Variations in antimicrobial resistance genes present in the rectal faeces of seals in Scottish and Liverpool Bay coastal waters.

Antibiotic resistance genes originating from human activity are considered important environmental pollutants. Wildlife species can act as sentinels for coastal environmental contamination and in this study we used qPCR array technology to investigate the variety and abundance of antimicrobial resistance genes (ARGs), mobile genetic elements (MGEs) and integrons circulating within seal populations both near to and far from large human populations located around the Scottish and northwest English coast. Rectal swabs were taken from 50 live grey seals and nine live harbour seals. Nucleic acids were stabilised upon collection, enabling extraction of sufficient quality and quantity DNA for downstream analysis. 78 ARG targets, including genes of clinical significance, four MGE targets and three integron targets were used to monitor genes within 22 sample pools. 30 ARGs were detected, as well as the integrons intl1 and intl2 and tnpA transposase. Four ß-lactam, nine tetracycline, two phenicol, one trimethoprim, three aminoglycoside and ten multidrug resistance genes were detected as well as mcr-1 which confers resistance to colistin, an important drug of last resort. No sulphonamide, vancomycin, macrolide, lincosamide or streptogramin B (MLSB) resistance genes were detected. Resistance genes were detected in all sites but the highest number of ARGs (n = 29) was detected in samples derived from grey seals on the Isle of May, Scotland during the breeding season, and these genes also had the highest average abundance in relation to the 16S rRNA gene. This pilot study demonstrates the effectiveness of a culture-independent workflow for global analysis of ARGs within the microbiota of live, free-ranging, wild animals from habitats close to and remote from human habitation, and highlights seals as a valuable indicator species for monitoring the presence, abundance and land-sea transference of resistance genes within and between ecosystems.

Corrigendum: Staged use of ordinal and linear disability scales: a practical approach to granular assessment of acute stroke outcome.

[This corrects the article DOI: 10.3389/fneur.2023.1174686.].

MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial.

This multi-site, randomized, double-blind, confirmatory phase 3 study evaluated the efficacy and safety of 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) versus placebo with identical therapy in participants with moderate to severe post-traumatic stress disorder (PTSD). Changes in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score (primary endpoint) and Sheehan Disability Scale (SDS) functional impairment score (key secondary endpoint) were assessed by blinded independent assessors. Participants were randomized to MDMA-AT (n = 53) or placebo with therapy (n = 51). Overall, 26.9% (28/104) of participants had moderate PTSD, and 73.1% (76/104) of participants had severe PTSD. Participants were ethnoracially diverse: 28 of 104 (26.9%) identified as Hispanic/Latino, and 35 of 104 (33.7%) identified as other than White. Least squares (LS) mean change in CAPS-5 score (95% confidence interval (CI)) was -23.7 (-26.94, -20.44) for MDMA-AT versus -14.8 (-18.28, -11.28) for placebo with therapy (P < 0.001, d = 0.7). LS mean change in SDS score (95% CI) was -3.3 (-4.03, -2.60) for MDMA-AT versus -2.1 (-2.89, -1.33) for placebo with therapy (P = 0.03, d = 0.4). Seven participants had a severe treatment emergent adverse event (TEAE) (MDMA-AT, n = 5 (9.4%); placebo with therapy, n = 2 (3.9%)). There were no deaths or serious TEAEs. These data suggest that MDMA-AT reduced PTSD symptoms and functional impairment in a diverse population with moderate to severe PTSD and was generally well tolerated. ClinicalTrials.gov identifier: NCT04077437 .

Large-scale optical characterization of solid-state quantum emitters.

Solid-state quantum emitters have emerged as a leading quantum memory for quantum networking applications. However, standard optical characterization techniques are neither efficient nor repeatable at scale. Here we introduce and demonstrate spectroscopic techniques that enable large-scale, automated characterization of colour centres. We first demonstrate the ability to track colour centres by registering them to a fabricated machine-readable global coordinate system, enabling a systematic comparison of the same colour centre sites over many experiments. We then implement resonant photoluminescence excitation in a widefield cryogenic microscope to parallelize resonant spectroscopy, achieving two orders of magnitude speed-up over confocal microscopy. Finally, we demonstrate automated chip-scale characterization of colour centres and devices at room temperature, imaging thousands of microscope fields of view. These tools will enable the accelerated identification of useful quantum emitters at chip scale, enabling advances in scaling up colour centre platforms for quantum information applications, materials science and device design and characterization.

