Anion Exchange and Lateral Heterostructure Formation in Ferromagnetic PEA2Cr(Cl,Br)4 Two-Dimensional Perovskites.

Postsynthetic vapor-phase anion exchange in the ferromagnetic two-dimensional (2D) hybrid metal-halide perovskite, PEA2CrCl4 (PEA+ = phenethylammonium), is reported. Anion exchange using vaporous trimethylsilyl bromide (TMS-Br) is shown to drive complete conversion of solution-processed PEA2CrCl4 polycrystalline thin films to PEA2CrBr4. Low-temperature magnetic circular dichroism spectroscopy indicates ferromagnetic ordering in these PEA2CrCl4 and PEA2CrBr4 films. Via partial anion exchange of exfoliated flakes of PEA2CrCl4 single crystals, we demonstrate that it is possible to generate abrupt lateral PEA2CrCl4/PEA2CrBr4 magneto-heterointerfaces. Kinetic studies reveal that lateral heterostructure formation is dictated by rapid edge-site halide exchange followed by slower intralayer bromide diffusion, and there is negligible interlayer (3D) bromide or TMS-Br diffusion. The importance of the bulky PEA+ interlayer cation in suppressing 3D diffusion is highlighted by parallel anion-exchange experiments on MA2CrCl4 (MA+ = methylammonium), which instead show 3D exchange. Comparison of anion-exchange reactions in PEA2CrCl4, PEA2MnCl4, and PEA2PbCl4 shows that 2D bromide diffusion is slowest in PEA2CrCl4, attributed to the antiferrodistortive ordering found in this composition. In addition to demonstrating both postsynthetic composition control and heterostructure formation in ferromagnetic Cr-based 2D perovskites for the first time, these results also advance our fundamental understanding of ion-exchange processes in this relatively unexplored family of 2D perovskites, broadening opportunities for investigation and control of novel spin effects in low-dimensional metal-halide perovskites.

Preclinical immunogenicity and safety of hemagglutinin-encoding modRNA influenza vaccines.

Seasonal epidemics of influenza viruses are responsible for a significant global public health burden. Vaccination remains the most effective way to prevent infection; however, due to the persistence of antigenic drift, vaccines must be updated annually. The selection of vaccine strains occurs months in advance of the influenza season to allow adequate time for production in eggs. RNA vaccines offer the potential to accelerate production and improve efficacy of influenza vaccines. We leveraged the nucleoside-modified RNA (modRNA) platform technology and lipid nanoparticle formulation process of the COVID-19 mRNA vaccine (BNT162b2; Comirnaty®) to create modRNA vaccines encoding hemagglutinin (HA) (modRNA-HA) for seasonal human influenza strains and evaluated their preclinical immunogenicity and toxicity. In mice, a monovalent modRNA vaccine encoding an H1 HA demonstrated robust antibody responses, HA-specific Th1-type CD4+ T cell responses, and HA-specific CD8+ T cell responses. In rhesus and cynomolgus macaques, the vaccine exhibited durable functional antibody responses and HA-specific IFN-γ+ CD4+ T cell responses. Immunization of mice with monovalent, trivalent, and quadrivalent modRNA-HA vaccines generated functional antibody responses targeting the seasonal influenza virus(es) encoded in the vaccines that were greater than, or similar to, those of a licensed quadrivalent influenza vaccine. Monovalent and quadrivalent modRNA-HA vaccines were well-tolerated by Wistar Han rats, with no evidence of systemic toxicity. These nonclinical immunogenicity and safety data support further evaluation of the modRNA-HA vaccines in clinical studies.

The Effects of Onychectomy (Declawing) on Forearm and Leg Myology in a Kinkajou (Potos flavus).

