High-throughput continuous dielectrophoretic separation of neural stem cells.

We created an integrated microfluidic cell separation system that incorporates hydrophoresis and dielectrophoresis modules to facilitate high-throughput continuous cell separation. The hydrophoresis module consists of a serpentine channel with ridges and trenches to generate a diverging fluid flow that focuses cells into two streams along the channel edges. The dielectrophoresis module is composed of a chevron-shaped electrode array. Separation in the dielectrophoresis module is driven by inherent cell electrophysiological properties and does not require cell-type-specific labels. The chevron shape of the electrode array couples with fluid flow in the channel to enable continuous sorting of cells to increase throughput. We tested the new system with mouse neural stem cells since their electrophysiological properties reflect their differentiation capacity (e.g., whether they will differentiate into astrocytes or neurons). The goal of our experiments was to enrich astrocyte-biased cells. Sorting parameters were optimized for each batch of neural stem cells to ensure effective and consistent separations. The continuous sorting design of the device significantly improved sorting throughput and reproducibility. Sorting yielded two cell fractions, and we found that astrocyte-biased cells were enriched in one fraction and depleted from the other. This is an advantage of the new continuous sorting device over traditional dielectrophoresis-based sorting platforms that target a subset of cells for enrichment but do not provide a corresponding depleted population. The new microfluidic dielectrophoresis cell separation system improves label-free cell sorting by increasing throughput and delivering enriched and depleted cell subpopulations in a single sort

Effectiveness of mental health warnings on tobacco packaging in people with and without common mental health conditions:an online randomised experiment

BACKGROUND: Health warning labels on tobacco packaging are a cost-effective means of health risk communication. However, while an extensive range of physical health risks are well-portrayed via current tobacco health warnings in the UK, there are none that currently portray the negative impact of smoking on mental health. AIMS: (i) develop novel mental health warning labels for tobacco packaging and (ii) test perceptions of these warnings in smokers and non-smokers, with and without mental health problems. METHODS: Six mental health warning labels were developed with a consultancy focus group. These warning labels were tested in an online randomised experiment, where respondents (N = 687) rated six Mental Health Warning Labels (MHWLs) and six Physical Health Warning Labels (PHWLs) on measures of perceived effectiveness, believability, arousal, valence, acceptability, reactance and novelty of information. RESULTS: MHWLs were perceived as low to moderately effective (mean = 4.02, SD = 2.40), but less effective than PHWLs (mean = 5.78, SD = 2.55, p < 0.001, η(p)(2) = 0.63). MHWLs were perceived as less believable, arousing, unpleasant, and acceptable than PHWLs. MHWLs evoked more reactance and were rated as more novel. Perceptions of MHWLs did not differ in people with and without mental health problems except for reactance and acceptability, but consistent with the PHWL literature, perceptions of MHWLs differed between non-smokers and smokers. CONCLUSION: MHWLs could be an effective means to communicate novel information about the effects of smoking on mental health. MHWLs are perceived as less effective, believable, arousing, unpleasant, and acceptable than PHWLs, but MHWLs evoke more reactance and are rated as more novel

An Algorithm for Fitting Mixtures of Gompertz Distributions to Censored Survival Data

We consider the fitting of a mixture of two Gompertz distributions to censored survival data. This model is therefore applicable where there are two distinct causes for failure that act in a mutually exclusive manner, and the baseline failure time for each cause follows a Gompertz distribution. For example, in a study of a disease such as breast cancer, suppose that failure corresponds to death, whose cause is attributed either to breast cancer or some other cause. In this example, the mixing proportion for the component of the mixture representing time to death from a cause other than breast cancer may be interpreted to be the cure rate for breast cancer (Gordon,'90a and'90b). This Gompertz mixture model whose components are adjusted multiplicatively to reflect the age of the patient at the origin of the survival time, is fitted by maximum likelihood via the EM algorithm (Dempster, Laird and Rubin,'77). There is the provision to handle the case where the mixing proportions are formulated in terms of a logistic model to depend on a vector of covariates associated with each survival time. The algorithm can also handle the case where there is only one cause of failure, but which may happen at infinity for some patients with a nonzero probability (Farewell,'82).

A high-throughput in vivo micronucleus assay for genome instability screening in mice.

