A Modified Delphi Consensus Approach to Define Entrustable Professional Activities for Neurocritical Care Advanced Practice Providers.

OBJECTIVES: To define consensus entrustable professional activities (EPAs) for neurocritical care (NCC) advanced practice providers (APPs), establish validity evidence for the EPAs, and evaluate factors that inform entrustment expectations of NCC APP supervisors. DESIGN: A three-round modified Delphi consensus process followed by application of the EQual rubric and assessment of generalizability by clinicians not affiliated with academic medical centers. SETTING: Electronic surveys. SUBJECTS: NCC APPs (n = 18) and physicians (n = 12) in the United States with experience in education scholarship or APP program leadership. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The steering committee generated an initial list of 61 possible EPAs. The panel proposed 30 additional EPAs. A total of 47 unique nested EPAs were retained by consensus opinion. The steering committee defined six core EPAs addressing medical knowledge, procedural competencies, and communication proficiency which encompassed the nested EPAs. All core EPAs were retained and subsequently met the previously described cut score for quality and structure using the EQual rubric. Most clinicians who were not affiliated with academic medical centers rated each of the six core EPAs as very important or mandatory. Entrustment expectations did not vary by prespecified groups. CONCLUSIONS: Expert consensus was used to create EPAs for NCC APPs that reached a predefined quality standard and were important to most clinicians in different practice settings. We did not identify variables that significantly predicted entrustment expectations. These EPAs may aid in curricular design for an EPA-based assessment of new NCC APPs and may inform the development of EPAs for APPs in other critical care subspecialties.

Meningeal contrast enhancement in multiple sclerosis: assessment of field strength, acquisition delay, and clinical relevance.

Background/Purpose: Leptomeningeal enhancement (LME) on post-contrast FLAIR is described as a potential biomarker of meningeal inflammation in multiple sclerosis (MS). Here we report a comprehensive assessment of the impact of MRI field strength and acquisition timing on meningeal contrast enhancement (MCE). Methods: This was a cross-sectional, observational study of 95 participants with MS and 17 healthy controls (HC) subjects. Each participant underwent an MRI of the brain on both a 7 Tesla (7T) and 3 Tesla (3T) MRI scanner. 7T protocols included a FLAIR image before, soon after (Gd+ Early 7T FLAIR), and 23 minutes after gadolinium (Gd+ Delayed 7T FLAIR). 3T protocol included FLAIR before and 21 minutes after gadolinium (Gd+ Delayed 3T FLAIR). Results: LME was seen in 23.3% of participants with MS on Gd+ Delayed 3T FLAIR, 47.4% on Gd+ Early 7T FLAIR (p = 0.002) and 57.9% on Gd+ Delayed 7T FLAIR (p < 0.001 and p = 0.008, respectively). The count and volume of LME, leptomeningeal and paravascular enhancement (LMPE), and paravascular and dural enhancement (PDE) were all highest for Gd+ Delayed 7T FLAIR and lowest for Gd+ Delayed 3T FLAIR. Non-significant trends were seen for higher proportion, counts, and volumes for LME and PDE in MS compared to HCs. The rate of LMPE was different between MS and HCs on Gd+ Delayed 7T FLAIR (98.9% vs 82.4%, p = 0.003). MS participants with LME on Gd+ Delayed 7T FLAIR were older (47.6 (10.6) years) than those without (42.0 (9.7), p = 0.008). Conclusion: 7T MRI and a delay after contrast injection increased sensitivity for all forms of MCE. However, the lack of difference between groups for LME and its association with age calls into question its relevance as a biomarker of meningeal inflammation in MS.

Safety of the immediate use of nonsteroidal anti-inflammatory drugs after adult craniotomy for tumor.