Recently, onychectomy, the "declaw" surgery in which all or part of the distal phalanges are removed, has been shown to have significant effects on the forearm muscles of felids. While this surgery should clearly affect the limb muscles (especially those that insert on the removed or modified bone), these effects have not been studied beyond felids or in the hindlimb. To that end, we herein evaluated the muscle architecture of a kinkajou (Potos flavus) that was declawed on all four of its limbs and compared its anatomy to that of intact specimens and the felid findings. As expected, some of the declawed kinkajou's muscles were substantially different from those of the intact specimens, and as was seen in felids, its digital muscles appear to have been weaker. However, unlike in the felids, the declawed kinkajou had relatively larger forearm muscles. Also, contrary to expectation, the leg muscles of the declawed kinkajou were not substantially different, perhaps reflecting important differences in limb use. Future analyses should examine this anatomy in other declawed kinkajou specimens and also look at the effects of this surgery in other taxa, for instance, non-arboreal relatives of the kinkajou as well as other arboreal taxa.

Real-world experience in treatment of donor-derived Hepatitis C virus in kidney transplant recipients with delayed initiation, shortened course glecaprevir/pibrentasvir versus standard of care.

BACKGROUND: There is limited literature describing the real-world practice of delayed initiation and shortened duration direct-acting antiviral (DAA) in kidney transplant recipients. We compared Hepatitis C virus (HCV) cure rates among kidney transplant recipients who received an HCV nucleic acid test positive (NAT +) kidney and were treated with sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks or glecaprevir/pibrentasvir (G/P) for 8 weeks, a duration that is 4 weeks shorter than the guideline recommendation for treatment delay beyond 1-week post-transplant. METHODS: Retrospective study of HCV-negative adult patients who received a kidney transplant from an HCV NAT+ donor between April 2019 and April 2022 treated with either SOF/VEL for 12 weeks or G/P for 8 weeks. The primary outcome was sustained virologic response 12 weeks after completion of therapy (SVR12). Secondary outcomes included time to DAA initiation, renal function, graft loss, patient death, liver function tests, and opportunistic infections. RESULTS: 102 kidney transplant recipients were included with 36 treated with G/P and 66 treated with SOF/VEL. All 36 (100%) treated with G/P achieved SVR12. One patient in the SOF/VEL group failed to achieve SVR12 but received additional therapy and was cured. Time to DAA initiation was similar with a mean of 4 weeks. There was no difference in AST/ALT > 3x ULN or renal function. One rejection occurred in each group. No patient death or graft loss was observed. There was no difference in cytomegalovirus and BK viremia between groups.  CONCLUSION: Delayed initiation of DAA therapy with 12 weeks of SOF/VEL or 8 weeks of G/P achieves SVR12 in kidney transplant recipients without significant adverse effects.

Virtual stimulation of the interictal EEG network localizes the EZ as a measure of cortical excitability.

Introduction: For patients with drug-resistant epilepsy, successful localization and surgical treatment of the epileptogenic zone (EZ) can bring seizure freedom. However, surgical success rates vary widely because there are currently no clinically validated biomarkers of the EZ. Highly epileptogenic regions often display increased levels of cortical excitability, which can be probed using single-pulse electrical stimulation (SPES), where brief pulses of electrical current are delivered to brain tissue. It has been shown that high-amplitude responses to SPES can localize EZ regions, indicating a decreased threshold of excitability. However, performing extensive SPES in the epilepsy monitoring unit (EMU) is time-consuming. Thus, we built patient-specific in silico dynamical network models from interictal intracranial EEG (iEEG) to test whether virtual stimulation could reveal information about the underlying network to identify highly excitable brain regions similar to physical stimulation of the brain. Methods: We performed virtual stimulation in 69 patients that were evaluated at five centers and assessed for clinical outcome 1 year post surgery. We further investigated differences in observed SPES iEEG responses of 14 patients stratified by surgical outcome. Results: Clinically-labeled EZ cortical regions exhibited higher excitability from virtual stimulation than non-EZ regions with most significant differences in successful patients and little difference in failure patients. These trends were also observed in responses to extensive SPES performed in the EMU. Finally, when excitability was used to predict whether a channel is in the EZ or not, the classifier achieved an accuracy of 91%. Discussion: This study demonstrates how excitability determined via virtual stimulation can capture valuable information about the EZ from interictal intracranial EEG.

