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Rocky Mountain spotted fever (RMSF) is a fatal tick-borne zoonotic disease that has emerged as an epidemic in western North America since the turn of the 21st century. Along the US south-western border and across northern Mexico, the brown dog tick, Rhipicephalus sanguineus, is responsible for spreading the disease between dogs and humans. The widespread nature of the disease and the ongoing epidemics contrast with historically sporadic patterns of the disease. Because dogs are amplifying hosts for the Rickettsia rickettsii bacteria, transmission dynamics between dogs and ticks are critical for understanding the epidemic. In this paper, we developed a compartment metapopulation model and used it to explore the dynamics and drivers of RMSF in dogs and brown dog ticks in a theoretical region in western North America. We discovered that there is an extended lag-as much as two years-between introduction of the pathogen to a naïve population and epidemic-level transmission, suggesting that infected ticks could disseminate extensively before disease is detected. A single large city-size population of dogs was sufficient to maintain the disease over a decade and serve as a source for disease in surrounding smaller towns. This model is a novel tool that can be used to identify high risk areas and key intervention points for epidemic RMSF spread by brown dog ticks.

The cultural challenge of educating Haitian rehabilitation professionals was identified by a Canadian francophone university which collaborated in the implementation and organization of international internships. Ethical cross-border internationalization should ensure reciprocity for partners. With this as a central value and in a context of pedagogical resource scarcity in Haiti, an intercultural educational partnership involved Haitian and Canadian university students situated in their respective countries in a Problem-Based Learning (PBL) course. Teachers and students applied principles of decolonization of health pedagogy principles were applied by teacher and students throughout this cross-border virtual synchronous PBL course. The aim of this study was to determine the feasibility and to identify facilitators and obstacles to conducting a cross-border virtual synchronous PBL course and its perceived benefits in the development of professional competencies. Five Canadian students and five Haitian students, all volunteers, took part in a 3-week cross-border virtual synchronous PBL course. Deductive qualitative content analysis of the transcripts from a 120-minute focus group discussion held one week after the course and a logbook kept during the project was conducted. The criteria deemed important to successfully replicate this project relate to: 1) The attributes of the students and teachers involved; 2) pedagogical preparation activities; and 3) the use of multiple communication strategies and connectivity plans. In addition to the acquisition of course content not readily available in Haiti, the student interactions inherent in the PBL method supported the acquisition of competencies such as collaboration, communication, and change agent advocacy promoted by the Canadian association of occupational therapy which contribute greatly to strengthening the students' professional identity.

Many educators and professional organizations recommend Quantitative Reasoning as the best entrylevel postsecondary mathematics course for non-STEM majors. However, novice and veteran instructors who have no prior experience in teaching a QR course often express their ignorance of the content to choose for this course, the instruction to offer students, and the assessments to measure student learning. We conducted a case study to investigate the initial implementation of an entry-level university quantitative reasoning course during fall semester, 2018. The participants were the course instructor and students. We examined the instructor's motives and actions and the students' responses to the course. The instructor had no prior experience teaching a QR course but did have 15 years of experience teaching student-centered mathematics. Data included course artifacts, class observations, an instructor interview, and students' written reflections. Because this was a new course--and to adapt to student needs--the instructor employed his instructional autonomy and remained flexible in designing and enacting the course content, instruction, and assessment. His instructional decision making and flexible approach helped the instructor tailor the learning activities and teaching practices to the needs and interests of the students. The students generally appreciated and benefited from this approach, enjoyed the course, and provided positive remarks about the instructors' practices.

Currently, there are no existing measures to screen for or diagnose Social (Pragmatic) Communication Disorder (SPCD). We conducted an exploratory factor analysis (EFA) of the Social Communication Disorder Screener (SCDS), a 14-item, parent-report measure based on the DSM-5 diagnostic criteria for SPCD. This EFA examined the internal consistency and factor structure of the SCDS for a sample of 500 parents of children, ages 5-18 years, representative of the U.S. census. Results yielded a correlated three-factor solution with good internal consistency reliability. Findings supported the presence of three subscale as well as the derivation of a total composite score reflecting overall verbal and non-verbal communication and limitations across contexts. Clinical and research implications are discussed.

