Establishing Non-Inferiority of a New Treatment in a Three-Arm Trial: Apply a Step-Down Hierarchical Model in a Papulopustular Acne Study and an Oral Prophylactic Antibiotics Study

Clinical trials comparing a test treatment with an active control therapy have become very popular in drug and medical device development in the last decade. An active controlled trial without a placebo, however, exhibits some major challenges in design, analysis, and interpretation, such as the determination of the non-inferiority margin or the assumption of constancy condition. When there are no ethical concerns, the comparison of a test drug with placebo usually provides the most convincing proof of the efficacy of a new treatment. Therefore, it may be advisable to conduct a three-arm trial — including placebo, active control, and the new treatment - if it is ethically justifiable such as a papulopustular acne study and an oral prophylactic antibiotics study. In this paper, we propose a statistical methodology for a three-arm non-inferiority trial with binary outcomes. We adapt the step-down hierarchical hypotheses and give a three-step testing procedure which is more realistic in conducting a clinical trial. We derived an optimal sample size allocation rule in an ethical and reliable manner to minimize the total sample size and hence to shorten the duration of the trials. Real examples from a papulopustular acne study and an oral prophylactic antibiotics study are used to demonstrate our methodology

Modeling the impact of dam removal on the Formosan landlocked salmon in the context of climate change

Dam removal is analyzed as a conservation strategy for the Formosan landlocked salmon Oncorhynchus masou formosanus, a critically endangered species whose last refuge is the Wuling basin in central Taiwan. In a previous study, a stochastic age-structured simulation model was developed and used to assess the effectiveness of removing four dams in increasing salmon abundance in Kaoshan Stream in the context of climate change. Three check dams remain intact in Chichiawan Stream and one of its tributaries. In this study, the model is recalibrated for these regions and simulates the removal of each of these dams. Model analysis suggests that the combined effect of dam removal and climate change decreases the effectiveness of dam removal while increasing the negative impact of climate change on abundance. A simple graphing technique is presented for comparing the predicted impact of the removal of each dam under consideration. The model predicts that removing the dam in Chichiawan Stream has the largest potential for increasing the 2035 abundance, but only under narrow conditions of climate change and effectiveness of dam removal. The potential benefit from removing one of the tributary dams is smaller, but the conditions for reaching closer to its potential are less restrictive. This type of analysis is useful for dam removal management decisions regarding habitat restoration

Upstream migration and marine early life history of amphidromous gobies inferred from otolith increments and microchemistry

This Article challenges the standard account of the creation of the right of publicity. In the legal literature, the prevailing narrative is of the right of publicity being intimately linked to the commodification of celebrity. Ultimately, however, there is more to the story of the right of publicity than the decision to protect something of economic value. It took decades after it had become clear that celebrities could be valuable commercial spokespersons for lawmakers to agree to make the right inheritable, separate from the dignitary right of privacy, and potentially applicable to any economic, secondary use that invoked the celebrity plaintiff. It was only in the later part of the twentieth century, when American understandings of celebrity became rationalized and democratized, that the right of publicity was reconceptualized as a much more vigorous and far-reaching economic entitlement. By examining the discourse and political environment surrounding the emergence of this new right, I offer a new narrative for the right of publicity’s creation, provide some broader insights into the social forces that shape property rights, and contribute to a growing body of legal theory examining the public’s role in producing legal change

Sequence variations in the mitochondrial DNA control region and their implications for the phylogeny of the Cypriniformes

The mitochondrial DNA control region of six cobitids and two catostomids was sequenced and compared with sequences of other cypriniforms to study their sequence variations. The extended termination associated sequence (ETAS) domain, central domain, and conserved sequence block (CSB) domain were partitioned and the ETAS sequence, CSB-D, CSB-E, ECSB-F, CSB1, CSB2, and CSB3 were identified. It is suggested that the "hairpin" TACAT-ATGTA is the key sequence of ETAS and GACATA is the symbol of CSB1. Phylogenetic analysis based on the CSB domain showed that all cyprinids evolved as one monophyletic group, while the non-cyprinid Cypriniformes could be another monophyly that is in accordance with the hypothesis proposed by Siebert. Further analysis of the phylogeny of the Cobitoidei was also conducted and it is tentatively suggested that their relationships are Catostomidae + (Gyrinocheilidae + (Botiinae + (Homalopteridae + (Cobitinae + Nemacheilinae))))

Longitudinal variation in food sources and their use by aquatic fauna along a subtropical river in Taiwan

1. River food webs rely on two major food sources: autochthonous primary production within the river and allochthonous organic matter transferred to the river. We characterised the consumer communities and assessed the food sources of dominant consumers along a subtropical mountainous river (the Lanyang River of north-eastern Taiwan) at the catchment scale from the headwater to the estuary using natural abundances of stable carbon and nitrogen isotopes. 2. The downstream transport of fine particulate organic matter (FPOM) was two orders of magnitude greater than that of coarse particulate organic matter (CPOM). Transport of both materials increased from the headwater and reached a maximum in the midstream reach. CPOM composition exhibited a gradual shift from leaves and branches in the headwater, an area characterised by high canopy cover, to algae in the midstream reaches and marsh plants in the downstream reaches. 3. Consumer communities can be classified into two regional categories: the upland category in the headwater and upstream and midstream reaches and the lowland category comprised of samples from the downstream reach and estuary. The upland category revealed a clear and gradual seasonal shift in community composition, but a seasonal shift was not apparent for the lowland category. Nutrient concentrations and water temperature were the main factors explaining longitudinal and seasonal variations. 4. The use of sources of organic matter by dominant consumers along the Lanyang River was primarily determined by their availability. Riparian C3 plants were the major food sources in the headwater, upstream reach and estuary, but the contribution of periphyton increased in the upper midstream reach where the river flows through an agricultural area. In the lower midstream and downstream reaches, the contribution of riparian C4 plants became dominant. 5. The trophic transfer of organic materials in the Lanyang River may be influenced by the fast current velocity and by sewage nutrient loading in the river, both of which have important implications for predicting how the functioning of subtropical river food webs will respond to human-related changes in land use