A simple treatment regimen that is effective in a broad range of patients who are chronically infected with the hepatitis C virus (HCV) remains an unmet medical need.
We conducted a phase 3, ...double-blind, placebo-controlled study involving untreated and previously treated patients with chronic HCV genotype 1, 2, 4, 5, or 6 infection, including those with compensated cirrhosis. Patients with HCV genotype 1, 2, 4, or 6 were randomly assigned in a 5:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir in a once-daily, fixed-dose combination tablet or matching placebo for 12 weeks. Because of the low prevalence of genotype 5 in the study regions, patients with genotype 5 did not undergo randomization but were assigned to the sofosbuvir-velpatasvir group. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.
Of the 624 patients who received treatment with sofosbuvir-velpatasvir, 34% had HCV genotype 1a, 19% genotype 1b, 17% genotype 2, 19% genotype 4, 6% genotype 5, and 7% genotype 6. A total of 8% of patients were black, 19% had cirrhosis, and 32% had been previously treated for HCV. The rate of sustained virologic response among patients receiving sofosbuvir-velpatasvir was 99% (95% confidence interval, 98 to >99). Two patients receiving sofosbuvir-velpatasvir, both with HCV genotype 1, had a virologic relapse. None of the 116 patients receiving placebo had a sustained virologic response. Serious adverse events were reported in 15 patients (2%) in the sofosbuvir-velpatasvir group and none in the placebo group.
Once-daily sofosbuvir-velpatasvir for 12 weeks provided high rates of sustained virologic response among both previously treated and untreated patients infected with HCV genotype 1, 2, 4, 5, or 6, including those with compensated cirrhosis. (Funded by Gilead Sciences; ClinicalTrials.gov number, NCT02201940.).
In phase 2 trials, treatment with the combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir resulted in high rates of sustained virologic response in ...patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3.
We conducted two randomized, phase 3, open-label studies involving patients who had received previous treatment for HCV genotype 2 or 3 and those who had not received such treatment, including patients with compensated cirrhosis. In one trial, patients with HCV genotype 2 were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir, in a once-daily, fixed-dose combination tablet (134 patients), or sofosbuvir plus weight-based ribavirin (132 patients) for 12 weeks. In a second trial, patients with HCV genotype 3 were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir for 12 weeks (277 patients) or sofosbuvir-ribavirin for 24 weeks (275 patients). The primary end point for the two trials was a sustained virologic response at 12 weeks after the end of therapy.
Among patients with HCV genotype 2, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 99% (95% confidence interval CI, 96 to 100), which was superior to the rate of 94% (95% CI, 88 to 97) in the sofosbuvir-ribavirin group (P=0.02). Among patients with HCV genotype 3, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 95% (95% CI, 92 to 98), which was superior to the rate of 80% (95% CI, 75 to 85) in the sofosbuvir-ribavirin group (P<0.001). The most common adverse events in the two studies were fatigue, headache, nausea, and insomnia.
Among patients with HCV genotype 2 or 3 with or without previous treatment, including those with compensated cirrhosis, 12 weeks of treatment with sofosbuvir-velpatasvir resulted in rates of sustained virologic response that were superior to those with standard treatment with sofosbuvir-ribavirin. (Funded by Gilead Sciences; ASTRAL-2 ClinicalTrials.gov number, NCT02220998; and ASTRAL-3, NCT02201953.).
•Binders modified with polymer and wax were studied.•The mixing temperature was evaluated through the equiviscous method.•Short Term Aging procedure was studied with RTFOT at 163°C and mixing ...temperature.•Rheological and chemical properties of unaged and aged bitumens were studied.
This work is based on the characterization of road materials that combine high performance and reduction of the environmental impact during road construction and maintenance. In particular polymer modified bitumens with and without wax additives have been studied. The first increase the elasto-plasticity of the mixture, increasing its durability and fatigue resistance. As for the second the presence of paraffinic additive reduces the bitumen viscosity and consequently the asphalt mixing and compaction temperatures.
