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Characterizing interface trap states in commercial wide bandgap devices using frequency-based measurements requires unconventionally high probing frequencies to account for both fast and slow traps associated with wide bandgap materials. The C − ψ S technique has been suggested as a viable quasi-static method for determining the interface trap state densities in wide bandgap systems, but the results are shown to be susceptible to errors in the analysis procedure. This work explores the primary sources of errors present in the C − ψ S technique using an analytical model that describes the apparent response for wide bandgap MOS capacitor devices. Measurement noise is shown to greatly impact the linear fitting routine of the 1 / C S ∗ 2 vs ψ S plot to calibrate the additive constant in the surface potential/gate voltage relationship, and an inexact knowledge of the oxide capacitance is also shown to impede interface trap state analysis near the band edge. In addition, a slight nonlinearity that is typically present throughout the 1 / C S ∗ 2 vs ψ S plot hinders the accurate estimation of interface trap densities, which is demonstrated for a fabricated n-SiC MOS capacitor device. Methods are suggested to improve quasi-static analysis, including a novel method to determine an approximate integration constant without relying on a linear fitting routine. [ABSTRACT FROM AUTHOR]

N incorporation mechanisms in GaAs1−xNx alloys are probed using combined experimental and computational Rutherford backscattering spectrometry and nuclear reaction analysis angular yield scans. For xN < 0.025, in addition to substitutional nitrogen, NAs, (N-N)As, and (N-As)As split-interstitials are observed. However, for xN ≥ 0.025, evidence for N tetrahedral interstitials, Ntetra, emerges. We propose a mechanism for stabilization of Ntetra in which the elastic interaction between Ntetra and NAs is induced by the opposite signs of their misfit volumes. This work opens opportunities for exploring the formation of Ntetra and its influence on the properties of a variety of highly mismatched alloys. [ABSTRACT FROM AUTHOR]

In England, Wales, and Northern Ireland, people can choose to donate their bodies post-mortem to Medical School Anatomy Units. The body donation (BD) process is facilitated by anatomy unit staff (AUS). However, little is known about the extent and nature of AUS work with families, including when a body cannot be accepted. To address this gap, this paper draws on data from an ethnographic study, including a survey of 15 anatomy units (AUs) in England and Northern Ireland, a case study of one AU, 20 semi-structured interviews with 31 AUS and document analysis. We reveal the number of bodies (878) that are refused across AUs and examine how AUS deal with refusals. We argue that activities around refusals constitutes ‘over and above’ work for AUS, as it goes beyond their expected role. We suggest that this is done out of a duty of care, and is related to the discomfort of refusing the BD gift. Attention is given to the ‘over and above’ work of the AUS which allows for an exploration of gift relationships and emotion management in a new arena. We conclude with recommendations to address the lack of recognition and training around AUS refusal work. [ABSTRACT FROM AUTHOR]

DNA gyrase is an essential nucleoprotein motor present in all bacteria and is a major target for antibiotic treatment of Mycobacterium tuberculosis (MTB) infection. Gyrase hydrolyzes ATP to add negative supercoils to DNA using a strand passage mechanism that has been investigated using biophysical and biochemical approaches. To analyze the dynamics of substeps leading to strand passage, single-molecule rotor bead tracking (RBT) has been used previously to follow real-time supercoiling and conformational transitions in Escherichia coli (EC) gyrase. However, RBT has not yet been applied to gyrase from other pathogenically relevant bacteria, and it is not known whether substeps are conserved across evolutionarily distant species. Here, we compare gyrase supercoiling dynamics between two evolutionarily distant bacterial species, MTB and EC. We used RBT to measure supercoiling rates, processivities, and the geometries and transition kinetics of conformational states of purified gyrase proteins in complex with DNA. Our results show that E. coli and MTB gyrases are both processive, with the MTB enzyme displaying velocities ~5.5× slower than the EC enzyme. Compared with EC gyrase, MTB gyrase also more readily populates an intermediate state with DNA chirally wrapped around the enzyme, in both the presence and absence of ATP. Our substep measurements reveal common features in conformational states of EC and MTB gyrases interacting with DNA but also suggest differences in populations and transition rates that may reflect distinct cellular needs between these two species. [ABSTRACT FROM AUTHOR]

