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Outbreaks of emerging infectious diseases are influenced by local biotic and abiotic factors, with host declines occurring when conditions favour the pathogen. Deterioration in the population of the micro-endemic Tanzanian Kihansi spray toad (Nectophrynoides asperginis) occurred after the construction of a hydropower dam, implicating habitat modification in this species decline. Population recovery followed habitat augmentation; however, a subsequent outbreak of chytridiomycosis caused by Batrachochytrium dendrobatidis (Bd) led to the spray toad's extinction in the wild. We show using spatiotemporal surveillance and mitogenome assembly of Bd from archived toad mortalities that the outbreak was caused by invasion of the BdCAPE lineage and not the panzootic lineage BdGPL. Molecular dating reveals an emergence of BdCAPE across southern Africa overlapping with the timing of the spray toad's extinction. That our post-outbreak surveillance of co-occurring amphibian species in the Udzungwa Mountains shows widespread infection by BdCAPE yet no signs of ill-health or decline suggests these other species can tolerate Bd when environments are stable. We conclude that, despite transient success in mitigating the impact caused by dams' construction, invasion by BdCAPE caused the ultimate die-off that led to the extinction of the Kihansi spray toad. [ABSTRACT FROM AUTHOR]

Percentage changes greater than 100% are frequently used in consumer contexts; for example, a cordless vacuum cleaner may boast "125% longer runtime" compared to competitors. Via six studies (n  = 2,395) and 11 supplementary studies (n  = 3,249), the current research shows that consumers systematically underestimate the magnitude of percentage changes greater than 100%. Specifically, many consumers apply the relative size usage (e.g. "125% of," equivalent to 25% more) instead of the appropriate relative change (e.g. "125% more," equivalent to 100% more + 25% more), which leads them to be off by exactly 100% in their magnitude estimates. The rate of bias decreases when the difference between these two usages is emphasized. The Off by 100% bias occurs across a variety of consumer contexts, influencing behavioral intentions and incentive-compatible choice. The findings make theoretical contributions to research on processing of percentages, probability versus frequency formats, and magnitude judgments. Finally, understanding how different presentation formats of the same information can lead to different magnitude judgments enables marketers and policymakers to ensure more effective communication. [ABSTRACT FROM AUTHOR]

Shape‐conveying line drawings generated from 3D models normally create closed regions in image space. These lines and regions can be stylized to mimic various artistic styles, but for complex objects, the extracted topology is unnecessarily dense, leading to unappealing and unnatural results under stylization. Prior works typically simplify line drawings without considering the regions between them, and lines and regions are stylized separately, then composited together, resulting in unintended inconsistencies. We present a method for joint simplification of lines and regions simultaneously that penalizes large changes to region structure, while keeping regions closed. This feature enables region stylization that remains consistent with the outline curves and underlying 3D geometry. [ABSTRACT FROM AUTHOR]

Health services research is underpinned by partnerships between researchers and health services. Partnership-based research is increasingly needed to deal with the uncertainty of global pandemics, climate change induced severe weather events, and other disruptions. To date there is very little data on what has happened to health services research during the COVID-19 pandemic. This paper describes the establishment of an Australian multistate Decolonising Practice research project and charts its adaptation in the face of disruptions. The project used cooperative inquiry method, where partner health services contribute as coresearchers. When the COVID-19 pandemic hit, data collection needed to be immediately paused, and when restrictions started to lift, all research plans had to be renegotiated with services. Adapting the research surfaced health service, university, and staffing considerations. Our experience suggests that cooperative inquiry was invaluable in successfully navigating this uncertainty and negotiating the continuance of the research. Flexible, participatory methods such as cooperative inquiry will continue to be vital for successful health services research predicated on partnerships between researchers and health services into the future. They are also crucial for understanding local context and health services priorities and ways of working, and for decolonising Indigenous health research. [ABSTRACT FROM AUTHOR]

The amphibian‐infecting chytrid fungus, Batrachochytrium dendrobatidis (Bd), is widespread throughout Africa and is linked to declines of populations and species across the continent. While it is well established that the lineage of Bd encodes traits which determine disease severity, knowledge around how lineages are distributed according to environmental envelope is unclear. We here studied the distribution of Bd in South Africa based on the two lineages found, BdGPL and BdCAPE, in terms of their genome and environmental envelope statistically associated with their distribution. We used Bd surveillance data from published studies, as well as data collected during fieldwork from across South Africa, Lesotho, and eSwatini with samples collected along a transect spanning most of South Africa from Lesotho to the west coast. We utilized lineage‐typing qPCR to resolve the spatial distribution of BdGPL and BdCAPE across South Africa and used the resulting surveillance data to create a predictive ecological niche model for Bd lineages in South Africa. Phylogenomic analyses were performed on isolates sourced from across the transect. We show that BdGPL demonstrates a strong isolation by distance suggestive of stepping‐stone dispersal, while BdCAPE showed two distinct clusters within their genomic structure that appear geographically and temporally clustered, indicating two separate invasions. Our predictive niche model revealed that the two lineages tended to occur in different ecotypes; BdGPL was associated with lower altitude, arid regions while BdCAPE occurred across cooler, higher altitude environs. Niche predictions identified a zone of lineage contact, where genomics identified inter‐lineage recombinants. We argue that this zone of recombination should be prioritized for disease surveillance as it is a potential hotspot for the evolution of variants of amphibian chytrid with novel traits that may be epidemiologically relevant. [ABSTRACT FROM AUTHOR]

Background Carbapenem-resistant Enterobacterales (CRE) are an urgent public health threat in the United States. Objective Describe the clinical and molecular epidemiology of CRE in a multicenter pediatric cohort. Methods CRACKLE-1 and CRACKLE-2 are prospective cohort studies with consecutive enrollment of hospitalized patients with CRE infection or colonization between 24 December 2011 and 31 August 2017. Patients younger than age 18 years and enrolled in the CRACKLE studies were included in this analysis. Clinical data were obtained from the electronic health record. Carbapenemase genes were detected using polymerase chain reaction and whole-genome sequencing. Results Fifty-one children were identified at 18 healthcare system study sites representing all U.S. census regions. The median age was 8 months, with 67% younger than age 2 years. Median number of days from admission to culture collection was 11. Seventy-three percent of patients had required intensive care and 41% had a history of mechanical ventilation. More than half of children had no documented comorbidities (Q1, Q3 0, 2). Sixty-seven percent previously received antibiotics during their hospitalization. The most common species isolated were Enterobacter species (41%), Klebsiella pneumoniae (27%), and Escherichia coli (20%). Carbapenemase genes were detected in 29% of isolates tested, which was lower than previously described in adults from this cohort (61%). Thirty-four patients were empirically treated on the date of culture collection, but only 6 received an antibiotic to which the CRE isolate was confirmed susceptible in vitro. Thirty-day mortality was 13.7%. Conclusions CRE infection or colonization in U.S. children was geographically widespread, predominantly affected children younger than age 2 years, associated with significant mortality, and less commonly caused by carbapenemase-producing strains than in adults. [ABSTRACT FROM AUTHOR]