Modified Rankin Scale Disability Status at Day 4 Poststroke is an Informative Predictor of Long-Term Day 90 Outcome.

Background: Long-term disability after stroke is standardly assessed 3 months post-onset, using the modified Rankin Scale (mRS). The value of an early, day 4 mRS assessment for projecting the 3-month disability outcome has not been formally investigated. Methods: In this cohort of patients with acute cerebral ischemia and intracranial hemorrhage, we analyzed day 4 and day 90 mRS assessments in the NIH Field Administration of Stroke Therapy- Magnesium (FAST-MAG) Phase 3 trial. The performance of day 4 mRS, alone and as part of multivariate models, in predicting day 90 mRS was assessed using correlation coefficients, percent agreement, and the kappa statistics. Results: Among the 1573 acute cerebrovascular disease (ACVD) patients, 1206 (76.7%) had acute cerebral ischemia (ACI), while 367 (23.3%) had intracranial hemorrhage. Among all 1573 ACVD patients, day 4 mRS and day 90 mRS correlated strongly, Spearman's rho=0.79, in unadjusted analysis with weighted kappa of 0.59. For dichotomized outcomes, simple carry-forward of the day 4 mRS performed fairly well in agreeing with day 90 mRS: mRS 0-1 (k=0.67), 85.4%; mRS 0-2 (k=0.59), 79.5%; fatal outcome, 88.3% (k=0.33). Correlations of 4d and 90d mRS were stronger for ACI than ICH patients, 0.76 vs 0.71. Conclusions: In this acute cerebrovascular disease patient cohort, assessment of global disability performed on day 4 is highly informative regarding long-term, 3-month mRS disability outcome, alone, and even more strongly in combination with baseline prognostic variables. The day 4 mRS is a useful measure for imputing the final patient disability outcome in clinical trials and quality improvement programs.

A marine protected area network does not confer community structure resilience to a marine heatwave across coastal ecosystems.

Marine protected areas (MPAs) have gained attention as a conservation tool for enhancing ecosystem resilience to climate change. However, empirical evidence explicitly linking MPAs to enhanced ecological resilience is limited and mixed. To better understand whether MPAs can buffer climate impacts, we tested the resistance and recovery of marine communities to the 2014-2016 Northeast Pacific heatwave in the largest scientifically designed MPA network in the world off the coast of California, United States. The network consists of 124 MPAs (48 no-take state marine reserves, and 76 partial-take or special regulation conservation areas) implemented at different times, with full implementation completed in 2012. We compared fish, benthic invertebrate, and macroalgal community structure inside and outside of 13 no-take MPAs across rocky intertidal, kelp forest, shallow reef, and deep reef nearshore habitats in California's Central Coast region from 2007 to 2020. We also explored whether MPA features, including age, size, depth, proportion rock, historic fishing pressure, habitat diversity and richness, connectivity, and fish biomass response ratios (proxy for ecological performance), conferred climate resilience for kelp forest and rocky intertidal habitats spanning 28 MPAs across the full network. Ecological communities dramatically shifted due to the marine heatwave across all four nearshore habitats, and MPAs did not facilitate habitat-wide resistance or recovery. Only in protected rocky intertidal habitats did community structure significantly resist marine heatwave impacts. Community shifts were associated with a pronounced decline in the relative proportion of cold water species and an increase in warm water species. MPA features did not explain resistance or recovery to the marine heatwave. Collectively, our findings suggest that MPAs have limited ability to mitigate the impacts of marine heatwaves on community structure. Given that mechanisms of resilience to climate perturbations are complex, there is a clear need to expand assessments of ecosystem-wide consequences resulting from acute climate-driven perturbations, and the potential role of regulatory protection in mitigating community structure changes.