OBJECTIVE: Poor pain control has a negative impact on postoperative recovery and patient satisfaction. However, overzealous pain management, particularly with opioids, can confound serial neurological assessments, increase morbidity, and predispose patients to long-term dependence. Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in treating postoperative pain and can limit opioid intake, but their use has been limited in patients undergoing craniotomy for brain tumor resection due to concerns of an increased hemorrhage risk. Herein, the authors aim to 1) address the safety of NSAID use in the immediate postoperative setting and 2) determine whether NSAID administration decreases opioid use following craniotomy for tumor resection in adult patients. METHODS: The authors conducted a retrospective cohort study of patients 18 years and older with an estimated glomerular filtration rate ≥ 60 ml/min/body surface area who had undergone craniotomy for tumor resection at their institution between 2019 and 2021. NSAID use in the first 48 hours following surgery was recorded. Primary outcomes were postoperative hemorrhage requiring a return to the operating room before hospital discharge and within 30 days of surgery. Secondary outcomes were more-than-minimal hemorrhage that did not require reoperation, acute kidney injury, and total opioid use within 48 hours after craniotomy. RESULTS: Among 1765 reviewed patient records, 1182 were eligible for inclusion in this analysis. Amid these records were 114 patients (9.6%) who had received at least one dose of an NSAID within 48 hours of their craniotomy. Four (0.3%) patients experienced bleeding requiring a return to operating room, one of whom was from the NSAID-treated group (RR 3.12, 95% CI 0.33-29.77, p = 0.30). No significant difference in nonoperative intracranial hemorrhage (RR 1.34, 95% CI 0.54-3.35, p = 0.53), postoperative acute kidney injury, or clinically significant extracranial bleeding was found between the NSAID and no-NSAID groups. Patients in the NSAID group had significantly higher oral morphine equivalent use (median 68 vs 30, p < 0.001). CONCLUSIONS: Postoperative NSAID use following craniotomy for tumor resection was not associated with an increased risk of hemorrhage requiring a return to the operating room. The authors noted higher opioid use in the patients treated with NSAIDs, which may reflect underlying reasons for the decision to treat patients with NSAIDs in the immediate postoperative period. These data warrant further investigation of NSAIDs as a safe, opioid-sparing postoperative pain management strategy in patients with normal kidney function who are undergoing intracranial tumor resection.

Imaging chronic active lesions in multiple sclerosis: a consensus statement.

Chronic active lesions (CAL) are an important manifestation of chronic inflammation in multiple sclerosis (MS) and have implications for non-relapsing biological progression. In recent years, the discovery of innovative magnetic resonance imaging (MRI) and PET derived biomarkers has made it possible to detect CAL, and to some extent quantify them, in the brain of persons with MS, in vivo. Paramagnetic rim lesions on susceptibility-sensitive MRI sequences, MRI-defined slowly expanding lesions on T1-weighted (T1-w) and T2-w scans, and 18-kDa translocator protein-positive lesions on PET are promising candidate biomarkers of CAL. While partially overlapping, these biomarkers do not have equivalent sensitivity and specificity to histopathological CAL. Standardization in the use of available imaging measures for CAL identification, quantification, and monitoring is lacking. To fast-forward clinical translation of CAL, the North American Imaging in Multiple Sclerosis Cooperative developed a Consensus Statement, which provides guidance for the radiological definition and measurement of CAL. The proposed manuscript presents this Consensus Statement, summarizes the multistep process leading to it, and identifies the remaining major gaps in knowledge.

A pilot trial of ocrelizumab for modulation of meningeal enhancement in multiple sclerosis.