The purpose of this study was to explore career outcomes in young adulthood among adolescents with ADHD and/or high abilities. The sample included respondents who had the ability and ADHD measures from Waves 1 (1995), 3 (2002), and 4 (2009) of the National Longitudinal Study of Adolescent and Adult Health in-home questionnaire. Using multiple group path analysis, we examined the pathways for three groups of individuals (i.e., ADHD, high ability, and both/twice-exceptional). We discovered financial and educational family background predicted occupational status and career goal attainment, as well as supports and barriers among various family and adolescent predictors (e.g., school attachment, educational aspiration, depressive symptoms). Knowledge about these trajectories will help professionals design tailored career and educational services for adolescents with high ability, ADHD, and both.

Soft chemistry techniques, such as ion exchange, hold great potential for the development of battery electrode materials that cannot be stabilized via conventional equilibrium synthesis methods. Nevertheless, the intricate mechanisms governing ion exchange remain elusive. Herein, we investigate the evolution of the long-range and local structure, as well as the ion (de)intercalation mechanism during electrochemical Li-to-Na ion exchange initiated from an O3-type lithium-layered oxide cathode. The in situ-formed mixed-cation electrolyte leads to competitive intercalation of Li and Na ions. While Li ion intercalation predominates at the beginning of initial discharge, Na ion cointercalation into a different layer results in ion redistribution and phase separation, with the emergence of a P3-Na phase alongside an O3-Li phase. Further, this study spatially resolves the heterogeneous nature of electrochemical ion exchange reactions within individual particles and provides insights into the correlations between local Ni redox processes and phase separation. Overall, electrochemical ion exchange leads to a mixed-phase cathode and alters its reaction kinetics. Those findings have important implications for the development of new metastable materials for renewable energy devices and ion separation applications.

Autistic adults experience high rates of metal health difficulties and face significant barriers to accessing appropriate mental health care. Empirical research and recent professional guidelines emphasise the importance of modifying standard mental health interventions to best meet the needs of autistic adults. This systematic review explored mental health professionals' experiences of adapting mental health interventions for autistic adults. A systematic search was conducted on CINAHL, PsychINFO, PubMed, Scopus, and Web of Science in July 2022. The findings from 13 identified studies were synthesised using thematic synthesis. Three major analytical themes were generated, the unique experience of adapting interventions for autistic clients, factors which facilitate successful adaptations, and challenges to adapting interventions. Each theme contained a number of subsequent sub-themes. Professionals view the process of adapting interventions to be a highly individualised process. A range of personal traits, professional experiences, and systemic, service-based issues were identified in facilitating or challenging this individualised process. Further research regarding adaptations with different intervention models and increased supportive resources are required to enable professionals to successfully adapt interventions for autistic adult clients.

The twist-bend nematic liquid crystal phase is a three-dimensional fluid in which achiral bent molecules spontaneously form an orientationally ordered, macroscopically chiral, heliconical winding of a ten nanometer-scale pitch in the absence of positional ordering. Here, the structure of the twist-bend phase of the bent dimer CB7CB and its mixtures with 5CB is characterized, revealing a hidden invariance of the self-assembly of the twist-bend structure of CB7CB, such that over a wide range of concentrations and temperatures, the helix pitch and cone angle change as if the ground state for a pitch of the TB helix is an inextensible heliconical ribbon along the contour formed by following the local molecular long axis (the director). Remarkably, the distance along the length for a single turn of this helix is given by 2πRmol, where Rmol is the radius of bend curvature of a single all-trans CB7CB molecule. This relationship emerges from frustrated steric packing due to the bent molecular shape: space in the fluid that is hard to fill attracts the most flexible molecular subcomponents, a theme of nanosegregation that generates self-assembled, oligomer-like correlations of interlocking bent molecules in the form of a brickwork-like tiling of pairs of molecular strands into duplex double-helical chains. At higher temperatures in the twist-bend phase, the cone angle is small, the director contour is nearly along the helix axis z, and the duplex chains are sequences of biaxial elements formed by overlapping half-molecule pairs, with an approximately 45° rotation of the biaxis between each such element along the chain.