Context Thyroid nodule ultrasound-based risk stratification schemas rely on the presence of high-risk sonographic features. However, some malignant thyroid nodules have benign appearance on thyroid ultrasound. New methods for thyroid nodule risk assessment are needed. Objective We investigated polygenic risk score (PRS) accounting for inherited thyroid cancer risk combined with ultrasound-based analysis for improved thyroid nodule risk assessment. Methods The convolutional neural network classifier was trained on thyroid ultrasound still images and cine clips from 621 thyroid nodules. Phenome-wide association study (PheWAS) and PRS PheWAS were used to optimize PRS for distinguishing benign and malignant nodules. PRS was evaluated in 73 346 participants in the Colorado Center for Personalized Medicine Biobank. Results When the deep learning model output was combined with thyroid cancer PRS and genetic ancestry estimates, the area under the receiver operating characteristic curve (AUROC) of the benign vs malignant thyroid nodule classifier increased from 0.83 to 0.89 (DeLong, P value =.007). The combined deep learning and genetic classifier achieved a clinically relevant sensitivity of 0.95, 95% CI [0.88-0.99], specificity of 0.63 [0.55-0.70], and positive and negative predictive values of 0.47 [0.41-0.58] and 0.97 [0.92-0.99], respectively. AUROC improvement was consistent in European ancestry-stratified analysis (0.83 and 0.87 for deep learning and deep learning combined with PRS classifiers, respectively). Elevated PRS was associated with a greater risk of thyroid cancer structural disease recurrence (ordinal logistic regression, P value =.002). Conclusion Augmenting ultrasound-based risk assessment with PRS improves diagnostic accuracy. [ABSTRACT FROM AUTHOR]

This report surveys advances in deep learning‐based modelling techniques that address four different 3D indoor scene analysis tasks, as well as synthesis of 3D indoor scenes. We describe different kinds of representations for indoor scenes, various indoor scene datasets available for research in the aforementioned areas, and discuss notable works employing machine learning models for such scene modelling tasks based on these representations. Specifically, we focus on the analysis and synthesis of 3D indoor scenes. With respect to analysis, we focus on four basic scene understanding tasks – 3D object detection, 3D scene segmentation, 3D scene reconstruction and 3D scene similarity. And for synthesis, we mainly discuss neural scene synthesis works, though also highlighting model‐driven methods that allow for human‐centric, progressive scene synthesis. We identify the challenges involved in modelling scenes for these tasks and the kind of machinery that needs to be developed to adapt to the data representation, and the task setting in general. For each of these tasks, we provide a comprehensive summary of the state‐of‐the‐art works across different axes such as the choice of data representation, backbone, evaluation metric, input, output and so on, providing an organized review of the literature. Towards the end, we discuss some interesting research directions that have the potential to make a direct impact on the way users interact and engage with these virtual scene models, making them an integral part of the metaverse. [ABSTRACT FROM AUTHOR]

Neural image representations offer the possibility of high fidelity, compact storage, and resolution-independent accuracy, providing an attractive alternative to traditional pixel- and grid-based representations. However, coordinate neural networks fail to capture discontinuities present in the image and tend to blur across them; we aim to address this challenge. In many cases, such as rendered images, vector graphics, diffusion curves, or solutions to partial differential equations, the locations of the discontinuities are known. We take those locations as input, represented as linear, quadratic, or cubic Bézier curves, and construct a feature field that is discontinuous across these locations and smooth everywhere else. Finally, we use a shallow multi-layer perceptron to decode the features into the signal value. To construct the feature field, we develop a new data structure based on a curved triangular mesh, with features stored on the vertices and on a subset of the edges that are marked as discontinuous. We show that our method can be used to compress a 100, 0002-pixel rendered image into a 25MB file; can be used as a new diffusion-curve solver by combining with Monte-Carlo-based methods or directly supervised by the diffusion-curve energy; or can be used for compressing 2D physics simulation data. [ABSTRACT FROM AUTHOR]

Aspergillus fumigatus has been found to coinfect patients with severe SARS-CoV-2 virus infection, leading to COVID-19-associated pulmonary aspergillosis (CAPA). The CAPA all-cause mortality rate is approximately 50% and may be complicated by azole resistance. Genomic epidemiology can help shed light on the genetics of A. fumigatus causing CAPA, including the prevalence of resistance-associated alleles. We present a population genomic analysis of 21 CAPA isolates from four European countries with these isolates compared against 240 non-CAPA A. fumigatus isolates from a wider population. Bioinformatic analysis and antifungal susceptibility testing were performed to quantify resistance and identify possible genetically encoded azole-resistant mechanisms. The phylogenetic analysis of the 21 CAPA isolates showed that they were representative of the wider A. fumigatus population with no obvious clustering. The prevalence of phenotypic azole resistance in CAPA was 14.3% (n = 3/21); all three CAPA isolates contained a known resistance-associated cyp51A polymorphism. The relatively high prevalence of azole resistance alleles that we document poses a probable threat to treatment success rates, warranting the enhanced surveillance of A. fumigatus genotypes in these patients. Furthermore, potential changes to antifungal first-line treatment guidelines may be needed to improve patient outcomes when CAPA is suspected. [ABSTRACT FROM AUTHOR]

Several tendon and ligament animal models were presented at the 2022 Orthopaedic Research Society Tendon Section Conference held at the University of Pennsylvania, May 5 to 7, 2022. A key objective of the breakout sessions at this meeting was to develop guidelines for the field, including for preclinical tendon and ligament animal models. This review summarizes the perspectives of experts for eight surgical small and large animal models of rotator cuff tear, flexor tendon transection, anterior cruciate ligament tear, and Achilles tendon injury using the framework: "Why, Who, What, Where, When, and How" (5W1H). A notable conclusion is that the perfect tendon model does not exist; there is no single gold standard animal model that represents the totality of tendon and ligament disease. Each model has advantages and disadvantages and should be carefully considered in light of the specific research question. There are also circumstances when an animal model is not the best approach. The wide variety of tendon and ligament pathologies necessitates choices between small and large animal models, different anatomic sites, and a range of factors associated with each model during the planning phase. Attendees agreed on some guiding principles including: providing clear justification for the model selected, providing animal model details at publication, encouraging sharing of protocols and expertise, improving training of research personnel, and considering greater collaboration with veterinarians. A clear path for translating from animal models to clinical practice was also considered as a critical next step for accelerating progress in the tendon and ligament field. [ABSTRACT FROM AUTHOR]