Staged use of ordinal and linear disability scales: a practical approach to granular assessment of acute stroke outcome.

Background: The modified Rankin Scale (mRS) assessment of global disability is the most common primary endpoint in acute stroke trials but lacks granularity (7 broad levels) and is ordinal (scale levels unknown distances apart), which constrains study power. Disability scales that are linear and continuous may better discriminate outcomes, but computerized administration in stroke patients is challenging. We, therefore, undertook to develop a staged use of an ordinal followed by a linear scale practical to use in multicenter trials. Methods: Consecutive patients undergoing 3-month final visits in the NIH FAST-MAG phase 3 trial were assessed with the mRS followed by 15 mRS level-specific yes-no items of the Academic Medical Center Linear Disability Score (ALDS), a linear disability scale derived using item response theory. Results: Among 55 patients, aged 71.2 (SD ± 14.2), 67% were men and the entry NIHSS was 10.7 (SD ± 9.5). At 90 days, the median mRS score was 3 (IQR, 1-4), and the median ALDS score was 78.8 (IQR, 3.3-100). ALDS scores correlated strongly with 90 days outcome measures, including the Barthel Index (r = 0.92), NIHSS (r = 0.87), and mRS (r = 0.94). ALDS scores also correlated modestly with entry NIHSS (r = 0.38). At 90 days, the ALDS showed greater scale granularity than the mRS, with fewer patients with identical values, 1.9 (SD ± 3.2) vs. 8.0 (SD ± 3.6), p < 0.001. When treatment effect magnitudes were small to moderate, projected trial sample size requirements were 2-12-fold lower when the ALDS rather than the mRS was used as the primary trial endpoint. Conclusion: Among patients enrolled in an acute neuroprotective stroke trial, the ALDS showed strong convergent validity and superior discrimination characteristics compared with the modified Rankin Scale and increased projected trial power to detect clinically meaningful treatment benefits.

MDMA-Assisted Therapy for Severe PTSD: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study.

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was -24.4 (s.d. 11.6) in the MDMA group and -13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation. Appeared originally in Nat Med 2021; 27:1025-1033.

Essential information for neurorecovery clinical trial design: trajectory of global disability in first 90 days post-stroke in patients discharged to acute rehabilitation facilities.

BACKGROUND: Many stroke recovery interventions are most beneficial when started 2-14d post-stroke, a time when patients become eligible for inpatient rehabilitation facilities (IRF) and neuroplasticity is often at its peak. Clinical trials focused on recovery need to expand the time from this plasticity to later outcome timepoints. METHODS: The disability course of patients with acute ischemic stroke (AIS) and intracranial hemorrhage (ICH) enrolled in Field Administration of Stroke Therapy Magnesium (FAST-MAG) Trial with moderate-severe disability (modified Rankin Scale [mRS] 3-5) on post-stroke day4 who were discharged to IRF 2-14d post-stroke were analyzed. RESULTS: Among 1422 patients, 446 (31.4%) were discharged to IRFs, including 23.6% within 2-14d and 7.8% beyond 14d. Patients with mRS 3-5 on day4 discharged to IRFs between 2-14d accounted for 21.7% (226/1041) of AIS patients and 28.9% (110/381) of ICH patients, (p < 0.001). Among these AIS patients, age was 69.8 (± 12.7), initial NIHSS median 8 (IQR 4-12), and day4 mRS = 3 in 16.4%, mRS = 4 in 50.0%, and mRS = 5 in 33.6%. Among these ICH patients, age was 62.4 (± 11.7), initial NIHSS median 9 (IQR 5-13), day 4 mRS = 3 in 9.4%, mRS = 4 in 45.3%, and mRS = 5 in 45.3% (p < 0.01 for AIS vs ICH). Between day4 to day90, mRS improved ≥ 1 levels in 72.6% of AIS patients vs 77.3% of ICH patients, p = 0.3. For AIS, mRS improved from mean 4.17 (± 0.7) to 2.84 (± 1.5); for ICH, mRS improved from mean 4.35 (± 0.7) to 2.75 (± 1.3). Patients discharged to IRF beyond day14 had less improvement on day90 mRS compared with patients discharged between 2-14d. CONCLUSIONS: In this acute stroke cohort, nearly 1 in 4 patients with moderate-severe disability on post-stroke day4 were transferred to IRF within 2-14d post-stroke. ICH patients had nominally greater mean improvement on mRS day90 than AIS patients. This course delineation provides a roadmap for future rehabilitation intervention studies.

