Response‐adaptive designs for binary responses: How to offer patient benefit while being robust to time trends?

Response‐adaptive randomisation (RAR) can considerably improve the chances of a successful treatment outcome for patients in a clinical trial by skewing the allocation probability towards better performing treatments as data accumulates. There is considerable interest in using RAR designs in drug development for rare diseases, where traditional designs are not either feasible or ethically questionable. In this paper, we discuss and address a major criticism levelled at RAR: namely, type I error inflation due to an unknown time trend over the course of the trial. The most common cause of this phenomenon is changes in the characteristics of recruited patients—referred to as patient drift. This is a realistic concern for clinical trials in rare diseases due to their lengthly accrual rate. We compute the type I error inflation as a function of the time trend magnitude to determine in which contexts the problem is most exacerbated. We then assess the ability of different correction methods to preserve type I error in these contexts and their performance in terms of other operating characteristics, including patient benefit and power. We make recommendations as to which correction methods are most suitable in the rare disease context for several RAR rules, differentiating between the 2‐armed and the multi‐armed case. We further propose a RAR design for multi‐armed clinical trials, which is computationally efficient and robust to several time trends considered.     

Meningococcal serogroup B outbreak response University of Wisconsin-Madison

A meningococcal serogroup B (MenB) outbreak at a large public university prompted an emergency response to immunize undergraduates. Objective: To report on a successful meningococcal serogroup B (MenB) vaccine clinic response at a large public university. Methods: We assembled the team leaders to write this case report. Results: Activation of the emergency plan and points of dispensing required cooperation of many units on campus under the leadership of university health officials with support from Centers for Disease Control and Prevention, state division of public health and the city-county health department. Significant efforts to provide consistent messages to students and parents regarding the outbreak and the availability of the MenB vaccines were made. Volunteers were recruited to staff the clinics alongside university healthcare providers. Over 22,000 doses of vaccine were administered. Conclusion: We report our experience and lessons learned which may be helpful to universities in preventing and responding to disease outbreaks.     

Building a Human Health Risk Assessment Ontology (RsO): A Proposed Framework

Over the last decade the health and environmental research communities have made significant progress in collecting and improving access to genomic, toxicology, exposure, health, and disease data useful to health risk assessment. One of the barriers to applying these growing volumes of information in fields such as risk assessment is the lack of informatics tools to organize, curate, and evaluate thousands of journal publications and hundreds of databases to provide new insights on relationships among exposure, hazard, and disease burden. Many fields are developing ontologies as a way of organizing and analyzing large amounts of complex information from multiple scientific disciplines. Ontologies include a vocabulary of terms and concepts with defined logical relationships to each other. Building from the recently published exposure ontology and other relevant health and environmental ontologies, this article proposes an ontology for health risk assessment (RsO) that provides a structural framework for organizing risk assessment information and methods. The RsO is anchored by eight major concepts that were either identified by exploratory curations of the risk literature or the exposure‐ontology working group as key for describing the risk assessment domain. These concepts are: (1) stressor, (2) receptor, (3) outcome, (4) exposure event, (5) dose‐response approach, (6) dose‐response metric, (7) uncertainty, and (8) measure of risk. We illustrate the utility of these concepts for the RsO with example curations of published risk assessments for ionizing radiation, arsenic in drinking water, and persistent pollutants in salmon.     

Overcoming the ‘tyranny of the urgent’: integrating gender into disease outbreak preparedness and response

ABSTRACT

This article contributes to discussions on the gender dimensions of disease outbreaks, and preparedness policies and responses, by providing a multi-level analysis of gender-related gaps, particularly illustrating how the failure to challenge gender assumptions and incorporate gender as a priority at the global level has national and local impacts. The implications of neglecting gender dynamics, as well as the potential of equity-based approaches to disease outbreak responses, is illustrated through a case study of the Social Enterprise Network for Development (SEND) Sierra Leone, a non-government organisation (NGO) based in Kailahun, during the Ebola outbreak.     

An improved cluster two-stage randomized response model

In this paper, Abdelfatah and Mazloum's (2015) two-stage randomized response model is extended to unequal probability sampling and stratified unequal probability sampling, both with and without replacement. The extended models result in more efficient estimators than Lee et al.'s (2014) estimators of the proportion of the population having a sensitive attribute.     

