Distemper, extinction, and vaccination of the Amur tiger.

Canine distemper virus (CDV) has recently emerged as an extinction threat for the endangered Amur tiger (Panthera tigris altaica). CDV is vaccine-preventable, and control strategies could require vaccination of domestic dogs and/or wildlife populations. However, vaccination of endangered wildlife remains controversial, which has led to a focus on interventions in domestic dogs, often assumed to be the source of infection. Effective decision making requires an understanding of the true reservoir dynamics, which poses substantial challenges in remote areas with diverse host communities. We carried out serological, demographic, and phylogenetic studies of dog and wildlife populations in the Russian Far East to show that a number of wildlife species are more important than dogs, both in maintaining CDV and as sources of infection for tigers. Critically, therefore, because CDV circulates among multiple wildlife sources, dog vaccination alone would not be effective at protecting tigers. We show, however, that low-coverage vaccination of tigers themselves is feasible and would produce substantive reductions in extinction risks. Vaccination of endangered wildlife provides a valuable component of conservation strategies for endangered species.

Selecting Remote Measurement Technologies to Optimize Assessment of Function in Early Alzheimer's Disease: A Case Study.

Despite the importance of function in early Alzheimer's disease (AD), current measures are outdated and insensitive. Moreover, COVID-19 has heighted the need for remote assessment in older people, who are at higher risk of being infection and are particularly advised to use social distancing measures, yet the importance of diagnosis and treatment of dementia remains unchanged. The emergence of remote measurement technologies (RMTs) allows for more precise and objective measures of function. However, RMT selection is a critical challenge. Therefore, this case study outlines the processes through which we identified relevant functional domains, engaged with stakeholder groups to understand participants' perspectives and worked with technical experts to select relevant RMTs to examine function. After an extensive literature review to select functional domains relevant to AD biomarkers, quality of life, rate of disease progression and loss of independence, functional domains were ranked and grouped by the empirical evidence for each. For all functional domains, we amalgamated feedback from a patient advisory board. The results were prioritized into: highly relevant, relevant, neutral, and less relevant. This prioritized list of functional domains was then passed onto a group of experts in the use of RMTs in clinical and epidemiological studies to complete the selection process, which consisted of: (i) identifying relevant functional domains and RMTs; (ii) synthesizing proposals into final RMT selection, and (iii) verifying the quality of these decisions. Highly relevant functional domains were, "difficulties at work," "spatial navigation and memory," and "planning skills and memory required for task completion." All functional domains were successfully allocated commercially available RMTs that make remote measurement of function feasible. This case study provides a set of prioritized functional domains sensitive to the early stages of AD and a set of RMTs capable of targeting them. RMTs have huge potential to transform the way we assess function in AD-monitoring for change and stability continuously within the home environment, rather than during infrequent clinic visits. Our decomposition of RMT and functional domain selection into identify, synthesize, and verify activities, provides a pragmatic structure with potential to be adapted for use in future RMT selection processes.

Evaluating the Feasibility of Frequent Cognitive Assessment Using the Mezurio Smartphone App: Observational and Interview Study in Adults With Elevated Dementia Risk.

BACKGROUND: By enabling frequent, sensitive, and economic remote assessment, smartphones will facilitate the detection of early cognitive decline at scale. Previous studies have sustained participant engagement with remote cognitive assessment over a week; extending this to a period of 1 month clearly provides a greater opportunity for measurement. However, as study durations are increased, the need to understand how participant burden and scientific value might be optimally balanced also increases. OBJECTIVE: This study explored the little but often approach to assessment employed by the Mezurio app when prompting participants to interact every day for over a month. Specifically, this study aimed to understand whether this extended duration of remote study is feasible, and which factors promote sustained participant engagement over such periods. METHODS: A total of 35 adults (aged 40-59 years) with no diagnosis of cognitive impairment were prompted to interact with the Mezurio smartphone app platform for up to 36 days, completing short, daily episodic memory tasks in addition to optional executive function and language tests. A subset (n=20) of participants completed semistructured interviews focused on their experience of using the app. RESULTS: Participants complied with 80% of the daily learning tasks scheduled for subsequent tests of episodic memory, with 88% of participants still actively engaged by the final task. A thematic analysis of the participants' experiences highlighted schedule flexibility, a clear user interface, and performance feedback as important considerations for engagement with remote digital assessment. CONCLUSIONS: Despite the extended study duration, participants demonstrated high compliance with the schedule of daily learning tasks and were extremely positive about their experiences. Long durations of remote digital interaction are therefore definitely feasible but only when careful attention is paid to the design of the users' experience.

