Ebola Virus Dose Response Model for Aerosolized Exposures: Insights from Primate Data

This study develops dose–response models for Ebolavirus using previously published data sets from the open literature. Two such articles were identified in which three different species of nonhuman primates were challenged by aerosolized Ebolavirus in order to study pathology and clinical disease progression. Dose groups were combined and pooled across each study in order to facilitate modeling. The endpoint of each experiment was death. The exponential and exact beta-Poisson models were fit to the data using maximum likelihood estimation. The exact beta-Poisson was deemed the recommended model because it more closely approximated the probability of response at low doses though both models provided a good fit. Although transmission is generally considered to be dominated by person-to-person contact, aerosolization is a possible route of exposure. If possible, this route of exposure could be particularly concerning for persons in occupational roles managing contaminated liquid wastes from patients being treated for Ebola infection and the wastewater community responsible for disinfection. Therefore, this study produces a necessary mathematical relationship between exposure dose and risk of death for the inhalation route of exposure that can support quantitative microbial risk assessment aimed at informing risk mitigation strategies including personal protection policies against occupational exposures.     

A perfect storm: Challenges encountered by family caregivers of persons with Alzheimer’s disease during natural disasters

ABSTRACT

Since Hurricane Katrina there has been a movement across the U.S. to examine best practice for disaster response within the aging population. However, little is known about the experience of natural disasters from the perspective of family caregivers of persons with Alzheimer’s disease and related dementia (ADRD). In this exploratory, qualitative study, family caregivers (n=27) were interviewed about their experience with the historic 2015 South Carolina flood. By using thematic analysis, themes were identified to better understand what unique challenges caregivers of person with ADRD experienced. While many caregivers stated they had experienced a natural disaster previously, none had ever done so in their current caregiving role. The caregiving role affected their ability to prepare for the storm and influenced their decision-making regarding evacuation and utilization of recovery resources. Thus, caregivers were confronted by a “perfect storm” of circumstances and uncertainty. Family caregivers need to have actionable emergency plans for disasters that are specific to their role as caregivers of persons with ADRD. Study implications also suggest the role social work professionals can have in educating, advocating, evaluating, and coordinating support to assist caregivers of persons with ADRD as a potentially vulnerable and at-risk population during all phases of disaster.     

Sex differences in the development of mild cognitive impairment and probable Alzheimer’s disease as predicted by hippocampal volume or white matter hyperintensities

This study examined biological sex differences in the development of mild cognitive impairment (MCI) and probable Alzheimer’s disease (AD) development as predicted by changes in the hippocampus or white matter hyperintensities. A secondary data analysis of the National Alzheimer’s Coordinating Center Uniform Data Set was conducted. We selected samples of participants with normal cognition at baseline who progressed to MCI (n = 483) and those who progressed to probable AD (n = 211) to determine if hippocampal volume or white matter hyperintensities (WMH) at baseline predicted progression to probable AD or MCI and whether the rate of progression differed between men and women. The survival analyses indicated that changes in hippocampal volumes affected the progression to probable AD (HR = 0.535, 95% CI [0.300–0.953]) only among women. White men had an increased rate of progression to AD (HR = 4.396, CI [1.012–19.08]; HR = 4.665, 95% CI [1.072–20.29]) compared to men in other race and ethnic groups. Among women, increases in hippocampal volume ratio led to decreased rates of progressing to MCI (HR = 0.386, 95% CI [0.166–0.901]). Increased WMH among men led to faster progression to MCI (HR = 1.048. 95% CI [1.011–1.086]). Women and men who were older at baseline were more likely to progress to MCI. In addition, results from longitudinal analyses showed that women with a higher CDR global score, older age at baseline, or more disinhibition symptoms experienced higher odds of MCI development. Changes in hippocampal volumes affect the progression to or odds of probable AD (and MCI) more so among women than men, while changes in WMH affected the progression to MCI only among men.     

Re‐framing the Analysis: A 3‐dimensional Perspective of Prisoners’ Children's Well‐being

This article highlights three dimensions to understanding children's well‐being during and after parental imprisonment which have not been fully explored in current research. A consideration of ‘time’ reveals the importance of children's past experiences and their anticipated futures. A focus on ‘space’ highlights the impact of new or altered environmental dynamics. A study of ‘agency’ illuminates how children cope within structural, material and social confines which intensify vulnerability and dependency. This integrated perspective reveals important differences in individual children's experiences and commonalities in broader systemic and social constraints on prisoners’ children. The paper analyses data from a prospective longitudinal study of 35 prisoners’ children during and after their (step) father's imprisonment to illustrate the arguments.     

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.     

Bayesian hierarchical joint modeling using skew-normal/independent distributions

The multiple longitudinal outcomes collected in many clinical trials are often analyzed by multilevel item response theory (MLIRT) models. The normality assumption for the continuous outcomes in the MLIRT models can be violated due to skewness and/or outliers. Moreover, patients’ follow-up may be stopped by some terminal events (e.g., death or dropout), which are dependent on the multiple longitudinal outcomes. We proposed a joint modeling framework based on the MLIRT model to account for three data features: skewness, outliers, and dependent censoring. Our method development was motivated by a clinical study for Parkinson’s disease.     

‘Occupation Children’ in Germany after World War II — Problems and Coping Strategies

The article focuses on the autobiographical memories of people born in Germany after the Second World War, whose mothers were local women and whose fathers were members of the allied forces. Based on the analysis of narrative interviews, we ask how these people experienced their growing up and their sociocultural environment in the post‐war era, and what kind of coping strategies they developed to deal with adverse living conditions.     

Analysis of a two incongruent arrivals and services M/G/1 queue with random feedback

A queuing system with two incongruent arrivals and services is considered. Two kinds of customers enter the system by Poisson process and the service times are assumed to have general distribution. After first kind service completion, it may feedback to repeat the first service, leave the system or go to give second service. The same policy is applied for the other kind of customer. All stochastic processes involved in this system are independent. We derive the probability generating function for each kind and for the system that yield the performance measures. Some numerical approaches examined the validity of the results.     

Response-adaptive trial designs with accelerated Thompson sampling

In a clinical trial, sometimes it is desirable to allocate as many patients as possible to the best treatment, in particular, when a trial for a rare disease may contain a considerable portion of the whole target population. The Gittins index rule is a powerful tool for sequentially allocating patients to the best treatment based on the responses of patients already treated. However, its application in clinical trials is limited due to technical complexity and lack of randomness. Thompson sampling is an appealing approach, since it makes a compromise between optimal treatment allocation and randomness with some desirable optimal properties in the machine learning context. However, in clinical trial settings, multiple simulation studies have shown disappointing results with Thompson samplers. We consider how to improve short-run performance of Thompson sampling and propose a novel acceleration approach. This approach can also be applied to situations when patients can only be allocated by batch and is very easy to implement without using complex algorithms. A simulation study showed that this approach could improve the performance of Thompson sampling in terms of average total response rate. An application to a redesign of a preference trial to maximize patient's satisfaction is also presented.