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Lower urinary tract infection (UTI) is common but only rarely complicated by pyelonephritis. However, the mechanisms preventing extension to the kidney are unclear. Here, we identified neutrophil extracellular traps (NETs) in healthy human urine that provide an antibacterial defense strategy within the urinary tract. In both in vivo murine models of UTI where uropathogenic E. coli are inoculated into the bladder and ex vivo human urine models, NETs interacted with uromodulin to form large webs that entrapped the bacteria. Peptidyl arginine deiminase 4 (PADI4) inhibition in mice blocked NETosis and resulted in progression of cystitis into pyelonephritis, suggesting that NETosis of urinary neutrophils acts to prevent bacterial ascent into the kidney. Analysis of UK Biobank data revealed that genetic variants in PADI4 that associated with increased risk of rheumatoid arthritis in multiple genome-wide association studies were consistently associated with reduced susceptibility to UTI. Last, we showed that urine dipstick testing for leukocyte esterase was negative in the presence of intact blood neutrophils but became positive when neutrophils were stimulated to NET, and this could be prevented by selective PADI4 inhibition, demonstrating that this test does not detect absolute neutrophil count, as has long been assumed, but specifically detects neutrophils that have undergone NETosis. These findings highlight the role of NETosis in preventing ascending infections in the urinary tract and improve our understanding of one of the most common clinical tests in medicine. Editor's summary: Lower urinary tract infections (UTIs) rarely ascend to the kidney, but the mechanisms underlying this protection are not fully understood. Here, Stewart and colleagues identified neutrophil extracellular traps (NETs) in the urine of healthy individuals that interacted with uromodulin to form webs and entrap bacteria. Inhibition of peptidyl arginine deiminase type 4 (PADI4) reduced NETosis and increased pyelonephritis in mice challenged with uropathogenic E. coli, and an analysis of UK Biobank data revealed that variants in PADI4 were associated with reduced incidence of UTI. The authors also showed that the leukocyte esterase urine dipstick test specifically detects the presence of NETosing neutrophils, highlighting the importance of NETs in both the prevention and diagnosis of UTI. —Melissa L. Norton [ABSTRACT FROM AUTHOR]

The ability to characterize immune cells and explore the molecular interactions that govern their functions has never been greater, fueled in recent years by the revolutionary advance of single‐cell analysis platforms. However, precisely how immune cells respond to different stimuli and where differentiation processes and effector functions operate remain incompletely understood. Inferring cellular fate within single‐cell transcriptomic analyses is now omnipresent, despite the assumptions typically required in such analyses. Recently developed experimental models support dynamic analyses of the immune response, providing insights into the temporal changes that occur within cells and the tissues in which such transitions occur. Here we will review these approaches and discuss how these can be combined with single‐cell technologies to develop a deeper understanding of the immune responses that should support the development of better therapeutic options for patients. [ABSTRACT FROM AUTHOR]

A collectivist approach to public health during a crisis., In response to a spike in COVID-19 cases, Governor Asa Hutchinson announced on 19 July 2020 that the state of Arkansas would implement a new mask mandate. (1) The following [...]

The last two decades have witnessed an increasing intensity of quality management in higher education institutions and quality discourses which were followed by debates about and attempts of evaluating the efficacy of quality management in the sector. Accordingly, the article presents a SWOT analysis of impact evaluation of quality management in higher education institutions. The analysis is based on a contemporary SWOT conceptualisation and on reflections of impact evaluation, ranging from theoretical models through case studies to practical experience in a European research project. The analysis reveals that certain weaknesses can be overcome (e.g. budget and process time restrictions) while others cannot (e.g. systematic limitations of methodologies). Similarly, certain threats can be tackled (e.g. proper implementation of methodologies) while others at most can only approximately be solved (e.g. attribution problem). The article concludes that a SWOT analysis may be a tool for bridging the gap between methodological challenges and the implementation of impact measurement in systematic quality management.

We describe a new Fortran computer program to solve the system of equations for the NH 4+ –Na + –Ca 2+ –K + –Mg 2+ –SO 42- –NO 3- –Cl - –H 2 O system, based on the algorithms of ISORROPIA II. Specifically, the code solves the system of equations describing the "forward" (gas + aerosol input) metastable state but with algorithm improvements and corrections. These algorithm changes allow the code to deliver more accurate solution results in formal evaluations of accuracy of the roots of the systems of equations, while reducing processing time in practical applications by about 50 %. The improved solution performance results from several implementation improvements relative to the original ISORROPIA algorithms. These improvements include (i) the use of the "interpolate, truncate and project" (ITP) root-finding approach rather than bisection, (ii) the allowance of search interval endpoints as valid roots at the onset of a search, (iii) the use of a more accurate method to solve polynomial subsystems of equations, (iv) the elimination of negative concentrations during iterative solutions, (v) corrections for mass conservation enforcement, and (vi) several code structure improvements. The new code may be run in either a "vectorization" mode wherein a global convergence criterion is used across multiple tests within the same chemical subspace or a "by case-by-case" mode wherein individual test cases are solved with the same convergence criteria. The latter approach was found to be more efficient on the compiler tested here, but users of the code are recommended to test both options on their own systems. The new code has been constructed to explicitly conserve the input mass for all species considered in the solver and is provided as open-source Fortran shareware. [ABSTRACT FROM AUTHOR]

