Ecological and anthropogenic drivers of waterfowl productivity are synchronous across species, space, and time.

Knowledge of interspecific and spatiotemporal variation in demography-environment relationships is key for understanding the population dynamics of sympatric species and developing multispecies conservation strategies. We used hierarchical random-effects models to examine interspecific and spatial variation in annual productivity in six migratory ducks (i.e., American wigeon [Mareca americana], blue-winged teal [Spatula discors], gadwall [Mareca strepera], green-winged teal [Anas crecca], mallard [Anas platyrhynchos] and northern pintail [Anas acuta]) across six distinct ecostrata in the Prairie Pothole Region of North America. We tested whether breeding habitat conditions (seasonal pond counts, agricultural intensification, and grassland acreage) or cross-seasonal effects (indexed by flooded rice acreage in primary wintering areas) better explained variation in the proportion of juveniles captured during late summer banding. The proportion of juveniles (i.e., productivity) was highly variable within species and ecostrata throughout 1961-2019 and generally declined through time in blue-winged teal, gadwall, mallard, pintail, and wigeon, but there was no support for a trend in green-winged teal. Productivity in Canadian ecostrata declined with increasing agricultural intensification and increased with increasing pond counts. We also found a strong cross-seasonal effect, whereby more flooded rice hectares during winter resulted in higher subsequent productivity. Our results suggest highly consistent environmental and anthropogenic effects on waterfowl productivity across species and space. Our study advances our understanding of current year and cross-seasonal effects on duck productivity across a suite of species and at finer spatial scales, which could help managers better target working-lands conservation programs on both breeding and wintering areas. We encourage other researchers to evaluate environmental drivers of population dynamics among species in a single modeling framework for a deeper understanding of whether conservation plans should be generalized or customized given limited financial resources.

Endovascular thrombectomy plus medical care versus medical care alone for large ischaemic stroke: 1-year outcomes of the SELECT2 trial.

BACKGROUND: Multiple randomised trials have shown efficacy and safety of endovascular thrombectomy in patients with large ischaemic stroke. The aim of this study was to evaluate long-term (ie, at 1 year) evidence of benefit of thrombectomy for these patients. METHODS: SELECT2 was a phase 3, open-label, international, randomised controlled trial with blinded endpoint assessment, conducted at 31 hospitals in the USA, Canada, Spain, Switzerland, Australia, and New Zealand. Patients aged 18-85 years with ischaemic stroke due to proximal occlusion of the internal carotid artery or of the first segment of the middle cerebral artery, showing large ischaemic core on non-contrast CT (Alberta Stroke Program Early Computed Tomographic Score of 3-5 [range 0-10, with lower values indicating larger infarctions]) or measuring 50 mL or more on CT perfusion and MRI, were randomly assigned, within 24 h of ischaemic stroke onset, to thrombectomy plus medical care or to medical care alone. The primary outcome for this analysis was the ordinal modified Rankin Scale (range 0-6, with higher scores indicating greater disability) at 1-year follow-up in an intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT03876457) and is completed. FINDINGS: The trial was terminated early for efficacy at the 90-day follow-up after 352 patients had been randomly assigned (178 to thrombectomy and 174 to medical care only) between Oct 11, 2019, and Sept 9, 2022. Thrombectomy significantly improved the 1-year modified Rankin Scale score distribution versus medical care alone (Wilcoxon-Mann-Whitney probability of superiority 0·59 [95% CI 0·53-0·64]; p=0·0019; generalised odds ratio 1·43 [95% CI 1·14-1·78]). At the 1-year follow-up, 77 (45%) of 170 patients receiving thrombectomy had died, compared with 83 (52%) of 159 patients receiving medical care only (1-year mortality relative risk 0·89 [95% CI 0·71-1·11]). INTERPRETATION: In patients with ischaemic stroke due to a proximal occlusion and large core, thrombectomy plus medical care provided a significant functional outcome benefit compared with medical care alone at 1-year follow-up. FUNDING: Stryker Neurovascular.

Endovascular Thrombectomy Treatment Effect in Direct vs Transferred Patients With Large Ischemic Strokes: A Prespecified Analysis of the SELECT2 Trial.

