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We report the two-photon absorption laser-induced fluorescence rotational spectrum of the CO B 1Σ+ ← X 1Σ+ Hopfield–Birge system (v′ = 0, v″ = 0) Q-branch in an ∼4850 K, atmospheric pressure plasma torch plume at thermal equilibrium in both the quenching-dominated (low laser intensity) and photoionization-dominated (high laser intensity) regimes. We provide a detailed analysis of the photophysics in these two regimes using a rate equation approach and propose modeling considerations for them as well. In the experimental spectra, distinct rotational transitions up to J″ = 83 are observed, allowing analysis over a very large range of rotational states. Evidence of predissociation is observed for J′ ≥ 64 and is likely due to the interaction with the D′1Σ+ electronic state, which has been proposed in the literature but never observed in the v′ = 0 state. The line positions of higher rotational states show disagreement with line positions calculated from molecular constants in the available literature, suggesting the need for modifications to the constants, which are reported here. A shift in the B 1Σ+ ← X 1Σ+ absorption spectrum toward higher two-photon energy as a result of the second-order Stark shift was observed in the photoionization-dominated spectrum, and the second-order Stark shift cross section was estimated to be 7 ± 3 × 10−18 cm2. The mean photoionization cross section of the excited upper state was inferred by comparing the line broadening of the two spectra and was estimated to be 11 ± 7 × 10−18 cm2. In addition, weak J′-dependent variations of the photoionization cross section were observed and are reported here. [ABSTRACT FROM AUTHOR]

The body plan of the human parasite Toxoplasma gondii has a well-defined polarity. The minus ends of the 22 cortical microtubules are anchored to the apical polar ring, which is a putative microtubule-organizing center. The basal complex caps and constricts the parasite posterior end and is crucial for cytokinesis. How this apical–basal polarity is initiated is unknown. Here, we have examined the development of the apical polar ring and the basal complex using expansion microscopy. We found that substructures in the apical polar ring have different sensitivities to perturbations. In addition, apical– basal differentiation is already established upon nucleation of the cortical microtubule array: arc forms of the apical polar ring and basal complex associate with opposite ends of the microtubules. As the nascent daughter framework grows towards the centrioles, the apical and basal arcs co-develop ahead of the microtubule array. Finally, two apical polar ring components, APR2 and KinesinA, act synergistically. The removal of individual proteins has a modest impact on the lytic cycle. However, the loss of both proteins results in abnormalities in the microtubule array and in highly reduced plaquing and invasion efficiency. [ABSTRACT FROM AUTHOR]

Neural activity and behavior vary within an individual (states) and between individuals (traits). However, the mapping of state-trait neural variation to behavior is not well understood. To address this gap, we quantify moment-to-moment changes in brain-wide co-activation patterns derived from resting-state functional magnetic resonance imaging. In healthy young adults, we identify reproducible spatiotemporal features of co-activation patterns at the single-subject level. We demonstrate that a joint analysis of state-trait neural variations and feature reduction reveal general motifs of individual differences, encompassing state-specific and general neural features that exhibit day-to-day variability. The principal neural variations co-vary with the principal variations of behavioral phenotypes, highlighting cognitive function, emotion regulation, alcohol and substance use. Person-specific probability of occupying a particular co-activation pattern is reproducible and associated with neural and behavioral features. This combined analysis of state-trait variations holds promise for developing reproducible neuroimaging markers of individual life functional outcome. Neural activity and behavior vary within and between individuals, but how these variations are linked to behavior is not well understood. This neuroimaging study shows that the human brain shows co-activation patterns that are highly reproducible and associated with neural and behavioral features. [ABSTRACT FROM AUTHOR]

This study investigates the influence of microstructure patterns on the hydrophobic properties of surfaces of 3D-printed objects generated using photopolymer resin. Various arrangements and designs of microstructures on the surface of 3D-printed objects were examined. Leveraging the superior resolution of stereolithography printers (SLA) over fused deposition modeling, intricate microfeature designs were well-implemented. The experiments involved a range of structures on the surface of the 3D-printed objects, including precisely defined arrays of microcylinders, microchannels, and other complex designs generated by parametric equations. The hydrophobicity of the 3D-printed objects was assessed through the water droplet test, revealing a spectrum of results ranging from hydrophobic to weakly hydrophobic, and to hydrophilic surfaces. Light microscopy was employed to characterize the surface morphological properties of the 3D-printed objects, which were then correlated with the measured contact angles. It was discovered that the 3D-printed objects with microstructures formed using parametric functions exhibited patterns with irregularities and fluctuations along all directions or axes, resulting in a higher degree of hydrophobicity compared to structured matrices with pillared arrays. However, some surfaces created with parametric functions resulted in an anisotropic system where the material properties varied along one direction, while the other direction exhibited a flat, planar surface. These anisotropic systems were found to be less hydrophobic according to the water droplet test. [ABSTRACT FROM AUTHOR]