Tumour dendritic cells (DCs) internalise antigen and upregulate CCR7, which directs their migration to tumour-draining lymph nodes (dLN). CCR7 expression is coupled to an activation programme enriched in regulatory molecule expression, including PD-L1. However, the spatio-temporal dynamics of CCR7+ DCs in anti-tumour immune responses remain unclear. Here, we use photoconvertible mice to precisely track DC migration. We report that CCR7+ DCs are the dominant DC population that migrate to the dLN, but a subset remains tumour-resident despite CCR7 expression. These tumour-retained CCR7+ DCs are phenotypically and transcriptionally distinct from their dLN counterparts and heterogeneous. Moreover, they progressively downregulate the expression of antigen presentation and pro-inflammatory transcripts with more prolonged tumour dwell-time. Tumour-residing CCR7+ DCs co-localise with PD-1+CD8+ T cells in human and murine solid tumours, and following anti-PD-L1 treatment, upregulate stimulatory molecules including OX40L, thereby augmenting anti-tumour cytolytic activity. Altogether, these data uncover previously unappreciated heterogeneity in CCR7+ DCs that may underpin a variable capacity to support intratumoural cytotoxic T cells. Recognition of tumour antigen induces dendritic cell activation and migration to the lymph node. Here, the authors use photoconvertible mice to demonstrate that some activated dendritic cells are retained in tumours and gradually lose function, but their ability to support local anti-tumour responses can be augmented by anti-PD-L1 blockade. [ABSTRACT FROM AUTHOR]

Below-cloud scavenging (BCS) is the process of aerosol removal from the atmosphere between cloud base and the ground by precipitation (e.g., rain or snow), and affects aerosol number or mass concentrations, size distribution, and lifetime. An accurate representation of precipitation phases is important in treating BCS as the efficiency of aerosol scavenging differs significantly between liquid and solid precipitation. The impact of different representations of BCS on existing model biases was examined through implementing a new aerosol BCS scheme in the Environment and Climate Change Canada (ECCC) air quality prediction model GEM-MACH and comparing it with the existing scavenging scheme in the model. Further, the current GEM-MACH employs a single-phase precipitation for BCS: total precipitation is treated as either liquid or solid depending on a fixed environment temperature threshold. Here, we consider co-existing liquid and solid precipitation phases as they are predicted by the GEM microphysics. GEM-MACH simulations, in a local-area domain over the Athabasca oil sands areas, Canada, are compared with observed precipitation samples, with a focus on the particulate base cation NH 4+ ; acidic anions NO 3- , SO 4= , HSO 3- in precipitation; and observed ambient particulate sulfate, ammonium, and nitrate concentrations. Overall, the introduction of the multi-phase approach and the new scavenging scheme enhances GEM-MACH performance compared to previous methods. Including a multi-phase approach leads to altered SO 4= scavenging and impacts the BCS of SO 2 into the aqueous phase over the domain. Sulfate biases improved from +46% to -5% relative to Alberta Precipitation Quality Monitoring Program wet sulfate observations. At Canadian Air and Precipitation Monitoring Network stations the biases became more negative, from -10% to -30% for the tests carried out here. These improvements contrast with prior annual average biases of +200% for SO 4= , indicating enhanced model performance. Improvements in model performance (via scores for correlation coefficient, normalized mean bias, and/or fractional number of model values within a factor of 2 of observations) could also be seen between the base case and the two simulations based on multi-phase partitioning for NO 3- , NH 4+ , and SO 4=. Whether or not these improvements corresponded to increases or decreases in NO 3- and NH 4+ wet deposition varied over the simulation region. The changes were episodic in nature – the most significant changes in wet deposition were likely at specific geographic locations and represent specific cloud precipitation events. The changes in wet scavenging resulted in a higher formation rate and larger concentrations of atmospheric particle sulfate. [ABSTRACT FROM AUTHOR]

