Search

Influenza viruses continually evolve new antigenic variants, through mutations in epitopes of their major surface proteins, hemagglutinin (HA) and neuraminidase (NA). Antigenic drift potentiates the reinfection of previously infected individuals, but the contribution of this process to variability in annual epidemics is not well understood. Here, we link influenza A(H3N2) virus evolution to regional epidemic dynamics in the United States during 1997-2019. We integrate phenotypic measures of HA antigenic drift and sequence-based measures of HA and NA fitness to infer antigenic and genetic distances between viruses circulating in successive seasons. We estimate the magnitude, severity, timing, transmission rate, age-specific patterns, and subtype dominance of each regional outbreak and find that genetic distance based on broad sets of epitope sites is the strongest evolutionary predictor of A(H3N2) virus epidemiology. Increased HA and NA epitope distance between seasons correlates with larger, more intense epidemics, higher transmission, greater A(H3N2) subtype dominance, and a greater proportion of cases in adults relative to children, consistent with increased population susceptibility. Based on random forest models, A(H1N1) incidence impacts A(H3N2) epidemics to a greater extent than viral evolution, suggesting that subtype interference is a major driver of influenza A virus infection ynamics, presumably via heterosubtypic cross-immunity.

With increasing battery demand comes a need for diversified Li sources beyond brines. Among all Li-bearing minerals, spodumene is most often used for its high Li content and natural abundance. However, the traditional approach to process spodumene is costly and energy-intensive, requiring the mineral be transformed from its natural α to β phase at >1000 °C. Acid leaching is then applied, followed by neutralization to precipitate Li2CO3. In this work, we report an alternative method to extract Li directly from α-spodumene, which is performed at lower temperatures and avoids the use of acids. It is shown that Li2CO3 is formed with >90% yield at 750 °C by reacting α-spodumene with Na2CO3 and Al2O3. The addition of Al2O3 is critical to reduce the amount of Li2SiO3 that forms when only Na2CO3 is used, instead providing increased thermodynamic driving force to form NaAlSiO4 and Li2CO3 as the sole products. We find that this reaction is most effective at 4 h, after which volatility limits the yield. Following its extraction, Li2CO3 can be isolated by washing the sample using deionized water. This energy-saving and acid-free route to obtain Li2CO3 directly from spodumene can help meet the growing demand for Li.

Abstract Background The targeted application of cutting-edge high-throughput molecular data technologies provides an enormous opportunity to address key health, economic and environmental issues in the tropics within the One Health framework. The Earth’s tropical regions are projected to contain > 50% of the world’s population by 2050 coupled with 80% of its biodiversity however these regions are relatively less developed economically, with agricultural productivity substantially lower than temperate zones, a large percentage of its population having limited health care options and much of its biodiversity understudied and undescribed. The generation of high-throughput molecular data and bespoke bioinformatics capability to address these unique challenges offers an enormous opportunity for people living in the tropics. Main In this review we discuss in depth solutions to challenges to populations living in tropical zones across three critical One Health areas: human health, biodiversity and food production. This review will examine how some of the challenges in the tropics can be addressed through the targeted application of advanced omics and bioinformatics and will discuss how local populations can embrace these technologies through strategic outreach and education ensuring the benefits of the One Health approach is fully realised through local engagement. Conclusion Within the context of the One Health framework, we will demonstrate how genomic technologies can be utilised to improve the overall quality of life for half the world’s population.

Abstract Background Predicting which children and young people (CYP) are at the highest risk of developing post-COVID-19 condition (PCC) could improve care pathways. We aim to develop and validate prediction models for persistent PCC up to 24 months post-infection in CYP. Methods CYP who were PCR-positive between September 2020 and March 2021, with follow-up data up to 24-months post-infection, were analysed. Persistent PCC was defined in two ways, as PCC at (a) 3, 6, 12 and 24 months post-infection (N = 943) or (b) 6, 12 and 24 months post-infection (N = 2373). Prediction models were developed using logistic regression; performance was assessed using calibration and discrimination measures; internal validation was performed via bootstrapping; the final model was adjusted for overfitting. Results While 24.7% (233/943) of CYP met the PCC definition 3 months post-infection, only 7.2% (68/943) continued to meet the PCC definition at all three subsequent timepoints, i.e. at 6, 12 and 24 months. The final models predicting risk of persistent PCC (at 3, 6, 12 and 24 months and at 6, 12 and 24 months) contained sex (female), history of asthma, allergy problems, learning difficulties at school and family history of ongoing COVID-19 problems, with additional variables (e.g. older age at infection and region of residence) in the model predicting PCC at 6, 12 and 24 months. Internal validation showed minimal overfitting of models with good calibration and discrimination measures (optimism-adjusted calibration slope: 1.064–1.142; C-statistic: 0.724–0.755). Conclusions To our knowledge, these are the only prediction models estimating the risk of CYP persistently meeting the PCC definition up to 24 months post-infection. The models could be used to triage CYP after infection. CYP with factors predicting longer-term symptomology, may benefit from earlier support.

