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Cell manufacturing facilities need to define the potency of mesenchymal stromal cells (MSCs) as cellular therapeutics in advanced clinical trials or marketing approval. Since MSCs' mechanism of action in humans is not well defined, more than a single functional property of MSCs needs to be captured as a surrogate measure of potency utilizing assay matrix technologies. However, the current limitation is the sole investigation of MSC-mediated T-cell suppression as a surrogate measure of potency. We investigated the effect of MSCs on B-cell matrix responses to be incorporated into the assay matrix potency analytical system. Our results demonstrate that MSCs inhibit B-cell differentiation and block pan-antibody secretion upon activation of B cells in the PBMCs. In contrast, MSCs are inferior in blocking B-cell matrix responses when purified B cells are used. Mechanistic analysis has demonstrated that MSC-mediated inhibition of B-cell matrix responses is non-contact dependent and Tryptophan metabolic pathway plays a major role, akin to the mechanism of MSC-mediated T-cell suppression. MSCs also inhibit both T-cell and B-cell responses when both of these lymphoid populations are concurrently activated in the PBMCs. Secretome analysis of MSC and T/B cell-activated PBMC cocultures identified direct and inverse correlative matrix signatures between humoral antibody isotypes and secretory molecules. The current analysis of the combined and concomitant investigation of T-cell and B-cell matrix responses fulfills the potency assay matrix strategy by incorporating MSCs' interaction with more than a single inflammatory immune responder.
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Leucócitos Mononucleares , Células-Tronco Mesenquimais , Humanos , Leucócitos Mononucleares/metabolismo , Medula Óssea , Linfócitos T , Técnicas de Cocultura , Células-Tronco Mesenquimais/metabolismo , Proliferação de Células , Células da Medula ÓsseaRESUMO
BACKGROUND AND PURPOSE: Real-time quaking-induced conversion (RT-QuIC) assays offer a sensitive and specific means for detection of prions, although false negative results are recognized in clinical practice. We profile the clinical, laboratory, and pathologic features associated with false negative RT-QuIC assays and extend these to frame the diagnostic approach to patients with suspected prion disease. METHODS: A total of 113 patients with probable or definite prion disease were assessed at Mayo Clinic (Rochester, MN; Jacksonville, FL; Scottsdale, AZ) or Washington University School of Medicine (Saint Louis, MO) from 2013 to 2021. RT-QuIC testing for prions was performed in cerebrospinal fluid (CSF) at the National Prion Disease Pathology Surveillance Center (Cleveland, OH). RESULTS: Initial RT-QuIC testing was negative in 13 of 113 patients (sensitivity = 88.5%). RT-QuIC negative patients were younger (median = 52.0 years vs. 66.1 years, p < 0.001). Other demographic and presenting features, and CSF cell count, protein, and glucose levels were similar in RT-QuIC negative and positive patients. Frequency of 14-3-3 positivity (4/13 vs. 77/94, p < 0.001) and median CSF total tau levels were lower in RT-QuIC negative patients (2517 vs. 4001 pg/mL, p = 0.020), and time from symptom onset to first presentation (153 vs. 47 days, p = 0.001) and symptomatic duration (710 vs. 148 days, p = 0.001) were longer. CONCLUSIONS: RT-QuIC is a sensitive yet imperfect measure necessitating incorporation of other test results when evaluating patients with suspected prion disease. Patients with negative RT-QuIC had lower markers of neuronal damage (CSF total tau and protein 14-3-3) and longer symptomatic duration of disease, suggesting that false negative RT-QuIC testing associates with a more indolent course.
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Síndrome de Creutzfeldt-Jakob , Doenças Priônicas , Príons , Humanos , Príons/líquido cefalorraquidiano , Síndrome de Creutzfeldt-Jakob/diagnóstico , Sensibilidade e Especificidade , Doenças Priônicas/diagnóstico , Proteínas 14-3-3RESUMO
This article discusses clinical ethics consultation (CEC), and thereby ethics support services in the Canadian context. Commonalities and differences between the three models of ethics support and CEC shared in this article are identified, set within the broader context of the Canadian healthcare system, accreditation, and professionalization of practicing healthcare ethicists.
