Impact of genetic SLC28 transporter and ITPA variants on ribavirin serum level, hemoglobin drop and therapeutic response in patients with HCV infection.

BACKGROUND & AIMS: In the last decade, pegylated interferon-α (PegIFN-α) plus ribavirin (RBV) was the standard treatment of chronic hepatitis C for genotype 1, and it remains the standard for genotypes 2 and 3. Recent studies reported associations between RBV-induced anemia and genetic polymorphisms of concentrative nucleoside transporters such as CNT3 (encoded by SLC28A3) and inosine triphosphatase (encoded by ITPA). We aimed at studying genetic determinants of RBV kinetics, efficacy and treatment-associated anemia. METHODS: We included 216 patients from two Swiss study cohorts (61% HCV genotype 1, 39% genotypes 2 or 3). Patients were analyzed for SLC28A2 single nucleotide polymorphism (SNP) rs11854484, SLC28A3 rs56350726, and SLC28A3 rs10868138 as well as ITPA SNPs rs1127354 and rs7270101, and followed for treatment-associated hemoglobin changes and sustained virological response (SVR). In 67 patients, RBV serum levels were additionally measured during treatment. RESULTS: Patients with SLC28A2 rs11854484 genotype TT had higher dosage- and body weight-adjusted RBV levels than those with genotypes TC or CC (p=0.02 and p=0.06 at weeks 4 and 8, respectively). ITPA SNP rs1127354 was associated with hemoglobin drop ≥3 g/dl during treatment, in genotype (relative risk (RR)=2.1, 95% CI 1.3-3.5) as well as allelic analyses (RR=2.0, 95%CI 1.2-3.4). SLC28A3 rs56350726 was associated with SVR in genotype (RR=2.2; 95% CI 1.1-4.3) as well as allelic analyses (RR=2.0, 95% CI 1.1-3.4). CONCLUSIONS: The newly identified association between RBV serum levels and SLC28A2 rs11854484 genotype, as well as the replicated association of ITPA and SLC28A3 genetic polymorphisms with RBV-induced anemia and treatment response, may support individualized treatment of chronic hepatitis C and warrant further investigation in larger studies.

Is There a Crime Drop in Western Europe?

Combining data from police statistics and crime victim surveys, this article analyses the evolution of crime in Western Europe from 1988 to 2007. The results show that there is no general drop in crime. Property offences and homicide have been decreasing since the mid 1990s, while violent and drug offences have increased during the period under study. These trends highlight the limits of the explanations to the crime drop in the United States, which are based on the premise of a correlation in the evolution of all offences. The drop in property offences seems related to changes in the socioeconomic situation in Europe as well as to increases in security measures in households, and the reinforcement of private security. The increase in violent offences can be explained by the combination of several factors, including changes in youth's free time provoked by the development of the Internet, changing demographics, and the rise of episodic heavy alcohol consumption and street gangs.

Safety Impacts of Pavement Edge Drop-offs, 2006

A vehicle may leave its travel lane for a number of reasons, such as driver error, poor surface conditions, or avoidance of a collision with another vehicle in the travel lane. When a vehicle leaves the travel lane, pavement edge drop-off poses a potential safety hazard because significant vertical differences between surfaces can affect vehicle stability and reduce a driver’s ability to handle the vehicle. Numerous controlled studies have tested driver response to encountering drop-offs under various conditions, including different speeds, vehicle types, drop-off height and shape, and tire scrubbing versus non-scrubbing conditions. The studies evaluated the drivers’ ability to return to and recover within their own travel lane after leaving the roadway and encountering a drop-off. Many of these studies, however, have used professional drivers as test subjects, so results may not always apply to the population of average drivers. Furthermore, test subjects are always briefed on what generally is to be expected and how to respond; thus, the sense of surprise that a truly naïve driver may experience upon realizing that one or two of his or her tires have just dropped off the edge of the pavement, is very likely diminished. Additionally, the studies were carried out under controlled conditions. The actual impact of pavement edge drop-off on drivers’ ability to recover safely once they leave the roadway, however, is not well understood under actual driving conditions. Additionally, little information is available that quantifies the number or severity of crashes that occur where pavement edge drop-off may have been a contributing factor. Without sufficient information about the frequency of edge drop-off-related crashes, agencies are not fully able to measure the economic benefits of investment decisions, evaluate the effectiveness of different treatments to mitigate edge drop-off, or focus maintenance resources. To address these issues, this report details research to quantify the contribution of pavement edge drop-off to crash frequency and severity. Additionally, the study evaluated federal and state guidance in sampling and addressing pavement edge drop-off and quantified the extent of pavement edge drop-off in two states. This study focused on rural two-lane paved roadways with unpaved shoulders, since they are often high speed facilities (55+ mph), have varying levels of maintenance, and are likely to be characterized by adverse roadway conditions such as narrow lanes or no shoulders.

