Photorefractive incoherent-to-coherent optical converter

Photorefractive materials have been extensively used in recent years as real-time recording media for optical holography.(^1,2) One prospective application of real-time holography is in the area of optical information processing; for example, the correlation between two mutually incoherent images has recently been demonstrated in real time in a four-wave mixing geometry. (^3) Often, however, the information to be processed exists only in incoherent form. High performance spatial light modulators(^4) are thus necessary in many optical information processing systems to convert incoherent images to coherent replicas for subsequent processing. We report in this Communication the successful demonstration of real-time incoherent-to-coherent images transduction through the use of holographic recording in photorefractive crystals. Several possible configurations and experimental results are presented

Comparative Analysis Of Zebrafish And Planarian Model Systems For Developmental Neurotoxicity Screens Using An 87-Compound Library

There is a clear need to establish and validate new methodologies to more quickly and efficiently screen chemicals for potential toxic effects, particularly on development. The emergence of alternative animal systems for rapid toxicology screens presents valuable opportunities to evaluate how systems complement each other. In this article, we compare a chemical library of 87-compounds in two such systems, developing zebrafish and freshwater planarians, by screening for developmental neurotoxic effects. We show that the systems’ toxicological profiles are complementary to each other, with zebrafish yielding more detailed morphological endpoints and planarians more behavioral endpoints. Overall, zebrafish was more sensitive to this chemical library, yielding 86/87 hits, compared to 50/87 hits in planarians. The difference in sensitivity could not be attributed to molecular weight, Log Kow or the bioconcentration factor. Of the 87 chemicals, 28 had previously been evaluated in mammalian developmental neuro- (DNT), neuro- or developmental toxicity studies. Of the 28, 20 were hits in the planarian, and 27 were hits in zebrafish. Eighteen of the 28 had previously been identified as DNT hits in mammals and were highly associated with activity in zebrafish and planarian behavioral assays in this study. Only 1 chemical (out of 28) was a false negative in both zebrafish and planarian systems. Differences in endpoint coverage and system sensitivity illustrate the value of a dual systems approach to rapidly query a large chemical-bioactivity space and provide weight-of-evidence for prioritization of chemicals for further testing

Dynamic Double Flash Illusion: Auditory Triggered Replay of Illusory Visual Expansion

In the original double flash illusion, a visual flash (e.g., a sharp-edged disk, or uniformly filled circle) presented with two short auditory tones (beeps) is often followed by an illusory flash. The illusory flash has been previously shown to be triggered by the second auditory beep. The current study extends the double flash illusion by showing that this paradigm can not only create the illusory repeat of an on-off flash, but also trigger an illusory expansion (and in some cases a subsequent contraction) that is induced by the flash of a circular brightness gradient (gradient disk) to replay as well. The perception of the dynamic double flash illusion further supports the interpretation of the illusory flash (in the double flash illusion) as similar in its spatial and temporal properties to the perception of the real visual flash, likely by replicating the neural processes underlying the illusory expansion of the real flash. We show further that if a gradient disk (generating an illusory expansion) and a sharp-edged disk are presented simultaneously side by side with two sequential beeps, often only one visual stimulus or the other will be perceived to double flash. This indicates selectivity in auditory–visual binding, suggesting the usefulness of this paradigm as a psychophysical tool for investigating crossmodal binding phenomena

Dynamic Double Flash Illusion: Auditory Triggered Replay of Illusory Visual Expansion

In the original double flash illusion, a visual flash (e.g., a sharp-edged disk, or uniformly filled circle) presented with two short auditory tones (beeps) is often followed by an illusory flash. The illusory flash has been previously shown to be triggered by the second auditory beep. The current study extends the double flash illusion by showing that this paradigm can not only create the illusory repeat of an on-off flash, but also trigger an illusory expansion (and in some cases a subsequent contraction) that is induced by the flash of a circular brightness gradient (gradient disk) to replay as well. The perception of the dynamic double flash illusion further supports the interpretation of the illusory flash (in the double flash illusion) as similar in its spatial and temporal properties to the perception of the real visual flash, likely by replicating the neural processes underlying the illusory expansion of the real flash. We show further that if a gradient disk (generating an illusory expansion) and a sharp-edged disk are presented simultaneously side by side with two sequential beeps, often only one visual stimulus or the other will be perceived to double flash. This indicates selectivity in auditory–visual binding, suggesting the usefulness of this paradigm as a psychophysical tool for investigating crossmodal binding phenomena