BACKGROUND: Autopsy data suggests that meningeal inflammation in multiple sclerosis (MS) is driven by CD20+ B-cells. Ocrelizumab is an anti-CD20 monoclonal antibody, and thus could potentially ameliorate meningeal inflammation in MS. Leptomeningeal enhancement (LME) on MRI is suggested as a surrogate biomarker of meningeal inflammation in MS, and thus may be a way of monitoring for this treatment effect. OBJECTIVES: To determine if ocrelizumab impacts meningeal enhancement (ME) on 7T MRI in MS. METHODS: Twenty-two patients with MS started on ocrelizumab by their treating physician were enrolled into this single-center, open-label, prospective trial. Participants underwent 7T MRI of the brain prior to first infusion, with screening for the presence of LME. Fourteen patients (48 ± 11 years; 11 women) had LME on the baseline scan and were invited to return for an additional 7T MRI after 1 year of treatment. Fourteen MS patients (49 ± 10 years; 11 women) on non-CD20 treatment from a separate observational cohort of annual 7T MRIs were used for comparison - matched for LME at baseline, age, and sex. Post-contrast FLAIR and subtraction images were reviewed for LME and paravascular and dural enhancement (PDE). RESULTS: All subjects in the ocrelizumab and comparison groups had LME and PDE on their baseline scan. At the beginning of the study the mean number of foci of LME and PDE in the study group were 2.3 ± 1.7 and 6.6 ± 3.9 respectively. Mean LME and PDE count for the comparison group were 1.7 ± 1.5 and 7.8 ± 5.5. Mean volume of LME in the study group was 50.5 mm3 ± 65.0 mm3 and that of the PDE was 866 mm3 ± 937.9. Mean volume of LME and PDE for comparison group were 28.4 mm3 ± 36.0 and 885 mm3 ± 947.7 respectively. At follow-up, the number of patients with LME decreased to 8 (57 %) in both groups, whereas the proportion of patients with PDE was unchanged. Minimal mean change in the number of LME after 1 year were seen in both the study group (0.07 ± 2.9, p = 0.97) and comparison group (-0.71 ± 1.5, p = 0.08). Minimal mean change was seen in the volume of LME in both the study group (-21.91 mm3 ± 77.66, p = 0.27) and comparison group (3.4 mm3 ± 32.11, p = 0.77). There was minimal change in the mean number of foci of PDE after 1 year in both the study group (-0.71 ± 2.36, p = 0.32) and in the comparison group (-0.17 ± 3.89, p = 0.15). Mean change in volume of PDE was measurable, but not significant in both the study group (-397.1 mm3 ±959.6, p = 0.80) and in the comparison group (-417.0 mm3 ± 922.7) (p = 0.80). Comparisons between the changes in foci count and volume for both LME and PDE in the study versus comparison groups showed no significant differences. CONCLUSION: In this small pilot trial, ocrelizumab did not significantly reduce the number or volume of foci of LME or PDE in MS patients.

Evaluation of the Blood-Brain Barrier, Demyelination, and Neurodegeneration in Paramagnetic Rim Lesions in Multiple Sclerosis on 7 Tesla MRI.

BACKGROUND: Paramagnetic rim lesions (PRLs) are associated with chronic inflammation in multiple sclerosis (MS). 7-Tesla (7T) magnetic resonance imaging (MRI) can evaluate the integrity of the blood-brain barrier (BBB) in addition to the tissue myelination status and cell loss. PURPOSE: To use MRI metrics to investigate underlying physiology and clinical importance of PRLs. STUDY TYPE: Prospective. SUBJECTS: Thirty-six participants (mean-age 47, 23 females, 13 males) of mixed MS subtypes. FIELD STRENGTH/SEQUENCE: 7T, MP2RAGE, MULTI-ECHO 3D-GRE, FLAIR. ASSESSMENT: Lesion heterogeneity; longitudinal changes in lesion counts; comparison of T1, R2*, and χ; association between baseline lesion types and disease progression (2-3 annual MRI visits with additional years of annual clinical follow-up). STATISTICAL TESTS: Two-sample t-test, Wilcoxon Rank-Sum test, Pearson's chi-square test, two-group comparison with linear-mixed-effect model, mixed-effect ANOVA, logistic regression. P-values <0.05 were considered significant. RESULTS: A total of 58.3% of participants had at least one PRL at baseline. Higher male proportion in PRL+ group was found. Average change in PRL count was 0.20 (SD = 2.82) for PRLs and 0.00 (SD = 0.82) for mottled lesions. Mean and median pre-/post-contrast T1 were longer in PRL+ than in PRL-. No differences in mean χ were seen for lesions grouped by PRL (P = 0.310, pre-contrast; 0.086, post-contrast) or PRL/M presence (P = 0.234, pre-contrast; 0.163, post-contrast). Median χ were less negative in PRL+ and PRL/M+ than in PRL- and PRL/M-. Mean and median pre-/post-contrast R2* were slower in PRL+ compared to PRL-. Mean and median pre-/post-contrast R2* were slower in PRL/M+ than in PRL/M-. PRL presence at baseline was associated with confirmed EDSS Plus progression (OR 3.75 [1.22-7.59]) and PRL/M+ at baseline with confirmed EDSS Plus progression (OR 3.63 [1.14-7.43]). DATA CONCLUSION: Evidence of BBB breakdown in PRLs was not seen. Quantitative metrics confirmed prior results suggesting greater demyelination, cell loss, and possibly disruption of tissue anisotropy in PRLs. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Nonsteroidal Anti-inflammatory Medications in Cranial Neurosurgery: Balancing Opioid-Sparing Analgesia with Bleeding Risk.

