Structure-Activity Relationships of the Fentanyl Scaffold: Identification of Antagonists as Potential Opioid Overdose Reversal Agents.

Opioid-related overdoses account for almost half of all drug overdose deaths in the United States and cause more preventable deaths every year than car crashes. Fentanyl, a highly potent mu opioid receptor (MOR) agonist and its analogues (fentalogues) are increasingly found in illicit drug samples, both where the primary drug of abuse is an opioid and where it is not. The prevalence of fentalogues in the illicit drug market is thought to be the primary driver of the increased number of opioid-related overdose deaths since 2016. In fact, fentanyl and its analogues are involved in more than 70% of opioid-related overdoses. The standard opioid overdose rescue therapy naloxone is often insufficient to reverse opioid overdoses caused by fentalogue agonists under current treatment paradigms. However, the pharmacology of many fentalogues is unknown. Moreover, within the fentalogue series of compounds, it is possible that antagonists could be identified that might be superior to naloxone as opioid overdose reversal agents. In this report, we explore the pharmacology of 70 fentalogues and identify compounds that behave as MOR antagonists in vitro and demonstrate with one of these reversals of fentanyl-induced respiratory depression in the mouse. Such compounds could provide leads for the development of effective agents for the reversal of opioid overdose.

Contribution of Microorganisms with the Clade II Nitrous Oxide Reductase to Suppression of Surface Emissions of Nitrous Oxide.

The sources and sinks of nitrous oxide, as control emissions to the atmosphere, are generally poorly constrained for most environmental systems. Initial depth-resolved analysis of nitrous oxide flux from observation wells and the proximal surface within a nitrate contaminated aquifer system revealed high subsurface production but little escape from the surface. To better understand the environmental controls of production and emission at this site, we used a combination of isotopic, geochemical, and molecular analyses to show that chemodenitrification and bacterial denitrification are major sources of nitrous oxide in this subsurface, where low DO, low pH, and high nitrate are correlated with significant nitrous oxide production. Depth-resolved metagenomes showed that consumption of nitrous oxide near the surface was correlated with an enrichment of Clade II nitrous oxide reducers, consistent with a growing appreciation of their importance in controlling release of nitrous oxide to the atmosphere. Our work also provides evidence for the reduction of nitrous oxide at a pH of 4, well below the generally accepted limit of pH 5.

Health Care Workers Online YouTube Content Compared to AUA Prevention of Recurrent Urinary Tract Infections in Women Guidelines: An Integrative Review of Quality and Comprehensiveness Analysis.

INTRODUCTION: We document the quality, veracity, and comprehensiveness of recurrent UTI information on YouTube to increase health care workers' (HCWs') awareness of UTI-related content online, and to identify deficits in understanding, clarify misconceptions, and reduce stigmatization risk. METHODS: High-traffic topic search terms were curated by Google Trends to extract 200 videos, of which 45 met inclusion criteria. Five independent reviewers used a standardized questionnaire based on the AUA recurrent UTI guidelines to assess the definition of UTI, marketing content, prophylaxis/prevention strategies, and antibiotic use/stewardship. RESULTS: Incongruent or incomplete guideline UTI definitions were found in 78% (35/45) of videos (K = 0.40), despite 80% (36/45) being authored by HCWs. Forty-two percent (19/45) promoted nonguideline-based hygiene practices; 25% (11/45) advocated front-to-back wiping (K = 0.71). Descriptors identified within the videos included the mention of women with UTI as unclean. Only 55% (25/45) discussed increasing fluid intake (K = 0.59), while 33% (15/45) discussed the use of cranberry supplementation (K = 0.81). CONCLUSIONS: Discussion of hygiene practices which lack a specific guideline statement is particularly evident. Descriptors that characterize women with UTI as "unclean" may create a health equity concern for women experiencing UTIs. These findings should alert HCWs to the scope and emphasis in online education that patients may view to self-educate; both the errors and the issues of equity are problematic. Educational materials on UTI should be based on evidence-based guidelines, such as those by the AUA.

Applying Sydney Triage to Admission Risk Tool (START) to improve patient flow in emergency departments: a multicentre randomised, implementation study.