Risk it for a biscuit: Food safety behaviours and food insecurity of older adults.

Foodborne disease presents a significant public health issue, costing the UK economy £9 billion annually, with many incidences being due to food-related behaviours in the home. Adults aged 60 and over account for around a quarter of the population in England and Wales and are at a greater risk of foodborne disease and may suffer a much higher burden. Research into risky food behaviours has previously focused on larger cohorts and typically treats the over 60's as one homogenous group. The current paper aims to identify the characteristics associated with risky food-related practices related to cooking, cleaning, chilling, cross-contamination, and use-by date adherence. The current research analysed data from the Official Statistics survey, Food and You 2: Wave 6 (2022-23). A series of binary logistic regression models examined the characteristics associated with risky food-related practices. We demonstrate that the characteristics associated with risky behaviours are not uniform, with different factors being associated with specific behaviours. We suggest that risky behaviours cannot be targeted efficiently with a one size fits all approach. This research provides an evidence base for policy makers to target risky food behaviours in this understudied vulnerable group.

Air pollution, traffic noise, mental health, and cognitive development: A multi-exposure longitudinal study of London adolescents in the SCAMP cohort.

BACKGROUND: There is increasing evidence that air pollution and noise may have detrimental psychological impacts, but there are few studies evaluating adolescents, ground-level ozone exposure, multi-exposure models, or metrics beyond outdoor residential exposure. This study aimed to address these gaps. METHODS: Annual air pollution and traffic noise exposure at home and school were modelled for adolescents in the Greater London SCAMP cohort (N=7555). Indoor, outdoor and hybrid environments were modelled for air pollution. Cognitive and mental health measures were self-completed at two timepoints (baseline aged 11-12 and follow-up aged 13-15). Associations were modelled using multi-level multivariate linear or ordinal logistic regression. RESULTS: This is the first study to investigate ground-level ozone exposure in relation to adolescent executive functioning, finding that a 1 interquartile range increase in outdoor ozone corresponded to -0.06 (p < 0.001) z-score between baseline and follow-up, 38 % less improvement than average (median development + 0.16). Exposure to nitrogen dioxide (NO2), 24-hour traffic noise, and particulate matter < 10 µg/m3 (PM10) were also significantly associated with slower executive functioning development when adjusting for ozone. In two-pollutant models, particulate matter and ozone were associated with increased externalising problems. Daytime and evening noise were associated with higher anxiety symptoms, and 24-hour noise with worse speech-in-noise perception (auditory processing). Adjusting for air pollutants, 24-hour noise was also associated with higher anxiety symptoms and slower fluid intelligence development. CONCLUSIONS: Ozone's potentially detrimental effects on adolescent cognition have been overlooked in the literature. Our findings also suggest harmful impacts of other air pollutants and noise on mental health. Further research should attempt to replicate these findings and use mechanistic enquiry to enhance causal inference. Policy makers should carefully consider how to manage the public health impacts of ozone, as efforts to reduce other air pollutants such as NO2 can increase ozone levels, as will the progression of climate change.

Effects of Menopause and High Fat Diet on Metabolic Outcomes in a Mouse Model of Alzheimer's Disease.

Background: About two-thirds of those with Alzheimer's disease (AD) are women, most of whom are post-menopausal. Menopause accelerates dementia risk by increasing the risk for metabolic, cardiovascular, and cerebrovascular diseases. Mid-life metabolic disease (obesity, diabetes/prediabetes) is a well-known risk factor for dementia. A high fat diet can lead to poor metabolic health in both humans and rodents. Objective: Our goal was to determine the effects of a high fat diet on metabolic outcomes in the AppNL-F knock-in mouse model of AD and assess the effects of menopause. Methods: First, 3-month-old AppNL-F and WT female mice were placed on either a control or a high fat diet until 10 months of age then assessed for metabolic outcomes. Next, we did a more extensive assessment in AppNL-F mice that were administered VCD (4-vinylcyclohexene diepoxide) or vehicle (oil) and placed on a control or high fat diet for 7 months. VCD was used to model menopause by causing accelerated ovarian failure. Results: Compared to WT controls, AD female mice had worse glucose intolerance. Menopause led to metabolic impairment (weight gain and glucose intolerance) and further exacerbated obesity in response to a high fat diet. There were interactions between diet and menopause on some metabolic health serum biomarkers and the expression of hypothalamic markers related to energy balance. Conclusions: This work highlights the need to model endocrine aging in animal models of dementia and will contribute to further understanding the interaction between menopause and metabolic health in the context of AD.