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Spatiotemporal clustering of data is an important analytical technique with many applications in air quality, including source identification, monitoring network analysis and airshed partitioning. Hierarchical agglomerative clustering is one such algorithm, where sets of input data are grouped by a chosen similarity metric, without requiring any a priori information about the final arrangement of clusters. Modern implementations of the algorithm have O(n² 10 log (n)) computational complexity and O;(n²) memory usage, where n is the number of initial clusters. This dependence can strain the resources of even very large individual computers as the number of initial clusters increases into the tens or hundreds of thousands, for example, to cluster all the points in an air-quality model’s simulation grid as part of airshed analysis (~105 to 106 time series to be clustered). Using two parallelization techniques – the Message Passing Interface (MPI) and Open Multi-Processing (OpenMP) – we have reduced the amount of wallclock time while increasing the memory available to a new hierarchical clustering program, by dividing up the program into blocks which are run on separate CPUs but communicate with each other to produce a single result. The new algorithm opens up new directions for large data analysis which had previously not been possible. Here we present a massively parallelized version of an agglomerative hierarchical clustering algorithm which is able to cluster an entire year of hourly regional air-quality model output (538x540 domain; 290,520 hourly concentration timeseries) in 12 hours 37 minutes of wallclock time, by spreading the computation across 8000 Intel® Xeon® Platinum 8830 CPU cores with a total of 2TB of RAM. We then show how the new algorithm allows a new form of air-quality analysis to be carried out starting from air-quality model output. We present maps of the different airsheds within the model domain, identifying equally unique regions for each chemical species. These regions can be used as an aid in determining the placement of surface air-quality monitors which gives the most representative sampling given a fixed number of monitors, or the number of monitors required for a given level of similarity between airsheds. We then demonstrate the new algorithm’s application towards source apportionment of very large observation data sets, through the analysis of a year of Canada’s hourly National Air Pollution Surveillance Program data, comprising 366,427 original observation vectors, a problem size that would be impossible with other source apportionment programs such as Positive Matrix Factorization. [ABSTRACT FROM AUTHOR]

Nervous systems of vertebrates and invertebrates show a common modular theme in the flow of information for cost-benefit decisions. Sensory inputs are incentivized by integrating stimulus qualities with motivation and memory to affect appetitive state, a system of homeostatic drives, and labelled for directionality. Appetitive state determines action responses from a repertory of possibles and transmits the decision to a premotor system that frames the selected action in motor arousal and appropriate postural and locomotion commands. These commands are then sent to the primary motor pattern generators controlling the motorneurons, with feedback at each stage. In the vertebrates, these stages are mediated by forebrain pallial derivatives for incentive and directionality (olfactory bulb, cerebral cortex, pallial amygdala, etc.) interacting with hypothalamus (homeostasis, motivation, and reward) for action selection in the forebrain basal ganglia, the mid/hindbrain reticular formation as a premotor translator for posture, locomotion, and arousal state, and the spinal cord and cranial nuclei as primary motor pattern generators. Gastropods, like the predatory sea slug Pleurobranchaea californica, show a similar organization but with differences that suggest how complex brains evolved from an ancestral softbodied bilaterian along with segmentation, jointed skeletons, and complex exteroceptors. Their premotor feeding network combines functions of hypothalamus and basal ganglia for homeostasis, motivation, presumed reward, and action selection for stimulus approach or avoidance. In Pleurobranchaea, the premotor analogy to the vertebrate reticular formation is the bilateral "A-cluster" of cerebral ganglion neurons that controls posture, locomotion, and serotonergic motor arousal. The A-cluster transmits motor commands to the pedal ganglia analogs of the spinal cord, for primary patterned motor output. Apparent pallial precursors are not immediately evident in Pleurobranchaea's central nervous system, but a notable candidate is a subepithelial nerve net in the peripheral head region that integrates chemotactile stimuli for incentive and directionality. Evolutionary centralization of its computational functions may have led to the olfaction-derived pallial forebrain in the ancestor's vertebrate descendants and their analogs in arthropods and annelids. [ABSTRACT FROM AUTHOR]

We describe a new FORTRAN 90 computer program to solve the system of equations for the NH4+-Na+-Ca2+-K+-Mg2+- SO42--NO3--Cl- system, based on the algorithms of ISORROPIA II, but containing algorithm improvements and corrections. These allow the code to deliver more accurate solution results in formal evaluations of accuracy of the roots of the systems of equations, while reducing processing time in practical applications by about 50%. The improved solution performance results from several implementation improvements relative to the original ISORROPIA algorithms. These improvements include (the use of the 'interpolate, truncate and project' (ITP) root-finding approach rather than bisection, (ii) the allowance of search interval endpoints as valid roots at the onset of a search, (iii) the use of a more accurate method to solve polynomial subsystems of equations, (iv) the elimination of negative concentrations during iterative solutions, (v) corrections for mass conservation enforcement, and (vi) several code structure improvements. The new code may be run in either a "vectorization" mode wherein a global convergence criterion is used across multiple tests within the same chemical subspace, or a "by gridpoint" mode wherein individual test cases are solved with the same convergence criteria. The latter approach was found to be more efficient on the compiler tested here, but users of the code are recommended to test both options on their own systems. We also note that implementation of inorganic chemistry within chemical transport models should take care to retain residual or "free" mass of aerosol species remaining after partitioning, to ensure mass conservation - the new code has been constructed to explicitly conserve the input mass. The new code is provided as open-source FORTRAN 90 shareware. [ABSTRACT FROM AUTHOR]

