Spectral Autofluorescence Imaging of the Retina for Drusen Detection

The presence and characteristics of drusen in retinal images, namely their size, location, and distribution, can be used to aid in the diagnosis and monitoring of Age Related Macular Degeneration (AMD); one of the leading causes for blindness in the elderly population. Current imaging techniques are effective at determining the presence and number of drusen, but fail when it comes to classifying their size and form. These distinctions are important for correctly characterising the disease, especially in the early stages where the development of just one larger drusen can indicate progression. Another challenge for automated detection is in distinguishing them from other retinal features, such as cotton wool spots. We describe the development of a multi-spectral scanning-laser ophthalmoscope that records images of retinal autofluorescence (AF) in four spectral bands. This will offer the potential to detect drusen with improved contrast based on spectral discrimination for automated classification. The resulting improved specificity and sensitivity for their detection offers more reliable characterisation of AMD. We present proof of principle images prior to further system optimisation and clinical trials for assessment of enhanced detection of drusen

Acute alcohol intoxication and the cocktail party problem: do “mocktails” help or hinder?

Rationale To test the notion that alcohol impairs auditory attentional control by reducing the listener’s cognitive capacity. Objectives We examined the effect of alcohol consumption and working memory span on dichotic speech shadowing and the cocktail party effect – the ability to focus on one of many simultaneous speakers yet still detect mention of one’s name amidst the background speech. Alcohol was expected either to increase name detection, by weakening the inhibition of irrelevant speech, or reduce name detection, by restricting auditory attention on to the primary input channel. Low-span participants were expected to show larger drug impairments than high-span counterparts. Methods On completion of the working memory span task, participants (n = 81) were randomly assigned to an alcohol or placebo beverage treatment. After alcohol absorption they shadowed speech presented to one ear while ignoring the synchronised speech of a different speaker presented to the other. Each participant’s first name was covertly embedded in to-be-ignored speech. Results The “cocktail party effect” was not affected by alcohol or working memory span, though low-span participants made more shadowing errors and recalled fewer words from the primary channel than high-span counterparts. Bayes factors support a null effect of alcohol on the cocktail party phenomenon, on shadowing errors, and on memory for either shadowed or ignored speech. Conclusion Findings suggest that an alcoholic beverage producing a moderate level of intoxication (M BAC ≈ 0.08%) neither enhances nor impairs the cocktail party effect

Testing Alcohol Myopia Theory: Examining the effects of alcohol intoxication on simultaneous central and peripheral attention.

The effect of alcohol intoxication on central and peripheral attention was examined as a test of Alcohol Myopia Theory (AMT). Previous research has supported AMT in the context of visual attention, but few studies have examined the effects of alcohol intoxication on central and peripheral attention. The study followed a 2(alcohol treatment) x 2(array size) x 2(task type) mixed design. Forty-one participants (placebo or intoxicated) viewed an array of 4 or 6 coloured circles, while simultaneously counting the flashes of a centrally presented fixation cross. Participants were instructed to prioritise flash counting accuracy. The subsequently presented coloured probe matched the cued peripheral stimulus on 50% of trials. Flash counting and probe identification accuracy were recorded. There was a significant main effect of alcohol treatment on accuracy scores, as well as an alcohol treatment by task type interaction. Accuracy scores for the central flash counting task did not differ between treatment groups, but scores for peripheral probe identification were lower in the alcohol group. As predicted by AMT, alcohol impairment was greater for peripheral probe detection than for the central and prioritised flash counting task. The findings support the notion that alcohol intoxication narrows attentional focus to the central aspects of a task