Gallery Game: Smartphone-based assessment of long-term memory in adults at risk of Alzheimer's disease.

Introduction: Gallery Game, deployed within the Mezurio smartphone app, targets the processes of episodic memory hypothesized to be first vulnerable to neurofibrillary tau-related degeneration in Alzheimer's Disease, prioritizing both perirhinal and entorhinal cortex/hippocampal demands.Methods: Thirty-five healthy adults (aged 40-59 years), biased toward those at elevated familial risk of dementia, completed daily Gallery Game tasks for a month. Assessments consisted of cross-modal paired-associate learning, with subsequent tests of recognition and free recall following delays ranging from one to 13 days.Results: Retention intervals of at least three days were needed to evidence significant forgetting at both recognition and paired-associate recall test. The association between Gallery Game outcomes and established in-clinic memory assessments were small but numerically in the anticipated direction. In addition, there was preliminary support for utilizing the perirhinal-dependent pattern of semantic false alarms during object recognition as a marker of early impairment.Conclusions: These results support the need for tests of longer-term memory to sensitively record behavioral differences in adults with no diagnosis of cognitive impairment. Aggregate behavioral outcomes promote Gallery Game's utility as a digital assessment of episodic memory, aligning with established theoretical models of object memory and showing small yet uniform associations with existing in-clinic tests. Initial support for the discriminatory value of perirhinal-targeted outcomes justifies ongoing large-sample validation against traditional biomarkers of Alzheimer's disease.

Digital technologies for the assessment of cognition: a clinical review.

Dementia is the most widespread form of neurodegenerative disorder and is associated with an immense societal and personal cost. Prevalence of this disorder is projected to triple worldwide by 2050 leading to an urgent need to make advances in the efficiency of both its care and therapy research. Digital technologies are a rapidly advancing field that provide a previously unavailable opportunity to alleviate challenges faced by clinicians and researchers working in this area. This clinical review aimed to summarise currently available evidence on digital technologies that can be used to monitor cognition. We identified a range of pervasive digital systems, such as smartphones, smartwatches and smart homes, to assess and assist elderly demented, prodromal and preclinical populations. Generally, the studies reported good level of agreement between the digital measures and the constructs they aimed to measure. However, most of the systems are still only in the initial stages of development with limited data on acceptability in patients. Although it is clear that the use of digital technology to monitor and support the cognitive domains affected by dementia is a promising area of development, additional research validating the efficacy, utility and cost-effectiveness of these systems in patient populations is needed.

Comparison of Next-Generation Sequencing Technologies for Comprehensive Assessment of Full-Length Hepatitis C Viral Genomes.

Affordable next-generation sequencing (NGS) technologies for hepatitis C virus (HCV) may potentially identify both viral genotype and resistance genetic motifs in the era of directly acting antiviral (DAA) therapies. This study compared the ability of high-throughput NGS methods to generate full-length, deep, HCV sequence data sets and evaluated their utility for diagnostics and clinical assessment. NGS methods using (i) unselected HCV RNA (metagenomics), (ii) preenrichment of HCV RNA by probe capture, and (iii) HCV preamplification by PCR implemented in four United Kingdom centers were compared. Metrics of sequence coverage and depth, quasispecies diversity, and detection of DAA resistance-associated variants (RAVs), mixed HCV genotypes, and other coinfections were compared using a panel of samples with different viral loads, genotypes, and mixed HCV genotypes/subtypes [geno(sub)types]. Each NGS method generated near-complete genome sequences from more than 90% of samples. Enrichment methods and PCR preamplification generated greater sequence depth and were more effective for samples with low viral loads. All NGS methodologies accurately identified mixed HCV genotype infections. Consensus sequences generated by different NGS methods were generally concordant, and majority RAVs were consistently detected. However, methods differed in their ability to detect minor populations of RAVs. Metagenomic methods identified human pegivirus coinfections. NGS provided a rapid, inexpensive method for generating whole HCV genomes to define infecting genotypes, RAVs, comprehensive viral strain analysis, and quasispecies diversity. Enrichment methods are particularly suited for high-throughput analysis while providing the genotype and information on potential DAA resistance.