Postcraniotomy pain is a common problem frequently encountered by neurosurgeons. This is typically managed with opioids; however, opioids have been shown to increase intracranial pressure by way of hypercapnia and straining from the associated constipation. Additionally, opioids can confound and mask the neurologic examination of postcraniotomy patients, as well as be the nidus for a potential opioid addiction. Thus, alternative solutions for opioids have been a major topic of investigation within the neurosurgical community. Nonsteroidal anti-inflammatory drugs (NSAIDs) present as a potential solution due to their nonaddictive and analgesic properties, but utilization of NSAIDs in neurosurgical patients has been controversial given that NSAIDs alter platelet function. The degree to which NSAIDs alter platelet function and bleeding time to a clinically relevant manner has remained controversial, although several well-designed studies concluded that the utilization of NSAIDs in post-craniotomy patients does not increase the risk of postoperative bleeding. Herein, we review the pharmacology, efficacy, and safety of NSAIDs with a particular emphasis on NSAID use for postintracranial neurosurgical procedure pain management.

Neuroimaging to monitor worsening of multiple sclerosis: advances supported by the grant for multiple sclerosis innovation.

Key unmet needs in multiple sclerosis (MS) include detection of early pathology, disability worsening independent of relapses, and accurate monitoring of treatment response. Collaborative approaches to address these unmet needs have been driven in part by industry-academic networks and initiatives such as the Grant for Multiple Sclerosis Innovation (GMSI) and Multiple Sclerosis Leadership and Innovation Network (MS-LINK™) programs. We review the application of recent advances, supported by the GMSI and MS-LINK™ programs, in neuroimaging technology to quantify pathology related to central pathology and disease worsening, and potential for their translation into clinical practice/trials. GMSI-supported advances in neuroimaging methods and biomarkers include developments in magnetic resonance imaging, positron emission tomography, ocular imaging, and machine learning. However, longitudinal studies are required to facilitate translation of these measures to the clinic and to justify their inclusion as endpoints in clinical trials of new therapeutics for MS. Novel neuroimaging measures and other biomarkers, combined with artificial intelligence, may enable accurate prediction and monitoring of MS worsening in the clinic, and may also be used as endpoints in clinical trials of new therapies for MS targeting relapse-independent disease pathology.

Evaporative Cooling Does Not Prevent Vertical Dispersion of Effervescent Seawater Aerosol for Brightening Clouds.

Marine cloud brightening (MCB) is a potential intervention to mitigate the effects of climate change by increasing the reflectance of low-level maritime clouds, including those over the Great Barrier Reef. The technique involves dispersing a plume of submicrometer seawater droplets over the ocean, which evaporate, generating nanosized sea-salt aerosols (SSAs) that disperse through the atmosphere with some fraction incorporated into clouds. Droplet evaporation, which occurs in the immediate vicinity (meters to tens of meters) of the source, has been theorized to produce a negatively buoyant plume hindering the mixing of the sea-salt aerosol to cloud height and compromising the effectiveness of MCB. We characterized in situ for the first time the nearfield aerosol dispersion from a point source of atomized seawater produced using the effervescent technique. We observed consistent vertical mixing of the plume up to 150 ± 5 m height at 1 km downwind. The extent of vertical dispersion was influenced by wind velocity and atmospheric stability. We found no evidence that negative buoyancy due to the evaporation of the 0.068 kg/s water fraction significantly suppressed vertical mixing. Our results can be attributed to the small droplet sizes generated by the effervescent spray technology and associated low flow rates required to generate around 1014 droplets s-1. We estimate that, for a hypothetical implementation producing up to 1016 s-1 similarly sized SSAs, evaporative cooling is unlikely to significantly suppress the vertical dispersion of aerosol for MCB.

Cellular-Level Visualization of Retinal Pathology in Multiple Sclerosis With Adaptive Optics.