Mark Brommeyer,1,2 Maxine Whittaker,1 Zhanming Liang1 1James Cook University, Townsville, QLD, Australia; 2Flinders University, Adelaide, SA, AustraliaCorrespondence: Mark Brommeyer, College of Business, Government and Law, Flinders University, GPO Box 2100, Adelaide, SA, 5001, Australia, Email mark.brommeyer@flinders.edu.auIntroduction: Healthcare is experiencing a global period of profound transformation, and digital health shows the promise of dispensing innovative and contemporary service models. However, changes are required to improve the capabilities of health managers in driving successful digital transformation.Objective: This paper aims to explore the organizational barriers that health service managers have encountered when realizing the benefits of a digitally transforming environment. This is part of a larger research study exploring digital competencies for health service managers, with the findings from focus group discussions providing a baseline from which to address the organizational improvements and changes in system capabilities required to assist in realizing the benefits of digital health transformation.Methods: The study is qualitative in nature. It employs focus group discussions to gain an in-depth understanding of the experiences and views of health service managers and identify the benefits and barriers that managers have experienced in introducing digital health in their workplace.Results: Barriers encountered in realizing digital health benefits in the workplace were evidenced across five major themes: (1) change resistance and usage, (2) trust and uniformity, (3) resourcing and procurement, (4) digital literacy, and (5) siloed systems.Discussion: Findings from this study demonstrate that in driving the realization of digital health transformation benefits, health service managers need organizational and system-wide efforts to support managing in the digital health context. The key identified barriers experienced by health service managers include facing human and technical challenges with system adoption and the governance of data-driven decision-making in the digital context.Conclusion: The importance of digital transformation in healthcare is evident and will increasingly become a necessity for organizational survival and success. This study adds important insights into the organizational barriers that health service managers have encountered when realizing the benefits resulting from digital transformation. Addressing these barriers requires macro-, meso- and micro-level system investments. These benefits are enhanced by enabling factors critical for digital health adoption that have been described in key categories involving health system related: (1) policy and system, (2) organizational structure and processes, and human resource management, and (3) people factors. The importance of ensuring the organizational factors driving the realization of benefits in a digitally transforming environment is also addressed and capitalized upon for health service managers.Keywords: healthcare management, health service manager, digital transformation, digital health benefits, workforce development, digital health barriers

Abstract Background Incorporating patient and public involvement (PPI) in research is crucial for ensuring the relevance and success of studies, yet it remains significantly underutilised in surgical research. Main body This commentary presents insights from our neurosurgical research team’s experience with establishing and working with a PPI group called “Science for Tomorrow’s Neurosurgery” on research regarding novel intra-operative optical imaging techniques. Through collaboration with patient-focused charities, we have successfully incorporated patient perspectives into our work at each stage of the research pipeline, whilst adhering to core PPI principles, such as reciprocal relationships, co-learning, partnerships, and transparency. Conclusion We highlight the specific value added to our work in terms of participant recruitment, research ethics and results dissemination.

Abstract It has long been recognised that spreading ridges are kept in place by competing subduction forces that drive plate motions. Asymmetric strain rates pull spreading ridges in the direction of the strongest slab pull force, which partially explains why spreading ridges can migrate vast distances. However, the interaction between mantle plumes and spreading ridges plays a relatively unknown role on the evolution of plate boundaries. Using a numerical model of mantle convection, we show that plumes with high buoyancy flux (>3000 kg/s) can capture spreading ridges within a 1000 km radius and anchor them in place. Exceptionally high buoyancy fluxes may fragment the overriding plate into smaller plates to accommodate more efficient plate motion. If the plume buoyancy flux wanes below 1000 kg/s the ridge may be de-anchored, leading to rapid ridge migration rates when combined with asymmetric plate boundary forces. Our results show that plume-ridge de-anchoring may have contributed to the rapid migration of the SE Indian Ridge from 43 million years ago (Ma) due to waning buoyancy flux from the Kerguelen plume, supported by magma flux estimates and radiogenic isotope geochemistry of eruption products. The plume-ridge de-anchoring mechanism we have identified has global implications for the evolution of plate boundaries near mantle plumes.

