External validation of the PAGE-B score for HCC risk prediction in people living with HIV/HBV coinfection

Background & Aims: HBV coinfection is common among people living with HIV (PLWH) and is the most important cause of hepatocellular carcinoma (HCC). While risk prediction tools for HCC have been validated in patients with HBV monoinfection, they have not been evaluated in PLWH. Thus, we performed an external validation of PAGE-B in people with HIV/HBV coinfection. Methods: We included data on PLWH from four European cohorts who were positive for HBsAg and did not have HCC before starting tenofovir. We estimated the predictive performance of PAGE-B for HCC occurrence over 15 years in patients receiving tenofovir-containing antiretroviral therapy. Model discrimination was assessed after multiple imputation using Cox regression with the prognostic index as a covariate, and by calculating Harrell's c-index. Calibration was assessed by comparing our cumulative incidence with the PAGE-B derivation study using Kaplan-Meier curves. Results: In total, 2,963 individuals with HIV/HBV coinfection on tenofovir-containing antiretroviral therapy were included. PAGE-B was <10 in 26.5%, 10–17 in 57.7%, and ≥18 in 15.7% of patients. Within a median follow-up of 9.6 years, HCC occurred in 68 individuals (2.58/1,000 patient-years, 95% CI 2.03–3.27). The regression slope of the prognostic index for developing HCC within 15 years was 0.93 (95% CI 0.61–1.25), and the pooled c-index was 0.77 (range 0.73–0.80), both indicating good model discrimination. The cumulative incidence of HCC was lower in our study compared to the derivation study. A PAGE-B cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. Restricting efforts to individuals with a PAGE-B of ≥10 would spare unnecessary HCC screening in 27% of individuals. Conclusions: For individuals with HIV/HBV coinfection, PAGE-B is a valid tool to determine the need for HCC screening. Impact and implications: Chronic HBV infection is the most important cause of hepatocellular carcinoma (HCC) among people living with HIV. Valid risk prediction may enable better targeting of HCC screening efforts to high-risk individuals. We aimed to validate PAGE-B, a risk prediction tool that is based on age, sex, and platelets, in 2,963 individuals with HIV/HBV coinfection who received tenofovir-containing antiretroviral therapy. In the present study, PAGE-B showed good discrimination, adequate calibration, and a cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. These results indicate that PAGE-B is a simple and valid risk prediction tool to determine the need for HCC screening among people living with HIV and HBV

Impact of operating temperature on the electrical and magnetic properties of the bottom-pinned perpendicular magnetic tunnel junctions

© 2018 Author(s). Analogous device parameters in both the parallel (P) and anti-parallel (AP) states ensure a symmetric spin-transfer-torque magnetic random-access memory operation scheme. In this study, however, we observe an increasing asymmetry in the performance metrics with operating temperature of the bottom-pinned perpendicular magnetic tunnel junction (p-MTJ) devices. A temperature-dependent increase in the contribution of the stray field is observed in the tunneling magnetoresistance loop analysis. The switching current for P-to-AP decreases by 30% in the thermally activated switching regime by increasing the temperature from 300 K to 400 K, while it remains similar for AP-to-P. In addition, with the same temperature range, the thermal stability factor for the P state decreases 20% more than that for the AP state. We attribute those observations to the increase in the overcompensation of the stray field from the synthetic anti-ferromagnet structure. Saturation magnetization (M S ) of the [Co/Pt] x -based multilayers is much less affected by temperature [M S (400 K)/M S (300 K) = 97%] compared to that of the CoFeB-based multilayers (88%). Such an impact can be more severe during the electrical switching process due to the Joule heating effect. These results suggest that, to understand and to evaluate the performance in a wide range of temperatures, it is crucial to consider the contribution of the entire magnetic components in the p-MTJ stack.status: publishe

Microsatellite marker development and putative SNP detection for a northward expanding damselfly species using next generation sequencing

In this study we used Roche's 454 sequencing to develop genetic markers for Coenagrion scitulum, a Mediterranean damselfly currently expanding its range northward. With a modest amount of sequencing we detected 6,318 potential microsatellite markers and 832 putative single nucleotide polymorphisms (SNPs). From the potential microsatellite markers we developed thirteen novel microsatellite markers. Among other applications, these markers can be used to unravel the micro-evolutionary consequences of range expansion in this species

Species identification in the trematomid family using nuclear genetic markers

The Trematominae, a subfamily of the Nototheniidae, are typical of the high-Antarctic shelf waters. Within the Trematominae examples of phenotypic plasticity and possible cryptic speciation have been observed. Morphological identification of adult stages can be problematic in cases of high phenotypic plasticity or cryptic speciation. Additionally, postlarval and juvenile stages often have traits still under development and which lack distinction. A microsatellite DNA multiplex of six markers has been developed for Trematomus newnesi (Van Houdt et al. 2006). This multiplex was tested on five additional trematomid taxa: Pagothenia borchgrevinki, Trematomus bernacchii, Trematomus eulepidotus, Trematomus hansoni and Trematomus scotti. We used these six microsatellite loci to assess the genetic differentiation among species and the resolution power of these loci for individual-based assignment methods. The six species could be well discriminated by conventional methods such as principal component analysis and distance-based methods, and individual Bayesian assignment methods. This marker set can be used for a number of purposes, including the identification of eggs and larval and adult stages. It is also useful for the investigation of recent phylogenetic patterns, as well as the detection of cryptic speciation, which has been suggested for T. bernacchii and T. newnesi but never confirmed with high polymorphic genetic markers