Soil microorganisms help transform plant inputs into mineral-associated soil organic carbon (SOC) – the largest and slowest-cycling pool of organic carbon on land. However, the microbial traits that influence this process are widely debated. While current theory and biogeochemical models have settled on carbon-use efficiency (CUE) and growth rate as positive predictors of mineral-associated SOC, empirical tests are sparse, with contradictory observations. Using 13C-labeling of an annual grass (Avena barbata) under two moisture regimes, we found that microbial traits associated with formation of 13C-mineral-associated SOC varied by soil habitat, as did active microbial taxa and SOC chemical composition. In the rhizosphere, bacterial-dominated communities with fast growth, high biomass, and high extracellular polymeric substance (EPS) production were positively associated with 13C-mineral-associated SOC. In contrast, the detritusphere held communities dominated by fungi and more filamentous bacteria, and with greater exoenzyme activity; there, 13C-mineral-associated SOC was associated with slower microbial growth and lower microbial biomass. CUE was a negative predictor of 13C-mineral-associated SOC in both habitats. Using 13C-quantitative stable isotope probing, we found that the majority of 13C assimilation in the rhizosphere and detritusphere at week 12 of the experiment was performed by very few bacterial and fungal taxa (3–5% of the total taxa that assimilated 13C). Several complementary chemical analyses (13C-NMR, FTICR-MS, and STXM-NEXAFS) suggested that SOC in the rhizosphere had a more oxidized chemical signature, while SOC in the detritusphere had a less oxidized, more lignin-like chemical signature. Our findings challenge current theory by demonstrating that microbial traits linked with mineral-associated SOC are not universal, but vary with soil habitat and moisture conditions, and are shaped by a small number of active taxa. Emerging SOC models that explicitly reflect these interactions may better predict SOC storage, since climate change causes shifts in soil moisture regimes and the ratio of living versus decaying roots.

Vocal production learning (vocal learning) is a convergently evolved trait in vertebrates. To identify brain genomic elements associated with mammalian vocal learning, we integrated genomic, anatomical, and neurophysiological data from the Egyptian fruit bat (Rousettus aegyptiacus) with analyses of the genomes of 215 placental mammals. First, we identified a set of proteins evolving more slowly in vocal learners. Then, we discovered a vocal motor cortical region in the Egyptian fruit bat, an emergent vocal learner, and leveraged that knowledge to identify active cis-regulatory elements in the motor cortex of vocal learners. Machine learning methods applied to motor cortex open chromatin revealed 50 enhancers robustly associated with vocal learning whose activity tended to be lower in vocal learners. Our research implicates convergent losses of motor cortex regulatory elements in mammalian vocal learning evolution.

OBJECTIVE: ACTN2, encoding alpha-actinin-2, is essential for cardiac and skeletal muscle sarcomeric function. ACTN2 variants are a known cause of cardiomyopathy without skeletal muscle involvement. Recently, specific dominant monoallelic variants were reported as a rare cause of core myopathy of variable clinical onset, although the pathomechanism remains to be elucidated. The possibility of a recessively inherited ACTN2-myopathy has also been proposed in a single series. METHODS: We provide clinical, imaging, and histological characterization of a series of patients with a novel biallelic ACTN2 variant. RESULTS: We report seven patients from five families with a recurring biallelic variant in ACTN2: c.1516A>G (p.Arg506Gly), all manifesting with a consistent phenotype of asymmetric, progressive, proximal, and distal lower extremity predominant muscle weakness. None of the patients have cardiomyopathy or respiratory insufficiency. Notably, all patients report Palestinian ethnicity, suggesting a possible founder ACTN2 variant, which was confirmed through haplotype analysis in two families. Muscle biopsies reveal an underlying myopathic process with disruption of the intermyofibrillar architecture, Type I fiber predominance and atrophy. MRI of the lower extremities demonstrate a distinct pattern of asymmetric muscle involvement with selective involvement of the hamstrings and adductors in the thigh, and anterior tibial group and soleus in the lower leg. Using an in vitro splicing assay, we show that c.1516A>G ACTN2 does not impair normal splicing. INTERPRETATION: This series further establishes ACTN2 as a muscle disease gene, now also including variants with a recessive inheritance mode, and expands the clinical spectrum of actinopathies to adult-onset progressive muscle disease.

