| 1. |
- Hagell, Peter, et al.
(författare)
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Apomorphine formulation may influence subcutaneous complications from continuous subcutaneous apomorphine infusion in Parkinson's disease
- 2020
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Ingår i: Journal of Neurology. - 0340-5354 .- 1432-1459. ; 267:11, s. 3411-3417
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Tidskriftsartikel (refereegranskat)abstract
- Continuous subcutaneous (s.c.) apomorphine infusion is an effective therapy for Parkinson's disease (PD), but a limitation is the formation of troublesome s.c. nodules. Various chemically non-identical apomorphine formulations are available. Anecdotal experiences have suggested that shifting from one of these (Apo-Go PumpFill®; apoGPF) to another (Apomorphine PharmSwed®; apoPS) may influence the occurrence and severity of s.c. nodules. We, therefore, followed 15 people with advanced PD (median PD-duration, 15 years; median "off"-phase Hoehn and Yahr, IV) on apoGPF and with troublesome s.c. nodules who were switched to apoPS. Data were collected at baseline, at the time of switching, and at a median of 1, 2.5, and 7.3 months post-switch. Total nodule numbers (P < 0.001), size (P < 0.001), consistency (P < 0.001), skin changes (P = 0.058), and pain (P ≤ 0.032) improved over the observation period. PD severity and dyskinesias tended to improve and increase, respectively. Apomorphine doses were stable, but levodopa doses increased by 100 mg/day. Patient-reported apomorphine efficacy tended to increase and all participants remained on apoPS throughout the observation period; with the main patient-reported reason being improved nodules. These observations suggest that patients with s.c. nodules caused by apoGPF may benefit from switching to apoPS in terms of s.c. nodule occurrence and severity. Alternatively, observed benefits may have been due to the switch itself. As nodule formation is a limiting factor in apomorphine treatment, a controlled prospective study comparing local tolerance with different formulations is warranted.
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| 2. |
- Tyden, Eva, et al.
(författare)
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Deep amplicon sequencing of preselected isolates of Parascaris equorum in beta-tubulin codons associated with benzimidazole resistance in other nematodes
- 2014
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Ingår i: Parasites & Vectors. - : Springer Science and Business Media LLC. - 1756-3305. ; 7, s. 410-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The development of anthelmintic resistance (AR) to macrocyclic lactones in the equine roundworm Parascaris equorum has resulted in benzimidazoles now being the most widely used substance to control Parascaris infections. However, over-reliance on one drug class is a risk factor for the development of AR. Consequently, benzimidazole resistance is widespread in several veterinary parasites, where it is associated with single nucleotide polymorphisms (SNPs) in drug targets encoded by the beta-tubulin genes. The importance of these SNPs varies between different parasitic nematodes, but it has been hypothesised that they occur, at low allele frequencies, even in unselected populations. This study investigated whether these SNPs exist in the P. equorum population and tested the hypothesis that BZ resistance can develop from pre-existing SNPs in codons 167, 198 and 200 of the beta-tubulin isotype 1 and 2 genes, reported to be associated with AR in strongylids. The efficacy of the oral paste formula fenbendazole on 11 farms in Sweden was also assessed. Methods: Two isotype-specific primer pairs were designed, one on either side of the codon 167 and one on either side of codons 198 and 200. A pool of 100 000 larvae was sequenced using deep amplicon sequencing by Illumina HiSeq. Faecal egg count reduction test was used to assess the efficacy of fenbendazole. Results: No SNPs were observed in codons 167, 198 or 200 of the beta-tubulin isotype 1 or 2 genes of P. equorum, even though 100 000 larvae were sequenced. Faecal egg count reduction testing of fenbendazole showed that this anthelmintic was still 100% effective, meaning that the likelihood of finding high allele frequency of SNPs associated with benzimidazoles resistance in P. equorum was low. Unexpectedly, the allele frequencies observed in single worms were comparable to those in pooled samples. Conclusions: We concluded that fenbendazole does not exert selection pressure on the beta-tubulin genes of isotypes 1 and 2 in P. equorum. The fact that no pre-existing SNPs were found in codons 167, 198 and 200 in P. equorum also illustrates the difficulties in generalising about AR mechanisms between different taxonomic groups of nematodes.
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| 3. |
- Andersson, C David, et al.
(författare)
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Discovery of Ligands for ADP-Ribosyltransferases via Docking-Based Virtual Screening
- 2012
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:17, s. 7706-7718
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Tidskriftsartikel (refereegranskat)abstract
- The diphtheria toxin-like ADP-ribosyltransferases (ARTDs) are an enzyme family that catalyses the transfer of ADP-ribose units onto substrate proteins, using nicotinamide adenine dinucleotide (NAD(+)) as a co-substrate. They have a documented role in chromatin remodelling and DNA repair; and inhibitors of ARTD1 and 2 (PARP1 and 2) are currently in clinical trials for the treatment of cancer. The detailed function of most other ARTDs is still unknown. Using virtual screening we identified small ligands of ARTD7 (PARP15/BAL3) and ARTD8 (PARP14/BAL2). Thermal-shift assays confirmed that 16 compounds, belonging to eight structural classes, bound to ARTD7/ARTD8. Affinity measurements with isothermal titration calorimetry for two isomers of the most promising hit compound confirmed binding in the low micromolar range to ARTD8. Crystal structures showed anchoring of the hits in the nicotinamide pocket. These results form a starting point in the development of chemical tools for the study of the role and function of ARTD7 and ARTD8.