Neurologic Improvement in Acute Cerebral Ischemia: Frequency, Magnitude, Predictors, and Clinical Outcomes.

BACKGROUND AND OBJECTIVES: Investigations of rapid neurologic improvement (RNI) in patients with acute cerebral ischemia (ACI) have focused on RNI occurring after hospital arrival. However, with stroke routing decisions and interventions increasingly migrating to the prehospital setting, there is a need to delineate the frequency, magnitude, predictors, and clinical outcomes of patients with ACI with ultra-early RNI (U-RNI) in the prehospital and early postarrival period. METHODS: We analyzed prospectively collected data of the prehospital Field Administration of Stroke Therapy-Magnesium (FAST-MAG) randomized clinical trial. Any U-RNI was defined as improvement by 2 or more points on the Los Angeles Motor Scale (LAMS) score between the prehospital and early post-emergency department (ED) arrival examinations and classified as moderate (2-3 point) or dramatic (4-5 point) improvement. Outcome measures included excellent recovery (modified Rankin Scale [mRS] score 0-1) and death by 90 days. RESULTS: Among the 1,245 patients with ACI, the mean age was 70.9 years (SD 13.2); 45% were women; the median prehospital LAMS was 4 (interquartile range [IQR] 3-5); the median last known well to ED-LAMS time was 59 minutes (IQR 46-80 minutes), and the median prehospital LAMS to ED-LAMS time was 33 minutes (IQR 28-39 minutes). Overall, any U-RNI occurred in 31%, moderate U-RNI in 23%, and dramatic U-RNI in 8%. Any U-RNI was associated with improved outcomes, including excellent recovery (mRS score 0-1) at 90 days 65.1% (246/378) vs 35.4% (302/852), p < 0.0001; decreased mortality by 90 days 3.7% (14/378) vs 16.4% (140/852), p < 0.0001; decreased symptomatic intracranial hemorrhage 1.6% (6/384) vs 4.6% (40/861), p = 0.0112; and increased likelihood of being discharged home 56.8% (218/384) vs 30.2% (260/861), p < 0.0001. DISCUSSION: U-RNI occurs in nearly 1 in 3 ambulance-transported patients with ACI and is associated with excellent recovery and decreased mortality at 90 days. Accounting for U-RNI may be useful for routing decisions and future prehospital interventions. TRIAL REGISTRATION INFORMATION: clinicaltrials.gov. Unique identifier: NCT00059332.

Marine protected areas, marine heatwaves, and the resilience of nearshore fish communities.

Anthropogenic stressors from climate change can affect individual species, community structure, and ecosystem function. Marine heatwaves (MHWs) are intense thermal anomalies where water temperature is significantly elevated for five or more days. Climate projections suggest an increase in the frequency and severity of MHWs in the coming decades. While there is evidence that marine protected areas (MPAs) may be able to buffer individual species from climate impacts, there is not sufficient evidence to support the idea that MPAs can mitigate large-scale changes in marine communities in response to MHWs. California experienced an intense MHW and subsequent El Niño Southern Oscillation event from 2014 to 2016. We sought to examine changes in rocky reef fish communities at four MPAs and associated reference sites in relation to the MHW. We observed a decline in taxonomic diversity and a profound shift in trophic diversity inside and outside MPAs following the MHW. However, MPAs seemed to dampen the loss of trophic diversity and in the four years following the MHW, taxonomic diversity recovered 75% faster in the MPAs compared to reference sites. Our results suggest that MPAs may contribute to long-term resilience of nearshore fish communities through both resistance to change and recovery from warming events.

