The European Prevention of Alzheimer's Dementia (EPAD) Longitudinal Cohort Study: Baseline Data Release V500.0.

BACKGROUND: The European Prevention of Alzheimer's Dementia (EPAD) Programme is a pan-European project whose objective is to deliver a platform, adaptive, Phase 2 proof of concept (PoC) trial for the secondary prevention of Alzheimer's dementia. A component of this platform is the Longitudinal Cohort Study (LCS) which acts as a readiness cohort for the PoC Trial as well as generating data for disease modelling work in the preclinical and prodromal phases of Alzheimer's dementia. OBJECTIVES: The first data wave has been collected, quality checked, released and now available for analysis to answer numerous research questions. Here we describe the results from key variables in the EPAD LCS with the objective of using these results to compliment analyses of these data in the future. DESIGN: EPAD LCS is a cohort study whose primary objective is as a readiness cohort for the EPAD PoC Trial. As such recruitment is not capped at any particular number but will continue to facilitate delivery of the EPAD PoC Trial. Research Participants are seen annually (with an additional 6 month visit in the first year). SETTING: The EPAD Trial Delivery Network comprises currently 21 centres across Europe. PARTICIPANTS: Research participants are included if they are over 50 years old and do not have a diagnosis of dementia. MEASUREMENTS: All research participants undergo multiple assessments to fully characterise the biology of Alzheimer's disease and relate this to risk factors (both fixed and modifiable) and biomarker expression of disease through brain imaging, fluid samples (CSF, blood, urine and saliva), cognitive performance, functional abilities and neuropsychiatric symptomatology. RESULTS: V500.0 represents the first 500 research participants baselined into EPAD LCS. The mean age was 66.4 (SD=6.7) and 47.8% were male. The data was split for presentation into 4 groups: [1] CDR=0 and Amyloid + (preclinical AD), [2] CDR=0 and Amyloid -, [3] CDR=0.5 and Amyloid + (prodromal AD) and [4] CDR=0.5 and Amyloid -. CONCLUSIONS: The EPAD LCS is achieving its primary objective of trial readiness and the structured approach to data release as manifest by this first data release of V500.0 will assist researchers to describe and compare their findings as well as in systematic reviews and meta-analyses. It is anticipated given current recruitment rates that V1500.0 data release will take place in Autumn 2019. V500.1 (when the 1 year follow up is completed on the V500.0 (sub)cohort will be in Autumn 2019 also.IMI Fundin

Gastrointestinal-Sparing Effects of Novel NSAIDs in Rats with Compromised Mucosal Defence

Nonsteroidal anti-inflammatory drugs are among the most commonly used prescription and over-the-counter medications, but they often produce significant gastrointestinal ulceration and bleeding, particularly in elderly patients and patients with certain co-morbidities. Novel anti-inflammatory drugs are seldom tested in animal models that mimic the high risk human users, leading to an underestimate of the true toxicity of the drugs. In the present study we examined the effects of two novel NSAIDs and two commonly used NSAIDs in models in which mucosal defence was expected to be impaired. Naproxen, celecoxib, ATB-346 (a hydrogen sulfide- and naproxen-releasing compound) and NCX 429 (a nitric oxide- and naproxen-releasing compound) were evaluated in healthy, arthritic, obese, and hypertensive rats and in rats of advanced age (19 months) and rats co-administered low-dose aspirin and/or omeprazole. In all models except hypertension, greater gastric and/or intestinal damage was observed when naproxen was administered in these models than in healthy rats. Celecoxib-induced damage was significantly increased when co-administered with low-dose aspirin and/or omeprazole. In contrast, ATB-346 and NCX 429, when tested at doses that were as effective as naproxen and celecoxib in reducing inflammation and inhibiting cyclooxygenase activity, did not produce significant gastric or intestinal damage in any of the models. These results demonstrate that animal models of human co-morbidities display the same increased susceptibility to NSAID-induced gastrointestinal damage as observed in humans. Moreover, two novel NSAIDs that release mediators of mucosal defence (hydrogen sulfide and nitric oxide) do not induce significant gastrointestinal damage in these models of impaired mucosal defence

Is pre-operative urodynamic bladder function the true predictor of outcome of male sling for post prostatectomy incontinence?

PURPOSE: To investigate pre-operative urodynamic parameters in male sling patients to ascertain whether this might better predict surgical outcomes and facilitate patient selection. METHODS: We performed a retrospective, case notes and video-urodynamics, review of men who underwent AdVanceXP male sling in three London hospitals between 2012 and 2019. Urodynamics were performed in all centres, while retrograde leak point pressure (RLPP) was performed in one centre. RESULTS: Successful outcome was seen in 99/130 (76%) of men who required one pad or less per day. The dry rate was 51%. Pad usage was linked to worse surgical outcomes, mean 2.6 (range 1-6.5) for success vs 3.6 (range 1-10) although the ranges were wide (p = 0.002). 24 h pad weight also reached statistical significance (p = 0.05), with a mean of 181 g for success group versus 475 g for the non-successful group. The incidence of DO in the non-successful group was significantly higher than in successful group (55% versus 29%, p = 0.0009). Bladder capacity less than 250 ml was also associated with worse outcomes (p = 0.003). Reduced compliance was not correlated with outcomes (31% for success groups vs 45% for non-successful group, p = 0.15). Preoperative RLPP was performed in 60/130 patients but did not independently reach statistical significance (p = 0.25). CONCLUSION: Urodynamic parameters related to bladder function-detrusor overactivity and reduced maximum cystometric capacity predict male sling outcomes and may help in patient selection for male sling (or sphincter) surgery; whereas urodynamic parameters of sphincter incompetency (RLPP) were not predictive. Further larger scale studies are required to confirm these findings

