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| 2. |
- Patel, Riyaz S., et al.
(författare)
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Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
- 2019
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Ingår i: Circulation. - 2574-8300. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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| 3. |
- Patel, Riyaz S., et al.
(författare)
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Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
- 2019
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Ingår i: Circulation. - 2574-8300. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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| 4. |
- Gerasimov, Jennifer, et al.
(författare)
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An Evolvable Organic Electrochemical Transistor for Neuromorphic Applications
- 2019
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Ingår i: Advanced Science. - : Wiley-VCH Verlagsgesellschaft. - 2198-3844. ; 6:7
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Tidskriftsartikel (refereegranskat)abstract
- An evolvable organic electrochemical transistor (OECT), operating in the hybrid accumulation-depletion mode is reported, which exhibits short-term and long-term memory functionalities. The transistor channel, formed by an electropolymerized conducting polymer, can be formed, modulated, and obliterated in situ and under operation. Enduring changes in channel conductance, analogous to long-term potentiation and depression, are attained by electropolymerization and electrochemical overoxidation of the channel material, respectively. Transient changes in channel conductance, analogous to short-term potentiation and depression, are accomplished by inducing nonequilibrium doping states within the transistor channel. By manipulating the input signal, the strength of the transistor response to a given stimulus can be modulated within a range that spans several orders of magnitude, producing behavior that is directly comparable to short- and long-term neuroplasticity. The evolvable transistor is further incorporated into a simple circuit that mimics classical conditioning. It is forecasted that OECTs that can be physically and electronically modulated under operation will bring about a new paradigm of machine learning based on evolvable organic electronics.
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| 5. |
- Gryszel, Maciej, et al.
(författare)
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Vertical Organic Electrochemical Transistor Platforms for Efficient Electropolymerization of Thiophene Based Oligomers
- 2024
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Ingår i: Journal of Materials Chemistry C. - : ROYAL SOC CHEMISTRY. - 2050-7526 .- 2050-7534.
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Tidskriftsartikel (refereegranskat)abstract
- Organic electrochemical transistors (OECTs) have emerged as promising candidates for various fields, including bioelectronics, neuromorphic computing, biosensors, and wearable electronics. OECTs operate in aqueous solutions, exhibit high amplification properties, and offer ion-to-electron signal transduction. The OECT channel consists of a conducting polymer, with PEDOT:PSS receiving the most attention to date. While PEDOT:PSS is highly conductive, and benefits from optimized protocols using secondary dopants and detergents, new p-type and n-type polymers are emerging with desirable material properties. Among these, low-oxidation potential oligomers are highly enabling for bioelectronics applications, however the polymers resulting from their polymerization lag far behind in conductivity compared with the established PEDOT:PSS. In this work we show that by careful design of the OECT geometrical characteristics, we can overcome this limitation and achieve devices that are on-par with transistors employing PEDOT:PSS. We demonstrate that the vertical architecture allows for facile electropolymerization of a family of trimers that are polymerized in very low oxidation potentials, without the need for harsh chemicals or secondary dopants. Vertical and planar OECTs are compared using various characterization methods. We show that vOECTs are superior platforms in general and propose that the vertical architecture can be expanded for the realization of OECTs for various applications.
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| 6. |
- Mahmoodi, Bakhtawar K., et al.
(författare)
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Association of Factor V Leiden With Subsequent Atherothrombotic Events A GENIUS-CHD Study of Individual Participant Data
- 2020
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Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 142:6, s. 546-555
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD.Methods: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality.Results: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16];I-2=28%;P-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality were also close to identity.Conclusions: Factor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population.
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| 7. |
- Nissa, Josefin, 1987-
(författare)
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Interacting with biological membranes using organic electronic devices
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Many physiological processes are reliant on activities in the cell membrane. These activities are of great importance to our well-being since they allow the cells to respond to their environment and communicate with each other to function as tissues and organs. In this thesis the use of organic electronic devices to interface with cell membranes has been explored. Organic electronics are especially suited for the task given their ability to transduce ionic to electronic signals. Four scientific papers are included in the thesis, where organic electronic devices are used together with living cells and supported lipid bilayers (SLB). In the first paper a ferroelectric cell release surface is presented. Release of cells cultured on the surface was induced by a polarization change in the ferroelectric polymer. This non-enzymatic release method was developed primarily for treatment of severe burns.The remaining three papers strive to combine lipid bilayers and the conjugated polymer poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS) in biosensors. The target device is an organic electrochemical transistor (OECT) functionalized with a supported lipid bilayer. Several aspects of the integration are explored, including promotion of vesicle fusion onto PEDOT:PSS and optimization of OECT design and biasing conditions for sensing. For SLB formation on PEDOT:PSS two different silica material systems, one PEDOT:PSS/silica composite and one mesoporous silica film, were evaluated with respect to electrical properties and quality of the resulting bilayer. The electrical properties were found to be similar, but the quality of the bilayer was better on the mesoporous silica film.In the last two papers the focus is on optimization of OECTs for sensing purposes. Biasing conditions for operation at high transconductance were identified, as well as design principles for large sensor output in impedance sensing.
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| 9. |
- Osman, Amr, 1993, et al.
(författare)
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Simplified Josephson-junction fabrication process for reproducibly high-performance superconducting qubits
- 2021
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 118:6
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Tidskriftsartikel (refereegranskat)abstract
- We introduce a simplified fabrication technique for Josephson junctions and demonstrate superconducting Xmon qubits with T1 relaxation times averaging above 50 μs (Q > 1.5 × 1 0 6). Current shadow-evaporation techniques for aluminum-based Josephson junctions require a separate lithography step to deposit a patch that makes a galvanic, superconducting connection between the junction electrodes and the circuit wiring layer. The patch connection eliminates parasitic junctions, which otherwise contribute significantly to dielectric loss. In our patch-integrated cross-type junction technique, we use one lithography step and one vacuum cycle to evaporate both the junction electrodes and the patch. This eliminates a key bottleneck in manufacturing superconducting qubits by reducing the fabrication time and cost. In a study of more than 3600 junctions, we show an average resistance variation of 3.7% on a wafer that contains forty 0.5 × 0.5-cm2 chips, with junction areas ranging between 0.01 and 0.16 μm2. The average on-chip spread in resistance is 2.7%, with 20 chips varying between 1.4% and 2%. For the junction sizes used for transmon qubits, we deduce a wafer-level transition-frequency variation of 1.7%-2.5%. We show that 60%-70% of this variation is attributed to junction-area fluctuations, while the rest is caused by tunnel-junction inhomogeneity. Such high frequency predictability is a requirement for scaling-up the number of qubits in a quantum computer.
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