Key Points: Question: Why do genetic risk studies of mental disorders find consistent associations with CACNA1C? Findings: In this study, the dorsolateral prefrontal cortical pyramidal cells most affected in cognitive disorders express elevated calcium-related signaling, delineated by CALB1 (calcium-buffering protein calbindin), and high CACNA1C (L-type calcium channel [LTCC] Cav1.2), GRIN2B (NMDA receptor GluN2B), and KCNN3 (SK3 channel) expression. These neurons require LTCC actions to sustain memory-related firing, but excessive levels, such as during stress, reduce firing via SK channel opening and induce pathology, especially when calbindin is lost with age and/or inflammation. Meaning: These data explain why both loss- and gain-of function variants in CACNA1C are associated with an increase in risk of cognitive disorders. This study evaluates the role of CACNA1C variants in altered prefrontal neurons in cognitive disorders. Importance: The risk of mental disorders is consistently associated with variants in CACNA1C (L-type calcium channel Cav1.2) but it is not known why these channels are critical to cognition, and whether they affect the layer III pyramidal cells in the dorsolateral prefrontal cortex that are especially vulnerable in cognitive disorders. Objective: To examine the molecular mechanisms expressed in layer III pyramidal cells in primate dorsolateral prefrontal cortices. Design, Setting, and Participants: The design included transcriptomic analyses from human and macaque dorsolateral prefrontal cortex, and connectivity, protein expression, physiology, and cognitive behavior in macaques. The research was performed in academic laboratories at Yale, Harvard, Princeton, and the University of Pittsburgh. As dorsolateral prefrontal cortex only exists in primates, the work evaluated humans and macaques. Main Outcomes and Measures: Outcome measures included transcriptomic signatures of human and macaque pyramidal cells, protein expression and interactions in layer III macaque pyramidal cells using light and electron microscopy, changes in neuronal firing during spatial working memory, and working memory performance following pharmacological treatments. Results: Layer III pyramidal cells in dorsolateral prefrontal cortex coexpress a constellation of calcium-related proteins, delineated by CALB1 (calbindin), and high levels of CACNA1C (Cav1.2), GRIN2B (NMDA receptor GluN2B), and KCNN3 (SK3 potassium channel), concentrated in dendritic spines near the calcium-storing smooth endoplasmic reticulum. L-type calcium channels influenced neuronal firing needed for working memory, where either blockade or increased drive by β1-adrenoceptors, reduced neuronal firing by a mean (SD) 37.3% (5.5%) or 40% (6.3%), respectively, the latter via SK potassium channel opening. An L-type calcium channel blocker or β1-adrenoceptor antagonist protected working memory from stress. Conclusions and Relevance: The layer III pyramidal cells in the dorsolateral prefrontal cortex especially vulnerable in cognitive disorders differentially express calbindin and a constellation of calcium-related proteins including L-type calcium channels Cav1.2 (CACNA1C), GluN2B-NMDA receptors (GRIN2B), and SK3 potassium channels (KCNN3), which influence memory-related neuronal firing. The finding that either inadequate or excessive L-type calcium channel activation reduced neuronal firing explains why either loss- or gain-of-function variants in CACNA1C were associated with increased risk of cognitive disorders. The selective expression of calbindin in these pyramidal cells highlights the importance of regulatory mechanisms in neurons with high calcium signaling, consistent with Alzheimer tau pathology emerging when calbindin is lost with age and/or inflammation. [ABSTRACT FROM AUTHOR]

This study explores the potential of micro-credentialing and digital badges in developing and validating the knowledge, skills, and other attributes (KSaOs) required for diverse Remotely Piloted Aircraft Systems (RPAS) operations. The rapid proliferation of drone usage has outpaced the development of necessary KSaOs for safe and efficient drone operations. This research aims to bridge this gap by identifying the unique and specific KSaOs required for different types of drone operations and examining how micro-credentialing and digital badges can provide tangible evidence of these KSaOs. The study also investigates the potential benefits and challenges of implementing digital badges in the RPAS sector and how these challenges can be addressed. Furthermore, it explores how digital badges can contribute to the standardization and recognition of RPAS competencies across different national regulatory bodies. The methodology involves observational studies of publicly available videos of drone operations, with a focus on agriculture spraying operations. The findings highlight the importance of both generic and specific KSaOs in RPAS operations and suggest that digital badges may provide an effective means of evidencing mastery of these competencies. This research contributes to the ongoing discourse on drone regulation and competency development, offering practical insights for regulators, training providers, and drone operators. [ABSTRACT FROM AUTHOR]

The aim of the present study was to develop and examine the initial psychometrics of an instrument, the Charter School Teacher Development Inventory (CSTDI), designed to measure the professional development opportunities available in U.S. charter schools. Exploratory factor analysis suggested that the CSTDI was comprised of five factors: traditional, content, coherence, duration, and collaboration. Confirmatory factor analysis also supported a five-factor structure of the CSTDI. This study provides promising support for a five-factor instrument that assesses professional development practices in charter schools and further research is warranted to determine its relevance for use in traditional public schools. [ABSTRACT FROM AUTHOR]