Cutaneous Wound Healing Through Paradoxical Mapk Activation By Braf Inhibitors

BRAF inhibitors are highly effective therapies for the treatment of BRAF(V600)-mutated melanoma, with the main toxicity being a variety of hyperproliferative skin conditions due to paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway in BRAF wild-type cells. Most of these hyperproliferative skin changes improve when a MEK inhibitor is co-administered, as it blocks paradoxical MAPK activation. Here we show how the BRAF inhibitor vemurafenib accelerates skin wound healing by inducing the proliferation and migration of human keratinocytes through extracellular signal-regulated kinase (ERK) phosphorylation and cell cycle progression. Topical treatment with vemurafenib in two wound-healing mice models accelerates cutaneous wound healing through paradoxical MAPK activation; addition of a mitogen-activated protein kinase kinase (MEK) inhibitor reverses the benefit of vemurafenib-accelerated wound healing. The same dosing regimen of topical BRAF inhibitor does not increase the incidence of cutaneous squamous cell carcinomas in mice. Therefore, topical BRAF inhibitors may have clinical applications in accelerating the healing of skin wounds.7NIH [P01 CA168585, R35 CA197633, CA-16042, AI-28697]Ressler Family FoundationGrimaldi Family FundGarcia-Corsini Family FundJames B. Pendleton Charitable TrustUCLA CFAR [5P30 AI028697]UCLA AIDS InstituteJohnson Comprehensive Cancer Center (JCCC)David Geffen School of Medicin

Genetic manipulation of biosynthetic pathways in mint

In recent years, the study of aromatic plants has seen an increase, with great interest from industrial, academic, and pharmaceutical industries. Among plants attracting increased attention are the Mentha spp. (mint), members of the Lamiaceae family. Mint essential oils comprise a diverse class of molecules known as terpenoids/isoprenoids, organic chemicals that are among the most diverse class of naturally plant derived compounds. The terpenoid profile of several Mentha spp. is dominated by menthol, a cyclic monoterpene with some remarkable biological properties that make it useful in the pharmaceutical, medical, cosmetic, and cleaning product industries. As the global market for Mentha essential oils increases, the desire to improve oil composition and yield follows. The monoterpenoid biosynthesis pathway is well characterised so metabolic engineering attempts have been made to facilitate this improvement. This review focuses on the Mentha spp. and attempts at altering the carbon flux through the biosynthetic pathways to increase the yield and enhance the composition of the essential oil. This includes manipulation of endogenous and heterologous biosynthetic enzymes through overexpression and RNAi suppression. Genes involved in the MEP pathway, the menthol and carvone biosynthetic pathways and transcription factors known to affect secondary metabolism will be discussed along with non-metabolic engineering approaches including environmental factors and the use of plant growth regulators

Do intoxicated witnesses produce poor facial composite images?

The effect of alcohol intoxication on witness memory and performance has been the subject of research for some time, however, whether intoxication affects facial composite construction has not been investigated. Intoxication was predicted to adversely affect facial composite construction. Thirty-two participants were allocated to one of four beverage conditions consisting of factorial combinations of alcohol or placebo at face encoding, and later construction. Participants viewed a video of a target person and constructed a composite of this target the following day. The resulting images were presented as a full face composite, or a part face consisting of either internal or external facial features to a second sample of participants who provided likeness ratings as a measure of facial composite quality. Intoxication at face encoding had a detrimental impact on the quality of facial composites produced the following day, suggesting that alcohol impaired the encoding of the target faces. The common finding that external compared to internal features are more accurately represented was demonstrated, even following alcohol at encoding. This finding was moderated by alcohol and target face gender such that alcohol at face encoding resulted in reduced likeness of external features for male composite faces only. Moderate alcohol intoxication impairs the quality of facial composites, adding to existing literature demonstrating little effect of alcohol on line-up studies. The impact of intoxication on face perception mechanisms, and the apparent narrowing of processing to external face areas such as hair, is discussed in the context of alcohol myopia theory

Marine heatwaves threaten global biodiversity and the provision of ecosystem services