BACKGROUND: To determine the effectiveness of applying the Sydney Triage to Admission Risk Tool (START) in conjunction with senior early assessment in different Emergency Departments (EDs). METHODS: This multicentre implementation study, conducted in two metropolitan EDs, used a convenience sample of ED patients. Patients who were admitted, after presenting to both EDs, and were assessed using the existing senior ED clinician assessment, were included in the study. Patients in the intervention group were assessed with the assistance of START, while patients in the control group were assessed without the assistance of START. Outcomes measured were ED length of stay and proportion of patients correctly identified as an in-patient admission by START. RESULTS: A total of 773 patients were evaluated using the START tool at triage across both sites (Intervention group n = 355 and control group n = 418 patients). The proportion of patients meeting the 4-hour length of stay thresholds was similar between the intervention and control groups (30.1% vs. 28.2%; p = 0.62). The intervention group was associated with a reduced ED length of stay when compared to the control group (351 min, interquartile range (IQR) 221.0-565.0 min versus 383 min, IQR 229.25-580.0 min; p = 0.85). When stratified into admitted and discharged patients, similar results were seen. CONCLUSION: In this extension of the START model of care implementation study in two metropolitan EDs, START, when used in conjunction with senior early assessment was associated with some reduced ED length of stay.

Investigating the Readability and Linguistic, Psychological, and Emotional Characteristics of Digital Dementia Information Written in the English Language: Multitrait-Multimethod Text Analysis.

BACKGROUND: Past research in the Western context found that people with dementia search for digital dementia information in peer-reviewed medical research articles, dementia advocacy and medical organizations, and blogs written by other people with dementia. This past work also demonstrated that people with dementia do not perceive English digital dementia information as emotionally or cognitively accessible. OBJECTIVE: In this study, we sought to investigate the readability; linguistic, psychological, and emotional characteristics; and target audiences of digital dementia information. We conducted a textual analysis of 3 different types of text-based digital dementia information written in English: 300 medical articles, 35 websites, and 50 blogs. METHODS: We assessed the text's readability using the Flesch Reading Ease and Flesch-Kincaid Grade Level measurements, as well as tone, analytical thinking, clout, authenticity, and word frequencies using a natural language processing tool, Linguistic Inquiry and Word Count Generator. We also conducted a thematic analysis to categorize the target audiences for each information source and used these categorizations for further statistical analysis. RESULTS: The median Flesch-Kincaid Grade Level readability score and Flesch Reading Ease score for all types of information (N=1139) were 12.1 and 38.6, respectively, revealing that the readability scores of all 3 information types were higher than the minimum requirement. We found that medical articles had significantly (P=.05) higher word count and analytical thinking scores as well as significantly lower clout, authenticity, and emotional tone scores than websites and blogs. Further, blogs had significantly (P=.48) higher word count and authenticity scores but lower analytical scores than websites. Using thematic analysis, we found that most of the blogs (156/227, 68.7%) and web pages (399/612, 65.2%) were targeted at people with dementia. Website information targeted at a general audience had significantly lower readability scores. In addition, website information targeted at people with dementia had higher word count and lower emotional tone ratings. The information on websites targeted at caregivers had significantly higher clout and lower authenticity scores. CONCLUSIONS: Our findings indicate that there is an abundance of digital dementia information written in English that is targeted at people with dementia, but this information is not readable by a general audience. This is problematic considering that people with <12 years of education are at a higher risk of developing dementia. Further, our findings demonstrate that digital dementia information written in English has a negative tone, which may be a contributing factor to the mental health crisis many people with dementia face after receiving a diagnosis. Therefore, we call for content creators to lower readability scores to make the information more accessible to a general audience and to focus their efforts on providing information in a way that does not perpetuate overly negative narratives of dementia.

The Human Need for Equilibrium: Qualitative Study on the Ingenuity, Technical Competency, and Changing Strategies of People With Dementia Seeking Health Information.