Lithium is commonly prescribed as a mood stabilizer in a variety of mental health conditions, yet its molecular mode of action is incompletely understood. Many cellular events associated with lithium appear tied to mitochondrial function. Further, recent evidence suggests that lithium bioactivities are isotope specific. Here we focus on lithium effects related to mitochondrial calcium handling. Lithium protected against calcium-induced permeability transition and decreased the calcium capacity of liver mitochondria at a clinically relevant concentration. In contrast, brain mitochondrial calcium capacity was increased by lithium. Surprisingly, 7Li acted more potently than 6Li on calcium capacity, yet 6Li was more effective at delaying permeability transition. The size distribution of amorphous calcium phosphate colloids formed in vitro was differentially affected by lithium isotopes, providing a mechanistic basis for the observed isotope specific effects on mitochondrial calcium handling. This work highlights a need to better understand how mitochondrial calcium stores are structurally regulated and provides key considerations for future formulations of lithium-based therapeutics. [ABSTRACT FROM AUTHOR]

Sexual reproduction involving meiosis is essential in most eukaryotes. This produces offspring with novel genotypes, both by segregation of parental chromosomes as well as crossovers between homologous chromosomes. A sexual cycle for the opportunistic human pathogenic fungus Aspergillus fumigatus is known, but the genetic consequences of meiosis have remained unknown. Among other Aspergilli, it is known that A. flavus has a moderately high recombination rate with an average of 4.2 crossovers per chromosome pair, whereas A. nidulans has in contrast a higher rate with 9.3 crossovers per chromosome pair. Here, we show in a cross between A. fumigatus strains that they produce an average of 29.9 crossovers per chromosome pair and large variation in total map length across additional strain crosses. This rate of crossovers per chromosome is more than twice that seen for any known organism, which we discuss in relation to other genetic model systems. We validate this high rate of crossovers through mapping of resistance to the laboratory antifungal acriflavine by using standing variation in an undescribed ABC efflux transporter. We then demonstrate that this rate of crossovers is sufficient to produce one of the common multidrug resistant haplotypes found in the cyp51A gene (TR34/L98H) in crosses among parents harboring either of 2 nearby genetic variants, possibly explaining the early spread of such haplotypes. Our results suggest that genomic studies in this species should reassess common assumptions about linkage between genetic regions. The finding of an unparalleled crossover rate in A. fumigatus provides opportunities to understand why these rates are not generally higher in other eukaryotes. Aspergillus fumigatus is a saprotrophic fungus that can cause serious life-threatening invasive infections in immunocompromised individuals. By constructing a recombination map, this study shows that A. fumigatus produces the highest number of crossovers per chromosome ever described. [ABSTRACT FROM AUTHOR]

Aspergillus fumigatus is a genetically diverse fungal species, which is near ubiquitous in its global distribution and is the major cause of the life-threatening disease invasive aspergillosis. We present 3 de novo genome assemblies that were selected to be representative of the genetic diversity of clinical and environmental A. fumigatus. Sequencing using long-read Oxford Nanopore and subsequent assembly of the genomes yielded 10–23 contigs with an N50 of 4.05 Mbp to 4.93 Mbp. [ABSTRACT FROM AUTHOR]

Issues Addressed: Several national governments are showing interest in policies to promote wellbeing. One common strategy is to devise systems to measure indictors of wellbeing, presuming that governments act on what they measure. This article will argue instead that formation of multisectoral policies to promote psychological wellbeing requires a different kind of theoretical and evidentiary basis. Methods: The article integrates ideas from literature on wellbeing, health in all policies, political science, mental health promotion, and social determinants of health to make a case for place‐based policy as the central feature of multi‐sectoral policy for psychological wellbeing. Results and Discussion: I argue that the required theoretical foundation for policy action on psychological wellbeing lies with understanding certain basic functions of human social psychology including the role of stress arousal. I then draw on policy theory to propose three steps to translate this theoretical understanding of psychological wellbeing into practicable, multi‐sectoral policies. Step one is concerned with adopting a thoroughly revised conception of psychological wellbeing as a policy problem. Step two involves uptake of a theory of change in policy, grounded on recognition of essential social conditions required to promote psychological wellbeing. Proceeding from these, I will argue that a necessary (but not sufficient) third step is to implement place‐based strategies involving government‐community partnerships, to generate essential conditions for psychological wellbeing on a universal basis. Finally, I examine implications of the proposed approach for current theory and practice in mental health promotion policy. Conclusions: Place‐based policy is foundational for effective multi‐sectoral policy to promote psychological wellbeing. So What?: Governments aiming to promote psychological wellbeing should position place‐based policy at the centre of their strategies. [ABSTRACT FROM AUTHOR]

The chromobox-containing protein CBX4 is an important regulator of epithelial cell proliferation and differentiation, and has been implicated in several cancer types. The cancer stem cell (CSC) population is a key driver of metastasis and recurrence. The undifferentiated, plastic state characteristic of CSCs relies on cues from the microenvironment. Cancer-associated fibroblasts (CAFs) are a major component of the microenvironment that can influence the CSC population through the secretion of extracellular matrix and a variety of growth factors. Here we show CBX4 is a critical regulator of the CSC phenotype in squamous cell carcinomas of the skin and hypopharynx. Moreover, CAFs can promote the expression of CBX4 in the CSC population through the secretion of interleukin-6 (IL-6). IL-6 activates JAK/STAT3 signaling to increase ∆Np63α—a key transcription factor that is essential for epithelial stem cell function and the maintenance of proliferative potential that is capable of regulating CBX4. Targeting the JAK/STAT3 axis or CBX4 directly suppresses the aggressive phenotype of CSCs and represents a novel opportunity for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Ophüls (l.c.) considered that I C. immitis i Rixford & Gilchrist and I C. pyogenes i Rixford & Gilchrist represented a single species that should be included in I Oidium i and stated "[...] Its name then would be I Oidium coccidioides i , or, if there should be objections to the adoption of coccidioides, I Oidium protozoides i ." There was always a greater likelihood that I C. pyogenes i was I C. immitis i than I C. posadasii i because of the prevalence of I C. immitis i in California. A second species, I C. pyogenes i , was simultaneously described with I C. immitis i in 1896 and could have been either I C. immitis i itself or I C. posadasii i . Additionally, B we hereby designate CBS No. H-19784 as epitype to the lectotype b (MBT 10011884), thus maintaining Tintelnot & al.'s (l.c.) application of the name, I C. immitis i , as a species distinct from I C. posadasii i . [Extracted from the article]