Associations between datasets can be discovered through multivariate methods like Canonical Correlation Analysis (CCA) or Partial Least Squares (PLS). A requisite property for interpretability and generalizability of CCA/PLS associations is stability of their feature patterns. However, stability of CCA/PLS in high-dimensional datasets is questionable, as found in empirical characterizations. To study these issues systematically, we developed a generative modeling framework to simulate synthetic datasets. We found that when sample size is relatively small, but comparable to typical studies, CCA/PLS associations are highly unstable and inaccurate; both in their magnitude and importantly in the feature pattern underlying the association. We confirmed these trends across two neuroimaging modalities and in independent datasets with n ≈ 1000 and n = 20,000, and found that only the latter comprised sufficient observations for stable mappings between imaging-derived and behavioral features. We further developed a power calculator to provide sample sizes required for stability and reliability of multivariate analyses. Collectively, we characterize how to limit detrimental effects of overfitting on CCA/PLS stability, and provide recommendations for future studies. Multivariate associations discovered by CCA/PLS can be highly unstable and inaccurate with relatively small but typical sample sizes, inspiring the development of a sample size calculator for stable associations. [ABSTRACT FROM AUTHOR]

Motivation Cell fate is commonly studied by profiling the gene expression of single cells to infer developmental trajectories based on expression similarity, RNA velocity, or statistical mechanical properties. However, current approaches do not recover microenvironmental signals from the cellular niche that drive a differentiation trajectory. Results We resolve this with environment-aware trajectory inference (ENTRAIN), a computational method that integrates trajectory inference methods with ligand-receptor pair gene regulatory networks to identify extracellular signals and evaluate their relative contribution towards a differentiation trajectory. The output from ENTRAIN can be superimposed on spatial data to co-localize cells and molecules in space and time to map cell fate potentials to cell-cell interactions. We validate and benchmark our approach on single-cell bone marrow and spatially resolved embryonic neurogenesis datasets to identify known and novel environmental drivers of cellular differentiation. Availability and implementation ENTRAIN is available as a public package at https://github.com/theimagelab/entrain and can be used on both single-cell and spatially resolved datasets. [ABSTRACT FROM AUTHOR]

Some types of collagens, including transmembrane MACIT collagens and C. elegans cuticle collagens, are N-terminally cleaved at a dibasic site that resembles the consensus for furin or other proprotein convertases of the subtilisin/kexin (PCSK) family. Such cleavage may release transmembrane collagens from the plasma membrane and affect extracellular matrix assembly or structure. However, the functional consequences of such cleavage are unclear and evidence for the role of specific PCSKs is lacking. Here, we used endogenous collagen fusions to fluorescent proteins to visualize the secretion and assembly of the first collagen-based cuticle in C. elegans and then tested the role of the PCSK BLI-4 in these processes. Unexpectedly, we found that cuticle collagens SQT-3 and DPY-17 are secreted into the extraembryonic space several hours before cuticle matrix assembly. Furthermore, this early secretion depends on BLI-4/PCSK; in bli-4 and cleavage-site mutants, SQT-3 and DPY-17 are not efficiently secreted and instead form large intracellular puncta. Their later assembly into cuticle matrix is reduced but not entirely blocked. These data reveal a role for collagen N-terminal processing in intracellular trafficking and the control of matrix assembly in vivo. Our observations also prompt a revision of the classic model for C. elegans cuticle matrix assembly and the pre-cuticle-to-cuticle transition, suggesting that cuticle layer assembly proceeds via a series of regulated steps and not simply by sequential secretion and deposition. Author summary: Extracellular matrices coat cell surfaces to affect many aspects of animal biology. Collagens are among the most common constituents of such matrices and often form fibrillar- or mesh-like structures. It is important that these structures form only at the right time and place in the extracellular environment, and not prematurely during intracellular trafficking. Type I collagen matrix assembly typically occurs after proteolytic cleavage to remove both the N- and C-terminal ends of collagen molecules, and defects in this cleavage can cause a variety of human matrix disorders. Nevertheless, many questions remain about how N-terminal cleavage impacts collagen matrix assembly, particularly within other families of collagens that may be regulated differently than Type I collagen. The nematode Caenorhabditis elegans has an exoskeleton or cuticle that is composed of many collagens, and sequential secretion and membrane-proximal assembly of different collagens has been supposed to explain the eventual layered structure of the cuticle. Here we visualized tagged collagens during cuticle assembly and investigated the roles of N-terminal cleavage by characterizing mutants in the predicted collagen protease BLI-4 (a member of the furin/PCSK family) and also mutants in the predicted N-terminal cleavage sites within the tagged cuticle collagens. We observed that collagen secretion normally precedes cuticle matrix assembly by several hours, requiring a new way of thinking about cuticle layer formation. Furthermore, in both bli-4 mutants and N-terminal cleavage site mutants, collagens were not secreted efficiently and instead formed intracellular puncta. These data reveal an unexpected role for N-terminal cleavage in cuticle collagen secretion, which could be relevant to the cell biology of human matrix disorders. [ABSTRACT FROM AUTHOR]