Health assessment of nesting loggerhead sea turtles (Caretta caretta) in one of their largest rookeries (central eastern Florida coast, USA).

Reproduction is a physiologically demanding process for sea turtles. Health indicators, including morphometric indices and blood analytes, provide insight into overall health, physiology and organ function for breeding sea turtles as a way to assess population-level effects. The Archie Carr National Wildlife Refuge (ACNWR) on Florida's central eastern coast is critical nesting habitat for loggerhead sea turtles (Caretta caretta), but health variables from this location have not been documented. Objectives of the study were to (1) assess morphometrics and blood analyte data (including haematology, plasma biochemistry, protein electrophoresis, ß-hydroxybutyrate, trace nutrients, vitamins and fatty acid profiles) from loggerheads nesting on or near the beaches of the ACNWR, (2) investigate correlations of body condition index (BCI) with blood analytes and (3) analyse temporal trends in morphometric and blood analyte data throughout the nesting season. Morphometric and/or blood analyte data are reported for 57 nesting loggerheads encountered between 2016 and 2019. Plasma copper and iron positively correlated with BCI. Mass tended to decline across nesting season, whereas BCI did not. Many blood analytes significantly increased or decreased across nesting season, reflecting the catabolic state and haemodynamic variations of nesting turtles. Twenty-three of 34 fatty acids declined across nesting season, which demonstrates the physiological demands of nesting turtles for vitellogenesis and reproductive activities, thus suggesting potential utility of fatty acids for the assessment of foraging status and phases of reproduction. The findings herein are relevant for future spatiotemporal and interspecies comparisons, investigating stressor effects and understanding the physiological demands in nesting sea turtles. This information provides comparative data for individual animals in rescue or managed care settings and for assessment of conservation strategies.

We Don't Talk About X(Twitter): A Cross-Sectional Analysis of Social Media Utilization Among Neurologists.

BACKGROUND AND OBJECTIVES: Medical professionals use social media for career development, education, clinical outreach, or advocacy. Prior studies estimate that 25% to 65% of health care providers use social media professionally; however, the number of users and platforms are rapidly changing. Therefore, as part of a broader study, we set out to assess platform preferences and social media usage among neurologists. METHODS: This was a multisite cross-sectional analysis consisting of a REDCap survey of clinicians, residents, and medical students. Faculty, trainees, or clinical year medical students interested in child neurology or adult neurology residency or fellowship programs within the United States were eligible to participate. Recruitment methods were broad to encompass as diverse and extensive participation as possible. Results were analyzed using descriptive statistics. Data are presented according to the STROBE guidelines. RESULTS: Of the 226 neurology respondents, 55% (n = 124) were child neurology and 45% (n = 102) were adult neurology across all career stages, including students. Of the 70% who reported using social media in a professional capacity, the most commonly reported reasons were for networking and collaboration (n = 95, 60%), self-directed medical learning (n = 90, 57%), and brand building and reputation (n = 62, 39%). Twitter and Facebook were the most common and versatile platforms used by neurologists. Medical students had the highest documentation of social media scholarships on their curriculum vitae (37%, P = .016) and the most interest (33%, P = .016) in learning how to document social media scholarships if they were not already. Early faculty shared this interest more than residents, fellows, or mid-late career faculty. In all groups except for mid-late career faculty, a majority of respondents (>75%) showed interest in learning how to leverage social media for career development. DISCUSSION: Social media is used professionally by a majority of neurologists, most commonly for networking, self-directed learning, and building individual brands. Opportunities exist to better understand platform preferences and ways to optimize their use for various professional activities as well as to provide education on effective professional use of social media including documentation for promotion.