A number of studies have shown that the mechanical characteristics of pavement are strongly influenced by the oxidation degree of the organic components of the bitumen during mixing and compaction phases. This phenomenon is known as short-term aging.
Binders modified with polymer and wax were analyzed according to the viscoelasticity theory and different aging conditions were simulated. Tests of advanced rheological characterization were carried out by using the Dynamic Shear Rheometer and the short-term aging was simulated by Rolling Thin Film Oven Test. A new procedure of bitumen aging at the equiviscous temperature or Tmixing was proposed. Further rheological tests on aged binders were carried out at this temperature. The results have been supported by FTIR (Fourier Transform Infrared Spectroscopy) analytical chemical tests, analyzing the molecular changes on the aged binders. The standard temperature of 163°C does not correctly simulate the short term aging of polymer modified and waxes bitumens.
•A 3D DEM approach was developed to predict bitumen complex modulus and phase angle.•The particle interaction at microscale was simulated with a Burger contact model.•Microscale response was analyzed ...by contact forces with their internal distribution.
The mechanical performance of an asphalt mixture is largely dependent on the material properties of its components and the way they are reciprocally interacting. Asphalt binder plays a very significant role because it displays a time and temperature dependent behavior that is characteristic of a viscoelastic material.
An understanding of the contacts mechanisms of the system through a 3D micromechanical model provides insight into the macroscale material behavior, and guides its design and performance prediction.
Based on such considerations, a micromechanical based three-dimensional discrete element approach was used in order to capture the time-dependent behavior usually studied with the Dynamic Shear Rheometer analysis.
The results, obtained comparing the numerical simulation of a frequency sweep test with a laboratory one, show that the adopted approach is found to be successful in predicting, both quantitatively and qualitatively, the complex modulus and the phase angle of the studied polymer modified bitumen, over a wide range of temperatures and frequencies. In addition the microstructural analysis has permitted to evaluate the internal forces configuration induced by shear stress in the specimen.
Summary
The current COVID‐19 pandemic is caused by the SARS‐CoV‐2 coronavirus. The initial recognized symptoms were respiratory, sometimes culminating in severe respiratory distress requiring ...ventilation, and causing death in a percentage of those infected. As time has passed, other symptoms have been recognized. The initial reports of cutaneous manifestations were from Italian dermatologists, probably because Italy was the first European country to be heavily affected by the pandemic. The overall clinical presentation, course and outcome of SARS‐CoV‐2 infection in children differ from those in adults as do the cutaneous manifestations of childhood. In this review, we summarize the current knowledge on the cutaneous manifestations of COVID‐19 in children after thorough and critical review of articles published in the literature and from the personal experience of a large panel of paediatric dermatologists in Europe. In Part 1, we discuss one of the first and most widespread cutaneous manifestation of COVID‐19, chilblain‐like lesions. In Part 2, we review other manifestations, including erythema multiforme, urticaria and Kawasaki disease‐like inflammatory multisystemic syndrome, while in Part 3, we discuss the histological findings of COVID‐19 manifestations, and the testing and management of infected children, for both COVID‐19 and any other pre‐existing conditions.
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Skin manifestations of COVID‐19 in children: Part 2 Andina, D.; Belloni‐Fortina, A.; Bodemer, C. ...
