A randomized control trial of high-dose micronutrient-antioxidant supplementation in healthy persons with untreated HIV infection.

BACKGROUND: Although micronutrient and antioxidant supplementation are widely used by persons with human immunodeficiency virus (HIV), a therapeutic role beyond recommended daily allowances (RDA) remains unproven. An oral high-dose micronutrient and antioxidant supplement (Treatment) was compared to an RDA supplement (Control) for time to progressive immunodeficiency or initiation of antiretroviral therapy (ART) in people living with HIV (PLWH). METHODS: This study was a randomized, double-blind, placebo-controlled multicenter clinical trial. PLWH were recruited from Canadian HIV Trials Network sites, and followed quarterly for two years. Eligible participants were asymptomatic, antiretroviral treatment (ART)-naïve, HIV-seropositive adults with a CD4 T lymphocyte count (CD4 count) between 375-750 cells/µL. Participants were randomly allocated 1:1 to receive Treatment or Control supplements. The primary outcome was a composite of time-to-first of confirmed CD4 count below 350 cells/µL, initiation of ART, AIDS-defining illness or death. Primary analysis was by intention-to-treat. Secondary outcomes included CD4 count trajectory from baseline to ART initiation or two years. A Data and Safety Monitoring Board reviewed the study for safety, recruitment and protocol adherence every six months. RESULTS: Of 171 enrolled participants: 66 (38.6%) experienced a primary outcome: 27 reached a CD4 count below 350 cells/µL, and 57 started ART. There was no significant difference in time-to-first outcome between groups (Hazard Ratio = 1.05; 95%CI: 0.65, 1.70), or in time to any component outcome. Using intent-to-treat censoring, mean annualized rates of CD4 count decline were -42.703 cells/µL and -79.763 cells/µL for Treatment and Control groups, with no statistical difference in the mean change between groups (-37.06 cells/µL/52 weeks, 95%CI: (-93.59, 19.47); p = 0.1993). Accrual was stopped at 171 of the 212 intended participants after an interim analysis for futility, although participant follow-up was completed. CONCLUSIONS: In ART-naïve PLWH, high-dose antioxidant, micronutrient supplementation compared to RDA supplementation had no significant effect on disease progression or ART initiation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00798772.

The School Attachment Monitor-A novel computational tool for assessment of attachment in middle childhood.

BACKGROUND: Attachment research has been limited by the lack of quick and easy measures. We report development and validation of the School Attachment Monitor (SAM), a novel measure for largescale assessment of attachment in children aged 5-9, in the general population. SAM offers automatic presentation, on computer, of story-stems based on the Manchester Child Attachment Story Task (MCAST), without the need for trained administrators. SAM is delivered by novel software which interacts with child participants, starting with warm-up activities to familiarise them with the task. Children's story completion is video recorded and augmented by 'smart dolls' that the child can hold and manipulate, with movement sensors for data collection. The design of SAM was informed by children of users' age range to establish their task understanding and incorporate their innovative ideas for improving SAM software. METHODS: 130 5-9 year old children were recruited from mainstream primary schools. In Phase 1, sixty-one children completed both SAM and MCAST. Inter-rater reliability and rating concordance was compared between SAM and MCAST. In Phase 2, a further 44 children completed SAM complete and, including those children completing SAM in Phase 1 (total n = 105), a machine learning algorithm was developed using a "majority vote" procedure where, for each child, 500 non-overlapping video frames contribute to the decision. RESULTS: Using manual rating, SAM-MCAST concordance was excellent (89% secure versus insecure; 97% organised versus disorganised; 86% four-way). Comparison of human ratings of SAM versus the machine learning algorithm showed over 80% concordance. CONCLUSIONS: We have developed a new tool for measuring attachment at the population level, which has good reliability compared to a validated attachment measure and has the potential for automatic rating-opening the door to measurement of attachment in large populations.

A multi-period optimisation approach for deployment and optimal design of an aerospace CFRP waste management supply chain.