Importance: Patients with large ischemic core stroke have poor clinical outcomes and are frequently not considered for interfacility transfer for endovascular thrombectomy (EVT). Objective: To assess EVT treatment effects in transferred vs directly presenting patients and to evaluate the association between transfer times and neuroimaging changes with EVT clinical outcomes. Design, Setting, and Participants: This prespecified secondary analysis of the SELECT2 trial, which evaluated EVT vs medical management (MM) in patients with large ischemic stroke, evaluated adults aged 18 to 85 years with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) as well as an Alberta Stroke Program Early CT Score (ASPECTS) of 3 to 5, core of 50 mL or greater on imaging, or both. Patients were enrolled between October 2019 and September 2022 from 31 EVT-capable centers in the US, Canada, Europe, Australia, and New Zealand. Data were analyzed from August 2023 to January 2024. Interventions: EVT vs MM. Main Outcomes and Measures: Functional outcome, defined as modified Rankin Scale (mRS) score at 90 days with blinded adjudication. Results: A total of 958 patients were screened and 606 patients were excluded. Of 352 enrolled patients, 145 (41.2%) were female, and the median (IQR) age was 66.5 (58-75) years. A total of 211 patients (59.9%) were transfers, while 141 (40.1%) presented directly. The median (IQR) transfer time was 178 (136-230) minutes. The median (IQR) ASPECTS decreased from the referring hospital (5 [4-7]) to an EVT-capable center (4 [3-5]). Thrombectomy treatment effect was observed in both directly presenting patients (adjusted generalized odds ratio [OR], 2.01; 95% CI, 1.42-2.86) and transferred patients (adjusted generalized OR, 1.50; 95% CI, 1.11-2.03) without heterogeneity (P for interaction = .14). Treatment effect point estimates favored EVT among 82 transferred patients with a referral hospital ASPECTS of 5 or less (44 received EVT; adjusted generalized OR, 1.52; 95% CI, 0.89-2.58). ASPECTS loss was associated with numerically worse EVT outcomes (adjusted generalized OR per 1-ASPECTS point loss, 0.89; 95% CI, 0.77-1.02). EVT treatment effect estimates were lower in patients with transfer times of 3 hours or more (adjusted generalized OR, 1.15; 95% CI, 0.73-1.80). Conclusions and Relevance: Both directly presenting and transferred patients with large ischemic stroke in the SELECT2 trial benefited from EVT, including those with low ASPECTS at referring hospitals. However, the association of EVT with better functional outcomes was numerically better in patients presenting directly to EVT-capable centers. Prolonged transfer times and evolution of ischemic change were associated with worse EVT outcomes. These findings emphasize the need for rapid identification of patients suitable for transfer and expedited transport. Trial Registration: ClinicalTrials.gov Identifier: NCT03876457.

Endovascular intervention for the treatment of epistaxis: cone beam CT review of anatomy, collateral, and treatment implications/efficacy.

Epistaxis is common, impacting more than half the population, and can require procedural intervention in approximately 10% of cases. With an aging population and increasing use of antiplatelets and anticoagulants, severe epistaxis is likely to increase in frequency significantly over the next two decades. Sphenopalatine artery embolization is rapidly becoming the most common type of procedural intervention. The efficacy of endovascular embolization is dependent on a refined understanding of the anatomy and collateral physiology of this circulation as well as the impact of temporizing measures such as nasal packing and inflation of a nasal balloon. Likewise, safety is dependent on a detailed appreciation of collateralization with the internal carotid artery and ophthalmic artery. Cone beam CT imaging has the resolution to enable a clear visualization of the anatomy and collateral circulation associated with the arterial supply to the nasal cavity, in addition to assisting with hemorrhage localization. We present a review of epistaxis treatment, a detailed description of anatomic and physiologic considerations informed by cone beam CT imaging, and a proposed protocol for sphenopalatine embolization for which there is currently no standard.

A surfactant-based dressing can reduce the appearance of Pseudomonas aeruginosa pigments and uncover the dermal extracellular matrix in an ex vivo porcine skin wound model.

From previous studies, we have shown that viable colony forming units of bacteria and bacterial biofilms are reduced after sequential treatment with a surfactant-based dressing. Here, we sought to test the impact on visible bacterial pigments and the ultrastructural impact following the sequential treatment of the same surfactant-based dressing. Mature Pseudomonas aeruginosa biofilms were grown on ex vivo porcine skin explants, and an imaging-based analysis was used to compare the skin with and without a concentrated surfactant. In explants naturally tinted by bacterial chromophores, wiping alone had no effect, while the use of a surfactant-based dressing reduced coloration. Similarly, daily wiping led to increased immunohistochemical staining for P. aeruginosa antigens, but not in the surfactant group. Confocal immunofluorescent imaging revealed limited bacterial penetration and coating of the dermis and loose pieces of sloughing material. Ultrastructural analysis confirmed that the biofilms were masking the extracellular matrix (ECM), but the surfactant could remove them, re-exposing the ECM. The masking of the ECM may provide another non-inflammatory explanation for delayed healing, as the ECM is no longer accessible for wound cell locomotion. The use of a poloxamer-based surfactant appears to be an effective way to remove bacterial chromophores and the biofilm coating the ECM fibres.

Dopamine Release Plateau and Outcome Signals in Dorsal Striatum Contrast with Classic Reinforcement Learning Formulations.

