A case study in identifying targeted patients population in major depressive disorder by enhanced enrichment design

Despite advances in clinical trial design, failure rates near 80% in phase 2 and 50% in phase 3 have recently been reported. The challenges to successful drug development are particularly acute in central nervous system trials such as for pain, schizophrenia, mania, and depression because high‐placebo response rates lessen assay sensitivity, diminish estimated treatment effect sizes, and thereby decrease statistical power. This paper addresses the importance of rigorous patient selection in major depressive disorder trials through an enhanced enrichment paradigm. This approach led to a redefinition of an ongoing, blinded phase 3 trial algorithm for patient inclusion (1) to eliminate further randomization of transient placebo responders and (2) to exclude previously randomized transient responders from the primary analysis of the double blind phase of the trial. It is illustrated for a case study for the comparison between brexpiprazole + antidepressant therapy and placebo + antidepressant therapy. Analysis of the primary endpoint showed that efficacy of brexpiprazole versus placebo could not be established statistically if the original algorithm for identification of placebo responders was used, but the enhanced enrichment approach did statistically demonstrate efficacy. Additionally, the enhanced enrichment approach identified a target population with a clinically meaningful treatment effect. Through its successful identification of a target population, the innovative enhanced enrichment approach enabled the demonstration of a positive treatment effect in a very challenging area of depression research.     

生物安全实验室活毒废水处理工艺研究

目的在借鉴吸收国外生物安全实验室（BSL）活毒废水处理工艺技术的基础上,结合我国国情,研究开发节能、环保、安全型成套处理技术工艺和设备,实现关键技术和产品国产化。方法处理系统采用序批式工艺,通过高温高压方式消毒灭菌。结果该处理工艺的技术指标：灭菌温度100～150℃（可调）,加热时间≤30rain,灭菌时间30—120min（可调）;处理后排放指标：活微生物为0,温度≤40℃,pH=6～9。结论该处理工艺整体设计简便灵活,符合BSL设计越简单越安全的理念,适合我国国情,可用于生物安全三级、四级实验室（BSL一3,-4）活毒废水处理。     

商标平行进口与权利用尽理论

论及商标平行进口,学者普遍引用权利用尽理论探讨商标平行进口是否具有合法性。从商标与无形财产和其他知识产权的区别来看,仅依权利用尽理论解释商标平行进口是否具有合法性就会略显片面。从商标的功能、商标专用权的法律性质等多重角度出发,为商标平行进口定性应该会更全面、客观。同时,在区域贸易协定框架下对商标平行进口进行协调,权利的互惠用尽或许将会成为可行的方案。     

Pre-commitment in gambling: a review of the empirical evidence

Norway, a Canadian province and Australia have introduced, or are considering introducing, voluntary or mandatory pre-commitment systems for electronic gaming machines. This paper critically reviews the empirical literature evaluating the effectiveness of such systems as a responsible gambling strategy. A literature search identified 17 relevant peer- and non-peer-reviewed publications. Self-report data suggests the majority of gamblers are positively predisposed to the concept of pre-commitment but non-problem and low-risk gamblers regard the system as personally unnecessary. Overall, studies reported variable findings relating to adherence to money limits and expenditure. Few gamblers appear to use options to set time limits. Methodological flaws such as low participation rates, compromised data integrity resulting from card sharing and failure to control for concurrent gambling outside trials limit conclusions drawn regarding the effectiveness of pre-commitment. It is recommended that further systematic trials should be implemented to determine the impact of pre-commitment systems on gamblers' behaviour.     

Too close to home? The relationships between residential distance to venue and gambling outcomes

Although gambling accessibility is generally viewed as a multidimensional construct, few studies have successfully untangled the specific role of spatial accessibility in determining gambling outcomes relative to other forms (i.e. temporal, social and psychological). In this paper, we explore the association between gambling outcomes and the distance travelled from a person's home to their most-frequented gambling venue. To this end, we conducted a geocoded mail survey of 7044 households in the Northern Territory of Australia. We employed a geographic information system to calculate the network distance from each household to all visited electronic gaming machine (EGM) venues (n = 64). Multivariate regression modelling revealed that, when adjusted for individual and neighbourhood-level characteristics, frequency of venue visitation and gambling participation were inversely related to residential distance from venue. There was no additional distance effect for problem gambling. Spatial accessibility of EGMs is an important determinant of gambling risk and should be explicitly considered by regulators.     

