Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Re-oxygenation after anoxia induces brain cell death and memory loss in the anoxia-tolerant crucian carp

Crucian carp (Carassius carassius) survive without oxygen for several months, but it is unknown whether they are able to protect themselves from cell death normally caused by the absence, and particularly return, of oxygen. Here, we quantified cell death in brain tissue from crucian carp exposed to anoxia and re-oxygenation using the terminal deoxy-nucleotidyl transferase dUTP nick-end labelling (TUNEL) assay, and cell proliferation by immunohistochemical staining for proliferating cell nuclear antigen (PCNA) as well as PCNA mRNA expression. We also measured mRNA and protein expression of the apoptosis executer protease caspase 3, in laboratory fish exposed to anoxia and re-oxygenation and fish exposed to seasonal anoxia and re-oxygenation in their natural habitat over the year. Finally, a behavioural experiment was used to assess the ability to learn and remember how to navigate in a maze to find food, before and after exposure to anoxia and re-oxygenation. The number of TUNEL-positive cells in the telencephalon increased after 1 day of re-oxygenation following 7 days of anoxia, indicating increased cell death. However, there were no consistent changes in whole-brain expression of caspase 3 in either laboratory-exposed or naturally exposed fish, indicating that cell death might occur via caspase-independent pathways or necrosis. Re-oxygenated crucian carp appeared to have lost the memory of how to navigate in a maze (learnt prior to anoxia exposure), while the ability to learn remained intact. PCNA mRNA was elevated after re-oxygenation, indicating increased neurogenesis. We conclude that anoxia tolerance involves not only protection from damage but also repair after re-oxygenation

A cross-cultural survey to identify Seniors' preferences towards the Empathic Virtual Coach

The present investigation is part of the EMPATHIC project aiming at develop an Empathic Virtual Coach (VC) able to promote seniors' healthy lifestyle and independent aging. To this end, it is fundamental to investigate users' preferences towards the implemented automatic system refined on the basis of users' preferences derived from previous field trials with Wizard of Oz (WoZ) experimental sessions. Data collection has been carried out involving three different countries (France, Norway and Spain) and a total of 71 volunteers was enrolled in the planned field trials. Five Virtual Agents (VAs) named Natalie, Alice, Lena, Christian and Adam were purposely designed and users' preferences were assessed using the shortened version of the Virtual Agent Acceptance Questionnaire (VAAQ). This specific tool, developed by members of the EMPATHIC project, includes 7 different sections, and the present work aims to disseminate results of four of the seven sections administered to participants, devoted at assessing respectively: users' willingness to interact (section II); pragmatic, hedonic (Identity and Feeling) and attractiveness qualities (section III); the type of task participants entrusted to the proposed agents among healthcare, housework, protection/security, and front office jobs (section V) and agents voice' quality (section VI). Results reveal seniors' appreciation of agents' pleasantness, originality, voice' quality and ability to engage users in a long lasting interaction with them

Expression of ANK3 moderates the association between childhood trauma and affective traits in severe mental disorders

Abstract Exposure to early life trauma increases the risk of psychopathology later in life. Here we investigated if ANK3 mRNA levels influence the relationship between childhood trauma experiences and clinical characteristics in mental disorders. A sample of 174 patients with bipolar disorder and 291 patients with schizophrenia spectrum disorder were included. Patients were diagnosed using the Structured Clinical Interview for DSM-IV, and childhood trauma was assessed using the childhood trauma questionnaire. Age at illness onset and number of psychotic and affective episodes were assessed from interview and medical records. Current depressive symptoms were measured using the calgary depression scale for schizophrenia and the inventory for depressive symptomatology. ANK3 expression was analyzed in whole blood using the Illumina HumanHT-12 v4 Expression BeadChip. Analyses were carried out with the Process adjusted for confounders. Within the total sample, patients with both high ANK3 expression and with the most severe childhood sexual abuse had more manic/hypomanic episodes and an earlier age at onset of the first episode. ANK3 mRNA levels also moderated the relationship between emotional neglect and manic/hypomanic episodes. Our results suggest that ANK3 expression levels moderate the association between specific types of childhood trauma and affective traits in mental disorders

Analysis of the interaction between elderly people and a simulated virtual coach

The EMPATHIC project develops and validates new interaction paradigms for personalized virtual coaches (VC) to promote healthy and independent aging. To this end, the work presented in this paper is aimed to analyze the interaction between the EMPATHIC-VC and the users. One of the goals of the project is to ensure an end-user driven design, involving senior users from the beginning and during each phase of the project. Thus, the paper focuses on some sessions where the seniors carried out interactions with a Wizard of Oz driven, simulated system. A coaching strategy based on the GROW model was used throughout these sessions so as to guide interactions and engage the elderly with the goals of the project. In this interaction framework, both the human and the system behavior were analyzed. The way the wizard implements the GROW coaching strategy is a key aspect of the system behavior during the interaction. The language used by the virtual agent as well as his or her physical aspect are also important cues that were analyzed. Regarding the user behavior, the vocal communication provides information about the speaker’s emotional status, that is closely related to human behavior and which can be extracted from the speech and language analysis. In the same way, the analysis of the facial expression, gazes and gestures can provide information on the non verbal human communication even when the user is not talking. In addition, in order to engage senior users, their preferences and likes had to be considered. To this end, the effect of the VC on the users was gathered by means of direct questionnaires. These analyses have shown a positive and calm behavior of users when interacting with the simulated virtual coach as well as some difficulties of the system to develop the proposed coaching strategy