Sporotrichosis is the main subcutaneous mycosis worldwide transmitted by animal or plant vectors and often escalates to outbreaks or epidemics. The current cat-transmitted sporotrichosis driven by Sporothrix brasiliensis has become a significant public health issue in South America. Transmission dynamics remain enigmatic due to the lack of development of polymorphic markers for molecular epidemiological analysis. This study used a high-throughput mining strategy to characterize simple sequence repeat (SSR) markers from Sporothrix genomes. A total of 118,140--143,912 SSR loci were identified (82,841--98,369 unique markers), with a 3651.55--3804.65 SSR/Mb density and a majority of dinucleotides motifs (GC/CG).We developed a panel of 15 highly polymorphic SSR markers suitable for genotyping S. brasiliensis, S. schenckii, and S. globosa. PCR amplification revealed 240 alleles in 180 Sporothrix isolates with excellent polymorphic information content (PIC = 0.9101), expected heterozygosity (H = 0.9159), and discriminating power (D = 0.7127), supporting the effectiveness of SSR markers in uncovering cryptic genetic diversity. A systematic population genetic study estimated three clusters, corresponding to S. brasiliensis (population 1, n = 97), S. schenckii (population 2, n = 49), and S. globosa (population 3, n = 34), with a weak signature of mixed ancestry between populations 1 and 2 or 3 and 2. Partitioning of genetic variation via AMOVA revealed highly structured populations (FPT = 0.539; Nm = 0.213; p < 0.0001), with approximately equivalent genetic variability within (46%) and between (54%) populations. Analysis of SSR diversity supports Rio de Janeiro (RJ) as the center of origin for contemporary S. brasiliensis infections. The recent emergence of cat-transmitted sporotrichosis in northeastern Brazil indicates an RJ-Northeast migration resulting in founder effects during the introduction of diseased animals into sporotrichosis-free areas. Our results demonstrated high cross-species transferability, reproducibility, and informativeness of SSR genetic markers, helping dissect deep and fine-scale genetic structures and guiding decision making to mitigate the harmful effects of the expansion of cat-transmitted sporotrichosis. [ABSTRACT FROM AUTHOR]

Cell turnover in adult tissues is essential for maintaining tissue homeostasis over a life span and for inducing the morphological changes associated with the reproductive cycle. However, the underlying mechanisms that coordinate the balance of cell death and proliferation remain unsolved. Using the mammary gland, we have discovered that Rac1 acts as a nexus to control cell turnover. Postlactational tissue regression is characterised by the death of milk secreting alveoli, but the process is reversible within the first 48 h if feeding recommences. In mice lacking epithelial Rac1, alveolar regression was delayed. This defect did not result from failed cell death but rather increased cell turnover. Fitter progenitor cells inappropriately divided, regenerating the alveoli, but cell death also concomitantly accelerated. We discovered that progenitor cell hyperproliferation was linked to nonautonomous effects of Rac1 deletion on the macrophageal niche with heightened inflammation. Moreover, loss of Rac1 impaired cell death with autophagy but switched the cell death route to apoptosis. Finally, mammary gland reversibility failed in the absence of Rac1 as the alveoli failed to recommence lactation upon resuckling. [ABSTRACT FROM AUTHOR]

The origins and evolution of virulence in amphibian-infecting chytrids Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal) are largely unknown. Here, we use deep nanopore sequencing of Bsal and comparative genomics against 21 high-quality genome assemblies that span the fungal Chytridiomycota. We discover that Bsal has the most repeat-rich genome of the Chytridiomycota, comprising 40.9% repetitive elements; this genome has expanded to more than 3× the length of its conspecific Bd, with autonomous and fully functional LTR/Gypsy elements contributing significantly to the expansion. The M36 metalloprotease virulence factors are highly expanded (n = 177) in Bsal, most of which (53%) are flanked by transposable elements, suggesting they have a repeat-associated expansion. We find enrichment upstream of M36 metalloprotease genes of three novel repeat families belonging to the repeat superfamily of LINEs that are implicated with gene copy number variations. Additionally, Bsal has a highly compartmentalized genome architecture, with virulence factors enriched in gene-sparse/repeat-rich compartments, while core conserved genes are enriched in gene-rich/repeat-poor compartments. Genes upregulated during infection are primarily found in the gene-sparse/repeat-rich compartment in both Bd and Bsal. Furthermore, genes with signatures of positive selection in Bd are enriched in repeat-rich regions, suggesting these regions are a cradle for the evolution of chytrid pathogenicity. These are the hallmarks of two-speed genome evolution, and this study provides evidence of two-speed genomes in an animal pathogen, shedding light on the evolution of fungal pathogens of vertebrates driving global declines and extinctions. [ABSTRACT FROM AUTHOR]

Phosphates and polyphosphates play ubiquitous roles in biology as integral structural components of cell membranes and bone, or as vehicles of energy storage via adenosine triphosphate and phosphocreatine. The solution phase space of phosphate species appears more complex than previously known. We present nuclear magnetic resonance (NMR) and cryogenic transmission electron microscopy (cryo-TEM) experiments that suggest phosphate species including orthophosphates, pyrophosphates, and adenosine phosphates associate into dynamic assemblies in dilute solutions that are spectroscopically "dark." Cryo-TEM provides visual evidence of the formation of spherical assemblies tens of nanometers in size, while NMR indicates that a majority population of phosphates remain as unassociated ions in exchange with spectroscopically invisible assemblies. The formation of these assemblies is reversibly and entropically driven by the partial dehydration of phosphate groups, as verified by diffusion-ordered spectroscopy (DOSY), indicating a thermodynamic state of assembly held together by multivalent interactions between the phosphates. Molecular dynamics simulations further corroborate that orthophosphates readily cluster in aqueous solutions. This study presents the surprising discovery that phosphate-containing molecules, ubiquitously present in the biological milieu, can readily form dynamic assemblies under a wide range of commonly used solution conditions, highlighting a hitherto unreported property of phosphate's native state in biological solutions. [ABSTRACT FROM AUTHOR]

