The performance of biased-coin minimization in multicenter randomized clinical trials

Randomized clinical trials (RCTs) are widely used as the gold standard for comparative medical studies. Using randomization to determine treatment assignment assures that all patients have the same chance of being assigned to each treatment group and that the treatment groups are comparable in terms of the distributions of prognostic factors. When treatment groups are not comparable, the power of statistical test will be decreased. Moreover, the problem of imbalance becomes more notable when it occurs in the important prognostic factors because it could result in a significant bias when assessing differences by treatment group. The most intuitive and simple form of randomization is complete randomization. However, with complete randomization there is still a chance for an imbalance on prognostic factors. In order to overcome the problem of imbalance when using complete randomization, restricted randomization procedures were proposed. However, some have argued that an unintended consequence of the restrictions placed on randomization is that they could create patterns that allow for the prediction of future treatment allocation. Furthermore, some have questioned the accuracy of model-based statistical inference using conventional asymptotic test under restrictions placed on the treatment allocation. This dissertation is concerned with an assessment of the performance of biased-coin minimization. The assessment is twofold. The first aspect is to determine in terms of balancing properties and also in terms of the probability of predicting treatment assignment when using biased-coin minimization. The second aspect is to compare the results from the classical statistical test, log-rank test, based on population model and the randomization test from the randomization model while biased-coin minimization is applied. Randomized clinical trials are the gold standard of research for demonstrating the efficacy of therapies used to treat patients in the general community. Allocation methods that promote balance in key prognostic factors between treatment groups are important to assure the accuracy and validity of results from clinical trials. It is important to assess the properties of dynamic allocation methods to demonstrate the validity of these methods as they are applied in research that is designed to develop treatments that are used to enhance the public health

Elucidation of the mechanisms underlying the anticholecystitis effect of the Tibetan medicine “Dida” using Network pharmacology

Purpose: To study the mechanism involved in the anti-cholecystitis effect the Tibetan medicine “Dida”, using network pharmacology-integrated molecular docking simulationsMethods: In this investigation, the bioactive compounds of Dida were collected, network pharmacology methods to predict their targets, and networks were constructed through GO and KEGG pathway analyses. The potential binding between the bioactive compounds and the targets were demonstrated using molecular docking simulations.Results: A total of 12 bioactive compounds and 50 key targets of Dida were identified. Two networks, namely, protein-protein interaction (PPI) network of cholecystitis targets, and compound-target-pathway network, were established. Network analysis showed that 10 targets (GAPDH, AKT1, CASP3, EGFR, TNF, MAPK3, MAPK1, HSP90AA1, STAT3, and BCL2L1) may be the therapeutic targets of Dida in cholecystitis. Analysis of the KEGG pathway indicated that the anti-cholecystitis effect of Dida may its regulation of a few crucial pathways, such as apoptosis, as well as toll-like  receptor, T cell receptor, NOD-like receptor, and MAPK signaling pathways. Furthermore, molecular docking simulation revealed that CASP3, CAPDH, HSP90AA1, MAPK3, MAPK1, and STAT3 had well-characterized interactions with the corresponding compounds.Conclusion: The mechanism underlying the anti-cholecystitis effect of Dida was successfully predicted and verified using a combination of network pharmacology and molecular docking simulation. This provides a firm basis for the experimental verification of the use of Dida in the treatment of cholecystitis, and enhances its rational application in clinical medication. Keywords: Tibetan medicine, Dida, Cholecystitis, Mechanism of effect, Network pharmacology, Molecular docking simulatio

Elucidation of the mechanism of action of the anticholecystitis effect of the Tibetan medicine “Dida” using network pharmacology

