Functional and pharmacological characterization of volume-regulated anion channels in human normal and cystic fibrosis bronchial and nasal epithelial cells

Volume-regulated anion channels (VRACs) are widely present in various cell types and have important functions ranging from regulatory volume decrease to control of cell proliferation and apoptosis. Here we aimed to compare the biophysical features and pharmacological profiles of VRAC currents in healthy and cystic fibrosis (CF) respiratory epithelial cells in order to characterize these currents both functionally and pharmacologically. Whole-cell electrophysiology was used to characterize the VRAC current in normal (16HBE14o-; HBE) and CF cell lines (CFBE14o-; CFBE), as well as in native human nasal epithelial cells. Application of hypotonic solution produced current responses of similar sizes in both HBE and CFBE cells. Biophysical properties of VRACs, such as instantaneous activation and deactivation upon voltage step, some inactivation at potentials positive to 40 mV and outwardly-rectifying I-V curves, were indistinguishable in both cell types. Extensive pharmacological analysis of the currents revealed a similar pharmacological profile in response to three blockers--NPPB, DCPIB and DIDS. Native primary human nasal epithelial cells from both healthy and CF volunteers also showed typical VRAC responses of comparable sizes. VRACs in these cells were more sensitive to external solution hypotonicity compared to HBE and CFBE cells. In all cell types studied robust VRAC currents could be induced at constant cell volume by G-protein activation with GTPγS infusion. This study provides the first extensive comparative functional and pharmacological analysis of VRAC currents in normal and CF airway epithelial cells and shows that VRACs are unimpaired molecularly or functionally in CF.

The significance of interconnector counter-trading in a security constrained electricity market

Throughout the European Union there is an increasing amount of wind generation being dispatched-down due to the binding of power system operating constraints from high levels of wind generation. This paper examines the impact a system non-synchronous penetration limit has on the dispatch-down of wind and quantifies the significance of interconnector counter-trading to the priority dispatching of wind power. A fully coupled economic dispatch and security constrained unit commitment model of the Single Electricity Market of the Republic of Ireland and Northern Ireland and the British Electricity Trading and Transmission Arrangement was used in this study. The key finding was interconnector counter-trading reduces the impact the system non-synchronous penetration limit has on the dispatch-down of wind. The capability to counter-trade on the interconnectors and an increase in system non-synchronous penetration limit from 50% to 55% reduces the dispatch-down of wind by 311 GW h and decreases total electricity payments to the consumer by €1.72/MW h. In terms of the European Union electricity market integration, the results show the importance of developing individual electricity markets that allow system operators to counter-trade on interconnectors to ensure the priority dispatch of the increasing levels of wind generation.

Is the raised volume rapid thoracic compression technique ready for use in clinical trials in infants with cystic fibrosis?

The European Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN) has established a Standardization Committee to undertake a rigorous evaluation of promising outcome measures with regard to use in multicentre clinical trials in cystic fibrosis (CF). The aim of this article is to present a review of literature on clinimetric properties of the infant raised-volume rapid thoracic compression (RVRTC) technique in the context of CF, to summarise the consensus amongst the group on feasibility and answer key questions regarding the promotion of this technique to surrogate endpoint status.

METHODS: A literature search (from 1985 onwards) identified 20 papers that met inclusion criteria of RVRTC use in infants with CF. Data were extracted and tabulated regarding repeatability, validity, correlation with other outcome measures, responsiveness and reference values. A working group discussed the tables and answered 4 key questions.

RESULTS: Overall, RVRTC in particular forced expiratory volume in 0.5s, showed good clinimetric properties despite presence of individual variability. Few studies showed a relationship between RVRTC and inflammation and infection, and to date, data remains limited regarding the responsiveness of RVRTC after an intervention. Concerns were raised regarding feasibility in multi-centre studies and availability of reference values.

CONCLUSION: The ECFS-CTN Working Group considers that RVRTC cannot be used as a primary outcome in clinical trials in infants with CF before universal standardization of this measurement is achieved and implementation of inter-institutional networking is in place. We advise its use currently in phase I/II trials and as a secondary endpoint in phase III studies. We emphasise the need for (1) more short-term variability and longitudinal 'natural history' studies, and (2) robust reference values for commercially available devices.

