Biosimilars in Oncology: From Development to Clinical Practice

Biologics play an integral role in the treatment of cancer not only for their therapeutic effects and ability to improve outcomes, but also as supportive care agents. Biologics are more complex to manufacture and take longer to bring to market. Because biologics are considerably more costly than small-molecule drugs, their use has placed an increasing economic demand on healthcare systems worldwide. Biosimilars are designed to be highly similar to existing branded biologics, but because biologics cannot be exactly copied, biosimilars should not be referred to as generic, exact versions of the innovator biologic. Biosimilars have the potential to increase access and provide lower cost options for cancer care as patent protection for some of the most widely used biologics begins to expire. Regulatory requirements for biosimilars are evolving, as are global harmonization and/or standardization strategies that can facilitate their robust clinical development. This review highlights critical factors involved with the integration of biosimilars into oncology treatment paradigms and practices. Clinicians will likely seek out practice guidelines and position statements from established scientific societies to help evaluate key information regarding biosimilars, such as efficacy, safety, comparability, and interchangeability with the reference biologic. Automatic substitution, nomenclature, extrapolation of clinical data from one indication to another, as well as parameters for ongoing pharmacovigilance are evolving considerations. Education of physicians and other healthcare providers, payers, and patients about biosimilars may facilitate informed decision making, promote acceptance of biosimilars into clinical practice, increase accessibility, and expedite associated health and economic benefits

Damage-Induced Modeling of Asphalt Mixtures through Computational Micromechanics and Cohesive Zone Fracture

This paper presents a computational micromechanics modeling approach to predict damage-induced mechanical response of asphalt mixtures. Heterogeneous geometric characteristics and inelastic mechanical behavior were taken into account by introducing finite element modeling techniques and a viscoelastic material model. The modeling also includes interface fracture to represent crack growth and damage evolution. The interface fracture is modeled by using a micromechanical nonlinear viscoelastic cohesive-zone constitutive relation. Fundamental material properties and fracture characteristics were measured from simple laboratory tests and then incorporated into the model to predict rate-dependent viscoelastic damage behavior of the asphalt mixture. Simulation results demonstrate that each model parameter significantly influences the mechanical behavior of the overall asphalt mixture. Within a theoretical framework of micromechanics, this study is expected to be suitable for evaluating damage-induced performance of asphalt mixtures by measuring only material properties and fracture properties of each mix component and not by recursively performing expensive laboratory tests that are typically required for continuum damage mechanics modeling

Design GUI of Simulation and Numerical Solution of Equation and Non Linier Equation Systems

Penelitian ini bertujuan untuk mengembangkan aplikasi project GUI Matlab dalam mensimulasi dan menentukan solusi persamaan dan sistem persamaan non linier dengan menggunakan metode terbuka, metode tertutup, Jacobian, Gauss Seidel, dan  Newton Raphson. Pengembangan aplikasi ini menggunakan metode desain pengembangan 4-D yang dilakukan melalui 4 tahap yakni: Define, Design, Develop, dan Diseminate. Hasil uji coba terbatas dan lapangan rata-rata mahasiswa memberikan respon yang sangat baik. Aplikasi ini dapat membantu mahasiswa dalam memahami dan menguasai materi kuliah metode numerik, karena aplikasi dibangun dengan desain yang sesuai kebutuhan mahasiswa khususnya pada langkah-langkah penyelesaian dari persamalahan yang disajikan tanpa harus menyusun ulang scribs di m-file dan Command Windows

The impacts of monsoon and dry seasons on physical water quality changes and farmed Asian seabass Lates calcarifer (Bloch, 1790) mortality at Sri Tujuh lagoon, Tumpat, Kelantan, Malaysia

