Too stressed to think? A scoping review of the literature for healthcare educators utilising high acuity clinical scenarios.

BACKGROUND: The practise of paramedicine can be highly stressful particularly where urgent lifesaving decisions need to be made. Traditionally, educators have adopted the approach of placing students in simulated stressful situations as a way of learning to cope with these challenges. It is unclear from the literature whether traditional stress inoculation enhances or hinders learning. This scoping review aims to identify and examine both the peer-reviewed and grey literature reporting physiological stress responses to high-acuity scenarios in paramedicine and cognate healthcare disciplines. METHODS: Adhering strictly to JBI Evidence Synthesis Manual for conducting a scoping review, medical subject headings and areas, keywords and all other possible index terms were searched across EBSCOhost (Medline, CINAHL and APA PsycInfo), Scopus and, PubMed. English language articles both published (peer-reviewed academic papers, reports and conference proceedings) and unpublished (grey literature, Google Scholar reports) were included, and publications citing retrieved articles were also checked. RESULTS: Searches performed across five electronic databases identified 52 articles where abstracts indicated potential inclusion. From this, 22 articles which reported physiological or psychophysiological responses to stressful scenario-based education were included. CONCLUSION: This review identified that an acceptable level of stress during simulation can be beneficial, however a point can be exceeded where stress becomes a hinderance to learning resulting in underperformance. By identifying strategies to moderate the impact of acute stress, educators of paramedic and other healthcare students can utilise high-acuity clinical scenarios to their andragogical armamentarium which has the potential to improve real-world clinical outcomes.

MYC is Sufficient to Generate Mid-Life High-Grade Serous Ovarian and Uterine Serous Carcinomas in a p53-R270H Mouse Model.

Genetically engineered mouse models (GEMM) have fundamentally changed how ovarian cancer etiology, early detection, and treatment are understood. MYC, an oncogene, is amongst the most amplified genes in high-grade serous ovarian cancer (HGSOC), but it has not previously been utilized to drive HGSOC GEMMs. We coupled Myc and dominant-negative mutant p53-R270H with a fallopian tube epithelium (FTE)-specific promoter Ovgp1 to generate a new GEMM of HGSOC. Female mice developed lethal cancer at an average of 14.5 months. Histopathologic examination of mice revealed HGSOC characteristics, including nuclear p53 and nuclear MYC in clusters of cells within the FTE and ovarian surface epithelium. Unexpectedly, nuclear p53 and MYC clustered cell expression was also identified in the uterine luminal epithelium, possibly from intraepithelial metastasis from the FTE. Extracted tumor cells exhibited strong loss of heterozygosity at the p53 locus, leaving the mutant allele. Copy-number alterations in these cancer cells were prevalent, disrupting a large fraction of genes. Transcriptome profiles most closely matched human HGSOC and serous endometrial cancer. Taken together, these results demonstrate that the Myc and Trp53-R270H transgenes were able to recapitulate many phenotypic hallmarks of HGSOC through the utilization of strictly human-mimetic genetic hallmarks of HGSOC. This new mouse model enables further exploration of ovarian cancer pathogenesis, particularly in the 50% of HGSOC which lack homology-directed repair mutations. Histologic and transcriptomic findings are consistent with the hypothesis that uterine serous cancer may originate from the FTE. SIGNIFICANCE: Mouse models using transgenes which generate spontaneous cancers are essential tools to examine the etiology of human diseases. Here, the first Myc-driven spontaneous model is described as a valid HGSOC model. Surprisingly, aspects of uterine serous carcinoma were also observed in this model.

Autophagy unrelated transcriptional mechanisms of hydroxychloroquine resistance revealed by integrated multi-omics of evolved cancer cells.

