Efficacy and Safety of Biosimilar FYB201 Compared with Ranibizumab in Neovascular Age-Related Macular Degeneration.

Abstract Purpose This trial was conducted to investigate the clinical equivalence of the proposed biosimilar FYB201 and reference ranibizumab in patients with treatment-naive, subfoveal choroidal neovascularization caused by neovascular age-related macular degeneration (nAMD). Design This was a prospective, multicenter, evaluation-masked, parallel-group, 48-week, phase III randomized study. Participants A total of 477 patients were randomly assigned to receive FYB201 (n = 238) or reference ranibizumab (n = 239). Methods Patients received FYB201 or ranibizumab 0.5 mg by intravitreal injection in the study eye every four weeks. Main Outcome Measures The primary end point was change from baseline in best corrected visual acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 8 weeks prior to the third monthly intravitreal injection. Biosimilarity of FYB201 to its originator was assessed via a two-sided equivalence test, with an equivalence margin in BCVA of 3 ETDRS letters. Results BCVA improved in both groups, with a mean improvement of +5.1 (FYB201) and +5.6 (reference ranibizumab) ETDRS letters at week 8. The analysis of covariance (ANCOVA) least squares mean difference for the change from baseline between FYB201 and reference ranibizumab was –0.4 ETDRS letters with a 90% confidence interval (CI) of –1.6 to 0.9. Primary end point was met as the 90% CI was within the predefined equivalence margin. Adverse events were comparable between treatment groups. Conclusions FYB201 is biosimilar to reference ranibizumab in terms of clinical efficacy and ocular and systemic safety in the treatment of patients with nAMD

Automated analysis of slow crack growth in hydrous soda-lime silicate glasses

To explore the impact of ambient and structural water on static fatigue, the initiation and growth of 3279 Vickers induced median radial cracks were automatically recorded and analyzed. We find that humidity is more efficient in initiating cracks and promoting their growth than water, which is dissolved in the glass structure. In particular for slow crack growth (< 3 × 10−6 m s−1), tests in dry nitrogen showed a considerable decrease in the crack growth exponent with increasing water content of the glasses. On the other hand, if tests were performed in humid air, the crack growth exponent was independent of the water content of the hydrous glasses, while stress intensity decreased slightly. These observations indicate that water promotes the processes at the crack-tip regardless of its origin. However, ambient water is more efficient

Water in Alkali Aluminosilicate Glasses

To understand the influence of water and alkalis on aluminosilicate glasses, three polymerized glasses with varying ratios of Na/K were synthesized [(22. 5-x)Na2O-xK2O-22.5 Al2O3-55 SiO2 with x = 0, 7.5, and 11.25]. Subsequently, these glasses were hydrated (up to 8 wt% H2O) in an internally heated gas pressure vessel. The density of hydrous glasses linearly decreased with water content above 1 wt%, consistent with the partial molar volume of H2O of 12 cm3/mol. Near-infrared spectroscopy revealed that hydroxyl groups are the dominant species at water content of &lt;4 wt%, and molecular water becomes dominating at water content of &gt;5 wt%. The fraction of OH is particularly high in the pure Na-bearing glass compared to the mixed alkali glasses. 27Al magic angle spinning-NMR spectroscopy shows that aluminum is exclusively fourfold coordinated with some variations in the local geometry. It appears that the local structure around Al becomes more ordered with increasing K/Na ratio. The incorporation of H2O reinforces this effect. The differential thermal analysis of hydrous glasses shows a significant mass loss in the range of glass transition already during the first upscan, implying the high mobility of water in the glasses. This observation can be explained by the open structure of the aluminosilicate network and by the low dissociation enthalpy of H2O in the glasses (≈ 8 kJ/mol). The effect of the dissolved H2O on the glass transition temperature is less pronounced than for other aluminosilicate glasses, probably because of the large fraction of Al in the glasses. © Copyright © 2020 Balzer, Behrens, Waurischk, Reinsch, Müller, Kiefer, Deubener and Fechtelkord

Automated Analysis of Slow Crack Growth in Hydrous Soda-Lime Silicate Glasses

To explore the impact of ambient and structural water on static fatigue, the initiation and growth of 3279 Vickers induced median radial cracks were automatically recorded and analyzed. We find that humidity is more efficient in initiating cracks and promoting their growth than water, which is dissolved in the glass structure. In particular for slow crack growth (< 3 × 10–6 m s–1), tests in dry nitrogen showed a considerable decrease in the crack growth exponent with increasing water content of the glasses. On the other hand, if tests were performed in humid air, the crack growth exponent was independent of the water content of the hydrous glasses, while stress intensity decreased slightly. These observations indicate that water promotes the processes at the crack-tip regardless of its origin. However, ambient water is more efficient

Biology of Plasmopara viticola - Approach to a biological control of grapevine downy mildew