Preoperative radial artery volume flow is predictive of arteriovenous fistula outcomes

Objective: Guidelines recommend the creation of a wrist radiocephalic arteriovenous fistula (RAVF) as initial hemodialysis vascular access. This study explored the potential of preoperative ultrasound vessel measurements to predict AVF failure to mature (FTM) in a cohort of patients with end-stage renal disease in Northern Ireland

.Methods: A retrospective analysis was performed of all patients who had preoperative ultrasound mapping of upper limb blood vessels carried out from August 2011 to December 2014 and whose AVF reached a functional outcome by March 2015.

Results: There were 152 patients (97% white) who had ultrasound mapping andan AVF functional outcome recorded; 80 (54%) had an upper arm AVF created, and 69 (46%) had a RAVF formed. Logistic regression revealed that female gender (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.12-5.55; P = .025), minimum venous diameter (OR, 0.6; 95% CI, 0.39-0.95; P = .029), and RAVF (OR, 0.4; 95% CI, 0.18-0.89; P = .026) were associated with FTM. On subgroup analysis of the RAVF group, RAVFs with an arterial volume flow <50 mL/min were seven times as likely to fail as RAVFs with higher volume flows (OR, 7.0; 95% CI, 2.35-20.87; P < .001).

Conclusions: In this cohort, a radial artery flow rate <50 mL/min was associated with a sevenfold increased risk of FTM in RAVF, which to our knowledge has not been previously reported in the literature. Preoperative ultrasound mapping adds objective assessment in the clinical prediction of AVF FTM.

A method of measuring anterior chamber volume using the anterior segment optical coherence tomographer and specialized software.

PURPOSE: To describe and evaluate a new method for measuring anterior chamber volume (ACV). DESIGN: Observational case series. METHODS: The authors measured ACV using the anterior chamber (AC) optical coherence tomographer (OCT) and applied image-processing software developed by them. Repeatability was evaluated. The ACV was measured in patient groups with normal ACs, shallow ACs, and deep ACs. The volume difference before and after laser peripheral iridotomy (LPI) was analyzed for the shallow and deep groups. RESULTS: Coefficients of repeatability for intraoperator, interoperator, and interimage measurements were 0.406%, 0.958%, and 0.851%, respectively. The limits of agreement for intraoperator and interoperator measurement were -0.911 microl to 1.343 microl and -7.875 microl to -2.463 microl, respectively. There were significant ACV differences in normal, shallow, and deep AC eyes (P < .001) and before and after LPI in shallow AC (P < .001) and deep AC (P = .008) eyes. CONCLUSIONS: The ACV values obtained by this method were repeatable and in accord with clinical observation.

Modelling of Evaporator in Waste Heat Recovery System using Finite Volume Method and Fuzzy Technique

The evaporator is an important component in the Organic Rankine Cycle (ORC)-based Waste Heat Recovery (WHR) system since the effective heat transfer of this device reflects on the efficiency of the system. When the WHR system operates under supercritical conditions, the heat transfer mechanism in the evaporator is unpredictable due to the change of thermo-physical properties of the fluid with temperature. Although the conventional finite volume model can successfully capture those changes in the evaporator of the WHR process, the computation time for this method is high. To reduce the computation time, this paper develops a new fuzzy based evaporator model and compares its performance with the finite volume method. The results show that the fuzzy technique can be applied to predict the output of the supercritical evaporator in the waste heat recovery system and can significantly reduce the required computation time. The proposed model, therefore, has the potential to be used in real time control applications.

Eurozone Network Connectedness During Calm and Crisis: Evidence from the MTS Platform for Interdealer Trading of European Sovereign Debt

This paper examines the connectedness of the Eurozone sovereign debt market over the period 2005–2011. By employing measures built from the variance decompositions of approximating models we are able to define weighted, directed networks that enable a deeper understanding of the relationships between the Eurozone countries. We find that connectedness in the Eurozone was very high during the calm market conditions preceding the global financial crisis but decreased dramatically when the crisis took hold, and worsened as the Eurozone sovereign debt crisis emerged. The drop in connectedness was especially prevalent in the case of the peripheral countries with some of the most peripheral countries deteriorating into isolation. Our results have implications for both market participants and regulators.