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A challenge of teacher education is to produce graduate primary school teachers who are confident and competent teachers of mathematics. Various approaches to primary school teacher education in mathematics have been investigated, but primary teacher education graduates still tend to be diffident in their teaching of mathematics. In an age where personal use of mobile technologies is becoming ubiquitous, such technologies could provide a conduit into making mathematics teaching and learning more accessible to primary teacher education students. This paper introduces the use of a pedagogical framework which can scaffold mobile learning in mathematics teacher education programs. The paper discusses ways in which this framework, the Mobile Pedagogical Framework, can contribute to enhanced primary teacher education in mathematics, using mobile technologies. The Framework has three major dimensions: authenticity, collaboration and personalisation. Each of these will be discussed in terms of their alignment with current ideas about quality teaching in mathematics.

Purpose: This paper is based on the emergency changes we have had to make in the European DEIMP Project (2017-2020), "Designing and Evaluating Innovative Mobile Pedagogies" (DEIMP). DEIMP is undertaken by a transnational consortium comprising partner institutions and schools from the UK (coordinating), Australia, Belgium, Cyprus, Ireland and The Netherlands. As well as the enforced changes to the project, there have been major adjustments in how education is being provided in each of our countries, across all sectors: primary, secondary and tertiary. The purpose of this paper is to provide pragmatic guidelines that will help us respond effectively in the uncertain present, and plan systematically for an unpredictable, post-pandemic future. Design/methodology/approach: The authors outline 21 design principles underpinning innovative mobile learning, which will be of pragmatic use to all using mobile learning in the COVID-19 pandemic. These principles have emerged in the context of the three-year European DEIMP Project (2017-2020). The authors also examine major educational changes that have recently been imposed upon teachers and educational researchers, and key aspects of the current emergency response in education internationally, and resultant implications for educational technology and mobile learning. Findings: A living record highlighting what is currently happening in the educational systems of the DEIMP project's respective partner countries. The paper outlines design concerns and issues, which will need to be addressed as the authors endeavour to bridge both the digital divide and digital use divide in remote education. Furthermore, the paper illustrates 21 pragmatic design principles underpinning innovative mobile pedagogies. Originality/value: A comparative study of the effects of the pandemic across six countries, including The UK, Australia, Belgium, Cyprus, Ireland and The Netherlands. The authors outline 21 design principles for mobile learning, which is hoped will help us respond effectively in the uncertain present, and plan systematically for an unpredictable, post-pandemic future.

Career changers form a substantial proportion of teacher education (TE) students. They bring a broader set of life and work experiences than do their younger, school-leaving counterparts. This paper investigates the needs and concerns of career change student teachers (CCSTs) in Australia. The study on which this article reports analysed survey data from 508 CCSTs enrolled in 29 of Australia's 34 universities. The article explores what this group brings to their TE courses, and how their needs and contributions may differ from those of younger students. The data confirmed career changers' reasons for choosing teaching are primarily driven by intrinsic and altruistic motivations. Concerns regarding flexibility in course offerings was expressed. We advise that attracting and retaining career change teachers is likely to become increasingly important in the context of rising school student numbers, teacher attrition, and the impending departure from the profession of many 'baby boomers'.

The rate of change in the use of digital technologies in schools means that professional learning regarding technology-enhanced learning is constantly required for school teachers. The focus of this article is on how an action learning (AL) approach supported the professional learning of teachers regarding adoption of mobile technologies in their teaching. In particular, the article investigates the role of facilitation in the action learning process and explores an AL process implemented at two schools, one a primary school and the other a secondary school. Drawing on qualitative methodology, a multi-site case study using observations, field notes and interviews was implemented to investigate the effectiveness of the AL approach. It was found that different kinds of facilitation were central to the success of the process, and that facilitation impacted on teacher agency. The article concludes with recommendations for action learning projects.