In 2015, DFO released the Musquash MPA Ecosystem Monitoring Plan (2014-2019). This plan, listed twelve indicators to monitor the ecological performance of the Musquash Estuary in support of broad conservation objectives. The objective of this review was to provide advice and recommendations as to the extent that data derived from the plan provides a baseline for detecting changes within the Musquash environment. Twenty-four data sets contained information to support at least one of the twelve indicators for productivity, biodiversity, habitat, and pressure threats. The sampling design for each dataset was reviewed in terms of spatial and temporal variability, as well as observed trends. While progress has been made to identify a baseline of information for each indicator, data gaps persist within the current ecosystem-based monitoring plan that has sought to inform on all key species, trophic groups, habitat types, and environments. The ecosystem approach to monitoring requires a diversity of data needs from multiple stakeholders. Developing a robust data management plan that can track available data and identify important data gaps for future planning and collaboration with stakeholders will improve the assessment of baseline information. This Research Document was presented and peer-reviewed at the Maritimes Region Science Advisory Process held virtually on May 11-12, 2021. [ABSTRACT FROM AUTHOR]

Background: Engaging users of health research, namely knowledge users, as partners in the research process may to lead to evidence that is more relevant to the users. This may optimize the uptake of evidence in healthcare practice, resulting in improved health outcomes or more efficient healthcare systems. However, barriers to involving knowledge users in the research process exist. Theories, models and frameworks may help guide the process of involving knowledge users and address barriers to engaging with knowledge users in research; however, there is little evidence identifying or describing the theories, models and frameworks of health research partnerships.Objectives: Identify and describe theories, models and frameworks of health research partnerships. Report on concepts of knowledge user engagement represented in identified theories, models and frameworks.Methods: We conducted a scoping review. Database (MEDLINE, Embase, CINAHL, PCORI) and ancestry and snowball searches were utilized. Included articles were written in English, published between January 2005 and June 2021, specific to health, a research partnership, and referred to a theory, model or framework. No critical appraisal was conducted. We developed a coding framework to extract details related to the publication (e.g. country, year) and theory, model or framework (e.g. intended users, theoretical underpinning, methodology, methods of development, purpose, concepts of knowledge user engagement). One reviewer conducted data extraction. Descriptive statistics and narrative synthesis were utilized to report the results.Results: We identified 21 874 articles in screening. Thirty-nine models or frameworks were included in data analysis, but no theory. Two models or frameworks (5%) were underpinned by theory. Literature review was the method (n = 11, 28%) most frequently used to develop a model or framework. Guiding or managing a partnership was the most frequently reported purpose of the model/framework (n = 14, 36%). The most represented concept of knowledge user engagement was principles/values (n = 36, 92%).Conclusions: The models and frameworks identified could be utilized by researchers and knowledge users to inform aspects of a health research partnership, such as guidance or implementation of a partnership. Future research evaluating the quality and applicability of the models and frameworks is necessary to help partners decide which model or framework to implement. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is the fourth most common neurodevelopmental disorder, with a prevalence of 1 in 160 children. Accurate diagnosis relies on experts, but such individuals are scarce. This has led to increasing interest in the development of machine learning (ML) models that can integrate neuroimaging features from functional and structural MRI (fMRI and sMRI) to help reveal central nervous system alterations characteristic of ASD. We optimized and compared the performance of 12 of the most popular and powerful ML models. Each was separately trained using 15 different combinations of fMRI and sMRI features and optimized with an unbiased model search. Deep learning models predicted ASD with the highest diagnostic accuracy and generalized well to other MRI datasets. Our model achieves state-of-the-art 80% area under the ROC curve (AUROC) in diagnosis on test data from the IMPAC dataset; and 86% and 79% AUROC on the external ABIDE I and ABIDE II datasets (with further improvement to 93% and 90% after supervised domain adaptation). The highest performing models identified reproducible putative biomarkers for accurate ASD diagnosis in accord with known ASD markers as well as novel cerebellar biomarkers. Such reproducibility lends credence to their tremendous potential for defining and using a set of truly generalizable ASD biomarkers that will advance scientific understanding of neuronal changes in ASD. [ABSTRACT FROM AUTHOR]