This study aimed to monitor the water quality in Sri Tujuh lagoon during monsoon and dry seasons, as well as the impact of the two seasons on the production of Asian seabass (Lates calcarifer). The water quality parameters such as temperature, pH, dissolved oxygen (DO), salinity, conductivity, turbidity and total dissolved solid of Sri Tujuh lagoon were assessed using water samples collected from 13 sampling points at 1ft, 4ft and 7ft water depth during dry season (March-August 2014) and monsoon (September-November 2014). Fish mortality was recorded from Asian seabass farmers in the lagoon. Water quality data during dry seasoon and monsoon was compared using T-Test and data from 3 different depths was analysed by using One Way Anova followed by Tukey test at p < 0.05. The water parameters in dry season, monsoon season, combination of dry and monsoon season were subjected to Pearson correlation analysis separately and a matrix was tabulated. Water parameters were also subjected to cluster analysis by using Ward’s method with squared Euclidean distances as a measure of similarity. In the present study Ward’s method was used ANOVA followed by Tukey post hoc in order to minimize the sum of squares. The result was represented by a dendrogram. The findings of the present study showed water parameters such as DO, salinity and turbidity were significantly different between dry and monsoon seasons. However no significant difference was found in term of fish mortality. The water parameters of Sri Tujuh lagoon during the study were as follow: temperature 29.4-33.3 oC; pH 7.0-9.3; DO 0.8-6.8 mg L -1 ; salinity 10.7-31.3 ppt; conductivity 17.5-50.5 µs cm-1 ; turbidity 5.4-59.8 NTU; TDS 23.3-32 ppt. The fish mortality was recorded ranging from 9.3 to 15.5% from March to November, 2014. The positive and significance (p < 0.01) correlation was recorded between temperature and pH (0.434), temperature and DO (0.472), DO and pH (0.315), salinity and pH (0.615), conductivity and pH (0.595), conductivity and salinity (0.992), TDS and pH (0.340), TDS and salinity (0.322) and TDS and conductivity (0.322). Fish mortality showed no correlation with all water parameters changing in the whole study at Sri Tujuh lagoon. Based on the water parameter records from 13 sampling stations, the sampling stations can be divided into 5 clusters. Cluster 1 possesses the greatest number of stations namely S3, S4, S6, S7, S8, S11 and S12 whereas Cluster 2 has S1, S10 and S13. Only one station was found in the Cluster 3 (S5), Cluster 4 (S2) and Cluster 5 (S9). Based on the findings of the present study, Sri Tujuh lagoon can be considered as one of the best places to conduct aquaculture activities in Kelantan

Jet quenching in relativistic heavy ion collisions

Parton propagation in dense nuclear matter results in elastic, inelastic and coherent multiple soft scattering with the in-medium color charges. Such scattering leads to calculable modifications of the hadron production cross section that is evaluated in the framework of the perturbative QCD factorization approach. Final state medium-induced gluon bremsstrahlung is arguably the most efficient way of suppressing large transverse momentum particle production in nucleus-nucleus collisions. The observed hadronic attenuation, known as jet quenching, can be related to the properties of the medium, such as density and temperature, and carries valuable information about the early stages of heavy ion reactions. Non-Abelian energy loss in the quark-gluon plasma can be studied in much greater detail through the modification of the two particle back-to-back correlations. Perturbative calculations give good description of the redistribution of the lost energy in lower transverse momentum particles and predict significant increase of the correlation width of away-side di-hadrons. In contrast, energy loss in cold nuclear matter was found to be small but for large values of Feynman-x is expected to complement the dynamical higher twist shadowing in experimentally observable forward rapidity hadron suppression.Comment: Invited plenary talk at the V-th international conference on the physics and astrophysics of the quark-gluon plasma. 8 pages, 4 figure

Quantitative features of multifractal subtleties in time series

Based on the Multifractal Detrended Fluctuation Analysis (MFDFA) and on the Wavelet Transform Modulus Maxima (WTMM) methods we investigate the origin of multifractality in the time series. Series fluctuating according to a qGaussian distribution, both uncorrelated and correlated in time, are used. For the uncorrelated series at the border (q=5/3) between the Gaussian and the Levy basins of attraction asymptotically we find a phase-like transition between monofractal and bifractal characteristics. This indicates that these may solely be the specific nonlinear temporal correlations that organize the series into a genuine multifractal hierarchy. For analyzing various features of multifractality due to such correlations, we use the model series generated from the binomial cascade as well as empirical series. Then, within the temporal ranges of well developed power-law correlations we find a fast convergence in all multifractal measures. Besides of its practical significance this fact may reflect another manifestation of a conjectured q-generalized Central Limit Theorem