Background: Thirty-five laboratory-confirmed legionellosis cases were reported to the Simcoe Muskoka District Health Unit (Ontario, Canada) between September 27, 2022, and October 15, 2022, resulting in one death and 29 hospitalizations. This article describes the Legionella outbreak and highlights activities for managing the outbreak, including various environmental and infrastructural controls associated with the public health response and some of the unique challenges and potential solutions to mitigate future outbreaks. Methods: All cases of legionellosis were reported to and investigated by the local provincial health unit. Within a 6 km radius around the community, 27 cooling towers (CTs) were identified as potential sources of Legionella. Environmental samples were collected from 19 CTs and a long-term care home. Outcome: Of the 35 cases, 29 (83%) were hospitalized (including three long-term care residents) with two requiring intubation/ventilation. Of the five sputa (clinical isolates) collected from confirmed cases, four tested positive for Legionella pneumophila (one was positive for L. pneumophila serogroup 1—with the same sequence type as one of the CT isolates). Education and recommendations were provided by the local provincial health unit to operators to improve CT operation. Conclusion: Detection and management of community legionellosis outbreaks associated with CTs involve resources and time to properly identify and control risks. Measures for community risk mitigation included coordinating with provincial and community partners, developing methods to rapidly identify CTs as a likely source of infection and applying operational/ maintenance/testing standards for CTs to control bacterial growth and minimize the dispersion of contaminated aerosols. [ABSTRACT FROM AUTHOR]

Similar design characterizes neuronal networks for goal-directed motor control across the complex, segmented vertebrates, insects, and polychaete annelids with jointed appendages. Evidence is lacking for whether this design evolved independently in those lineages, evolved in parallel with segmentation and appendages, or could have been present in a soft-bodied common ancestor. We examined coordination of locomotion in an unsegmented, ciliolocomoting gastropod, the sea slug Pleurobranchaea californica, which may better resemble the urbilaterian ancestor. Previously, bilateral A-cluster neurons in cerebral ganglion lobes were found to compose a multifunctional premotor network controlling the escape swim and feeding suppression, and mediating action selection for approach or avoidance turns. Serotonergic As interneurons of this cluster were critical elements for swimming, turning, and behavioral arousal. Here, known functions were extended to show that the As2/3 cells of the As group drove crawling locomotion via descending signals to pedal ganglia effector networks for ciliolocomotion and were inhibited during fictive feeding and withdrawal. Crawling was suppressed in aversive turns, defensive withdrawal, and active feeding, but not during stimulus-approach turns or prebite proboscis extension. Ciliary beating was not inhibited during escape swimming. These results show how locomotion is adaptively coordinated in tracking, handling, and consuming resources, and in defense. Taken with previous results, they also show that the A-cluster network acts similarly to the vertebrate reticular formation with its serotonergic raphe nuclei in facilitating locomotion, postural movements, and motor arousal. Thus, the general scheme controlling locomotion and posture might well have preceded the evolution of segmented bodies and articulated appendages. [ABSTRACT FROM AUTHOR]

Context: In contrast to marine environments, microplastic pollution in freshwater systems is understudied. Previous research suggests that freshwater macrophytes function as microplastic sinks, which, because they are at the base of food webs, has implications for higher trophic levels. Aim: This study compares the ability of freshwater plants with different leaf morphologies to trap downwelling microplastics. Method: Microplastics (800–1000 μm polyamide grains) were deposited onto three macrophyte species, namely, Cabomba caroliniana , Egeria densa , and Hygrophila polysperma. Microplastic mass retained was calculated as the percentage of microplastic mass captured by the plant and standardised microplastic retention was calculated as the absolute microplastic mass retained (g) divided by plant dry mass (g). Results: The amount of trapped microplastics differed significantly among species, with the highest amount trapped by C. caroliniana (39.3%; 7.91 g g−1), followed by E. densa (28.8%; 5.30 g g−1) and H. polysperma (17.6%; 4.47 g g−1). Conclusion: Significant differences in microplastic retention among species may be attributed to variation in leaf morphology. Implications: These findings have potential applications in bioremediation and biomonitoring, where freshwater macrophytes could help with the tracking and mitigation of microplastics in the environment. Freshwater plants can accumulate microplastics, which, as they form the base of food webs, has implications for higher trophic levels. This study compares the ability of freshwater plants with different leaf shapes to trap downwelling microplastics. Results suggest that leaf shape complexity is associated with microplastic entrapment―findings that have potential applications in bioremediation and biomonitoring of plastic pollution. [ABSTRACT FROM AUTHOR]