Evidence for sea-level change during and around Marine Isotope Stage (MIS) 5e (ca. 125 ka) in southern Africa derives from a wide variety of geomorphic and sedimentological sea-level indicators, supported in the past 2 decades by absolute chronological control, particularly on littoral deposits, some of which have a quantifiable relationship to former sea level. In addition to these proxies, data provided by both terrestrial (dune sediments and archaeological remains) and marine (lagoonal and nearshore littoral sediments) limiting points provide broad constraints on sea level. Here, we review publications describing such data points. Using the framework of the World Atlas of Last Interglacial Shorelines, we insert in a standardized database (10.5281/zenodo.4459297, Cooper and Green, 2020) all the elements available to assess former palaeo-relative sea level (palaeo-RSL) and the chronological constraints associated with them (including uncertainties). Overall, we reviewed 71 studies, from which we extracted 39 sea-level indicators and 26 limiting points. As far as age attribution is concerned, early analysis of molluscs and whole-rock beachrock samples using U series allowed dating of several sea-level indicators during the 1980s, but the more widespread application of optically stimulated luminescence (OSL) dating since 2004 has yielded many more (and more accurate) sea-level indicators from several sites. This has helped resolve the nature and timing of MIS 5e shorelines and has the potential to further elucidate the apparent presence of two or more sea-level peaks at several South African sites during this interval. The standardized sea-level database presented in this paper is the first of its kind for this region. Future research should be directed to improve the stratigraphic description of last interglacial shorelines and to obtain better dating, high-accuracy elevation measurements with better palaeo-RSL interpretation. [ABSTRACT FROM AUTHOR]

The novel coronavirus disease 2019 (COVID-19) is a novel and exponentially growing disease, and consequently, the accelerated development of knowledge from good data is possible quickly and globally. In order to combat the global pandemic of COVID-19, all humans on earth need to make difficult strategic decisions on three very different scales, all fueled by Analytical and Artificial Intelligence-based predictive Models. [ABSTRACT FROM AUTHOR]

Displacement is detrimental not only to displaced individuals and families but also to the communities left behind and their ability to collectively resist and mobilize against global processes that negatively affect their ability to engage in practices of resilience and regeneration that support well-rooted communities. Critical approaches to the study of displacement should not only focus on mapping vulnerability factors and analyzing dominant power structures driving racial, social, and environmental injustice but should also include the collective resilience, everyday vitality, and community knowledge that characterize rooted urban neighborhoods and build immunity to serial forced displacement. Building on theoretical and methodological foundations in critical, Black, Latinx, and Indigenous geographies; Black feminist theory; and environmental justice, we argue that for mapping to have a positive change outside the already academic understanding of displacement and inequity, we need a methodology to (1) identify intersectional oppressions and name them as such, (2) center community knowledge and strengths enabling resilience, and (3) advance community activism. This methodology requires trust and community engagement but is vulnerable to systems that interrupt the embeddedness of researchers. The response to the COVID-19 pandemic is one such system; not only has the pandemic exacerbated displacement crises, making the need for engaged, critical, and cocreative partnerships even greater, it has abruptly halted opportunities for these community partnerships and regenerative work to happen. Drawing on our experiences attempting these approaches during the COVID-19 pandemic, we discuss challenges that arise when researchers are displaced from field sites, best practices, and implications for future research. [ABSTRACT FROM AUTHOR]