This paper presents a modelling framework for the deployment and design of aerospace CFRP (Carbon Fibre Reinforced Polymer) waste supply chain. The problem involves a multi-period Mixed Integer Linear Programming (MILP) formulation considering ε-constraint, lexicographic techniques and Multiple Criteria Decision Making (MCDM) tools. The methodology has been applied to a case study of France. In this model, the deployment of new recycling sites (Grinding, Pyrolysis, Supercritical Water, Microwave) is established. The system is optimised by bi-criteria optimisation including an economic objective based on cost minimisation or Net Present Value (NPV) maximisation and an environmental one (minimisation of Global Warming Potential). The potential for economic acceptability of recycled carbon fibres is assessed through a levelized cost derived from the supply chain total cost and the profitability via NPV with a range of various CFRP prices. The results show that the compromise strategy for both economic and environmental objectives leads to centralised configurations at the regions close to significant waste sources. The cooperation in the recovery system is needed to minimise cost and maximise profit. The improvement of recycling technology permits to achieve the compromise solution for both economic and environmental objectives. The results also highlight that a mix of technologies will be involved in deployment phase and that the answer is not straightforward due to the complexity of the system. The methodology is yet generic enough to be replicated in other contexts considering the upgrade of process database.

Age of transfused blood in critically ill adults.

BACKGROUND: Fresh red cells may improve outcomes in critically ill patients by enhancing oxygen delivery while minimizing the risks of toxic effects from cellular changes and the accumulation of bioactive materials in blood components during prolonged storage. METHODS: In this multicenter, randomized, blinded trial, we assigned critically ill adults to receive either red cells that had been stored for less than 8 days or standard-issue red cells (the oldest compatible units available in the blood bank). The primary outcome measure was 90-day mortality. RESULTS: Between March 2009 and May 2014, at 64 centers in Canada and Europe, 1211 patients were assigned to receive fresh red cells (fresh-blood group) and 1219 patients were assigned to receive standard-issue red cells (standard-blood group). Red cells were stored a mean (±SD) of 6.1±4.9 days in the fresh-blood group as compared with 22.0±8.4 days in the standard-blood group (P<0.001). At 90 days, 448 patients (37.0%) in the fresh-blood group and 430 patients (35.3%) in the standard-blood group had died (absolute risk difference, 1.7 percentage points; 95% confidence interval [CI], -2.1 to 5.5). In the survival analysis, the hazard ratio for death in the fresh-blood group, as compared with the standard-blood group, was 1.1 (95% CI, 0.9 to 1.2; P=0.38). There were no significant between-group differences in any of the secondary outcomes (major illnesses; duration of respiratory, hemodynamic, or renal support; length of stay in the hospital; and transfusion reactions) or in the subgroup analyses. CONCLUSIONS: Transfusion of fresh red cells, as compared with standard-issue red cells, did not decrease the 90-day mortality among critically ill adults. (Funded by the Canadian Institutes of Health Research and others; Current Controlled Trials number, ISRCTN44878718.).

Treatment-resistant bipolar disorder: a comparison of rapid cyclers and nonrapid cyclers.

BACKGROUND: We investigated clinical factors to determine their relationship to treatment resistance among bipolar patients who had a consultation at a tertiary care facility. METHODS: Patients were separated into two categories: rapid-cycling disorders and nonrapid-cycling disorders. We hypothesized that there would be less usage of lithium carbonate among nonrapid-cycling treatment-resistant patients than among rapid cyclers and also that there would be higher rates of comorbidity seen among nonrapid-cycling than rapid-cycling patients in order to account for these particular patients being treatment resistant. FINDINGS: Continued recycling and persistent depression characterized rapid cyclers, whereas persistent depression characterized nonrapid cyclers. Less than 30% of patients had adequate lithium treatment and there was no significant difference comparing rapid cyclers with nonrapid cyclers. Rates of comorbidity were also not significantly different between these groups. We also assessed a number of other factors. CONCLUSION: Some of these factors were significant, but when a Bonferonni correction was applied, these significant differences were not maintained. The study of treatment resistance among nonrapid-cycling bipolar patients merits further research.