Rocky Mountain spotted fever (RMSF) is a fatal tick-borne zoonotic disease that has emerged as an epidemic in western North America since the turn of the 21st century. Along the US south-western border and across northern Mexico, the brown dog tick, Rhipicephalus sanguineus, is responsible for spreading the disease between dogs and humans. The widespread nature of the disease and the ongoing epidemics contrast with historically sporadic patterns of the disease. Because dogs are amplifying hosts for the Rickettsia rickettsii bacteria, transmission dynamics between dogs and ticks are critical for understanding the epidemic. In this paper, we developed a compartment metapopulation model and used it to explore the dynamics and drivers of RMSF in dogs and brown dog ticks in a theoretical region in western North America. We discovered that there is an extended lag—as much as two years—between introduction of the pathogen to a naïve population and epidemic-level transmission, suggesting that infected ticks could disseminate extensively before disease is detected. A single large city-size population of dogs was sufficient to maintain the disease over a decade and serve as a source for disease in surrounding smaller towns. This model is a novel tool that can be used to identify high risk areas and key intervention points for epidemic RMSF spread by brown dog ticks.

The purpose of this study is to introduce a method for converting scored 4-option multiple-choice (MC) items into scored 3-option MC items without re-pretesting the 3-option MC items. This study describes a six-step process for achieving this goal. Data from a professional credentialing exam was used in this study and the method was applied to 24 forms of the exam. The results found 100% accuracy in predicting the rounded passing score for all forms.

Suburban inequality is the focus of this double issue of "RSF: The Russell Sage Foundation Journal of the Social Sciences." This introduction addresses the limited related scholarship, describes how inequality unfolds differently in suburban communities than in urban and rural communities, and draws attention to urgent issues related to stratification between and within suburban communities. We argue that inattention to the study of suburban space, methodological and disciplinary silos, and the changing nature of the suburbs have left large holes in our understanding of how inequality operates. This critical review covers areas such as measurement, forgotten suburban scholarship, demographic change, suburban poverty, social supports, race, immigration, education, politics, policing, and future directions for suburban studies. In our call for resisting amnesia, we also draw attention to forgotten suburban histories and studies of a diverse range of suburban communities.

In Australia, there is no one cohesive program design or curriculum which provides a framework for adult learning in Adult Community Education (ACE) organisations, with the two major states New South Wales (NSW) and Victoria leading the most developed systems. Many adult learners who learn in these education settings return to study to find pathways to employment, or to re-train for a new role after losing their job. In addition, later-life learners may attend because they want to remain healthy, participate in leisure activities, build friendships and remain active and engaged in their later years. Many of the learners are 'second chance learners' who have had prior negative experiences with the neoliberal system which assesses, ranks, and categorises learners according to their academic abilities. In this paper, we propose a comprehensive framework for the delivery of pre-accredited training in Australia, founded on social constructivist theory, learner-centred pedagogy, and course design enhanced by Nussbaum's Capability Framework. We commence the article by delivering a context for adult education policy and social justice education in the development of the ACE system. What we mean by a socially just education is one in which all people access a critical and democratic curriculum with equity and access to resources at its core. In this paper, we argue for the importance of adult learning, which is holistic, flexible, and nimble to cater for diverse learners and learning needs.

Despite the well-known relevance of polyamines to many forms of life, little is known about how polyamines regulate osteogenesis and skeletal homeostasis. Here, we report a series of in vitro studies conducted with human-bone-marrow-derived pluripotent stromal cells (MSCs). First, we show that during osteogenic differentiation, mRNA levels of most polyamine-associated enzymes are relatively constant, except for the catabolic enzyme spermidine/spermine N1-acetyltransferase 1 (SAT1), which is strongly increased at both mRNA and protein levels. As a result, the intracellular spermidine to spermine ratio is significantly reduced during the early stages of osteoblastogenesis. Supplementation of cells with exogenous spermidine or spermine decreases matrix mineralization in a dose-dependent manner. Employing N-cyclohexyl-1,3-propanediamine (CDAP) to chemically inhibit spermine synthase (SMS), the enzyme catalyzing conversion of spermidine into spermine, also suppresses mineralization. Intriguingly, this reduced mineralization is rescued with DFMO, an inhibitor of the upstream polyamine enzyme ornithine decarboxylase (ODC1). Similarly, high concentrations of CDAP cause cytoplasmic vacuolization and alter mitochondrial function, which are also reversible with the addition of DFMO. Altogether, these studies suggest that excess polyamines, especially spermidine, negatively affect hydroxyapatite synthesis of primary MSCs, whereas inhibition of polyamine synthesis with DFMO rescues most, but not all of these defects. These findings are relevant for patients with Snyder-Robinson syndrome (SRS), as the presenting skeletal defects-associated with SMS deficiency-could potentially be ameliorated by treatment with DFMO.