Digital games, especially simulations, have supported student learning outcomes in the areas of science and agriculture in classrooms and nonformal settings. Simulations contribute robustly to student achievement in science, technology, engineering, and mathematics (STEM), and agriculture content areas, especially when they are aligned with national education standards. The People in Ecosystems Watershed Integration (PEWI) simulation is a digital game that was evaluated for fit to two national standards: the Next Generation Science Standards (NGSS) and the Agriculture, Food, and Natural Resources Standards (AFNR). The evaluation of alignment of PEWI to NGSS provided "extensive" evidence on a four-point scale for meeting Criterion A: Explaining phenomenon/designing solutions; Criterion B: 3-D learning, science and engineering practices, rated for three areas: (a) "extensive" for science and engineering practices, (b) "adequate" for disciplinary core ideas, and (c) "extensive" for cross-cutting concepts. Additionally, PEWI aligned with nine high school-level NGSS student performance expectations categories. For AFNR Standards, the PEWI evaluation provided evidence for alignment to 10 standards and 17 indicators from the AFNR areas of Environmental Service Systems, Natural Resource Systems, and Plant Systems.

Excitons play an important role in the optical properties of 2D semiconductors, but their spatial characterization is usually constrained by the diffraction limit. Here, the authors report near-field optical spectroscopy of 2D transition metal dichalcogenides with 20 nm resolution, revealing their spatially dependent excitonic spectra and complex dielectric function.

Breast cancer is the second leading cause of cancer-related deaths in women and triple-negative breast cancer (TNBC), in particular, is an aggressive and highly metastatic type of breast cancer that does not respond to established targeted therapies and is associated with poor prognosis and worse survival. Previous studies identified a subgroup of triple-negative breast cancer patients with high expression of estrogen related receptor alpha (ERRα) that has better prognosis when treated with tamoxifen. We therefore set out to identify common targets of tamoxifen and ERRα in the context of TNBC using phosphoproteomic analysis. In this study, we discovered that phosphorylation of mitogen-activated protein kinase 1 (MAPK1) is regulated by tamoxifen as well as ERRα. Additionally, we showed that inhibition of MAPK signaling together with the use of a selective ERRα inverse agonist, XCT-790, leads to a significant upregulation of apoptosis and paves way for the therapeutic use of MAPK inhibitors for treatment of ERRα expressing TNBC.

Individual luminescent nanoparticles enable thermometry with sub-diffraction limited spatial resolution, but potential self-heating effects from high single-particle excitation intensities remain largely uninvestigated because thermal models predict negligible self-heating. Here, we report that the common "ratiometric" thermometry signal of individual NaYF4:Yb3+,Er3+ nanoparticles unexpectedly increases with excitation intensity, implying a temperature rise over 50 K if interpreted as thermal. Luminescence lifetime thermometry, which we demonstrate for the first time using individual NaYF4:Yb3+,Er3+ nanoparticles, indicates a similar temperature rise. To resolve this apparent contradiction between model and experiment, we systematically vary the nanoparticle's thermal environment: the substrate thermal conductivity, nanoparticle-substrate contact resistance, and nanoparticle size. The apparent self-heating remains unchanged, demonstrating that this effect is an artifact, not a real temperature rise. Using rate equation modeling, we show that this artifact results from increased radiative and non-radiative relaxation from higher-lying Er3+ energy levels. This study has important implications for single-particle thermometry.

Chemical sensing in living systems demands optical sensors that are bright, stable, and sensitive to the rapid dynamics of chemical signaling. Lanthanide-doped upconverting nanoparticles (UCNPs) efficiently convert near infrared (NIR) light to higher energy emission and allow biological systems to be imaged with no measurable background or photobleaching, and with reduced scatter for subsurface experiments. Despite their advantages as imaging probes, UCNPs have little innate chemical sensing ability and require pairing with organic fluorophores to act as biosensors, although the design of stable UCNP-fluorophore hybrids with efficient upconverted energy transfer (UET) has remained a challenge. Here, we report Yb3+- and Er3+-doped UCNP-fluorophore conjugates with UET efficiencies up to 88%, and photostabilities 100-fold greater by UET excitation than those of the free fluorophores under direct excitation. Despite adding distance between Er3+ donors and organic acceptors, thin inert shells significantly enhance overall emission without compromising UET efficiency. This can be explained by the large increase in quantum yield of Er3+ donors at the core/shell interface and the large number of fluorophore acceptors at the surface. Sensors excited by UET show increases in photostability well beyond those reported for other methods for increasing the longevity of organic fluorophores, and those covalently attached to UCNP surface polymers show greater chemical stability than those directly coordinated to the nanocrystal surface. By conjugating other fluorescent chemosensors to UCNPs, these hybrids may be extended to a series of NIR-responsive biosensors for quantifying the dynamic chemical populations critical for cell signaling.