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| 4. |
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| 5. |
- Beillon, Lena Marie, et al.
(författare)
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Does ambulance use differ between geographic areas? A survey of ambulance use in sparsely and densely populated areas.
- 2009
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Ingår i: The American journal of emergency medicine. - : Elsevier BV. - 1532-8171 .- 0735-6757. ; 27:2, s. 202-11
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The aim of this study was to analyze possible differences in the use of ambulance service between densely and sparsely populated areas. METHODS: This study was designed as a 2-step consecutive study that included the ambulance service in 4 different areas with different geographical characteristics. A specific questionnaire was distributed to the enrolled ambulance services. Completion of one questionnaire was required for each ambulance mission, that is, 1 per patient, during the study periods. For calculations of P values, geographic area was treated as a 4-graded ordered variable, from the most densely populated to the most sparsely populated (ie, urban-suburban-rural-remote rural area). Statistical tests used were Mann-Whitney U test and Spearman rank statistic, when appropriate. All P values are 2 tailed and considered significant if below .01. RESULTS: The medical status of the patients in the prehospital care situation was more often severe in the sparsely populated areas. In addition, drugs were more often used in the ambulances in these areas. In the sparsely populated areas, ambulance use was more frequently judged as the appropriate mode of transportation compared with the more densely populated areas. CONCLUSIONS: Our study suggests that the appropriateness of the use of ambulance is not optimal. Furthermore, our data suggest that geographical factors, that is, population density, is related to inappropriate use. Thus, strategies to improve the appropriateness of ambulance use should probably take geographical aspects into consideration.
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| 6. |
- Bennett, Elena, et al.
(författare)
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Toward a more resilient agriculture
- 2014
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Ingår i: Solutions : For a Sustainable & Desirable Future. - : Australian National University. - 2154-0926. ; 5:5, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- In Brief Agriculture is a key driver of change in the Anthropocene. It is both a critical factor for human well-being and development and a major driver of environmental decline. As the human population expands to more than 9 billion by 2050, we will be compelled to find ways to adequately feed this population while simultaneously decreasing the environmental impact of agriculture, even as global change is creating new circumstances to which agriculture must respond. Many proposals to accomplish this dual goal of increasing agricultural production while reducing its environmental impact are based on increasing the efficiency of agricultural production relative to resource use and relative to unintended outcomes such as water pollution, biodiversity loss, and greenhouse gas emissions. While increasing production efficiency is almost certainly necessary, it is unlikely to be sufficient and may in some instances reduce long-term agricultural resilience, for example, by degrading soil and increasing the fragility of agriculture to pest and disease outbreaks and climate shocks. To encourage an agriculture that is both resilient and sustainable, radically new approaches to agricultural development are needed. These approaches must build on a diversity of solutions operating at nested scales, and they must maintain and enhance the adaptive and transformative capacity needed to respond to disturbances and avoid critical thresholds. Finding such approaches will require that we encourage experimentation, innovation, and learning, even if they sometimes reduce short-term production efficiency in some parts of the world.
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| 7. |
- de Fraiture, C., et al.
(författare)
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Can rainfed agriculture feed the world?
- 2009
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Ingår i: Rainfed Agriculture. - Wallingford, UK : CABI. - 9781845933890 ; , s. 124-132
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 8. |
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| 9. |
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| 10. |
- Dile, Yihun, 1982-
(författare)
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Intensifying Agricultural Water Management in the Tropics : A cause of water shortage or a source of resilience?
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Frequent climatic shocks have presented challenges for rainfed agriculture in sub-Saharan Africa. Appropriate water management practices are among the solutions to the challenges. The role of water harvesting in achieving sustainable agricultural intensification and specified resilience was explored. Suitable areas for water harvesting in the Upper Blue Nile basin were identified. The usefulness of the Curve Number method for surface runoff estimation was evaluated, and was found to perform satisfactorily. The impact of climate change in the Lake Tana sub-basin was studied. A decision support system was developed for locating and sizing of water harvesting ponds in the SWAT model. Methodological developments enabled analysis of the implications of water harvesting intensification in a meso-scale watershed in the Lake Tana sub-basin.Results suggest that water harvesting can increase agricultural productivity, sustain ecosystems and build specified resilience, and thereby contribute to sustainable agricultural intensification. There is considerable potential for water harvesting in the Upper Blue Nile Basin. Rainfall may increase in the Lake Tana sub-basin due to climate change. Supplementary irrigation from water harvesting ponds and better nutrient application increased staple crop production by up to three-fold. Moreover, a substantial amount of cash crop was produced using dry seasonal irrigation. Water harvesting altered the streamflow regime, and reduced sediment loss from the watershed. Water harvesting can play an important role in food security. It showed potential to buffer climatic variability. In the watershed studied, water harvesting will not compromise the environmental water requirements. Instead, increased low flows, and reduced flooding and sediment loss may benefit the social-ecological systems. The adverse effects of disturbance of the natural flow variability and sediment influx to certain riverine ecosystems warrant detailed investigation.
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