicine (Print). - : Wiley-Blackwell. - 1582-1838 .- 1582-4934. ; 15:4, s. 718-746
  • Forskningsöversikt (refereegranskat)abstract
    • Introduction Bone fracture healing and healing problems Biomaterial scaffolds and tissue engineering in bone formation Bone tissue engineering Biomaterial scaffolds Synthetic scaffolds Micro- and nanostructural properties of scaffolds Conclusion Mesenchymal stem cells and osteogenesis Bone tissue Origin of osteoblasts Isolation and characterization of bone marrow derived MSC In vitro differentiation of MSC into osteoblast lineage cells In vivo differentiation of MSC into bone Factors and pathways controlling osteoblast differentiation of hMSC Defining the relationship between osteoblast and adipocyte differentiation from MSC MSC and sex hormones Effect of aging on osteoblastogenesis Conclusion Embryonic, foetal and adult stem cells in osteogenesis Cell-based therapies for bone Specific features of bone cells needed to be advantageous for clinical use Development of therapeutic biological agents Clinical application concerns Conclusion Platelet-rich plasma (PRP), growth factors and osteogenesis PRP effects in vitro on the cells involved in bone repair PRP effects on osteoblasts PRP effects on osteoclasts PRP effects on endothelial cells PRP effects in vivo on experimental animals The clinical use of PRP for bone repair Non-union Distraction osteogenesis Spinal fusion Foot and ankle surgery Total knee arthroplasty Odontostomatology and maxillofacial surgery Conclusion Molecular control of osteogenesis TGF-beta signalling FGF signalling IGF signalling PDGF signalling MAPK signalling pathway Wnt signalling pathway Hedgehog signalling Notch signalling Ephrin signalling Transcription factors regulating osteoblast differentiation Conclusion Summary This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed.
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  • Atsawawaranunt, Kamolphat, et al. (författare)
  • The SISAL database : a global resource to document oxygen and carbon isotope records from speleothems
  • 2018
  • Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 10:3, s. 1687-1713
  • Tidskriftsartikel (refereegranskat)abstract
    • Stable isotope records from speleothems provide information on past climate changes, most particularly information that can be used to reconstruct past changes in precipitation and atmospheric circulation. These records are increasingly being used to provide "out-of-sample" evaluations of isotope-enabled climate models. SISAL (Speleothem Isotope Synthesis and Analysis) is an international working group of the Past Global Changes (PAGES) project. The working group aims to provide a comprehensive compilation of speleothem isotope records for climate reconstruction and model evaluation. The SISAL database contains data for individual speleothems, grouped by cave system. Stable isotopes of oxygen and carbon (delta O-18, delta C-13) measurements are referenced by distance from the top or bottom of the speleothem. Additional tables provide information on dating, including information on the dates used to construct the original age model and sufficient information to assess the quality of each data set and to erect a standardized chronology across different speleothems. The metadata table provides location information, information on the full range of measurements carried out on each speleothem and information on the cave system that is relevant to the interpretation of the records, as well as citations for both publications and archived data.
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  • Comas-Bru, Laia, et al. (författare)
  • Evaluating model outputs using integrated global speleothem records of climate change since the last glacial
  • 2019
  • Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 15:4, s. 1557-1579
  • Tidskriftsartikel (refereegranskat)abstract
    • Although quantitative isotope data from speleothems has been used to evaluate isotope-enabled model simulations, currently no consensus exists regarding the most appropriate methodology through which to achieve this. A number of modelling groups will be running isotope-enabled palaeoclimate simulations in the framework of the Coupled Model Intercomparison Project Phase 6, so it is timely to evaluate different approaches to using the speleothem data for data-model comparisons. Here, we illustrate this using 456 globally distributed speleothem delta O-18 records from an updated version of the Speleothem Isotopes Synthesis and Analysis (SISAL) database and palaeoclimate simulations generated using the ECHAM5-wiso isotope-enabled atmospheric circulation model. We show that the SISAL records reproduce the first-order spatial patterns of isotopic variability in the modern day, strongly supporting the application of this dataset for evaluating model-derived isotope variability into the past. However, the discontinuous nature of many speleothem records complicates the process of procuring large numbers of records if data-model comparisons are made using the traditional approach of comparing anomalies between a control period and a given palaeoclimate experiment. To circumvent this issue, we illustrate techniques through which the absolute isotope values during any time period could be used for model evaluation. Specifically, we show that speleothem isotope records allow an assessment of a model's ability to simulate spatial isotopic trends. Our analyses provide a protocol for using speleothem isotope data for model evaluation, including screening the observations to take into account the impact of speleothem mineralogy on delta O-18 values, the optimum period for the modern observational baseline and the selection of an appropriate time window for creating means of the isotope data for palaeo-time-slices.