Optical methods for imaging and stimulation of biological events based on the use of visible light are limited to the superficial layers of tissue due to the significant absorption and scattering of light. Here, we demonstrate the design and implementation of passive micro-structured lightbulbs (MLBs) containing bright-emitting lanthanide-doped upconverting nanoparticles (UCNPs) for light delivery deep into the tissue. The MLBs are realized as cylindrical pillars made of Parylene C polymer that can be implanted deep into the tissue. The encapsulated UCNPs absorb near-infrared (NIR) light at λ = 980 nm, which undergoes much less absorption than the blue light in the brain tissue, and then locally emit blue light (1G4→3H6 and 1D2→3F4 transitions) that can be used for optogenetic excitation of neurons in the brain. The 3H4→3H6 transition will result in the emission of higher energy NIR photons at λ = 800 nm that can be used for imaging and tracking MLBs through thick tissue.

Multiphoton imaging techniques that convert low-energy excitation to higher energy emission are widely used to improve signal over background, reduce scatter, and limit photodamage. Lanthanide-doped upconverting nanoparticles (UCNPs) are among the most efficient multiphoton probes, but even UCNPs with optimized lanthanide dopant levels require laser intensities that may be problematic. Here, we develop protein-sized, alloyed UCNPs (aUCNPs) that can be imaged individually at laser intensities >300-fold lower than needed for comparably sized doped UCNPs. Using single UCNP characterization and kinetic modeling, we find that addition of inert shells changes optimal lanthanide content from Yb3+, Er3+-doped NaYF4 nanocrystals to fully alloyed compositions. At high levels, emitter Er3+ ions can adopt a second role to enhance aUCNP absorption cross-section by desaturating sensitizer Yb3+ or by absorbing photons directly. Core/shell aUCNPs 12 nm in total diameter can be imaged through deep tissue in live mice using a laser intensity of 0.1 W cm-2.

Reducing the size of lasers to microscale dimensions enables new technologies1 that are specifically tailored for operation in confined spaces ranging from ultra-high-speed microprocessors2 to live brain tissue3. However, reduced cavity sizes increase optical losses and require greater input powers to reach lasing thresholds. Multiphoton-pumped lasers4-7 that have been miniaturized using nanomaterials such as lanthanide-doped upconverting nanoparticles (UCNPs)8 as lasing media require high pump intensities to achieve ultraviolet and visible emission and therefore operate under pulsed excitation schemes. Here, we make use of the recently described energy-looping excitation mechanism in Tm3+-doped UCNPs9 to achieve continuous-wave upconverted lasing action in stand-alone microcavities at excitation fluences as low as 14 kW cm-2. Continuous-wave lasing is uninterrupted, maximizing signal and enabling modulation of optical interactions10. By coupling energy-looping nanoparticles to whispering-gallery modes of polystyrene microspheres, we induce stable lasing for more than 5 h at blue and near-infrared wavelengths simultaneously. These microcavities are excited in the biologically transmissive second near-infrared (NIR-II) window and are small enough to be embedded in organisms, tissues or devices. The ability to produce continuous-wave lasing in microcavities immersed in blood serum highlights practical applications of these microscale lasers for sensing and illumination in complex biological environments.

Accurate assessment of the long-term security of geologic carbon sequestration requires knowledge of the mobility of carbon dioxide in brines under pressure and temperature conditions that prevail in subsurface aquifers. Here, we report Raman spectroscopic measurements of the rate of CO2 diffusion in water and brines as a function of pressure, salinity, and concentration of CO2. In pure water at 50 ± 2 °C and 90 ± 2 bar, we find the diffusion coefficient, D, to be (3.08 ± 0.03) × 10-9 m2/s, a value that is consistent with a recent microfluidic study but lower than earlier PVT measurements. Under reservoir conditions, salinity affects the mobility of CO2 significantly and D decreased by 45% for a 4 M solution of NaCl. We find significant differences of diffusivity of CO2 in brines (0-4 M NaCl), in both the absolute values and the trend compared to the Stokes-Einstein prediction under our experimental conditions. We observe that D decreases significantly at the high CO2 concentrations expected in subsurface aquifers (∼15% reduction at 0.55 mol/kg of CO2) and provides an empirical correction to the commonly reported D values that assume a tracer concentration dependence on diffusivity.