We describe a sensitive, robust, high-throughput method for quantifying the formation of micronuclei, markers of genome instability, in mouse erythrocytes. Micronuclei are whole chromosomes or chromosome segments that have been separated from the nucleus. Other methods of detection rely on labor-intensive, microscopy-based techniques. Here we describe a 2-d, 96-well plate-based flow cytometric method of micronucleus scoring that is simple enough for a research technician experienced in flow cytometry to perform. The assay detects low levels of genome instability that cannot be readily identified by classic phenotyping, using 25 μl of blood. By using this assay, we have screened >10,000 blood samples and discovered novel genes that contribute to vertebrate genome maintenance, as well as novel disease models and mechanisms of genome instability disorders. We discuss experimental design considerations, including statistical power calculation, we provide troubleshooting tips and we discuss factors that contribute to a false-positive increase in the number of micronucleated red blood cells and to experimental variability.Acknowledgments We thank M. Hitcham and N. Harman for assistance with blood collections, W. Cheng for assistance with flow cytometry during high-throughput screening and K. Dry for comments on the manuscript. R.E.M. is supported by Cancer Research UK (CRUK; project grant C20510/A12401). D.J.A. is supported by CRUK. D.J.A. and B.L.N. are supported by the Wellcome Trust. Research in the Jackson Laboratory is funded by CRUK program grant no. C6/A11224, the European Research Council and the European Community Seventh Framework Programme grant agreement no. HEALTH-F2-2010-259893 (DDResponse). Core funding is provided by CRUK (C6946/A14492) and the Wellcome Trust (WT092096). S.P.J. receives his salary from the University of Cambridge, UK, supplemented by CRUK. G.B. is funded by CRUK program grant no. C6/A11224.This is the accepted manuscript for a paper published in Nature Protocols 10, 205–215 (2015) doi:10.1038/nprot.2015.010, Published online 31 December 201

Distance Learning—Predictions and Possibilities

Education systems, educational institutions and educational professions, including those of distance learning, can often be inward-looking, backward-looking and self-referential, meaning that they are often fixated on their own concerns, values and processes. In many respects, this is necessary and valuable but the topic of challenges and future trends in distance learning is an opportunity to explore the place of distance learning in a wider world where cultures and ideologies clash, where education and employment are no longer stable and secure, where universities and colleges are under unprecedented pressures, where the technologies and trends of educational technology represent a crowded and chaotic space and where a critical examination of distance learning is necessary to underpin its methods and its mission. This paper addresses in essence three questions, firstly, is the distance learning community clear about the definition and purpose of its work, secondly, what are global political, economic and technological pressures on the institutions of higher education delivering distance learning, and thirdly, what do typical innovations and trends in educational technology signify for distance learning? These are linked questions and the answers constitute challenging predictions and possibilities. The nature of these questions means there are no simple answers only a more complete understanding of a fluid, partial and complex environment within which education, including distance learning, cannot operate in ignorance or isolation

The Effects of Leadership Curricula With and Without Implicit Bias Training on Graduate Medical Education: A Multicenter Randomized Trial

Purpose: To determine whether a brief leadership curriculum including high-fidelity simulation can improve leadership skills among resident physicians. Method: This was a double-blind randomized controlled trial among obstetrics and gynecology (OB/GYN) and emergency medicine (EM) residents across 5 academic medical centers from different geographic areas of the United States, 2015–2017. Participants were assigned to 1 of 3 study arms: the LEADS (Leadership Education Advanced During Simulation) curriculum, a shortened TeamSTEPPS (Team Strategies and Tools to Enhance Performance and Patient Safety) curriculum, or as active controls (no leadership curriculum). Active controls were recruited from a separate site and not randomized in order to limit any unintentional introduction of materials from the leadership curricula. The LEADS curriculum was developed in partnership with the Council on Resident Education in Obstetrics and Gynecology and Council of Residency Directors in Emergency Medicine as a novel way to provide a leadership toolkit. Both LEADS and the abbreviated TeamSTEPPS were designed as six 10-minute interactive web-based modules. The primary outcome of interest was the leadership performance score from the validated Clinical Teamwork Scale instrument measured during standardized high-fidelity simulation scenarios. Secondary outcomes were 9 key components of leadership from the detailed leadership evaluation measured on 5-point Likert scales. Both outcomes were rated by a blinded clinical video reviewer. Results: One hundred and ten OB/GYN and EM residents participated in this 2-year trial. Participants in both LEADS and TeamSTEPPS had statistically significant improvement in leadership scores from “average” to “good” ranges both immediately and at the 6-month follow-up, while controls remained unchanged in the “average” category throughout the study. There were no differences between the LEADS and TeamSTEPPS curricula with respect to the primary outcome. Conclusions: Residents who participated in a brief structured leadership training intervention had improved leadership skills that were maintained at 6-month follow-up