High speed techniques for synthetic aperture radar image formation

One possible approach to high speed synthetic aperture radar signal reconstruction involves the utilization of two dimensional real time spatial light modulators as recyclable replacements for photographic film in the input transducer plane of a modified synthetic aperture radar (SAR) coherent optical processor. Leading candidate spatial light modulators include modified Pockels readout optical modulators (PROM), charge coupled devices (CCD) addressed liquid crystal light valves, and CCD addressed membrane light modulators. The fundamental physical limitations affecting SAR processor performance characteristics of such real time devices are under investigation. Current research on PROM is focused on the effects of device operatonal mode, device constitutive parameters, electro-optic crystal orientation, writing wavelength, frame rate/data overwrite/presuming, erasure completeness, and image retention on the overall quality of SAR image formation. Both modulated laser scanning and intensified CRT temporal to spatial input approaches are being examined

Implications of the antiplatelet therapy gap left with discontinuation of prasugrel in Canada

Background The current Canadian Cardiovascular Society antiplatelet therapy guidelines recommend the use of ticagrelor or prasugrel over clopidogrel as first-line platelet P2Y12 receptor antagonists for treatment of moderate- to high-risk acute coronary syndromes. Recently, Effient (prasugrel [Eli Lilly Canada Inc, Toronto, Canada]) was discontinued by its distributor in Canada. Methods Five members of the Canadian Cardiovascular Society antiplatelet therapy 2018 guidelines committee undertook an independent, evidence-based review to outline patients for whom prasugrel should be the optimal P2Y12 agent and discuss alternative strategies to consider without prasugrel. Results Several clinical scenarios where prasugrel should be indicated are identified and discussed. Considerations to be undertaken for alternative therapies are summarized, including a review of national and international guidelines for de-escalation of P2Y12 receptor antagonists. Conclusions The discontinuation of prasugrel poses a challenge for clinicians. Clinicians must consider key factors in determining the best alternate therapy.Introduction Dans ses lignes directrices actuelles sur la thérapie antiplaquettaire, la Société canadienne de cardiologie recommande l’utilisation du ticagrélor ou du prasugrel plutôt que l’utilisation du clopidogrel comme antagonistes des récepteurs plaquettaires P2Y12 de première intention dans le traitement des patients qui présentent un risque modéré à élevé de syndromes coronariens aigus. Depuis peu, le distributeur a cessé la distribution d’Effient (prasugrel) au Canada. Méthodes Cinq membres du comité des lignes directrices 2018 sur la thérapie antiplaquettaire de la Société canadienne de cardiologie ont entrepris une revue indépendante fondée sur les données probantes pour dresser le profil des patients pour lesquels le prasugrel devrait être la meilleure option parmi les antagonistes des récepteurs P2Y12 et se pencher sur les traitements alternatifs en l'absence de prasugrel. Résultats Plusieurs scénarios cliniques où le prasugrel devrait être indiqué sont recensés et abordés. Les réflexions sur les solutions de rechange au traitement, notamment une revue des lignes directrices nationales et internationales en matière de désescalade des antagonistes des récepteurs P2Y12, sont présentées. Conclusions La cessation de la distribution du prasugrel pose problème aux cliniciens. Les cliniciens doivent tenir compte des facteurs clés pour déterminer le meilleur traitement de remplacement

918-7 Limitations of Percutaneous Interventions in the Treatment of Bifurcation Lesions Involving the Left Anterior Descending Coronary Artery