We recorded dopamine release signals in medial and lateral sectors of the striatum as mice learned consecutive visual cue-outcome conditioning tasks including cue association, cue discrimination, reversal, and probabilistic discrimination task versions. Dopamine release responses in medial and lateral sites exhibited learning-related changes within and across phases of acquisition. These were different for the medial and lateral sites. In neither sector could these be accounted for by classic reinforcement learning as applied to dopamine-containing neuron activity. Cue responses ranged from initial sharp peaks to modulated plateau responses. In the medial sector, outcome (reward) responses during cue conditioning were minimal or, initially, negative. By contrast, in lateral sites, strong, transient dopamine release responses occurred at both cue and outcome. Prolonged, plateau release responses to cues emerged in both regions when discriminative behavioral responses became required. In most sites, we found no evidence for a transition from outcome to cue signaling, a hallmark of temporal difference reinforcement learning as applied to midbrain dopamine activity. These findings delineate reshaping of dopamine release activity during learning and suggest that current views of reward prediction error encoding need review to accommodate distinct learning-related spatial and temporal patterns of striatal dopamine release in the dorsal striatum.

Symptomatic Intracranial Hemorrhage With Tenecteplase vs Alteplase in Patients With Acute Ischemic Stroke: The Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) Collaboration.

Importance: Symptomatic intracranial hemorrhage (sICH) is a serious complication of stroke thrombolytic therapy. Many stroke centers have adopted 0.25-mg/kg tenecteplase instead of alteplase for stroke thrombolysis based on evidence from randomized comparisons to alteplase as well as for its practical advantages. There have been no significant differences in symptomatic intracranial hemorrhage (sICH) reported from randomized clinical trials or published case series for the 0.25-mg/Kg dose. Objective: To assess the risk of sICH following ischemic stroke in patients treated with tenecteplase compared to those treated with alteplase. Design, Setting, and Participants: This was a retrospective observational study using data from the large multicenter international Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) collaboration comprising deidentified data on patients with ischemic stroke treated with intravenous thrombolysis. Data from more than 100 hospitals in New Zealand, Australia, and the US that used alteplase or tenecteplase for patients treated between July 1, 2018, and June 30, 2021, were included for analysis. Participating centers included a mix of nonthrombectomy- and thrombectomy-capacity comprehensive stroke centers. Standardized data were abstracted and harmonized from local or regional clinical registries. Consecutive patients with acute ischemic stroke who were considered eligible and received thrombolysis at the participating stroke registries during the study period were included. All 9238 patients who received thrombolysis were included in this retrospective analysis. Main Outcomes and Measures: sICH was defined as clinical worsening of at least 4 points on the National Institutes of Health Stroke Scale (NIHSS), attributed to parenchymal hematoma, subarachnoid, or intraventricular hemorrhage. Differences between tenecteplase and alteplase in the risk of sICH were assessed using logistic regression, adjusted for age, sex, NIHSS score, and thrombectomy. Results: Of the 9238 patients included in the analysis, the median (IQR) age was 71 (59-80) years, and 4449 patients (48%) were female. Tenecteplase was administered to 1925 patients. The tenecteplase group was older (median [IQR], 73 [61-81] years vs 70 [58-80] years; P < .001), more likely to be male (1034 of 7313 [54%] vs 3755 of 1925 [51%]; P < .01), had higher NIHSS scores (median [IQR], 9 [5-17] vs 7 [4-14]; P < .001), and more frequently underwent endovascular thrombectomy (38% vs 20%; P < .001). The proportion of patients with sICH was 1.8% for tenecteplase and 3.6% for alteplase (P < .001), with an adjusted odds ratio (aOR) of 0.42 (95% CI, 0.30-0.58; P < .01). Similar results were observed in both thrombectomy and nonthrombectomy subgroups. Conclusions and Relevance: In this large study, ischemic stroke treatment with 0.25-mg/kg tenecteplase was associated with lower odds of sICH than treatment with alteplase. The results provide evidence supporting the safety of tenecteplase for stroke thrombolysis in real-world clinical practice.

Beringia as a high-latitude engine of avian speciation.

