bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma Efavirenz Exposure, Sex, and Age Predict Virological Response in HIV-Infected African Children
Authors: Bienczak Andrzej , Denti Paolo , Cook Adrian , Wiesner Lubbe , Mulenga Veronica , Kityo Cissy , Kekitiinwa Addy , Gibb Diana M. , Burger David , Walker A. Sarah , McIlleron Helen 
Published: April 2016

Background:
Owing to insufficient evidence in children, target plasma concentrations of efavirenz are based on studies in adults. Our analysis aimed to evaluate the pediatric therapeutic thresholds and characterize the determinants of virological suppression in African children.

Methods:
We analyzed data from 128 African children (aged 1.7–13.5 years) treated with efavirenz, lamivudine, and one among abacavir, stavudine, or zidovudine, and followed up to 36 months. Individual pharmacokinetic (PK) measures [plasma concentration 12 hours after dose (C12h), plasma concentration 24 hours after dose (C24h), and area under the curve (AUC0-24)] were estimated using population PK modeling. Cox multiple failure regression and multivariable fractional polynomials were used to investigate the risks of unsuppressed viral load associated with efavirenz exposure and other factors among 106 initially treatment-naive children, and likelihood profiling was used to identify the most predictive PK thresholds.

Results:
The risk of viral load >100 copies per milliliter decreased by 42% for every 2-fold increase in efavirenz mid-dose concentration [95% confidence interval (CI): 23% to 57%; P < 0.001]. The most predictive PK thresholds for increased risk of unsuppressed viral load were C12h 1.12 mg/L [hazard ratio (HR): 6.14; 95% CI: 2.64 to 14.27], C24h 0.65 mg/L (HR: 6.57; 95% CI: 2.86 to 15.10), and AUC0-24 28 mg·h/L (HR: 5.77; 95% CI: 2.28 to 14.58). Children older than 8 years had a more than 10-fold increased risk of virological nonsuppression (P = 0.005); among children younger than 8 years, boys had a 5.31 times higher risk than girls (P = 0.007). Central nervous system adverse events were infrequently reported.

Conclusions:
Our analysis suggests that the minimum target C24h and AUC0-24 could be lowered in children. Our findings should be confirmed in a prospective pediatric trial.
Non–AIDS-Defining Cancer Mortality: Emerging Patterns in the Late HAART Era
Authors: Zucchetto Antonella , Virdone Saverio , Taborelli Martina , Grande Enrico , Camoni Laura , Pappagallo Marilena , Regine Vincenza , Grippo Francesco , Polesel Jerry , Dal Maso Luigino , Suligoi Barbara , Frova Luisa , Serraino Diego 
Published: April 2016

Background:
Non–AIDS-defining cancers (non-ADCs) have become the leading non-AIDS-related cause of death among people with HIV/AIDS. We aimed to quantify the excess risk of cancer-related deaths among Italian people with AIDS (PWA), as compared with people without AIDS (non-PWA).

Methods:
A nationwide, population-based, retrospective cohort study was carried out among 5285 Italian PWA, aged 15–74 years, diagnosed between 2006 and 2011. Date of death and multiple-cause-of-death data were retrieved up to December 2011. Excess mortality, as compared with non-PWA, was estimated using sex- and age-standardized mortality ratios (SMRs) and the corresponding 95% confidence intervals (CIs).

Results:
Among 1229 deceased PWA, 10.3% reported non-ADCs in the death certificate, including lung (3.1%), and liver (1.4%), cancers. A 7.3-fold (95% CI: 6.1 to 8.7) excess mortality was observed for all non-ADCs combined. Statistically significant SMRs emerged for specific non-ADCs, ie, anus (5 deaths, SMR = 227.6, 95% CI: 73.9 to 531.0), Hodgkin lymphoma (12 deaths, SMR = 122.0, 95% CI: 63.0 to 213.0), unspecified uterus (4 deaths, SMR = 52.5, 95% CI: 14.3 to 134.5), liver (17 deaths, SMR = 13.2, 95% CI: 7.7 to 21.1), skin melanoma (4 deaths, SMR = 10.9, 95% CI: 3.0 to 27.8), lung (38 deaths, SMR = 8.0, 95% CI: 5.7 to 11.0), head and neck (9 deaths, SMR = 7.8, 95% CI: 3.6 to 14.9), leukemia (5 deaths, SMR = 7.6, 95% CI: 2.4 to 17.7), and colon-rectum (10 deaths, SMR = 5.4, 95% CI: 2.6 to 10.0). SMRs for non-ADCs were particularly elevated among PWA infected through injecting drug use.

