Barriers to enrollment in a randomized controlled trial of hydrocortisone for cardiovascular insufficiency in term and late preterm newborn infants.

ObjectiveTo analyze reasons for low enrollment in a randomized controlled trial (RCT) of the effect of hydrocortisone for cardiovascular insufficiency on survival without neurodevelopmental impairment (NDI) in term/late preterm newborns.Study designThe original study was a multicenter RCT. Eligibility: ⩾34 weeks' gestation, <72 h old, mechanically ventilated, receiving inotrope. Primary outcome was NDI at 2 years; infants with diagnoses at high risk for NDI were excluded. This paper presents an analysis of reasons for low patient enrollment.ResultsTwo hundred and fifty-seven of the 932 otherwise eligible infants received inotropes; however, 207 (81%) had exclusionary diagnoses. Only 12 infants were randomized over 10 months; therefore, the study was terminated. Contributing factors included few eligible infants after exclusions, open-label steroid therapy and a narrow enrollment window.ConclusionDespite an observational study to estimate the population, very few infants were enrolled. Successful RCTs of emergent therapy may require fewer exclusions, a short-term primary outcome, waiver of consent and/or other alternatives

Relativistic Compression and Expansion of Experiential Time in the Left and Right Space

Time, space and numbers are closely linked in the physical world. However, the relativistic-like effects on time perception of spatial and magnitude factors remain poorly investigated. Here we wanted to investigate whether duration judgments of digit visual stimuli are biased depending on the side of space where the stimuli are presented and on the magnitude of the stimulus itself. Different groups of healthy subjects performed duration judgment tasks on various types of visual stimuli. In the first two experiments visual stimuli were constituted by digit pairs (1 and 9), presented in the centre of the screen or in the right and left space. In a third experiment visual stimuli were constituted by black circles. The duration of the reference stimulus was fixed at 300 ms. Subjects had to indicate the relative duration of the test stimulus compared with the reference one. The main results showed that, regardless of digit magnitude, duration of stimuli presented in the left hemispace is underestimated and that of stimuli presented in the right hemispace is overestimated. On the other hand, in midline position, duration judgments are affected by the numerical magnitude of the presented stimulus, with time underestimation of stimuli of low magnitude and time overestimation of stimuli of high magnitude. These results argue for the presence of strict interactions between space, time and magnitude representation on the human brain

Red wine polyphenols prevent metabolic and cardiovascular alterations associated with obesity in Zucker fatty rats (Fa/Fa)

Peer reviewedPublisher PD

Magnetotransport and magnetic properties of amorphous [Formula: see text] thin films.

[Formula: see text] is an intermetallic compound with a bulk Curie temperature ([Formula: see text]) of 6-13 K. While existing studies have focused on [Formula: see text] crystals, amorphous thin-films of [Formula: see text] are potentially important since they would be magnetically soft without magnetocrystalline anisotropy, meaning that small external magnetic fields could reverse the direction of their magnetization. Here, we report [Formula: see text] thin-films with a thickness in the 5-200 nm range, deposited by DC magnetron sputtering onto Si(100). Films are amorphous with a weak temperature-dependent resistivity with values ranging between 150 and 300 [Formula: see text] cm. By means of noise spectroscopy, by analyzing the time-dependence of fluctuation-induced voltages, it is found that at low temperatures the resistance fluctuations are due to the Kondo effect. Volume magnetometry indicates [Formula: see text] K with a magnetic coercive field of 30 mT at 5 K for a 125-nm-thick film. The results are promising for the development of Ferromagnet(F)/Superconductor(S)/Ferromagnet(F) pseudo spin-valve devices based on amorphous [Formula: see text] thin films

The incidence of arthropathy adverse events in efalizumab-treated patients is low and similar to placebo and does not increase with long-term treatment: pooled analysis of data from Phase III clinical trials of efalizumab

A large-scale, pooled analysis of safety data from five Phase III clinical trials (including open-label extensions of two of these studies) and two Phase III open-label clinical trials of efalizumab was conducted to explore whether arthropathy adverse events (AEs) were associated with efalizumab treatment in patients with moderate-to-severe chronic plaque psoriasis. Data from patients who received subcutaneous injections of efalizumab or placebo were stratified for analysis into phases according to the nature and duration of treatment. These included: the ‘first treatment’ phase (0–12-week data from patients who received either efalizumab, 1 mg/kg once weekly, or placebo in the five placebo-controlled studies); the ‘extended treatment’ phase (13–24-week data from seven trials for all efalizumab-treated patients); and the ‘long-term treatment’ phase (data from efalizumab-treated patients who received treatment for up to 36 months in two long-term trials). Descriptive statistics were performed and the incidence of arthropathy AEs per patient-year was calculated using 95% confidence intervals (CIs). During the first treatment phase, a similar proportion of patients had an arthropathy AE in the efalizumab group (3.3%; 58/1740 patients) compared with the placebo group (3.5%; 34/979 patients); the incidence of arthropathy AEs per patient-year was 0.15 in the efalizumab group (95% CI 0.11–0.19) and 0.16 in the placebo group (95% CI 0.11–0.22). Analysis of first treatment phase data from one study (n = 793) showed that the incidence of psoriatic arthropathy per patient-year was lower in efalizumab-treated patients (0.10; 95% CI 0.05–0.18) than in those given placebo (0.17; 95% CI 0.08–0.30). During the extended treatment phase, the incidence of arthropathy remained low (0.17; 95% CI 0.14–0.22). Data from two long-term studies showed that there was no increase in the incidence of arthropathy AEs over time in patients treated with efalizumab for up to 36 months. Patients who had an arthropathy AE during treatment with efalizumab appeared to be more likely to have a history of arthropathy prior to treatment. Efalizumab does not appear to increase the risk of arthropathy AEs compared with placebo

