| 1. |
- Datry, T., et al.
(författare)
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A global analysis of terrestrial plant litter dynamics in non-perennial waterways
- 2018
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Ingår i: Nature Geoscience. - : Nature Publishing Group. - 1752-0894 .- 1752-0908. ; 11:7, s. 497-503
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Tidskriftsartikel (refereegranskat)abstract
- Perennial rivers and streams make a disproportionate contribution to global carbon (C) cycling. However, the contribution of intermittent rivers and ephemeral streams (IRES), which sometimes cease to flow and can dry completely, is largely ignored although they represent over half the global river network. Substantial amounts of terrestrial plant litter (TPL) accumulate in dry riverbeds and, upon rewetting, this material can undergo rapid microbial processing. We present the results of a global research collaboration that collected and analysed TPL from 212 dry riverbeds across major environmental gradients and climate zones. We assessed litter decomposability by quantifying the litter carbon-to-nitrogen ratio and oxygen (O2) consumption in standardized assays and estimated the potential short-term CO2 emissions during rewetting events. Aridity, cover of riparian vegetation, channel width and dry-phase duration explained most variability in the quantity and decomposability of plant litter in IRES. Our estimates indicate that a single pulse of CO2 emission upon litter rewetting contributes up to 10% of the daily CO2 emission from perennial rivers and stream, particularly in temperate climates. This indicates that the contributions of IRES should be included in global C-cycling assessments.
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| 2. |
- von Schiller, D., et al.
(författare)
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Sediment Respiration Pulses in Intermittent Rivers and Ephemeral Streams
- 2019
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Ingår i: Global Biogeochemical Cycles. - : American Geophysical Union (AGU). - 0886-6236 .- 1944-9224. ; 33:10, s. 1251-1263
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Tidskriftsartikel (refereegranskat)abstract
- Intermittent rivers and ephemeral streams (IRES) may represent over half the global stream network, but their contribution to respiration and carbon dioxide (CO2) emissions is largely undetermined. In particular, little is known about the variability and drivers of respiration in IRES sediments upon rewetting, which could result in large pulses of CO2. We present a global study examining sediments from 200 dry IRES reaches spanning multiple biomes. Results from standardized assays show that mean respiration increased 32-fold to 66-fold upon sediment rewetting. Structural equation modeling indicates that this response was driven by sediment texture and organic matter quantity and quality, which, in turn, were influenced by climate, land use, and riparian plant cover. Our estimates suggest that respiration pulses resulting from rewetting of IRES sediments could contribute significantly to annual CO2 emissions from the global stream network, with a single respiration pulse potentially increasing emission by 0.2-0.7%. As the spatial and temporal extent of IRES increases globally, our results highlight the importance of recognizing the influence of wetting-drying cycles on respiration and CO2 emissions in stream networks.
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| 3. |
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| 4. |
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| 5. |
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| 6. |
- Bonetti, A, et al.
(författare)
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RADICL-seq identifies general and cell type-specific principles of genome-wide RNA-chromatin interactions
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 1018-
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Tidskriftsartikel (refereegranskat)abstract
- Mammalian genomes encode tens of thousands of noncoding RNAs. Most noncoding transcripts exhibit nuclear localization and several have been shown to play a role in the regulation of gene expression and chromatin remodeling. To investigate the function of such RNAs, methods to massively map the genomic interacting sites of multiple transcripts have been developed; however, these methods have some limitations. Here, we introduce RNA And DNA Interacting Complexes Ligated and sequenced (RADICL-seq), a technology that maps genome-wide RNA–chromatin interactions in intact nuclei. RADICL-seq is a proximity ligation-based methodology that reduces the bias for nascent transcription, while increasing genomic coverage and unique mapping rate efficiency compared with existing methods. RADICL-seq identifies distinct patterns of genome occupancy for different classes of transcripts as well as cell type–specific RNA-chromatin interactions, and highlights the role of transcription in the establishment of chromatin structure.
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| 7. |
- Berntorp, Erik, et al.