Objectives: Pediatric anterior cruciate ligament (ACL) injuries are on the rise and result in high rates of post-traumatic osteoarthritis (PTOA). The pro-inflammatory biomarker monocyte chemoattractant protein-1 (MCP-1) is elevated in serum and synovial fluid (SF) in skeletally mature ACL injured patients as well as patients with OA, making it a potential target for treatments to prevent PTOA. Understanding the time course of MCP-1 after ACL injury and how it relates to cartilage health in skeletally immature subjects is important for identifying OA risk and developing novel treatment targets for OA prevention. Therefore, the objective of this study was to evaluate the time course of MCP-1 levels in serum and synovial fluid (SF) after ACL injury in a skeletally immature porcine model and assess how MCP-1 levels relate to T2* magnetic resonance imaging (MRI) measurements, indicative of cartilage matrix organization. We hypothesized that higher levels of MCP-1 in serum and synovial fluid post-injury would correspond to higher cartilage T2* values 12 weeks after ACL injury. Methods: All experimental protocols were approved by the NC State IACUC. Juvenile (3 month old) female Yorkshire cross-breed pigs (n=7) underwent unilateral arthroscopic ACL transection (ACLT) and a sham operation in the contralateral joint (Fig. 1A). Prior to surgery and at 2, 4, and 12 weeks post- operatively, injured stifle SF and serum samples were collected (pre-op synovial fluid only obtained from 4 animals). MRI scans were performed prior to surgery and at 12 weeks postoperatively. MCP-1 levels in serum and SF samples were evaluated longitudinally using a commercial enzyme-linked immunosorbent assay. Cartilage matrix organization was evaluated longitudinally using T2* MRI. Specifically, both knee joints were imaged using a 3T Siemens MAGNETOM Skyra MRI system (T2 SWI sequence, FA=15°, TR=50ms, TE: 3.4, 7, 13.47, 21, 29, 37.07ms, voxel size: 0.5x0.5x0.8mm). T2* relaxation maps were created in MATLAB by fitting mono-exponential curves on a voxel-by-voxel basis. Weight-bearing cartilage was segmented from the medial and lateral compartments of the femur, and the median T2* value of each compartment was calculated. Paired MCP-1 levels in the serum and injured stifle SF across all time points were compared using linear regression. Multiple paired t-tests with Holm-Sidak correction were performed to compare cartilage T2* values between ACLT and sham- operated joints at each time point. The interlimb percent difference in femoral cartilage T2* at 12 weeks was calculated and compared to MCP-1 levels in serum and SF using linear regressions and several methods to assess MCP-1 levels (Fig. 2). Statistical significance was set at a=0.05 overall for each analysis. Results: Generally, MCP-1 levels in serum and ACLT stifle SF were elevated after ACLT (Fig. 1). The serum MCP-1 response over time differed between animals. Specifically, serum MCP-1 levels peaked at 2 weeks in 2 animals, peaked at 4 weeks in 3 animals, and decreased after ACLT in 2 animals (Fig 1A). Contrastingly, ACLT stifle SF MCP-1 responses were more consistent between animals; six peaked at 2 week and returned near baseline levels by 12 weeks (Fig 1B). The linear regression between paired measurements of MCP-1 concentrations in the serum and ACLT stifle SF were associated (p=0.053), yet had high variability (r²=0.15, Fig. 1C). Interlimb differences in cartilage matrix organization were largest and most consistent at 12 weeks in the medial femoral cartilage compartment, where median T2* times were 8% longer in the medial femoral cartilage compartment of the ACLT limb compared to sham limb, yet this was not statistically significant due to variability between animals (p>0.05, Fig. 2). In the lateral femoral cartilage, the median T2* times were 3-4% longer at 12 weeks (p>0.05) and were more variable between subjects compared to the medial femoral cartilage. Associations between the interlimb percent difference in medial femoral cartilage T2* and serum MCP-1 fit well (r²=0.25-0.69), with Methods 2, 3, and 5 achieving statistical significance (p=0.02, p=0.03, p=0.03), but resulted in poor fits for associations with SF MCP-1 (r²=0.07-0.45) using a variety of MCP-1 measurement methods (Fig 2C). Similar associations between lateral femoral cartilage T2* and serum MCP- resulted in poor fits (r²=0.01-0.24), and associations with SF MCP-1 resulted in negative slopes (Methods 2-5, r²=0.00-0.58). Conclusions: This preliminary study showed that inflammatory biomarker MCP-1 levels in serum displayed a subject-dependent response, which correlated with later femoral cartilage compositional changes after ACLT in the skeletally immature porcine model. This partially supported our hypothesis. The poor correlation between serum and SF MCP-1 indicate different local and systemic responses to ACLT. The stronger correlations between serum MCP-1 and cartilage T2* values could point to the importance of the systemic inflammatory response to OA progression. The increases in cartilage T2* values and serum MCP-1 levels after ACL injury in this study are consistent with those reported in adult humans. This study includes several limitations, including the use of an animal model to study human disease, the small sample size, and the relatively short time-course. However, the results demonstrate feasibility of using a large animal porcine model to longitudinally study the link between early MCP-1 serum levels and long-term cartilage health after ACL injury. Establishing the pig as a preclinical model to study longitudinal inflammation and OA progression after ACL injury will enable development of effective treatments before translating to humans. [ABSTRACT FROM AUTHOR]

Across many different contexts, individuals consult customer ratings to inform their purchase decisions. The present studies document a novel phenomenon, dubbed “the binary bias,” which plays an important role in how individuals evaluate customer reviews. Our main proposal is that people tend to make a categorical distinction between positive ratings (e.g. 4s and 5s) and negative ratings (e.g. 1s and 2s). However, within those bins, people do not sufficiently distinguish between more extreme values (5s and 1s) and less extreme values (4s and 2s). As a result, people’s subjective representations of distributions are heavily impacted by the extent to which those distributions are imbalanced (having more 4s and 5s vs. more 1s and 2s). Ten studies demonstrate that this effect has important consequences for people’s product evaluations and purchase decisions. Additionally, we show this effect is not driven by the salience of particular bars, unrealistic distributions, certain statistical properties of a distribution, or diminishing subjective utility. Furthermore, we demonstrate this phenomenon’s relevance to other domains besides product reviews, and discuss the implications for existing research on how people integrate conflicting evidence. [ABSTRACT FROM AUTHOR]

Background: Debate continues in public health on the roles of universal or targeted policies in providing equity of access to health-related goods or services, and thereby contributing to health equity. Research examining policy implementation can provide fresh insights on these issues. Methods: We synthesised findings across case studies of policy implementation in four policy areas of primary healthcare (PHC), telecommunications, Indigenous health and land use policy, which incorporated a variety of universal and targeted policy structures. We analysed findings according to three criteria of equity in access - availability, affordability and acceptability - and definitions of universal, proportionate-universal, targeted and residual policies, and devolved governance structures. Results: Our analysis showed that existing universal, proportionate-universal and targeted policies in an Australian context displayed strengths and weaknesses in addressing availability, affordability and acceptability dimensions of equity in access. Conclusion: While residualist policies are unfavourable to equity of access, other forms of targeting as well as universal and proportionate-universal structure have the potential to be combined in context-specific ways favourable to equity of access to health-related goods and services. To optimise benefits, policies should address equity of access in the three dimensions of availability, affordability and acceptability. Devolved governance structures have the potential to augment equity benefits of either universal or targeted policies. [ABSTRACT FROM AUTHOR]

Growing evidence suggests that the origins of the panzootic amphibian pathogens Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal) are in Asia. In Taiwan, an island hotspot of high amphibian diversity, no amphibian mass mortality events linked to Bd or Bsal have been reported. We conducted a multi-year study across this subtropical island, sampling 2517 individuals from 30 species at 34 field sites, between 2010 and 2017, and including 171 museum samples collected between 1981 and 2009. We analyzed the skin microbiome of 153 samples (6 species) from 2017 in order to assess any association between the amphibian skin microbiome and the probability of infection amongst different host species. We did not detect Bsal in our samples, but found widespread infection by Bd across central and northern Taiwan, both taxonomically and spatially. Museum samples show that Bd has been present in Taiwan since at least 1990. Host species, geography (elevation), climatic conditions and microbial richness were all associated with the prevalence of infection. Host life-history traits, skin microbiome composition and phylogeny were associated with lower prevalence of infection for high altitude species. Overall, we observed low prevalence and burden of infection in host populations, suggesting that Bd is enzootic in Taiwan where it causes subclinical infections. While amphibian species in Taiwan are currently threatened by habitat loss, our study indicates that Bd is in an endemic equilibrium with the populations and species we investigated. However, ongoing surveillance of the infection is warranted, as changing environmental conditions may disturb the currently stable equilibrium. [ABSTRACT FROM AUTHOR]

