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- Cotofana, S., et al.
(författare)
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Relationship between knee pain and the presence, location, size and phenotype of femorotibial denuded areas of subchondral bone as visualized by MRI
- 2013
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 21:9, s. 1214-1222
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Conflicting associations between imaging biomarkers and pain in knee osteoarthritis (OA) have been reported. A relation between pain and denuded areas of subchondral bone (dABs) has been suggested and this study explores this relationship further by relating the presence, phenotype, location and size of dABs to different measures of knee pain. Methods: 633 right knees from the Osteoarthritis Initiative (OAI) (250 men, age 61.7 +/- 9.6 yrs, BMI 29.4 +/- 4.7 kg/m(2)) were included. Manual segmentation of the femorotibial cartilage plates was performed on 3 T coronal fast low angle shot with water excitation (FLASHwe) images. dABs were defined as areas where the subchondral bone was uncovered by cartilage. The following measures of pain were used: weightbearing-, non-weightbearing-, moderate-to-severe-, infrequent- and frequent knee pain. Results: Using pain measures from subjects without dABs as a reference, those with at least one dAB had a 1.64-fold higher prevalence ratio [PR, 95% confidence interval (CI) 1.24-2.18] to have frequent and 1.45-fold higher for moderate-to-severe knee pain (95% CI 1.13-1.85). Subjects with dABs in central subregions had a 1.53-fold increased prevalence of having weightbearing pain (95% Cl 1.20-1.97), especially when the central subregion was moderately (>10%) denuded (PR 1.81, 95% CI 135-2.42). Individuals with cartilage-loss-type dABs had a slightly higher prevalence (PR 1.13, 95% CI 1.00-1.27) of having frequent knee pain compared to individuals with intra-chondral-osteophyte-type dABs. Conclusion: This study supports a positive relation between femorotibial dABs and knee pain, especially when the dABs are located centrally (i.e., in weightbearing regions) or when the respective central subregion is moderately denuded. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 2. |
- Herman, Jonathan D., et al.
(författare)
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A genomic and evolutionary approach reveals non-genetic drug resistance in malaria
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:11, s. 511-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Drug resistance remains a major public health challenge for malaria treatment and eradication. Individual loci associated with drug resistance to many antimalarials have been identified, but their epistasis with other resistance mechanisms has not yet been elucidated. Results: We previously described two mutations in the cytoplasmic prolyl-tRNA synthetase (cPRS) gene that confer resistance to halofuginone. We describe here the evolutionary trajectory of halofuginone resistance of two independent drug resistance selections in Plasmodium falciparum. Using this novel methodology, we discover an unexpected non-genetic drug resistance mechanism that P. falciparum utilizes before genetic modification of the cPRS. P. falciparum first upregulates its proline amino acid homeostasis in response to halofuginone pressure. We show that this non-genetic adaptation to halofuginone is not likely mediated by differential RNA expression and precedes mutation or amplification of the cPRS gene. By tracking the evolution of the two drug resistance selections with whole genome sequencing, we further demonstrate that the cPRS locus accounts for the majority of genetic adaptation to halofuginone in P. falciparum. We further validate that copy-number variations at the cPRS locus also contribute to halofuginone resistance. Conclusions: We provide a three-step model for multi-locus evolution of halofuginone drug resistance in P. falciparum. Informed by genomic approaches, our results provide the first comprehensive view of the evolutionary trajectory malaria parasites take to achieve drug resistance. Our understanding of the multiple genetic and non-genetic mechanisms of drug resistance informs how we will design and pair future anti-malarials for clinical use.
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| 3. |
- Holfeld, B., et al.
(författare)
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Stable Matching for Adaptive Cross-Layer Scheduling in LTE Downlink
- 2013
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Ingår i: 2013 IEEE 77TH VEHICULAR TECHNOLOGY CONFERENCE (VTC SPRING). - : IEEE conference proceedings. - 9781467363372
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Konferensbidrag (refereegranskat)abstract
- Resource allocation from base stations to mobile users in realistic MIMO-OFDMA systems such as the 3GPP Long Term Evolution (LTE) downlink is based on limited and quantized channel feedback over a fine-granular resource grid of multiple dimensions. This allows for opportunistic scheduling but impedes application of enhanced cross-layer strategies due to the discrete and combinatorial problem space. Integer optimization for this allocation problem is strongly complex and prohibits use of efficient algorithms. Provided solutions in practice are given by sub-optimal greedy heuristics. In this paper, we apply two-sided stable matchings for adaptive multi-user scheduling. Our framework gives Pareto-efficient allocations and yields a tunable tradeoff between system throughput and user fairness. We form stable pairings of system resources and users based on queue-and channel-aware lists of preferred matches. The derived concept aims to find a stable matching state under presence of non-strict preference relations if such exist or redefines the allocation problem to a solvable strict problem instance. A performance evaluation for scheduling is done by system level simulations for high traffic loads in a realistically modeled LTE deployment.
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