Motility is essential for apicomplexan parasites to infect their hosts. In a three-dimensional (3D) environment, the apicomplexan parasite Toxoplasma gondii moves along a helical path. The cortical microtubules, which are ultra-stable and spirally arranged, have been considered to be a structure that guides the long-distance movement of the parasite. Here, we address the role of the cortical microtubules in parasite motility, invasion and egress by utilizing a previously generated mutant (dubbed 'TKO') in which these microtubules are destabilized in mature parasites. We found that the cortical microtubules in ~80% of the non-dividing (i.e. daughterfree) TKO parasites are much shorter than normal. The extent of depolymerization was further exacerbated upon commencement of daughter formation or cold treatment, but parasite replication was not affected. In a 3D Matrigel matrix, the TKO mutant moved directionally over long distances, but along trajectories that were significantly more linear (i.e. less helical) than those of wild-type parasites. Interestingly, this change in trajectory did not impact either movement speed in the matrix or the speed and behavior of the parasite during entry into and egress from the host cell. [ABSTRACT FROM AUTHOR]

Motility is essential for apicomplexan parasites to infect their hosts. In a three-dimensional (3D) environment, the apicomplexan parasite Toxoplasma gondii moves along a helical path. The cortical microtubules, which are ultra-stable and spirally arranged, have been considered to be a structure that guides the long-distance movement of the parasite. Here, we address the role of the cortical microtubules in parasite motility, invasion and egress by utilizing a previously generated mutant (dubbed ‘TKO’) in which these microtubules are destabilized in mature parasites. We found that the cortical microtubules in ∼80% of the non-dividing (i.e. daughterfree) TKO parasites are much shorter than normal. The extent of depolymerization was further exacerbated upon commencement of daughter formation or cold treatment, but parasite replication was not affected. In a 3D Matrigel matrix, the TKO mutant moved directionally over long distances, but along trajectories that were significantly more linear (i.e. less helical) than those of wild-type parasites. Interestingly, this change in trajectory did not impact either movement speed in the matrix or the speed and behavior of the parasite during entry into and egress from the host cell. [ABSTRACT FROM AUTHOR]

Accounts of technological change during industrialization processes based on labor-saving innovations are commonplace, even more so in the coal mining industry, in which the focus has until now been placed on the steam engine water pump and the coal cutting machine. However, to better understand technological change, we need to bear in mind the study of complementary capital. While previous research on complementary capital relies on evidence for manufacturing or the aggregate economy, this paper focuses on a case study, which provides more details on technology adoption decisions. This paper considers mechanical ventilation, a prominent and largely overlooked technology complementary to labor, as a response to stale air and explosions in the exploitation of coal. We examine the determinants in the adoption of the newer technology—the mechanical ventilator—through an economic model that is established at a high level of disaggregation: the mine. We concentrate on the West Virginia coalfield at the turn of the twentieth century, an apt historical setting for the study of technology adoption. We quantify characteristics of mines over time, so we are able to estimate a panel. We show the importance of various costs and benefits in explaining which type of mine converted from older technologies to the newer technology. The model is complemented with qualitative information, which helps to explain why an older technology slowed the process of adopting the newer as a result of different costs associated with the substitution. [ABSTRACT FROM AUTHOR]

Current research in 3D printing focuses on improving printing performance through various techniques, including decomposition, but targets only single printers. With improved hardware costs increasing printer availability, more situations can arise involving a multitude of printers, which offers substantially more throughput in combination that may not be best utilised by current decomposition approaches. A novel approach to 3D printing is introduced that attempts to exploit this as a means of significantly increasing the speed of printing models. This was approached as a problem akin to the parallel delegation of computation tasks in a multi-core environment, where optimal performance involves computation load being distributed as evenly as possible. To achieve this, a decomposition framework was designed that combines recursive symmetric slicing with a hybrid tree-based analytical and greedy strategy to optimally minimise the maximum volume of subparts assigned to the set of printers. Experimental evaluation of the algorithm was performed to compare our approach to printing models normally ("in serial") as a control. The algorithm was subjected to a range of models and a varying quantity of printers in parallel, with printer parameters held constant, and yielded mixed results. Larger, simpler, and more symmetric objects exhibited more significant and reliable improvements in fabrication duration at larger amounts of parallelisation than smaller, more complex, or more asymmetric objects. [ABSTRACT FROM AUTHOR]