COBALT: A Confirmatory Trial of Obeticholic Acid in Primary Biliary Cholangitis With Placebo and External Controls.

INTRODUCTION: Obeticholic acid (OCA) treatment for primary biliary cholangitis (PBC) was conditionally approved in the phase 3 POISE trial. The COBALT confirmatory trial assessed whether clinical outcomes in patients with PBC improve with OCA therapy. METHODS: Patients randomized to OCA (5-10 mg) were compared with placebo (randomized controlled trial [RCT]) or external control (EC). The primary composite endpoint was time to death, liver transplant, model for end-stage liver disease score ≥15, uncontrolled ascites, or hospitalization for hepatic decompensation. A prespecified propensity score-weighted EC group was derived from a US healthcare claims database. RESULTS: In the RCT, the primary endpoint occurred in 28.6% of OCA (n = 168) and 28.9% of placebo patients (n = 166; intent-to-treat analysis hazard ratio [HR] = 1.01, 95% confidence interval = 0.68-1.51), but functional unblinding and crossover to commercial therapy occurred, especially in the placebo arm. Correcting for these using inverse probability of censoring weighting and as-treated analyses shifted the HR to favor OCA. In the EC (n = 1,051), the weighted primary endpoint occurred in 10.1% of OCA and 21.5% of non-OCA patients (HR = 0.39; 95% confidence interval = 0.22-0.69; P = 0.001). No new safety signals were identified in the RCT. DISCUSSION: Functional unblinding and treatment crossover, particularly in the placebo arm, confounded the intent-to-treat estimate of outcomes associated with OCA in the RCT. Comparison with the real-world EC showed that OCA treatment significantly reduced the risk of negative clinical outcomes. These analyses demonstrate the value of EC data in confirmatory trials and suggest that treatment with OCA improves clinical outcomes in patients with PBC.

Rethinking the Three Rs: Growing Momentum Toward a New Gold Standard in Australian Research.

Recent years have seen increasing recognition of the scientific, economic and ethical benefits of the use of non-animal models in advancing preclinical research, giving reason to rethink the application and framework of the Three Rs. However, to benefit from the economic advantages of shifting to such alternative methods, and to realise Australia's drug development potential, legislative reform is essential. Such reform should be responsive to international regulations that encourage the use of animal-free methods, and be coupled with a corresponding re-evaluation of current Three Rs frameworks and principles. If these supportive changes, and the recommendations from the 2023 Australian Commonwealth Scientific and Industrial Research Organisation (CSIRO) Futures Non-animal models report, are implemented concurrently - with government support paramount- then a new gold standard for scientific research in Australia could be created in which the use of non-animal models and animal-free methods is the default.

Vivifying Outbreaks: Investigating the Influence of a Forecast Visual on Risk Perceptions, Time-Urgency, and Behavioral Intentions.

Although visual depictions of epidemiological data are not new in public health, the US public saw more of them during the COVID-19 pandemic than ever before. In this study, we considered visualizations of forecasts (i.e. predictions of how a disaster will unfold over time) formatted as line charts. We investigated how two choices scientists make when creating a forecast visual - the outcome of focus (cases or deaths) and the amount of data provided (more or less data) about the past or the potential future - shape behavioral intentions via risk-related appraisals (e.g. threat and efficacy). In an online experiment, participants (N = 236) viewed a written health alert about a novel airborne virus, with one of the eight versions of a forecast visual or no visual (text only). The results of the experiment showed that exposing people to a health alert with a forecast visual in it may be less effective than anticipated. Reading a written health alert with a forecast visual was, at best, equal to outcomes from reading an alert without it, and sometimes it performed worse: participants appraised the novel virus as a less urgent threat and the recommended solutions as less efficacious. Implications of the findings for theories of risk and visual health communication and practical considerations for future health communicators were discussed.

Supporting Timor-Leste midwives and nurses through an educational program: An evaluative study.