Beringia is a biogeographically dynamic region that extends from northeastern Asia into northwestern North America. This region has affected avian divergence and speciation in three important ways: (i) by serving as a route for intercontinental colonisation between Asia and the Americas; (ii) by cyclically splitting (and often reuniting) populations, subspecies, and species between these continents; and (iii) by providing isolated refugia through glacial cycles. The effects of these processes can be seen in taxonomic splits of shallow to increasing depths and in the presence of regional endemics. We review the taxa involved in the latter two processes (splitting-reuniting and isolation), with a focus on three research topics: avian diversity, time estimates of the generation of that diversity, and the regions within Beringia that might have been especially important. We find that these processes have generated substantial amounts of avian diversity, including 49 pairs of avian subspecies or species whose breeding distributions largely replace one another across the divide between the Old World and the New World in Beringia, and 103 avian species and subspecies endemic to this region. Among endemics, about one in three is recognised as a full biological species. Endemic taxa in the orders Charadriiformes (shorebirds, alcids, gulls, and terns) and Passeriformes (perching birds) are particularly well represented, although they show very different levels of diversity through evolutionary time. Endemic Beringian Charadriiformes have a 1.31:1 ratio of species to subspecies. In Passeriformes, endemic taxa have a 0.09:1 species-to-subspecies ratio, suggesting that passerine (and thus terrestrial) endemism might be more prone to long-term extinction in this region, although such 'losses' could occur through their being reconnected with wider continental populations during favourable climatic cycles (e.g. subspecies reintegration with other populations). Genetic evidence suggests that most Beringian avian taxa originated over the past 3 million years, confirming the importance of Quaternary processes. There seems to be no obvious clustering in their formation through time, although there might be temporal gaps with lower rates of diversity generation. For at least 62 species, taxonomically undifferentiated populations occupy this region, providing ample potential for future evolutionary diversification.

Prospective donors' perspectives on hematopoietic cell donation for cell and gene therapy research and development.

Aim: To explore prospective donors' attitudes and perceptions toward donating hematopoietic stem cells (HSCs) for novel treatments research and development (R&D). Methods: A survey was launched by Anthony Nolan (AN) to assess prospective donors' willingness to donate HSCs for novel therapies R&D, and their degree of comfort with the AN collaborating with and receiving payment from external organizations. Results: Most participants (87%) were willing to donate for novel treatment R&D and were comfortable with AN collaborating with external organizations and receiving payment (91% and 80%, respectively). Conclusion: Results reveal an overall positive response toward donating HSCs for R&D. These findings can support stakeholders and policymakers in outlining donation practices that uphold donors' safety and welfare.

Recent interest in the development of cell-based novel treatments using stem cells from healthy donors as opposed to patients' own stem cells may place pressure on stem cell donor registries to adapt and provide donor stem cells to the cell and gene industry. Since stem cell donor registries were originally established to connect patients in need of stem cell transplantation with matched willing stem cell donors, this shift in practice might result in several implications. Therefore, Anthony Nolan (AN), an unrelated stem cell donor registry in the UK, launched a survey to explore the willingness of potential donors to donate stem cells for novel treatment research and development (R&D). The results show that most participants (87%) would be willing to donate stem cells for novel treatment research and development. Most participants were comfortable with AN collaborating with external organizations (91%) and receiving payment from these organizations (80%). Additionally, some participants provided written responses that explained their answers to the questions in the survey. While some participants had positive views on collaborations with external establishments, others had apprehensions over their donations leading to profiteering. Moreover, participants had concerns over their privacy, especially if external collaborations with pharmaceutical companies were to take place. Informed consent and transparency over the nature of collaborations could relieve some of the above-mentioned concerns. These findings can support stakeholders and policymakers in outlining donation practices that uphold donors' safety and welfare.

Trial of Endovascular Thrombectomy for Large Ischemic Strokes.

BACKGROUND: Trials of the efficacy and safety of endovascular thrombectomy in patients with large ischemic strokes have been carried out in limited populations. METHODS: We performed a prospective, randomized, open-label, adaptive, international trial involving patients with stroke due to occlusion of the internal carotid artery or the first segment of the middle cerebral artery to assess endovascular thrombectomy within 24 hours after onset. Patients had a large ischemic-core volume, defined as an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower scores indicating larger infarction) or a core volume of at least 50 ml on computed tomography perfusion or diffusion-weighted magnetic resonance imaging. Patients were assigned in a 1:1 ratio to endovascular thrombectomy plus medical care or to medical care alone. The primary outcome was the modified Rankin scale score at 90 days (range, 0 to 6, with higher scores indicating greater disability). Functional independence was a secondary outcome. RESULTS: The trial was stopped early for efficacy; 178 patients had been assigned to the thrombectomy group and 174 to the medical-care group. The generalized odds ratio for a shift in the distribution of modified Rankin scale scores toward better outcomes in favor of thrombectomy was 1.51 (95% confidence interval [CI], 1.20 to 1.89; P<0.001). A total of 20% of the patients in the thrombectomy group and 7% in the medical-care group had functional independence (relative risk, 2.97; 95% CI, 1.60 to 5.51). Mortality was similar in the two groups. In the thrombectomy group, arterial access-site complications occurred in 5 patients, dissection in 10, cerebral-vessel perforation in 7, and transient vasospasm in 11. Symptomatic intracranial hemorrhage occurred in 1 patient in the thrombectomy group and in 2 in the medical-care group. CONCLUSIONS: Among patients with large ischemic strokes, endovascular thrombectomy resulted in better functional outcomes than medical care but was associated with vascular complications. Cerebral hemorrhages were infrequent in both groups. (Funded by Stryker Neurovascular; SELECT2 ClinicalTrials.gov number, NCT03876457.).