Background: Hospitalizations are a vital opportunity for the initiation of life-saving opioid agonist therapy (OAT) for patients with opioid use disorder. A novel approach to OAT initiation is the use of IV buprenorphine for low dose induction, which allows patients to immediately start buprenorphine at any point in a hospitalization without stopping full agonist opioids or experiencing significant withdrawal. Methods: This is a retrospective case series of 33 patients with opioid use disorder concurrently treated with full agonist opioids for pain who voluntarily underwent low dose induction at a tertiary academic medical center. Low dose induction is the process of initiating very low doses of buprenorphine at fixed intervals with gradual dose increases in patients who recently received or are simultaneously treated with full opioid agonists. Our study reports one primary outcome: successful completion of the low dose induction (i.e. transitioned from low dose IV buprenorphine to sublingual buprenorphine-naloxone) and three secondary outcomes: discharge from the hospital with buprenorphine-naloxone prescription, self-reported pain scores, and nursing-assessed clinical opiate withdrawal scale (COWS) scores over a 6-day period, using descriptive statistics. COWS and pain scores were obtained from day 0 (prior to starting the low dose induction) to day 5 to assess the effect on withdrawal symptoms and pain control. Results: Thirty patients completed the low dose induction (30/33, 90.9%). Thirty patients (30/33, 90.9%) were discharged with a buprenorphine prescription. Pain and COWS scores remained stable over the course of the study period. Mean COWS scores for all patients were 2.6 (SD 2.8) on day 0 and 1.6 (SD 2.6) on day 5. Mean pain scores for all patients were 4.4 (SD 2.1) on day 0 and 3.5 on day 5 (SD 2.1). Conclusions: This study found that an IV buprenorphine low dose induction protocol was well-tolerated by a group of 33 hospitalized patients with opioid use disorder with co-occurring pain requiring full agonist opioid therapy. COWS and pain scores improved for the majority of patients. This is the first case series to report mean daily COWS and pain scores over an extended period throughout a low dose induction process. [ABSTRACT FROM AUTHOR]

Introduction: Neuroimaging technology has experienced explosive growth and transformed the study of neural mechanisms across health and disease. However, given the diversity of sophisticated tools for handling neuroimaging data, the field faces challenges inmethod integration, particularly acrossmultiplemodalities and species. Specifically, researchers often have to rely on siloed approaches which limit reproducibility, with idiosyncratic data organization and limited software interoperability. Methods: To address these challenges, we have developed Quantitative Neuroimaging Environment & Toolbox (QuNex), a platform for consistent end- to-end processing and analytics. QuNex provides several novel functionalities for neuroimaging analyses, including a "turnkey" command for the reproducible deployment of custom workflows, from onboarding raw data to generating analytic features. Results: The platform enables interoperable integration of multi-modal, community-developed neuroimaging software through an extension framework with a software development kit (SDK) for seamless integration of community tools. Critically, it supports high-throughput, parallel processing in high- performance compute environments, either locally or in the cloud. Notably, QuNex has successfully processed over 10,000 scans across neuroimaging consortia, including multiple clinical datasets. Moreover, QuNex enables integration of human and non-human workflows via a cohesive translational platform. Discussion: Collectively, this effort stands to significantly impact neuroimaging method integration across acquisition approaches, pipelines, datasets, computational environments, and species. Building on this platform will enable more rapid, scalable, and reproducible impact of neuroimaging technology across health and disease. [ABSTRACT FROM AUTHOR]

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The article tackles the conceptual ambiguity regarding the interpretation of the Export Clause of the U.S. Constitution. Topics discussed include constitutionality of an excise charge on oil exports used to remediate environmental damage from oil spills in the case Trafigura Trading LLC v. United States, history of the Export Clause and precedent cases, user fees in the Export Clause context, and economic and common law approaches to evaluate whether a charge passes the use test.

Drawing on the aesthetics literature, this study examines how typicality, novelty, unity and variety help to explain consumers' aesthetic pleasure and approach/avoidance behaviours. Comparisons are made between consumers' perceptions of actual store designs in a recently remodelled fashion store and that of an older, established store prototype owned by the same retailer. The research findings establish how novelty, typicality and variety confer aesthetic pleasure and approach behaviours in-store atmosphere appraisals contexts where there is a limited introduction of novelty, with one established prototype. The findings also suggest that moderation effects explain that consumers who place a greater value on the importance of design evaluate the novelty and aesthetic pleasure association differently compared to consumers with less design value orientation. [ABSTRACT FROM AUTHOR]

This study investigates the temporal and spatial distribution of the causal impacts of major beltway facilities on housing prices using quasi-experimental econometric approaches. Difference-in-differences methods are employed to quantify construction and anticipation effects and explore how impacts evolve and differ over space and time. The study particularly focuses on spatial variations and seeks to identify potentially heterogeneous effects in the inner and outer sides of a beltway. Two methods for control group selection are adopted to test the robustness of the estimated treatment effects. Using data from three major beltway facilities in the US, we find that impacts are nonlinear with distance from an interchange, with the maximum effect found between a 0.75 and 1.5-mile distance. In two of the studied beltway projects, properties outside the beltway experienced significant positive effects, while effects on properties inside the beltway were negative within the first 0.25 miles from an interchange and insignificant thereafter. We also find that effects during construction differ by project, while after the end of construction, prices typically increase and fully materialize after 6–8 years. This research makes a significant contribution to the very limited literature on the causal identification of highway impacts on surrounding properties as well as the small group of studies that have investigated the spatial extent and distribution of transportation-induced effects. The results can be used to inform stakeholders and planning decisions of future highway facilities. [ABSTRACT FROM AUTHOR]

