Engineering considerations for practical lithium-air electrolytes.

Lithium-air batteries promise exceptional energy density while avoiding the use of transition metals in their cathodes, however, their practical adoption is currently held back by their short lifetimes. These short lifetimes are largely caused by electrolyte breakdown, but despite extensive searching, an electrolyte resistant to breakdown has yet to be found. This paper considers the requirements placed on an electrolyte for it to be considered usable in a practical cell. We go on to examine ways, through judicious cell design, of relaxing these requirements to allow for a broader range of compounds to be considered. We conclude by suggesting types of molecules that could be explored for future cells. With this work, we aim to broaden the scope of future searches for electrolytes and inform new cell design.

Spiers Memorial Lecture: Lithium air batteries - tracking function and failure.

The lithium-air battery (LAB) is arguably the battery with the highest energy density, but also a battery with significant challenges to be overcome before it can be used commercially in practical devices. Here, we discuss experimental approaches developed by some of the authors to understand the function and failure of lithium-oxygen batteries. For example, experiments in which nuclear magnetic resonance (NMR) spectroscopy was used to quantify dissolved oxygen concentrations and diffusivity are described. 17O magic angle spinning (MAS) NMR spectra of electrodes extracted from batteries at different states of charge (SOC) allowed the electrolyte decomposition products at each stage to be determined. For instance, the formation of Li2CO3 and LiOH in a dimethoxyethane (DME) solvent and their subsequent removal on charging was followed. Redox mediators have been used to chemically reduce oxygen or to chemically oxidise Li2O2 in order to prevent electrode clogging by insulating compounds, which leads to lower capacities and rapid degradation; the studies of these mediators represent an area where NMR and electron paramagnetic resonance (EPR) studies could play a role in unravelling reaction mechanisms. Finally, recently developed coupled in situ NMR and electrochemical impedance spectroscopy (EIS) are used to characterise the charge transport mechanism in lithium symmetric cells and to distinguish between electronic and ionic transport, demonstrating the formation of transient (soft) shorts in common lithium-oxygen electrolytes. More stable solid electrolyte interphases are formed under an oxygen atmosphere, which helps stabilise the lithium anode on cycling.

The tricot approach: an agile framework for decentralized on-farm testing supported by citizen science. A retrospective.

Matching crop varieties to their target use context and user preferences is a challenge faced by many plant breeding programs serving smallholder agriculture. Numerous participatory approaches proposed by CGIAR and other research teams over the last four decades have attempted to capture farmers' priorities/preferences and crop variety field performance in representative growing environments through experimental trials with higher external validity. Yet none have overcome the challenges of scalability, data validity and reliability, and difficulties in capturing socio-economic and environmental heterogeneity. Building on the strengths of these attempts, we developed a new data-generation approach, called triadic comparison of technology options (tricot). Tricot is a decentralized experimental approach supported by crowdsourced citizen science. In this article, we review the development, validation, and evolution of the tricot approach, through our own research results and reviewing the literature in which tricot approaches have been successfully applied. The first results indicated that tricot-aggregated farmer-led assessments contained information with adequate validity and that reliability could be achieved with a large sample. Costs were lower than current participatory approaches. Scaling the tricot approach into a large on-farm testing network successfully registered specific climatic effects of crop variety performance in representative growing environments. Tricot's recent application in plant breeding networks in relation to decision-making has (i) advanced plant breeding lines recognizing socio-economic heterogeneity, and (ii) identified consumers' preferences and market demands, generating alternative breeding design priorities. We review lessons learned from tricot applications that have enabled a large scaling effort, which should lead to stronger decision-making in crop improvement and increased use of improved varieties in smallholder agriculture.

Fatal Human Rabies Infection With Suspected Host-Mediated Failure of Post-Exposure Prophylaxis Following a Recognized Zoonotic Exposure-Minnesota, 2021.