Serious complications may occur when intervention is unsuccessful in bifurcation lesions involving the left anterior descending (LAD) and first major diagonal (D), because of the large amount of involved myocardium. To determine this complication rate, we reviewed 82 consecutive cases, over a 3 year period, in which these lesions were attempted. Sixty-six percent of the subjects were male, and 37% had unstable angina. The mean age was 59 and the mean ejection fraction was 56%. Digital calipers were used to measure vessel minimum lumen (MLD) and reference diameters. For the LAD the final MLD was 1.81mm and for the 0 1.32mm. The final percent mean diameter stenoses for the LAD and D were 41% and 45%, respectively. There were no significant differences in the rates of success or complication between groups treated with angioplasty only (N=68) or directional atherectomy (N=14). The in-hospital event-free success rate was 55%. The in-hospital complication rates were:Recurrent Ischemia16%Ventricular Tachycardia2%Myocardial Infarction14%Stroke2%Bypass Surgery12%Death1%Repeat Procedure4%Composite34%ConclusionLAD bifurcation lesion intervention is associated with a high in-hospital complication rate. Since these lesions are not amenable to stent placement or atherectomy with simultaneous protection of both vessels, these cases should be carefully evaluated before intervention, and bypass surgery should be considered as a treatment option

The Anti-Inflammatory Drug Leflunomide Is an Agonist of the Aryl Hydrocarbon Receptor

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the toxicity and biological activity of dioxins and related chemicals. The AhR influences a variety of processes involved in cellular growth and differentiation, and recent studies have suggested that the AhR is a potential target for immune-mediated diseases.During a screen for molecules that activate the AhR, leflunomide, an immunomodulatory drug presently used in the clinic for the treatment of rheumatoid arthritis, was identified as an AhR agonist. We aimed to determine whether any biological activity of leflunomide could be attributed to a previously unappreciated interaction with the AhR. The currently established mechanism of action of leflunomide involves its metabolism to A771726, possibly by cytochrome P450 enzymes, followed by inhibition of de novo pyrimidine biosynthesis by A771726. Our results demonstrate that leflunomide, but not its metabolite A771726, caused nuclear translocation of AhR into the nucleus and increased expression of AhR-responsive reporter genes and endogenous AhR target genes in an AhR-dependent manner. In silico Molecular Docking studies employing AhR ligand binding domain revealed favorable binding energy for leflunomide, but not for A771726. Further, leflunomide, but not A771726, inhibited in vivo epimorphic regeneration in a zebrafish model of tissue regeneration in an AhR-dependent manner. However, suppression of lymphocyte proliferation by leflunomide or A771726 was not dependent on AhR.These data reveal that leflunomide, an anti-inflammatory drug, is an agonist of the AhR. Our findings link AhR activation by leflunomide to inhibition of fin regeneration in zebrafish. Identification of alternative AhR agonists is a critical step in evaluating the AhR as a therapeutic target for the treatment of immune disorders

Antidepressants use during pregnancy and child psychomotor, cognitive and language development at 2 years of age—Results from the 3D Cohort Study

Introduction: Approximately 5.5% of pregnant women take antidepressants. Studies on prenatal exposure to antidepressants reported no association with child cognition, and inconsistent results with motor function and language development. A limitation has been the failure to adjust for prenatal maternal distress.Objectives: Assess the associations between prenatal exposure to antidepressants and child development at age two, while adjusting for maternal depressive symptoms and stress during pregnancy. Explore indirect effects through birth complications and consider sex-specific associations.Methods: This is an ancillary study of the 3D (Design Develop, Discover) Study initiated during pregnancy. Data on antidepressants were collected through medication logs spanning the entire pregnancy. Depressive symptoms and stress were assessed during pregnancy by self-reported questionnaires, motor and cognitive development with the Bayley Scales of Infant and Toddler Development (BSID-III), and language development with the MacArthur Communicative Development Inventories at age 2. Multiple linear regressions were used to assess the associations between exposure and developmental outcomes. Mediation models were used to assess indirect effects. Interaction terms were introduced to assess sex-specific associations.Results: 1,489 mother-child dyads were included, of whom 61 (4.1%) reported prenatal antidepressant use. Prenatal exposure was negatively associated with motor development (B = −0.91, 95% CI -1.73, −0.09 for fine motor, B = −0.89, 95% CI -1.81, 0.02 for gross motor), but not with cognitive (B = −0.53, 95% CI -1.82, 0.72) and language (B = 4.13, 95% CI -3.72, 11.89) development. Adjusting for maternal prenatal distress only slightly modified these associations. No indirect effect or differential effect according to child sex were found.Conclusion: This study supports evidence of a negative association between prenatal exposure to antidepressants and motor development at age two, after adjusting for maternal distress, but the effect size remains very small, with about only one BSID-III point lower in average