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  • Derner, Ondrej, et al. (författare)
  • Incidence of Kidney Replacement Therapy and Subsequent Outcomes Among Patients With Systemic Lupus Erythematosus : Findings From the ERA Registry
  • 2022
  • Ingår i: American Journal of Kidney Diseases. - : Elsevier BV. - 0272-6386. ; 79:5, s. 635-645
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale & Objective: There is a dearth of data characterizing patients receiving kidney replacement therapy (KRT) for kidney failure due to systemic lupus erythematosus (SLE) and their clinical outcomes. The aim of this study was to describe trends in incidence and prevalence of KRT among these patients as well as to compare their outcomes versus those of patients treated with KRT for diseases other than SLE. Study Design: Retrospective cohort study based on kidney registry data. Setting & Participants: Patients recorded in 14 registries of patients receiving KRT that provided data to the European Renal Association Registry between 1992 and 2016. Predictor: SLE as cause of kidney failure. Outcomes: Incidence and prevalence of KRT, patient survival while receiving KRT, patient and graft survival after kidney transplant, and specific causes of death. Analytical Approach: Kaplan-Meier methods and Cox regression models were fit to compare patient survival between the SLE and non-SLE groups, overall KRT, dialysis, and patient and graft survival after kidney transplant. Results: In total, 1,826 patients commenced KRT for kidney failure due to SLE, representing an incidence of 0.80 per million population (pmp) per year. The incidence remained stable during the study period (annual percent change, 0.1% [95% CI, −0.6% to 0.8%]). Patient survival among patients with SLE receiving KRT was similar to survival in the comparator group (hazard ratio [HR], 1.11 [95% CI, 0.99-1.23]). After kidney transplant, the risk of death was greater among patients with SLE than among patients in the comparator group (HR, 1.25 [95% CI, 1.02-1.53]), whereas the risk of all-cause graft failure was similar (HR, 1.09 [95% CI, 0.95-1.27]). Ten-year patient overall survival during KRT and patient and graft survival after kidney transplant improved over the study period (HRs of 0.71 [95% CI, 0.56-0.91], 0.43 [95% CI, 0.27-0.69], and 0.60 [95% CI, 0.43-0.84], respectively). Patients with SLE receiving KRT were significantly more likely to die of infections (24.8%) than patients in the comparator group (16.9%; P < 0.001). Limitations: No data were available on extrarenal manifestations of SLE, drug treatments, comorbidities, kidney transplant characteristics, or relapses of SLE. Conclusions: The prognosis of patients with SLE receiving KRT has improved over time. Survival of patients with SLE who required KRT was similar compared with patients who required KRT for other causes of kidney failure. Survival following kidney transplants was worse among patients with SLE.
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  • Hirsch, Jan-Mikael, et al. (författare)
  • A clinical evaluation of the Zygoma fixture: one year of follow-up at 16 clinics.