Beachrocks are a common characteristic of tropical and subtropical coastlines. It is known that they have a substantial influence on beach morphodynamics and they are commonly utilised as indicators of palaeo‐sea levels. At the same time, facies variability in beachrocks is understudied and their effect on shoreline evolution is poorly understood. At Mission Rocks on the KwaZulu‐Natal coastline of South Africa a narrow beach with isolated sand patches occupies low points of an otherwise continuous 3 m thick, raised shore platform of sandy and gravelly beachrocks. These beachrocks are in the process of disintegrating into megagravel deposits through chemical and mechanical weathering in a wave‐dominated, high‐energy setting. The breakdown is potentially slowed by a contemporary, fast‐forming beachrock facies, that blankets the surface and fills fractures and potholes within the older platform. The accumulation and cementation of this recent beachrock is the focus of this study. The beachrock is dated by historical evidence to post‐World War II. Data from field observations, petrographic and geochemical methods reveal that the cementing agents of the beachrock were precipitated from marine water in a phreatic setting despite its position above the intertidal zone. Not only does this facies have implications for the interpretation of palaeo‐beachrock as a sea‐level indicator, it also raises further questions regarding modelling of coastal erosion of beaches associated with outcrops of beachrock. [ABSTRACT FROM AUTHOR]

When compared to tide-dominated shelves, shelves swept by geostrophic flows are relatively understudied, yet geostrophic currents have the potential to construct substantial current-generated shelf bedforms. This paper examines the evolution of a series of bedforms encountered along the narrow Agulhas Current-swept northern KwaZulu-Natal shelf. Their evolution is placed in the context of progressive current impingement and variation in flows associated with the postglacial transgression and culminating in the present-day highstand. Ultra-high resolution seismic reflection, multibeam, side-scan sonar and single beam data sets reveal several bedform scales and morphologies; wave ripples and shoreface-connected ridges are associated only with the inner shelf, and 2D and 3D very large dunes are more cosmopolitan and span the entire shelf sector. The inner shelf is marked by rock outcrop (aeolianite), surrounded by sandy sediment, grading seaward into sediment starved bedforms associated with bioclastic gravels. Where sufficient sediment exists in local depocenters, very large dunes form discontinuous fields along the outer shelf. The seismic stratigraphy of the outer shelf reflects the effects of postglacial flooding by rising sea levels and increasing current impingement by the Agulhas Current. The Holocene wave ravinement surface is overlain by flat-lying strata (early dune development and dune amalgamation with first current exposure), in turn covered by hummocky, sub-horizontal aggrading beds (amalgamation), overlain by inclined cross-bedded packages (lee faces of the bedforms formed during migration and full current interaction). Morphometric analyses show that for both the inner and outer shelf, no relationships exist between water depth, wavelength and spacing. Height to spacing (H/L) relationships are weak but nevertheless show a broadly positive trend. Bedform heights are lower on the inner shelf compared to the outer shelf, but bedform spacing is greater on the inner shelf, with a 40% overlap in H/L indices observed between the two areas. The departures in overlap can be linked to the competing offshore Agulhas Current and the inshore wave-dominated processes. Bedforms of the inner shelf plot below the global H/L mean and can be related to the more infrequent incursions of the Agulhas Current core. At the time of survey, the Agulhas Current was likely situated well offshore, resulting in reduced current activity in the survey area resulting in rounding of the dune crests, degradation of the dune crests and trough infilling. On the outer shelf, the H/L values plot above the mean global trend, suggesting vertical accretion due to the faster currents. Crest rounding and downlapping of the upstream lee faces onto the downstream stoss faces indicate dune degradation, which is related to a seaward location of the Agulhas Current at the time of survey. [ABSTRACT FROM AUTHOR]