(författare)
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Consensus perspectives on prophylactic therapy for haemophilia: summary statement.
- 2003
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 9:Suppl 1, s. 41278-41278
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Tidskriftsartikel (refereegranskat)abstract
- Participants in an international conference on prophylactic therapy for severe haemophilia developed a consensus summary of the findings and conclusions of the conference. In the consensus, participants agreed upon revised definitions for primary and secondary prophylaxis and also made recommendations concerning the need for an international system of pharmacovigilance. Considerations on starting prophylaxis, monitoring outcomes, and individualizing treatment regimens were discussed. Several research questions were identified as needing further investigation, including when to start and when to stop prophylaxis, optimal dosing and dose interval, and methods for assessment of long-term treatment effects. Such studies should include carefully defined cohorts, validated orthopaedic and quality-of-life assessment instruments, and cost-benefit analyses.
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| 8. |
- Brown, S A, et al.
(författare)
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Unresolved issues in prophylaxis
- 2002
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 8:6, s. 817-821
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Tidskriftsartikel (refereegranskat)
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| 9. |
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| 10. |
- Globe, Dennis, et al.
(författare)
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Measuring patient-reported outcomes in haemophilia clinical research
- 2009
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 15:4, s. 843-852
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Forskningsöversikt (refereegranskat)abstract
- Patient-reported outcome (PRO) measures have been used to assess quality of life and health state preferences from the patient's perspective. However, they have not been fully utilized in haemophilia clinical practice and research. A series of meetings were convened to review and document the state of the art in PROs relevant to haemophilia. Experts developed a process for selection of measures and identified published measures of health-related quality of life (HRQoL) relevant to patients with haemophilia. These were synthesized and reviewed. Patient preference measures were also identified and reviewed. Although the majority of measures were developed for and validated in adults, several measures were identified for use in paediatric populations. This paper recommends an approach to the selection of PROs for application in haemophilia clinical research and practice and identifies several potential measures relevant for application in haemophilia clinical research and practice.
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| 11. |
- Lundin, Björn, et al.
(författare)
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An MRI scale for assessment of haemophilic arthropathy from the International Prophylaxis Study Group.
- 2012
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 18:6, s. 962-970
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Tidskriftsartikel (refereegranskat)abstract
- Evaluation of prophylactic treatment of haemophilia requires sensitive methods. To design and test a new magnetic resonance imaging (MRI) scale for haemophilic arthropathy, two scales of a combined MRI scoring scheme were merged into a single scale which includes soft tissue and osteochondral subscores. Sixty-one joint MRI's of 46 patients with haemophilia were evaluated by four radiologists using the new and older scales. Forty-six of the joints were evaluated using two X-ray scales. For all MRI scores, interreader agreement and correlations with X-ray scores and lifetime number of haemarthroses were analysed. The interreader agreement intraclass correlation coefficient was 0.82, 0.89 and 0.88 for the soft tissue and osteochondral subscores and the total score, as evaluated according to the new MRI scale, compared to 0.80 and 0.89 as for the older scales. The total score and osteochondral subscore according to the new scale, as well as scores according to the older scales were correlated (P < 0.01) with number of haemarthroses (Spearman correlation 0.35-0.68) and with the X-ray scores (Spearman correlation 0.40-0.76), but no correlation (P > 0.05) was found between the soft tissue subscore of the new MRI scale and the X-ray scores. The new MRI scale is simpler to apply than the older and has similar reader reliability and correlation with lifetime number of haemarthroses, and by separating soft tissue and osteochondral changes it gives additional information. The new scale is useful for analyses of early and moderate stages of arthropathy, and may help to evaluate prophylactic haemophilia treatment.
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| 12. |
- Slotte, Tanja, et al.