The idea of a “cognitive map” was originally developed to ex-plain planning and generalization in spatial domains througha representation of inferred relationships between experiences.Recently, new research has suggested similar principles mayalso govern the representation of more abstract, conceptualknowledge in the brain. We test whether the search for rewardsin conceptual spaces follows similar computational principlesas in spatial environments. Using a within-subject design, par-ticipants searched for both spatially and conceptually corre-lated rewards in multi-armed bandit tasks. We use a GaussianProcess model combining generalization with an optimisticsampling strategy to capture human search decisions and judg-ments in both domains, and to simulate human-level perfor-mance when specified with participant parameter estimates. Inline with the notion of a domain-general generalization mecha-nism, parameter estimates correlate across spatial and concep-tual search, yet some differences also emerged, with partici-pants generalizing less and exploiting more in the conceptualdomain.

The Observation of Human-Animal Interaction for Research (OHAIRE) is a coding tool developed to capture the behavior of children when interacting with social partners and animals in naturalistic settings. The OHAIRE behavioral categories of focus are emotional displays, social communication behaviors toward adults and peers, behaviors directed toward animals or experimental control objects, and interfering behaviors. To date, the OHAIRE has been used by 14 coders to code 2,732 min of video across four studies with a total of 201 participants ages 5 to 18 years (M = 10.1, SD = 2.5). Studies involved animal-assisted intervention with three species (i.e., dogs, horses, and guinea pigs) and three populations (i.e., autism spectrum disorder, attention-deficit hyperactivity disorder, and typically developing children) in a school, a therapeutic horseback riding program, a group therapy program, and the hospital setting. We explored the psychometric properties of the OHAIRE through analyses of its inter-rater reliability, intra-rater reliability, convergent and divergent validity, and internal structure, using data from these four human-animal interaction studies. The average inter-rater reliability was excellent (kappa = 0.81), with good reliability in most of the behavioral categories coded. Intra-rater reliability was consistently excellent (0.87 ≤ kappa ≤0.96). Internal structure analyses with Cronbach's alpha supported the exploratory use of subscales to measure social communication behaviors toward peers (α = 0.638) and adults (α = 0.605), and interactions experimental control objects (α = 0.589), and the use of a subscale to measure interactions with animals (α = 0.773). Correlation analyses with multiple questionnaires showed a convergence between positive emotional display and social behaviors as assessed by the OHAIRE and social skills as assessed by the Social Skills Rating System (SSRS) and the Social Communication Questionnaires (SCQ). Little concordance was found between the OHAIRE and the Social Responsiveness Scale (SRS) or the Aberrant Behavior Checklist-Community (ABC). The OHAIRE shows promise for wider use in the field of Human-Animal Interaction, with a need for generalization across more settings and ages.

Attention Deficit/Hyperactivity Disorder (ADHD), the most ubiquitous mental health problem in children, has been associated with poor self-esteem. Psychosocial interventions have aimed to improve self-esteem among this group, with the aim of reducing the development of comorbid depression and anxiety. The present study implemented a randomized control design to examine the possibility of Animal Assisted Interventions (AAI) as a viable approach to improving self-esteem among children with ADHD. Children's self-esteem across multiple domains as measured by the Self-Perception Profile for Children was evaluated (n = 80, ages 7-9, 71% male). To test the hypothesis that AAI improves self-esteem, stratified Wilcoxon Signed-Rank Tests (SAS NPAR1WAY procedure) were used to compare pre- to post-treatment ratings. Analyses indicated that scores of children's self-perceptions in the domains of behavioral conduct, social, and scholastic competence, were significantly increased from baseline to post-treatment in the AAI group (z = 2.320, p = .021, z = 2.631, p = .008, and z = 2.541, p = .011, respectively), whereas pre-post-treatment differences in self-perceptions were not found for the children in the control group without AAI. Findings suggest that AAI is a viable strategy for improving ratings of self-perceived self-esteem in children with ADHD.