BACKGROUND: No human rabies post-exposure prophylaxis (PEP) failure has been documented in the United States using modern cell culture-based vaccines. In January 2021, an 84-year-old male died from rabies 6 months after being bitten by a rabid bat despite receiving timely rabies PEP. We investigated the cause of breakthrough infection. METHODS: We reviewed medical records, laboratory results, and autopsy findings and performed whole-genome sequencing (WGS) to compare patient and bat virus sequences. Storage, administration, and integrity of PEP biologics administered to the patient were assessed; samples from leftover rabies immunoglobulin were evaluated for potency. We conducted risk assessments for persons potentially exposed to the bat and for close patient contacts. RESULTS: Rabies virus antibodies present in serum and cerebrospinal fluid were nonneutralizing. Antemortem blood testing revealed that the patient had unrecognized monoclonal gammopathy of unknown significance. Autopsy findings showed rabies meningoencephalitis and metastatic prostatic adenocarcinoma. Rabies virus sequences from the patient and the offending bat were identical by WGS. No deviations were identified in potency, quality control, administration, or storage of administered PEP. Of 332 persons assessed for potential rabies exposure to the case patient, 3 (0.9%) warranted PEP. CONCLUSIONS: This is the first reported failure of rabies PEP in the Western Hemisphere using a cell culture-based vaccine. Host-mediated primary vaccine failure attributed to previously unrecognized impaired immunity is the most likely explanation for this breakthrough infection. Clinicians should consider measuring rabies neutralizing antibody titers after completion of PEP if there is any suspicion for immunocompromise.

Effect of Aging on the Viscoelastic Properties of Hippocampal Subfields Assessed with High-Resolution MR Elastography.

Age-related memory impairments have been linked to differences in structural brain parameters, including the integrity of the hippocampus (HC) and its distinct hippocampal subfields (HCsf). Imaging methods sensitive to the underlying tissue microstructure are valuable in characterizing age-related HCsf structural changes that may relate to cognitive function. Magnetic resonance elastography (MRE) is a noninvasive MRI technique that can quantify tissue viscoelasticity and may provide additional information about aging effects on HCsf health. Here, we report a high-resolution MRE protocol to quantify HCsf viscoelasticity through shear stiffness, µ, and damping ratio, ξ, which reflect the integrity of tissue composition and organization. HCsf exhibit distinct mechanical properties-the subiculum had the lowest µ and both subiculum and entorhinal cortex had the lowest ξ. Both measures correlated with age: HCsf µ was lower with age (P < 0.001) whereas ξ was higher (P = 0.002). The magnitude of age-related differences in ξ varied across HCsf (P = 0.011), suggesting differential patterns of brain aging. This study demonstrates the feasibility of using MRE to assess HCsf microstructural integrity and suggests incorporation of these metrics to evaluate HC health in neurocognitive disorders.

Medicolegal Implications of Mild Neurocognitive Disorder.

INTRODUCTION: The syndromes of mild cognitive impairment (MCI) or mild neurocognitive disorder (MiND), often prodromal to dementia (Major Neurocognitive Disorder), are characterized by acquired clinically significant changes in one or more cognitive domains despite preserved independence. Mild impairment has significant medicolegal consequences for an affected person and their care system. We review the more common etiologies of MiND and provide a systematic review of its medicolegal implications. METHODS: We conducted a systematic review of the peer-reviewed English literature on medicolegal aspects of MCI or MiND using comprehensive search terms and expanding our review to include sources cited by these reports. RESULTS: Impairment of memory, executive function, social cognition, judgment, insight or abstraction can alter an individual's abilities in a variety of areas that include decision making, informed consent, designation of a surrogate decision-maker such as a health care proxy, understanding and management of financial affairs, execution of a will, or safe driving. CONCLUSION: Even mild cognitive impairment can have significant behavioral consequences. Clinicians can assist care partners and persons with MCI or MiND by alerting them to the medicolegal concerns that often accompany cognitive decline. Early recognition and discussion can help a care system manage medicolegal risk more effectively and promote thoughtful advance planning.

Ketogenic Diet for the Treatment and Prevention of Dementia: A Review.

