Notes on Hypothesis Testing under a Single-Stage Design in Phase II Trial

A primary objective of a phase II trial is to determine future development is warranted for a new treatment based on whether it has sufficient activity against a specified type of tumor. Limitations exist in the commonly-used hypothesis setting and the standard test procedure for a phase II trial. This study reformats the hypothesis setting to mirror the clinical decision process in practice. Under the proposed hypothesis setting, the critical points and the minimum required sample size for a desired power of finding a superior treatment at a given α -level are presented. An example is provided to illustrate how the power of finding a superior treatment by accounting for a secondary endpoint may be improved without inflating the given Type I error

Fixed or mobile-bearing total knee arthroplasty

Fixed and mobile-bearing in total knee arthroplasty are still discussed controversially. In this article, biomechanical and clinical aspects in both fixed and mobile-bearing designs were reviewed. In biomechanical aspect, the mobile-bearing design has proved to provide less tibiofemoral contact stresses under tibiofemoral malalignment conditions. It also provides less wear rate in in-vitro simulator test. Patients with posterior stabilized mobile-bearing knees had more axial tibiofemoral rotation than patients with posterior stabilized fixed-bearing knees during gait as well as in a deep knee-bend activity. However, in clinical aspect, the mid-term or long-term survivorship of mobile-bearing knees has no superiority over that of fixed-bearing knees. The theoretical advantages for mobile-bearing design to provide a long-term durability have not been demonstrated by any outcome studies. Finally, the fixed-bearing design with all-polyethylene tibial component is suggested for relatively inactive, elder people. The mobile-bearing design is suggested for younger or higher-demand patients due to the potential for reduced polyethylene wear and more normal kinematics response after joint replacement. For younger surgeon, the fixed-bearing design is suggested due to less demand for surgical technique. For experienced surgeon, one familiar surgical protocol and instrumentation is suggested rather than implant design, either fixed-bearing or mobile-bearing

Prescriptions of Chinese Herbal Medicines for Insomnia in Taiwan during 2002

Chinese herbal medicine (CHM) has been commonly used for treating insomnia in Asian countries for centuries. The aim of this study was to conduct a large-scale pharmaco-epidemiologic study and evaluate the frequency and patterns of CHM use in treating insomnia. We obtained the traditional Chinese medicine (TCM) outpatient claims from the National Health Insurance in Taiwan for the year 2002. Patients with insomnia were identified from the diagnostic code of International Classification of Disease among claimed visiting files. Corresponding prescription files were analyzed, and an association rule was applied to evaluate the co-prescription of CHM. Results showed that there were 16 134 subjects who visited TCM clinics for insomnia in Taiwan during 2002 and received a total of 29 801 CHM prescriptions. Subjects between 40 and 49 years of age comprised the largest number of those treated (25.3%). In addition, female subjects used CHMs for insomnia more frequently than male subjects (female : male = 1.94 : 1). There was an average of 4.8 items prescribed in the form of either an individual Chinese herb or formula in a single CHM prescription for insomnia. Shou-wu-teng (Polygonum multiflorum) was the most commonly prescribed single Chinese herb, while Suan-zao-ren-tang was the most commonly prescribed Chinese herbal formula. According to the association rule, the most commonly prescribed CHM drug combination was Suan-zao-ren-tang plus Long-dan-xie-gan-tang, while the most commonly prescribed triple drug combination was Suan-zao-ren-tang, Albizia julibrissin, and P. multiflorum. Nevertheless, further clinical trials are needed to evaluate the efficacy and safety of these CHMs for treating insomnia

Prism-Based Sunlight Concentrator Layout: A Genetic Algorithm Solution

Solar energy is a promising source of energy because it is abundant and harmless to the environment. One of the critical issues involving solar energy is the layout design of sunlight concentrators. This study presents a computational method for reforming the layout of a special sunlight concentrator that consists of a set of prisms to significantly enhance its light intensity. Sunlight movement toward the prisms is modeled, and a genetic algorithm is applied to find a good concentrator layout. Experiments under various light transmission rates validate the performance of our proposed method. The proposed optimal sunlight concentrator layout improves the intensity of light by 55%

Hazard Analysis of Critical Control Points Assessment as a Tool to Respond to Emerging Infectious Disease Outbreaks