This study aims to evaluate the dose sensitivity of MAGIC-f gel irradiated by high-energy photon beams, comparing quantification using different MRI sequences. Irradiation was performed using 6 MV photons with 600 cGy/min dose rate, field size of 20x20 cm², and 94 cm source-to-surface distance. Two gel batches were produced on different days and placed in vials. In the first batch, doses of 0, 2, 4, 6, 8, 10, 20, and 40 Gy were planned. The second batch was irradiated with doses of 0, 2, 4, 6, 10, 12, 14, and 16 Gy. MR images were acquired with Spin Echo (SE, TR=3 s) and Multi Spin Echo (MSE, TR = 3s or 10s, turbo factor 24) sequences. The dose is assessed via changes in the transverse relaxation time in the irradiated gel. In MSE, dose sensitivity in the first batch was 0.27 (TR=3 s) and 0.28 Gy-1s-1 (TR=10 s) and in the second batch, 0.31 and 0.31 Gy-1s-1 (TR = 3 s and TR = 10 s, respectively). In the SE sequence, dose sensitivity was 0.42 for the first batch and 0.43 Gy-1s-1 for the second batch. Linearity of dose-response was only obtained for doses below 10 Gy. Comparing the dose sensitivity extracted from MSE and SE sequences using TR= 3s, differences around 30% were found. Thus, although MSE-MRI offers a faster protocol of imaging acquisition it is less precise for quantification of relaxation times, as TE is not a well-defined quantity. The performance of the gel as a dosimeter is consequently sequence dependent.

Previous studies indicate a role of dopamine in spatial navigation. Although neural representations of direction are an important aspect of spatial cognition, it is not well understood whether dopamine directly affects these representations, or only impacts other aspects of spatial brain function. Moreover, both dopamine and spatial cognition decline sharply during age, raising the question which effect dopamine has on directional signals in the brain of older adults. To investigate these questions, we used a double-blind cross-over L-DOPA/Placebo intervention design in which 43 younger and 37 older adults navigated in a virtual spatial environment while undergoing functional magnetic resonance imaging (fMRI). We studied the effect of L-DOPA, a dopamine precursor, on fMRI activation patterns that encode spatial walking directions that have previously been shown to lose specificity with age. This was done in predefined regions of interest, including the early visual cortex, retrosplenial cortex, and hippocampus. Classification of brain activation patterns associated with different walking directions was improved across all regions following L-DOPA administration, suggesting that dopamine broadly enhances neural representations of direction. No evidence for differences between regions was found. In the hippocampus these results were found in both age groups, while in the retrosplenial cortex they were only observed in younger adults. Taken together, our study provides evidence for a link between dopamine and the specificity of neural responses during spatial navigation. Significance Statement: The sense of direction is an important aspect of spatial navigation, and neural representations of direction can be found throughout a large network of space-related brain regions. But what influences how well these representations track someone’s true direction? Using a double-blind cross-over L-DOPA/Placebo intervention design, we find causal evidence that the neurotransmitter dopamine impacts the fidelity of direction selective neural representations in the human hippocampus and retrosplenial cortex. Interestingly, the effect of L-DOPA was either equally present or even smaller in older adults, despite the well-known age related decline of dopamine. These results provide novel insights into how dopamine shapes the neural representations that underlie spatial navigation.

Evaluating and tuning the properties of two-dimensional (2D) materials is a major focus of advancing 2D science and technology. While many claim that the photonic properties of a 2D layer provide evidence that the material is "high quality", this may not be true for electronic performance. In this work, we deconvolute the photonic and electronic response of synthetic monolayer molybdenum disulfide. We demonstrate that enhanced photoluminescence can be robustly engineered via the proper choice of substrate, where growth of MoS2 on r-plane sapphire can yield >100x enhancement in PL and carrier lifetime due to increased molybdenum-oxygen bonding compared to that of traditionally grown MoS2 on c-plane sapphire. These dramatic enhancements in optical properties are similar to those of super-acid treated MoS2, and suggest that the electronic properties of the MoS2 are also superior. However, a direct comparison of the charge transport properties indicates that the enhanced PL due to increased Mo-O bonding leads to p-type compensation doping, and is accompanied by a 2x degradation in transport properties compared to MoS2 grown on c-plane sapphire. This work provides a foundation for understanding the link between photonic and electronic performance of 2D semiconducting layers, and demonstrates that they are not always correlated.