Summary: There is equipoise regarding the use of prothrombin complex concentrate vs. fresh frozen plasma in bleeding patients undergoing cardiac surgery. We performed a pilot randomised controlled trial to determine the recruitment rate for a large trial, comparing the impact of prothrombin complex concentrate vs. fresh frozen plasma on haemostasis (1 h and 24 h post‐intervention), and assessing safety. Adult patients who developed bleeding within 24 h of cardiac surgery that required coagulation factor replacement were randomly allocated to receive prothrombin complex concentrate (15 IU.kg−1 based on factor IX) or fresh frozen plasma (15 ml.kg−1). If bleeding continued after the first administration of prothrombin complex concentrate or fresh frozen plasma administration, standard care was administered. From February 2019 to October 2019, 180 patients were screened, of which 134 (74.4% (95%CI 67–81%)) consented, 59 bled excessively and 50 were randomly allocated; 25 in each arm, recruitment rate 35% (95%CI 27–44%). There were 23 trial protocol deviations, 137 adverse events (75 prothrombin complex concentrate vs. 62 fresh frozen plasma) and 18 serious adverse events (5 prothrombin complex concentrate vs. 13 fresh frozen plasma). There was no increase in thromboembolic events with prothrombin complex concentrate. No patient withdrew from the study, four were lost to follow‐up and two died. At 1 h after administration of the intervention there was a significant increase in fibrinogen, Factor V, Factor XII, Factor XIII, α2‐antiplasmin and antithrombin levels in the fresh frozen plasma arm, while Factor II and Factor X were significantly higher in the prothrombin complex concentrate group. At 24 h, there were no significant differences in clotting factor levels. We conclude that recruitment to a larger study is feasible. Haemostatic tests have provided useful insight into the haemostatic changes following prothrombin complex concentrate or fresh frozen plasma administration. A definitive trial is needed to ascertain the benefits and safety for each. [ABSTRACT FROM AUTHOR]

Background: Enhanced recovery protocols (ERPs) after metabolic and bariatric surgery (MBS) may help decrease length of stay (LOS) and postoperative nausea/vomiting but implementation is often fraught with challenges. The primary aim of this pilot study was to standardize a MBS ERP with a real-time data support dashboard and checklist and assess impact on global and individual element compliance. The secondary aim was to evaluate 30 day outcomes including LOS, hospital readmissions, and re-operations. Methods and procedures: An ERP, paper checklist, and virtual dashboard aligned on MBS patient care elements for pre-, intra-, and post-operative phases of care were developed and sequentially deployed. The dashboard includes surgical volumes, operative times, ERP compliance, and 30 day outcomes over a rolling 18 month period. Overall and individual element ERP compliance and outcomes were compared pre- and post-implementation via two-tailed Student's t-tests. Results: Overall, 471 patients were identified (pre-implementation: 193; post-implementation: 278). Baseline monthly average compliance rates for all patient care elements were 1.7%, 3.7%, and 6.2% for pre-, intra-, and post-operative phases, respectively. Following ERP integration with dashboard and checklist, the intra-operative phase achieved the highest overall monthly average compliance at 31.3% (P < 0.01). Following the intervention, pre-operative acetaminophen administration had the highest monthly mean compliance at ≥ 99.1%. Overall TAP block use increased 3.2-fold from a baseline mean rate of 25.4–80.8% post-implementation (P < 0.01). A significant decrease in average intra-operative monthly morphine milligram equivalents use was noted with a 56% drop pre- vs. post-implementation. Average LOS decreased from 2.0 to 1.7 days post-implementation with no impact on post-operative outcomes. Conclusion: Implementation of a checklist and dashboard facilitated ERP integration and adoption of process measures with many improvements in compliance but no impact on 30 day outcomes. Further research is required to understand how clinical support tools can impact ERP adoption among MBS patients. [ABSTRACT FROM AUTHOR]