Effect of Magnesium on Deterioration and Symptomatic Hemorrhagic Transformation in Cerebral Ischemia: An Ancillary Analysis of the FAST-MAG Trial.

BACKGROUND: Magnesium (Mg) is a neuroprotectant in preclinical models. Lower serum Mg levels have been associated with symptomatic hemorrhagic transformation (HT) in patients with ischemic stroke. Early treatment of acute ischemic stroke with Mg may reduce rates of symptomatic HT. METHODS: In this post hoc study of the Field Administration of Stroke Therapy Magnesium (FAST-MAG) trial, 1,245 participants with a diagnosis of cerebral ischemia received 20 g of Mg or placebo initiated in the prehospital setting. Posttreatment serum Mg level was measured for 809 participants. Cases of clinical deterioration, defined as worsening by ≥4 points on the National Institute of Health Stroke Scale (NIHSS), were imaged and evaluated for etiology. Symptomatic HT was defined as deterioration with imaging showing new hemorrhage. RESULTS: Clinical deterioration occurred in 187 and symptomatic HT in 46 of 1,245 cases of cerebral ischemia. Rates of deterioration and symptomatic HT were not significantly lower in those who received Mg (15.7% vs. 14.4%, p = 0.591; 2.8% vs. 4.6%, p = 0.281). In cases where serum Mg level was obtained posttreatment, lower serum Mg level (<1.7 mg/dL) was associated with significantly higher rates of deterioration and symptomatic HT (27.5% vs. 15.5%, p = 0.0261; 11.6% vs. 3.65%, p = 0.00819). CONCLUSIONS: Treatment with Mg did not significantly reduce rates of clinical deterioration or symptomatic HT. Future analysis should address whether treatment with Mg could have influenced the subgroup with low serum Mg at baseline.

Association Between Hyperacute Blood Pressure Variability and Hematoma Expansion After Intracerebral Hemorrhage: Secondary Analysis of the FAST-MAG Database.

BACKGROUND: Blood pressure variability (BPV) has emerged as a significant factor associated with clinical outcomes after intracerebral hemorrhage (ICH). Although hematoma expansion (HE) is associated with clinical outcomes, the relationship between BPV that encompasses prehospital data and HE is unknown. We hypothesized that BPV was positively associated with HE. METHODS: We analyzed 268 patients with primary ICH enrolled in the National Institutes of Health-funded Field Administration of Stroke Therapy-Magnesium (FAST-MAG) study who received head computed tomography or magnetic resonance imaging on arrival to the emergency department (ED) and repeat imaging within 6-48 h. BPV was calculated by standard deviation (SD) and coefficient of variation (CV) from prehospital data as well as systolic blood pressure (SBP) measurements taken on ED arrival, 15 min post antihypertensive infusion start, 1 h post maintenance infusion start, and 4 h after ED arrival. HE was defined by hematoma volume expansion increase > 6 mL or by 33%. Univariate logistic regression was used for presence of HE in quintiles of SD and CV of SBP for demographics and clinical characteristics. RESULTS: Of the 268 patients analyzed from the FAST-MAG study, 116 (43%) had HE. Proportions of patients with HE were not statistically significant in the higher quintiles of the SD and CV of SBP for either the hyperacute or the acute period. Presence of HE was significantly more common in patients on anticoagulation. CONCLUSIONS: Higher BPV was not found to be associated with occurrence of HE in the hyperacute or the acute period of spontaneous ICH. Further study is needed to determine the relationship.

Delocalized photonic deep learning on the internet's edge.

Advanced machine learning models are currently impossible to run on edge devices such as smart sensors and unmanned aerial vehicles owing to constraints on power, processing, and memory. We introduce an approach to machine learning inference based on delocalized analog processing across networks. In this approach, named Netcast, cloud-based "smart transceivers" stream weight data to edge devices, enabling ultraefficient photonic inference. We demonstrate image recognition at ultralow optical energy of 40 attojoules per multiply (<1 photon per multiply) at 98.8% (93%) classification accuracy. We reproduce this performance in a Boston-area field trial over 86 kilometers of deployed optical fiber, wavelength multiplexed over 3 terahertz of optical bandwidth. Netcast allows milliwatt-class edge devices with minimal memory and processing to compute at teraFLOPS rates reserved for high-power (>100 watts) cloud computers.