The role of brand loyalty and social media in e-commerce interfaces: survey results and implications for user interfaces

This paper explores the role of brand loyalty and social media in e-commerce interfaces. A survey consisting of 118 respondents was contacted to address the questions relating to online shopping and brand loyalty. Link between the frequency of access and time spent on an e-commerce user interface, and brand loyalty, gender and age profile differences, and the role of social media to branding and on-line shopping was analyzed. It was found that online loyalty differs from offline loyalty and loyalty also differed across genders, showing men were more loyal than women when shopping online. Information shared about products on social media by friends and family played an important role in purchase decision making. Website interface and ease of navigation were also key aspects for online shopping. The research concluded with recommendations to create multimodal websites which are more interactive and targeted so customer experience is enhanced and loyalty is achieved through the use of interactivity and social media

Vigorous star formation hidden by dust in a galaxy at z=1.4z=1.4

Near-infrared surveys have revealed a substantial population of enigmatic faint galaxies with extremely red optical-to-near-infrared colours and with a sky surface density comparable to that of faint quasars. There are two scenarios for these extreme colours: (i) these distant galaxies have formed virtually all their stars at very high redshifts and, due to the absence of recently formed stars, the colours are extremely red and (ii) these distant galaxies contain large amounts of dust, severely reddening the rest-frame UV--optical spectrum. HR10 ($z = 1.44$) is considered the archetype of the extremely red galaxies. Here we report the detection of the continuum emission from HR10 at 850$\mu$m and at 1250$\mu$m, demonstrating that HR10 is a very dusty galaxy undergoing a major episode of star formation. Our result provides a clear example of a high-redshift galaxy where the star formation rate inferred from the ultraviolet luminosity would be underestimated by a factor up to 1000, and shows that great caution should be used to infer the global star formation history of the Universe from optical observations only.Comment: 12 pages, 1 figure, Nature, in press (30 April 1998

Super-resolving phase measurements with a multi-photon entangled state

Using a linear optical elements and post-selection, we construct an entangled polarization state of three photons in the same spatial mode. This state is analogous to a ``photon-number path entangled state'' and can be used for super-resolving interferometry. Measuring a birefringent phase shift, we demonstrate two- and three-fold improvements in phase resolution.Comment: 4 pages, 3 figure

When Can Antibiotic Treatments for Trachoma Be Discontinued? Graduating Communities in Three African Countries

Trachoma, the major cause of infectious blindness in the world, occurs when repeated infections of the ocular strains of Chlamydia trachomatis lead to a cascade of conjunctival scarring, in-turned eyelids and eyelashes, and eventually blindness due to corneal opacity. To reduce the prevalence of infection, the World Health Organization (WHO) advocates at least three annual community-wide distributions of oral antibiotics in affected areas. This approach has proven effective, but there is room to explore other treatment strategies which reduce the use of antibiotics. Here, we used mathematical models and data from three trachoma-endemic countries (Tanzania, The Gambia, and Ethiopia) to analyze different treatment strategies. In the simulations, we show that a graduation strategy can reduce antibiotic distributions more than 2-fold in moderately affected areas. Both treatment strategies provide favorable results in reducing the prevalence of ocular chlamydia, but high costs and the potential for resistance are important issues to consider when administering mass doses of antibiotics

Recombination and positive selection identified in complete genome sequences of Japanese encephalitis virus

The mosquito-borne Japanese encephalitis virus (JEV) causes encephalitis in man but not in pigs. Complete genomes of a human, mosquito and pig isolate from outbreaks in 1982 and 1985 in Thailand were sequenced with the aim of identifying determinants of virulence that may explain the differences in outcomes of JEV infection between pigs and man. Phylogenetic analysis revealed that five of these isolates belonged to genotype I, but the 1982 mosquito isolate belonged to genotype III. There was no evidence of recombination among the Thai isolates, but there were phylogenetic signals suggestive of recombination in a 1994 Korean isolate (K94P05). Two sites of the genome under positive selection were identified: codons 996 and 2296 (amino acids 175 of the non-structural protein NS1 and 24 of NS4B, respectively). A structurally significant substitution was seen at NS4B position 24 of the human isolate compared with the mosquito and pig isolates from the 1985 outbreak in Thailand. The potential importance of the two sites in the evolution and ecology of JEV merits further investigation