Hydroxychloroquine (HCQ) and chloroquine are repurposed drugs known to disrupt autophagy, a molecular recycling pathway essential for tumor cell survival, chemotherapeutic resistance, and stemness. We pursued a multi-omic strategy in OVCAR3 ovarian cancer and CCL218 colorectal cancer cells. Two genome-scale screens were performed. In the forward genetic screen, cell populations were passaged for 15 drug pulse-chases with HCQ or vehicle control. Evolved cells were collected and processed for bulk RNA-seq, exome-seq, and single-cell RNA-seq (scRNA-seq). In the reverse genetic screen, a pooled CRISPR-Cas9 library was used in cells over three pulse-chases of HCQ or vehicle control treatments. HCQ evolved cells displayed remarkably few mutational differences, but substantial transcriptional differences. Transcriptomes revealed multiple pathways associated with resistance to HCQ, including upregulation of glycolysis, exocytosis, and chromosome condensation/segregation, or downregulation of translation and apoptosis. The Cas9 screen identified only one autophagy gene. Chromosome condensation and segregation were confirmed to be disrupted by HCQ in live cells and organelle-free in vitro extracts. Transcriptional plasticity was the primary mechanism by which cells evolved resistance to HCQ. Neither autophagy nor the lysosome were substantive hits. Our analysis may serve as a model for how to better position repurposed drugs in oncology.

'You can be as vigilant as you can, yet they make their way in': A descriptive study of parent and caregiver perspectives towards keeping children safe from button batteries.

Objectives: Button batteries pose a significant threat to young children, and parents and caregivers play an important role in keeping children safe from button batteries, especially in the home environment. However, little is known regarding parent or caregiver perspectives on button battery safety, in particular, the threat they pose to children. The aim of this study was to examine perspectives on button battery safety to enable tailored prevention strategies and to examine parent and caregiver perspectives on button battery safety in the home. Methods: One hundred and seventy-four parents and caregivers of children aged 0-5 completed a cross-sectional online survey. Distribution occurred via social media. The survey contained multiple-choice questions pertaining to button battery knowledge and attitudes. Results: Most respondents recognised the dangers of button battery ingestion, yet only 37% knew of button battery ingestion symptoms. While 68% knew of household items containing button batteries, 21% were aware of product-recall information sources. Approximately 64% understood immediate post-ingestion steps, but only 31% were familiar with first-aid procedures. From an attitudinal standpoint, 95% understood the importance of child supervision around button batteries, 78% prioritised battery safety in toy purchases, and 17% found current safety labels unsatisfactory. This study provides a foundation for ongoing investigation of parent and caregiver perspectives on button battery home safety. Conclusion: Ongoing, comprehensive education and public-safety campaigns are needed to rectify gaps in knowledge regarding button battery safety, and to reduce the risk of button battery ingestion in children.

Single-cell transcriptomics identifies aberrant glomerular angiogenic signalling in the early stages of WT1 kidney disease.

WT1 encodes a podocyte transcription factor whose variants can cause an untreatable glomerular disease in early childhood. Although WT1 regulates many podocyte genes, it is poorly understood which of them are initiators in disease and how they subsequently influence other cell-types in the glomerulus. We hypothesised that this could be resolved using single-cell RNA sequencing (scRNA-seq) and ligand-receptor analysis to profile glomerular cell-cell communication during the early stages of disease in mice harbouring an orthologous human mutation in WT1 (Wt1R394W/+). Podocytes were the most dysregulated cell-type in the early stages of Wt1R394W/+ disease, with disrupted angiogenic signalling between podocytes and the endothelium, including the significant downregulation of transcripts for the vascular factors Vegfa and Nrp1. These signalling changes preceded glomerular endothelial cell loss in advancing disease, a feature also observed in biopsy samples from human WT1 glomerulopathies. Addition of conditioned medium from murine Wt1R394W/+ primary podocytes to wild-type glomerular endothelial cells resulted in impaired endothelial looping and reduced vascular complexity. Despite the loss of key angiogenic molecules in Wt1R394W/+ podocytes, the pro-vascular molecule adrenomedullin was upregulated in Wt1R394W/+ podocytes and plasma and its further administration was able to rescue the impaired looping observed when glomerular endothelium was exposed to Wt1R394W/+ podocyte medium. In comparative analyses, adrenomedullin upregulation was part of a common injury signature across multiple murine and human glomerular disease datasets, whilst other gene changes were unique to WT1 disease. Collectively, our study describes a novel role for altered angiogenic signalling in the initiation of WT1 glomerulopathy. We also identify adrenomedullin as a proangiogenic factor, which despite being upregulated in early injury, offers an insufficient protective response due to the wider milieu of dampened vascular signalling that results in endothelial cell loss in later disease. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

SGLT1 contributes to glucose-mediated exacerbation of ischemia-reperfusion injury in ex vivo rat heart.