Bound states of 3He at the edge of a 4He drop on a cesium surface

We show that small amounts of 3He atoms, added to a 4He drop deposited on a flat cesium surface at zero temperature, populate bound states localized at the contact line. These edge states show up for drops large enough to develop well defined surface and bulk regions together with a contact line, and they are structurally different from the well-known Andreev states that appear at the free surface and at the liquid-solid interface of films. We illustrate the one-body density of 3He in a drop with 1000 4He atoms, and show that for a sufficiently large number of impurities the density profiles spread beyond the edge, coating both the curved drop surface and its flat base and eventually isolating it from the substrate.

Impact of Duration of Primary Education on School Enrollment, Graduation and Drop-outs: A Cross- Country Analysis

Using a panel data for non-OECD countries covering the period 1970-2012, this chapter analyzes the impact of the duration of primary education on school enrollment, drop-out and completion rates. The empirical results show that for children in elementary school one ad- ditional grade of primary education have a negative impact on the enrollment rate, while the e ect on drop-outs is positive. Analogously, it is obtained that an additional grade in primary education reduces the enrollment rate in secondary education. These results are in line with the fertility model approach, that is, in developing and underdeveloped countries parents do not have incentive to send children to school given the high perceived economic value of children.

Fusion of the extended modified liquid drop model for nucleation and dynamical nucleation theory

We present a new phenomenological approach to nucleation, based on the combination of the extended modified liquid drop model and dynamical nucleation theory. The new model proposes a new cluster definition, which properly includes the effect of fluctuations, and it is consistent both thermodynamically and kinetically. The model is able to predict successfully the free energy of formation of the critical nucleus, using only macroscopic thermodynamic properties. It also accounts for the spinodal and provides excellent agreement with the result of recent simulations.

On an asymptotic formula for the maximum voltage drop in a on-chip power distribution network

We present a new asymptotic formula for the maximum static voltage in a simplified model for on-chip power distribution networks of array bonded integrated circuits. In this model the voltage is the solution of a Poisson equation in an infinite planar domain whose boundary is an array of circular pads of radius ", and we deal with the singular limit Ɛ → 0 case. In comparison with approximations that appear in the electronic engineering literature, our formula is more complete since we have obtained terms up to order Ɛ15. A procedure will be presented to compute all the successive terms, which can be interpreted as using multipole solutions of equations involving spatial derivatives of functions. To deduce the formula we use the method of matched asymptotic expansions. Our results are completely analytical and we make an extensive use of special functions and of the Gauss constant G

Traffic Control in Work Zones with Edge Drop-Offs, 2002

Pavement and shoulder edge drop-offs commonly occur in work zones as the result of overlays, pavement replacement, or shoulder construction. The depth of these elevation differentials can vary from approximately one inch when a flexible pavement overlay is applied to several feet where major reconstruction is undertaken. The potential hazards associated with pavement edge differentials depend on several factors including depth of the drop-off, shape of the pavement edge, distance from traveled way, vehicle speed, traffic mix, volume, and other factors. This research was undertaken to review current practices in other states for temporary traffic control strategies addressing lane edge differentials and to analyze crash data and resultant litigation related to edge drop-offs. An objective was to identify cost-effective practices that would minimize the potential for and impacts of edge drop crashes in work zones. Considerable variation in addressing temporary traffic control in work zones with edge drop-off exposure was found among the states surveyed. Crashes related to pavement edge drop-offs in work zones do not commonly occur in the state of Iowa, but some have resulted in significant tort claims and settlements. The use of benefit/cost analysis may provide guidance in selection of an appropriate mitigation and protection of edge drop-off conditions. Development and adoption of guidelines for design of appropriate traffic control for work zones that include edge drop-off exposure, particularly identifying effective use of temporary barrier rail, may be beneficial in Iowa.

Effect of aminoethoxyvinilglycine (AVG) on preharvest fruit drop and maturity of apples

Apple trees cultivars Gala and Fuji were sprayed four weeks before commercial harvest with aminoethoxyvinilglycine (AVG), at doses of 0, 125, or 250 mg L-1, and assessed for preharvest fruit drop, fruit growth, and maturation on tree. In 'Gala', 64 days after AVG spraying, fruit drop for control treatment was 85%, and AVG (at 125 and 250 mg L-1) reduced it to 10%. In 'Fuji', 64 days after AVG spraying, fruit drop for control was 6%, while treatments with AVG (at 125 and 250 mg L-1) increased fruit drop to 10%. AVG was a powerful retardant of fruit maturation for 'Gala' but not for 'Fuji'. In 'Gala', the most affected attribute was the skin background color, followed, in decreasing order, by soluble solids content, the starch index, skin red color, the flesh firmness, and titratable acidity. In 'Gala', only flesh firmness retention was improved by increasing AVG dose from 125 mg L-1 to 250 mg L-1. The AVG at 250 mg L-1 inhibited "Gala" late fruit growth but not 'Fuji'.