(författare)
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The Capsella rubella genome and the genomic consequences of rapid mating system evolution
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:7, s. 831-U165
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Tidskriftsartikel (refereegranskat)abstract
- The shift from outcrossing to selfing is common in flowering plants(1,2), but the genomic consequences and the speed at which they emerge remain poorly understood. An excellent model for understanding the evolution of self fertilization is provided by Capsella rubella, which became self compatible <200,000 years ago. We report a C. rubella reference genome sequence and compare RNA expression and polymorphism patterns between C. rubella and its outcrossing progenitor Capsella grandiflora. We found a clear shift in the expression of genes associated with flowering phenotypes, similar to that seen in Arabidopsis, in which self fertilization evolved about 1 million years ago. Comparisons of the two Capsella species showed evidence of rapid genome-wide relaxation of purifying selection in C. rubella without a concomitant change in transposable element abundance. Overall we document that the transition to selfing may be typified by parallel shifts in gene expression, along with a measurable reduction of purifying selection.
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| 13. |
- Berntorp, Erik, et al.
(författare)
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Inhibitor treatment in haemophilas A and B: Summary statement for the 2006 International Consensus Conference
- 2006
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 12, s. 41281-41281
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Tidskriftsartikel (refereegranskat)abstract
- Participants in an international conference on the management of haemophilia patients with inhibitors developed a jointly authored summary of the findings and conclusions of the conference. Current knowledge of the genetic and immunologic mechanisms underlying inhibitor development was briefly summarized. Concerning the purported treatment-related risk factors, conference participants commented on the limitations of the available evidence and the need for more rigorous prospective research in a fully genotyped population. Other clinical considerations discussed included the unproved utility of routine surveillance, the need for assay standardization, the management of acute bleeding and approaches to joint disease prophylaxis and immune tolerance induction (ITI). A number of issues were identified as needing further investigation in larger prospective studies, ideally through international cooperation. Such studies should enrol cohorts that have been scrupulously defined in terms of mutation status and treatment exposure. Finally, conference participants urged their colleagues to participate in the currently ongoing international trials of ITI.
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| 14. |
- Björkman, Sven, et al.
(författare)
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Comparative pharmacokinetics of plasma- and albumin-free recombinant factor VIII in children and adults : the influence of blood sampling schedule on observed age-related differences and implications for dose tailoring
- 2010
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 8:4, s. 730-736
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dose tailoring of coagulation factors requires reliably estimated and reproducible pharmacokinetics (PK) in the individual patient. OBJECTIVES: To investigate the contribution of both biological and methodological factors to the observed variability of factor VIII (FVIII) PK, with the focus on differences between children and adults, and to examine the implications for dosing. PATIENTS: Data from 52 1-6-year-old and 100 10-65-year-old patients with hemophilia A (FVIII < or = 2 IU dL(-1)) in three clinical studies were included. RESULTS: In vivo recovery was lower, weight-adjusted clearance was higher and FVIII half-life was on average shorter in children than in adults. However, a reduced blood sampling schedule for children was estimated to account for up to one half of the total observed differences. Intrapatient variance in PK was smaller than interpatient variance in 10-65-year-olds. Age and ratio of actual to ideal weight only showed weak relationships with PK parameters. Variance in PK caused large variance in the calculated dose required to maintain a target FVIII trough level during prophylactic treatment. CONCLUSION: Differences in blood sampling schedules should be taken into account when results from different PK studies are compared. However, even with this consideration, PK cannot be predicted from observable patient characteristics but must be determined for the individual. Because the influence of reducing the blood sampling was minor in comparison to the true variance between patients, a reduced blood sampling protocol can be used. Low intrapatient variability supports the use of PK measurements for dose tailoring of FVIII.
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| 15. |
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| 16. |
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| 17. |
- Collins, P. W., et al.