  • 2004
  • Ingår i: Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. - : Elsevier BV. - 0278-2391 .- 1531-5053. ; 62:9 Suppl 2, s. 22-9
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To evaluate treatment outcome with Zygoma fixtures (Nobel Biocare, Göteborg, Sweden) with regard to fixture survival, patient satisfaction, and function of prosthesis replacement. MATERIALS AND METHODS: The treatment outcome of 76 patients treated with 145 Zygoma fixtures at 16 centers was evaluated. Patient's and dentist's evaluations of the functional and aesthetic outcome of the treatment were assessed at delivery of prosthesis and at the 1-year follow-up visit. At the 1-year follow-up visit, the status of the peri-implant mucosa around the abutments and the amount of plaque were registered. RESULTS: Sixty-six of the 76 patients, with 124 Zygoma fixtures supporting the prosthetic restorations, were evaluated at the 1-year follow-up. The overall survival rate for the Zygoma fixtures was 97.9% after 1-year of follow-up. Eighty percent of the patients were fully satisfied with both aesthetic and functional outcome at the time of prosthetic insertion and at the 1-year follow-up. All reported data from the dentists, with the exception of one restoration with several abutment screw loosenings, scored from acceptable to excellent for the aesthetic and functional outcome of the treatment. The status of peri-implant mucosa was recorded as normal in approximately 60% of the sites. Plaque, when present, was more often detected on the palatal surfaces compared with the buccal surfaces. CONCLUSION: This 1-year follow-up of Zygoma fixtures has shown good results with an acceptable number of minor complications and a majority of satisfied patients.
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  • Hruskova, Zdenka, et al. (författare)
  • Characteristics and Outcomes of Patients With Systemic Sclerosis (Scleroderma) Requiring Renal Replacement Therapy in Europe: Results From the ERA-EDTA Registry
  • 2019
  • Ingår i: American Journal of Kidney Diseases. - : W B SAUNDERS CO-ELSEVIER INC. - 0272-6386 .- 1523-6838. ; 73:2, s. 184-193
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale amp; Objective: Data for outcomes of patients with end-stage renal disease (ESRD) secondary to systemic sclerosis (scleroderma) requiring renal replacement therapy (RRT) are limited. We examined the incidence and prevalence of ESRD due to scleroderma in Europe and the outcomes among these patients following initiation of RRT. Study Design: Registry study of incidence and prevalence and a matched cohort study of clinical outcomes. Setting amp; Participants: Patients represented in any of 19 renal registries that provided data to the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry between 2002 and 2013. Predictor: Scleroderma as the identified cause of ESRD. Outcomes: Incidence and prevalence of ESRD from scleroderma. Recovery from RRT dependence, patient survival after ESRD, and graft survival after kidney transplantation. Analytical Approach: Incidence and prevalence were calculated using population data from the European Union and standardized to population characteristics in 2005. Patient and graft survival were compared with 2 age- and sex-matched control groups without scleroderma: (1) diabetes mellitus as the cause of ESRD and (2) conditions other than diabetes mellitus as the cause of ESRD. Survival analyses were performed using Kaplan-Meier analysis and Cox regression. Results: 342 patients with scleroderma (0.14% of all incident RRT patients) were included. Between 2002 and 2013, the range of adjusted annual incidence and prevalence rates of RRT for ESRD due to scleroderma were 0.11 to 0.26 and 0.73 to 0.95 per million population, respectively. Recovery of independent kidney function was greatest in the scleroderma group (7.6% vs 0.7% in diabetes mellitus and 2.0% in other primary kidney diseases control group patients, both Pamp;lt;0.001), though time required to achieve recovery was longer. The 5-year survival probability from day 91 of RRT among patients with scleroderma was 38.9% (95% CI, 32.0%-45.8%), whereas 5-year posttransplantation patient survival and 5-year allograft survival were 88.2% (95% CI, 75.3%-94.6%) and 72.4% (95% CI, 55.0%-84.0%), respectively. Adjusted mortality from day 91 on RRT was higher among patients with scleroderma than observed in both control groups (HRs of 1.25 [95% CI, 1.05-1.48] and 2.00 [95% CI, 1.69-2.39]). In contrast, patient and graft survival after kidney transplantation did not differ between patients with scleroderma and control groups. Limitations: No data for extrarenal manifestations, treatment, or recurrence. Conclusions: Survival of patients with scleroderma who receive dialysis for more than 90 days was worse than for those with other causes of ESRD. Patient survival after transplantation was similar to that observed among patients with ESRD due to other conditions. Patients with scleroderma had a higher rate of recovery from RRT dependence than controls.