南宋词科对南宋骈文发展的影响

南宋词科的恢复和改革不仅造就了又一个骈文繁荣时期的到来,而且对南宋骈文的发展有着深刻的影响,促使南宋骈文朝着格律更加严格、注重技巧形式的方向发展。     

国际贸易背景下专利权用尽原则探究——兼论平行进口问题

权利用尽原则是立法者在平衡知识产权人专有权和社会公众利益的基础上提出的。作为对权利人行使专有权的有效限制,该原则首先由美国司法机关提出,随后得到许多大陆法系国家的援引。尽管世界各国在其实践中普遍采用了专利权用尽原则,但不同国家对专利权用尽原则的法律基础有不同的理解,产生种种不同的理论,导致对类似案件的处理出现不一致的结论。由于专利权用尽原则以及与此相关的平行进口问题对世界各国利益有重要影响,借鉴各国经验对我国国际贸易中产品的进出口以及我国专利法相关条文的完善具有重要意义。     

Problem Gambling and the Circumstances Facing Older People

Local gambling venues are an important contemporary context for older people's gambling in many parts of the world typically being more accessible to this segment of the population than traditional, centralised gambling venues, such as casinos. This study, undertaken in South East Queensland, analyses older people's electronic gaming machine (EGM) behaviour and motivations, specifically in the context of licensed social and recreational clubs-a popular local gambling venue in many parts of Australia. The study gathered data via a postal survey of 80 managers of licensed clubs, interviews with Gambling Help services and a survey of 414 people aged 60+ who regularly play EGMs, self-administered on site at local clubs. The analysis undertaken suggests that certain age-related circumstances of older people-such as being without a partner, having a disability that impacts on everyday activities, having a low annual income, and no longer participating in the workforce-are associated with higher overall levels of motivation for playing EGMs and greater reliance on EGMs to meet social, recreational and mental health needs. Over a quarter of the older people surveyed (27%) reported drawing on their savings to fund their EGM gambling. Certain categories of older people, including those who were without a partner and those with a disability, were more likely to report drawing on their savings to fund EGM play and betting more than they could afford to lose, pointing to age-related vulnerabilities older people may experience to the negative impacts of gambling given the greater likelihood of their dependency on smaller, fixed incomes. The explanatory contribution of a range of demographic and motivational variables on problem/moderate risk gambling status was computed via a logistic regression model. Younger age (60-69), male gender, single marital status and being motivated to play EGMs to experience excitement and to win money all emerged as significant predictors in the model.     

化解管理理论与实践脱节的两种模式:串联型关联与并联型关联

理论与实践的关系应该是既分离,又关联的,典型的关联模式有串联型关联和并联型关联2种.当前管理学界的很多研究成果不属于这2种关联模式的任一种,它们属于管理理论与实践脱节.根据管理学的学科属性和发展阶段判断,未来可以借鉴或借助这2种关联模式,化解或缓解管理理论与实践脱节问题.     

Optimal Inventory Control with Retail Pre‐Packs

A pre‐pack is a collection of items used in retail distribution. By grouping multiple units of one or more stock keeping units (SKU), distribution and handling costs can be reduced; however, ordering flexibility at the retail outlet is limited. This paper studies an inventory system at a retail level where both pre‐packs and individual items (at additional handling cost) can be ordered. For a single‐SKU, single‐period problem, we show that the optimal policy is to order into a “band” with as few individual units as possible. For the multi‐period problem with modular demand, the band policy is still optimal, and the steady‐state distribution of the target inventory position possesses a semi‐uniform structure, which greatly facilitates the computation of optimal policies and approximations under general demand. For the multi‐SKU case, the optimal policy has a generalized band structure. Our numerical results show that pre‐pack use is beneficial when facing stable and complementary demands, and substantial handling savings at the distribution center. The cost premium of using simple policies, such as strict base‐stock and batch‐ordering (pre‐packs only), can be substantial for medium parameter ranges.