The global ocean has warmed substantially over the past century, with far-reaching implications for marine ecosystems 1 . Concurrent with long-term persistent warming, discrete periods of extreme regional ocean warming (marine heatwaves, MHWs) have increased in frequency 2 . Here we quantify trends and attributes of MHWs across all ocean basins and examine their biological impacts from species to ecosystems. Multiple regions in the Pacific, Atlantic and Indian Oceans are particularly vulnerable to MHW intensification, due to the co-existence of high levels of biodiversity, a prevalence of species found at their warm range edges or concurrent non-climatic human impacts. The physical attributes of prominent MHWs varied considerably, but all had deleterious impacts across a range of biological processes and taxa, including critical foundation species (corals, seagrasses and kelps). MHWs, which will probably intensify with anthropogenic climate change 3 , are rapidly emerging as forceful agents of disturbance with the capacity to restructure entire ecosystems and disrupt the provision of ecological goods and services in coming decades. © 2019, The Author(s), under exclusive licence to Springer Nature Limited

The effect of amblyopia treatment on stereoacuity

Purpose: To explore how stereoacuity changes in patients while they are being treated for amblyopia. Methods: The Monitored Occlusion Treatment for Amblyopia Study (MOTAS) comprised 3 distinct phases. In the first phase, baseline, assessments of visual function were made to confirm the initial visual and binocular visual deficit. The second phase, refractive adaptation, now commonly termed “optical treatment,” was an 18-week period of spectacle wear with measurements of logMAR visual acuity and stereoacuity with the Frisby test at weeks 0, 6, 12, and 18. In the third phase, occlusion, participants were prescribed 6 hours of patching per day. Results: A total of 85 children were enrolled (mean age, 5.1 ± 1.5 years). In 21 children amblyopia was associated with anisometropia; in 29, with strabismus; and in 35, with both. At study entry, poor stereoacuity was associated with poor visual acuity (P < 0.001) in the amblyopic eye and greater angle of strabismus (P < 0.001). Of 66 participants, 25 (38%) who received refractive adaptation and 19 (29%) who received occlusion improved by at least one octave in stereoacuity, exceeding test–retest variability. Overall, 38 (45%) improved one or more octaves across both treatment phases. Unmeasureable stereoacuity was observed in 56 participants (66%) at study entry and in 37 (43%) at study exit. Conclusions: Stereoacuity improved for almost one half of the study participants. Improvement was observed in both treatment phases. Factors associated with poor or nil stereoacuity at study entry and exit were poor visual acuity of the amblyopic eye and large-angle strabismus

The presentation, diagnosis and management of non-traumatic wrist pain: an evaluation of current practice in secondary care in the UK NHS

AbstractObjectivesThe study aims were to assess the burden of non-traumatic wrist pain in terms of numbers of referrals to secondary care, and to characterise how patients present, are diagnosed and are managed in secondary care in the United Kingdom National Health Service.MethodsTen consecutive patients presenting with non-traumatic wrist pain were identified retrospectively at each of 16 participating hospitals and data was extracted for twelve months following the initial referral.ResultsThe 160 patients consisted of 100 females and 60 males with a median age of 49, accounting for approximately 13% of all new hand/wrist referrals. The dominant wrist was affected in 60% of cases and the mean symptom duration was 13.3 months. Diagnoses were grouped into: osteoarthritis (OA) (31%), tendinopathy (13%), ganglion (14%), ulnar sided pain (17%) and other (25%). The OA group was significantly older than other groups, while other groups contained a predominance of females.The non-surgical interventions in decreasing frequency of usage were: steroid injections (39%), physiotherapy (32%), splint (31%) and analgesics (12%). Of those who underwent surgery, all patients had previously received non-surgical treatment, however 42% had undergone only one non-surgical intervention.ConclusionNon-traumatic wrist pain represents a significant burden to secondary care both in terms of new patient referrals and in terms of investigation, follow up and treatment. Those presenting with osteoarthritis are more likely to be older and male, while those presenting with other diagnoses are more likely to be younger and female