Dementia (major neurocognitive disorder) is an increasingly common syndrome with a significant burden on patients, caregivers, the health-care system, and the society. The prevalence of dementia will certainly continue to grow as the US population ages. Current treatments for dementia, though, are limited. One proposed nonpharmacologic approach for the delay or prevention of dementia is the use of a ketogenic diet. The ketogenic diet was originally employed to treat refractory epilepsy and has shown promise in many neurologic diseases. It has also gained recent popularity for its weight loss effects. Several preclinical studies have confirmed a benefit of ketosis on cognition and systemic inflammation. Given the renewed emphasis on neuroinflammation as a pathogenic contributor to cognitive decline, and the decreased systemic inflammation observed with the ketogenic diet, it is plausible that this diet may delay, ameliorate, or prevent progression of cognitive decline. Several small human studies have shown benefit on cognition in dementia with a ketogenic diet intervention. Future, large controlled studies are needed to confirm this benefit; however, the ketogenic diet has shown promise in regard to delay or mitigation of symptoms of cognitive decline.

Cause for Concern: Behavioral and Psychological Symptoms of Dementia in Delaware's Long-Term Care Facilities.

Introduction: Much of the suffering and expense associated with treatment of persons with dementia (Major Neurocognitive Disorder) arises from associated noncognitive behavioral and psychological symptoms of dementia (BPSD). Although a consensus on the prevalence of BPSD is lacking, evidence suggests that most people with dementia will manifest one or more of these symptoms during the disorder's progression. BPSD raise the cost of care by leading to more frequent emergency room visits, more and longer hospitalizations, and earlier admission to long-term care facilities (LTCF). Treatment of BPSD presents a stressful challenge in LTCFs. We sought to investigate the care burden of BPSD in Delaware's LTCFs and to gather data that can inform management approaches. Methods: Using REDCap, we created an anonymous cross-sectional survey designed for completion by LTCF administrators. The Delaware Health Care Facilities Association (DHCFA) and Delaware's Division of Services for Aging and Adults with Physical Disabilities (DSAAPD) encouraged participation. A link to the survey was emailed to the administrators of 81 facilities in Delaware. The resulting data were evaluated using descriptive statistics. Results: Forty-four of the 81 facilities surveyed opened the survey link. Thirty-eight facilities answered at least some of the questions, and 19 surveys were fully completed. The reported average prevalence of BPSD among Delaware LTCF residents with dementia was 49.3% (SD 28.9). The five most frequently reported BPSD symptoms were anxiety, agitation, wandering, dysphoria/depression, and appetite/eating abnormalities. All facilities reported employing a spectrum of pharmacologic and non-pharmacologic management strategies. Twenty-two of 24 respondents (91.7%) reported that behavioral health consultation was available at their facilities and 18 of 20 respondents (90.0%) indicated that they provided training on how to manage residents with BPSD. Conclusion: BPSD are a pervasive concern among Delaware's LTCFs. LTCFs may benefit from the development of training programs and dissemination of treatment guidelines incorporating evidence-based interventions and their implementation in managing BPSD to improve care, decrease stress on residents and caregivers, and reduce some avoidable health care costs.

Bat and Lyssavirus Exposure among Humans in Area that Celebrates Bat Festival, Nigeria, 2010 and 2013.

Using questionnaires and serologic testing, we evaluated bat and lyssavirus exposure among persons in an area of Nigeria that celebrates a bat festival. Bats from festival caves underwent serologic testing for phylogroup II lyssaviruses (Lagos bat virus, Shimoni bat virus, Mokola virus). The enrolled households consisted of 2,112 persons, among whom 213 (10%) were reported to have ever had bat contact (having touched a bat, having been bitten by a bat, or having been scratched by a bat) and 52 (2%) to have ever been bitten by a bat. Of 203 participants with bat contact, 3 (1%) had received rabies vaccination. No participant had neutralizing antibodies to phylogroup II lyssaviruses, but >50% of bats had neutralizing antibodies to these lyssaviruses. Even though we found no evidence of phylogroup II lyssavirus exposure among humans, persons interacting with bats in the area could benefit from practicing bat-related health precautions.

Human Rabies - Utah, 2018.