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  • Kahnberg, Karl-Erik, 1941, et al. (författare)
  • Clinical evaluation of the zygoma implant : 3-year follow-up at 16 clinics
  • 2007
  • Ingår i: Journal of oral and maxillofacial surgery (Print). - : Elsevier BV. - 0278-2391 .- 1531-5053. ; 65:10, s. 2033-2038
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The purpose of this clinical investigation was to evaluate the treatment outcome with zygoma implants with regard to implant survival, patient satisfaction, and function of prosthesis replacement after 3 years. Patients and Methods: The treatment outcome of 76 patients treated with 145 zygoma fixtures at 16 centers was evaluated with regard to implant survival. Status of peri-implant mucosa and amount of plaque were registered annually. Patients' and dentists' evaluations of the functional and esthetic outcome of the treatment were assessed at delivery of prosthesis and thereafter at each follow-up visit. Results: Sixty of 76 patients were followed for 3 years after prosthetic delivery. Five of 145 placed zygoma implants failed during the course of the study resulting in an overall implant survival rate of 96.3%. At the 3-year follow-up, 75% of the implants sites were registered with normal peri-implant mucosa and 68% with no visible plaque. The patients were fully satisfied with the esthetic and functional outcome of the treatment in 86% and 71%, respectively, at the 3-year follow-up visit. All reported data from dentists scored from acceptable to excellent. Conclusion: The multicenter study showed a high predictability of the zygoma implant-supported rehabilitation.
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  • Kleinhans, C., et al. (författare)
  • A perfusion bioreactor system efficiently generates cell-loaded bone substitute materials for addressing critical size bone defects
  • 2015
  • Ingår i: Biotechnology Journal. - : Wiley-VCH Verlagsgesellschaft. - 1860-6768 .- 1860-7314. ; 10:11, s. 1727-1738
  • Tidskriftsartikel (refereegranskat)abstract
    • Critical size bone defects and non-union fractions are still challenging to treat. Cell-loaded bone substitutes have shown improved bone ingrowth and bone formation. However, a lack of methods for homogenously colonizing scaffolds limits the maximum volume of bone grafts. Additionally, therapy robustness is impaired by heterogeneous cell populations after graft generation. Our aim was to establish a technology for generating grafts with a size of 10.5 mm in diameter and 25 mm of height, and thus for grafts suited for treatment of critical size bone defects. Therefore, a novel tailor-made bioreactor system was developed, allowing standardized flow conditions in a porous poly(L-lactide-co-caprolactone) material. Scaffolds were seeded with primary human mesenchymal stem cells derived from four different donors. In contrast to static experimental conditions, homogenous cell distributions were accomplished under dynamic culture. Additionally, culture in the bioreactor system allowed the induction of osteogenic lineage commitment after one week of culture without addition of soluble factors. This was demonstrated by quantitative analysis of calcification and gene expression markers related to osteogenic lineage. In conclusion, the novel bioreactor technology allows efficient and standardized conditions for generating bone substitutes that are suitable for the treatment of critical size defects in humans.