Purpose: To study the mechanism involved in the anti-cholecystitis effect the Tibetan medicine “Dida”, using network pharmacology-integrated molecular docking simulationsMethods: In this investigation, the bioactive compounds of Dida were collected, network pharmacology methods to predict their targets, and networks were constructed through GO and KEGG pathway analyses. The potential binding between the bioactive compounds and the targets were demonstrated using molecular docking simulations.Results: A total of 12 bioactive compounds and 50 key targets of Dida were identified. Two networks, namely, protein–protein interaction (PPI) network of cholecystitis targets, and compound–target– pathway network, were established. Network analysis showed that 10 targets (GAPDH, AKT1, CASP3, EGFR, TNF, MAPK3, MAPK1, HSP90AA1, STAT3, and BCL2L1) may be the therapeutic targets of Dida in cholecystitis. Analysis of the KEGG pathway indicated that the anti-cholecystitis effect of Dida may its regulation of a few crucial pathways, such as apoptosis, as well as toll-like  receptor, T cell receptor, NOD-like receptor, and MAPK signaling pathways. Furthermore, molecular docking simulation revealed that CASP3, CAPDH, HSP90AA1, MAPK3, MAPK1, and STAT3 had well-characterized interactions with the corresponding compounds.Conclusion: The mechanism underlying the anti-cholecystitis effect of Dida has been successfully predicted and verified using a combination of network pharmacology and molecular docking simulation. This provides a firm basis for the experimental verification of the use of Dida in the treatment of cholecystitis, and enhances its rational application in clinical practice. Keywords: Tibetan medicine, Dida, Cholecystitis, Mechanism, Network pharmacology, Molecular docking simulatio

Identifying the Riemann zeros by periodically driving a single qubit

The Riemann hypothesis, one of the most important open problems in pure mathematics, implies the most profound secret of prime numbers. One of the most interesting approaches to solve this hypothesis is to connect the problem with the spectrum of the physical Hamiltonian of a quantum system. However, none of the proposed quantum Hamiltonians have been experimentally feasible.Here, we report the first experiment to identify the first non-trivial zeros of the Riemann zeta function and the first two zeros of P\'olya's fake zeta function, using a novel Floquet method, through properly designed periodically driving functions. According to this method, the zeros of these functions are characterized by the occurrence of crossings of quasi-energies when the dynamics of the system are frozen. The experimentally obtained zeros are in excellent agreement with their exact values. Our study provides the first experimental realization of the Riemann zeros, which may provide new insights into this fundamental mathematical problem.Comment: 5 pages, 7 figure

Finite Element Simulations of Bone Temperature Rise During Bone Drilling Based on a Bone Analog

Abstract Many researchers have attempted to measure bone temperature using thermocouples; however, the limitations of thermocouples make it difficult to determine the bone temperature in the immediate vicinity of a drilled hole. This study develops a method of analysis that can be used to obtain the bone temperature rise in the immediate vicinity of a drilled hole. A three-dimensional finite element model, based on a bone analog, was used to simulate bone temperature rise during a drilling process. The effect of drilling speed on bone temperature distribution is discussed. The results indicate that, for a constant drill feed rate, the drill bit with a higher rotation speed can cause a noticeable increase in bone temperature as well as the size of the thermally affected zone. Based on the numerical results, an empirical equation is proposed to estimate the peak bone temperature using the value of the rotation drilling speed. The maximum difference between the peak bone temperatures predicted by the proposed equation and those obtained from the numerical model is less than 3.5%

An animal model of SARS produced by infection of Macaca mulatta with SARS coronavirus.

A new SARS animal model was established by inoculating SARS coronavirus (SARS-CoV) into rhesus macaques (Macaca mulatta) through the nasal cavity. Pathological pulmonary changes were successively detected on days 5-60 after virus inoculation. All eight animals showed a transient fever 2-3 days after inoculation. Immunological, molecular biological, and pathological studies support the establishment of this SARS animal model. Firstly, SARS-CoV-specific IgGs were detected in the sera of macaques from 11 to 60 days after inoculation. Secondly, SARS-CoV RNA could be detected in pharyngeal swab samples using nested RT-PCR in all infected animals from 5 days after virus inoculation. Finally, histopathological changes of interstitial pneumonia were found in the lungs during the 60 days after viral inoculation: these changes were less marked at later time points, indicating that an active healing process together with resolution of an acute inflammatory response was taking place in these animals. This animal model should provide insight into the mechanisms of SARS-CoV-related pulmonary disease and greatly facilitate the development of vaccines and therapeutics against SARS