On November 3, 2018, the Utah Department of Health (UDOH) was notified of a suspected human rabies case in a man aged 55 years. The patient's symptoms had begun 18 days earlier, and he was hospitalized for 15 days before rabies was suspected. As his symptoms worsened, he received supportive care, but he died on November 4. On November 7, a diagnosis of rabies was confirmed by CDC. This was the first documented rabies death in a Utah resident since 1944. This report summarizes the patient's clinical course and the subsequent public health investigation, which determined that the patient had handled several bats in the weeks preceding symptom onset. Public health agencies, in partnership with affected health care facilities, identified and assessed the risk to potentially exposed persons, facilitated receipt of postexposure prophylaxis (PEP), and provided education to health care providers and the community about the risk for rabies associated with bats. Human rabies is rare and almost always fatal. The findings from this investigation highlight the importance of early recognition of rabies, improved public awareness of rabies in bats, and the use of innovative tools after mass rabies exposure events to ensure rapid and recommended risk assessment and provision of PEP.

Human Rabies - Virginia, 2017.

On May 9, 2017, the Virginia Department of Health was notified regarding a patient with suspected rabies. The patient had sustained a dog bite 6 weeks before symptom onset while traveling in India. On May 11, CDC confirmed that the patient was infected with a rabies virus that circulates in dogs in India. Despite aggressive treatment, the patient died, becoming the ninth person exposed to rabies abroad who has died from rabies in the United States since 2008. A total of 250 health care workers were assessed for exposure to the patient, 72 (29%) of whom were advised to initiate postexposure prophylaxis (PEP). The total pharmaceutical cost for PEP (rabies immunoglobulin and rabies vaccine) was approximately $235,000. International travelers should consider a pretravel consultation with travel health specialists; rabies preexposure prophylaxis is warranted for travelers who will be in rabies endemic countries for long durations, in remote areas, or who plan activities that might put them at risk for a rabies exposures.

Machine Learning Enhances the Efficiency of Cognitive Screenings for Primary Care.

BACKGROUND: Incorporation of cognitive screening into the busy primary care will require the development of highly efficient screening tools. We report the convergence validity of a very brief, self-administered, computerized assessment protocol against one of the most extensively used, clinician-administered instruments-the Montreal Cognitive Assessment (MoCA). METHOD: Two hundred six participants (mean age = 67.44, standard deviation [SD] = 11.63) completed the MoCA and the computerized test. Three machine learning algorithms (ie, Support Vector Machine, Random Forest, and Gradient Boosting Trees) were trained to classify participants according to the clinical cutoff score of the MoCA (ie, < 26) from participant performance on 25 features of the computerized test. Analysis employed Synthetic Minority Oversampling TEchnic to correct the sample for class imbalance. RESULTS: Gradient Boosting Trees achieved the highest performance (accuracy = 0.81, specificity = 0.88, sensitivity = 0.74, F1 score = 0.79, and area under the curve = 0.81). A subsequent K-means clustering of the prediction features yielded 3 categories that corresponded to the unimpaired (mean = 26.98, SD = 2.35), mildly impaired (mean = 23.58, SD = 3.19), and moderately impaired (mean = 17.24, SD = 4.23) ranges of MoCA score ( F = 222.36, P < .00). In addition, compared to the MoCA, the computerized test correlated more strongly with age in unimpaired participants (ie, MoCA ≥26, n = 165), suggesting greater sensitivity to age-related changes in cognitive functioning. CONCLUSION: Future studies should examine ways to improve the sensitivity of the computerized test by expanding the cognitive domains it measures without compromising its efficiency.

A Delphi study of late-onset personality disorders.

OBJECTIVES: The DSM-5 describes personality disorders (PDs) as emerging in early life and remaining continuous throughout the life-span. Yet case studies and expert opinion support the existence of late-onset PDs. Little is known about PDs in late life, and our instruments for assessing them are not well validated. Thus, the focus of this exploratory Delphi study was the late-onset PD, with special attention to the accuracy of the core criteria for the diagnosis. DESIGN: A Delphi study was designed to assess the presentation of PDs in late life. The Delphi consisted of three successive rounds of inquiry. Between rounds, the participants were provided with a summary of the panel's responses. PARTICIPANTS: A panel of 21 experts included published authors, researchers, and teachers from the USA, the UK, Australia, France, Belgium, and the Netherlands. MEASUREMENTS: Researchers designed a survey that included an introduction, a demographic questionnaire, and five questions that varied in presentation and response format. RESULTS: Experts reached consensus that a variant of PD appears de novo in old age. The core features of inflexibility and pervasiveness may not pertain to late-onset PD. There was agreement that frequently occurring life events contribute selectively to the expression of late-onset PD, with the major ones being death of a spouse or partner and transition to a nursing or assisted-living facility. CONCLUSIONS: Nearly all participants took the position that PD can present for the first time in old age and be clinically identifiable without having been so identified earlier in life.