Association of Endovascular Thrombectomy vs Medical Management With Functional and Safety Outcomes in Patients Treated Beyond 24 Hours of Last Known Well: The SELECT Late Study.

Importance: The role of endovascular thrombectomy is uncertain for patients presenting beyond 24 hours of the time they were last known well. Objective: To evaluate functional and safety outcomes for endovascular thrombectomy (EVT) vs medical management in patients with large-vessel occlusion beyond 24 hours of last known well. Design, Setting, and Participants: This retrospective observational cohort study enrolled patients between July 2012 and December 2021 at 17 centers across the United States, Spain, Australia, and New Zealand. Eligible patients had occlusions in the internal carotid artery or middle cerebral artery (M1 or M2 segment) and were treated with EVT or medical management beyond 24 hours of last known well. Interventions: Endovascular thrombectomy or medical management (control). Main Outcomes and Measures: Primary outcome was functional independence (modified Rankin Scale score 0-2). Mortality and symptomatic intracranial hemorrhage (sICH) were safety outcomes. Propensity score (PS)-weighted multivariable logistic regression analyses were adjusted for prespecified clinical characteristics, perfusion parameters, and/or Alberta Stroke Program Early CT Score (ASPECTS) and were repeated in subsequent 1:1 PS-matched cohorts. Results: Of 301 patients (median [IQR] age, 69 years [59-81]; 149 female), 185 patients (61%) received EVT and 116 (39%) received medical management. In adjusted analyses, EVT was associated with better functional independence (38% vs control, 10%; inverse probability treatment weighting adjusted odds ratio [IPTW aOR], 4.56; 95% CI, 2.28-9.09; P < .001) despite increased odds of sICH (10.1% for EVT vs 1.7% for control; IPTW aOR, 10.65; 95% CI, 2.19-51.69; P = .003). This association persisted after PS-based matching on (1) clinical characteristics and ASPECTS (EVT, 35%, vs control, 19%; aOR, 3.14; 95% CI, 1.02-9.72; P = .047); (2) clinical characteristics and perfusion parameters (EVT, 35%, vs control, 17%; aOR, 4.17; 95% CI, 1.15-15.17; P = .03); and (3) clinical characteristics, ASPECTS, and perfusion parameters (EVT, 45%, vs control, 21%; aOR, 4.39; 95% CI, 1.04-18.53; P = .04). Patients receiving EVT had lower odds of mortality (26%) compared with those in the control group (41%; IPTW aOR, 0.49; 95% CI, 0.27-0.89; P = .02). Conclusions and Relevance: In this study of treatment beyond 24 hours of last known well, EVT was associated with higher odds of functional independence compared with medical management, with consistent results obtained in PS-matched subpopulations and patients with presence of mismatch, despite increased odds of sICH. Our findings support EVT feasibility in selected patients beyond 24 hours. Prospective studies are warranted for confirmation.

Climate change and commercial fishing practices codetermine survival of a long-lived seabird.

Understanding the environmental mechanisms that govern population change is a fundamental objective in ecology. Although the determination of how top-down and bottom-up drivers affect demography is important, it is often equally critical to understand the extent to which, environmental conditions that underpin these drivers fluctuate across time. For example, associations between climate and both food availability and predation risk may suggest the presence of trophic interactions that may influence inferences made from patterns in ecological data. Analytical tools have been developed to account for these correlations, while providing opportunities to ask novel questions regarding how populations change across space and time. Here, we combine two modeling disciplines-path analysis and mark-recapture-recovery models-to explore whether shifts in sea-surface temperatures (SSTs) influenced top-down (entanglement in fishing equipment) or bottom-up (forage fish production) population constraints over 60 years, and the extent to which these covarying processes shaped the survival of a long-lived seabird, the Royal tern. We found that hemispheric trends in SST were associated with variation in the amount of fish harvested along the Atlantic coast of North America and in the Caribbean, whereas reductions in forage fish production were mostly driven by shifts in the amount of fish harvested by commercial fisheries throughout the North Atlantic the year prior. Although the indirect (i.e., stock depletion) and direct (i.e., entanglement) impacts of commercial fishing on Royal tern mortality has declined over the last 60 years, increased SSTs during this time period has resulted in a comparable increase in mortality risk, which disproportionately impacted the survival of the youngest age-classes of Royal terns. Given climate projections for the North Atlantic, our results indicate that threats to Royal tern population persistence in the Mid-Atlantic will most likely be driven by failures to recruit juveniles into the breeding population.

Artificial intelligence aneurysm measurement tool finds growth in all aneurysms that ruptured during conservative management.