Hyperglycaemia is common during acute coronary syndromes (ACS) irrespective of diabetic status and portends excess infarct size and mortality, but the mechanisms underlying this effect are poorly understood. We hypothesized that sodium/glucose linked transporter-1 (SGLT1) might contribute to the effect of high-glucose during ACS and examined this using an ex-vivo rodent heart model of ischaemia-reperfusion injury. Langendorff-perfused rat hearts were subjected to 35 min ischemia and 2 h reperfusion, with variable glucose and reciprocal mannitol given during reperfusion in the presence of pharmacological inhibitors of SGLT1. Myocardial SGLT1 expression was determined in rat by rtPCR, RNAscope and immunohistochemistry, as well as in human by single-cell transcriptomic analysis. High glucose in non-diabetic rat heart exacerbated reperfusion injury, significantly increasing infarct size from 45 ± 3 to 65 ± 4% at 11-22 mmol/L glucose, respectively (p < 0.01), an association absent in diabetic heart (32 ± 1-37 ± 5%, p = NS). Rat heart expressed SGLT1 RNA and protein in vascular endothelium and cardiomyocytes, with similar expression found in human myocardium by single-nucleus RNA-sequencing. Rat SGLT1 expression was significantly reduced in diabetic versus non-diabetic heart (0.608 ± 0.08 compared with 1.116 ± 0.13 probe/nuclei, p < 0.01). Pharmacological inhibitors phlorizin, canagliflozin or mizagliflozoin in non-diabetic heart revealed that blockade of SGLT1 but not SGLT2, abrogated glucose-mediated excess reperfusion injury. Elevated glucose is injurious to the rat heart during reperfusion, exacerbating myocardial infarction in non-diabetic heart, whereas the diabetic heart is resistant to raised glucose, a finding which may be explained by lower myocardial SGLT1 expression. SGLT1 is expressed in vascular endothelium and cardiomyocytes and inhibiting SGLT1 abrogates excess glucose-mediated infarction. These data highlight SGLT1 as a potential clinical translational target to improve morbidity/mortality outcomes in hyperglycemic ACS patients.

Multi-source connectivity as the driver of solar wind variability in the heliosphere.

The ambient solar wind that fills the heliosphere originates from multiple sources in the solar corona and is highly structured. It is often described as high-speed, relatively homogeneous, plasma streams from coronal holes and slow-speed, highly variable, streams whose source regions are under debate. A key goal of ESA/NASA's Solar Orbiter mission is to identify solar wind sources and understand what drives the complexity seen in the heliosphere. By combining magnetic field modelling and spectroscopic techniques with high-resolution observations and measurements, we show that the solar wind variability detected in situ by Solar Orbiter in March 2022 is driven by spatio-temporal changes in the magnetic connectivity to multiple sources in the solar atmosphere. The magnetic field footpoints connected to the spacecraft moved from the boundaries of a coronal hole to one active region (12961) and then across to another region (12957). This is reflected in the in situ measurements, which show the transition from fast to highly Alfvénic then to slow solar wind that is disrupted by the arrival of a coronal mass ejection. Our results describe solar wind variability at 0.5 au but are applicable to near-Earth observatories.

Cardiotrophin-1 therapy reduces disease severity in a murine model of glomerular disease.