Plasmopara viticola, the causai agent of grapevine downy mildew is very well adapted to its host pianI. Therefore it is very difficult to develop methods for the biological control which meet the requests of ecological viticulture. One of the possibilities for a biological control of grapevine downy mildew is the usage of the natural resistance potential of the European cultivars of Vitis vinifera, more exactly the induced resistance. Another way is the use of specific inhibitors which either stop the infection process or have an effect on the interaction of the pathogen with the host pianI. Whereas generai information about the resistance reactions in plants is available and the first results were also won for vine, the knowledge about inhibitors is very scanty. The basic prerequisite to develop methods and strategies for the biological control of grapevine downy mildew is a comprehensive knowledge about the biology of P. viticola, especially so with respect to the interaction between pathogen and host. Since P. viticola is well adapted to the host plant, the development of biological methods is a scientific and technical challenge. P. viticola is indigenous in the south-eastern part of North America with a damp warm climate where it can be found on different autochtonous Vitis species. Due to the coevolution of the pathogen and the host a balanced relationship exists between the pathogen's virulence and the host's resistance. In contrast the European Vitis vinifera cultivars are highly susceptible for P. viticola; they have got in contact with the pathogen only 120 years ago and no adaptation has been developed in this short period of time. According to our hypothesis, a lack of a fast recognition of the pathogen results in a delayed resistance response of V. vinifera cultivars. The growth and development of P. viticola is \.ery fast on the host plant and reproduction as well as propagation potential is high. In addition, the growing conditions of grapevine, e.g. regional coverage of viticulture, dense canopy and humid climate, promote epidemic

Dual-source computed tomography of the lung with spectral shaping and advanced iterative reconstruction: potential for maximum radiation dose reduction

Abstract Background Radiation dose at CT should be as low as possible without compromising diagnostic quality. Objective To assess the potential for maximum dose reduction of pediatric lung dual-source CT with spectral shaping and advanced iterative reconstruction (ADMIRE). Materials and methods We retrospectively analyzed dual-source CT acquisitions in a full-dose group (FD: 100 kV, 64 reference mAs) and in three groups with spectral shaping and differing reference mAs values (Sn: 100 kV, 96/64/32 reference mAs), each group consisting of 16 patients (age mean 11.5 years, standard deviation 4.8 years, median 12.8 years, range 1.3–18 years). Advanced iterative reconstruction of images was performed with different strengths (FD: ADMIRE Level 2; Sn: ADMIRE Levels 2, 3 and 4). We analyzed dose parameters and measured noise. Diagnostic confidence and detectability of lung lesions as well as anatomical structures were assessed using a Likert scale (from 1 [unacceptable] to 4 [fully acceptable]). Results Compared to full dose, effective dose was reduced to 16.7% in the Sn 96 group, 11.1% in Sn64, and 5.5% in Sn32 (P3 was reached in Sn64ADM4 regarding diagnostic confidence (3.2) and detectability of lung lesions (3.3). For detectability of most anatomical structures, no significant differences were found between FDAM2 and Sn64ADM4 (P≥0.05). Conclusion In pediatric lung dual-source CT, spectral shaping together with ADMIRE 4 enable radiation dose reduction to about 10% of a full-dose protocol while maintaining an acceptable diagnostic quality

The SPARC water vapour assessment II: Comparison of stratospheric and lower mesospheric water vapour time series observed from satellites

Time series of stratospheric and lower mesospheric water vapour using 33 data sets from 15 different satellite instruments were compared in the framework of the second SPARC (Stratosphere-troposphere Processes And their Role in Climate) water vapour assessment (WAVAS-II). This comparison aimed to provide a comprehensive overview of the typical uncertainties in the observational database that can be considered in the future in observational and modelling studies, e.g addressing stratospheric water vapour trends. The time series comparisons are presented for the three latitude bands, the Antarctic (80\ub0-70\ub0S), the tropics (15\ub0S-15\ub0N) and the Northern Hemisphere mid-latitudes (50\ub0-60\ub0N) at four different altitudes (0.1, 3, 10 and 80hPa) covering the stratosphere and lower mesosphere. The combined temporal coverage of observations from the 15 satellite instruments allowed the consideration of the time period 1986-2014. In addition to the qualitative comparison of the time series, the agreement of the data sets is assessed quantitatively in the form of the spread (i.e. the difference between the maximum and minimum volume mixing ratios among the data sets), the (Pearson) correlation coefficient and the drift (i.e. linear changes of the difference between time series over time). Generally, good agreement between the time series was found in the middle stratosphere while larger differences were found in the lower mesosphere and near the tropopause. Concerning the latitude bands, the largest differences were found in the Antarctic while the best agreement was found for the tropics. From our assessment we find that most data sets can be considered in future observational and modelling studies, e.g. addressing stratospheric and lower mesospheric water vapour variability and trends, if data set specific characteristics (e.g. drift) and restrictions (e.g. temporal and spatial coverage) are taken into account

A Predictive Model of Intein Insertion Site for Use in the Engineering of Molecular Switches

Inteins are intervening protein domains with self-splicing ability that can be used as molecular switches to control activity of their host protein. Successfully engineering an intein into a host protein requires identifying an insertion site that permits intein insertion and splicing while allowing for proper folding of the mature protein post-splicing. By analyzing sequence and structure based properties of native intein insertion sites we have identified four features that showed significant correlation with the location of the intein insertion sites, and therefore may be useful in predicting insertion sites in other proteins that provide native-like intein function. Three of these properties, the distance to the active site and dimer interface site, the SVM score of the splice site cassette, and the sequence conservation of the site showed statistically significant correlation and strong predictive power, with area under the curve (AUC) values of 0.79, 0.76, and 0.73 respectively, while the distance to secondary structure/loop junction showed significance but with less predictive power (AUC of 0.54). In a case study of 20 insertion sites in the XynB xylanase, two features of native insertion sites showed correlation with the splice sites and demonstrated predictive value in selecting non-native splice sites. Structural modeling of intein insertions at two sites highlighted the role that the insertion site location could play on the ability of the intein to modulate activity of the host protein. These findings can be used to enrich the selection of insertion sites capable of supporting intein splicing and hosting an intein switch