BACKGROUND: Prior research on health information behaviors of people with dementia has primarily focused on examining the types of information exchanged by people with dementia using various web-based platforms. A previous study investigated the information behaviors of people with dementia within a month of their diagnosis. There is an empirical gap in the literature regarding the evolution of health information needs and behaviors of people with dementia as their condition progresses. OBJECTIVE: Our work primarily investigated the information behaviors of people with dementia who have been living with the condition for several (4 to 26) years. We also aimed to identify their motivations for changing their information behaviors over time. Our primary research questions were as follows: how do people with dementia get informed about their condition, and why do people with dementia seek information about their condition? METHODS: We adopted an action research approach by including 2 people with dementia as members of our research team. Collaboratively, we conducted 16 remote 1-hour contextual inquiry sessions with people living with mild to moderate dementia. During the study sessions, the first 40 minutes included semistructured interviews with participants concerning their information behaviors, followed by a 20-minute demonstration of their information-seeking strategies. Data from these interviews were analyzed using a constructivist grounded theory approach. RESULTS: Participants described their information needs in terms of managing the disrupted physiological, emotional, and social aspects of their lives following a diagnosis of dementia. They used various information behaviors, including active search, ongoing search, monitoring, proxy search, information avoidance, and selective exposure. These information behaviors were not stagnant; however, they were adapted to accommodate the changing circumstances of their dementia and their lives as they worked to re-establish equilibrium to continue to engage in life while living with a degenerative neurological condition. CONCLUSIONS: Our research revealed the motivations, changing abilities, and chosen strategies of people with dementia in their search for information as their condition evolves. This knowledge can be used to develop and improve person-centered information and support services for people with dementia so that they can more easily re-establish equilibrium and continue to engage in life.

Understanding How Sensory Changes Experienced by Individuals with a Range of Age-Related Cognitive Changes Can Effect Technology Use.

Clinical researchers have identified sensory changes people with age-related cognitive changes, such as dementia and mild cognitive impairment, experience that are different from typical age-related sensory changes. Technology designers and researchers do not yet have an understanding of how these unique sensory changes affect technology use. This work begins to bridge the gap between the clinical knowledge of sensory changes and technology research and design through interviews with people with mild to moderate dementia, mild cognitive impairment, subjective cognitive decline, and healthcare professionals. This extended version of our ASSETS conference paper includes people with a range of age-related cognitive changes describing changes in vision, hearing, speech, dexterity, proprioception, and smell. We discuss each of these sensory changes and ways to leverage optimal modes of sensory interaction for accessible technology use with existing and emerging technologies. Finally, we discuss how accessible sensory stimulation may change across the spectrum of age-related cognitive changes.

Barriers to Online Dementia Information and Mitigation.

There is growing interest in HCI to study ways to support access to accurate, accessible, relevant online health information for different populations. Yet, there remains a need to understand the barriers that are posed by the way our platforms are designed as well as how we might overcome these barriers for people with dementia. To address this, we conducted sixteen interviews and observation sessions with people with mild to moderate dementia. Our analysis uncovered four barriers to online health information and corresponding mitigation strategies that participants employed. We discuss how HCI researchers may apply these findings towards new technical approaches and standards concerning information accessibility and credibility for neurodiverse populations. Finally, we broaden the scope of HCI research to include investigations of the accessibility and credibility of online information for people with age-related cognitive impairment independent of proxies.

Investigating the Potential of Artificial Intelligence Powered Interfaces to Support Different Types of Memory for People with Dementia.

There has been a growing interest in HCI to understand the specific technological needs of people with dementia and supporting them in self-managing daily activities. One of the most difficult challenges to address is supporting the fluctuating accessibility needs of people with dementia, which vary with the specific type of dementia and the progression of the condition. Researchers have identified auto-personalized interfaces, and more recently, Artificial Intelligence or AI-driven personalization as a potential solution to making commercial technology accessible in a scalable manner for users with fluctuating ability. However, there is a lack of understanding on the perceptions of people with dementia around AI as an aid to their everyday technology use and its role in their overall self-management systems, which include other non-AI technology, and human assistance. In this paper, we present future directions for the design of AI-based systems to personalize an interface for dementia-related changes in different types of memory, along with expectations for AI interactions with the user with dementia.

A multidisciplinary, cross-sectional survey of burnout and wellbeing in emergency department staff during COVID-19.