Purpose: To apply adaptive optics-optical coherence tomography (AO-OCT) to quantify multiple sclerosis (MS)-induced changes in axonal bundles in the macular nerve fiber layer, ganglion cell somas, and macrophage-like cells at the vitreomacular interface. Methods: We used AO-OCT imaging in a pilot study of MS participants (n = 10), including those without and with a history of optic neuritis (ON, n = 4), and healthy volunteers (HV, n = 9) to reveal pathologic changes to inner retinal cells and structures affected by MS. Results: We found that nerve fiber layer axonal bundles had 38% lower volume in MS participants (1.5 × 10-3 mm3) compared to HVs (2.4 × 10-3 mm3; P < 0.001). Retinal ganglion cell (RGC) density was 51% lower in MS participants (12.3 cells/mm2 × 1000) compared to HVs (25.0 cells/mm2 × 1000; P < 0.001). Spatial differences across the macula were observed in RGC density. RGC diameter was 15% higher in MS participants (11.7 µm) compared to HVs (10.1 µm; P < 0.001). A nonsignificant trend of higher density of macrophage-like cells in MS eyes was also observed. For all AO-OCT measures, outcomes were worse for MS participants with a history of ON compared to MS participants without a history of ON. AO-OCT measures were associated with key visual and physical disabilities in the MS cohort. Conclusions: Our findings demonstrate the utility of AO-OCT for highly sensitive and specific detection of neurodegenerative changes in MS. Moreover, the results shed light on the mechanisms that underpin specific neuronal pathology that occurs when MS attacks the retina. The new findings support the further development of AO-based biomarkers for MS.

Sterically attenuated electronic communication in cobalt complexes of meridional isoquinoline-derived ligands for applications in electrocatalysis.

The ability to synthetically tune the ligand frameworks of redox-active molecules is of critical importance to the economy of solar fuels because manipulating their redox properties can afford control over the operating potentials of sustained electrocatalytic or photoelectrocatalytic processes. The electronic and steric properties of 2,2':6',2″-terpyridine (Terpy) ligand frameworks can be tuned by functional group substitution on ligand backbones, and these correlate strongly to their Hammett parameters. The synthesis of a new series of tridentate meridional ligands of 2,4,6-trisubstituted pyridines that engineers the ability to finely tune the redox potentials of cobalt complexes to more positive potentials than that of their Terpy analogs is achieved by aryl-functionalizing at the four-position and by including isoquinoline at the two- and six-positions of pyridine (Aryl-DiQ). Their cobalt complex syntheses, their electronic properties, and their catalytic activity for carbon dioxide (CO2) reduction are reported and compared to their Terpy analogs. The cobalt derivatives generally experience a positive shift in their redox features relative to the Terpy-based analogs, covering a complementary potential range. Although those evaluated fail to produce any quantifiable products for the reduction of CO2 and suffer from long-term instability, these results suggest possible alternate strategies for stabilizing these compounds during catalysis. We speculate that lower equilibrium association constants to the cobalt center are intrinsic to these ligands, which originate from a steric interaction between protons on the pyridine and isoquinoline moieties. Nevertheless, the new Aryl-DiQ ligand framework has been engineered to selectively tune homoleptic cobalt complexes' redox potentials.

Primary and Specialist Palliative Care in Neurosurgery: A Narrative Review and Bibliometric Analysis of Glioblastoma and Stroke.

OBJECTIVE: Due to the increased demand for palliative care (PC) in recent years, a model has been proposed to divide PC into primary PC and specialist PC. This article aimed to delineate the indications for primary and specialist PC within 2 common neurosurgical conditions-glioblastoma (GBM) and stroke. METHODS: A systematic review and bibliometric analysis was conducted to better appreciate the practice trends in PC utilization for GBM and stroke patients using several databases. RESULTS: There were 70 studies on PC for GBM, the majority of which related to patient preference (22 [31%]). During 1999-2022, there was significant growth in publications per year on this topic at a rate of approximately 0.3 publications per year (P < 0.01). There were 44 studies on PC for stroke, the majority of which related to communication strategies (14 [32%]). During 1999-2022, there was no significant growth in stroke publications per year (P = 0.22). CONCLUSIONS: Due to the progressively disabling neurological course of GBM, we suggest that a specialty PC team be used in conjunction with the neurosurgical team early in the disease trajectory while patients are still able to communicate their preferences, goals, and values. In contrast, short-term and long-term stages of management of stroke have differing implications for PC needs, with the short-term stage necessitating adept, time-sensitive communication between the patient, family, and care teams. Thus, we propose that primary PC should be included as a core competency in neurosurgery training, among other stroke specialists.

Association of moyamoya vasculopathy with autoimmune disease: a systematic review and pooled analysis.