Cardiotrophin-1 (CT-1), a member of the interleukin (IL)-6 cytokine family, has renoprotective effects in mouse models of acute kidney disease and tubulointerstitial fibrosis, but its role in glomerular disease is unknown. To address this, we used the mouse model of nephrotoxic nephritis to test the hypothesis that CT-1 also has a protective role in immune-mediated glomerular disease. Using immunohistochemistry and analysis of single-cell RNA-sequencing data of isolated glomeruli, we demonstrate that CT-1 is expressed in the glomerulus in male mice, predominantly in parietal epithelial cells and is downregulated in mice with nephrotoxic nephritis. Furthermore, analysis of data from patients revealed that human glomerular disease is also associated with reduced glomerular CT-1 transcript levels. In male mice with nephrotoxic nephritis and established proteinuria, administration of CT-1 resulted in reduced albuminuria, prevented podocyte loss, and sustained plasma creatinine, compared with mice administered saline. CT-1 treatment also reduced fibrosis in the kidney cortex, peri-glomerular macrophage accumulation and the kidney levels of the pro-inflammatory mediator complement component 5a. In conclusion, CT-1 intervention therapy delays the progression of glomerular disease in mice by preserving kidney function and inhibiting renal inflammation and fibrosis.

Single-modulator, dual comb serrodyne spectroscopy.

Dual optical frequency comb spectroscopy allows for high speed, broadband measurements without any moving parts. Here, we combine differential chirp downconversion to probe large spectral bandwidths and serrodyne modulation to separate the positive and negative sidebands in a single modulator. As an initial demonstration, we apply this approach to measure a sharp cavity resonance to illustrate the system performance. We then measure methane transitions in the near-infrared and compare the resulting spectra to models based upon the current spectroscopic databases. The serrodyne method has lower hardware requirements compared to many existing approaches, and its simplicity enables a high degree of mutual coherence between the two combs. Further, this method is readily amenable to chip-scale photonic integration.

Observation of Alfvén Wave Reflection in the Solar Chromosphere: Ponderomotive Force and First Ionization Potential Effect.

We investigate the propagation of Alfvén waves in the solar chromosphere, distinguishing between upward and downward propagating waves. We find clear evidence for the reflection of waves in the chromosphere and differences in propagation between cases with waves interpreted to be resonant or nonresonant with the overlying coronal structures. This establishes the wave connection to coronal element abundance anomalies through the action of the wave ponderomotive force on the chromospheric plasma, which interacts with chromospheric ions but not neutrals, thereby providing a novel mechanism of ion-neutral separation. This is seen as a "first ionization potential effect" when this plasma is lifted into the corona, with implications elsewhere on the Sun for the origin of the slow speed solar wind and its elemental composition.

MYC is sufficient to generate mid-life high-grade serous ovarian and uterine serous carcinomas in a p53-R270H mouse model.

Genetically engineered mouse models (GEMM) have fundamentally changed how ovarian cancer etiology, early detection, and treatment is understood. However, previous GEMMs of high-grade serous ovarian cancer (HGSOC) have had to utilize genetics rarely or never found in human HGSOC to yield ovarian cancer within the lifespan of a mouse. MYC, an oncogene, is amongst the most amplified genes in HGSOC, but it has not previously been utilized to drive HGSOC GEMMs. We coupled Myc and dominant negative mutant p53-R270H with a fallopian tube epithelium-specific promoter Ovgp1 to generate a new GEMM of HGSOC. Female mice developed lethal cancer at an average of 15.1 months. Histopathological examination of mice revealed HGSOC characteristics including nuclear p53 and nuclear MYC in clusters of cells within the fallopian tube epithelium and ovarian surface epithelium. Unexpectedly, nuclear p53 and MYC clustered cell expression was also identified in the uterine luminal epithelium, possibly from intraepithelial metastasis from the fallopian tube epithelium (FTE). Extracted tumor cells exhibited strong loss of heterozygosity at the p53 locus, leaving the mutant allele. Copy number alterations in these cancer cells were prevalent, disrupting a large fraction of genes. Transcriptome profiles most closely matched human HGSOC and serous endometrial cancer. Taken together, these results demonstrate the Myc and Trp53-R270H transgene was able to recapitulate many phenotypic hallmarks of HGSOC through the utilization of strictly human-mimetic genetic hallmarks of HGSOC. This new mouse model enables further exploration of ovarian cancer pathogenesis, particularly in the 50% of HGSOC which lack homology directed repair mutations. Histological and transcriptomic findings are consistent with the hypothesis that uterine serous cancer may originate from the fallopian tube epithelium.

αKG-mediated carnitine synthesis promotes homologous recombination via histone acetylation.

