Self-Assembled Charged Hydrogels Control the Alignment of Filamentous Actin

We demonstrate a novel route to control attachment of filamentous actin (F-actin) on hydrogel films. By incorporating an amine-terminated silane, the hydrogel surface charge and surface topography are varied. With increasing silane content, F-actin reorients from perpendicular to parallel to the hydrogel surface, ceases to wobble, and forms mainly elongated or cyclic structures. F-Actin coverage reaches a maximum at 2.5 vol% silane and declines at higher silane content. This biphasic behavior is explained by the simultaneous increase in surface charge and the self-assembly of a micron scale pattern of positively charged islands. Our approach provides guidelines for constructing nanoscale tracks to guide motor proteins underlying nano-engineered devices such as molecular shuttles

Observations of whistler mode waves with nonlinear parallel electric fields near the dayside magnetic reconnection separatrix by the Magnetospheric Multiscale mission

We show observations from the Magnetospheric Multiscale (MMS) mission of whistler mode waves in the Earth's low-latitude boundary layer (LLBL) during a magnetic reconnection event. The waves propagated obliquely to the magnetic field toward the X line and were confined to the edge of a southward jet in the LLBL. Bipolar parallel electric fields interpreted as electrostatic solitary waves (ESW) are observed intermittently and appear to be in phase with the parallel component of the whistler oscillations. The polarity of the ESWs suggests that if they propagate with the waves, they are electron enhancements as opposed to electron holes. The reduced electron distribution shows a shoulder in the distribution for parallel velocities between 17,000 and 22,000 km/s, which persisted during the interval when ESWs were observed, and is near the phase velocity of the whistlers. This shoulder can drive Langmuir waves, which were observed in the high-frequency parallel electric field data

Lactation and neonatal nutrition: defining and refining the critical questions.

This paper resulted from a conference entitled "Lactation and Milk: Defining and refining the critical questions" held at the University of Colorado School of Medicine from January 18-20, 2012. The mission of the conference was to identify unresolved questions and set future goals for research into human milk composition, mammary development and lactation. We first outline the unanswered questions regarding the composition of human milk (Section I) and the mechanisms by which milk components affect neonatal development, growth and health and recommend models for future research. Emerging questions about how milk components affect cognitive development and behavioral phenotype of the offspring are presented in Section II. In Section III we outline the important unanswered questions about regulation of mammary gland development, the heritability of defects, the effects of maternal nutrition, disease, metabolic status, and therapeutic drugs upon the subsequent lactation. Questions surrounding breastfeeding practice are also highlighted. In Section IV we describe the specific nutritional challenges faced by three different populations, namely preterm infants, infants born to obese mothers who may or may not have gestational diabetes, and infants born to undernourished mothers. The recognition that multidisciplinary training is critical to advancing the field led us to formulate specific training recommendations in Section V. Our recommendations for research emphasis are summarized in Section VI. In sum, we present a roadmap for multidisciplinary research into all aspects of human lactation, milk and its role in infant nutrition for the next decade and beyond

Impact of exposure measurement error in air pollution epidemiology: effect of error type in time-series studies

<p>Abstract</p> <p>Background</p> <p>Two distinctly different types of measurement error are Berkson and classical. Impacts of measurement error in epidemiologic studies of ambient air pollution are expected to depend on error type. We characterize measurement error due to instrument imprecision and spatial variability as multiplicative (i.e. additive on the log scale) and model it over a range of error types to assess impacts on risk ratio estimates both on a per measurement unit basis and on a per interquartile range (IQR) basis in a time-series study in Atlanta.</p> <p>Methods</p> <p>Daily measures of twelve ambient air pollutants were analyzed: NO₂, NO_x, O₃, SO₂, CO, PM₁₀mass, PM_2.5mass, and PM_2.5components sulfate, nitrate, ammonium, elemental carbon and organic carbon. Semivariogram analysis was applied to assess spatial variability. Error due to this spatial variability was added to a reference pollutant time-series on the log scale using Monte Carlo simulations. Each of these time-series was exponentiated and introduced to a Poisson generalized linear model of cardiovascular disease emergency department visits.</p> <p>Results</p> <p>Measurement error resulted in reduced statistical significance for the risk ratio estimates for all amounts (corresponding to different pollutants) and types of error. When modelled as classical-type error, risk ratios were attenuated, particularly for primary air pollutants, with average attenuation in risk ratios on a per unit of measurement basis ranging from 18% to 92% and on an IQR basis ranging from 18% to 86%. When modelled as Berkson-type error, risk ratios per unit of measurement were biased away from the null hypothesis by 2% to 31%, whereas risk ratios per IQR were attenuated (i.e. biased toward the null) by 5% to 34%. For CO modelled error amount, a range of error types were simulated and effects on risk ratio bias and significance were observed.</p> <p>Conclusions</p> <p>For multiplicative error, both the amount and type of measurement error impact health effect estimates in air pollution epidemiology. By modelling instrument imprecision and spatial variability as different error types, we estimate direction and magnitude of the effects of error over a range of error types.</p

