| 1. |
- Watson, Hunna J., et al.
(författare)
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Common Genetic Variation and Age of Onset of Anorexia Nervosa
- 2022
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Ingår i: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
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| 4. |
- Bodén, Roger, et al.
(författare)
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A metallic micropump for high-pressure microfluidics
- 2008
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Ingår i: Journal of Micromechanics and Microengineering. - : IOP Publishing. - 0960-1317 .- 1361-6439. ; 18:11, s. 115009-
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents one of the strongest mechanical sub-cm(3) sized micropumps for microfluidics. It consists of two active valves and one pumping chamber, each operated by a paraffin actuator that is driven by a low-voltage square pulse waveform. The pump is fabricated in a simple process using parylene-coated stainless steel stencils, paraffin and copper clad polyimide. When driving the pump at 0.07 Hz and 2.0 V (0.8 W) per actuator, it pumped water without leakage at a flow rate of 0.75 mu L min(-1) up to above 50 bar (5 MPa) back-pressure. The frequency dependence was evaluated and a maximum flow rate of 1 mu L min(-1) at 0.21 Hz and 1.8 V was observed. A thermomechanical FEM analysis, which was in good agreement with experiments at low frequencies, predicts the behaviour at higher frequencies.
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| 12. |
- Bodén, Roger, 1979-
(författare)
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Microactuators for Powerful Pumps
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- When paraffin wax melts it exhibits a large, relatively incompressible volume expansion. This can be used in microactuators for strong and large displacements, a rare combination among actuators. Furthermore, paraffin is inexpensive, inert and environmentally friendly, as well as easily processed and actuated. Together, these properties give paraffin actuators great potential for use in both low-cost and high-performance applications.In microfluidics, the miniaturization of various analysis systems decreases the volumes of samples and reagents needed, as well as the analysis throughput time. Using on-chip micropumps increases the efficiency of the microfluidic system, but a challenge for such pumps is the high back-pressure associated with separation, filtration or narrower channels.The objective of this thesis is to increase the understanding of paraffin in microactuators, as well as to further explore its possibilities and limitations. The main application area has been on-chip micropumps.For low-cost applications, actuators, pumps and dispensers have been fabricated in plastics and then evaluated. The dispenser is intended for on-chip storage and dispensing of liquids in a lab-on-a-chip that could be used in, e.g., point-of-care testing (POCT).For high-performance applications, metallic actuators, pumps and dispensers have been accomplished. The micropump is the world’s strongest mechanical micropump in sub-cubic centimetre size, capable of pressures of above 5 MPa. Possible applications are strong microhydraulics, on-chip chromatography, or medical microdosage systems.A limitation of paraffin is the relatively slow thermal actuation. In this thesis the thermal properties have also been turned into an advantage: Directional solidification is used to accomplish multiple stable states of the actuator displacement, withheld without any power consumption.For the future, the high-pressure capability may be improved by new designs. Optimization of speed and power consumption can be made by further work on modelling as well as on drive and control of the heating.
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| 13. |
- Bodén, Roger, et al.
(författare)
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Microdispenser with continuous flow and selectable target volume for microfluidic high-pressure applications
- 2014
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Ingår i: Journal of microelectromechanical systems. - 1057-7157 .- 1941-0158. ; 23:2, s. 452-458
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a reusable microdispenser intended for continuous flow dispensing of variable and controlled volumes of liquid against high back-pressures. The microdispenser consists of two active valves and a dispenser chamber, all actuated by the volume change associated with the solid-to-liquid phase transition of paraffin wax. It is fabricated using stainless steel sheets, a flexible printed circuit board, and a polyimide membrane. All are covered with Parylene C for insulation and fusion bonding at assembly. A finite element method (FEM) model of the paraffin actuator is used to predict the resulting flow characteristics. The results show dispensing of well-defined volumes of 350 and 540 nL, with a good repeatability between dispensing sequences, as well as reproducibility between devices. In addition, the flow characteristics show no back-pressure dependence of the dispensed flow in the interval 0.5--2.0 MPa. The FEM model can be used to predict the flow characteristics qualitatively
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| 14. |
- Bodén, Roger, et al.
(författare)
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On-chip liquid storage and dispensing for lab-on-a-chip applications
- 2008
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Ingår i: Journal of Micromechanics and Microengineering. - : IOP Publishing. - 0960-1317 .- 1361-6439. ; 18:7, s. 075036-
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Tidskriftsartikel (refereegranskat)abstract
- This work presents novel components for on-chip storage and dispensing inside a lab-on-a-chip (LOC) for applications in immunoassay point-of-care testing (POCT), where incubation and washing steps are essential. It involves easy-to-use on-chip solutions for the sequential thermo-hydraulic actuation of liquids. The novel concept of combining the use of a rubber plug, both as a non-return valve cap and as a liquid injection interface of a sealed reservoir, allows simple filling of a sterilized cavity, as well as the storage and dispensing of reagent and washing buffer liquids. Segmenting the flow with air spacers enables effective rinsing and the use of small volumes of on-chip stored liquids. The chip uses low-resistance resistors as heaters in the paraffin actuator, providing the low-voltage actuation that is preferred for handheld battery driven instruments.
