Tablet computers in assessing performance in a high stakes exam : opinion matters

The authors would like to thank Dr Craig brown, University of Aberdeen for assistance with data analysis.Peer reviewedPublisher PD

Clinical trials with endothelin receptor antagonists: What went wrong and where can we improve?

In the early 1990s, within three years of cloning of endothelin receptors, orally active endothelin receptor antagonists (ERAs) were tested in humans and the first clinical trial of ERA therapy in humans was published in 1995. ERAs were subsequently tested in clinical trials involving heart failure, pulmonary arterial hypertension, resistant arterial hypertension, stroke/subarachnoid hemorrhage and various forms of cancer. The results of most of these trials – except those for pulmonary arterial hypertension and scleroderma-related digital ulcers – were either negative or neutral. Problems with study design, patient selection, drug toxicity, and drug dosing have been used to explain or excuse failures. Currently, a number of pharmaceutical companies who had developed ERAs as drug candidates have discontinued clinical trials or further drug development. Given the problems with using ERAs in clinical medicine, at the Twelfth International Conference on Endothelin in Cambridge, UK, a panel discussion was held by clinicians actively involved in clinical development of ERA therapy in renal disease, systemic and pulmonary arterial hypertension, heart failure, and cancer. This article provides summaries from the panel discussion as well as personal perspectives of the panelists on how to proceed with further clinical testing of ERAs and guidance for researchers and decision makers in clinical drug development on where future research efforts might best be focused

Methodological shortcomings of wrist-worn heart rate monitors validations

Wearable sensor technology could have an important role for clinical research and in delivering health care. Accordingly, such technology should undergo rigorous evaluation prior to market launch, and its performance should be supported by evidence-based marketing claims. Many studies have been published attempting to validate wrist-worn photoplethysmography (PPG)-based heart rate monitoring devices, but their contrasting results question the utility of this technology. The reason why many validations did not provide conclusive evidence of the validity of wrist-worn PPG-based heart rate monitoring devices is mostly methodological. The validation strategy should consider the nature of data provided by both the investigational and reference devices. There should be uniformity in the statistical approach to the analyses employed in these validation studies. The investigators should test the technology in the population of interest and in a setting appropriate for intended use. Device industries and the scientific community require robust standards for the validation of new wearable sensor technology

The relation between repeated 6-minute walk test performance and outcome in patients with chronic heart failure

Objective: To assess the prognostic implications of the 6-minute walk test (6-MWT) distance measured twice, one year apart, in a large sample of patients with chronic heart failure (CHF) followed for an extended period ( > . 8. years from baseline). Material and methods: Patients undertook a 6-MWT at baseline and at one year, and were followed up for 8. years from baseline. Results: Six hundred patients (median [inter-quartile range, IQR]) (age 78 [72-84] years; 75% males; body mass index 27 [25-31] kg·m -2 ; left ventricular ejection fraction 34 [26-38] %) were included. At baseline, median 6-MWT distance was 232 (60-386) m. There was no significant change in 6-MWT distance at one year (change -12m; P=0.533). During a median follow-up of 8.0years in survivors, 396patients had died (66%). Four variables were independent predictors of all-cause mortality in a multivariable Cox model (adjusted for body mass index, age, QRS duration, left ventricular ejection fraction); increasing NT pro-BNP, decreasing 6-MWT distance at 1year, decreasing haemoglobin, and increasing urea. Conclusions: Distance walked during the 6-MWT is an independent predictor of all-cause mortality in patients with CHF. In survivors, the 6-MWT distance is stable at 1 year. The 6-MWT distance at 1 year carries similar prognostic information. © 2014 Elsevier Masson SAS

High-Frequency Nanofluidics: An Experimental Study using Nanomechanical Resonators

Here we apply nanomechanical resonators to the study of oscillatory fluid dynamics. A high-resonance-frequency nanomechanical resonator generates a rapidly oscillating flow in a surrounding gaseous environment; the nature of the flow is studied through the flow-resonator interaction. Over the broad frequency and pressure range explored, we observe signs of a transition from Newtonian to non-Newtonian flow at $\omega\tau\approx 1$, where $\tau$ is a properly defined fluid relaxation time. The obtained experimental data appears to be in close quantitative agreement with a theory that predicts purely elastic fluid response as $\omega\tau\to \infty$

Fish oil: what the prescriber needs to know

There is a general belief among doctors, in part grounded in experience, that patients with arthritis need nonsteroidal anti-inflammatory drugs (NSAIDs). Implicit in this view is that these patients require the symptomatic relief provided by inhibiting synthesis of nociceptive prostaglandin E(2), a downstream product of the enzyme cyclo-oxygenase (COX), which is inhibited by NSAIDs. However, the concept of 'safe' NSAIDs has collapsed following a multiplicity of observations establishing increased risk for cardiovascular events associated with NSAID use, especially but not uniquely with the new COX-2-selective NSAIDs. This mandates greater parsimony in the use of these agents. Fish oils contain a natural inhibitor of COX, reduce reliance on NSAIDs, and reduce cardiovascular risk through multiple mechanisms. Fish oil thus warrants consideration as a component of therapy for arthritis, especially rheumatoid arthritis, in which its symptomatic benefits are well established. A major barrier to the therapeutic use of fish oil in inflammatory diseases is ignorance of its mechanism, range of beneficial effects, safety profile, availability of suitable products, effective dose, latency of effects and instructions for administration. This review provides an evidence-based resource for doctors and patients who may choose to prescribe or take fish oil

Influence of random roughness on the Casimir force at small separations

The influence of random surface roughness of Au films on the Casimir force is explored with atomic force microscopy in the plate-sphere geometry. The experimental results are compared to theoretical predictions for separations ranging between 20 and 200 nm. The optical response and roughness of the Au films were measured and used as input in theoretical predictions. It is found that at separations below 100 nm, the roughness effect is manifested through a strong deviation from the normal scaling of the force with separation distance. Moreover, deviations from theoretical predictions based on perturbation theory can be larger than 100%.Comment: 18, 5 figure

Quantum Effects in the Mechanical Properties of Suspended Nanomechanical Systems

We explore the quantum aspects of an elastic bar supported at both ends and subject to compression. If strain rather than stress is held fixed, the system remains stable beyond the buckling instability, supporting two potential minima. The classical equilibrium transverse displacement is analogous to a Ginsburg-Landau order parameter, with strain playing the role of temperature. We calculate the quantum fluctuations about the classical value as a function of strain. Excitation energies and quantum fluctuation amplitudes are compared for silicon beams and carbon nanotubes.Comment: RevTeX4. 5 pages, 3 eps figures. Submitted to Physical Review Letter