Conclusion:
This population-based study documented extremely elevated risks of death for non-ADCs among PWA. These findings stress the need of preventive interventions for both virus-related and non–virus-related cancers among HIV-infected individuals.
Revisiting the Potential of Alternating Repetition Time Balanced Steady-State Free Precession Imaging of the Abdomen at 3 T
Authors: Gurney-Champion Oliver J. , Nederveen Aart J. , Klaassen Remy , Engelbrecht Marc R. , Bel Arjan , van Laarhoven Hanneke W.M. , Stoker Jaap , Goncalves Sonia I. 
Published: April 2016

Objective
The aim was to investigate the value of optimized 3-dimensional alternating repetition time balanced steady-state free precession (ATR-SSFP), as an alternative to conventional segmented balanced steady-state free precession (bSSFP) with fat suppression prepulse (FS-bSSFP), in single breath-hold abdominal magnetic resonance imaging at 3 T.

Methods
Bloch simulations were performed to determine the optimal flip angle (FA = 1–90 degrees) and τ (1–3) with respect to signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) between abdominal organs for ATR-SSFP. These were corroborated by phantom measurements for different T1/T2 values (5–47) as well as in a healthy volunteer. In addition, fat suppression efficiency was studied using phantom and volunteer measurements. The effect of resolution on image quality was studied in a healthy volunteer. Using the optimal settings, ATR-SSFP images as well as FS-bSSFP images were obtained in 15 pancreatic cancer patients. For 10 structures of interest, the signal ratio with respect to the pancreas was computed and compared between both sequences. Finally, 10 items on image quality (fat suppression, artifacts, and sharpness) and tissue conspicuity (ducts, vessels, and duodenum) were scored by 2 abdominal radiologists for both image sequences.

Results
The results of simulations, phantom measurements, and volunteer measurements showed that, considering scan time, fat suppression, and clinical relevance, the ideal settings for ATR-SSFP were as follows: τ = 3; TR1 = 3.46 milliseconds; radiofrequency phase cycling 0, 180, 180, 0 degrees; and FA = 13–16 degrees (highest SNR) and 24–26 degrees (highest CNR). The optimized feasible additional settings implemented for patient scans were FA = 18 degrees and resolution = 1.4 × 1.4 × 1.4 mm3. In patients, the signal ratios of both ATR-SSFP and FS-bSSFP were comparable and had a T2-like contrast behavior, although more accentuated in ATR-SSFP. The ATR-SSFP scored significantly higher than FS-bSSFP for 9 of 10 items scored.

Conclusions
For single breath-hold abdominal imaging at 3 T, ATR-SSFP performs best with τ = 3 and an FA between 13 degrees (highest SNR) and 26 degrees (highest CNR). The scoring of both abdominal radiologists indicated that, at τ = 3, FA = 18 degrees, and 1.4 × 1.4 × 1.4 mm3 resolution, ATR-SSFP was preferred over conventional FS-bSSFP with similar settings.
Adverse Reactions to Gadoterate Meglumine
Authors: de Kerviler Eric , Maravilla Kenneth , Meder Jean-François , Naggara Olivier , Dubourdieu Corinne , Jullien Vincent , Desché Pierre 
Published: April 2016

Objective
The aim of this study was to evaluate the safety profile of gadoterate meglumine from clinical trials, postmarketing observational studies, and pharmacovigilance reports of adverse drug reactions (ADRs) encompassing 25 years of clinical use and over 50 million administered doses.

Materials and Methods
Assessment of the safety of gadoterate meglumine through processing and review of all safety data was collected after magnetic resonance imaging procedures. All ADRs originated from 3 major sources: (1) a clinical study database including 50 phase I to IV studies involving 2822 patients, (2) a safety database including 8 postmarketing safety studies (PMSs) involving 151,050 patients, and (3) a pharmacovigilance database compiling safety experience following over 50 million doses administered between March 1989 and September 2015.

