| 1. |
- Ehrhardt, Carsten, et al.
(författare)
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Current Progress Toward a Better Understanding of Drug Disposition Within the Lungs : Summary Proceedings of the First Workshop on Drug Transporters in the Lungs
- 2017
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 106:9, s. 2234-2244
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Tidskriftsartikel (refereegranskat)abstract
- The School of Pharmacy and Pharmaceutical Sciences at Trinity College Dublin hosted the "1st Workshop on Drug Transporters in the Lungs" in September 2016 to discuss the impact of transporters on pulmonary drug disposition and their roles as drug targets in lung disease. The workshop brought together about 30 scientists from academia and pharmaceutical industry from Europe and Japan and addressed the primary questions: What do we know today, and what do we need to know tomorrow about transporters in the lung? The 3 themes of the workshop were: (1) techniques to study drug transporter expression and actions in the lungs; (2) drug transporter effects on pulmonary pharmacokinetics-case studies; and (3) transporters as drug targets in lung disease. Some of the conclusions of the workshop were: suitable experimental models that allow studies of transporter effects are available; data from these models convincingly show a contribution of both uptake and efflux transporters on pulmonary drug disposition; the effects of transporters on drug lung PK is now better conceptualized; some transporters are associated with lung diseases. However, more work is needed to establish which of the available models best translate to the clinical situation.
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| 2. |
- Imamura, Teruhiko, et al.
(författare)
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Late-onset right ventricular failure in patients with preoperative small left ventricle after implantation of continuous flow left ventricular assist device
- 2014
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Ingår i: Circulation Journal. - : Japanese Circulation Society. - 1346-9843 .- 1347-4820. ; 78:3, s. 625-633
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Tidskriftsartikel (refereegranskat)abstract
- Background: The continuous flow (CF) left ventricular assist device (LVAD) has replaced the pulsatile flow (PF) LVAD because of its advantages of better patient survival and higher quality of life. However, "late-onset right ventricular failure (RVF)" after CF LVAD implantation has emerged as an increasing concern, but little is known about the mechanism. Methods and Results: We retrospectively analyzed the 3-month hemodynamic and echocardiographic data from 38 consecutive patients who had received CF LVADs, and from 22 patients who had received PF LVADs. Late-onset RVF was defined as persistent right ventricular stroke work index (RVSWI) less than4.0 g/m(2) at any rotation speed and after saline infusion test at 5 weeks after implantation of CF LVAD. Patients with late-onset RVF had significantly impaired exercise tolerance indicated by shorter 6-min walking distance and lower peak (V) over dot O-2, and worsened tricuspid regurgitation, together with enlargement of the RV under CF LVAD treatment (all Pless than0.05). Univariable analyses demonstrated that preoperative smaller LV diastolic diameter (LVDd) was the risk factor for late-onset RVF with a cutoff value of 64 mm calculated by ROC analysis (area under curve, 0.925). In contrast, there was no correlation between preoperative LVDd and postoperative RVSWI in the PF LVAD group, though their preoperative background was worse than that of the CF group. Conclusions: In the setting of preoperative small LVDd, CF LVAD may cause late-onset RVF by leftward shift of the interventricular septum.
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| 3. |
- Kawabata, Shiro, et al.
(författare)
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Theory of two-dimensional macroscopic quantum tunneling in a Josephson junction coupled with an LC circuit
- 2009
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 150:5, s. 052105-
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Konferensbidrag (refereegranskat)abstract
- We investigate classical thermal activation (TA) and macroscopic quantum tunneling (MQT) for a Josephson junction coupled with an LC circuit theoretically. The TA and MQT escape rate are calculated analytically by taking into account the two-dimensional nature of the classical and quantum phase dynamics. We find that the MQT escape rate is largely suppressed by the coupling to the LC circuit. On the other hand, this coupling gives rise to slight reduction of the TA escape rate. These results are relevant for the interpretation of a recent experiment on the MQT and TA phenomena in grain boundary YBCO Josephson junctions.
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| 4. |
- Kawabata, Shiro, et al.
