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- Haghighi, Mona, et al.
(författare)
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A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
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| 4. |
- Kumar, Jitender, et al.
(författare)
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Influence of persistent organic pollutants on the complement system in a population-based human sample
- 2014
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 71, s. 94-100
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Tidskriftsartikel (refereegranskat)abstract
- Background: Persistent organic pollutants (POPS) are toxic compounds generated through various industrial activities and have adverse effects on human health. Studies performed in cell cultures and animals have revealed that POPs can alter immune-system functioning. The complement system is part of innate immune system that helps to clear pathogens from the body. We performed a large-scale population-based study to find out associations between summary measures of different POPs and different complement system markers.Methods: In this cross-sectional study, 16 polychlorinated biphenyls (PCBs), 3 organochlorine (OC) pesticides, octachloro-p-dibenzodioxin, and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) were analyzed for their association with levels of protein complement 3 (C3), 3a (C3a), 4 (C4) and C3a/C3 ratio. A total of 992 individuals (all aged 70 years, 50% females) were recruited from the Prospective Investigation of the Vasculature in Uppsala Seniors cohort. Regression analysis adjusting for a variety of confounders was performed to study the associations of different POP exposures (total toxic equivalency value or TEQ and sum of 16 PCBs) with protein complements.Results: The TEQ values were found to be positively associated with C3a (beta = 0.07, 95% CI = 0.017-0.131, p = 0.01) and C3a/C3 ratio (beta = 0.07, 95% Cl = 0.015-0.126, p = 0.01) taking possible confounders into account. The association observed was mainly driven by PCB-126.Conclusion: In this study involving 992 elderly individuals from the general population, we showed that POPs, mainly PCB-126, were associated with levels of complement system markers indicating that the association of these toxic compounds with downstream disease could be mediated by activation of immune system. (C) 2014 Elsevier Ltd. All rights reserved.
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| 5. |
- Lilliehorn, Tobias, et al.
(författare)
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Bioassays on ultrasonically trapped microbead clusters in microfluidic systems
- 2004
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Ingår i: Micro Total Analysis Systems 2004. - 0854048960 ; 2, s. 327-329
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Konferensbidrag (refereegranskat)abstract
- The handling of biochemically functionalised beads or particles is becoming increasingly important in µTAS. Bead-based analysis of e.g. proteins can be made sensitive due to the large active surface area and flexible by chemical design of the bead surface. We have developed a microfluidic device utilising an array of integrated and individually controlled ultrasonic microtransducers for particle trapping [1]. Particles inserted in the device are subjected to acoustic radiation forces [2] confining them at localised trapping sites. We would now, for the first time at an international conference, like to present a technique for performing bioassays on such ultrasonically trapped beads in microfluidic systems. The microfluidic device is shown in Fig. 1, where the piezoceramic ultrasonic transducers can be seen in the channel crossings in the insert. The device is designed as an acoustic resonator, to obtain localised standing acoustic waves at each transducer with essentially one pressure node in the middle of the 72 µm deep channel when operated near 10 MHz. This configuration is chosen to keep trapped particles away from the interior surfaces of the device, thus enabling fast switching of beads with a minimum in carry-over between assays. The fluidic chip, shown in Fig. 2, is designed to allow injection of microbeads, washing fluid and sample to the three trapping sites. It has been shown that the microbead clusters, as shown in Fig. 3, can be trapped at considerably high perfusion rates, up to 10 µl/min, Fig 4. As a model bioassay, 6.7 µm biotin-covered beads (PC-B-6.0, Gerlinde Kisker, Germany) were injected and transported to one tapping site using washing fluid (water). Activating the transducer trapped the beads. A solution of FITC-tagged avidin was perfused over the bead bed at 3 µl/min, using the corresponding orthogonal sample channel. After 100 s the sample flow was turned off and the bead trap was washed by perfusing water at 3 µl/min. The fluorescence response from the trapped bead clusters was monitored during the assay, and the result is shown in Fig. 5. After excess avidin was washed from the bead trap, a measured step response . indicated that avidin had bound to the beads. Finally the possibility of moving trapped microbeads between the individually controlled trapping sites in the device is shown in Fig. 6, where the transducers are activated sequentially while keeping the bead carrying washing fluid at 3 µl/min during the experiment. Work in the near future will be focused on optimising the device with respect to the bioassay performance, and in a longer perspective on expanding the concept to two dimensions to enable a new dynamic mode of generating bioanalytical arrays.
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| 9. |
- Nilsson, Mikael, et al.
(författare)
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Ultrasonic beadtrapping for bioassays
- 2004
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Ingår i: ; , s. 149-151
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This paper proposes a new dynamic mode of generating bioanalytical arrays based on ultrasonic trapping of microbeads in microfluidic systems. As compared to disposable glass slide microarrays, the proposed technology utilises exchangeable microbeads as the solid phase on which bioassays are performed. The use of microbeads in biochemical analysis is advantageous due to the increased surface area and thus the high binding capacity as compared to planar solid surfaces. By the integration of ultrasonic microtransducers in a microfluidic system, we have proved that it is possible to trap and manipulate microbead clusters by making use of acoustic standing wave forces. Functionalised microbeads have been trapped and moved between well-defined positions in a microchannel, thus for the first time showing trapping of microbeads within a flow-through device with individually controlled trapping sites in an array format. A device with three acoustic trapping sites was fabricated and evaluated. The lateral extension of each trapping site was essentially determined by the corresponding microtransducer dimensions, 0.8 x 0.8 mm2. The flow-through volume was approximately 1 µl and the active trapping site volumes about 100 nl each. The strength of trapping was investigated, showing that 50 % of the initially trapped beads were still trapped at a perfusion rate of 10 µl/min. Since the beads determine the chemical functionality in the device a high degree of flexibility is expected. A fluorescence based avidin bioassay was successfully performed on biotin-coated microbeads trapped in the flow-through device, providing a first proof of principle of the proposed dynamic arraying concept. The dynamic arraying is believed to be expandable to two dimensions, thus with a prospect of performing targeted and highly parallel protein analysis in microfluidics.
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| 10. |
- Nilsson, M, et al.
(författare)
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Versatile microchip utilising ultrasonic manipulation of microparticles
- 2005
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Ingår i: Proceedings of the International Federation for Medical & Biomedical Engineering. 13th Nordic Baltic Conference on Biomedical Engineering and Medical Physics. - 9173059102 ; , s. 123-124
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Konferensbidrag (refereegranskat)abstract
- This paper presents the concept and initial work on a microfluidic platform for bead-based analysis of biological sample. The core technology in this project is ultrasonic manipulation and trapping of particle in array configurations by means of acoustic forces. The platform is ultimately aimed for parallel multistep bioassays performed on biochemically activated microbeads (or particles) using submicrolitre sample volumes. A first prototype with three individually controlled particle trapping sites has been developed and evaluated. Standing ultrasonic waves were generated across a microfluidic channel by integrated PZT ultrasonic microtransducers. Particles in a fluid passing a transducer were drawn to pressure minima in the acoustic field, thereby being trapped and confined laterally over the transducer. It is anticipated that acoustic trapping using integrated transducers can be exploited in miniaturised total chemical analysis systems (μTAS), where e.g. microbeads with immobilised antibodies can be trapped in arrays and subjected to minute amounts of sample followed by a reaction, detected using fluorescence. Preliminary results indicate that the platform is capable of handling live cells as well as microbeads. A first model bioassay with detection of fluorescein marked avidin binding to trapped biotin beads has been evaluated
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