A system for gaze-contingent image analysis and multi-sensorial image display

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Discrete Event Simulation for Decision Modeling in Health Care: Lessons from Abdominal Aortic Aneurysm Screening

Markov models are often used to evaluate the cost-effectiveness of new healthcare interventions but they are sometimes not flexible enough to allow accurate modeling or investigation of alternative scenarios and policies. A Markov model previously demonstrated that a one-off invitation to screening for abdominal aortic aneurysm (AAA) for men aged 65 y in the UK and subsequent follow-up of identified AAAs was likely to be highly cost-effective at thresholds commonly adopted in the UK (£20,000 to £30,000 per quality adjusted life-year). However, new evidence has emerged and the decision problem has evolved to include exploration of the circumstances under which AAA screening may be cost-effective, which the Markov model is not easily able to address. A new model to handle this more complex decision problem was needed, and the case of AAA screening thus provides an illustration of the relative merits of Markov models and discrete event simulation (DES) models. An individual-level DES model was built using the R programming language to reflect possible events and pathways of individuals invited to screening v. those not invited. The model was validated against key events and cost-effectiveness, as observed in a large, randomized trial. Different screening protocol scenarios were investigated to demonstrate the flexibility of the DES. The case of AAA screening highlights the benefits of DES, particularly in the context of screening studies

Robust and stable transcriptional repression in Giardia using CRISPRi.

Giardia lamblia is a binucleate protistan parasite causing significant diarrheal disease worldwide. An inability to target Cas9 to both nuclei, combined with the lack of nonhomologous end joining and markers for positive selection, has stalled the adaptation of CRISPR/Cas9-mediated genetic tools for this widespread parasite. CRISPR interference (CRISPRi) is a modification of the CRISPR/Cas9 system that directs catalytically inactive Cas9 (dCas9) to target loci for stable transcriptional repression. Using a Giardia nuclear localization signal to target dCas9 to both nuclei, we developed efficient and stable CRISPRi-mediated transcriptional repression of exogenous and endogenous genes in Giardia. Specifically, CRISPRi knockdown of kinesin-2a and kinesin-13 causes severe flagellar length defects that mirror defects with morpholino knockdown. Knockdown of the ventral disk MBP protein also causes severe structural defects that are highly prevalent and persist in the population more than 5 d longer than defects associated with transient morpholino-based knockdown. By expressing two guide RNAs in tandem to simultaneously knock down kinesin-13 and MBP, we created a stable dual knockdown strain with both flagellar length and disk defects. The efficiency and simplicity of CRISPRi in polyploid Giardia allows rapid evaluation of knockdown phenotypes and highlights the utility of CRISPRi for emerging model systems

Psychological, psychophysical, and ergogenic effects of music in swimming

OBJECTIVES: Existing work using dry land exercise-related activities has shown that the careful application of music can lead to a range of benefits that include enhanced affect, lower perceived exertion, greater energy efficiency, and faster time trial performances. The purpose of this study was to assess the psychological, psychophysical, and ergogenic effects of asynchronous music in swimming using a mixed-methods approach. DESIGN: A mixed-model design was employed wherein there was a within-subjects factor (two experimental conditions and a control) and a between-subjects factor (gender). The experimental component of the study was supplemented by qualitative data that were analysed using inductive content analysis. METHODS: Twenty six participants (Mage = 20.0 years, age range: 18–23 years) underwent a period of habituation with Speedo Aquabeat MP3 players prior to the experimental phase. They were then administered two experimental trials (motivational and oudeterous music at 130 bpm) and a no-music control, during which they engaged in a 200-m freestyle swimming time trial. RESULTS: Participants swam significantly faster when exposed to either music condition relative to control (p = .022, ηp2=.18). Moreover, the music conditions were associated with higher state motivation (p = .016, ηp2=.15) and more dissociative thoughts (p = .014, ηp2=.16). CONCLUSIONS: Findings supported the hypothesis that the use of asynchronous music during a high-intensity task can have an ergogenic effect; this was in the order of 2% when averaged out across the two experimental conditions. The use of music, regardless of its motivational qualities, resulted in higher self-reported motivation as well as more dissociative thoughts

Localization in semi-infinite herringbone waveguides

The paper includes novel results for the scattering and localization of a time-harmonic flexural wave by a semi-infinite herringbone waveguide of rigid pins embedded within an elastic Kirchhoff plate. The analytical model takes into account the orientation and spacing of the constituent parts of the herringbone system, and incorporates dipole approximations for the case of closely spaced pins. Illustrative examples are provided, together with the predictive theoretical analysis of the localized waveforms

Controlling Flexural Waves in Semi-Infinite Platonic Crystals with Resonator-Type Scatterers

We address the scattering and transmission of a plane flexural wave through a semi-infinite array of point scatterers/resonators, which take a variety of physically interesting forms. The mathematical model accounts for several classes of point defects, including mass-spring resonators attached to the top surface of the flexural plate and their limiting case of concentrated point masses. We also analyse the special case of resonators attached to opposite faces of the plate. The problem is reduced to a functional equation of the Wiener–Hopf type, whose kernel varies with the type of scatterer considered. A novel approach, which stems from the direct connection between the kernel function of the semi-infinite system and the quasi-periodic Green's functions for corresponding infinite systems, is used to identify special frequency regimes. We thereby demonstrate dynamically anisotropic wave effects in semi-infinite platonic crystals, with particular attention paid to designing systems that exhibit dynamic neutrality (perfect transmission) and localisation close to the structured interface

Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye.

Accumulation of protein- and lipid-containing deposits external to the retinal pigment epithelium (RPE) is common in the aging eye, and has long been viewed as the hallmark of age-related macular degeneration (AMD). The cause for the accumulation and retention of molecules in the sub-RPE space, however, remains an enigma. Here, we present fluorescence microscopy and X-ray diffraction evidence for the formation of small (0.5-20 μm in diameter), hollow, hydroxyapatite (HAP) spherules in Bruch's membrane in human eyes. These spherules are distinct in form, placement, and staining from the well-known calcification of the elastin layer of the aging Bruch's membrane. Secondary ion mass spectrometry (SIMS) imaging confirmed the presence of calcium phosphate in the spherules and identified cholesterol enrichment in their core. Using HAP-selective fluorescent dyes, we show that all types of sub-RPE deposits in the macula, as well as in the periphery, contain numerous HAP spherules. Immunohistochemical labeling for proteins characteristic of sub-RPE deposits, such as complement factor H, vitronectin, and amyloid beta, revealed that HAP spherules were coated with these proteins. HAP spherules were also found outside the sub-RPE deposits, ready to bind proteins at the RPE/choroid interface. Based on these results, we propose a novel mechanism for the growth, and possibly even the formation, of sub-RPE deposits, namely, that the deposit growth and formation begin with the deposition of insoluble HAP shells around naturally occurring, cholesterol-containing extracellular lipid droplets at the RPE/choroid interface; proteins and lipids then attach to these shells, initiating or supporting the growth of sub-RPE deposits