BACKGROUND: Emergency department (ED) staff are at-risk of burnout, poor wellbeing and increased stress that can impact patient satisfaction, staff morale and retention. The aim of this survey was to determine level of burnout, stress and satisfaction with current employment role in ED during COVID-19. METHODS: A multisite cross-sectional survey captured ED employment data, wellbeing, burnout (Maslach Burnout Inventory), stress (Health Professions Stress Inventory), work environment (WES-10) and Caring for COVID-19 Patients questions. RESULTS: The response rate of 44.2% (n = 177) represented all healthcare disciplines. Only 58.8% (n = 104) of participants were happy in their role, satisfaction was low, burnout was high (M 71.0, SD 17.1) as was level of stress (M 90.6, SD 16.5). Nurses and allied health staff were more stressed than their medical or support staff colleagues. Participants perceived discriminatory behaviours from friends and family in caring for suspected or infected COVID-19 patients. CONCLUSIONS: ED staff are a vulnerable group. Programmes to promote wellbeing, personal resilience, and self-care together with personal and professional growth are needed to build individual capability and a culture of organisational resilience, particularly in the context of the COVID pandemic.

Mobile Phone Use by People with Mild to Moderate Dementia: Uncovering Challenges and Identifying Opportunities: Mobile Phone Use by People with Mild to Moderate Dementia.

With the rising usage of mobile phones by people with mild dementia, and the documented barriers to technology use that exist for people with dementia, there is an open opportunity to study the specifics of mobile phone use by people with dementia. In this work we provide a first step towards filling this gap through an interview study with fourteen people with mild to moderate dementia. Our analysis yields insights into mobile phone use by people with mild to moderate dementia, challenges they experience with mobile phone use, and their ideas to address these challenges. Based on these findings, we discuss design opportunities to help achieve more accessible and supportive technology use for people with dementia. Our work opens up new opportunities for the design of systems focused on augmenting and enhancing the abilities of people with dementia.

Designing for and with People with Dementia using a Human Rights-Based Approach.

User-centered design is typically framed around meeting the preferences and needs of populations involved in the design process. However, when designing technology for people with disabilities, in particular dementia, there is also a moral imperative to ensure that human rights of this segment of the population are consciously integrated into the process and respectfully included in the product. We introduce a human rights-based user-centered design process which is informed by the United Nations Convention on the Rights of Persons with Disabilities (CRPD). We conducted two editions of a three-day-long design workshop during which undergraduate students and dementia advocates came together to design technology for people with dementia. This case study demonstrates our novel approach to user-centered design that centers human rights through different stages of the workshop and actively involves people with dementia in the design process.

"Taking care of myself as long as I can": How People with Dementia Configure Self-Management Systems.

Self-management research in HCI has addressed a variety of conditions. Yet, this literature has largely focused on neurotypical populations and chronic conditions that can be managed, leaving open questions of what self-management might look like for populations with progressive cognitive impairment. Grounded in interviews with seventeen technology savvy people with mild to moderate dementia, our analysis reveals their use of technological and social resources as part of the work of self-management. We detail how participants design self-management systems to enable desired futures, function well in their social world, and maintain control. Our discussion broadens the notion of self-management to include future-oriented, sociotechnical, self-determinate design. We advocate for expanding the way technologists, designers, and HCI scholars view people with mild to moderate dementia to recognize them as inventive creators and capable actors in self-management.

Quantitative MRI susceptibility mapping reveals cortical signatures of changes in iron, calcium and zinc in malformations of cortical development in children with drug-resistant epilepsy.

