A comparison of adaptive designs in clinical trials : when multiple treatments are tested in multiple stages

textIn recent times, there has been an increasing interest in adaptive designs for clinical trials. As opposed to conventional designs, adaptive designs allow flexible design adaptation in the middle of a trial based on accumulated data. Although various models have been developed using both frequentist and Bayesian perspectives, relative statistical performances of adaptive designs are somewhat controversial and little is known about those of Bayesian adaptive designs. Most comparison studies also focused on single experimental treatment rather than multiple experimental treatments. In this report, both frequentist and Baysian adaptive designs were compared in terms of statistical power by a simulation study, assuming the situation when multiple experimental treatments are tested in multiple stages. The designs included in the current study are group sequential design (frequentist), adaptive design based on combination tests (frequentist), and Bayesian adaptive design (Bayesian). Based upon the results under multiple scenarios, the Bayesian adaptive design showed the highest power, and the design based on combination tests performed better than group sequential designs when proper interim adaptation could be conducted to increase power.Statistic

Understanding Results-based Conditionality in Development Cooperation: A Comparative Case Analysis

Growing concerns over aid effectiveness in recent years have changed views around the aid contract, in part the role of aid conditionality and its perceived limits. This research seeks answers to questions on how results-based conditionality has been applied by exploring the multiple results-based aid programs through a case study from a comparative perspective. By investigating theoretical background on conditionality and reviewing recent discussions on results-based conditionality, this paper proposes a conceptual framework to discover key elements of results-based conditionality and to analyze them to see how the new approach may affect the process and result of aid delivery in comparison with traditional conditionality. The case analysis shows that results-based approach shifts the focus of aid by altering and strengthening the nature of incentives from various aspects of non-financial incentives, selectivity, payment, performance management, and sustainability with varying degrees. The paper concludes with challenges and limitations of results-based approach

Postural feedback responses scale with biomechanical constraints in human standing

We tested whether human postural responses can be described in terms of feedback control gains, and whether these gains are scaled by the central nervous system to accommodate biomechanical constraints. A feedback control model can describe postural responses for a wide range of perturbations, but biomechanical constraints—such as on the torque that can be exerted on the ground—make a single set of feedback gains inappropriate for all perturbations. To observe how postural responses change with perturbation magnitude, we applied fast, backward perturbations of magnitudes 3–15 cm to 13 healthy young volunteers (4 men, 9 women, aged 20–32 years). We used a 3-segment, sagittal-plane biomechanical model and a linear state feedback controller to reproduce the observed postural responses. Optimization was used to identify the best-fit feedback control gains for each trial. Results showed that trajectories of joint angles and joint torques were scaled with perturbation magnitude. This scaling occurred gradually, rather than abruptly changing at magnitudes where biomechanical constraints became active. Feedback gains were found to fit reasonably well with data ( R 2 =0.92) and to be multivariate and heterogenic in character, meaning that the torque produced at any joint is generally a function of motions not only at the same joint, but other joints as well. Hip gains increased and ankle gains decreased nearly linearly with perturbation magnitude, in accordance with biomechanical limitations on ground reaction torque. These results indicate that postural adjustments can be described as a single feedback control scheme, with scalable heterogenic gains that are adjusted according to biomechanical constraints.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46537/1/221_2003_Article_1674.pd

Association between Obesity and Physical Fitness, and Hemoglobin A1c Level and Metabolic Syndrome in Korean Adults

BACKGROUND: The purpose of the current study was to investigate the association of obesity level, physical fitness level, hemoglobin A1c (HbA1c) level and metabolic syndrome (MetS) risk factors among Korean adults. METHODS: A total of 557 adults (272 males and 285 females) who underwent medical check-up at local hospital were recruited. In addition to regular health check-up, cardiopulmonary fitness, muscular endurance were measured and their association were analyzed. RESULTS: The prevalence of MetS was 31.7% for males and 23.7% for females. Females with the higher muscular endurance had lower waist circumference, triglyceride level, and HbA1c level than those with the lower muscular endurance. Males with the higher level of cardiopulmonary fitness had lower diastolic blood pressure, lower high-sensitivity C-reactive protein level and higher high density lipoprotein cholesterol level than males with the lower level of cardiopulmonary fitness. Females with the higher level of cardiopulmonary fitness had lower body weight, body mass index, systolic blood pressure, and fasting blood glucose level than females with the lower level of cardiopulmonary fitness. Participants with the higher level of adiposity and the lower level of physical fitness were 5.26 times (95% confidence interval [CI], 2.19 to 12.62), 5.71 times (95% CI, 2.23 to 14.60) more likely to have MetS, respectively, in male and female compared to participants who were neither obese nor have the lower level of fitness. CONCLUSION: This study suggests that maintaining a healthy body weight as well as a certain level of fitness is important for the prevention of MetS.ope

Human standing postural control adjusts to biomechanical constraints: Is the CNS using multiple control plans, or a single flexible control plan?