Background: The critically endangered kākāpō is a flightless, nocturnal parrot endemic to Aotearoa New Zealand. Recent efforts to describe the gastrointestinal microbial community of this threatened herbivore revealed a low-diversity microbiota that is often dominated by Escherichia-Shigella bacteria. Given the importance of associated microbial communities to animal health, and increasing appreciation of their potential relevance to threatened species conservation, we sought to better understand the development of this unusual gut microbiota profile. To this end, we conducted a longitudinal analysis of faecal material collected from kākāpō chicks during the 2019 breeding season, in addition to associated nest litter material. Results: Using an experimental approach rarely seen in studies of threatened species microbiota, we evaluated the impact of a regular conservation practice on the developing kākāpō microbiota, namely the removal of faecal material from nests. Artificially removing chick faeces from nests had negligible impact on bacterial community diversity for either chicks or nests (p > 0.05). However, the gut microbiota did change significantly over time as chick age increased (p < 0.01), with an increasing relative abundance of Escherichia-Shigella coli over the study period and similar observations for the associated nest litter microbiota (p < 0.01). Supplementary feeding substantially altered gut bacterial diversity of kākāpō chicks (p < 0.01), characterised by a significant increase in Lactobacillus bacteria. Conclusions: Overall, chick age and hand rearing conditions had the most marked impact on faecal bacterial communities. Similarly, the surrounding nest litter microbiota changed significantly over time since a kākāpō chick was first placed in the nest, though we found no evidence that removal of faecal material influenced the bacterial communities of either litter or faecal samples. Taken together, these observations will inform ongoing conservation and management of this most enigmatic of bird species. [ABSTRACT FROM AUTHOR]

Makerspace tools and technologies are becoming increasingly popular in K-12 educational settings. While makerspace education has the potential to democratize educational spaces, the integration of these new technologies into the classroom is not trivial. In this paper, we analyze a university-based makerspace apprenticeship program for pre-service teachers to learn makerspace tools and technologies for use in their future classrooms. We demonstrate how apprenticeship in this community of practice led to increased confidence in maker tools and technologies and a mindset toward learning in makerspaces as playful, collaborative, and iterative. We found that pre-service teachers require greater opportunities to see students engaged in making in elementary classrooms. We end with recommendations for supporting pre-service teachers to adopt making for their future classrooms. [ABSTRACT FROM AUTHOR]

Pediatric anterior cruciate ligament (ACL) injury rates are increasing and are highest in female adolescents. Complete ACL tears are typically surgically reconstructed, but few guidelines and very limited data exist regarding the need for surgical reconstruction or rehabilitation for partial ACL tears in skeletally immature patients. To evaluate the effects of partial (anteromedial bundle) and complete ACL transection on joint laxity and tissue forces under anterior and rotational loads in male and female stifle joints throughout skeletal growth in the porcine model. Descriptive laboratory study. Laboratory. We studied 60 male and female Yorkshire crossbreed pigs aged 1.5, 3, 4.5, 6, and 18 months (n = 6 pigs per age per sex). Joint laxity was measured in intact, anteromedial bundle-transected, and ACL-transected joints under applied anterior-posterior drawer and varus-valgus torque using a robotic testing system. Loading of the soft tissues in the stifle joint was measured under each condition. Anterior-posterior joint laxity increased by 13% to 50% (P <.05) after anteromedial bundle transection and 75% to 178% (P <.05) after ACL transection. Destabilization after anteromedial bundle transection increased with age (P <.05) and was greater in late female than late male adolescents (P <.05). In anteromedial bundle-transected joints, the posterolateral bundle resisted the anterior load. In ACL-transected joints, the medial collateral ligament (MCL) contribution was largest, followed by the medial meniscus. The MCL contribution was larger and the medial meniscus contribution was smaller in male versus female specimens. Partial ACL transection resulted in moderate increases in joint laxity, with the remaining bundle performing the primary ACL function. Destabilization due to partial ACL transection (anteromedial bundle) was largest in late adolescent joints, indicating that operative treatment should be considered in active, late-adolescent patients with this injury. Increased forces on the MCL and medial meniscus after ACL transection suggested that rehabilitation protocols may need to focus on protecting these tissues. [ABSTRACT FROM AUTHOR]

Adolescents and adults are treated similarly in rehabilitation and research despite differences in clinical recovery after anterior cruciate ligament reconstruction (ACLR). Aberrant gait is a clinical outcome associated with poor long-term health post-ACLR but has not been compared between adolescents and adults. To compare gait biomechanical waveforms throughout stance between adolescents (< 18 years old) and young adults (≥18 years old) post-ACLR. Case-control study. Laboratory. Adolescents (n = 13, girls = 77%, age = 16.7 ± 0.6 years, height = 1.7 ± 0.1 m, weight = 22.2 ± 3.7 kg/m2) were identified from a cross-sectional cohort assessing clinical outcomes 6 to 12 months post-ACLR. Young adults (n = 13, women = 77%, age = 22.3 ± 4.0 years, height = 1.7 ± 0.1 m, weight = 22.9 ± 3.3 kg/m2) were matched based on sex, time since surgery (±2 months), and body mass index (±3 kg/m2). Participants performed 5 gait trials at their habitual speed. Three-dimensional gait biomechanics and forces were collected. Vertical ground reaction force normalized to body weight (xBW), knee-flexion angle (°), knee-abduction moment (xBW × height), and knee-extension moment (BW × height) waveforms were calculated during the stance phase of gait (0%–100%). Habitual walking speed was compared using independent t tests. We used functional waveforms to compare gait biomechanics throughout stance with and without controlling for habitual walking speed by calculating mean differences between groups with 95% CIs. Adolescents walked with slower habitual speeds compared with adults (adolescents = 1.1 ± 0.1 m/s, adults = 1.3 ± 0.1 m/s, P <.001). When gait speed was not controlled, adolescents walked with less vertical ground reaction force (9%–15% of stance) and knee-abduction moment (12%–25% of stance) during early stance and less knee-extension moment during late stance (80%–99% of stance). Regardless of their habitual walking speed, adolescents walked with greater knee-flexion angle throughout most stances (0%–21% and 29%–100% of stance). Adolescents and adults demonstrated different gait patterns post-ACLR, suggesting that age may play a role in altered gait biomechanics. [ABSTRACT FROM AUTHOR]