In this study, the effect of cumulative ACEs experienced on human maternal DNA methylation (DNAm) was estimated while accounting for interaction with domains of ACEs in prenatal peripheral blood mononuclear cell samples from the Maternal and Developmental Risks from Environmental Stressors (MADRES) pregnancy cohort. The intergenerational transmission of ACE-associated DNAm was also explored used paired maternal (N = 120) and neonatal cord blood (N = 69) samples. Replication in buccal samples was explored in the Childrens Health Study (CHS) among adult parental (N = 31) and pediatric (N = 114) samples. We used a four-level categorical indicator variable for ACEs exposure: none (0 ACEs), low (1-3 ACEs), moderate (4-6 ACEs), and high (>6 ACEs). Effects of ACEs on maternal DNAm (N = 240) were estimated using linear models. To evaluate evidence for intergenerational transmission, mediation analysis (N = 60 mother-child pairs) was used. Analysis of maternal samples displayed some shared but mostly distinct effects of ACEs on DNAm across low, moderate, and high ACEs categories. CLCN7 and PTPRN2 was associated with maternal DNAm in the low ACE group and this association replicated in the CHS. CLCN7 was also nominally significant in the gene expression correlation analysis among maternal profiles (N = 35), along with 11 other genes. ACE-associated methylation was observed in maternal and neonatal profiles in the COMT promoter region, with some evidence of mediation by maternal COMT methylation. Specific genomic loci exhibited mutually exclusive maternal ACE effects on DNAm in either maternal or neonatal population. There is some evidence for an intergenerational effect of ACEs, supported by shared DNAm signatures in the COMT gene across maternal-neonatal paired samples.

Preserving and regulating cellular homeostasis in the light of changing environmental conditions or developmental processes is of pivotal importance for single cellular and multicellular organisms alike. To counteract an imbalance in cellular homeostasis transcriptional programs evolved, called the heat shock response, unfolded protein response, and integrated stress response, that act cell-autonomously in most cells but in multicellular organisms are subjected to cell-nonautonomous regulation. These transcriptional programs downregulate the expression of most genes but increase the expression of heat shock genes, including genes encoding molecular chaperones and proteases, proteins involved in the repair of stress-induced damage to macromolecules and cellular structures. Sixty-one years after the discovery of the heat shock response by Ferruccio Ritossa, many aspects of stress biology are still enigmatic. Recent progress in the understanding of stress responses and molecular chaperones was reported at the 12th International Symposium on Heat Shock Proteins in Biology, Medicine and the Environment in the Old Town Alexandria, VA, USA from 28th to 31st of October 2023.

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism.

Through diverse roles, zinc determines a greater number of critical life functions than any other single micronutrient. Beyond the well-recognized importance of zinc for child growth and resistance to infections, zinc has numerous specific roles covering the regulation of glucose metabolism, and growing evidence links zinc deficiency with increased risk of diabetes and cardiometabolic disorders. Zinc nutriture is, thus, vitally important to health across the life course. Zinc deficiency is also one of the most common forms of micronutrient malnutrition globally. A clearer estimate of the burden of health disparity attributable to zinc deficiency in adulthood and later life emerges when accounting for its contribution to global elevated fasting blood glucose and related noncommunicable diseases (NCDs). Yet progress attenuating its prevalence has been limited due, in part, to the lack of sensitive and specific methods to assess human zinc status. This narrative review covers recent developments in our understanding of zincs role in health, the impact of the changing climate and global context on zinc intake, novel functional biomarkers showing promise for monitoring population-level interventions, and solutions for improving population zinc intake. It aims to spur on implementation of evidence-based interventions for preventing and controlling zinc deficiency across the life course. Increasing zinc intake and combating global zinc deficiency requires context-specific strategies and a combination of complementary, evidence-based interventions, including supplementation, food fortification, and food and agricultural solutions such as biofortification, alongside efforts to improve zinc bioavailability. Enhancing dietary zinc content and bioavailability through zinc biofortification is an inclusive nutrition solution that can benefit the most vulnerable individuals and populations affected by inadequate diets to the greatest extent.