Highly pathogenic avian influenza virus (HPAI) strain H5N1 has had direct and indirect economic impacts arising from direct mortality and control programmes in over 50 countries reporting poultry outbreaks. HPAI H5N1 is now reported as the most widespread and expensive zoonotic disease recorded and continues to pose a global health threat. The aim of this research was to assess the potential of utilising Hazard Analysis of Critical Control Points (HACCP) assessments in providing a framework for a rapid response to emerging infectious disease outbreaks. This novel approach applies a scientific process, widely used in food production systems, to assess risks related to a specific emerging health threat within a known zoonotic disease hotspot. We conducted a HACCP assessment for HPAI viruses within Vietnam’s domestic poultry trade and relate our findings to the existing literature. Our HACCP assessment identified poultry flock isolation, transportation, slaughter, preparation and consumption as critical control points for Vietnam’s domestic poultry trade. Introduction of the preventative measures highlighted through this HACCP evaluation would reduce the risks posed by HPAI viruses and pressure on the national economy. We conclude that this HACCP assessment provides compelling evidence for the future potential that HACCP analyses could play in initiating a rapid response to emerging infectious diseases

Identifying Hendra Virus Diversity in Pteropid Bats

Hendra virus (HeV) causes a zoonotic disease with high mortality that is transmitted to humans from bats of the genus Pteropus (flying foxes) via an intermediary equine host. Factors promoting spillover from bats to horses are uncertain at this time, but plausibly encompass host and/or agent and/or environmental factors. There is a lack of HeV sequence information derived from the natural bat host, as previously sequences have only been obtained from horses or humans following spillover events. In order to obtain an insight into possible variants of HeV circulating in flying foxes, collection of urine was undertaken in multiple flying fox roosts in Queensland, Australia. HeV was found to be geographically widespread in flying foxes with a number of HeV variants circulating at the one time at multiple locations, while at times the same variant was found circulating at disparate locations. Sequence diversity within variants allowed differentiation on the basis of nucleotide changes, and hypervariable regions in the genome were identified that could be used to differentiate circulating variants. Further, during the study, HeV was isolated from the urine of flying foxes on four occasions from three different locations. The data indicates that spillover events do not correlate with particular HeV isolates, suggesting that host and/or environmental factors are the primary determinants of bat-horse spillover. Thus future spillover events are likely to occur, and there is an on-going need for effective risk management strategies for both human and animal health

Janus monolayers of transition metal dichalcogenides.

Structural symmetry-breaking plays a crucial role in determining the electronic band structures of two-dimensional materials. Tremendous efforts have been devoted to breaking the in-plane symmetry of graphene with electric fields on AB-stacked bilayers or stacked van der Waals heterostructures. In contrast, transition metal dichalcogenide monolayers are semiconductors with intrinsic in-plane asymmetry, leading to direct electronic bandgaps, distinctive optical properties and great potential in optoelectronics. Apart from their in-plane inversion asymmetry, an additional degree of freedom allowing spin manipulation can be induced by breaking the out-of-plane mirror symmetry with external electric fields or, as theoretically proposed, with an asymmetric out-of-plane structural configuration. Here, we report a synthetic strategy to grow Janus monolayers of transition metal dichalcogenides breaking the out-of-plane structural symmetry. In particular, based on a MoS2 monolayer, we fully replace the top-layer S with Se atoms. We confirm the Janus structure of MoSSe directly by means of scanning transmission electron microscopy and energy-dependent X-ray photoelectron spectroscopy, and prove the existence of vertical dipoles by second harmonic generation and piezoresponse force microscopy measurements

H5N1 Outbreaks and Enzootic Influenza

Highly pathogenic H5N1 influenza viruses continue to evolve and increase their geographic and host range

Hendra Virus Infection Dynamics in Australian Fruit Bats

Hendra virus is a recently emerged zoonotic agent in Australia. Since first described in 1994, the virus has spilled from its wildlife reservoir (pteropid fruit bats, or ‘flying foxes’) on multiple occasions causing equine and human fatalities. We undertook a three-year longitudinal study to detect virus in the urine of free-living flying foxes (a putative route of excretion) to investigate Hendra virus infection dynamics. Pooled urine samples collected off plastic sheets placed beneath roosting flying foxes were screened for Hendra virus genome by quantitative RT-PCR, using a set of primers and probe derived from the matrix protein gene. A total of 1672 pooled urine samples from 67 sampling events was collected and tested between 1 July 2008 and 30 June 2011, with 25% of sampling events and 2.5% of urine samples yielding detections. The proportion of positive samples was statistically associated with year and location. The findings indicate that Hendra virus excretion occurs periodically rather than continuously, and in geographically disparate flying fox populations in the state of Queensland. The lack of any detection in the Northern Territory suggests prevalence may vary across the range of flying foxes in Australia. Finally, our findings suggest that flying foxes can excrete virus at any time of year, and that the apparent seasonal clustering of Hendra virus incidents in horses and associated humans (70% have occurred June to October) reflects factors other than the presence of virus. Identification of these factors will strengthen risk minimization strategies for horses and ultimately humans