The importance of lung cancer as a complication of lung transplantation is increasingly recognised. It may become an important survival-limiting factor in lung transplant patients as management of other complications continues to improve and utilisation of extended criteria donors grows. Radiology can play a key role in tackling this issue at multiple stages in the transplantation pathway and follow-up process. Routine chest CT as part of pre-transplant recipient assessment (and donor assessment if available) can identify suspicious lung lesions with high sensitivity and detect chronic structural lung diseases such as pulmonary fibrosis associated with an increased risk of malignancy post-transplant. Pre-transplant CT also provides a comparison for later CT studies in the assessment of nodules or masses. The potential role of regular chest CT for lung cancer screening after transplantation is less certain due to limited available evidence on its efficacy. Radiologists should be cognisant of how the causes of pulmonary nodules in lung transplant patients may differ from the general population, vary with time since transplantation and require specific recommendations for further investigation/follow-up as general guidelines are not applicable. As part of the multidisciplinary team, radiology is involved in an aggressive diagnostic and therapeutic management approach for nodular lung lesions after transplant both through follow-up imaging and image-guided tissue sampling. This review provides a comprehensive overview of available clinical data and evidence on lung cancer in lung transplant recipients, and in particular an assessment of the current and potential roles of pre- and post-transplant imaging. Key Points: • Lung cancer after lung transplantation may become an increasingly important survival-limiting factor as mortality from other complications declines. • There are a number of important roles for radiology in tackling the issue which include pre-transplant CT and supporting an aggressive multidisciplinary management strategy where lung nodules are detected in transplant patients. • The introduction of routine surveillance chest CT after transplant in addition to standard clinical follow-up as a means of lung cancer screening should be considered. [ABSTRACT FROM AUTHOR]

The Jarrow assemblage is a Lagerstätte of Pennsylvanian tetrapods and fish preserved in the Leinster Coalfield, Ireland. Fossils from this site have an interesting taphonomy that is not observed in other Pennsylvanian coal swamp assemblages. Jarrow tetrapod bone material has undergone alteration and eventual coalification, causing specimens to become poorly defined from the surrounding coal matrix. Bone alteration at Jarrow has traditionally been linked to early diagenesis. A multi‐analytical approach, combining x‐ray scanning electron microscopy, cathodoluminescence, micro computed tomography and laser ablation quadrupole inductively coupled plasma mass spectrometry, was used to investigate the origin of alteration within the Jarrow fossil specimens. Original bone morphology is no longer present, being replaced by bituminous material and sphalerite surrounded by tabular apatite (a morphology atypical of bone apatite). Direct U–Pb dating of this recrystallized apatite provides an age of 302.03 ± 11.38 Ma. In this recrystallized apatite, core‐to‐rim variation in halogen elements, variably positive and negative Eu‐anomalies and depletion in light rare earth elements (REEs) suggest an influence of hydrothermal fluids sourced during the maturation of the Leinster Coalfield. A new taphonomic model for the Jarrow assemblage is proposed: alteration of primary fossil bone occurred primarily due to burial heating of the Leinster Coalfield caused by Variscan deformation. Bone apatite was dissolved and subsequently recrystalized as tabular crystals, probably concurrent with mineralization of sphalerite and during coalification, giving the Jarrow assemblage fossils their unique appearance. [ABSTRACT FROM AUTHOR]

In 2020, the US Department of Veterans Affairs Connecticut Healthcare System began its journey to becoming a high-reliability organization as part of Veterans Affairs efforts to become an enterprise-wide high-reliability organization through the Veterans Health Administration. The initiative was launched to create safe enterprise-wide health care systems and environments with robust continuous process improvements as a method for providing patients with safer and higher quality care. In this article, the authors describe a continuous process improvement initiative aimed at implementing system-wide initiatives along the journey to becoming a high-reliability organization. The initiatives are described from the perspectives of individuals representing staff from the frontline to executive leadership. The authors believe that the processes, strategies, and example initiatives described can be readily adopted and implemented in other health care organizations along the journey to high reliability. [ABSTRACT FROM AUTHOR]

In noisy but stationary environments, decisions should be based on the temporal integration of sequentially sampled evidence. This strategy has been supported by many behavioral studies and is qualitatively consistent with neural activity in multiple brain areas. By contrast, decision-making in the face of non-stationary sensory evidence remains poorly understood. Here, we trained monkeys to identify and respond via saccade to the dominant color of a dynamically refreshed bicolor patch that becomes informative after a variable delay. Animals' behavioral responses were briefly suppressed after evidence changes, and many neurons in the frontal eye field displayed a corresponding dip in activity at this time, similar to that frequently observed after stimulus onset but sensitive to stimulus strength. Generalized drift-diffusion models revealed consistency of behavior and neural activity with brief suppression of motor output, but not with pausing or resetting of evidence accumulation. These results suggest that momentary arrest of motor preparation is important for dynamic perceptual decision making. While evidence is constantly changing during real-world decisions, little is known about how the brain deals with such changes. Here, the authors show that the brain strategically suppresses motor output via the frontal eye fields in response to stimulus changes. [ABSTRACT FROM AUTHOR]