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| 15. |
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| 16. |
- Bryois, J., et al.
(författare)
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Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:5, s. 482-493
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 17. |
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| 18. |
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| 19. |
- Lehto, Marcus, et al.
(författare)
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A polymeric paraffin microactuator
- 2008
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Ingår i: Journal of microelectromechanical systems. - 1057-7157 .- 1941-0158. ; 17:5, s. 1172-1177
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Tidskriftsartikel (refereegranskat)abstract
- Paraffin wax is a promising material in microactuators not only because of its ability of producing large displacements and high forces at the same time but also because of the variety of manufacturing techniques available. In this paper, a simple actuator based on paraffin wax as the active material is fabricated and tested. Ultraviolet-curable epoxy is used in a technique combining simultaneous moulding and liquid-phase photopolymerization in a single-process step to build the stiff part of the actuator body. A heater is integrated in the paraffin reservoir, and a polyimide tape is used as the deflecting membrane. Thermornechanical analysis of the paraffin wax shows that it exhibits a volume expansion of 10%, including phase transitions and linear expansion. As for the actuator, a stroke of 90 mu m is obtained for the unloaded device, whereas 37 mu m is recorded with a 0.5-N contact load at a driving voltage of 0.71 V and a frequency of 1/32 Hz. The actuator can be used in microsystems, where both large strokes and forces are needed. The low-cost materials and low driving voltage also makes it suitable for disposable systems.
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| 20. |
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| 21. |
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| 22. |
- Lehto, Marcus, et al.
(författare)
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Rapid prototyping of a polymeric paraffin microactuator
- 2008
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Ingår i: Journal of microelectromechanical systems. - 1057-7157 .- 1941-0158. ; 17:5, s. 1172-1177
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Tidskriftsartikel (refereegranskat)abstract
- Paraffin wax is a promising material in microactuators not only because of its ability of producing large displacements and high forces at the same time but also because of the variety of manufacturing techniques available. In this paper, a simple actuator based on paraffin wax as the active material is fabricated and tested. Ultraviolet-curable epoxy is used in a technique combining simultaneous moulding and liquid-phase photopolymerization in a single-process step to build the stiff part of the actuator body. A heater is integrated in the paraffin reservoir, and a polyimide tape is used as the deflecting membrane. Thermomechanical analysis of the paraffin wax shows that it exhibits a volume expansion of 10%, including phase transitions and linear expansion. As for the actuator, a stroke of 90 mum is obtained for the unloaded device, whereas 37 mum is recorded with a 0.5-N contact load at a driving voltage of 0.71 V and a frequency of 1/32 Hz. The actuator can be used in microsystems, where both large strokes and forces are needed. The low-cost materials and low driving voltage also makes it suitable for disposable systems.
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| 23. |
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| 24. |
- Munn-Chernoff, M. A., et al.
(författare)
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Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
- 2021
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Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r(g)], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from similar to 2400 to similar to 537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r(g) = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r(g) = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r(g) = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r(gs) = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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| 25. |
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| 26. |
- Ogden, Sam, 1979-, et al.
(författare)
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A Latchable Valve for High-Pressure Microfluidics
- 2010
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Ingår i: Journal of microelectromechanical systems. - 1057-7157 .- 1941-0158. ; 19:2, s. 396-401
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, the strongest yet latchable valve in subcubic-centimeter size for microfluidic applications is presented. The device has an integrated actuator cavity consisting of three segments filled with paraffin, each operated by a separate heater. At one of the segments, a membrane valve head is deflected by the expansion of the resistively melted paraffin to close against its valve seat. Different heating sequences provide a latched closed or opened valve. The maximum pressure before any leakage occurred was 2.5 MPa. The leak pressure is found to be progressively dependent on the clamping pressure applied. The valve has an opening and closing time of 7 and 1 s, respectively. At an applied pressure of 0.3 MPa, the closed valve needs to be reactivated every 100 min to remain leakage free, leading to an average power consumption of 4.5 mW.
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| 27. |
- Ogden, Sam, 1979-, et al.