Homologous recombination (HR) deficiency enhances sensitivity to DNA damaging agents commonly used to treat cancer. In HR-proficient cancers, metabolic mechanisms driving response or resistance to DNA damaging agents remain unclear. Here we identified that depletion of alpha-ketoglutarate (αKG) sensitizes HR-proficient cells to DNA damaging agents by metabolic regulation of histone acetylation. αKG is required for the activity of αKG-dependent dioxygenases (αKGDDs), and prior work has shown that changes in αKGDD affect demethylases. Using a targeted CRISPR knockout library consisting of 64 αKGDDs, we discovered that Trimethyllysine Hydroxylase Epsilon (TMLHE), the first and rate-limiting enzyme in de novo carnitine synthesis, is necessary for proliferation of HR-proficient cells in the presence of DNA damaging agents. Unexpectedly, αKG-mediated TMLHE-dependent carnitine synthesis was required for histone acetylation, while histone methylation was affected but dispensable. The increase in histone acetylation via αKG-dependent carnitine synthesis promoted HR-mediated DNA repair through site- and substrate-specific histone acetylation. These data demonstrate for the first time that HR-proficiency is mediated through αKG directly influencing histone acetylation via carnitine synthesis and provide a metabolic avenue to induce HR-deficiency and sensitivity to DNA damaging agents.

A microfluidic platform integrating functional vascularized organoids-on-chip.

The development of vascular networks in microfluidic chips is crucial for the long-term culture of three-dimensional cell aggregates such as spheroids, organoids, tumoroids, or tissue explants. Despite rapid advancement in microvascular network systems and organoid technologies, vascularizing organoids-on-chips remains a challenge in tissue engineering. Most existing microfluidic devices poorly reflect the complexity of in vivo flows and require complex technical set-ups. Considering these constraints, we develop a platform to establish and monitor the formation of endothelial networks around mesenchymal and pancreatic islet spheroids, as well as blood vessel organoids generated from pluripotent stem cells, cultured for up to 30 days on-chip. We show that these networks establish functional connections with the endothelium-rich spheroids and vascular organoids, as they successfully provide intravascular perfusion to these structures. We find that organoid growth, maturation, and function are enhanced when cultured on-chip using our vascularization method. This microphysiological system represents a viable organ-on-chip model to vascularize diverse biological 3D tissues and sets the stage to establish organoid perfusions using advanced microfluidics.

Positive childhood experiences serve as protective factors for mental health in pandemic-era youth with adverse childhood experiences.

BACKGROUND: While adverse childhood experiences (ACEs) predict poorer mental health across the life course, positive childhood experiences (PCEs) predict better mental health. It is unclear whether PCEs protect against poor mental health outcomes and promote mental well-being in pandemic-era adolescents with ACEs. METHODS: We examined the individual and joint contributions of ACEs and PCEs to mental health and well-being (MHW) in eleventh-grade British Columbian adolescents (N = 8864) during the fifth wave of COVID-19. We used a novel measure of ACEs that included community- and societal-level ACEs in addition to ACEs experienced at home to investigate the role of social and structural determinants of mental health in supporting the MHW of pandemic-era adolescents. A series of two-way ANCOVAs were conducted comparing MHW outcomes between adolescents with and without ACEs. Interaction effects were examined to investigate whether PCEs moderated the association between ACEs and MHW. RESULTS: Adolescents with no ACEs had significantly better MHW than those with one or more ACE. Having six or more PCEs was associated with better MHW in adolescents with and without ACEs. PCEs significantly moderated the association between ACEs and depression. Effect sizes were larger for PCEs than ACEs in relation to depression, mental well-being, and life satisfaction. CONCLUSIONS: PCEs may protect against depression among adolescents with ACEs and promote MHW among all pandemic-era adolescents. These findings emphasize the importance of addressing social determinants of mental health to mitigate the impact of ACEs and promote PCEs as part of a public health approach to MHW.

Comprehensive phylogenomic time tree of bryophytes reveals deep relationships and uncovers gene incongruences in the last 500 million years of diversification.