For a variety of postural perturbations, balance disorder patients exhibit difficulties in producing appropriate postural adjustments governed by the central nervous system (CNS), but the nature and design of the postural control are unclear. This study addresses the biomechanics involved in postural adjustments, and proposes an interpretation that posture control can be described as a feedback scheme with scalable gains, rather than as a large number of feedforward responses triggered by a perturbation. Thirteen healthy young adults were subjected to backward perturbations of a support surface ranging from 1.5cm to 15cm applied for 273msec in two different initial postures: upright and forward lean. The results showed that kinematics and joint torques trajectories gradually scaled as a function of perturbation magnitudes and initial leans before the constraints imposed by maximum allowable ankle torque became active. This indicates that the biomechanical constraints are represented in a soft form. A linear time-invariant feedback control model was able to reproduce the adaptive postural responses to the above perturbations. Optimization was used to identify a linear feedback gain matrix for each trial. These gains were then implemented with gain scheduling based on perturbation magnitude and initial leans in a multivariate manner. To provide a parsimonious model of postural adjustments to biomechanical constraints, we developed an optimal control model penalizing the violation of the constraints within the objective function. The existence of a global objective reproducing postural adjustments implies that CNS control can be interpreted as a feedback process that takes into account body dynamics and biomechanical constraints. To examine the mechanism of multisensory processing in postural balance, we examined the frequency response function (FRF) of visually induced postural sway to sinusoidal visual field stimulus ranging from 0.075Hz to 1Hz. An optimal estimator was able to reproduce the FRF of the data. The results suggest that the CNS makes use of an internal representation of body dynamics, and integrates sensory information to estimate body orientation and movement.Ph.D.Applied SciencesBiomedical engineeringMechanical engineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/130366/2/3042152.pd

Frugal innovation for sustainable rural development

Sustainable development (SD) is a key concern for businesses, governments, and policymakers, with a particular emphasis on rural areas for achieving the sustainable development goals (SDGs). Frugal innovation offers a new and promising approach for sustainable rural development, but its specific contributions in this context remain underexplored in the existing literature. This study, therefore, aims to address this gap by examining how frugal innovation can contribute to sustainable development in rural areas. Using a grounded theory method and based on 22 interviews with key informants related to 13 cases of frugal enterprise in South Asia, this qualitative study attempts to accomplish the aim of the study. We developed a classification that identifies the increasing positive and decreasing negative parameters of SDGs to assess the extent to which frugal enterprises contribute to specific SDGs. Our findings show that frugal innovations tend to contribute more to SDGs than conventional products. However, certain SDGs have limited potential for frugal or other types of innovation to make significant contributions, as these goals are mainly intended to be assessed at the national level. Based on our findings, we discuss the implications and suggest future research avenues

Golf Swing Segmentation from a Single IMU Using Machine Learning

Golf swing segmentation with inertial measurement units (IMUs) is an essential process for swing analysis using wearables. However, no attempt has been made to apply machine learning models to estimate and divide golf swing phases. In this study, we proposed and verified two methods using machine learning models to segment the full golf swing into five major phases, including before and after the swing, from every single IMU attached to a body part. Proposed bidirectional long short-term memory-based and convolutional neural network-based methods rely on characteristics that automatically learn time-series features, including sequential body motion during a golf swing. Nine professional and eleven skilled male golfers participated in the experiment to collect swing data for training and verifying the methods. We verified the proposed methods using leave-one-out cross-validation. The results revealed average segmentation errors of 5–92 ms from each IMU attached to the head, wrist, and waist, accurate compared to the heuristic method in this study. In addition, both proposed methods could segment all the swing phases using only the acceleration data, bringing advantage in terms of power consumption. This implies that swing-segmentation methods using machine learning could be applied to various motion-analysis environments by dividing motion phases with less restriction on IMU placement

Understanding results-based conditionality in development cooperation: A comparative case analysis

Growing concerns over aid effectiveness in recent years have changed views around the aid contract, in part the role of aid conditionality and its perceived limits. This research seeks answers to questions on how results-based conditionality has been applied by exploring the multiple results based aid programs through a case study from a comparative perspective. By investigating theoretical background on conditionality and reviewing recent discussions on results-based conditionality, this paper proposes a conceptual framework to discover key elements of results-based conditionality and to analyze them to see how the new approach may affect the process and result of aid delivery in comparison with traditional conditionality. The case analysis shows that results-based approach shifts the focus of aid by altering and strengthening the nature of incentives from various aspects of nonfinancial incentives, selectivity, payment, performance management, and sustainability with varying degrees. The paper concludes with challenges and limitations of results-based approach