BACKGROUND: Cerebral aneurysm rupture is associated with high rates of morbidity and mortality. Detecting aneurysms at high risk of rupture is critical in management decision making. Rupture risk has traditionally been associated with size-measured as a maximum dimension. However, aneurysms are morphologically dynamic, a characteristic ignored by large prospective aneurysm risk studies. Manual measurement is challenging and fraught with error. We used an artificial intelligence (AI) measurement tool to study aneurysms that ruptured during conservative management to detect changes in size not appreciated by manual linear measurement. METHODS: A single practice database with >5000 aneurysms was queried. Patients followed conservatively for an unruptured aneurysm were identified using appropriate diagnosis codes. This cohort was screened for subsequent rupture using procedure codes. Only patients with two vascular imaging studies before rupture were included. RESULTS: Five patients met the criteria. All patients had aneurysm enlargement, two of which were not detected from manual linear measurements, including adjudication and analysis, during a multidisciplinary neurovascular conference in a high volume practice. Maximum dimension increased at a minimum of 1.8% (range 1.8-63.3%) from the first scan to the last, and aneurysm volume increased at a minimum of 5.9% (5.9-385.5%), highlighting the importance of volumetric measurement. CONCLUSIONS: AI-enabled volumetric measurements are more sensitive to changes in size and detected enlargement in all aneurysms that ruptured during conservative management. This finding has major implications for clinical practice and methods used for interval aneurysm measurement in patients being conservatively followed.

The association of wound factors and symptoms of fatigue and pain with wound healing in chronic venous leg ulcers.

The purpose of this study was: (1) to characterise the association of wound area, wound exudate C-reactive protein (CRP), broad-spectrum matrix metalloprotease protein (MMPs), and symptoms of fatigue and pain in individuals with chronic venous leg ulcers (CVLUs) over time and (2) to identify factors associated with the wound healing trajectory in CVLUs. Seventy four participants with CVLU who received weekly sharp debridement were recruited from a wound care clinic during the 8-week study period. To examine associations among wound CRP, MMPs, pain, fatigue, and wound healing trajectory over time, we calculated Bayes factors (BF) based on a linear mixed model. The mean age of participants was 71.8 (SD = 9.8) and the mean wound area was 2278 mm2 (SD = 7085 mm2 ) at baseline. Higher fatigue was strongly associated with higher MMPs (BF = 9, 95% HDI: [-.05, .43]), lower CRP (BF = 11, 95% HDI: [-.02, .002]), and large areas of wound (BF = 20, 95% HDI: [-.001, .01]). Higher CRP and MMPs activity in wound exudate and higher fatigue were associated with a larger wound area. To facilitate wound healing, clinicians need to utilise the multifactorial approach, which includes wound treatment and management of symptoms such as pain and fatigue, because of the molecular and psycho-behavioural factors involved in wound healing.

Synchronous Measurements of Extracellular Action Potentials and Neurochemical Activity with Carbon Fiber Electrodes in Nonhuman Primates.

Measuring the dynamic relationship between neuromodulators, such as dopamine, and neuronal action potentials is imperative to understand how these fundamental modes of neural signaling interact to mediate behavior. Here, we developed methods to measure concurrently dopamine and extracellular action potentials (i.e., spikes) and applied these in a monkey performing a behavioral task. Standard fast-scan cyclic voltammetric (FSCV) electrochemical (EChem) and electrophysiological (EPhys) recording systems are combined and used to collect spike and dopamine signals, respectively, from an array of carbon fiber (CF) sensors implanted in the monkey striatum. FSCV requires the application of small voltages at the implanted sensors to measure redox currents generated from target molecules, such as dopamine. These applied voltages create artifacts at neighboring EPhys-measurement sensors, producing signals that may falsely be classified as physiological spikes. Therefore, simple automated temporal interpolation algorithms were designed to remove these artifacts and enable accurate spike extraction. We validated these methods using simulated artifacts and demonstrated an average spike recovery rate of 84.5%. This spike extraction was performed on data collected from concurrent EChem and EPhys recordings made in a task-performing monkey to discriminate cell-type specific striatal units. These identified units were shown to correlate to specific behavioral task parameters related to reward size and eye-movement direction. Synchronous measures of spike and dopamine signals displayed contrasting relations to the behavioral task parameters, as taken from our small set of representative data, suggesting a complex relationship between these two modes of neural signaling. Future application of our methods will help advance our understanding of the interactions between neuromodulator signaling and neuronal activity, to elucidate more detailed mechanisms of neural circuitry and plasticity mediating behaviors in health and in disease.

Zero-inflated count distributions for capture-mark-reencounter data.