The hippocampus is associated with essential brain functions, such as learning and memory. Human hippocampal volume is significantly greater than expected compared with that of non-human apes, suggesting a recent expansion. Intermediate progenitors, which are able to undergo multiple rounds of proliferative division before a final neurogenic division, may have played a role in evolutionary hippocampal expansion. To investigate the evolution of gene regulatory networks underpinning hippocampal neurogenesis in apes, we leveraged the differentiation of human and chimpanzee induced pluripotent stem cells into TBR2 (or EOMES)-positive hippocampal intermediate progenitor cells (hpIPCs). We found that the gene networks active in hpIPCs are significantly different between humans and chimpanzees, with ~2500 genes being differentially expressed. We demonstrate that species-specific transposonderived enhancers contribute to these transcriptomic differences. Young transposons, predominantly endogenous retroviruses and SINE-Vntr-Alus (SVAs), were co-opted as enhancers in a speciesspecific manner. Human-specific SVAs provided substrates for thousands of novel TBR2-binding sites, and CRISPR-mediated repression of these SVAs attenuated the expression of ~25% of the genes that are upregulated in human intermediate progenitors relative to the same cell population in the chimpanzee. [ABSTRACT FROM AUTHOR]

The continuous emergence of SARS-CoV-2 variants favors potential co-infections and/or viral mutation events, leading to possible new biological properties. The aim of this work was to characterize SARS-CoV-2 genetic variability during the Delta–Omicron shift in patients and in a neighboring wastewater treatment plant (WWTP) in the same urban area. The surveillance of SARS-CoV-2 was performed by routine screening of positive samples by single nucleotide polymorphism analysis within the S gene. Moreover, additionally to national systematic whole genome sequencing (WGS) once a week in SARS-CoV-2-positive patients, WGS was also applied when mutational profiles were difficult to interpret by routine screening. Thus, WGS was performed on 414 respiratory samples and on four wastewater samples, northeastern France. This allowed us to report (i) the temporally concordant Delta to Omicron viral shift in patients and wastewaters; (ii) the characterization of 21J (Delta) and 21K (Omicron)/BA.1-21L (Omicron)/BA.2-BA.4 mixtures from humans or environmental samples; (iii) the mapping of composite mutations and the predicted impact on immune properties in the viral Spike protein. [ABSTRACT FROM AUTHOR]

The phylum Apicomplexa includes thousands of species of unicellular parasites that cause a wide range of human and animal diseases such as malaria and toxoplasmosis. To infect, the parasite must first initiate active movement to disseminate through tissue and invade into a host cell, and then cease moving once inside. The parasite moves by gliding on a surface, propelled by an internal cortical actomyosin-based motility apparatus. One of the most effective invaders in Apicomplexa is Toxoplasma gondii, which can infect any nucleated cell and any warm-blooded animal. During invasion, the parasite first makes contact with the host cell "head-on" with the apical complex, which features an elaborate cytoskeletal apparatus and associated structures. Here we report the identification and characterization of a new component of the apical complex, Preconoidal region protein 2 (Pcr2). Pcr2 knockout parasites replicate normally, but they are severely diminished in their capacity for host tissue destruction due to significantly impaired invasion and egress, two vital steps in the lytic cycle. When stimulated for calcium-induced egress, Pcr2 knockout parasites become active, and secrete effectors to lyse the host cell. Calcium-induced secretion of the major adhesin, MIC2, also appears to be normal. However, the movement of the Pcr2 knockout parasite is spasmodic, which drastically compromises egress. In addition to faulty motility, the ability of the Pcr2 knockout parasite to assemble the moving junction is impaired. Both defects likely contribute to the poor efficiency of invasion. Interestingly, actomyosin activity, as indicated by the motion of mEmerald tagged actin chromobody, appears to be largely unperturbed by the loss of Pcr2, raising the possibility that Pcr2 may act downstream of or in parallel with the actomyosin machinery. Author summary: The thousands of species of apicomplexan parasites are responsible for many devastating human and animal diseases, including malaria and toxoplasmosis. Cell movement, needed to disseminate among tissues and invade into a host cell, is essential for the apicomplexan parasites to maintain their intracellular parasitic life style. Here we investigate the movement of a very successful apicomplexan, Toxoplasma gondii. We discovered that Preconoidal region protein 2 (Pcr2), a new component of the parasite apical complex, is important for the persistence of Toxoplasma movement. The movement of the Pcr2 knockout parasite is spasmodic, which compromises egress and invasion, two vital steps in the parasite's lytic cycle. As a result, Pcr2 knockout parasites cause much less host tissue destruction. Furthermore, the ability of the Pcr2 knockout parasite to assemble a ring-like structure (the moving junction) at the entry point of invasion, is impaired. The discovery of Pcr2 and the analysis of its function open new opportunities to determine how mechanical interactions with its environment impact parasite motility, and how the regulation or maintenance of persistence in parasite movement is functionally connected with and imposed onto the motility apparatus and other structures involved in invasion and egress. [ABSTRACT FROM AUTHOR]