Abstract Severe febrile illnesses in children encompass life-threatening organ dysfunction caused by diverse pathogens and other severe inflammatory syndromes. A comparative approach to these illnesses may identify shared and distinct features of host immune dysfunction amenable to immunomodulation. Here, using immunophenotyping with mass cytometry and cell stimulation experiments, we illustrate trajectories of immune dysfunction in 74 children with multi-system inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2, 30 with bacterial infection, 16 with viral infection, 8 with Kawasaki disease, and 42 controls. We explore these findings in a secondary cohort of 500 children with these illnesses and 134 controls. We show that neutrophil activation and apoptosis are prominent in multi-system inflammatory syndrome, and that this is partially shared with bacterial infection. We show that memory T cells from patients with multi-system inflammatory syndrome and bacterial infection are exhausted. In contrast, we show viral infection to be characterized by a distinct signature of decreased interferon signaling and lower interferon receptor gene expression. Improved understanding of immune dysfunction may improve approaches to immunomodulator therapy in severe febrile illnesses in children.

Abstract Background Simulation assessment can result in anxiety for students. These assessments involve being observed by assessors, so there is a significant socio-evaluative stress component which may cause greater anxiety if assessors are visible to students during assessments. The aim of this study was to determine the effect of assessor visibility on biological and physiological markers of stress and levels of anxiety experienced by pre-hospital emergency care students in a simulation assessment environment. Methods A paired comparison, pre-post test research design was used with two conditions; an assessor visible condition with simulation assessors visible to students in the room and an assessor not visible condition with assessors not in the room but connected via video link. With a sample of 29 emergency care students anxiety was measured with the State-Trait Anxiety Inventory and stress was measured with salivary cortisol and heart rate variability (HRV). Results Differences in state anxiety scores, HRV variables and salivary cortisol suggested lower stress and anxiety in the assessor visible group. Only heart rate was significantly different between the groups (p = 0.016), with a higher heart rate in the assessor not visible group. Conclusions Greater stress and anxiety may be experienced by students during emergency care simulation assessments when assessors are not visible to students.

Abstract Per- and poly-fluoroalkyl substances (PFAS) have gained widespread attention due to their adverse effects on health and environment. Developing efficient technology to capture PFAS from contaminated sources remains a great challenge. In this study, we introduce a type of reusable polymeric sorbent (PFPE-IEX + ) for rapid, efficient, and selective removal of multiple PFAS impurities from various contaminated water sources. The resin achieves >98% removal efficiency ([PFPE-IEX + ] = 0.5–5 mg mL−1, [PFAS]0 = 1–10 ppb in potable water and landfill leachate) and >500 mg g−1 sorption capacity for the 11 types of examined PFAS. We achieve efficient PFAS removal without breakthrough and subsequent resin regeneration and demonstrate good PFAS recovery in a proof-of-concept cartridge setup. The outcomes of this study offer valuable guidance to the design of platforms for efficient and selective PFAS capture from contaminated water, such as drinking water and landfill leachate.

Abstract Background Low physical activity among older adults is related to adverse health outcomes such as depression and loneliness, poor physical function and increased risk of falls. This study was designed to increase physical activity through a digital, group-based, physical activity and music intervention and to examine its effectiveness on social, mental and physical health outcomes. Methods Participants were 34 older adults (65 years +) recruited across four care homes in Scotland to a pilot study. Surveys were administered at baseline and post-intervention, comprising measures of fear of falling, depression and anxiety, loneliness, sleep satisfaction and quality of life. A battery of physical function tests and saliva sampling for cortisol and dehydroepiandrosterone hormone analysis were also conducted at each time point. Additionally, process evaluation measures (recruitment, intervention fidelity, attendance, retention rates and safety) were monitored. The intervention comprised 12 weeks of three prescribed digital sessions per week: movement and music (n = 2) and music-only (n = 1), delivered by an activity coordinator in the care home. Post-intervention interviews with staff and participants were conducted to gain qualitative data on the acceptability of the intervention. Results An average of 88% of prescribed sessions were delivered. Pre- to post-intervention intention-to-treat analysis across all participants revealed significant improvements in anxiety, salivary DHEA, fear of falling and loneliness. There were no significant improvements in health-related quality of life, perceived stress, sleep satisfaction or physical function tests, including handgrip strength. Qualitative analysis highlighted benefits of and barriers to the programme. Conclusions The digital movement and music intervention was deemed acceptable and delivered with moderate fidelity, justifying progression to a full-scale trial. Although a proper control group would have yielded more confident causal relationships, preliminary psychosocial and biological effects were evident from this trial. To show significant improvements in physical function, it is likely that a bigger sample size providing sufficient power to detect significant changes, greater adherence, longer intervention and/or higher exercise volume may be necessary. Trial registration The trial is registered at ClinicalTrials.gov, number NCT05601102 on 01/11/2022.