Estimation of current density distribution under electrodes for external defibrillation

BACKGROUND: Transthoracic defibrillation is the most common life-saving technique for the restoration of the heart rhythm of cardiac arrest victims. The procedure requires adequate application of large electrodes on the patient chest, to ensure low-resistance electrical contact. The current density distribution under the electrodes is non-uniform, leading to muscle contraction and pain, or risks of burning. The recent introduction of automatic external defibrillators and even wearable defibrillators, presents new demanding requirements for the structure of electrodes. METHOD AND RESULTS: Using the pseudo-elliptic differential equation of Laplace type with appropriate boundary conditions and applying finite element method modeling, electrodes of various shapes and structure were studied. The non-uniformity of the current density distribution was shown to be moderately improved by adding a low resistivity layer between the metal and tissue and by a ring around the electrode perimeter. The inclusion of openings in long-term wearable electrodes additionally disturbs the current density profile. However, a number of small-size perforations may result in acceptable current density distribution. CONCLUSION: The current density distribution non-uniformity of circular electrodes is about 30% less than that of square-shaped electrodes. The use of an interface layer of intermediate resistivity, comparable to that of the underlying tissues, and a high-resistivity perimeter ring, can further improve the distribution. The inclusion of skin aeration openings disturbs the current paths, but an appropriate selection of number and size provides a reasonable compromise

Costs and Cost-Effectiveness of Training Traditional Birth Attendants to Reduce Neonatal Mortality in the Lufwanyama Neonatal Survival Study (LUNESP)

The Lufwanyama Neonatal Survival Project (“LUNESP”) was a cluster randomized, controlled trial that showed that training traditional birth attendants (TBAs) to perform interventions targeting birth asphyxia, hypothermia, and neonatal sepsis reduced all-cause neonatal mortality by 45%. This companion analysis was undertaken to analyze intervention costs and cost-effectiveness, and factors that might improve cost-effectiveness.We calculated LUNESP's financial and economic costs and the economic cost of implementation for a forecasted ten-year program (2011–2020). In each case, we calculated the incremental cost per death avoided and disability-adjusted life years (DALYs) averted in real 2011 US dollars. The forecasted 10-year program analysis included a base case as well as ‘conservative’ and ‘optimistic’ scenarios. Uncertainty was characterized using one-way sensitivity analyses and a multivariate probabilistic sensitivity analysis. The estimated financial and economic costs of LUNESP were $118,574 and$127,756, respectively, or $49,469 and$53,550 per year. Fixed costs accounted for nearly 90% of total costs. For the 10-year program, discounted total and annual program costs were $256,455 and$26,834 respectively; for the base case, optimistic, and conservative scenarios, the estimated cost per death avoided was $1,866,$591, and $3,024, and cost per DALY averted was$74, $24, and$120, respectively. Outcomes were robust to variations in local costs, but sensitive to variations in intervention effect size, number of births attended by TBAs, and the extent of foreign consultants' participation.Based on established guidelines, the strategy of using trained TBAs to reduce neonatal mortality was ‘highly cost effective’. We strongly recommend consideration of this approach for other remote rural populations with limited access to health care

Alternative Splicing of the Cardiac Sodium Channel Creates Multiple Variants of Mutant T1620K Channels

Alternative splicing creates several Nav1.5 transcripts in the mammalian myocardium and in various other tissues including brain, dorsal root ganglia, breast cancer cells as well as neuronal stem cell lines. In total nine Nav1.5 splice variants have been discovered. Four of them, namely Nav1.5a, Nav1.5c, Nav1.5d, and Nav1.5e, generate functional channels in heterologous expression systems. The significance of alternatively spliced transcripts for cardiac excitation, in particular their role in SCN5A channelopathies, is less well understood. In the present study, we systematically investigated electrophysiological properties of mutant T1620K channels in the background of all known functional Nav1.5 splice variants in HEK293 cells. This mutation has been previously associated with two distinct cardiac excitation disorders: with long QT syndrome type 3 (LQT3) and isolated cardiac conduction disease (CCD). When investigating the effect of the T1620K mutation, we noticed similar channel defects in the background of hNav1.5, hNav1.5a, and hNav1.5c. In contrast, the hNav1.5d background produced differential effects: In the mutant channel, some gain-of-function features did not emerge, whereas loss-of-function became more pronounced. In case of hNav1.5e, the neonatal variant of hNav1.5, both the splice variant itself as well as the corresponding mutant channel showed electrophysiological properties that were distinct from the wild-type and mutant reference channels, hNav1.5 and T1620K, respectively. In conclusion, our data show that alternative splicing is a mechanism capable of generating a variety of functionally distinct wild-type and mutant hNav1.5 channels. Thus, the cellular splicing machinery is a potential player affecting genotype-phenotype correlations in SCN5A channelopathies