Consequences of Warming and Acidification for the Temperate Articulated Coralline Alga, Calliarthron Tuberculosum (Florideophyceae, Rhodophyta).

Global climate changes, such as warming and ocean acidification (OA), are likely to negatively impact calcifying marine taxa. Abundant and ecologically important coralline algae may be particularly susceptible to OA; however, multi-stressor studies and those on articulated morphotypes are lacking. Here, we use field observations and laboratory experiments to elucidate the impacts of warming and acidification on growth, calcification, mineralogy, and photophysiology of the temperate articulated coralline alga, Calliarthron tuberculosum. We conducted a 4-week fully factorial mesocosm experiment exposing individuals from a southern CA kelp forest to current and future temperature and pH/pCO2 conditions (+2°C, -0.5 pH units). Calcification was reduced under warming (70%) and further reduced by high pCO2 or high pCO2 x warming (~150%). Growth (change in linear extension and surface area) was reduced by warming (40% and 50%, respectively), high pCO2 (20% and 40%, respectively), and high pCO2 x warming (50% and 75%, respectively). The maximum photosynthetic rate (Pmax ) increased by 100% under high pCO2 conditions, but we did not detect an effect of pCO2 or warming on photosynthetic efficiency (α). We also did not detect the effect of warming or pCO2 on mineralogy. However, variation in Mg incorporation in cell walls of different cell types (i.e., higher mol % Mg in cortical vs. medullary) was documented for the first time in this species. These results support findings from a growing body of literature suggesting that coralline algae are often more negatively impacted by warming than OA, with the potential for antagonistic effects when factors are combined.

Beyond the Golden Hour: Treating Acute Stroke in the Platinum 30 Minutes.

BACKGROUND: To emphasize treatment speed for time-sensitive conditions, emergency medicine has developed not only the concept of the golden hour, but also the platinum half-hour. Patients with acute stroke treated within the first half-hour of onset have not been previously characterized. METHODS: In this cohort study, we analyzed patients enrolled in the FAST-MAG (Field Administration of Stroke Therapy-Magnesium) trial, testing paramedic prehospital start of neuroprotective agent ≤2 hours of onset. The features of all acute cerebral ischemia, and intracranial hemorrhage patients with treatment starting at ≤30 m of last known well were compared with later-treated patients. RESULTS: Among 1680 patients, 203 (12.1%) received study agents within 30 minutes of last known well. Among platinum half-hour patients, median onset-to-treatment time was 28 minutes (interquartile range, 25-30), and final diagnoses were acute cerebral ischemia in 71.8% (ischemic stroke, 61.5%, TIA 10.3%); intracranial hemorrhage in 26.1%; and mimic in 2.5%. Clinical features among platinum half-hour patients were largely similar to later-treated patients and included age 69 (interquartile range, 57-79), 44.8% women, prehospital Los Angeles Motor Scale median 4 (3-5), and early-postarrival National Institutes of Health Stroke Scale deficit 8 (interquartile range, 3-18). Platinum half-hour acute cerebral ischemia patients did have more severe prehospital motor deficits and younger age; platinum half-hour intracranial hemorrhage patients had more severe motor deficits, were more often female, and less often of Hispanic ethnicity. Outcomes at 3 m in platinum half-hour patients were comparable to later-treated patients and included freedom-from-disability (modified Rankin Scale score, 0-1) in 35.5%, functional independence (modified Rankin Scale score, 0-2) in 53.2%, and mortality in 17.7%. CONCLUSIONS: Prehospital initiation permits treatment start within the platinum half-hour after last known well in a substantial proportion of acute ischemic and hemorrhagic stroke patients, accounting for more than 1 in 10 enrolled in a multicenter trial. Hyperacute platinum half-hour patients were largely similar to later-treated patients and are an attainable target for treatment in prehospital stroke trials.

