Design and Analysis of Field Experiments Incorporating Local and Remote Effects of Treatments

Design and analysis of field experiments in the presence of local and remote treatment effects are considered. The design criteria are optimality and balance for estimating local and remote effects. A nonlinear model, where remote effects are assumed to be proportional to the local effects, has been discussed.     

Relative efficiency of unequal versus equal cluster sizes in cluster randomized trials using generalized estimating equation models

There is growing interest in conducting cluster randomized trials (CRTs). For simplicity in sample size calculation, the cluster sizes are assumed to be identical across all clusters. However, equal cluster sizes are not guaranteed in practice. Therefore, the relative efficiency (RE) of unequal versus equal cluster sizes has been investigated when testing the treatment effect. One of the most important approaches to analyze a set of correlated data is the generalized estimating equation (GEE) proposed by Liang and Zeger, in which the “working correlation structure” is introduced and the association pattern depends on a vector of association parameters denoted by ρ. In this paper, we utilize GEE models to test the treatment effect in a two‐group comparison for continuous, binary, or count data in CRTs. The variances of the estimator of the treatment effect are derived for the different types of outcome. RE is defined as the ratio of variance of the estimator of the treatment effect for equal to unequal cluster sizes. We discuss a commonly used structure in CRTs—exchangeable, and derive the simpler formula of RE with continuous, binary, and count outcomes. Finally, REs are investigated for several scenarios of cluster size distributions through simulation studies. We propose an adjusted sample size due to efficiency loss. Additionally, we also propose an optimal sample size estimation based on the GEE models under a fixed budget for known and unknown association parameter (ρ) in the working correlation structure within the cluster.     

Wind and fairness in ski jumping: A computer modelling analysis

Wind is closely associated with the discussion of fairness in ski jumping. To counter-act its influence on the jump length, the International Ski Federation (FIS) has introduced a wind compensation approach. We applied three differently accurate computer models of the flight phase with wind (M1, M2, and M3) to study the jump length effects of various wind scenarios. The previously used model M1 is accurate for wind blowing in direction of the flight path, but inaccuracies are to be expected for wind directions deviating from the tangent to the flight path. M2 considers the change of airflow direction, but it does not consider the associated change in the angle of attack of the skis which additionally modifies drag and lift area time functions. M3 predicts the length effect for all wind directions within the plane of the flight trajectory without any mathematical simplification. Prediction errors of M3 are determined only by the quality of the input data: wind velocity, drag and lift area functions, take-off velocity, and weight. For comparing the three models, drag and lift area functions of an optimized reference jump were used. Results obtained with M2, which is much easier to handle than M3, did not deviate noticeably when compared to predictions of the reference model M3. Therefore, we suggest to use M2 in future applications. A comparison of M2 predictions with the FIS wind compensation system showed substantial discrepancies, for instance: in the first flight phase, tailwind can increase jump length, and headwind can decrease it; this is opposite of what had been anticipated before and is not considered in the current wind compensation system in ski jumping.     

Can altered muscle synergies control unimpaired gait?

Recent studies have postulated that the human motor control system recruits groups of muscles through low-dimensional motor commands, or muscle synergies. This scheme simplifies the neural control problem associated with the high-dimensional structure of the neuromuscular system. Several lines of evidence have suggested that neurological injuries, such as stroke or cerebral palsy, may reduce the dimensions that are available to the motor control system, and these altered dimensions or synergies are thought to contribute to impaired walking patterns. However, no study has investigated whether impaired low-dimensional control spaces necessarily lead to impaired walking patterns. In this study, using a two-dimensional model of walking, we developed a synergy-based control framework that can simulate the dynamics of walking. The simulation analysis showed that a synergy-based control scheme can produce well-coordinated movements of walking matching unimpaired gait. However, when the dimensions available to the controller were reduced, the simplified emergent pattern deviated from unimpaired gait. A system with two synergies, similar to those seen after neurological injury, could not produce an unimpaired walking pattern. These findings provide further evidence that altered muscle synergies can contribute to impaired gait patterns and may need to be directly addressed to improve gait after neurological injury.     

The effect of temperature on bacterial degradation of EDTA in pH-auxostat

The effect of temperature on the maximum specific growth rate and the cell yield was studied during cultivation of two bacterial strains (LPM-4 and Pseudomonas sp. LPM-410) on EDTA under unlimited cell growth conditions in a pH-auxostat. Both strains displayed linear dependence of reciprocal biomass yield against reciprocal specific growth rate, from which the values of rate of substrate expenditure for cell maintenance and the “maximum” yield (i.e., hypothetical yield without cell maintenance processes) were estimated. Analysis of the maximum yield values based on mass–energy balance theory suggested that oxidation of the carboxylic acid side chains of EDTA by a monooxygenase had zero or low energetic efficiency. An Arrhenius equation with different values of Arrhenius parameters within different temperature ranges gave a good fit with the temperature dependence of both growth rate and biomass yield. Specific growth rates of both strains showed a more pronounced temperature dependence than did the cell yields. A possible kinetic mechanism was suggested which might be responsible for the modes of the temperature dependences of specific growth rate and yield that were found. The mechanism is based on a hypothetical key substance governing the metabolic flows, which is formed in a zero-order reaction and destroyed in a first-order reaction, both rate constants depending on temperature according to the Arrhenius law.     

Assessing the Effect of the Best Treatment. A Non-parametric Inference Problem

For patients of a certain type, a number of treatments are available. The effect of each such treatment is assumed to be described by a shift model; it is, however, admitted that there may be an interaction between patient and treatment, meaning in particular that the treatment which is best for one patient is not necessarily best for another. The problem is the following: if each patient is given the treatment which is optimal for that particular patient, will this produce a significant effect and, if so, how large is the effect?     

MV-mimicking micelles loaded with PEG-serine-ACP nanoparticles to achieve biomimetic intra/extra fibrillar mineralization of collagen in vitro

Since their discovery, matrix vesicles (MVs) containing minerals have received considerable attention for their role in the mineralization of bone, dentin and calcified cartilage. Additionally, MVs' association with collagen fibrils, which serve as the scaffold for calcification in the organic matrix, has been repeatedly highlighted. The primary purpose of the present study was to establish a MVs–mimicking model (PEG-S-ACP/micelle) in vitro for studying the exact mechanism of MVs-mediated extra/intra fibrillar mineralization of collagen in vivo. In this study, high-concentration serine was used to stabilize the amorphous calcium phosphate (S-ACP), which was subsequently mixed with polyethylene glycol (PEG) to form PEG-S-ACP nanoparticles. The nanoparticles were loaded in the polysorbate 80 micelle through a micelle self-assembly process in an aqueous environment. This MVs–mimicking model is referred to as the PEG-S-ACP/micelle model. By adjusting the pH and surface tension of the PEG-S-ACP/micelle, two forms of minerals (crystalline mineral nodules and ACP nanoparticles) were released to achieve the extrafibrillar and intrafibrillar mineralization, respectively. This in vitro mineralization process reproduced the mineral nodules mediating in vivo extrafibrillar mineralization and provided key insights into a possible mechanism of biomineralization by which in vivo intrafibrillar mineralization could be induced by ACP nanoparticles released from MVs. Also, the PEG-S-ACP/micelle model provides a promising methodology to prepare mineralized collagen scaffolds for repairing bone defects in bone tissue engineering.