Ventricular pacing or dual-chamber pacing for sinus-node dysfunction

BACKGROUND Dual-chamber (atrioventricular) and single-chamber (ventricular) pacing are alternative treatment approaches for sinus-node dysfunction that causes clinically significant bradycardia. However, it is unknown which type of pacing results in the better outcome. METHODS We randomly assigned a total of 2010 patients with sinus-node dysfunction to dual-chamber pacing (1014 patients) or ventricular pacing (996 patients) and followed them for a median of 33.1 months. The primary end point was death from any cause or nonfatal stroke. Secondary end points included the composite of death, stroke, or hospitalization for heart failure; atrial fibrillation; heart-failure score; the pacemaker syndrome; and the quality of life. RESULTS The incidence of the primary end point did not differ significantly between the dual-chamber group (21.5 percent) and the ventricular-paced group (23.0 percent, P=0.48). In patients assigned to dual-chamber pacing, the risk of atrial fibrillation was lower (hazard ratio, 0.79; 95 percent confidence interval, 0.66 to 0.94; P=0.008), and heart-failure scores were better (P CONCLUSIONS In sinus-node dysfunction, dual-chamber pacing does not improve stroke-free survival, as compared with ventricular pacing. However, dual-chamber pacing reduces the risk of atrial fibrillation, reduces signs and symptoms of heart failure, and slightly improves the quality of life. Overall, dual-chamber pacing offers significant improvement as compared with ventricular pacing

Modifiable risk factors remain significant causes of medium term mortality after first time Coronary artery bypass grafting

<p>Abstract</p> <p>Background</p> <p>Whilst there is much current data on early outcomes after Coronary artery bypass grafting(CABG), there is relatively little data on medium term outcomes in the current era. The purpose of this study is to present a single surgeon series comprising of all first time CABG patients operated on with the technique of cross clamp fibrillation from Feb-1996 to through to Jan-2003, and to seek risk factors for medium term mortality in these patients.</p> <p>Methods</p> <p>Data was collected from Hospital Episode Statistics and departmental patient administration and tracking systems and cross checked using database techniques. Patient outcomes were searched using the National Health Service strategic tracing service.</p> <p>Results</p> <p>Mean follow up was 5.3 years(0–9.4 years) and was complete for all patients. 30-day survival was 98.4%, 1-year survival 95% and 8-year survival 79%. Cox-regression analysis revealed that several modifiable pre-operative risk factors remain significant predictors of medium term mortality, including Diabetes(Hazard Ratio(HR) 1.73, 95%CI 1.21–2.45), Chromic obstructive pulmonary disease(HR 2.02, 95%CI 1.09–3.72), Peripheral vascular disease(HR 1.68, 95%CI 1.13–2.5), Body mass index>30(HR 1.54, 95%CI 1.08–2.20) and current smoker at operation(HR 1.67, 95%CI 1.03–2.72). However hypertension(HR 1.31, 95%CI 0.95–1.82) and Hypercholestrolaemia(HR 0.81, 95%CI 0.58–1.13) were not predictive which may reflect adequate post-operative control.</p> <p>Conclusion</p> <p>Coronary artery bypass surgery using cross clamp fibrillation is associated with a very low operative mortality. Medium term survival is also good but risk factors such as smoking at operation, Chronic obstructive pulmonary disease, obesity and diabetes negatively impact this survival and should be aggressively treated in the years post-surgery.</p

False-negative PD-L1 immunostaining in ethanol-fixed EBUS-TBNA specimens of non-small cell lung cancer patients

Aims Programmed death-ligand 1 (PD-L1) immunostaining is used to predict which non-small-cell lung cancer (NSCLC) patients will respond best to treatment with programmed cell death protein 1/PD-L1 inhibitors. PD-L1 immunostaining is sometimes performed on alcohol-fixed cytological specimens instead of on formalin-fixed paraffin-embedded (FFPE) biopsies or resections. We studied whether ethanol prefixation of clots from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) results in diminished PD-L1 immunostaining as compared with formalin fixation. Methods and results FFPE cell blocks from EBUS-TBNA specimens of 54 NSCLC patients were identified. For each case, paired samples were available, consisting of clots directly immersed in formalin and clots prefixed in Fixcyt (50% ethanol). Serial sections were immunostained for PD-L1 by use of the standardised SP263 assay and the 22C3 antibody as a laboratory-developed test (LDT). PD-L1 positivity was determined with two cut-offs (1% and 50%). Concordance of PD-L1 positivity between the formalin-fixed (gold standard) and ethanol-prefixed material was assessed. When the 22C3 LDT was used, 30% and 36% of the ethanol-prefixed specimens showed false-negative results at the 1% and 50% cut-offs, respectively (kappa 0.64 and 0.68). When SP263 was used, 22% of the ethanol-prefixed specimens showed false-negative results at the 1% cut-off (kappa 0.67). At the 50% cut-off, concordance was higher (kappa 0.91), with 12% of the ethanol-prefixed specimens showing false-negative results. Conclusion Ethanol fixation of EBUS-TBNA specimens prior to formalin fixation can result in a considerable number of false-negative PD-L1 immunostaining results when a 1% cut-off is used and immunostaining is performed with SP263 or the 22C3 LDT. The same applies to use of the 50% cut-off when immunostaining is performed with the 22C3 LDT