PREMISE: Bryophytes form a major component of terrestrial plant biomass, structuring ecological communities in all biomes. Our understanding of the evolutionary history of hornworts, liverworts, and mosses has been significantly reshaped by inferences from molecular data, which have highlighted extensive homoplasy in various traits and repeated bursts of diversification. However, the timing of key events in the phylogeny, patterns, and processes of diversification across bryophytes remain unclear. METHODS: Using the GoFlag probe set, we sequenced 405 exons representing 228 nuclear genes for 531 species from 52 of the 54 orders of bryophytes. We inferred the species phylogeny from gene tree analyses using concatenated and coalescence approaches, assessed gene conflict, and estimated the timing of divergences based on 29 fossil calibrations. RESULTS: The phylogeny resolves many relationships across the bryophytes, enabling us to resurrect five liverwort orders and recognize three more and propose 10 new orders of mosses. Most orders originated in the Jurassic and diversified in the Cretaceous or later. The phylogenomic data also highlight topological conflict in parts of the tree, suggesting complex processes of diversification that cannot be adequately captured in a single gene-tree topology. CONCLUSIONS: We sampled hundreds of loci across a broad phylogenetic spectrum spanning at least 450 Ma of evolution; these data resolved many of the critical nodes of the diversification of bryophytes. The data also highlight the need to explore the mechanisms underlying the phylogenetic ambiguity at specific nodes. The phylogenomic data provide an expandable framework toward reconstructing a comprehensive phylogeny of this important group of plants.

Phenomenology of the Prethermal Many-Body Localized Regime.

The dynamical phase diagram of interacting disordered systems has seen substantial revision over the past few years. Theory must now account for a large prethermal many-body localized regime in which thermalization is extremely slow, but not completely arrested. We derive a quantitative description of these dynamics in short-ranged one-dimensional systems using a model of successive many-body resonances. The model explains the decay timescale of mean autocorrelators, the functional form of the decay-a stretched exponential-and relates the value of the stretch exponent to the broad distribution of resonance timescales. The Jacobi method of matrix diagonalization provides numerical access to this distribution, as well as a conceptual framework for our analysis. The resonance model correctly predicts the stretch exponents for several models in the literature. Successive resonances may also underlie slow thermalization in strongly disordered systems in higher dimensions, or with long-range interactions.

Glutathionylation of pyruvate dehydrogenase complex E2 and inflammatory cytokine production during acute inflammation are magnified by mitochondrial oxidative stress.

Lipopolysaccharide (LPS) is a known inducer of inflammatory signaling which triggers generation of reactive oxygen species (ROS) and cell death in responsive cells like THP-1 promonocytes and freshly isolated human monocytes. A key LPS-responsive metabolic pivot point is the 9 MDa mitochondrial pyruvate dehydrogenase complex (PDC), which provides pyruvate dehydrogenase (E1), lipoamide-linked transacetylase (E2) and lipoamide dehydrogenase (E3) activities to produce acetyl-CoA from pyruvate. While phosphorylation-dependent decreases in PDC activity following LPS treatment or sepsis have been deeply investigated, redox-linked processes have received less attention. Data presented here demonstrate that LPS-induced reversible oxidation within PDC occurs in PDCE2 in both THP-1 cells and primary human monocytes. Knockout of PDCE2 by CRISPR and expression of FLAG-tagged PDCE2 in THP-1 cells demonstrated that LPS-induced glutathionylation is associated with wild type PDCE2 but not mutant protein lacking the lipoamide-linking lysine residues. Moreover, the mitochondrially-targeted electrophile MitoCDNB, which impairs both glutathione- and thioredoxin-based reductase systems, elevates ROS similar to LPS but does not cause PDCE2 glutathionylation. However, LPS and MitoCDNB together are highly synergistic for PDCE2 glutathionylation, ROS production, and cell death. Surprisingly, the two treatments together had differential effects on cytokine production; pro-inflammatory IL-1ß production was enhanced by the co-treatment, while IL-10, an important anti-inflammatory cytokine, dropped precipitously compared to LPS treatment alone. This new information may expand opportunities to understand and modulate PDC redox status and activity and improve the outcomes of pathological inflammation.