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  • Madar Johansson, Miralda, et al. (författare)
  • The binding mechanism of the virulence factor Streptococcus suis adhesin P subtype to globotetraosylceramide is associated with systemic disease
  • 2020
  • Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 295:42, s. 14305-14324
  • Tidskriftsartikel (refereegranskat)abstract
    • Streptococcus suis is part of the pig commensal microbiome but strains can also be pathogenic, causing pneumonia and meningitis in pigs as well as zoonotic meningitis. According to genomic analysis, S. suis is divided into asymptomatic carriage, respiratory and systemic strains with distinct genomic signatures. Because the strategies to target pathogenic S. suis are limited, new therapeutic approaches are needed. The virulence factor S. suis adhesin P (SadP) recognizes the galabiose Gal alpha 1-4Gal-oligosaccharide. Based on its oligosaccharide fine specificity, SadP can be divided into subtypes P-N and P-O. We show here that subtype P-N is distributed in the systemic strains causing meningitis, whereas type P-O is found in asymptomatic carriage and respiratory strains. Both types of SadP are shown to predominantly bind to pig lung globotriaosylceramide (Gb3). However, SadP adhesin from systemic subtype P-N strains also binds to globotetraosylceramide (Gb4). Mutagenesis studies of the galabiose-binding domain of type P-N SadP adhesin showed that the amino acid asparagine 285, which is replaced by an aspartate residue in type P-O SadP, was required for binding to Gb4 and, strikingly, was also required for interaction with the glycomimetic inhibitor phenylurea-galabiose. Molecular dynamics simulations provided insight into the role of Asn-285 for Gb4 and phenylurea-galabiose binding, suggesting additional hydrogen bonding to terminal GalNAc of Gb4 and the urea group. Thus, the Asn-285-mediated molecular mechanism of type P-N SadP binding to Gb4 could be used to selectively target S. suis in systemic disease without interfering with commensal strains, opening up new avenues for interventional strategies against this pathogen.
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  • Massy, ZA, et al. (författare)
  • Nephrology and Public Policy Committee propositions to stimulate research collaboration in adults and children in Europe
  • 2019
  • Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 34:9, s. 1469-1480
  • Tidskriftsartikel (refereegranskat)abstract
    • The strengths and the limitations of research activities currently present in Europe are explored in order to outline how to proceed in the near future. Epidemiological and clinical research and public policy in Europe are generally considered to be comprehensive and successful, and the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) is playing a key role in the field of nephrology research. The Nephrology and Public Policy Committee (NPPC) aims to improve the current situation and translation into public policy by planning eight research topics to be supported in the coming 5 years by ERA-EDTA.
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  • Ohlsson, Jörgen, et al. (författare)
  • Structure–activity relationships of galabioside derivatives as inhibitors of E. coli and S. suis adhesins: nanomolar inhibitors of S. suis adhesins
  • 2005
  • Ingår i: Organic and Biomolecular Chemistry. - : Royal Society of Chemistry (RSC). - 1477-0539 .- 1477-0520. ; 3:5, s. 886-900
  • Tidskriftsartikel (refereegranskat)abstract
    • Four collections of Gal1-4Gal derivatives were synthesised and evaluated as inhibitors of the PapG class II adhesin of uropathogenic Escherichia coli and of the PN and PO adhesins of Streptococcus suis strains. Galabiosides carrying aromatic structures at C1, methoxyphenyl O-galabiosides in particular, were identified as potent inhibitors of the PapG adhesin. Phenylurea derivatisation at C3 and methoxymethylation at O2 of galabiose provided inhibitors of the S. suis strains type PN adhesin with remarkably high affinities (30 and 50 nM, respectively). In addition, quantitative structure–activity relationship models for E. coli PapG adhesin and S. suis adhesin type PO were developed using multivariate data analysis. The inhibitory lead structures constitute an advancement towards high-affinity inhibitors as potential anti-adhesion therapeutic agents targeting bacterial infections.