The maximum voltage drop in an on-chip power distribution network: analysis of square, triangular and hexagonal power pad arrangements

A mathematical model of the voltage drop which arises in on-chip power distribution networks is used to compare the maximum voltage drop in the case of different geometric arrangements of the pads supplying power to the chip. These include the square or Manhattan power pad arrangement, which currently predominates, as well as equilateral triangular and hexagonal arrangements. In agreement with the findings in the literature and with physical and SPICE models, the equilateral triangular power pad arrangement is found to minimize the maximum voltage drop. This headline finding is a consequence of relatively simple formulas for the voltage drop, with explicit error bounds, which are established using complex analysis techniques, and elliptic functions in particular.

SIMULATION OF AMB SUPPORTED ROTOR DURING DROP ON RETAINER BEARINGS

The active magnetic bearings present a new technology which has many advantages compared to traditional bearing designs. Active magnetic bearings, however, require retainer bearings order to prevent damages in the event of a component, power or a control loop failure. In the dropdown situation, when the rotor drops from the magnetic bearings to the retainer bearings, the design parameters of the retainer bearings have a significant influence on the behaviour of the rotor. In this study, the dynamics of an active magnetic bearings supported electric motor during rotor drop on retainer bearings is studied using a multibody simulation approach. Various design parameters of retainer bearings are studied using a simulation model while results are compared with those found in literature. The retainer bearings are modelled using a detailed ball bearing model, which accounts damping and stiffness properties, oil film and friction between races and rolling elements. The model of the ball bearings includes inertia description of rollingelements. The model of the magnetic bearing system contains unbalances of the rotor and stiffness and damping properties of support. In this study, a computationally efficient contact model between the rotor and the retainer bearings is proposed. In addition, this work introduces information for the design of physicalprototype and its retainer bearings.

Dynamic Simulations of Rotors during Drop on Retainer Bearings

The active magnetic bearings have recently been intensively developed because of noncontact support having several advantages compared to conventional bearings. Due to improved materials, strategies of control, and electrical components, the performance and reliability of the active magnetic bearings are improving. However, additional bearings, retainer bearings, still have a vital role in the applications of the active magnetic bearings. The most crucial moment when the retainer bearings are needed is when the rotor drops from the active magnetic bearings on the retainer bearings due to component or power failure. Without appropriate knowledge of the retainer bearings, there is a chance that an active magnetic bearing supported rotor system will be fatal in a drop-down situation. This study introduces a detailed simulation model of a rotor system in order to describe a rotor drop-down situation on the retainer bearings. The introduced simulation model couples a finite element model with component mode synthesis and detailed bearing models. In this study, electrical components and electromechanical forces are not in the focus. The research looks at the theoretical background of the finite element method with component mode synthesis that can be used in the dynamic analysis of flexible rotors. The retainer bearings are described by using two ball bearing models, which include damping and stiffness properties, oil film, inertia of rolling elements and friction between races and rolling elements. Thefirst bearing model assumes that the cage of the bearing is ideal and that the cage holds the balls in their predefined positions precisely. The second bearing model is an extension of the first model and describes the behavior of the cageless bearing. In the bearing model, each ball is described by using two degrees of freedom. The models introduced in this study are verified with a corresponding actual structure. By using verified bearing models, the effects of the parameters of the rotor system onits dynamics during emergency stops are examined. As shown in this study, the misalignment of the retainer bearings has a significant influence on the behavior of the rotor system in a drop-down situation. In this study, a stability map of the rotor system as a function of rotational speed of the rotor and the misalignment of the retainer bearings is presented. In addition, the effects of parameters of the simulation procedure and the rotor system on the dynamics of system are studied.

Effect of tow-drop gaps on the damage resistance and tolerance of Variable-Stiffness Panels

This paper presents an experimental study of the effects of tow-drop gaps in Variable Stiffness Panels under drop-weight impact events. Two different configurations, with and without ply-staggering, have been manufactured by Automated Fibre Placement and compared with their baseline counterpart without defects. For the study of damage resistance, three levels of low velocity impact energy are generated with a drop-weight tower. The damage area is analysed by means of ultrasonic inspection. Results of the analysed defect configurations indicate that the influence of gap defects is only relevant under small impact energy values. However, in the case of damage tolerance, the residual compressive strength after impact does not present significant differences to that of conventional straight fibre laminates. This indicates that the strength reduction is driven mainly by the damage caused by the impact event rather than by the influence of manufacturing-induced defects

The maximum voltage drop in an on-chip power distribution network: analysis of square, triangular and hexagonal power pad arrangements

A mathematical model of the voltage drop which arises in on-chip power distribution networks is used to compare the maximum voltage drop in the case of different geometric arrangements of the pads supplying power to the chip. These include the square or Manhattan power pad arrangement, which currently predominates, as well as equilateral triangular and hexagonal arrangements. In agreement with the findings in the literature and with physical and SPICE models, the equilateral triangular power pad arrangement is found to minimize the maximum voltage drop. This headline finding is a consequence of relatively simple formulas for the voltage drop, with explicit error bounds, which are established using complex analysis techniques, and elliptic functions in particular.