Nolanea is a well-known and long-established subgenus of the genus Entoloma traditionally defined mainly by the mycenoid basidiocarps of the included species. Until now, revisions of this subgenus including molecular data exist only on a regional scale. In this study, the phylogeny of species of Nolanea is analysed based on multi-gene DNA sequences including data of specimens from all continents. New primers are designed for the mitochondrial small subunit and RPB2. The performance of the DNA loci in reconstructing the phylogeny in subg. Nolanea is evaluated. An ancestral state reconstruction is used to infer the character state evolution as well as the importance and reliability of morphological characters used to define subclades below subgeneric rank. Based on the results, seven sections are recognised in Nolanea: the sections Holoconiota, Infularia, Mammosa, Nolanea, Papillata, Staurospora, and the newly described sect. Elegantissima. A large phylogeny based on the fungal barcode rDNA ITS with numerous type sequences is used to evaluate current species concepts. Several names are revealed to be synonyms of older names. Four species new to science are described, namely E. altaicum, E. argillaceum, E. cornicolor, and E. incognitum. Lectotypes, epitypes or neotypes are designated for E. cetratum, E. clandestinum, E. conferendum, E. cuspidiferum, E. hebes, E. minutum, E. nitens, and E. rhodocylix. The re-evaluation of the limits of subg. Nolanea leads to an altered concept excluding species with distinct, lageniform cheilocystidia. The section Ameides is placed in subg. Leptonia. For several species formerly accommodated in Nolanea, but excluded now, viz., E. lepiotoides, E. rhombisporum, E. subelegans, and E. velenovskyi the taxonomic position remains unclear, because of the yet unresolved phylogeny of the whole genus Entoloma. [ABSTRACT FROM AUTHOR]

Devices based on arrays of interconnected magnetic nano-rings with emergent magnetization dynamics have recently been proposed for use in reservoir computing applications, but for them to be computationally useful it must be possible to optimise their dynamical responses. Here, we use a phenomenological model to demonstrate that such reservoirs can be optimised for classification tasks by tuning hyperparameters that control the scaling and input-rate of data into the system using rotating magnetic fields. We use task-independent metrics to assess the rings’ computational capabilities at each set of these hyperparameters and show how these metrics correlate directly to performance in spoken and written digit recognition tasks. We then show that these metrics, and performance in tasks, can be further improved by expanding the reservoir’s output to include multiple, concurrent measures of the ring arrays’ magnetic states. [ABSTRACT FROM AUTHOR]

The physical aging of amorphous polymers induces changes in material properties, which are challenging to detect in situ in industrial settings. Here, we present a nondestructive nonlinear ultrasonic evaluation technique that enables localized measurements of the combined effects of temperature and time in amorphous polymers, without needing to remove materials. The proposed technique is demonstrated using commercial grade poly(vinyl chloride) samples and is supported by analysis of wave–material interactions. The results show that the physical aging of the polymer is described by the Arrhenius equation with an effective activation energy of 103 kJ/mol over the analyzed temperature range. [ABSTRACT FROM AUTHOR]

The Lactifluus clarkeae complex is a commonly observed, generally brightly coloured, group of mushrooms that are usually associated with Nothofagus or Myrtaceous hosts in Australia and New Zealand. For this study collections labelled as 'Lactarius clarkeae', 'Russula flocktoniae' and 'Lactarius subclarkeae' were examined morphologically and molecularly. Analyses of molecular data showed a high cryptic diversity, with sequences scattered across 11 clades in three subgenera within Lactifluus, and a single collection in Russula. We select epitypes to anchor the currently accepted concepts of Lf. clarkeae s.str. and Lf. flocktoniae s.str. The name Lf. subclarkeae could not be applied to any of the collections examined, as none had a lamprotrichoderm pileipellis. Lactifluus clarkeae var. aurantioruber is raised to species level, and six new species are described, three in subg. Lactifluus: Lf. jetiae, Lf. pagodicystidiatus, and Lf. rugulostipitatus, and three in subg. Gymnocarpi: Lf. albens, Lf. psammo philus, and Lf. pseudoflocktoniae. A new collection of Lf. russulisporus provides a significant range extension for the species. Untangling this complex will enable better identification of species and increase understanding of diversity and specific habitat associations of macrofungi. [ABSTRACT FROM AUTHOR]