Abstract POT1 variants have been identified in familial melanoma (FM) as well as a number of other germline and somatic malignancies. The functional validation of variants identified from the screening of patients with melanoma gene susceptibility panels is key to understanding the clinical significance of identified variants. Here we report a novel, likely pathogenic POT1 missense variant (p.G95V) in FM and investigate its functional impact. We demonstrate loss of function owing to the inability of the mutant POT1 protein to bind telomeric DNA compared to its wild‐type counterpart. This study provides important functional validation of a novel POT1 variant in FM.

As a “cold tumor”, triple-negative breast cancer (TNBC) exhibits limited responsiveness to current immunotherapy. How to enhance the immunogenicity and reverse the immunosuppressive microenvironment of TNBC remain a formidable challenge. Herein, an “in situ nanovaccine” Au/CuNDs-R848 was designed for imaging-guided photothermal therapy (PTT)/chemodynamic therapy (CDT) synergistic therapy to trigger dual immunoregulatory effects on TNBC. On the one hand, Au/CuNDs-R848 served as a promising photothermal agent and nanozyme, achieving PTT and photothermal-enhanced CDT against the primary tumor of TNBC. Meanwhile, the released antigens and damage-associated molecular patterns (DAMPs) promoted the maturation of dendritic cells (DCs) and facilitated the infiltration of T lymphocytes. Thus, Au/CuNDs-R848 played a role as an “in situ nanovaccine” to enhance the immunogenicity of TNBC by inducing immunogenic cell death (ICD). On the other hand, the nanovaccine suppressed the myeloid‐derived suppressor cells (MDSCs), thereby reversing the immunosuppressive microenvironment. Through the dual immunoregulation, “cold tumor” was transformed into a “hot tumor”, not only implementing a “turning foes to friends” therapeutic strategy but also enhancing immunotherapy against metastatic TNBC. Furthermore, Au/CuNDs-R848 acted as an excellent nanoprobe, enabling high-resolution near-infrared fluorescence and computed tomography imaging for precise visualization of TNBC. This feature offers potential applications in clinical cancer detection and surgical guidance. Collectively, this work provides an effective strategy for enhancing immune response and offers novel insights into the potential clinical applications for tumor immunotherapy.

The objective of the study was to examine how distinct psychopathic traits, including callous-unemotional (CU) traits, impulsivity and narcissism, as well as family, school and friend social support are longitudinally associated with cyberbullying and cyber-victimization. Associations were investigated by employing a four-year longitudinal design in a large sample of Greek-Cypriot adolescents. Findings suggested that cyber-bullying and cyber-victimization decreased from early to middle adolescence. Additionally, the longitudinal model suggested that both CU traits and narcissism, assessed in grade 7, were associated with the onset of cyber-bullying and cyber-victimization in grade 8, but not with change over time. Impulsivity did not predict cyber-bullying or cyber-victimization. Finally, none of the environmental factors were associated with the onset and growth of cyber-bullying, although family support predicted girls' initial levels and change over time in cyber-victimization. Current findings have major theoretical and practical implications for the development of cyber-bullying and victimization.