(författare)
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Factor VIII requirement to maintain a target plasma level in the prophylactic treatment of severe hemophilia A : influences of variance in pharmacokinetics and treatment regimens
- 2010
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Ingår i: Journal of Thrombosis and Haemostasis. - : International Society on Thrombosis and Haemostasis. - 1538-7933 .- 1538-7836. ; 8:2, s. 269-275
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prophylactic factor (F)VIII has been shown to reduce bleeds and arthropathy in patients with severe hemophilia A. OBJECTIVES: Assuming that the trough FVIII level is an important determinant of the efficacy of prophylaxis, this paper addresses the effect of the inter-patient variability in pharmacokinetics and different dosing regimens on trough levels. METHODS: Simulations used FVIII half-lives and in vivo recoveries (IVR), observed during clinical trials with Advate [Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method], and commonly used prophylactic regimens to calculate their effect on FVIII levels during prophylaxis. RESULTS AND CONCLUSIONS: Half-life and dose frequency had a larger effect on trough FVIII and time per week with FVIII<1 IU dL(-1) than IVR and infused dose per kg. The combined effect of these parameters resulted in substantial inter-patient variability in the amount of FVIII required to sustain a desired trough level. Prophylactic regimens based on Monday, Wednesday, Friday dosing were less cost effective in maintaining a desired trough level throughout the week. Dose escalation on Friday to cover the weekend would require potentially harmful doses of FVIII in many patients, especially in young children where more than 50% would require a Friday dose of over 100 IU kg(-1) and some would require more than 400 IU kg(-1). Knowledge of individual patients' half-lives and alteration of frequency of infusions may allow the more cost-effective use of FVIII and potentially expand access to prophylaxis to a greater number of patients, especially in regions where healthcare resources are scarce.
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| 18. |
- Edger, Patrick P., et al.
(författare)
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The butterfly plant arms-race escalated by gene and genome duplications
- 2015
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:27, s. 8362-8366
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Tidskriftsartikel (refereegranskat)abstract
- Coevolutionary interactions are thought to have spurred the evolution of key innovations and driven the diversification of much of life on Earth. However, the genetic and evolutionary basis of the innovations that facilitate such interactions remains poorly understood. We examined the coevolutionary interactions between plants (Brassicales) and butterflies (Pieridae), and uncovered evidence for an escalating evolutionary arms-race. Although gradual changes in trait complexity appear to have been facilitated by allelic turnover, key innovations are associated with gene and genome duplications. Furthermore, we show that the origins of both chemical defenses and of molecular counter adaptations were associated with shifts in diversification rates during the arms-race. These findings provide an important connection between the origins of biodiversity, coevolution, and the role of gene and genome duplications as a substrate for novel traits.
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| 19. |
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| 20. |
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| 21. |
- Björkman, Sven, et al.
(författare)
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Population pharmacokinetics of recombinant factor VIII : the relationships of pharmacokinetics to age and body weight
- 2012
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 119:2, s. 612-618
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Tidskriftsartikel (refereegranskat)abstract
- Comparison of the pharmacokinetics (PK) of a coagulation factor between groups of patients can be biased by differences in study protocols, in particular between blood sampling schedules. This could affect clinical dose tailoring, especially in children. The aim of this study was to describe the relationships of the PK of factor VIII (FVIII) with age and body weight by a population PK model. The potential to reduce blood sampling was also explored. A model was built for FVIII PK from 236 infusions of recombinant FVIII in 152 patients (1-65 years of age) with severe hemophilia A. The PK of FVIII over the entire age range was well described by a 2-compartment model and a previously reported problem, resulting from differences in blood sampling, to compare findings from children and adults was practically abolished. The decline in FVIII clearance and increase in half-life with age could be described as continuous functions. Retrospective reduction of blood sampling from 11 to 5 samples made no important difference to the estimates of PK parameters. The obtained findings can be used as a basis for PK-based dose tailoring of FVIII in clinical practice, in all age groups, with minimal blood sampling.
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| 22. |
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| 23. |
- Blanchette, V S, et al.
(författare)
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Optimizing factor prophylaxis for the haemophilia population: where do we stand?