Magnesium Sulfate and Hematoma Expansion: An Ancillary Analysis of the FAST-MAG Randomized Trial.

BACKGROUND: Intracerebral hemorrhage (ICH) is the deadliest form of stroke. In observational studies, lower serum magnesium has been linked to more hematoma expansion (HE) and intracranial hemorrhage, implying that supplemental magnesium sulfate is a potential acute treatment for patients with ICH and could reduce HE. FAST-MAG (Field Administration of Stroke Therapy - Magnesium) was a clinical trial of magnesium sulfate started prehospital in patients with acute stroke within 2 hours of last known well enrolled. CT was not required prior to enrollment, and several hundred patients with acute ICH were enrolled. In this ancillary analysis, we assessed the effect of magnesium sulfate treatment upon HE in patients with acute ICH. METHODS: We retrospectively analyzed data that were prospectively collected in the FAST-MAG study. Patients received intravenous magnesium sulfate or matched placebo within 2 hours of onset. We compared HE among patients allocated to intravenous magnesium sulfate or placebo with a Mann-Whitney U. We used the same method to compare neurological deficit severity (National Institutes of Health Stroke Scale) and global disability (modified Rankin Scale) at 3 months. RESULTS: Among 268 patients with ICH meeting study entry criteria, mean 65.4±13/4 years, 33% were female, and 211 (79%) had a history of hypertension. Initial deficit severities were median (interquartile range) of 4 (3-5) on the Los Angeles Motor Scale in the field and National Institutes of Health Stroke Scale score of 16 (9.5-25.5) early after hospital arrival. Follow-up brain imaging was performed a median of 17.1 (11.3-22.7) hours after first scan. The magnesium and placebo groups did not statistically differ in hematoma volume on arrival, 10.1 (5.6-28.7) versus 12.4 (5.6-28.7) mL (P=0.6), or HE, 2.0 (0.1-7.4) versus 1.5 (-0.2 to 8) mL (P=0.5). There was no difference in functional outcomes (modified Rankin Scale score of 3-6), 59% versus 50% (P=0.5). CONCLUSIONS: Magnesium sulfate did not reduce HE or improve functional outcomes at 90 days. A benefit for patients with initial hypomagnesemia was not addressed. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT00059332.

Coupled changes in pH, temperature, and dissolved oxygen impact the physiology and ecology of herbivorous kelp forest grazers.

Understanding species' responses to upwelling may be especially important in light of ongoing environmental change. Upwelling frequency and intensity are expected to increase in the future, while ocean acidification and deoxygenation are expected to decrease the pH and dissolved oxygen (DO) of upwelled waters. However, the acute effects of a single upwelling event and the integrated effects of multiple upwelling events on marine organisms are poorly understood. Here, we use in situ measurements of pH, temperature, and DO to characterize the covariance of environmental conditions within upwelling-dominated kelp forest ecosystems. We then test the effects of acute (0-3 days) and chronic (1-3 months) upwelling on the performance of two species of kelp forest grazers, the echinoderm, Mesocentrotus franciscanus, and the gastropod, Promartynia pulligo. We exposed organisms to static conditions in a regression design to determine the shape of the relationship between upwelling and performance and provide insights into the potential effects in a variable environment. We found that respiration, grazing, growth, and net calcification decline linearly with increasing upwelling intensity for M. francicanus over both acute and chronic timescales. Promartynia pulligo exhibited decreased respiration, grazing, and net calcification with increased upwelling intensity after chronic exposure, but we did not detect an effect over acute timescales or on growth after chronic exposure. Given the highly correlated nature of pH, temperature, and DO in the California Current, our results suggest the relationship between upwelling intensity and growth in the 3-month trial could potentially be used to estimate growth integrated over long-term dynamic oceanographic conditions for M. franciscanus. Together, these results indicate current exposure to upwelling may reduce species performance and predicted future increases in upwelling frequency and intensity could affect ecosystem function by modifying the ecological roles of key species.

National Institutes of Health Stroke Scale Correlates Well with Initial Intracerebral Hemorrhage Volume.