We report on results of spectropolarimetry of the afterglow of the long gamma-ray burst GRB 191221B, obtained with SALT/RSS and VLT/FORS2, as well as photometry from two telescopes in the MASTER Global Robotic Network, at the MASTER-SAAO (South Africa) and MASTER-OAFA (Argentina) stations. Prompt optical emission was detected by MASTER-SAAO 38 s after the alert, which dimmed from a magnitude (white-light) of ∼10–16.2 mag over a period of ∼10 ks, followed by a plateau phase lasting ∼10 ks and then a decline to ∼18 mag after 80 ks. The light curve shows complex structure, with four or five distinct breaks in the power-law decline rate. SALT/RSS linear spectropolarimetry of the afterglow began ∼2.9 h after the burst, during the early part of the plateau phase of the light curve. Absorption lines seen at ∼6010 and 5490 Å are identified with the Mg ii 2799 Å line from the host galaxy at z  = 1.15 and an intervening system located at z  = 0.96. The mean linear polarization measured over 3400–8000 Å was ∼1.5 per cent and the mean equatorial position angle (θ) was ∼65°. VLT/FORS2 spectropolarimetry was obtained ∼10 h post-burst, during a period of slow decline (α = −0.44), and the polarization was measured to be p  = 1.2 per cent and θ = 60°. Two observations with the MeerKAT radio telescope, taken 30 and 444 d after the GRB trigger, detected radio emission from the host galaxy only. We interpret the light curve and polarization of this long GRB in terms of a slow-cooling forward shock. [ABSTRACT FROM AUTHOR]

[Display omitted] • Microglial cell activation in SNpc precedes alpha-synuclein inclusion formation. • In striatum a significant astrogliosis was observed 90 dpi. • Alpha-synuclein monomer did not result in long-term glia activation. • Neuroinflammation is an early event in PD pathogenesis. Neuroinflammation is increasingly recognized as an important feature in the pathogenesis of Parkinson's disease (PD). However, it remains unclear whether neuroinflammation contributes to nigral degeneration in PD or is merely a secondary marker of neurodegeneration. We aimed to investigate the temporal relationship between synucleopathy, neuroinflammation and nigrostriatal degeneration in a mouse model of PD. Mice received unilateral intrastriatal injection of alpha-synuclein pre-formed fibrils, alpha-synuclein monomer or vehicle and were sacrificed at 15, 30 and 90 days post-injection. Intrastriatal inoculation of alpha-synuclein fibrils led to significant alpha-synuclein aggregation in the substantia nigra peaking at 30 days after injection while the significant increase in Iba-1 cells, GFAP cells and IL-1β expression peaked earlier at 15 days. At 90 days, the striatal dopaminergic denervation was associated with astroglial activation. Alpha-synuclein monomer did not result in long-term glia activation or increase in inflammatory markers. The spread of alpha-synuclein aggregates into the cortex was not associated with any changes to neuroinflammatory markers. Our results demonstrate that in the substantia nigra glial activation is an early event that precedes alpha-synuclein inclusion formation, suggesting neuroinflammation could play an important early role in the pathogenesis of PD. [ABSTRACT FROM AUTHOR]

There is increased interest in the use of prothrombin complex concentrate (PCC) to treat bleeding in patients who do not require reversal of vitamin K antagonists. Here, we describe in detail the coagulation abnormalities before administration of intervention(s) and during bleeding episodes, and we compare the correction of these abnormalities between different doses of interventions. [Extracted from the article]