Despite more than six decades of extensive research, the etiology of moyamoya disease (MMD) remains unknown. Inflammatory or autoimmune (AI) processes have been suggested to instigate or exacerbate the condition, but the data remains mixed. The objective of the present systematic review was to summarize the available literature investigating the association of MMD and AI conditions as a means of highlighting potential treatment strategies for this subset of moyamoya patients. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the PubMed, Embase, Scopus, Web of Science, and Cochrane databases were queried to identify studies describing patients with concurrent diagnoses of MMD and AI disease. Data were extracted on patient demographics, clinical outcomes, and treatment. Stable or improved symptoms were considered favorable outcomes, while worsening symptoms and death were considered unfavorable. Quantitative pooled analysis was performed with individual patient-level data. Of 739 unique studies identified, 103 comprising 205 unique patients (80.2% female) were included in the pooled analysis. Most patients (75.8%) identified as Asian/Pacific Islanders, and the most commonly reported AI condition was Graves' disease (57.6%), with 55.9% of these patients presenting in a thyrotoxic state. Of the 148 patients who presented with stroke, 88.5% of cases (n = 131) were ischemic. Outcomes data was available in 152 cases. There were no significant baseline differences between patients treated with supportive therapy alone and those receiving targeted immunosuppressant therapy. Univariable logistic regression showed that surgery plus medical therapy was more likely than medical therapy alone to result in a favorable outcome. On subanalysis of operated patients, 94.1% of patients who underwent combined direct and indirect bypass reported favorable outcomes, relative to 76.2% of patients who underwent indirect bypass and 82% who underwent direct bypass (p < 0.05). On univariable analysis, the presence of multiple AI disorders was associated with worse outcomes relative to having a single AI disorder. Autoimmune diseases have been uncommonly reported in patients with MMD, but the presence of multiple AI comorbidities portends poorer prognosis. The addition of surgical intervention appears to improve outcomes and for patients deemed surgical candidates, combined direct and indirect bypass appears to offer better outcomes that direct or indirect bypass alone.

The utility of PET for detecting corticotropinomas in Cushing disease: a scoping review.

While magnetic resonance imaging (MRI) is the current standard imaging method for diagnosing and localizing corticotropinomas in Cushing disease, it can fail to detect adenomas in up to 40% of cases. Recently, positron emission tomography (PET) has shown promise as a diagnostic tool to detect pituitary adenomas in Cushing disease. We perform a scoping review to characterize the uses of PET in diagnosing Cushing disease, with a focus on describing the types of PET investigated and defining PET-positive disease. A scoping review was conducted following the PRISMA-ScR guidelines. Thirty-one studies fulfilled our inclusion criteria, consisting of 10 prospective studies, 8 retrospective studies, 11 case reports, and 2 illustrative cases with a total of 262 patients identified. The most commonly utilized PET modalities in prospective/retrospective studies were FDG PET (n = 5), MET PET (n = 5), 68 Ga-DOTATATE PET (n = 2), 13N-ammonia PET (n = 2), and 68 Ga-DOTA-CRH PET (n = 2). MRI positivity ranged from 13 to 100%, while PET positivity ranged from 36 to 100%. In MRI-negative disease, PET positivity ranged from 0 to 100%. Five studies reported the sensitivity and specificity of PET, which ranged from 36 to 100% and 50 to 100%, respectively. PET shows promise in detecting corticotropinomas in Cushing disease, including MRI-negative disease. MET PET has been highly investigated and has demonstrated excellent sensitivity and specificity. However, preliminary studies with FET PET and 68 Ga-DOTA-CRH PET show promise for achieving high sensitivity and specificity and warrant further investigation.

A Review of the Aquatic Environmental Transformations of Engineered Nanomaterials.

Once released into the environment, engineered nanomaterials (ENMs) undergo complex interactions and transformations that determine their fate, exposure concentration, form, and likely impact on biota. Transformations are physical, chemical, or biological changes that occur to the ENM or the ENM coating. Over time, these transformations have an impact on their behaviour and properties. The interactions and transformations of ENMs in the environment depend on their pristine physical and chemical characteristics and the environmental or biological compartment into which they are released. The uniqueness of each ENM property or lifecycle results in a great deal of complexity. Even small changes may have a significant impact on their potential transformations. This review outlines the key influences and outcomes of ENM evolution pathways in aquatic environments and provides an assessment of potential environmental transformations, focusing on key chemical, physical, and biological processes. By obtaining a comprehensive understanding of the potential environmental transformations that nanomaterials can undergo, more realistic models of their probable environmental behaviour and potential impact can be developed. This will, in turn, be crucial in supporting regulatory bodies in their efforts to develop environmental policy in the field of nanotechnology.