OBJECTIVE: Malformations of cortical development (MCD), including focal cortical dysplasia (FCD), are the most common cause of drug-resistant focal epilepsy in children. Histopathological lesion characterisation demonstrates abnormal cell types and lamination, alterations in myelin (typically co-localised with iron), and sometimes calcification. Quantitative susceptibility mapping (QSM) is an emerging MRI technique that measures tissue magnetic susceptibility (χ) reflecting it's mineral composition. We used QSM to investigate abnormal tissue composition in a group of children with focal epilepsy with comparison to effective transverse relaxation rate (R2*) and Synchrotron radiation X-ray fluorescence (SRXRF) elemental maps. Our primary hypothesis was that reductions in χ would be found in FCD lesions, resulting from alterations in their iron and calcium content. We also evaluated deep grey matter nuclei for changes in χ with age. METHODS: QSM and R2* maps were calculated for 40 paediatric patients with suspected MCD (18 histologically confirmed) and 17 age-matched controls. Patients' sub-groups were defined based on concordant electro-clinical or histopathology data. Quantitative investigation of QSM and R2* was performed within lesions, using a surface-based approach with comparison to homologous regions, and within deep brain regions using a voxel-based approach with regional values modelled with age and epilepsy as covariates. Synchrotron radiation X-ray fluorescence (SRXRF) was performed on brain tissue resected from 4 patients to map changes in iron, calcium and zinc and relate them to MRI parameters. RESULTS: Compared to fluid-attenuated inversion recovery (FLAIR) or T1-weighted imaging, QSM improved lesion conspicuity in 5% of patients. In patients with well-localised lesions, quantitative profiling demonstrated decreased χ, but not R2*, across cortical depth with respect to the homologous regions. Contra-lateral homologous regions additionally exhibited increased χ at 2-3 mm cortical depth that was absent in lesions. The iron decrease measured by the SRXRF in FCDIIb lesions was in agreement with myelin reduction observed by Luxol Fast Blue histochemical staining. SRXRF analysis in two FCDIIb tissue samples showed increased zinc and calcium in one patient, and decreased iron in the brain region exhibiting low χ and high R2* in both patients. QSM revealed expected age-related changes in the striatum nuclei, substantia nigra, sub-thalamic and red nucleus. CONCLUSION: QSM non-invasively revealed cortical/sub-cortical tissue alterations in MCD lesions and in particular that χ changes in FCDIIb lesions were consistent with reduced iron, co-localised with low myelin and increased calcium and zinc content. These findings suggest that measurements of cortical χ could be used to characterise tissue properties non-invasively in epilepsy lesions.

Investigating Best Practices for Remote Summative Usability Testing with People with Mild to Moderate Dementia.

People with dementia may miss out on the benefits of using technology, because they often find it difficult to use. Usability testing is one method to identify barriers and areas for improvement in technology. Unfortunately, usability testing is often not conducted with people with dementia, independent of their caregivers. Difficulty recruiting local participants with dementia who regularly use technology further compounds the problem. Remote methods have been proposed as one approach to recruiting hard-to-reach populations. Currently, it is unclear how to effectively conduct remote summative usability testing with people with dementia. We recruited 15 participants. Five took part in the pilot study and 10 participated in the main study. We identify best practices and make suggestions for remote summative usability tests with people who have mild to moderate dementia, independent of caregivers. We discuss our findings in three sections: (1) logistics for planning remote summative usability testing, (2) approaches for conducting remote summative usability testing, including modifications of research methods, and (3) considerations when evaluating findings from remote summative usability sessions. We also present modified usability testing methods we developed to meet the unique needs of users with mild to moderate dementia, and summarize lessons learned and new directions for research on this topic.

Approach Matters: Linking Practitioner Approaches to Technology Design for People with Dementia.

Technology design for dementia is an active and growing area. Though work to date has largely addressed functional needs, there is a growing recognition of the importance of supporting meaningful activities. However, technology for active, rather than passive, engagement is relatively novel beyond specific applications (e.g., music or reminiscence therapy). To better understand how to support active engagement of people with dementia in activities, we interviewed nineteen practitioners. Our findings reveal differing approaches to making sense of the actions of people with dementia, as well as to engaging them in activities. We discuss the importance of tracing epistemological understandings of dementia to different configurations of technology for people living with dementia and provide a practical guide to support designers to do so. Finally, we discuss considerations for the design of dementia technologies around facilitating self-actualization and managing emotional exposure for care-providers.

Examining the Self-Harm and Suicide Contagion Effects of the Blue Whale Challenge on YouTube and Twitter: Qualitative Study.