- 2004
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 10:4, s. 97-104
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Tidskriftsartikel (refereegranskat)abstract
- The hallmark of severe haemophilia, defined as a circulating level of factor (F) VIII (haemophilia A cases) or FIX (haemophilia B cases) of < 1%, is recurrent bleeding into muscles and joints (haemarthroses) from an early age of life. The inevitable result of such bleeding is progressive joint damage, leading to disabling arthritis that is typically evident within the first 2 decades of life in people with haemophilia who have limited or no access to regular factor replacement therapy, or those in whom factor replacement therapy is ineffective because of the presence of high-titre inhibitors. For children with severe haemophilia and no evidence of inhibitors, the unwanted musculoskeletal complications of severe haemophilia can be effectively prevented by the early initiation of a programme of long-term factor prophylaxis. In order to achieve the best outcome (a perfect musculoskeletal status for age) the programme of prophylaxis should be started before the onset of joint damage (primary prophylaxis). The gold standard primary prophylaxis regimen (the Malmo protocol) was pioneered and tested in Sweden and involves the infusion of 20-40 IU of FVIII per kg body weight on alternate days (minimum three times per week) for haemophilia A cases, and 20-40 IU kg(-1) of FIX twice weekly for haemophilia B cases. This protocol is, however, demanding on peripheral veins and very expensive. Modifications of the parent protocol such as starting primary prophylaxis with once-weekly infusions via peripheral veins with rapid escalation to full-dose prophylaxis or dose escalation based on frequency of bleeding are increasingly implemented in haemophilia treatment centres in countries that can afford the high cost of such programmes. These modified programmes can be achieved in the majority of young children with severe haemophilia without the need for central venous access devices (e.g. Port-a-Caths) and with avoidance of device-associated complications such as infection and thrombosis. In at least one centre, experience with arteriovenous fistulae as a strategy to ensure reliable venous access is being accumulated. The issues of compliance (adherence) to recommended prophylaxis protocols and when, if ever, to stop a programme of primary prophylaxis once started are real and require ongoing prospective studies. Such studies should incorporate outcome measures such as health-related quality-of-life and economic analyses.
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| 24. |
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| 25. |
- Collins, P. W., et al.
(författare)
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Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A
- 2009
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 7:3, s. 413-420
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The role of prophylactic factor VIII (FVIII) to decrease hemophilic bleeding and arthropathy is well established. The rationale for this strategy is to convert patients with severe hemophilia A to a moderate clinical phenotype by reducing time spent with a FVIII level <1 IU dL(-1). Studies to date, however, have not demonstrated a strong link between FVIII level and the bleeding rate. OBJECTIVES: To assess the effect of FVIII level on break-through bleeding in patients with severe hemophilia A on prophylaxis. PATIENTS/METHODS: This study analysed data from 44 patients aged 1-6 and 99 patients aged 10-65 years with severe hemophilia A (FVIII <1 IU dL(-1)) who were treated with prophylactic FVIII as part of clinical studies assessing pharmacokinetics, safety and efficacy of a recombinant FVIII (Advate). Each patient had pharmacokinetic measurements and FVIII infusions recorded, and these were used to calculate time spent with a FVIII below 1, 2 and 5 IU dL(-1). RESULTS: The data demonstrate that increasing time with a FVIII below 1 IU dL(-1) is associated with increased total bleeds and hemarthroses. Lack of adherence to the intended frequency of FVIII infusion was the most important determinant of low FVIII and increased bleeding. In children aged 1-6 years, the rate of bleeding was also influenced by FVIII half-life and clearance. Conclusions: These data have important implications for the management of patients with severe hemophilia.
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| 26. |
- Collins, P. W., et al.