OBJECTIVES: The US Centers for Medicare and Medicaid Services (CMS) currently publicly reports hospital-quality, risk-adjusted mortality measure for ischemic stroke but not intracerebral hemorrhage (ICH). The NIHSS, which is captured in CMS administrative claims data, is a candidate metric for use in ICH risk adjustment and has been shown to predict clinical outcome with accuracy similar to the ICH Score. Correlation between early NIHSS and initial ICH volume would further support use of the NIHSS for ICH risk adjustment. MATERIALS AND METHODS: Among 372 ICH patients enrolled in a large multicenter trial (FAST-MAG), the relation between early NIHSS and early ICH volume was assessed with correlation and linear trend analysis. RESULTS: Overall, there was strong correlation between NIHSS and ICH volume, r = 0.77 (p < 0.001), and for every 10cc increase in ICH the NIHSS increased by 4.5 points. Correlation coefficients were comparable in all subgroups, but magnitude of NIHSS increase with ICH unit volume increase was greater with left than right hemispheric ICH, with presence rather than absence of IVH, with imaging done within the first hour than second hour after last known well, with men than women, and with younger than older patients. CONCLUSION: Early NIHSS neurologic deficit severity values correlate strongly with initial ICH hematoma volume. As with ischemic stroke, lesion volume increases produce greater NIHSS change in the left than right hemisphere, reflecting greater NIHSS sensitivity to left hemisphere function. These findings provide further support for the use of NIHSS in risk-adjusted mortality measures for intracerebral hemorrhage.

Diffuse Axonal Injury Grade on Early MRI is Associated with Worse Outcome in Children with Moderate-Severe Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) is the leading cause of death and disability in children, but effective tools for predicting outcome remain elusive. Although many pediatric patients receive early magnetic resonance imaging (MRI), data on its utility in prognostication are lacking. Diffuse axonal injury (DAI) is a hallmark of TBI detected on early MRI and was shown previously to improve prognostication in adult patients with TBI. In this exploratory study, we investigated whether DAI grade correlates with functional outcome and improves prognostic accuracy when combined with core clinical variables and computed tomography (CT) biomarkers in pediatric patients with moderate-severe TBI (msTBI). METHODS: Pediatric patients (≤ 19 years) who were admitted to two regional level one trauma centers with a diagnosis of msTBI (Glasgow Coma Scale [GCS] score < 13) between 2011 and 2019 were identified through retrospective chart review. Patients who underwent brain MRI within 30 days of injury and had documented clinical follow-up after discharge were included. Age, pupil reactivity, and initial motor GCS score were collected as part of the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model. Imaging was reviewed to calculate the Rotterdam score (CT) and DAI grade (MRI) and to evaluate for presence of hypoxic-ischemic injury (MRI). The primary outcome measure was the Pediatric Cerebral Performance Category Scale (PCPCS) score at 6 months after TBI, with favorable outcome defined as PCPCS scores 1-3 and unfavorable outcome defined as PCPCS scores 4-6. The secondary outcome measure was discharge disposition to home versus to an inpatient rehabilitation facility. RESULT: Of 55 patients included in the study, 45 (82%) had severe TBI. The most common mechanism of injury was motor vehicle collision (71%). Initial head CT scans showed acute hemorrhage in 84% of patients. MRI was acquired a median of 5 days after injury, and hemorrhagic DAI lesions were detected in 87% of patients. Each 1-point increase in DAI grade increased the odds of unfavorable functional outcome by 2.4-fold. When controlling for core IMPACT clinical variables, neither the DAI grade nor the Rotterdam score was independently correlated with outcome and neither significantly improved outcome prediction over the IMPACT model alone. CONCLUSIONS: A higher DAI grade on early MRI is associated with worse 6-month functional outcome and with discharge to inpatient rehabilitation in children with acute msTBI in a univariate analysis but does not independently correlate with outcome when controlling for the GCS score. Addition of the DAI grade to the core IMPACT model does not significantly improve prediction of poor neurological outcome. Further study is needed to elucidate the utility of early MRI in children with msTBI.