The estimation of demographic parameters is a key component of evolutionary demography and conservation biology. Capture-mark-recapture methods have served as a fundamental tool for estimating demographic parameters. The accurate estimation of demographic parameters in capture-mark-recapture studies depends on accurate modeling of the observation process. Classic capture-mark-recapture models typically model the observation process as a Bernoulli or categorical trial with detection probability conditional on a marked individual's availability for detection (e.g., alive, or alive and present in a study area). Alternatives to this approach are underused, but may have great utility in capture-recapture studies. In this paper, we explore a simple concept: in the same way that counts contain more information about abundance than simple detection/non-detection data, the number of encounters of individuals during observation occasions contains more information about the observation process than detection/non-detection data for individuals during the same occasion. Rather than using Bernoulli or categorical distributions to estimate detection probability, we demonstrate the application of zero-inflated Poisson and gamma-Poisson distributions. The use of count distributions allows for inference on availability for encounter, as well as a wide variety of parameterizations for heterogeneity in the observation process. We demonstrate that this approach can accurately recover demographic and observation parameters in the presence of individual heterogeneity in detection probability and discuss some potential future extensions of this method.

Leukocytapheresis variables and transit time for allogeneic cryopreserved hpc: better safe than sorry.

Cryopreservation was recommended to ensure continuity in allogeneic hematopoietic progenitor cells (HPC) transplantation during the COVID-19 pandemic. Several groups have shown no impact on clinical outcomes for patients who underwent HPC transplantation with cryopreserved products during the first months of this pandemic. However, concerns about quality control attributes after cryopreservation have been raised. We investigated, in 155 allogeneic peripheral blood cryopreserved HPC, leukocytapheresis characteristics influencing viable CD34+ and CD3+ cells, and CFU-GM recoveries after thawing. Collection characteristics such as volume, nucleated cells (NC)/mL and hematocrit correlated with viable CD34+ and CD3+ cells recoveries after thawing in univariate analysis but only CD3+ cells remained statistically significant in multivariate analysis (r2 = 0.376; P = < 0.001). Additionally, transit time also showed correlation with viable CD34+ (r2 = 0.186), CD3+ (r2 = 0.376) and CFU-GM recoveries (r2 = 0.212) in multivariate analysis. Thus, diluting leukocytapheresis below 200 × 106 NC/mL, avoiding red cells contamination above 2%, cryopreserving below 250 × 106 NC/mL and minimizing transit time below 36 h, prevented poor viable CD34+ and CD3+ cells, and CFU-GM recoveries. In summary, optimizing leukocytapheresis practices and minimizing transportation time may better preserve the quality attributes of HPC when cryopreservation is indicated.

Ethnic diversity and cord blood banking: satisfying the unmet need.

BACKGROUND AIMS: In this study, the authors sought to assess whether cord blood units (CBUs) collected from donors of non-European ethnic backgrounds are utilized for umbilical cord blood transplantation (UCBT) at a different rate than those of European ethnic backgrounds. The authors also examined potential methods of enriching these under-represented ethnic backgrounds in cord blood bank (CBB) inventories without increasing financial overheads and without compromising total inventory utilization or post-transplant outcomes. METHODS: Data from N = 6506 searchable or shipped Anthony Nolan Cell Therapy Centre grafts were used in this study. Banked grafts were graded from A+ to D based on total nucleated cell and CD34+ cell content. Utilizations of each grade group were further stratified by graft ethnic background. The Mantel-Cox log-rank test was performed in conjunction with Kaplan-Meier survival analysis to compare utilization rates and post-transplant outcomes. For shipped grafts, levels of HLA matching at HLA-A, HLA-B and HLA-DR loci were also analyzed by graft ethnic background and grade using data from the Eurocord/EBMT registry. RESULTS: Overall utilization of non-European grafts did not significantly differ from that of European grafts (2.5% versus 2.2%, P = 0.23). However, significant differences were found when stratifying utilization rates by cell content. The probability of non-European D grade grafts being utilized was 3-fold higher than that of European D grade grafts (1.1% versus 0.4%, P = 0.03) and comparable to that of European C grade grafts (1.1% versus 0.9%, P = 0.90). No significant differences were found between D and C grade grafts in terms of overall survival (OS) (P = 0.12), in part due to a disproportionate utilization of D grade grafts for pediatric UCBT (74% versus 39%, age difference P < 0.001). Furthermore, non-European graft shipments were 4-fold less likely to be a 6/6 HLA match to their recipients relative to European graft shipments (7% versus 29%). CONCLUSIONS: The authors have identified a niche for CBUs of low cell content collected from donors of non-European ethnic backgrounds that has been overlooked by previous studies. Banking of these CBUs for pediatric UCBT instead of CBUs from European donors containing modestly higher cell content is an ethical approach to increasing the ethnic diversity of CBB inventory-and, consequently, the probability of non-European recipients finding a 6/6 HLA-matched graft-without compromising post-transplant OS or overall rate of inventory utilization.

Thrombectomy versus Medical Management in Mild Strokes due to Large Vessel Occlusion: Exploratory Analysis from the EXTEND-IA Trials and a Pooled International Cohort.