Results
Among the 2822 patients receiving gadoterate meglumine in the clinical trials, 241 (8.5%) experienced 405 postinjection adverse events (AEs), considered related to the contrast agent for 113 patients (4.0%). Serious AEs were reported for 27 patients (1.0%) and assessed as related to gadoterate meglumine for 2 patients (0.07%). None of the PMS studies showed evidence of unexpected safety issues, with a very low rate of AEs (<1%). Postmarketing safety experience with over 50 million doses of gadoterate meglumine prescribed for 25 years of approved use worldwide compiled spontaneous reports for 3797 patients who experienced 8397 ADRs, yielding a very low reported incidence of ADRs of 0.007% of patients. There was no single-agent case of confirmed nephrogenic systemic fibrosis with gadoterate meglumine either from clinical development programs or from postmarketing experience.

Conclusions
Based on clinical trials, postmarketing observational studies and pharmacovigilance data, a very low incidence of ADRs was reported with gadoterate meglumine, which has no impact on its favourable benefit-risk ratio.
Annotation Regression for Genome-Wide Association Studies with an Application to Psychiatric Genomic Consortium Data
Authors: Shin Sunyoung , Keleş Sündüz 
Published: April 2016

AbstractAlthough genome-wide association studies (GWAS) have been successful at finding thousands of disease-associated genetic variants (GVs), identifying causal variants and elucidating the mechanisms by which genotypes influence phenotypes are critical open questions. A key challenge is that a large percentage of disease-associated GVs are potential regulatory variants located in noncoding regions, making them difficult to interpret. Recent research efforts focus on going beyond annotating GVs by integrating functional annotation data with GWAS to prioritize GVs. However, applicability of these approaches is challenged by high dimensionality and heterogeneity of functional annotation data. Furthermore, existing methods often assume global associations of GVs with annotation data. This strong assumption is susceptible to violations for GVs involved in many complex diseases. To address these issues, we develop a general regression framework, named Annotation Regression for GWAS (ARoG). ARoG is based on finite mixture of linear regression models where GWAS association measures are viewed as responses and functional annotations as predictors. This mixture framework addresses heterogeneity of effects of GVs by grouping them into clusters and high dimensionality of the functional annotations by enabling annotation selection within each cluster. ARoG further employs permutation testing to evaluate the significance of selected annotations. Computational experiments indicate that ARoG can discover distinct associations between disease risk and functional annotations. Application of ARoG to autism and schizophrenia data from Psychiatric Genomics Consortium led to identification of GVs that significantly affect interactions of several transcription factors with DNA as potential mechanisms contributing to these disorders.
The rate and potential relevance of new mutations in a colonizing plant lineage
Authors: Exposito-Alonso Moises , Becker Claude , Schuenemann Verena J. , Reiter Ella , Setzer Claudia , Slovak Radka , Brachi Benjamin , Hagmann Jörg , Grimm Dominik G. , Chen Jiahui , Busch Wolfgang , Bergelson Joy , Ness Rob W. , Krause Johannes , Burbano Hernán A. , Weigel Detlef 
Published: April 2016

ABSTRACTBy following the evolution of populations that are initially genetically homogeneous, much can be learned about core biological principles. For example, it allows for detailed studies of the rate of emergence ofde novomutations and their change in frequency due to drift and selection. Unfortunately, in multicellular organisms with generation times of months or years, it is difficult to set up and carry out such experiments over many generations. An alternative is provided by “natural evolution experiments” that started from colonizations or invasions of new habitats by selfing lineages. With limited or missing gene flow from other lineages, new mutations and their effects can be easily detected. North America has been colonized in historic times by the plantArabidopsis thaliana, and although multiple intercrossing lineages are found today, many of the individuals belong to a single lineage, HPG1. To determine in this lineage the rate of substitutions – the subset of mutations that survived natural selection and drift –, we have sequenced genomes from plants collected between 1863 and 2006. We identified 73 modern and 27 herbarium specimens that belonged to HPG1. Using the estimated substitution rate, we infer that the last common HPG1 ancestor lived in the early 17thcentury, when it was most likely introduced by chance from Europe. Mutations in coding regions are depleted in frequency compared to those in other portions of the genome, consistent with purifying selection. Nevertheless, a handful of mutations is found at high frequency in present-day populations. We link these to detectable phenotypic variance in traits of known ecological importance, life history and growth, which could reflect their adaptive value. Our work showcases how, by applying genomics methods to a combination of modern and historic samples from colonizing lineages, we can directly study new mutations and their potential evolutionary relevance.
A Land Plant-Specific Transcription Factor Directly Enhances Transcription of a Pathogenic Noncoding RNA Template by DNA-Dependent RNA Polymerase II
Authors: Wang Ying , Qu Jie , Ji Shaoyi , Wallace Andrew J. , Wu Jian , Li Yi , Gopalan Venkat , Ding Biao 
Published: April 2016