The combination of superconducting nanowire single photon detectors and electro-optically reconfigurable circuits in a cryogenic environment is notoriously difficult to reach. Here, the authors realise this on a Lithium-Niobate-On-Insulator platform, reaching high speed modulation at a frequency up to 1 GHz.

Stratospheric inorganic chlorine (Cly) is predominantly released from long-lived chlorinated source gases and, to a small extent, very short-lived chlorinated substances. Cly includes the reservoir species (HCl and ClONO2) and active chlorine species (i.e., ClOx). The active chlorine species drive catalytic cycles that deplete ozone in the polar winter stratosphere. This work presents calculations of inorganic chlorine (Cly) derived from chlorinated source gas measurements on board the High Altitude and Long Range Research Aircraft (HALO) during the Southern Hemisphere Transport, Dynamic and Chemistry (SouthTRAC) campaign in austral late winter and early spring 2019. Results are compared to Cly in the Northern Hemisphere derived from measurements of the POLSTRACC-GW-LCYCLE-SALSA (PGS) campaign in the Arctic winter of 2015/2016. A scaled correlation was used for PGS data, since not all source gases were measured. Using the SouthTRAC data, Cly from a scaled correlation was compared to directly determined Cly and agreed well. An air mass classification based on in situ N2O measurements allocates the measurements to the vortex, the vortex boundary region, and midlatitudes. Although the Antarctic vortex was weakened in 2019 compared to previous years, Cly reached 1687±19 ppt at 385 K; therefore, up to around 50 % of total chlorine was found in inorganic form inside the Antarctic vortex, whereas only 15 % of total chlorine was found in inorganic form in the southern midlatitudes. In contrast, only 40 % of total chlorine was found in inorganic form in the Arctic vortex during PGS, and roughly 20 % was found in inorganic form in the northern midlatitudes. Differences inside the two vortices reach as much as 540 ppt, with more Cly in the Antarctic vortex in 2019 than in the Arctic vortex in 2016 (at comparable distance to the local tropopause). To our knowledge, this is the first comparison of inorganic chlorine within the Antarctic and Arctic polar vortices. Based on the results of these two campaigns, the differences in Cly inside the two vortices are substantial and larger than the inter-annual variations previously reported for the Antarctic.

We report on measurements of total bromine (Brtot) in the upper troposphere and lower stratosphere taken during 15 flights with the German High Altitude and LOng range research aircraft (HALO). The research campaign WISE (Wave-driven ISentropic Exchange) included regions over the North Atlantic, Norwegian Sea, and northwestern Europe in fall 2017. Brtot is calculated from measured total organic bromine (Brorg) added to inorganic bromine (Bryinorg), evaluated from measured BrO and photochemical modeling. Combining these data, the weighted mean [Brtot] is 19.2±1.2 ppt in the northern hemispheric lower stratosphere (LS), in agreement with expectations for Brtot in the middle stratosphere (Engel and Rigby et al., 2018). The data reflect the expected variability in Brtot in the LS due to variable influx of shorter lived brominated source and product gases from different regions of entry. A closer look into Brorg and Bryinorg, as well as simultaneously measured transport tracers (CO and N2O) and an air mass lag time tracer (SF6), suggests that bromine-rich air masses persistently protruded into the lowermost stratosphere (LMS) in boreal summer, creating a high bromine region (HBrR). A subsection, HBrR∗, has a weighted average of [Brtot] = 20.9±0.8 ppt. The most probable source region is air recently transported from the tropical upper troposphere and tropopause layer (UT/TTL) with a weighted mean of [Brtot] = 21.6±0.7 ppt. CLaMS Lagrangian transport modeling shows that the HBrR air mass consists of 51.2 % from the tropical troposphere, 27.1 % from the stratospheric background, and 6.4 % from the midlatitude troposphere (as well as contributions from other domains). The majority of the surface air reaching the HBrR is from the Asian monsoon and its adjacent tropical regions, which greatly influences trace gas transport into the LMS in boreal summer and fall. Tropical cyclones from Central America in addition to air associated with the Asian monsoon region contribute to the elevated Brtot observed in the UT/TTL. TOMCAT global 3-D model simulations of a concurrent increase of Brtot show an associated O3 change of -2.6±0.7 % in the LS and -3.1±0.7 % near the tropopause. Our study of varying Brtot in the LS also emphasizes the need for more extensive monitoring of stratospheric Brtot globally and seasonally to fully understand its impact on LMS O3 and its radiative forcing of climate, as well as in aged air in the middle stratosphere to elucidate the stratospheric trend in bromine.