We present ASSET, a neural architecture for automatically modifying an input high-resolution image according to a user's edits on its semantic segmentation map. Our architecture is based on a transformer with a novel attention mechanism. Our key idea is to sparsify the transformer's attention matrix at high resolutions, guided by dense attention extracted at lower image resolutions. While previous attention mechanisms are computationally too expensive for handling high-resolution images or are overly constrained within specific image regions hampering long-range interactions, our novel attention mechanism is both computationally efficient and effective. Our sparsified attention mechanism is able to capture long-range interactions and context, leading to synthesizing interesting phenomena in scenes, such as reflections of landscapes onto water or fora consistent with the rest of the landscape, that were not possible to generate reliably with previous convnets and transformer approaches. We present qualitative and quantitative results, along with user studies, demonstrating the effectiveness of our method. Our code and dataset are available at our project page: https://github.com/DifanLiu/ASSET [ABSTRACT FROM AUTHOR]

Pediatric anterior cruciate ligament (ACL) injuries are on the rise, and females experience higher ACL injury risk than males during adolescence. Studies in skeletally immature patients indicate differences in ACL size and joint laxity between males and females after the onset of adolescence. However, functional data regarding the ACL and its anteromedial and posterolateral bundles in the pediatric population remain rare. Therefore, this study uses a porcine model to investigate the sex‐specific morphology and biomechanics of the ACL and its bundles throughout skeletal growth. Hind limbs from male and female Yorkshire pigs aged early youth to late adolescence were imaged using magnetic resonance imaging to measure the size and orientation of the ACL and its bundles, then biomechanically tested under anterior‐posterior drawer using a robotic testing system. Joint laxity decreased (p < 0.001) while joint stiffness increased (p < 0.001) throughout skeletal growth in both sexes. The ACL was the primary stabilizer against anterior tibial loading, while the functional role of the anteromedial bundle increased with age (p < 0.001), with an earlier increase in males. ACL and posterolateral bundle cross‐sectional area and ACL and anteromedial bundle length were larger in males than females during adolescence (p < 0.01 for all), while ACL and bundle sagittal angle remained similar between sexes. Additionally, in situ ACL stiffness versus cross‐sectional area regressions were significant across skeletal growth (r2 = 0.75, p < 0.001 in males and r2 = 0.64, p < 0.001 in females), but not within age groups. This study has implications for age and sex‐specific surgical intervention strategies and suggests the need for human studies. [ABSTRACT FROM AUTHOR]

Anterior cruciate ligament (ACL) injuries are increasingly common in adolescents, and injuries in this age‐group are associated with many unique challenges. Recent large animal studies suggest that the size and function of the major bundles of the ACL change differently throughout skeletal growth. To better aid clinical treatment of pediatric partial ACL tears and better predict outcomes from age‐specific treatments, there is a need to measure changes in ACL bundle size in humans during growth. As such, the objective of this study was to compare changes in the length and cross‐sectional area (CSA) of the ACL and its primary bundles in adolescent human subjects. Magnetic resonance imaging (MRI) scans were analyzed to determine the visibility and integrity of the ACL and its anteromedial and posterolateral bundles. MRI scans were considered from a retrospective database of subjects ranging from 10 to 18 years of age. The ACL and its anteromedial and posterolateral bundles were segmented and reconstructed into 3D models, and length and CSA were calculated. Total ACL length and CSA were greater in males compared with females, with a statistically significant interaction between age and sex for CSA. Sex had a significant effect on the CSA of both bundles. These sex‐dependent differences emerge with moderate to large effect sizes (range: d = 0.50 to d = 1.23) beginning around 13 years of age. Along with ACL bundle structure–function relationships previously established in preclinical animal models, these findings may point toward biomechanical changes in the adolescent human ACL. [ABSTRACT FROM AUTHOR]

Issue addressed: We sought to examine barriers to access to, use of, and benefits from digital health services in an area of socioeconomic disadvantage of Adelaide, Australia. Methods: We conducted waiting room surveys in two hospital diabetes clinics and one hospital antenatal clinic in South Australia, and follow‐up telephone interviews with 20 patients. We examined the extent of access to, use of and benefits from digital health services, and what barriers people encountered. We undertook mixed methods, with quantitative descriptive analysis and qualitative analysis. Results: Thirty‐seven diabetes clinic patients (54% response rate) and 99 antenatal clinic patients (33% response rate) participated. Sixty‐two percent of the patients with diabetes and 27% of antenatal clinic patients had never used digital health services. Seventeen percent of patients with diabetes and 30% of antenatal clinic patients were hesitant users, and 22% of patients with diabetes and 44% of antenatal clinic patients were confident users. Barriers included struggling to afford the technology or to stay connected and a lack of trust in online health information. Potential benefits included feeling more empowered and complementing face‐to‐face care. Conclusions: There are socioeconomic barriers to access, use of, and ability to benefit from digital health strategies that mean not everyone will be able to benefit from digital health services. So What?: As COVID‐19 accelerates the shift towards digital health services, people experiencing socioeconomic disadvantage may be excluded. If barriers to access and use are not addressed, they will exacerbate already increasing health inequities. [ABSTRACT FROM AUTHOR]

In the face of global epidemics of mental ill-health, the future of social policy lies with promotion of public wellbeing. This article aims to provide an explanatory rationale and methods for a fundamental shift in social policy; away from a remedial focus on mental ill-health defined in terms of disease or aberrant behaviour and toward a focus on universal access to social conditions favourable to psychological wellbeing. The paper begins with prefacing argument about the urgent need for such a shift, noting the high rates of mental ill-health globally and the failure of current biomedical responses to reduce these. Building on recent theoretical work on public wellbeing and evidence on social determinants of mental health, the paper then proposes nine domains for social policy and broader public policy action, to create conditions supportive of wellbeing abilities. Finally, the paper presents several conceptual issues relating to the challenge of putting such action into practice and concludes that contemporary understanding of wellbeing offers a theory of change to shift social policy from mental illness to public wellbeing. [ABSTRACT FROM AUTHOR]

Cells maintain tensional homeostasis by monitoring the mechanics of their microenvironment. In order to understand this mechanotransduction phenomenon, hydrogel materials have been developed with either controllable linear elastic or viscoelastic properties. Native biological tissues, and biomaterials used for medical purposes, often have complex mechanical properties. However, due to the difficulty in completely decoupling the elastic and viscous components of hydrogel materials, the effect of complex composite materials on cellular responses has largely gone unreported. Here, we characterize a novel composite hydrogel system capable of decoupling and individually controlling both the bulk stiffness and surface viscoelasticity of the material by combining polyacrylamide (PA) gels with microgel thin films. By taking advantage of the high degree of control over stiffness offered by PA gels and viscoelasticity, in terms of surface loss tangent, of microgel thin films, it is possible to study the influence that bulk substrate stiffness and surface loss tangent have on complex fibroblast responses, including cellular and nuclear morphology and gene expression. This material system provides a facile method for investigating cellular responses to complex material mechanics with great precision and allows for a greater understanding of cellular mechanotransduction mechanisms than previously possible through current model material platforms. [ABSTRACT FROM AUTHOR]