Clinical and experimental dermatology,
April 2021, 2021-Apr, 2021-04-00, 20210401, 2021-04, Letnik:
46, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Summary
The current COVID‐19 pandemic is caused by the SARS‐CoV‐2 coronavirus. The initial recognized symptoms were respiratory, sometimes culminating in severe respiratory distress requiring ...ventilation, and causing death in a percentage of those infected. As time has passed, other symptoms have been recognized. The initial reports of cutaneous manifestations were from Italian dermatologists, probably because Italy was the first European country to be heavily affected by the pandemic. The overall clinical presentation, course and outcome of SARS‐CoV‐2 infection in children differ from those in adults, as do the cutaneous manifestations of childhood. In this review, we summarize the current knowledge on the cutaneous manifestations of COVID‐19 in children after thorough and critical review of articles published in the literature and from the personal experience of a large panel of paediatric dermatologists in Europe. In Part 1, we discussed one of the first and most widespread cutaneous manifestations of COVID‐19, chilblain‐like lesions. In this part of the review, we describe other manifestations, including erythema multiforme, urticaria and Kawasaki disease‐like inflammatory multisystemic syndrome. In Part 3, we discuss the histological findings of COVID‐19 manifestations, and the testing and management of infected children for both COVID‐19 and any other pre‐existing conditions.
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Display omitted
•A 3D DEM approach was adopted to predict mastics complex modulus and phase angle.•Macroscale response was analyzed by temperature sweep and Multiple Stress Creep Recovery ...tests.•Microscale response was analyzed by contact forces inside the specimens and spheres displacements.
Cold recycling with bitumen emulsion represents one of the most attractive pavements rehabilitation methods. This technique has increased its popularity because it combines environmental and economical efficiency to the production of bituminous layers of adequate strength.
The binder matrix obtained from this application is generally represented by mastic of bitumen, cement and filler. The percentage of these three elements affects the mixture performance in terms of stiffness, fatigue and rutting resistance as well as durability.
The main purpose of this study is to evaluate how cement and limestone filler contents affect the rutting response of mastics. Laboratory testing and 3D Discrete Element Method were performed using different percentages of filler and cement, keeping constant the overall volume fraction of both compared to the total volume of the mastic samples.
Temperature sweep and Multiple Stress Creep Recovery tests were implemented to study the behavior of mastics in terms of permanent deformation by shear stress.
Summary
The current COVID‐19 pandemic is caused by the SARS‐CoV‐2 coronavirus. The initial recognized symptoms were respiratory, sometimes culminating in severe respiratory distress requiring ...ventilation, and causing death in a percentage of those infected. As time has passed, other symptoms have been recognized. The initial reports of cutaneous manifestations were from Italian dermatologists, probably because Italy was the first European country to be heavily affected by the pandemic. The overall clinical presentation, course and outcome of SARS‐CoV‐2 infection in children differ from those in adults as do the cutaneous manifestations of childhood. In this review, we summarize the current knowledge on the cutaneous manifestations of COVID‐19 in children after thorough and critical review of articles published in the literature and from the personal experience of a large panel of paediatric dermatologists in Europe. In Part 1, we discuss one of the first and most widespread cutaneous manifestations of COVID‐19, chilblain‐like lesions, and in Part 2 we expanded to other manifestations, including erythema multiforme, urticaria and Kawasaki disease‐like inflammatory multisystemic syndrome. In this part of the review, we discuss the histological findings of COVID‐19 manifestations, and the testing and management of infected children for both COVID‐19 and any other pre‐existing conditions.
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COVID-19 toes represent the main dermatological COVID-19 cutaneous manifestation in pediatric patients. Its diagnosis exposes the whole family to social stigma and this aspect was not previously ...evaluated.
This was a multicenter, case-control, observational study that compared the family impact of COVID-19 toes vs. psoriasis (PsO). We enrolled 46 pediatric patients (23 with psoriasis and 23 with COVID-19 toes, age and gender matched) and their parents/caregivers that had to fill the Dermatitis Family Impact (DFI) questionnaire.
DFI index did not differ significantly between both subgroups (p=0.48), and in psoriatic patients did not correlate with both Psoriasis Area Severity Index (PASI) (p=0.59) and itch-VAS (p=0.16).
COVID-19 toes, a transitory dermatosis, exerted a similar impact/perturbation on family dynamics than PsO, a well-known stigmatizing, chronic inflammatory dermatosis.
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