(författare)
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Theory of two-dimensional macroscopic quantum tunneling in YBa2Cu3O7-delta Josephson junctions coupled to an LC circuit
- 2009
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Ingår i: Physical Review B - Condensed Matter and Materials Physics. - 2469-9950 .- 2469-9969. ; 80:17, s. 174513-
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Tidskriftsartikel (refereegranskat)abstract
- We investigate classical thermal activation (TA) and macroscopic quantum tunneling (MQT) for a YBa2Cu3O7−δ (YBCO) Josephson junction coupled to an LC circuit theoretically. Due to the coupling between the junction and the LC circuit, the macroscopic phase dynamics can be described as the escape process of a fictitious particle with an anisotropic mass moving in a two-dimensional potential. We analytically calculate the escape rate including both the TA and MQT regime by taking into account the peculiar dynamical nature of the system. In addtion to large suppression of the MQT rate at zero temperature, we study details of the temperature dependence of the escape rate across a crossover region. These results are in an excellent agreement with recent experimental data for the MQT and TA rate in a YBCO biepitaxial Josephson junction. Therefore the coupling to the LC circuit is essential in understanding the macroscopic quantum dynamics and the qubit operation based on the YBCO biepitaxial Josephson junctions.
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| 5. |
- Kawabata, Shiro, et al.
(författare)
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TWO-DIMENSIONAL MACROSCOPIC QUANTUM DYNAMICS IN YBCO JOSEPHSON JUNCTIONS
- 2009
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Ingår i: International Journal of Modern Physics B. - 0217-9792. ; 23:20-21, s. 4329-
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Tidskriftsartikel (refereegranskat)abstract
- We theoretically study classical thermal activation (TA) and macroscopic quantum tunneling (MQT) for a YBa2Cu3O7-δ(YBCO) Josephson junction coupled with an LC circuit. The TA and MQT escape rate are calculated by taking into account the two-dimensional nature of the classical and quantum phase dynamics. We find that the MQT escape rate is largely suppressed by the coupling to the LC circuit. On the other hand, this coupling leads to the slight reduction of the TA escape rate. These results are relevant for the interpretation of a recent experiment on the MQT and TA phenomena in YBCO bi-epitaxial Josephson junctions.
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| 6. |
- Pennells, Lisa, et al.
(författare)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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| 7. |
- Perkiö Kato, Naoko, 1980-, et al.
(författare)
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Quality of Life and Influential Factors in Patients Implanted With a Left Ventricular Assist Device
- 2015
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Ingår i: Circulation Journal. - : JAPANESE CIRCULATION SOC. - 1346-9843 .- 1347-4820. ; 79:10, s. 2186-2192
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Tidskriftsartikel (refereegranskat)abstract
- Background: Improving quality of life (QOL) has become an important goal in left ventricular assist device (LVAD) therapy. We aimed (1) to assess the effect of an implantable LVAD on patients QOL, (2) to compare LVAD patients QOL to that of patients in different stages of heart failure (HF), and (3) to identify factors associated with patients QOL.Methods and Results: The QOL of 33 Japanese implantable LVAD patients was assessed using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and Short-form 8 (SF-8), before and at 3 and 6 months afterwards. After LVAD implantation, QOL significantly improved [MLHFQ, SF-8 physical component score (PCS), SF-8 mental component score (MCS), all Pless than0.05]. Implanted LVAD patients had a better QOL than extracorporeal LVAD patients (n=33, 32.1 +/- 21.9 vs. n=17, 47.6 +/- 18.2), and Stage D HF patients (n=32, 51.1 +/- 17.3), but the score was comparable to that of patients who had undergone a heart transplant (n=13). In multiple regression analyses, postoperative lower albumin concentration and right ventricular failure were independently associated with poorer PCS. Female sex and postoperative anxiety were 2 of the independent factors for poorer MCS (all Pless than0.05).Conclusions: Having an implantable LVAD improves patients QOL, which is better than that of patients with an extracorporeal LVAD. Both clinical and psychological factors are influence QOL after LVAD implantation.
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