AbstractSome DNA-dependent RNA polymerases (DdRPs) possess RNA-dependent RNA polymerase activity, as was first discovered in the replication of Potato spindle tuber viroid (PSTVd) RNA genome in tomato (Solanum lycopersicum). Recent studies revealed that this activity in bacteria and mammals is important for transcriptional and posttranscriptional regulatory mechanisms. Here, we used PSTVd as a model to uncover auxiliary factors essential for RNA-templated transcription by DdRP. PSTVd replication in the nucleoplasm generates (−)-PSTVd intermediates and (+)-PSTVd copies. We found that the Nicotiana benthamiana canonical 9-zinc finger (ZF) Transcription Factor IIIA (TFIIIA-9ZF) as well as its variant TFIIIA-7ZF interacted with (+)-PSTVd, but only TFIIIA-7ZF interacted with (−)-PSTVd. Suppression of TFIIIA-7ZF reduced PSTVd replication, and overexpression of TFIIIA-7ZF enhanced PSTVd replication in planta. Consistent with the locale of PSTVd replication, TFIIIA-7ZF was found in the nucleoplasm and nucleolus, in contrast to the strictly nucleolar localization of TFIIIA-9ZF. Footprinting assays revealed that only TFIIIA-7ZF bound to a region of PSTVd critical for initiating transcription. Furthermore, TFIIIA-7ZF strongly enhanced the in vitro transcription of circular (+)-PSTVd by partially purified Pol II. Together, our results identify TFIIIA-7ZF as a dedicated cellular transcription factor that acts in DdRP-catalyzed RNA-templated transcription, highlighting both the extraordinary evolutionary adaptation of viroids and the potential of DdRPs for a broader role in cellular processes.
An anti-windup control strategy to actuator saturating input voltage for active magnetic bearing system
Authors: Pati Avadh , Negi Richa 
Published: April 2016

Purpose
The active magnetic bearing is highly nonlinear and unstable system. In general most of physical systems, conventional PID control strategies are employed for their stable operation but the dynamics of the system are influenced by input voltage saturation that degrades the performance of the system. The conventional PID control scheme does not work properly alone. In such a situation, PID faces windup phenomenon that leads to instability in the system. To overcome this problem, an anti-windup control scheme leads to stable and smooth operation of active magnetic bearing system.

Design/methodology/approach
The proposed anti-windup control strategy is based on dynamic output feedback that is applied on linearized active magnetic bearing (AMB) system to stabilize and avoid the input voltage saturation effect in the actuator.

Findings
An anti-windup controller is designed for active magnetic bearing system in presence of input voltage saturation. The stability of AMB system with anti-windup controller is derived in sense of Lyapunov and expressed as linear matrix inequality problem for AMB system and the designed anti-windup controller also enlarges the region of attraction of considered AMB system.

Originality/value
T-S fuzzy technique is used for obtaining local linear model of nonlinear active magnetic bearing system for easy and simple implementation of anti-windup control scheme. In proposed methodology the region of attraction for anti-windup compensator is also discussed. The effectiveness of proposed method is verified by the numerical simulation results for considered active magnetic bearing system and domain of attraction or stability region of closed loop AMB system are also calculated using Eigen Value Optimization technique for both the cases such as with and without anti-windup controller. The comparative result and the contribution of proposed control strategy are also discussed.
A polynomial approach to determine the time-dependent electric and magnetic fields in anisotropic materials by symbolic computations
Authors: Yakhno Valery George , Altunkaynak Meltem 
Published: April 2016

Purpose
The purpose of this paper is to calculate the time-dependent electric and magnetic fields in anisotropic media with a general structure of anisotropy by symbolic computations.

