Patient Engagement: The Fundacio ACE Framework for Improving Recruitment and Retention in Alzheimer's Disease Research

Alzheimer's disease (AD) research is at a critical time. The global society is increasingly aware of the frightening rate of growth of the human and financial burden caused by this condition and of the urgent need to halt its progression. Consequently, the scientific community holds great responsibility to quickly put in place and optimize the machinery necessary for testing newtreatments or interventions. In this context demand for participants forADresearch is at an all-time high. In this review, we will focus on a methodological factor that is increasingly recognized as a key factor that shapes trial populations and affects validity of results in clinical trials: patient engagement, recruitment, and retention. We outline specific problems relevant to patient engagement in AD including recruiting enough participants, difficulties in participant retention, ensuring the recruited sample is representative of the general AD population, the burden of screening failures, and new challenges related to recruiting in preclinical disease. To address the urgent need for more research studying the applicability and cost-effectiveness of different recruitment strategies across different settings and nationalities, we describe the Models of Patient Engagement for Alzheimer's Disease (MOPEAD) project, a public-private partnership promoted by the Innovative Medicine Initiative (IMI), which will provide a large multinational quantitative analysis comparing different innovative recruitment models. We also discuss strategies that address each problem and draw on the experience of Fundacio Ace to argue that focusing resources on comprehensive AD centers that offer coordinated clinical and social care and participate in basic and clinical research, is an effective and efficient way of implementing many of the discussed strategies

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

Comparison of a high temperature torch integrated sample introduction system with a desolvation system for the analysis of microsamples through inductively coupled plasma mass spectrometry

International audienceThis work describes for the first time the comparison of the analytical performances obtained with a high temperaturetorch integrated sample introduction system(hTISIS) against those foundwith a commercially availabledesolvation system (APEX) associated with inductively coupled plasma mass spectrometry (ICP-MS). A doublepass spray chamber was taken as the reference system. Similar detection limits and sensitivities were obtainedin continuous injection mode at low liquid flow rates for the APEX and hTISIS operating at high temperatures.In contrast, in the air-segmented injection mode, the detection limits obtained with hTISIS at high temperatureswere up to 12 times lower than those found for the APEX. Regarding memory effects, wash out times wereshorter in continuous mode and peaks were narrower in air segmented mode for the hTISIS as compared tothe APEX. Non spectral interferences (matrix effects) were studied with 10percent nitric acid, 2percent methanol, for anICP multielemental solution and a hydro-organic matrix containing 70percent (v-v) acetonitrile in water,15 mmol Let8722;1 ammonium acetate and 0.5percent formic acid containing lanthanide complexes. In all the cases, matrixeffects were less severe for the hTISIS operating at 200 DC and the APEX than for the double pass spray chamber.Finally, two spiked reference materials (sea water and Antartic krill) were analyzed. The hTISIS operating at200 DC gave the best results compared to those obtained with the APEX and the double pass spray chamber. Inconclusion, despite the simplicity of the hTISIS, it provided, at low liquid flow rates, results similar to or betterthan those obtained with the by other sample introduction systems

Steroidal Compounds in Commercial Parenteral Lipid Emulsions

Parenteral nutrition lipid emulsions made from various plant oils contain steroidal compounds, called phytosterols. During parenteral administration of lipid emulsions, phytosterols can reach levels in the blood that are many fold higher than during enteral administration. The elevated phytosterol levels have been associated with the development of liver dysfunction and the rare development of liver failure. There is limited information available in the literature related to phytosterol concentrations in lipid emulsions. The objective of the current study was to validate an assay for steroidal compounds found in lipid emulsions and to compare their concentrations in the most commonly used parenteral nutrition lipid emulsions: Liposyn<sup>®</sup> II, Liposyn<sup>®</sup> III, Lipofundin<sup>®</sup> MCT, Lipofundin<sup>®</sup> N, Structolipid<sup>®</sup>, Intralipid<sup>®</sup>, Ivelip<sup>®</sup> and ClinOleic<sup>®</sup>. Our data demonstrates that concentrations of the various steroidal compounds varied greatly between the eight lipid emulsions, with the olive oil-based lipid emulsion containing the lowest levels of phytosterols and cholesterol, and the highest concentration of squalene. The clinical impression of greater incidences of liver dysfunction with soybean versus MCT/LCT and olive/soy lipid emulsions may be reflective of the levels of phytosterols in these emulsions. This information may help guide future studies and clinical care of patients with lipid emulsion-associated liver dysfunction

Irrigation with treated wastewater affected the minor components of virgin olive oil from cv. Chemlali in Tunisia

Water limitation for agriculture is a problem in many countries and irrigation with treated wastewater (TWW) can be a tool to face the decreasing availability of water for important domestic crops such as olive. Taking into account this aspect, a research was carried out for 13 years in an olive grove (Chemlali cultivar) located in the area of Sfax (Tunisia). Two different irrigation treatments were applied: (a) irrigation with good quality water (GQW) and (b) irrigation with TWW. The main objective of this 13-year study was to verify the effects of the irrigation with TWW vs. GQW on some minor parameters of the virgin olive oil. Many oil parameters significantly increased in the TWW irrigated plot, in particular lutein, total tocopherols, squalene, campesterol and stigmasterol whereas β-carotene, α-tocopherol, δ-tocopherol, β-sitosterol and total sterols decreased with respect to the GQW treatment. Irrigation with TWW can be a possible tool to irrigate olive groves with two positive effects: saving of freshwater and production of olive oil of good quality