(författare)
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Implications of coagulation factor VIII and IX pharmacokinetics in the prophylactic treatment of haemophilia
- 2011
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 17:1, s. 2-10
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Forskningsöversikt (refereegranskat)abstract
- The pharmacokinetic (PK) response to factor VIII (FVIII) and factor IX varies between patients and this has important clinical implications for treatment. Although PK is affected by patient characteristics, this relationship is too weak to infer a result for an individual and, if required, PK must be measured. An important determinant of the efficacy of prophylaxis is the length of time an individual spends with a low level of coagulation factor. This time is more dependent on the patient's coagulation factor half-life and the frequency of dosing than in vivo recovery and dose infused. Improved understanding of the effect of PK and dose frequency on factor levels in patients on prophylaxis will help tailor regimens to individuals better and allow more cost effective use of coagulation factor concentrates. Calculations suggest that adults need less FVIII per kg body weight than children. The effect of half-life on trough levels questions the logic of Monday, Wednesday, Friday dosing and suggests a role for innovative regimens including low-dose daily treatment which leads to either higher trough levels or decreased FVIII requirement. This may expand access to prophylaxis in healthcare systems with limited resources and potentially improve patient outcomes. The ideal trough level will vary between individuals and at different times of their lives and may be <1 IU dL(-1). If PK is to be used in routine clinical practice, a simplified method for its measurement is required and this methodology is becoming available.
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| 27. |
- Dimichele, D M, et al.
(författare)
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Clinical trial design in haemophilia.
- 2012
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 18 Suppl 4, s. 18-23
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Tidskriftsartikel (refereegranskat)abstract
- Summary: Progress in the evidence-based care of haemophilia A and B worldwide has been historically challenged by the dearth of evaluable outcome data, including but not limited to the safety and effectiveness of therapeutic interventions. These challenges are partially rooted in the inherent difficulty of conducting prospective clinical trials and observational studies with statistically meaningful endpoints in a rare disease such as haemophilia. Despite the logistical barriers, the need for outcome data has never been more critical than in this time of expansive therapeutic advance tempered by the shrinking economic capacity to fund the rapidly increasing cost of treatment. Given that systematic analyses of published literature have been largely unsuccessful in compensating for the lack of rigorous and purposeful data collection, new approaches to clinical study design and statistical modelling are urgently needed. However, even as these are considered, the lack of broadly accepted and well-defined clinical outcome endpoints poses an additional barrier to progress. The three presentations encompassed by this paper highlight the timely need for quality data from the perspectives of the clinicians, regulatory agencies and health care funders, and describe the ongoing coordinated efforts by the international haemophilia community to further understand and dismantle the barriers to harmonized and standardized data collection on a global scale using well-defined clinical outcome endpoints.
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| 28. |
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| 29. |
- Fischer, K., et al.
(författare)
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Trends in bleeding patterns during prophylaxis for severe haemophilia : observations from a series of prospective clinical trials
- 2011
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 17:3, s. 433-438
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Tidskriftsartikel (refereegranskat)abstract
- Replacement therapy or prophylaxis, has become the standard of care for the treatment of severe haemophilia A. To describe bleeding patterns in children, adolescents and adults on prophylaxis and their observed relationships to times of infusion (during the week and during the day) as well as season of the year. Data from Advate pre-licensure prospective clinical trials from 145 patients with factor VIII (FVIII) < 1%, were used. All patients underwent a 48-h pharmacokinetic study. The 10-65 year group had >= 75 exposure days on fixed prophylaxis (25-40 IU kg-1 3-4x per week). Prophylaxis was not fixed but similar for 1-6 year olds. Bleeding patterns were analysed. Overall, 700 bleeds were observed in 110/145 patients. All were treated with prophylaxis, mean dose 108 IU kg-1 week-1 in on average 2.9 infusions (1-6 years), 86 IU kg -1week-1 in 2.7 infusions (10-17 years),and 75 IU kg -1week-1 in 2.6 infusions (18-65 years), respectively. On prophylaxis, median total bleeds per year were low at 3.1 for patients aged 1-6 years, 3.3 for those aged 10-17 years and 2.1 for patients aged 18-65 years. Patients aged 1-6 years had predominantly soft tissue bleeds (79%). Incidence of joint bleeding was not associated with season, but was significantly lower in patients who infused FVIII in the mornings: median 0 per year (IQR 0.0-0.4) compared to those who infused later [median 1.8 per year (IQR 0.0-5.2)]. Older patients predominantly experienced joint bleeds (50% and 62%, respectively). More joint bleeds occurred during the summer [43 and 46% respectively, (P < 0.01)]. Bleeding patterns in patients on prophylaxis varied according to age. In addition, the 10-65 year olds showed increased bleeding during the summer. After confirmation in prospective studies, this information may be used to improve tailoring of prophylactic treatment.