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  • Pippias, Maria, et al. (författare)
  • Long-term Kidney Transplant Outcomes in Primary Glomerulonephritis: Analysis From the ERA-EDTA Registry
  • 2016
  • Ingår i: Transplantation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0041-1337 .- 1534-6080. ; 100:9, s. 1955-1962
  • Tidskriftsartikel (refereegranskat)abstract
    • Background We evaluated the 15-year kidney allograft survival in patients with primary glomerulonephritis and determined if the risk of graft loss varied with donor source within each glomerulonephritis group. Methods Using data from the European Renal Association-European Dialysis and Transplant Association Registry, Kaplan-Meier, competing risk, and Cox regression analyses were performed on adult, first kidney transplant recipients during 1991 to 2010 (n = 14 383). Follow-up was set to December 31, 2011. Adjustments for pretransplant dialysis duration, sex, country, and transplant era were made. Death-adjusted graft survival was assessed in patients with glomerulonephritis and compared with those with autosomal dominant polycystic kidney disease (ADPKD), in which the native kidney disease cannot recur. Additionally, death-adjusted graft survival was compared between living and deceased donor transplants within each glomerulonephritis group. Results All glomerulonephritides had a 15-year death-adjusted graft survival probability above 55%. The 15-year risk of death-adjusted graft failure compared to ADPKD ranged from 1.17 (95% confidence interval [95% CI], 1.05-1.31) for immunoglobulin A nephropathy to 2.09 (95% CI, 1.56-2.78) for membranoproliferative glomerulonephritis type II. The expected survival benefits of living over deceased donor transplants were not present in membranoproliferative glomerulonephritis type I (adjusted hazard ratios [HRa], 1.08; 95% CI, 0.73-1.60) or type II (HRa, 0.90; 95% CI, 0.32-2.52) but present in immunoglobulin A nephropathy (HRa, 0.74; 95% CI, 0.59-0.92), membranous nephropathy (HRa, 0.47; 95% CI, 0.29-0.75), and focal segmental glomerulosclerosis (HRa, 0.69; 95% CI, 0.45-1.06). Conclusions This large European study shows favorable long-term kidney graft survival in all primary glomerulonephritides, although this remains lower than graft survival in ADPKD, and confirms that the reluctance to use living donors in some primary glomerulonephritides remains unfounded. These data will further inform prospective renal transplant recipients and donors during pretransplant counselling.
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  • Stel, Vianda S., et al. (författare)
  • International comparison of trends in patients commencing renal replacement therapy by primary renal disease
  • 2019
  • Ingår i: Nephrology. - : Wiley. - 1320-5358 .- 1440-1797. ; 24:10, s. 1064-1076
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To examine international time trends in the incidence of renal replacement therapy (RRT) for end-stage renal disease (ESRD) by primary renal disease (PRD). Methods: Renal registries reporting on patients starting RRT per million population for ESRD by PRD from 2005 to 2014, were identified by internet search and literature review. The average annual percentage change (AAPC) with a 95% confidence interval (CI) of the time trends was computed using Joinpoint regression. Results: There was a significant decrease in the incidence of RRT for ESRD due to diabetes mellitus (DM) in Europe (AAPC = −0.9; 95%CI −1.3; −0.5) and to hypertension/renal vascular disease (HT/RVD) in Australia (AAPC = −1.8; 95%CI −3.3; −0.3), Canada (AAPC = −2.9; 95%CI −4.4; −1.5) and Europe (AAPC = −1.1; 95%CI −2.1; −0.0). A decrease or stabilization was observed for glomerulonephritis in all regions and for autosomal dominant polycystic kidney disease (ADPKD) in all regions except for Malaysia and the Republic of Korea. An increase of 5.2–16.3% was observed for DM, HT/RVD and ADPKD in Malaysia and the Republic of Korea. Conclusion: Large international differences exist in the trends in incidence of RRT by primary renal disease. Mapping of these international trends is the first step in defining the causes and successful preventative measures of CKD.
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33.