Information decomposition of symbolic sequences

We developed a non-parametric method of Information Decomposition (ID) of a content of any symbolical sequence. The method is based on the calculation of Shannon mutual information between analyzed and artificial symbolical sequences, and allows the revealing of latent periodicity in any symbolical sequence. We show the stability of the ID method in the case of a large number of random letter changes in an analyzed symbolic sequence. We demonstrate the possibilities of the method, analyzing both poems, and DNA and protein sequences. In DNA and protein sequences we show the existence of many DNA and amino acid sequences with different types and lengths of latent periodicity. The possible origin of latent periodicity for different symbolical sequences is discussed.Comment: 18 pages, 8 figure

Ultrafast High-Energy Micro-Supercapacitors Based On Open-Shell Polymer-Graphene Composites

Micro-supercapacitors are poised to serve as on-chip power sources for electronics. However, the challenge to simultaneously increase their power, energy, and lifetime demands new material combinations beyond current carbon-based systems. Here, we demonstrate that electro-deposition of an open-shell conjugated polymer with reduced graphene oxide achieves electrodes with capacitance up to 186 mF cm−2 (372 F cm−3). The extended delocalization within the open-shell polymer stabilizes redox states and facilitates a 3 V wide potential window, while the hierarchical electrode structure promotes ultrafast kinetics. The micro-supercapacitor shows a high power density of 227 mW cm−2 with an energy density of 10.5 μWh cm−2 and stability of 84% capacitance retention after 11,000 cycles. These attributes allow operation at 120 Hz for fast charging and alternating current (AC) line filtering applications, which may be suitable to replace bulky electrolytic capacitors or serve as high-endurance energy storage for wireless electronics

Semi-localized instability of the Kaluza-Klein linear dilaton vacuum

The Kaluza-Klein linear dilaton background of the bosonic string and the Scherk-Schwarz linear dilaton background of the superstring are shown to be unstable to the decay of half of spacetime. The decay proceeds via a condensation of a semi-localized tachyon when the circle is smaller than a critical size, and via a semiclassical instanton process when the circle is larger than the critical size. At criticality the two pictures are related by a duality of the corresponding two-dimensional conformal field theories. This provides a concrete realization of the connection between tachyonic and semiclassical instabilities in closed string theory, and lends strong support to the idea that non-localized closed string tachyon condensation leads to the annihilation of spacetime.Comment: 27 pages, 4 figures; v2: References adde

Real-Time On-Board Airborne Demonstration of High-Speed On-Board Data Processing for Science Instruments (HOPS)

The project called High-Speed On-Board Data Processing for Science Instruments (HOPS) has been funded by NASA Earth Science Technology Office (ESTO) Advanced Information Systems Technology (AIST) program since April, 2012. The HOPS team recently completed two flight campaigns during the summer of 2014 on two different aircrafts with two different science instruments. The first flight campaign was in July, 2014 based at NASA Langley Research Center (LaRC) in Hampton, VA on the NASA's HU-25 aircraft. The science instrument that flew with HOPS was Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) CarbonHawk Experiment Simulator (ACES) funded by NASA's Instrument Incubator Program (IIP). The second campaign was in August, 2014 based at NASA Armstrong Flight Research Center (AFRC) in Palmdale, CA on the NASA's DC-8 aircraft. HOPS flew with the Multifunctional Fiber Laser Lidar (MFLL) instrument developed by Excelis Inc. The goal of the campaigns was to perform an end-to-end demonstration of the capabilities of the HOPS prototype system (HOPS COTS) while running the most computationally intensive part of the ASCENDS algorithm real-time on-board. The comparison of the two flight campaigns and the results of the functionality tests of the HOPS COTS are presented in this paper