This study used a person-centered approach to identify school readiness profiles in a sample of kindergartners (n=1,826) from a large and diverse school district in the United States. Using latent profile analyses and multilevel modeling, we examined three aims: 1) whether patterns of readiness skills at kindergarten entry could be detected, 2) the extent to which detected patterns predicted gains in academic and social-emotional skills, and 3) whether the quality of teacher-child interactions moderated the associations between profile membership and end of kindergarten outcomes. Based on a comparison of fit indices, a 4-profile solution best represented the data. Eighteen percent of children were in the "High Risk" profile, 34% were in the "Ready" profile, 20% percent of children were in the "Social-Emotional Risk" profile, and 28% of children were in the "High Readiness" profile. For all outcomes, we found that profile membership predicted spring scores, after controlling for fall scores of each skill, suggesting that the constellation of kindergarten readiness skills matters more than any one skill. We also found that the quality of teacher-child interactions moderated associations between profile membership and changes in achievement and problem behavior for children within some groups. Results suggest that children enter kindergarten with unique profiles of skills and that supports for children may need to be individualized based on profiles to maximize social, emotional, and academic development. Results also suggest that high quality teacher-child interactions may serve as an important protective and promotive factor for children with certain clusters of readiness skills at kindergarten entry.

This article considers a pilot research project that examines the successes, failures, and best practice approaches for delivering online performing arts education experiences to young people around Australia. In conversation with 15 teaching artists and 18 youth-based arts organisations nationally, it evaluates the challenges and innovations in live online arts education experienced during the COVID-19 pivot. In doing so it examines pedagogies that foreground embodied and playful collaboration and diversified access for participants. It recognises the role of youth arts in reshaping creativity learning and opens considerations of the role digital educations may play in increased arts accessibility.

In England, music education policy is deeply rooted in neoliberal ideologies, shaping classroom practice and assessments. This paper presents findings from a four-year funded longitudinal project exploring the impact of musical partnerships on young people at risk of educational exclusion. Through a posthuman lens, the researchers made a methodological shift, acknowledging the agency of non-human elements and physical spaces in musical interactions. Posthumanism offered alternative insights, challenging traditional notions of music education practice and extended human-centric perspectives and school assessment metrics. It expanded our understanding of what it means to be a musician and pedagogue. This paper proposes that posthumanism can challenge existing notions of music education practice while simultaneously moving the discussion of important matters in music education research into new areas of thinking, doing, and being.

Subcortical white matter stroke (WMS) is a progressive disorder which is demarcated by the formation of small ischemic lesions along white matter tracts in the CNS. As lesions accumulate, patients begin to experience severe motor and cognitive decline. Despite its high rate of incidence in the human population, our understanding of the cause and outcome of WMS is extremely limited. As such, viable therapies for WMS remain to be seen. This study characterizes myelin recovery following stroke and motor learning-based rehabilitation in a mouse model of subcortical WMS. Following WMS, a transient increase in differentiating oligodendrocytes occurs within the peri-infarct in young male adult mice, which is completely abolished in male aged mice. Compound action potential recording demonstrates a decrease in conduction velocity of myelinated axons at the peri-infarct. Animals were then tested on one of three distinct motor learning-based rehabilitation strategies (skilled reach, restricted access to a complex running wheel, and unrestricted access to a complex running wheel) for their capacity to induce repair. These studies determined that unrestricted access to a complex running wheel alone increases the density of differentiating oligodendrocytes in infarcted white matter in young adult male mice, which is abolished in aged male mice. Unrestricted access to a complex running wheel was also able to enhance conduction velocity of myelinated axons at the peri-infarct to a speed comparable to naive controls suggesting functional recovery. However, there was no evidence of motor rehabilitation-induced remyelination or myelin protection.SIGNIFICANCE STATEMENT White matter stroke is a common disease with no medical therapy. A form of motor rehabilitation improves some aspects of white matter repair and recovery.

Circadian disruptions impact nearly all people with Alzheimer's disease (AD), emphasizing both their potential role in pathology and the critical need to investigate the therapeutic potential of circadian-modulating interventions. Here, we show that time-restricted feeding (TRF) without caloric restriction improved key disease components including behavioral timing, disease pathology, hippocampal transcription, and memory in two transgenic (TG) mouse models of AD. We found that TRF had the remarkable capability of simultaneously reducing amyloid deposition, increasing Aβ42 clearance, improving sleep and memory, and normalizing daily transcription patterns of multiple genes, including those associated with AD and neuroinflammation. Thus, our study unveils for the first time the pleiotropic nature of timed feeding on AD, which has far-reaching effects beyond metabolism, ameliorating neurodegeneration and the misalignment of circadian rhythmicity. Since TRF can substantially modify disease trajectory, this intervention has immediate translational potential, addressing the urgent demand for accessible approaches to reduce or halt AD progression.