Objectives: Patients with anterior cruciate ligament (ACL) injury are at high risk for the development of post-traumatic osteoarthritis (PTOA), despite ACL reconstruction (ACLR). ACL injuries are frequently associated with damage of other structures within the knee, such as the meniscus. The meniscus is an important structure that provides protection for articular cartilage and stabilization of the joint. Long-term studies of PTOA after ACLR mainly used radiographs. Conventional magnetic resonance imaging (MRI) has been used in a limited number of studies to evaluate structural damages, but this only provides information on morphologic changes that occur at relatively late stages of the disease. In this study, we aim to use quantitative MRI (qMRI) to evaluate cartilage and meniscus degeneration in patients at 10 years after ACLR. Methods: This is a multi-site multi-vendor study that involves three sites and two MR platforms (Siemens 3T and Philips 3T). MRI protocols have been harmonized between sites and cross validation data were collected using phantoms. The patients are from a nested cohort within Multicenter Orthopaedic Outcomes Network (MOON) Onsite Cohort at 10 years after ACLR. Inclusion/Exclusion criteria were: 22-50 years old; ACL tear during a sport; no previous knee injury; no graft rupture during follow-up. In this preliminary report, 51 patients (age 32.8 ± 6.4 years; 25 females; body mass index [BMI] 25.7 ± 5.7 kg/m2; 40 hamstring autograft, 9 bone-patellar tendon-bone autograft, and 2 allograft) and 17 healthy control participants (age 30.8 ± 7.8 years; 10 females; BMI 23.8 ± 5.6 kg/m2) were studied. The MRI protocol included high-resolution Dual-Echo Steady State (DESS), and combined gradient echo MAPSS T1ρ and T2 mapping. Cartilage and meniscus were automatically segmented on DESS images using an in-house developed deep-learning model into medial/lateral femoral condyle (MFC/LFC), medial/lateral tibia (MT/LT), trochlear (TRO), and patellar cartilage (PAT), and medial and lateral menisci (MM/LM). Each cartilage compartment was further divided into sub-regions based on a modified MRI Osteoarthritis Knee Score (MOAKS) definition: central and posterior for MFC/LMC (cMFC/cLMC, pMFC/pLMC); anterior, central, and posterior for MT/LT (aMT/aLT, cMT/cLT, pMT/pLT); medial, central, and lateral for PAT/TRO (mPAT/mTRO, cPAT/cTRO, lPAT/lTRO). Menisci were further divided into anterior horn (aMM, aLM), central (body) (cMM, cLM), and posterior horn (pMM, pLM) subregions. These cartilage and menisci subregions were then transformed and overlaid onto the T1ρ and T2 parameter maps after co-registering the DESS image to the first echo of the 3D MAPSS sequence using the Elastix toolbox. T1ρ and T2 parameter maps were obtained by a voxel-wise two-parameter monoexponential fitting. The mean and standard deviation for each subregion was recorded and compared between three knee groups: operated and contralateral knees from patients, and control knees from healthy controls, using a mixed-effects regression model, adjusted for age, sex, and BMI. Results: For cartilage, compared to contralateral knees, operated knees in patients had significantly higher T1ρ and T2 values in MFC, MT, and TRO compartments. Looking into subcompartments, for MFC, MT, and TRO, most of the subcompartments (cMFC, pMFC; cMT, pMT; mTRO, cTRO) showed significantly higher T1ρ and T2 values compared to contralateral knees. For LFC and LT, only the posterior subcompartments showed significantly higher T1ρ and T2 values compared to contralateral knees. For PAT, no significant differences were observed between operated and contralateral knees. Compared to healthy control knees, operated knees in patients had significantly higher T1ρ and T2 values in all the six compartments. Besides, contralateral knees also showed higher T1ρ and T2 values in LFC, LT and PAT compartments compared to healthy control knees (Figure 1 for T1ρ, T2 with similar trend was not shown). For meniscus, no significant differences in T1ρ and T2 values were observed between injured and contralateral knees. Compared to healthy control knees, both operated and contralateral knees in patients had significantly higher T1ρ values in LM and significantly higher T2 values in MM (Figure 2). Conclusions: Cartilage T1ρ and T2 values were higher in operated knees compared to contralateral knees at 10 years after ACLR, except for patellar compartment. In patellar cartilage, no significant differences were observed between sides in patients, but both sides were significantly higher than control knees. Our data showed that contralateral knees after ACLR may not represent 'healthy controls' as there might be compensatory changes and early degeneration in contralateral knees as a result of injury and surgery to their other knee. Although we observed this general trend of higher cartilage T1ρ and T2 values in the operated knees compared to contralateral knees, no significant differences were observed in meniscus T1ρ and T2 values between sides in patients, suggesting the timing of cartilage and meniscus degeneration may be different for patients after ACLR. Meniscus T1ρ and T2 values in both sides are higher than control knees, suggesting early degeneration in meniscus in patients in both sides. The results will be confirmed with more patient data being collected in the ongoing study. The relationship between qMRI, morphological tissue changes, and patient-reported outcomes after ACLR will also be evaluated in future work. Figure 1. T1p comparisons of cartilage among operated, contralateral, and healthy control knees. *P < 0.05, **P < 0.01. ***P < 0.001. Figure 2. T1p and T2 comparisons of menisci among operated, contralateral, and healthy control knees. *P < 0.05. **P < 0.01. ***P < 0.001. [ABSTRACT FROM AUTHOR]