Abstract Tau neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimer’s disease (AD). To elucidate patterns of structural change in the MTL specifically associated with tau pathology, we compared high-resolution ex vivo MRI scans of human postmortem MTL specimens with histology-based pathological assessments of the MTL. MTL specimens were obtained from twenty-nine brain donors, including patients with AD, other dementias, and individuals with no known history of neurological disease. Ex vivo MRI scans were combined using a customized groupwise diffeomorphic registration approach to construct a 3D probabilistic atlas that captures the anatomical variability of the MTL. Using serial histology imaging in eleven specimens, we labelled the MTL subregions in the atlas based on cytoarchitecture. Leveraging the atlas and neuropathological ratings of tau and TAR DNA-binding protein 43 (TDP-43) pathology severity, morphometric analysis was performed to correlate regional MTL thickness with the severity of tau pathology, after correcting for age and TDP-43 pathology. We found significant correlations between tau pathology and thickness in the entorhinal cortex (ERC) and stratum radiatum lacunosum moleculare (SRLM). When focusing on cases with low levels of TDP-43 pathology, we found strong associations between tau pathology and thickness in the ERC, SRLM and the subiculum/cornu ammonis 1 (CA1) subfields of the hippocampus, consistent with early Braak stages.

Here, the authors investigate the lattice dynamics of twisted hexagonal boron nitride layers via nano-infrared spectroscopy, showing local and stacking-dependent variations of the optical phonon frequencies associated to the interaction with the graphite substrate.

BackgroundLong COVID—a condition with persistent symptoms post COVID-19 infection—is the first illness arising from social media. In France, the French hashtag #ApresJ20 described symptoms persisting longer than 20 days after contracting COVID-19. Faced with a lack of recognition from medical and official entities, patients formed communities on social media and described their symptoms as long-lasting, fluctuating, and multisystemic. While many studies on long COVID relied on traditional research methods with lengthy processes, social media offers a foundation for large-scale studies with a fast-flowing outburst of data. ObjectiveWe aimed to identify and analyze Long Haulers’ main reported symptoms, symptom co-occurrences, topics of discussion, difficulties encountered, and patient profiles. MethodsData were extracted based on a list of pertinent keywords from public sites (eg, Twitter) and health-related forums (eg, Doctissimo). Reported symptoms were identified via the MedDRA dictionary, displayed per the volume of posts mentioning them, and aggregated at the user level. Associations were assessed by computing co-occurrences in users’ messages, as pairs of preferred terms. Discussion topics were analyzed using the Biterm Topic Modeling; difficulties and unmet needs were explored manually. To identify patient profiles in relation to their symptoms, each preferred term’s total was used to create user-level hierarchal clusters. ResultsBetween January 1, 2020, and August 10, 2021, overall, 15,364 messages were identified as originating from 6494 patients of long COVID or their caregivers. Our analyses revealed 3 major symptom co-occurrences: asthenia-dyspnea (102/289, 35.3%), asthenia-anxiety (65/289, 22.5%), and asthenia-headaches (50/289, 17.3%). The main reported difficulties were symptom management (150/424, 35.4% of messages), psychological impact (64/424,15.1%), significant pain (51/424, 12.0%), deterioration in general well-being (52/424, 12.3%), and impact on daily and professional life (40/424, 9.4% and 34/424, 8.0% of messages, respectively). We identified 3 profiles of patients in relation to their symptoms: profile A (n=406 patients) reported exclusively an asthenia symptom; profile B (n=129) expressed anxiety (n=129, 100%), asthenia (n=28, 21.7%), dyspnea (n=15, 11.6%), and ageusia (n=3, 2.3%); and profile C (n=141) described dyspnea (n=141, 100%), and asthenia (n=45, 31.9%). Approximately 49.1% of users (79/161) continued expressing symptoms after more than 3 months post infection, and 20.5% (33/161) after 1 year. ConclusionsLong COVID is a lingering condition that affects people worldwide, physically and psychologically. It impacts Long Haulers’ quality of life, everyday tasks, and professional activities. Social media played an undeniable role in raising and delivering Long Haulers’ voices and can potentially rapidly provide large volumes of valuable patient-reported information. Since long COVID was a self-titled condition by patients themselves via social media, it is imperative to continuously include their perspectives in related research. Our results can help design patient-centric instruments to be further used in clinical practice to better capture meaningful dimensions of long COVID.