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| 30. |
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| 31. |
- Manco-Johnson, MJ, et al.
(författare)
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Physical therapy and imaging outcome measures in a haemophilia population treated with factor prophylaxis: current status and future directions
- 2004
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 10, s. 88-93
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Tidskriftsartikel (refereegranskat)abstract
- Routine infusions of factor VIII to prevent bleeding, known as prophylaxis, and other intensive therapies are being more broadly applied to patients with haemophilia. These therapies differ widely in replacement product usage, cost, frequency of venous access and parental effort. In order to address residual issues relating to recommendations, implementation, and evaluations of prophylaxis therapy in persons with haemophila, a multinational working group was formed and called the International Prophylaxis Study Group (IPSG). The group was comprised of haemophilia treaters actively involved in studies of prophylaxis from North America and Europe. Two expert committees, the Physical Therapy (PT) Working Group and the Magnetic Resonance Imaging (MRI) Working Group were organized to critically assess existing tools for assessment of Joint outcome. These two committees independently concluded that the WFH Physical Examination Scale (WFH PE Scale) and the WFH X-ray Scale (WFH XR Scale) were inadequately sensitive to detect early changes in Joints. New scales were developed based on suggested modifications of the existing scales and called the Haemophilia joint Health Score (HJHS) and the International MRI Scales. The new scales were piloted. Concordance was measured by the intra-class correlation coefficient of variation. Reliability of the HJHS was excellent with an inter-observer co-efficient of 0.83 and a test-retest value of 0.89. The MRI study was conducted using both Denver and European scoring approaches; inter-reader reliability using the two approaches was 0.88 and 0.87; test-retest reliability was 0.92 and 0.93. These new PT and MRI scales promise to improve outcome assessment in children on early preventive treatment regimens.
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| 32. |
- Shumilova, Oleksandra, et al.
(författare)
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Simulating rewetting events in intermittent rivers and ephemeral streams : A global analysis of leached nutrients and organic matter
- 2019
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Ingår i: Global Change Biology. - : WILEY. - 1354-1013 .- 1365-2486. ; 25:5, s. 1591-1611
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Tidskriftsartikel (refereegranskat)abstract
- Climate change and human pressures are changing the global distribution and the extent of intermittent rivers and ephemeral streams (IRES), which comprise half of the global river network area. IRES are characterized by periods of flow cessation, during which channel substrates accumulate and undergo physico-chemical changes (preconditioning), and periods of flow resumption, when these substrates are rewetted and release pulses of dissolved nutrients and organic matter (OM). However, there are no estimates of the amounts and quality of leached substances, nor is there information on the underlying environmental constraints operating at the global scale. We experimentally simulated, under standard laboratory conditions, rewetting of leaves, riverbed sediments, and epilithic biofilms collected during the dry phase across 205 IRES from five major climate zones. We determined the amounts and qualitative characteristics of the leached nutrients and OM, and estimated their areal fluxes from riverbeds. In addition, we evaluated the variance in leachate characteristics in relation to selected environmental variables and substrate characteristics. We found that sediments, due to their large quantities within riverbeds, contribute most to the overall flux of dissolved substances during rewetting events (56%-98%), and that flux rates distinctly differ among climate zones. Dissolved organic carbon, phenolics, and nitrate contributed most to the areal fluxes. The largest amounts of leached substances were found in the continental climate zone, coinciding with the lowest potential bioavailability of the leached OM. The opposite pattern was found in the arid zone. Environmental variables expected to be modified under climate change (i.e. potential evapotranspiration, aridity, dry period duration, land use) were correlated with the amount of leached substances, with the strongest relationship found for sediments. These results show that the role of IRES should be accounted for in global biogeochemical cycles, especially because prevalence of IRES will increase due to increasing severity of drying events.
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| 33. |
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