Although morphologically persistent in the long term, Multiple Intertidal Bar Systems (MITBs) display short-term, especially seasonal, morphodynamic behaviour. Analysis of high-density, monthly DGPS surveys conducted at Murlough and Ballykinler beaches, inter- and supratidal sediment volumes and hydrodynamic forcing (wave conditions and water levels), demonstrates a link between strong seasonality in wave climate and MITB beach behaviour. Summer, low-energy conditions limit cross-shore sediment exchange during which MITB beach morphology tends to stabilise throughout the season. With the onset of high-energy winter conditions cross-shore sediment exchanges occur between inter- and supratidal areas. Sediment transport is then enhanced during storm conditions that are coincident with spring tides, leading to high total water levels (TWL). Ultimately the storm sequencing, (frequency, magnitude and inter-storm interval), is the key parameter driving the beach morphological response. Major erosional patterns occur when the most energetic event, combined with spring high tide, occurs at the beginning of the winter season. Subsequent, less energetic storms then promote bar recovery until another extreme event occurs. Seasonality is also evident in alongshore dynamics. Cross-shore drainage channels that dissect the intertidal bars migrate alongshore, driving alongshore sediment transport and MITB longshore migration patterns. In summer migration of drainage channels is limited, whereas the winter high-energy forcing enhances channel migration rates and resulting sediment transport. Differences in dynamics between the two study sites are attributed to differences in local geology, beach morphology and sediment size, but in both locations, drainage channels are in fine migrating toward the inlet and associated ebb delta that divides the bay. Subsequent transport vectors are unknown, but the observations highlight the primary role of the inlet in the sediment circulation dynamics in the system as a whole. • Long-term Multiple Intertidal Bar systems stability is based on a dynamic equilibrium driven by short-term seasonal morphodynamics • Low-energy conditions limit cross-shore sediment transport and longshore drainage channels migration, supporting MITB system stability • High-energy forcing drive sediment exchanges between upper and lower beach; patterns are enhanced by storm events and high-water levels • Winter forcing increases alongshore drainage channels migration rates and subsequent sediment transport leading to alongshore bar migrations • MITB beach dynamics are driven by wave forcing, water levels, storm sequencing, local geomorphology and the presence of hard features and an inlet [ABSTRACT FROM AUTHOR]

Globally, regulatory authorities grapple with the challenge of assessing the hazards and risks to human and ecosystem health that may result from exposure to chemicals that disrupt the normal functioning of endocrine systems. Rapidly increasing number of chemicals in commerce, coupled with the reliance on traditional, costly animal experiments for hazard characterization - often with limited sensitivity to many important mechanisms of endocrine disruption -, presents ongoing challenges for chemical regulation. The consequence is a limited number of chemicals for which there is sufficient data to assess if there is endocrine toxicity and hence few chemicals with thorough hazard characterization. To address this challenge, regulatory assessment of endocrine disrupting chemicals (EDCs) is benefiting from a revolution in toxicology that focuses on New Approach Methodologies (NAMs) to more rapidly identify, prioritize, and assess the potential risks from exposure to chemicals using novel, more efficient, and more mechanistically driven methodologies and tools. Incorporated into Integrated Approaches to Testing and Assessment (IATA) and guided by conceptual frameworks such as Adverse Outcome Pathways (AOPs), emerging approaches focus initially on molecular interactions between the test chemical and potentially vulnerable biological systems instead of the need for animal toxicity data. These new toxicity testing methods can be complemented with in silico and computational toxicology approaches, including those that predict chemical kinetics. Coupled with exposure data, these will inform risk-based decision-making approaches. Canada is part of a global network collaborating on building confidence in the use of NAMs for regulatory assessment of EDCs. Herein, we review the current approaches to EDC regulation globally (mainly from the perspective of human health), and provide a perspective on how the advances for regulatory testing and assessment can be applied and discuss the promises and challenges faced in adopting these novel approaches to minimize risks due to EDC exposure in Canada, and our world. [Display omitted] • Traditional testing approaches for endocrine effects are costly and animal-intensive. • Emerging technologies are increasingly available to rapidly and reliably test many chemicals. • Testing and assessment frameworks support use and integration of novel evidence. • Using data from New Approach Methods is critical to modernizing the assessment of EDCs. [ABSTRACT FROM AUTHOR]