  • Suliman, Salwa, et al. (författare)
  • Release and bioactivity of bone morphogenetic protein-2 are affected by scaffold binding techniques in vitro and in vivo
  • 2015
  • Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 197, s. 148-157
  • Tidskriftsartikel (refereegranskat)abstract
    • A low dose of 1 mu g rhBMP-2 was immobilised by four different functionalising techniques on recently developed poly(L-lactide)-co-(epsilon-caprolactone) [(poly(LLA-co-CL)] scaffolds. It was either (i) physisorbed on unmodified scaffolds [PHY], (ii) physisorbed onto scaffolds modified with nanodiamond particles [nDP-PHY], (iii) covalently linked onto nDPs that were used to modify the scaffolds [nDP-COV] or (iv) encapsulated in microspheres distributed on the scaffolds [MICS]. Release kinetics of BMP-2 from the different scaffolds was quantified using targeted mass spectrometry for up to 70 days. PHY scaffolds had an initial burst of release while MICS showed a gradual and sustained increase in release. In contrast, NDP-PHY and nDP-COV scaffolds showed no significant release, although nDP-PHY scaffolds maintained bioactivity of BMP-2. Human mesenchymal stem cells cultured in vitro showed upregulated BMP-2 and osteocalcin gene expression at both week 1 and week 3 in the MICS and nDP-PHY scaffold groups. These groups also demonstrated the highest BMP-2 extracellular protein levels as assessed by ELISA, and mineralization confirmed by Alizarin red. Cells grown on the PHY scaffolds in vitro expressed collagen type 1 alpha 2 early but the scaffold could not sustain rhBMP-2 release to express mineralization. After 4 weeks post-implantation using a rat mandible critical-sized defect model, micro-CT and Masson trichrome results showed accelerated bone regeneration in the PHY, nDP-PHY and MICS groups. The results demonstrate that PHY scaffolds may not be desirable for clinical use, since similar osteogenic potential was not seen under both in vitro and in vivo conditions, in contrast to nDP-PHY and MICS groups, where continuous low doses of BMP-2 induced satisfactory bone regeneration in both conditions. The nDP-PHY scaffolds used here in critical-sized bone defects for the first time appear to have promise compared to growth factors adsorbed onto a polymer alone and the short distance effect prevents adverse systemic side effects.
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34.
  • van Lier, LI, et al. (författare)
  • Predictors of Societal Costs of Older Care-Dependent Adults Living in the Community in 11 European Countries
  • 2019
  • Ingår i: Health services insights. - : SAGE Publications. - 1178-6329. ; 12, s. 1178632918820947-
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective was to identify predictors of societal costs covering formal and informal care utilization by older home care clients in 11 European countries. Methods: Societal costs of 1907 older clients receiving home care for 12 months from the Aged in Home care (AdHoc) study were estimated using the InterRAI Minimum Data Set for Home Care’s (MDS-HC) resource use items. Predictors (medical, functional, and psychosocial domains) of societal costs were identified by performing univariate and multivariate generalized linear model analyses. Results: Mean societal costs per participant were €36 442, ranging from €14 865 in Denmark to €78 836 in the United Kingdom. In the final multivariate model, country, being married, activities of daily living (ADL) dependency, cognitive impairment, limitations of going out, oral conditions, number of medications, arthritis, and cerebro vascular accident (CVA) were significantly associated with societal costs. Conclusions: Of the predictors, ADL dependency and limitations of going out may be modifiable. Developing interventions targeted at improving these conditions may create opportunities to curtail societal costs.
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35.
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36.
  • Weiberg, Erika, 1971-, et al. (författare)
  • The socio-environmental history of the Peloponnese during the Holocene: Towards an integrated understanding of the past
  • 2016
  • Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 136, s. 40-65
  • Tidskriftsartikel (refereegranskat)abstract
    • Published archaeological, palaeoenvironmental, and palaeoclimatic data from the Peloponnese in Greece are compiled, discussed and evaluated in order to analyse the interactions between humans and the environment over the last 9000 years. Our study indicates that the number of human settlements found scattered over the peninsula have quadrupled from the prehistoric to historical periods and that this evolution occurred over periods of climate change and seismo-tectonic activity. We show that societal development occurs both during periods of harsh as well as favourable climatic conditions. At some times, some settlements develop while others decline. Well-known climate events such as the 4.2 ka and 3.2 ka events are recognizable in some of the palaeoclimatic records and a regional decline in the number and sizes of settlements occurs roughly at the same time, but their precise chronological fit with the archaeological record remains uncertain. Local socio-political processes were probably always the key drivers behind the diverse strategies that human societies took in times of changing climate. The study thus reveals considerable chronological parallels between societal development and palaeoenvironmental records, but also demonstrates the ambiguities in these correspondences and, in doing so, highlights some of the challenges that will face future interdisciplinary projects. We suggest that there can be no general association made between societal expansion phases and periods of advantageous climate. We also propose that the relevance of climatic and environmental regionality, as well as any potential impacts of seismo-tectonics on societal development, need to be part of the interpretative frameworks.
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