Little is currently known about the impacts of participation in a five-week Australian maternal and newborn health training program for Timorese midwives and nurses. BACKGROUND: The maternal mortality rate in Timor-Leste is estimated to be around 204 per 100,000 live births, and there is a correlation between safe and quality maternal and newborn health services. Hence, there is a need to develop the nation's maternity workforce. Whilst numerous training programs have been geared towards improving the knowledge and skills of Timorese midwives and nurses, to date, no published study has evaluated their impact on participants. AIM: To describe satisfaction of an Australian maternal and newborn health training program for Timorese midwives and nurses and its impact based upon the participants survey and qualitative evaluations. METHODS: An evaluative study was conducted using a survey to explore the impacts of a five-week Australian residential training program on 12 Timorese midwives and one nurse. FINDINGS: The survey data demonstrated an increase in the participants knowledge and skills required to provide enhanced maternal and newborn care; post-training, most participants demonstrated increased knowledge of obstetric emergencies. The participants showed the most pronounced increase in Advanced Clinical Skills in the subjects of fetal assessment, neonatal resuscitation and obstetric emergencies. The qualitative data identified two main themes and six subthemes related to professionalism, communication, and connections. CONCLUSION: An Australian residential training program, provided in collaboration with local Rotary clubs can enhance the development of maternal and newborn healthcare skills for midwives and nurses from Timor-Leste.

Network excitability of stimulation-induced spectral responses helps localize the seizure onset zone.

OBJECTIVE: While evoked potentials elicited by single pulse electrical stimulation (SPES) may assist seizure onset zone (SOZ) localization during intracranial EEG (iEEG) monitoring, induced high frequency activity has also shown promising utility. We aimed to predict SOZ sites using induced cortico-cortical spectral responses (CCSRs) as an index of excitability within epileptogenic networks. METHODS: SPES was conducted in 27 epilepsy patients undergoing iEEG monitoring and CCSRs were quantified by significant early (10-200 ms) increases in power from 10 to 250 Hz. Using response power as CCSR network connection strengths, graph centrality measures (metrics quantifying each site's influence within the network) were used to predict whether sites were within the SOZ. RESULTS: Across patients with successful surgical outcomes, greater CCSR centrality predicted SOZ sites and SOZ sites targeted for surgical treatment with median AUCs of 0.85 and 0.91, respectively. We found that the alignment between predicted and targeted SOZ sites predicted surgical outcome with an AUC of 0.79. CONCLUSIONS: These findings indicate that network analysis of CCSRs can be used to identify increased excitability of SOZ sites and discriminate important surgical targets within the SOZ. SIGNIFICANCE: CCSRs may supplement traditional passive iEEG monitoring in seizure localization, potentially reducing the need for recording numerous seizures.

The ecology of giant kelp colonization and its implications for kelp forest restoration.

The success and cost-effectiveness of kelp forest restoration hinges on understanding the colonization ecology of kelps, particularly with respect to dispersal potential, recruitment success, and subsequent establishment. To gain needed insight into these processes we examined spatial patterns and temporal trajectories of the colonization of a large artificial reef by the giant kelp Macrocystis pyrifera. The 151 ha artificial reef complex was constructed in three phases over 21 years, enabling dispersal, recruitment, and subsequent establishment to be examined for a wide range of environmental conditions, dispersal distances, and source population sizes. Natural colonization of all phases of the artificial reef by giant kelp was rapid (within 1 year) and extended across the entire 7-km-long reef complex. Colonization density declined with distance from the nearest source population, but only during the first phase when the distance from the nearest source population was ≤3.5 km. Despite this decline, recruitment on artificial reef modules farthest from the source population was sufficient to produce dense stands of kelp within a couple of years. Experimental outplanting of the artificial reef with laboratory-reared kelp embryos was largely successful but proved unnecessary, as the standing biomass of kelp resulting from natural recruitment exceeded that observed on nearby natural reefs within 2-3 years of artificial reef construction for all three phases. Such high potential for natural colonization following disturbance has important implications for kelp forest restoration efforts that employ costly and logistically difficult methods to mimic this process by active seeding and transplanting.