ABSTRACT In this study, we observed that burrows of Rhinella dorbignyi (Duméril & Bibron, 1841) are distributed in a non-random manner in the habitat, suggesting a microhabitat selection for digging. This conclusion was based on a characterization of 36 burrows and surrounding micro-habitat. We established a 1 m x 1 m quadrat with the burrow in its central point (n=36) to measure the percentage (density) and the average heights of grasses, herbs, and shrubs. All measurements were repeated in two unused quadrats (without burrows) to evaluate the available microhabitat (n=72). The burrows are built in specific areas of the habitat with a higher percentage of grass, taller herbs, lower density of shrubs and low shaded sites than the founded at control sites. Based on three-dimensional models of the interior of the burrow (n=15), we observed that all of them were constructed with an elliptical opening that opens into a narrow channel perpendicular to the ground. Channels had a mean maximum diameter of 38 mm and a mean minimum diameter of 18 mm. The mean length of the burrows is 182 mm, and the mean volume is 95 mL.

Candida albicans causes severe invasive candidiasis. C. albicans infection requires the virulence factor candidalysin (CL) which damages target cell membranes. However, the mechanism that CL uses to permeabilize membranes is unclear. We reveal that CL forms membrane pores using a unique mechanism. Unexpectedly, CL readily assembled into polymers in solution. We propose that the basic structural unit in polymer formation is a CL oligomer, which is sequentially added into a string configuration that can close into a loop. CL loops appear to spontaneously insert into the membrane to become pores. A CL mutation (G4W) inhibited the formation of polymers in solution and prevented pore formation in synthetic lipid systems. Epithelial cell studies showed that G4W CL failed to activate the danger response pathway, a hallmark of the pathogenic effect of CL. These results indicate that CL polymerization in solution is a necessary step for the damage of cellular membranes. Analysis of CL pores by atomic force microscopy revealed co-existence of simple depressions and more complex pores, which are likely formed by CL assembled in an alternate oligomer orientation. We propose that this structural rearrangement represents a maturation mechanism that stabilizes pore formation to achieve more robust cellular damage. To summarize, CL uses a previously unknown mechanism to damage membranes, whereby pre-assembly of CL loops in solution leads to formation of membrane pores. Our investigation not only unravels a new paradigm for the formation of membrane pores, but additionally identifies CL polymerization as a novel therapeutic target to treat candidiasis.

This paper describes a case of an aggressive primary splenic angiosarcoma in a 29-year-old man and makes a review of its clinicai findings, pathologic reports, treatment and prognosis. Angiosarcomas comprise less than 1% of soft tissue sarcomas, and only a small percentage of these tumors arise in the spleen. These tumors usually represent a diagnostic challenge for the pathologist in view of its variegated histology, and the development of new immu-nohistochemical markers for vascular tumors like CD31 (platelet-endothelial cell adhesion molecule) helps to rule out other diagnoses. There is no standard chemotherapy treatment for angiosarcomas, and the prognosis of splenic angiosarcoma is particularly poor.