Improved randomized response in additive scrambling models

Randomized response models deal with stigmatizing variables appearing in health surveys. Additive and subtractive scrambling in split sample and double response yield unbiased mean and sensitivity estimators of high precision. The split sample method is protective of privacy. The double response method is as protective only conditionally. To achieve the maximum efficiency, the scrambling variables must be similar to each other and the probability of obtaining a true response must be as large as possible. The randomized response procedures yield more efficient estimates of the average total number of classes missed by university students.     

尼采哲学中的虚无主义概念

虚无主义是尼采哲学的核心观念之一.学术界大多从消极的、单-的角度理解这一概念,实际上,虚无主义被尼采赋予了众多的复杂内涵：它既指旧价值本身的无价值,又指价值消解后意义的真空;它可指思想武器,又是思想目标.虚无主义是尼采观察世界的最深刻的心理背景.尼采以虚无主义作为批判武器,对欧洲传统价值 ——基督教、道德及其科学理性文明进行批判,对自己的核心观念——权力意志也进行批判.尼采哲学思想发轫于虚无主义,超越了虚无主义而最终不能摆脱虚无主义.虚无主义对尼采具有本体论的意义.     

马克思的现代性哲学批判及其当代价值

在马克思唯物史观的哲学视野下,现代性无论是在社会存在还是在社会意识层面,都呈现出尖锐的矛盾。就现代性诸矛盾现象的深刻本质或其哲学基础而言,乃是近代形而上学的理性主义。马克思的现代性哲学批判,是对资本主义现代性的形而上学哲学思维方式的彻底颠覆,对目前我国所面临的现代性建构具有重要的方法论价值。在社会主义的现代性建构过程中,必须克服形而上学的哲学思维方式,最终实现社会主义生产力的普遍、高度发展与人的自由、全面发展的辩证统一。     

Evaluation of Inhaled Versus Deposited Dose Using the Exponential Dose‐Response Model for Inhalational Anthrax in Nonhuman Primate,Rabbit, and Guinea Pig

The application of the exponential model is extended by the inclusion of new nonhuman primate (NHP), rabbit, and guinea pig dose‐lethality data for inhalation anthrax. Because deposition is a critical step in the initiation of inhalation anthrax, inhaled doses may not provide the most accurate cross‐species comparison. For this reason, species‐specific deposition factors were derived to translate inhaled dose to deposited dose. Four NHP, three rabbit, and two guinea pig data sets were utilized. Results from species‐specific pooling analysis suggested all four NHP data sets could be pooled into a single NHP data set, which was also true for the rabbit and guinea pig data sets. The three species‐specific pooled data sets could not be combined into a single generic mammalian data set. For inhaled dose, NHPs were the most sensitive (relative lowest LD₅₀) species and rabbits the least. Improved inhaled LD₅₀s proposed for use in risk assessment are 50,600, 102,600, and 70,800 inhaled spores for NHP, rabbit, and guinea pig, respectively. Lung deposition factors were estimated for each species using published deposition data from Bacillus spore exposures, particle deposition studies, and computer modeling. Deposition was estimated at 22%, 9%, and 30% of the inhaled dose for NHP, rabbit, and guinea pig, respectively. When the inhaled dose was adjusted to reflect deposited dose, the rabbit animal model appears the most sensitive with the guinea pig the least sensitive species.     

在“思辨”与自然的现实观照之间——关于“自然辩证法”的思考

黑格尔辩证法"否定"与其神秘形式存在着对立,其内在革命性同样被恩格斯"否定性"的汲取,恩格斯自然辩证法延展了黑格尔的逻辑与历史研究方法,更从思辨走向了历史现实,从而奠定与确立人在"辩证法"与"自然"中的地位,确立了自然辩证体系存在的意义,使得自然辩证法也成为"人"的哲学而非"精神"哲学的一部分,作为实践、开放的哲学体系,自然辩证法的理论生命力存在于恩格斯对黑格尔哲学汲取的思辨内核中,更存在于对自然的现实观照之中。