Design/methodology/approach
An analytical approach for the computation of the time-dependent electric and magnetic fields is suggested. This approach consists of the following. Input data, electric and magnetic fields are presented in polynomial form.The exact formulae for electric and magnetic fields are computed by symbolic transformations in Maple.

Findings
The time-dependent second order partial differential equations for the electric and magnetic fields with polynomial data were obtained from Maxwell's equations when the current density is presented in a polynomial form with respect to space variables in a bounded region of three dimensional space. The exact solutions of obtained equations were computed symbolically using Maple.

Originality/value
The obtained polynomial solutions do not contain errors if data are polynomials. We have shown that these solutions are approximate solutions with good accuracy for data which are approximated by polynomials in a bounded region of 3D space.
Low power modular redundancy: a power efficient fault tolerant approach for digital circuits
Authors: Ansari M. Saeed , Mahani Ali , Mohammadi Karim 
Published: April 2016

Purpose
To increase protection level against transient faults, circuit designers usually take advantage of redundant structures like Triple Modular Redundancy (TMR). Since redundancy compel a significant power overhead, proposing a low power fault tolerant technique in digital circuits is the main objective of this research work.

Design/methodology/approach
In order to moderate power consumption, we use a dual to triple modular redundancy. In fact, we put one of the modules in a TMR system in sleep mode while the other two operating modules are producing the same outputs. Once a mismatch is detected, the third one exits the sleep mode and the dual modular redundancy (DMR) approach turns into a conventional TMR. Also a novel stoppable clock generator is proposed to handle the sleep mode of the third module. Finally, a new three-input majority voter, compatible with our proposed technique, is presented.

Findings
Power analysis of combinational circuit benchmarks, ISCAS85, and ISCAS89 as sequential circuit benchmarks are depicted. Simulation results show the power reduction of up to 30% in comparison with the conventional modular redundancy approach.

Originality/value
Since modular redundancy is the most effective and the most well-known fault tolerant approach which is widely used in reliable circuits designs, it is important to reduce its power consumption. In this paper configuring the sleep mode operation of a circuit and stoppable clock generator lead to a new TMR technique in which the power consumption is strongly reduced.
Power analysis approach and its application to IP-based SoC design
Authors: Durrani Yaseer Arafat , Riesgo Teresa , Khan Muhammad Imran , Mahmood Tariq 
Published: April 2016

Purpose
Low-power consumption has become an important issue that cannot be ignored in System-on-Chip (SoC) design. The key challenge encountered by system design is how to maintain balance between the estimation accuracy and speed. This paper aims at demonstrating an accurate and fast power estimation technique.

Design/methodology/approach
The methodology adopted in the paper is to use input patterns with the predefined statistical characteristics which helps to analyze the average power consumption of the different intellectual-property (IP) cores and the interconnects/buses in SoC design. Similarly the paper has implemented Genetic algorithm (GA) to generate sequences of input signals during the power estimation procedure.

Findings
The GA concurrently optimizes the input signal characteristics that influence the final solution of the pattern. In addition to that, a Monte-Carlo zero-delay simulation is also performed for individual IP core and bus at high-level. By the simple addition of these cores/buses, power is predicted by a novel macro-model function. In experiments, the average error is estimated at 13.84%.

Research limitations/implications
To present the research findings with clarity and to avoid complexities, the paper does not consider delay factors like glitches, jitter etc. in the power model.

Practical implications
The proposed methodology allowed accurate power/energy analysis of practical applications mapped onto Network-on-Chip (NoC) based Multiprocessors SoC platform. It enables the performance analysis of different design alternatives under the load imposed by complex applications.

Originality/value
This paper is an original contribution and the results demonstrate that our novel technique could be implemented to achieve fast and accurate power estimation in the early stage of any SoC design.