Potential Confounding of Diagnosis of Rabies in Patients with Recent Receipt of Intravenous Immune Globulin.

Rabies is an acute encephalitis that is nearly always fatal. It is caused by infection with viruses of the genus Lyssavirus, the most common of which is Rabies lyssavirus. The Council of State and Territorial Epidemiologists (CSTE) defines a confirmed human rabies case as an illness compatible with rabies that meets at least one of five different laboratory criteria.* Four of these criteria do not depend on the patient's rabies vaccination status; however, the remaining criterion, "identification of Lyssavirus-specific antibody (i.e. by indirect fluorescent antibody…test or complete [Rabies lyssavirus] neutralization at 1:5 dilution) in the serum," is only considered diagnostic in unvaccinated patients. Lyssavirus-specific antibodies include Rabies lyssavirus-specific binding immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies and Rabies lyssavirus neutralizing antibodies (RLNAs). This report describes six patients who were tested for rabies by CDC and who met CSTE criteria for confirmed human rabies because they had illnesses compatible with rabies, had not been vaccinated for rabies, and were found to have serum RLNAs (with complete Rabies lyssavirus neutralization at a serum dilution of 1:5). An additional four patients are described who were tested for rabies by CDC who were found to have serum RLNAs (with incomplete Rabies lyssavirus neutralization at a serum dilution of 1:5) despite having not been vaccinated for rabies. None of these 10 patients received a rabies diagnosis; rather, they were considered to have been passively immunized against rabies through recent receipt of intravenous immune globulin (IVIG). Serum RLNA test results should be interpreted with caution in patients who have not been vaccinated against rabies but who have recently received IVIG.

Cognitively Impaired Physicians: How Do We Detect Them? How Do We Assist Them?

Our older physicians, an increasing number of those in practice, constitute a valuable human resource in the medical profession. Professional satisfaction, increasing life expectancy, concerns regarding financial security, and reluctance to retire are among the many reasons a physician might choose to extend practice into later adulthood. Despite the benefits of experience and expertise acquired by older physicians, cognitive changes associated with normal or pathological aging have been shown to have a significant negative effect on physician performance. Age-based cognitive assessment of physicians has been adopted in some countries and by some U.S. healthcare institutions for patient protection and improvement of physician quality of life, but there is no general guideline for the assessment and assistance of cognitively impaired late career physicians in the United States. Self-reports and reports from peers are an inadequate safeguard, leaving impaired physicians and their patients at risk. In this discussion, we will describe cognitive aging, the effects of cognitive aging on physician performance, some current monitoring systems, and recommendations for identifying and assisting physicians found to be impaired.

A cross-validation Delphi method approach to the diagnosis and treatment of personality disorders in older adults.

INTRODUCTION: The Delphi method is a consensus-building technique using expert opinion to formulate a shared framework for understanding a topic with limited empirical support. This cross-validation study replicates one completed in the Netherlands and Belgium, and explores US experts' views on the diagnosis and treatment of older adults with personality disorders (PD). METHODS: Twenty-one geriatric PD experts participated in a Delphi survey addressing diagnosis and treatment of older adults with PD. The European survey was translated and administered electronically. RESULTS: First-round consensus was reached for 16 out of 18 items relevant to diagnosis and specific mental health programs for personality disorders in older adults. Experts agreed on the usefulness of establishing criteria for specific types of treatments. The majority of psychologists did not initially agree on the usefulness of pharmacotherapy. Expert consensus was reached following two subsequent rounds after clarification addressing medication use. CONCLUSIONS: Study results suggest consensus among regarding psychosocial treatments. Limited acceptance amongst US psychologists about the suitability of pharmacotherapy for late-life PDs contrasted with the views expressed by experts surveyed in Netherlands and Belgium studies.