BACKGROUND: Research suggests that direct exposure to suicidal behaviors and acts of self-harm through social media may increase suicidality through imitation and modeling, particularly in more vulnerable populations. One example of a social media phenomenon that demonstrates how self-harming behavior could potentially be propagated is the blue whale challenge. In this challenge, adolescents and young adults are encouraged to engage in self-harm and eventually kill themselves. OBJECTIVE: This paper aimed to investigate the way individuals portray the blue whale challenge on social media, with an emphasis on factors that could pose a risk to vulnerable populations. METHODS: We first used a thematic analysis approach to code 60 publicly posted YouTube videos, 1112 comments on those videos, and 150 Twitter posts that explicitly referenced the blue whale challenge. We then deductively coded the YouTube videos based on the Suicide Prevention Resource Center (SPRC) safe messaging guidelines as a metric for the contagion risk associated with each video. RESULTS: The thematic analysis revealed that social media users post about the blue whale challenge to raise awareness and discourage participation, express sorrow for the participants, criticize the participants, or describe a relevant experience. The deductive coding of the YouTube videos showed that most of the videos violated at least 50% of the SPRC safe and effective messaging guidelines. CONCLUSIONS: These posts might have the problematic effect of normalizing the blue whale challenge through repeated exposure, modeling, and reinforcement of self-harming and suicidal behaviors, especially among vulnerable populations such as adolescents. More effort is needed to educate social media users and content generators on safe messaging guidelines and factors that encourage versus discourage contagion effects.

Characterization of subsurface media from locations up- and down-gradient of a uranium-contaminated aquifer.

The processing of sediment to accurately characterize the spatially-resolved depth profiles of geophysical and geochemical properties along with signatures of microbial density and activity remains a challenge especially in complex contaminated areas. This study processed cores from two sediment boreholes from background and contaminated core sediments and surrounding groundwater. Fresh core sediments were compared by depth to capture the changes in sediment structure, sediment minerals, biomass, and pore water geochemistry in terms of major and trace elements including pollutants, cations, anions, and organic acids. Soil porewater samples were matched to groundwater level, flow rate, and preferential flows and compared to homogenized groundwater-only samples from neighboring monitoring wells. Groundwater analysis of nearby wells only revealed high sulfate and nitrate concentrations while the same analysis using sediment pore water samples with depth was able to suggest areas high in sulfate- and nitrate-reducing bacteria based on their decreased concentration and production of reduced by-products that could not be seen in the groundwater samples. Positive correlations among porewater content, total organic carbon, trace metals and clay minerals revealed a more complicated relationship among contaminant, sediment texture, groundwater table, and biomass. The fluctuating capillary interface had high concentrations of Fe and Mn-oxides combined with trace elements including U, Th, Sr, Ba, Cu, and Co. This suggests the mobility of potentially hazardous elements, sediment structure, and biogeochemical factors are all linked together to impact microbial communities, emphasizing that solid interfaces play an important role in determining the abundance of bacteria in the sediments.

Supporting Remote Participation when Designing with People with Dementia.

Exploring accessible remote design methods has become the need of the hour for supporting participation in research and collaborative design with individuals with dementia. Existing remote design approaches face specific challenges when facilitating best practices for co-design with participants with dementia. These challenges include, enabling sensory engagement with physical design materials and prototypes and observing these interactions in a natural manner. We present a system architecture and use cases for a portable system with a range of connected devices that support real-time, embodied design activities with individuals with dementia.

The Role of Sensory Changes in Everyday Technology use by People with Mild to Moderate Dementia.

Technology design for dementia primarily focuses on cognitive needs. This includes providing task support, accommodating memory changes, and simplifying interfaces by reducing complexity. However, research has demonstrated that dementia affects not only the cognitive abilities of people with dementia, but also their sensory and motor abilities. This work provides a first step towards understanding the interaction between sensory changes and technology use by people with dementia through interviews with people with mild to moderate dementia and practitioners. Our analysis yields an understanding of strategies to use technology to overcome sensory changes associated with dementia as well as barriers to using certain technologies. We present new directions for the design of technologies for people with mild to moderate dementia, including intentional sensory stimulation to facilitate comprehension, as well as opportunities to leverage advances in technology design from other disabilities for dementia.