OBJECTIVE: This study was undertaken to evaluate functional and safety outcomes for endovascular thrombectomy (EVT) versus medical management (MM) in patients with large vessel occlusion (LVO) and mild neurological deficits, stratified by perfusion imaging mismatch. METHODS: The pooled cohort consisted of patients with National Institutes of Health Stroke Scale (NIHSS) < 6 and internal carotid artery (ICA), M1, or M2 occlusions from the Extending the Time for Thrombolysis in Emergecy Neurological Deficits - Intra-Arterial (EXTEND-IA) Trial,  Tenecteplase vs Alteplase before Endovascular Thrombectomy in Ischemic Stroke (EXTEND-IA TNK) trials Part I/II and prospective data from 15 EVT centers from October 2010 to April 2020. RAPID software estimated ischemic core and mismatch. Patients receiving primary EVT (EVTpri ) were compared to those who received primary MM (MMpri ), including those who deteriorated and received rescue EVT, in overall and propensity score (PS)-matched cohorts. Patients were stratified by target mismatch (mismatch ratio ≥ 1.8 and mismatch volume ≥ 15ml). Primary outcome was functional independence (90-day modified Rankin Scale = 0-2). Secondary outcomes included safety (symptomatic intracerebral hemorrhage [sICH], neurological worsening, and mortality). RESULTS: Of 540 patients, 286 (53%) received EVTpri and demonstrated larger critically hypoperfused tissue (Tmax > 6 seconds) volumes (median [IQR]: 64 [26-96] ml vs MMpri : 40 [14-76] ml, p < 0.001) and higher presentation NIHSS (median [IQR]: 4 [2-5] vs MMpri : 3 [2-4], p < 0.001). Functional independence was similar (EVTpri : 77.4% vs MMpri : 75.6%, adjusted odds ratio [aOR] = 1.29, 95% confidence interval [CI] = 0.82-2.03, p = 0.27). EVT had worse safety regarding sICH (EVTpri : 16.3% vs MMpri : 1.3%, p < 0.001) and neurological worsening (EVTpri : 19.6% vs MMpri : 6.7%, p < 0.001). In 414 subjects (76.7%) with target mismatch, EVT was associated with improved functional independence (EVTpri : 77.4% vs MMpri : 72.7%, aOR = 1.68, 95% CI = 1.01-2.81, p = 0.048), whereas there was a trend toward less favorable outcomes with primary EVT (EVTpri : 77.4% vs MMpri : 83.3%, aOR = 0.39, 95% CI = 0.12-1.34, p = 0.13) without target mismatch (pinteraction  = 0.06). Similar findings were observed in a propensity score-matched subpopulation. INTERPRETATION: Overall, EVT was not associated with improved clinical outcomes in mild strokes due to LVO, and sICH was increased. However, in patients with target mismatch profile, EVT was associated with increased functional independence. Perfusion imaging may be helpful to select mild stroke patients for EVT. ANN NEUROL 2022;92:364-378.

Effect of Nanosulfur Against Multidrug-Resistant Staphylococcus pseudintermedius and Pseudomonas aeruginosa.

Multidrug resistance (MDR) has significantly increased in the past decades and the use of nanotechnology has opened new venues for novel treatments. Nanosulfur is a potent antimicrobial agent and a cheaper alternative to other nanomaterials. However, very few studies have been published on its activity against MDR organisms. Therefore, the goal of this in vitro study was to assess cytotoxicity, antimicrobial, and anti-biofilm activity of nanosulfur (47 nm, orthorhombic) against clinical isolates of MDR Staphylococcus pseudintermedius (SP) and Pseudomonas aeruginosa (PA) in planktonic and biofilm state using canine skin explants. Nanosilver (50 nm, spherical) was tested as a comparative control. Concentrations between 1866.7 and 0.11 µg/mL of both nanoparticles were tested. The ultrastructure of nanosulfur was assessed via electron microscopy. Both types of nanoparticles showed no direct cytotoxicity on a canine keratinocyte cell line. In the planktonic phase, nanosulfur was able to inhibit or kill (6-log10 reduction of CFU) 7 of 10 MDR-SP isolates at 233.3 µg/mL, whereas, when in biofilm state, 6 of 10 isolates were killed at different concentrations (233.33 to 1866.7 µg/mL). Nanosilver did not show any antimicrobial or anti-biofilm activity at any concentrations tested. Both types of nanoparticles were ineffective against MDR-PA in either state. Ultrastructurally, nanosulfur was present in individual nanoparticles as well as forming larger nanoclusters. This is the first study showing an antimicrobial and anti-biofilm activity of nanosulfur for MDR-SP in absence of cytotoxicity. Nanosulfur has the potential to be used in veterinary and human medicine as effective, safe, and cheap alternative to antimicrobials and anti-biofilm agents currently available. KEY POINTS: • Nanosulfur is a better alternative than nanosilver to treat MDR-Staphylococci. • Nanosulfur is an effective agent against MDR-Staphyloccocal biofilm. • Canine skin explant model is reliable for testing anti-biofilm agents.