(författare)
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Fluid behavior of supercritical carbon dioxide with water in a double-Y-channel microfluidic chip
- 2014
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Ingår i: Microfluidics and Nanofluidics. - : Springer Science and Business Media LLC. - 1613-4982 .- 1613-4990. ; 17:6, s. 1105-1112
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Tidskriftsartikel (refereegranskat)abstract
- The use of supercritical carbon dioxide (scCO(2)) as an apolar solvent has been known for decades. It offers a greener approach than, e.g., hexane or chloroform, when such solvents are needed. The use of scCO(2) in microsystems, however, has only recently started to attract attention. In microfluidics, the flow characteristics need to be known to be able to successfully design such components and systems. As supercritical fluids exhibit the exciting combination of low viscosity, high density, and high diffusion rates, the fluidic behavior is not directly transferrable from aqueous systems. In this paper, three flow regimes in the scCO(2)-liquid water two-phase microfluidic system have been mapped. The effect of both total flow rate and relative flow rate on the flow regime is evaluated. Furthermore, the droplet dynamics at the bifurcating exit channel are analyzed at different flow rates. Due to the low viscosity of scCO(2), segmented flows were observed even at fairly high flow rates. Furthermore, the carbon dioxide droplet behavior exhibited a clear dependence on both flow rate and droplet length.
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| 28. |
- Ogden, Sam, 1979-, et al.
(författare)
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Fluid mechanics of supercritical carbon dioxide with water in a double-y-channel microfluidic chip
- 2013
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Ingår i: Micromechanics and microsystems europe.
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Konferensbidrag (refereegranskat)abstract
- In this paper, three flow regimes in thesupercritical carbon dioxide-water two-phase microfluidicsystem are mapped. The effect of both totalflow rate and relative flow rate on the flow regime isevaluated. Furthermore, the droplet dynamics at thebifurcating exit channel is analysed at different flowrates. The influence of the capillary number ondroplet splitting at the exit is also evaluated.
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| 29. |
- Ogden, Sam, 1979-, et al.
(författare)
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Latchable Valve for Microfluidic Sampling from a Miniature Submersible
- 2012
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Ingår i: Actuator. ; , s. 717-720
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Konferensbidrag (refereegranskat)abstract
- This work presents latchable high-pressure valves. Such valves are useful in a number of applications, e.g deep-sea sampling. Actuation and latching are achieved by using sequential melting and solidification of three connected paraffin-filled cavities, as well as a compliant valve seat. The valve seat design uses the applied back pressure to improve sealing, shown both in the valve’s endurance and burst pressure. The valves were evaluated by pressurizing them with both compressed air and water. At an applied hydrostatic back pressure kept above 2.1 MPa, the valve managed to stay closed without power consumption for 19 hours. The burst pressure was determined to 20 MPa when subjected to a hydrostatic pressure, and 5.6 MPa when subjected to a pneumatic pressure.
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| 30. |
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| 31. |
- Ogden, Sam, 1979-, et al.
(författare)
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On-chip pump system for high-pressure microfluidic applications
- 2013
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Konferensbidrag (refereegranskat)abstract
- This paper presents a micropump system with four integrated paraffin actuated pumps: Two mobile phase pumps and two sample injector pumps. The mobile phase pumps are evaluated by their ability to deliver a stable, low-ripple flow to be used in chip-based high performance liquid chromatography. It is shown that the two mobile phase pumps can be driven in combined operation with an induced offset to significantly lower flow fluctuations.
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| 32. |
- Ogden, Sam, 1979-, et al.
(författare)
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Review on miniaturized paraffin phase change actuators, valves, and pumps
- 2014
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Ingår i: Microfluidics and Nanofluidics. - : Springer Science and Business Media LLC. - 1613-4982 .- 1613-4990. ; 17:1, s. 53-71
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Forskningsöversikt (refereegranskat)abstract
- During the last fifteen years, miniaturised paraffin actuation has evolved through the need of a simple actuation principle, still able to deliver large strokes and high actuation forces at small scales. This is achieved by the large and rather incompressible volume expansion associated with the solid-to-liquid phase transition of paraffin. The common approach has been to encapsulate the paraffin by a stiff surrounding that directs the volume expansion towards a flexible membrane, which deflects in a directed stroke. However, a number of alternative methods have also been used in the literature. The most common applications to this date have been switches, positioning actuators, and microfluidic valves and pumps. This review will treat the historical background, as well as the fundamentals in paraffin actuation, including material properties of paraffin. Besides reviewing the three major groups of paraffin actuator applications; actuators, valves, and pumps, the modelling done on paraffin actuation will be explored. Furthermore, a section focusing on fabrication of paraffin microactuators is also included. The review ends with conclusions and outlook of the field, identifying unexplored potential of paraffin actuation.
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| 33. |
- Watson, H. J., et al.
(författare)
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Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:8
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Tidskriftsartikel (refereegranskat)abstract
- Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness(1), affecting 0.9-4% of women and 0.3% of men(2-4), with twin-based heritability estimates of 50-60%(5). Mortality rates are higher than those in other psychiatric disorders(6), and outcomes are unacceptably poor(7). Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)(8,9) and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
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