Background: Universal health coverage (UHC) is central to current international debate on health policy. The primary healthcare (PHC) system is crucial to achieving UHC, in order to address the rising incidence of non-communicable diseases (NCDs) more effectively and equitably. In this paper, we examine the Australian case as a mature system of UHC and identify lessons for UHC policy to support equity of access to PHC and reduce NCDs. Methods: Our qualitative research used policy mapping and monitoring and 30 key informant interviews, and applied policy theory, to investigate the implementation of Australian PHC policy between 2008 and 2018. Results: Although the Australian PHC system does support equity of access to primary medical care, other ideational, actor-centred and structural features of policy detract from the capacities of the system to prevent and manage NCDs effectively, deliver equity of access according to need, and support equity in health outcomes. These features include a dominant focus on episodic primary medical care, which is a poor model of care for NCDs, and an inequitable distribution of these services. Also, a mixed system of public and private insurance coverage in PHC contributes to inequities in access and health outcomes, driving additional NCD demand into the health system. Conclusion: Countries aiming to achieve UHC to support health equity and reduce NCDs can learn from strengths and weaknesses in the Australian system. We recommend a range of ideational, actor-centred and structural features of UHC systems in PHC that will support effective action on NCDs, equity of access to care according to need, and equity in health outcomes across geographically and ethnically diverse populations. [ABSTRACT FROM AUTHOR]

The Internet has radically shifted how people access information. Instead of storing information internally, increasingly, people outsource to the Internet and retrieve it when needed. While this is an efficient strategy in many ways, its downstream consequences remain largely unexplored. This research examines how accessing online information impacts how people remember information in a learning context. Across five experiments, participants studied for a quiz either by searching online to access relevant information or by directly receiving that same information without online search. Those who searched the Internet performed worse in the learning assessment, indicating that they stored less new knowledge in internal memory. However, participants who searched the Internet were as confident, or even more confident, that they had mastered the study material compared to those who did not search online. We argue that, by making information retrievability salient, Internet search reduces the likelihood of information being stored in memory. Further, these results suggest that searching online leads to the misattribution of online information to internal memory, thus masking the Internet-induced learning deficits. [ABSTRACT FROM AUTHOR]

Storytelling can stimulate learning by delivering scientific content within a narrative that increases comprehension and engagement. In this article I describe the coevolutionary arms race between toxic newts and predatory garter snakes. This engaging story centers on the use of a deadly neurotoxin called tetrodotoxin (TTX) as an antipredator defense. Some species of newts contain TTX in their tissues, but resistance to TTX has developed through convergent evolution in garter snakes and other species. TTX resistance results from mutated voltage-gated sodium channels. These channels, whether TTX resistant or not, are found in all animals and are vital to the function of nervous and muscle tissues. Through reciprocal selection, coevolution has created phenotypic matching between toxic newts and TTX-resistant garter snakes across their range in the western United States. In other words, as newts became more poisonous, garter snakes became more resistant. These results and the scientific process behind them are discussed in detail. This story can be used by educators to provide a unifying and engaging backdrop as students learn multiple aspects of biology, such as protein structure, genetics, phylogenetics, electrical signaling, evolution, and the process of science. [ABSTRACT FROM AUTHOR]

Summary: Azole‐resistant environmental Aspergillus fumigatus presents a threat to public health but the extent of this threat in Southeast Asia is poorly described. We conducted environmental surveillance in the Mekong Delta region of Vietnam, collecting air and ground samples across key land‐use types, and determined antifungal susceptibilities of Aspergillus section Fumigati (ASF) isolates and azole concentrations in soils. Of 119 ASF isolates, 55% were resistant (or non‐wild type) to itraconazole, 65% to posaconazole and 50% to voriconazole. Azole resistance was more frequent in A. fumigatus sensu stricto isolates (95%) than other ASF species (32%). Resistant isolates and agricultural azole residues were overrepresented in samples from cultivated land. cyp51A gene sequence analysis showed 38/56 resistant A. fumigatus sensu stricto isolates carried known resistance mutations, with TR34/L98H most frequent (34/38). [ABSTRACT FROM AUTHOR]

Microplastics (MPs), a new class of pollutants that pose a threat to aquatic biodiversity, are of increasing global concern. In tandem, the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) causing the disease chytridiomycosis is emerging worldwide as a major stressor to amphibians. We here assess whether synergies exist between this infectious disease and MP pollution by mimicking natural contact of a highly susceptible species (midwife toads, Alytes obstetricans) with a Bd-infected reservoir species (fire salamanders, Salamandra salamandra) in the presence and absence of MPs. We found that MP ingestion increases the burden of infection by Bd in a dose-dependent manner. However, MPs accumulated to a greater extent in amphibians that were not exposed to Bd, likely due to Bd-damaged tadpole mouthparts interfering with MP ingestion. Our experimental approach showed compelling interactions between two emergent processes, chytridiomycosis and MP pollution, necessitating further research into potential synergies between these biotic and abiotic threats to amphibians. [ABSTRACT FROM AUTHOR]

Although rising rates of obesity are recognized as a major concern for Australian public health, debate on what (if any) responsive action should be undertaken is conceptually and normatively complex. It is shaped by diverse values and interests; different representations of the problem; and many options for action by government, the private sector or individuals. This paper presents research documenting arguments for and against implementing a sugar tax in Australia. It is based on semi-structured interviews with representatives from industry (n  = 4), public health (n  = 4), policy think tanks (n  = 2); and document and media analyses. The research design was informed by framing and agenda setting theory with results reported under four main themes: framing economic impacts, framing equity, framing obesity and framing the 'nanny state' versus individual liberty argument. We found that proposals for a sugar tax as part of policy responses to the issue of overweight and obesity in Australia are framed very differently by actors who either support or oppose it. A conclusion is that policy makers and public health advocates involved in policy debates on a sugar tax need to understand the role of problem and 'solution' framing, and develop positions based on protecting the public interest as a basic ethical responsibility of governments and public agencies. [ABSTRACT FROM AUTHOR]

Respiratory infections caused by fungal pathogens present a growing global health concern and are a major cause of death in immunocompromised patients. Worryingly, coronavirus disease-19 (COVID-19) resulting in acute respiratory distress syndrome has been shown to predispose some patients to airborne fungal co-infections. These include secondary pulmonary aspergillosis and mucormycosis. Aspergillosis is most commonly caused by the fungal pathogen Aspergillus fumigatus and primarily treated using the triazole drug group, however in recent years, this fungus has been rapidly gaining resistance against these antifungals. This is of serious clinical concern as multi-azole resistant forms of aspergillosis have a higher risk of mortality when compared against azole-susceptible infections. With the increasing numbers of COVID-19 and other classes of immunocompromised patients, early diagnosis of fungal infections is critical to ensuring patient survival. However, time-limited diagnosis is difficult to achieve with current culture-based methods. Advances within fungal genomics have enabled molecular diagnostic methods to become a fast, reproducible, and cost-effective alternative for diagnosis of respiratory fungal pathogens and detection of antifungal resistance. Here, we describe what techniques are currently available within molecular diagnostics, how they work and when they have been used. [ABSTRACT FROM AUTHOR]