Comparative performance of the new Aptima HIV-1 Quant Dx assay with three commercial PCR-based HIV-1 RNA quantitation assays

AbstractBackgroundQuantitative measurement of HIV-1 RNA levels in plasma (‘viral load’) plays a central role in clinical management. The choice of assay platform can influence results and treatment decisions.ObjectiveTo compare the analytical performance of the new TMA-based Hologic Aptima® HIV-1 Quant Dx assay with that of three PCR-based assays: Abbott RealTime HIV-1, Qiagen Artus® HI Virus-1 QS-RGQ, and Roche CAP/CTM HIV-1 Test v2.Study designAssay performance was evaluated using Acrometrix HIV-1 RNA Standard panels; the 3rd WHO HIV-1 RNA International Standard (12–500copies/ml; 6 dilutions; 9 replicates); and plasma samples from 191 HIV-positive patients.ResultsAptima showed high (>0.99) precision, accuracy and concordance with the Acrometrix Standards across a wide dynamic range (2.0–6.7 log10copies/ml). Variance caused up to 2.1 (Aptima), 1.7 (RealTime), 7.5 (Artus), and 1.9 (CAP/CTM) fold changes in the International Standard quantifications at 50–500copies/ml. HIV-1 RNA detection rates in plasma samples were 141/191 (74%), 119/191 (62%), 108/191 (57%), and 145/191 (76%) for Aptima, RealTime, Artus and CAP/CTM, respectively. For categorising samples either side of 50 copies/ml, Aptima had excellent agreement with RealTime (kappa 0.92; 95% CI 0.87–0.98); lowest agreement was with Artus (kappa 0.79; 95%CI 0.70–0.88). Aptima quantifications were mean 0.12 and 0.06 log10copies/ml higher compared with RealTime and CAP/CTM, respectively, and 0.05 log10copies/ml lower compared with Artus. Limits of agreement were narrowest when comparing Aptima to RealTime.ConclusionsThe new Aptima HIV assay is sensitive, precise, and accurate. HIV assays exhibit discordance at low HIV-1 RNA copy numbers

Amyloid-β nanotubes are associated with prion protein-dependent synaptotoxicity

Growing evidence suggests water-soluble, non-fibrillar forms of amyloid-β protein (Aβ) have important roles in Alzheimer’s disease with toxicities mimicked by synthetic Aβ1–42. However, no defined toxic structures acting via specific receptors have been identified and roles of proposed receptors, such as prion protein (PrP), remain controversial. Here we quantify binding to PrP of Aβ1–42 after different durations of aggregation. We show PrP-binding and PrP-dependent inhibition of long-term potentiation (LTP) correlate with the presence of protofibrils. Globular oligomers bind less avidly to PrP and do not inhibit LTP, whereas fibrils inhibit LTP in a PrP-independent manner. That only certain transient Aβ assemblies cause PrP-dependent toxicity explains conflicting reports regarding the involvement of PrP in Aβ-induced impairments. We show that these protofibrils contain a defined nanotubular structure with a previously unidentified triple helical conformation. Blocking the formation of Aβ nanotubes or their interaction with PrP might have a role in treatment of Alzheimer’s disease

Analysing NSW state policy for child obesity prevention: strategic policy versus practical action

There is increasing worldwide recognition of the need for government policies to address the recent increases in the incidence and prevalence of childhood obesity. The complexity and inter-relatedness of the determinants of obesity pose a genuine policy challenge, both scientifically and politically. This study examines the characteristics of one of the early policy responses, the NSW Government\u27s Prevention of Obesity in Children and Young People: NSW Government Action Plan 2003-2007 (GAP), as a case study, assessing it in terms of its content and capacity for implementation. This policy was designed as an initial set of practical actions spanning five government sectors. Most of the policy actions fitted with existing implementation systems within NSW government, and reflected an incremental approach to policy formulation and implementation. As a case study, the NSW Government Action Plan illustrates that childhood obesity policy development and implementation are at an early stage. This policy, while limited, may have built sufficient commitment and support to create momentum for more strategic policy in the future. A more sophisticated, comprehensive and strategic policy which can also be widely implemented and evaluated should now be built on this base

Amyloid-b nanotubes are associated with prion protein-dependent synaptotoxicity

Growing evidence suggests water-soluble, non-fibrillar forms of amyloid-β protein (Aβ) have important roles in Alzheimer's disease with toxicities mimicked by synthetic Aβ(1-42). However, no defined toxic structures acting via specific receptors have been identified and roles of proposed receptors, such as prion protein (PrP), remain controversial. Here we quantify binding to PrP of Aβ(1-42) after different durations of aggregation. We show PrP-binding and PrP-dependent inhibition of long-term potentiation (LTP) correlate with the presence of protofibrils. Globular oligomers bind less avidly to PrP and do not inhibit LTP, whereas fibrils inhibit LTP in a PrP-independent manner. That only certain transient Aβ assemblies cause PrP-dependent toxicity explains conflicting reports regarding the involvement of PrP in Aβ-induced impairments. We show that these protofibrils contain a defined nanotubular structure with a previously unidentified triple helical conformation. Blocking the formation of Aβ nanotubes or their interaction with PrP might have a role in treatment of Alzheimer's disease.UK Medical Research CouncilWellcome TrustFoundation for Neurologic Disease