Response of planktonic microbial assemblages to disturbance in an urban sub-tropical estuary.

Microbes are sensitive indicators of estuarine processes because they respond rapidly to dynamic disturbance events. As most of the world's population lives in urban areas and climate change-related disturbance events are becoming more frequent, estuaries bounded by cities are experiencing increasing stressors, at the same time that their ecosystem services are required more than ever. Here, using a multidisciplinary approach, we determined the response of planktonic microbial assemblages in response to seasonality and a rainfall disturbance in an urban estuary bounded by Australia's largest city, Sydney. We used molecular barcoding (16S, 18S V4 rRNA) and microscopy-based identification to compare microbial assemblages at locations with differing characteristics and urbanisation histories. Across 142 samples, we identified 8,496 unique free-living bacterial zOTUs, 8,175 unique particle associated bacterial zOTUs, and 1,920 unique microbial eukaryotic zOTUs. Using microscopy, we identified only the top <10% abundant, larger eukaryotic taxa (>10 µm), however quantification was possible. The site with the greater history of anthropogenic impact showed a more even community of associated bacteria and eukaryotes, and a significant increase in dissolved inorganic nitrogen following rainfall, when compared to the more buffered site. This coincided with a reduced proportional abundance of Actinomarina and Synechococcus spp., a change in SAR 11 clades, and an increase in the eukaryotic microbial groups Dinophyceae, Mediophyceae and Bathyoccocaceae, including a temporary dominance of the harmful algal bloom dinoflagellate Prorocentrum cordatum (syn. P. minimum). Finally, a validated hydrodynamic model of the estuary supported these results, showing that the more highly urbanised and upstream location consistently experienced a higher magnitude of salinity reduction in response to rainfall events during the study period. The best abiotic variables to explain community dissimilarities between locations were TDP, PN, modelled temperature and salinity (r = 0.73) for the free living bacteria, TP for the associated bacteria (r = 0.43), and modelled temperature (r = 0.28) for the microbial eukaryotic communities. Overall, these results show that a minor disturbance such as a brief rainfall event can significantly shift the microbial assemblage of an anthropogenically impacted area within an urban estuary to a greater degree than a seasonal change, but may result in a lesser response to the same disturbance at a buffered, more oceanic influenced location. Fine scale research into the factors driving the response of microbial communities in urban estuaries to climate related disturbances will be necessary to understand and implement changes to maintain future estuarine ecosystem services.

Imaging of the meningeal lymphatic network in healthy adults: A 7T MRI study.

BACKGROUND AND PURPOSE: Meningeal lymphatic vessels (MLVs) along the dural venous sinuses are suspected to be important in connecting the glymphatic and peripheral lymphatic system. Understanding the topography of MLVs may clarify the role of the glymphatic system in neurological diseases. The aim of this analysis was to use high resolution pre- and post-contrast FLAIR 7T MRI to identify and characterize the morphology of MLV in a cohort of healthy volunteers. MATERIALS AND METHODS: MRI examinations of seventeen healthy volunteers enrolled as controls in a larger 7T MRI study were reviewed. Pre- and post-contrast 3-D FLAIR subtractions and MP2RAGE sequences were spatially normalized and reviewed for signal intensity and enhancement patterns within putative MLVs along pre-determined dural and venous structures. Frequency of occurrence of MLVs at the above-described locations and patterns of their enhancement were analyzed. RESULTS: Putative MLVs are commonly located along the superior sagittal sinus (SSS) and cortical veins. A "fixed enhancement" signal pattern was more frequent at these locations (p<.05). The morphology of MLVs along the SSS qualitatively changes in an antero-posterior direction. Lack of signal was more frequent along the straight and transverse sinuses (p<.05). CONCLUSION: Putative MLVs in healthy individuals are concentrated along the SSS and cortical veins. FLAIR signal and enhancement characteristics suggest these structures may transport proteinaceous fluid. Pathways connecting MLVs to cervical lymph nodes however remain unclear.