Development and validation of a youth climate anxiety scale for the Youth Development Instrument survey.

Emerging terms in the literature such as climate anxiety describe heightened concern, fear, and anxiety related to the climate crisis. Recent efforts have attempted to develop and validate scales to measure climate anxiety; however, extant research is largely focused on adults. Consequently, it is unclear whether developed measures are appropriate for adolescent populations, despite disproportionate impacts of the climate crisis experienced by this age group. The purpose of this study was two-fold; first, we aimed to assess levels of climate concern among Canadian adolescents using the Youth Development Instrument (YDI), a population-level youth well-being survey administered in schools with students (ages 15-18). Secondly, we collaborated with adolescents to adapt an existing climate anxiety scale to be included in the YDI survey. We used survey results to validate the adapted scale for use with adolescents and assessed levels of climate anxiety within our sample. In consultation with adolescents, the 13-item Climate Change Anxiety Scale (CCAS) was adapted to create the Climate Change Anxiety Scale - Short-form (CCAS-S) which consists of four-items adapted from the original CCAS. A total of 2306 respondents were included in analyses. Most adolescents reported feeling climate change concern (75.8%). A smaller proportion reported experiences of climate anxiety (48.7%). Confirmatory factor analysis supported a one-factor structure for the CCAS-S, with high internal consistency (Cronbach's alpha = 0.95) and good model fit with error co-variance. Findings from this study provide construct validity evidence and reliability for the use of the CCAS-S in adolescent populations.

Investigation of the Copper Requirements of the Metallophyte Liverworts Cephaloziella nicholsonii Douin and C. massalongoi (Spruce) Müll.Frib.

Former mine sites can provide habitat for many rare specialised bryophyte species that have adapted to metal-rich soil conditions that are toxic to most other plant species. Some of the bryophyte species found in this habitat are facultative metallophytes, and others are regarded as strict metallophytes, the so-called 'copper mosses'. It is a general assumption in the literature that Cephaloziella nicholsonii and C. massalongoi, both categorised as Endangered in the IUCN Red List for Europe, are also strict metallophytes and obligate copper bryophytes. This in vitro experiment investigated the growth and gemma production of these two species from different sites in Ireland and Britain on treatment plates of 0 ppm, 3 ppm, 6 ppm, 12 ppm, 24 ppm, 48 ppm and 96 ppm copper. Results show that elevated copper is not an obligate requirement for optimum growth. Differences in response to the copper treatment levels among populations evident within both species could possibly be due to ecotypic variation. A case is also made for the taxonomic revision of the Cephaloziella genus. Implications for the species' conservation are discussed.

Micro to macro scale analysis of the intact human renal arterial tree with Synchrotron Tomography.

Background: The kidney vasculature is exquisitely structured to orchestrate renal function. Structural profiling of the vasculature in intact rodent kidneys, has provided insights into renal haemodynamics and oxygenation, but has never been extended to the human kidney beyond a few vascular generations. We hypothesised that synchrotron-based imaging of a human kidney would enable assessment of vasculature across the whole organ. Methods: An intact kidney from a 63-year-old male was scanned using hierarchical phase-contrast tomography (HiP-CT), followed by semi-automated vessel segmentation and quantitative analysis. These data were compared to published micro-CT data of whole rat kidney. Results: The intact human kidney vascular network was imaged with HiP-CT at 25 µm voxels, representing a 20-fold increase in resolution compared to clinical CT scanners. Our comparative quantitative analysis revealed the number of vessel generations, vascular asymmetry and a structural organisation optimised for minimal resistance to flow, are conserved between species, whereas the normalised radii are not. We further demonstrate regional heterogeneity in vessel geometry between renal cortex, medulla, and hilum, showing how the distance between vessels provides a structural basis for renal oxygenation and hypoxia. Conclusions: Through the application of HiP-CT, we have provided the first quantification of the human renal arterial network, with a resolution comparable to that of light microscopy yet at a scale several orders of magnitude larger than that of a renal punch biopsy. Our findings bridge anatomical scales, profiling blood vessels across the intact human kidney, with implications for renal physiology, biophysical modelling, and tissue engineering.