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Eticistas , Consultoria Ética , Canadá , Atenção à Saúde , Ética Clínica , HumanosRESUMO
BACKGROUND: The process of informed consent in National Institutes of Health randomized, placebo-controlled trials is poorly studied. There are several issues regarding informed consent in emergency neurologic trials, including a shared decision-making process with the patient or a legally authorized representative about overall risks, benefits, and alternative treatments. METHODS: To evaluate the informed consent process, we collected best and worst informed consent practice information from a National Institutes of Health trial and used this in medical simulation videos to educate investigators at multiple sites to improve the consent process. Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR III) (clinicaltrials.gov, NCT00784134) studied the effect of intraventricular alteplase (n = 251) versus saline (placebo) injections (n = 249) for intraventricular hemorrhage reduction. Reasons for ineligibility (including refusing to consent) for all screen failures were analyzed. The broadcasted presentation outlined best practices for doctor-patient interactions during the consenting process, as well as anecdotal, study-specific reasons for consent refusal. Best and worst consent elements were then incorporated into a simulation video to enhance the informed consent process. This video was disseminated to trial sites as a webinar around the midpoint of the trial to improve the consent process. Pre- and post-intervention consent refusals were compared. RESULTS: During the trial, 10,538 patients were screened for eligibility, of which only three were excluded due to trial timing. Pre-intervention, 77 of 5686 (1.40%) screen eligible patients or their proxies refused consent. Post-intervention, 55 of 4849 (1.10%) refused consent, which was not significantly different from pre-intervention (P = 0.312). The incidence of screen failures was significantly lower post-intervention (P = 0.006), possibly due to several factors for patient exclusion. CONCLUSION: The informed consent process for prospective randomized trials may be enhanced by studying and refining best practices based on trial-specific plans and patient concerns particular to a study.
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Tomada de Decisão Compartilhada , Consentimento Livre e Esclarecido , Procurador , Ensaios Clínicos Controlados Aleatórios como Assunto , Recusa de Participação , Hemorragia Cerebral Intraventricular/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Emergências , Fibrinolíticos/uso terapêutico , Humanos , Injeções Intraventriculares , Avaliação de Processos em Cuidados de Saúde , Ativador de Plasminogênio Tecidual/uso terapêuticoRESUMO
There are a growing number of patients with acute and recurrent pustular reactive dermatitis reported without clear parameters to define the entities. Consolidation of cases under the term acute and recurrent pustulosis (ARP) will aid dermatologists in diagnosing such patients in the future. Objective: Describe the parameters which define acute and recurrent pustulosis and communicate the high predominance for onset in young women based on reported cases. Methods: PubMed literature search for reports of recurrent follicularly centered neutrophilic eruptions. Results: According to the clinical characteristics of ARP, 23 patients were identified from prior reports. Interestingly, 20 out of 23 patients were women with a high predominance in early adulthood. Limitations: This is an understudied and underreported clinical entity. Therefore, limitations include availability of case reports and lack of prior research available on PubMed. Conclusion: ARP is defined as follicular pustules that occur and remit without treatment and within a week of an identifiable trigger, predominantly affecting women. Consolidating reports of ARP under clear criteria will aid clinical dermatologists in diagnosing this unreported dermatitis.
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Purpose of Review: Cryopreservation and its associated freezing and thawing procedures-short "freeze-thawing"-are among the final steps in economically viable manufacturing and clinical application of diverse cellular therapeutics. Translation from preclinical proof-of-concept studies to larger clinical trials has indicated that these processes may potentially present an Achilles heel to optimal cell product safety and particularly efficacy in clinical trials and routine use. Recent Findings: We review the current state of the literature on how cryopreservation of cellular therapies has evolved and how the application of this technique to different cell types is interlinked with their ability to engraft and function upon transfer in vivo, in particular for hematopoietic stem and progenitor cells (HSPCs), their progeny, and therapeutic cell products derived thereof. We also discuss pros and cons how this may differ for non-hematopoietic mesenchymal stromal/stem cell (MSC) therapeutics. We present different avenues that may be crucial for cell therapy optimization, both, for hematopoietic (e.g., effector, regulatory, and chimeric antigen receptor (CAR)-modified T and NK cell based products) and for non-hematopoietic products, such as MSCs and induced pluripotent stem cells (iPSCs), to achieve optimal viability, recovery, effective cell dose, and functionality of the cryorecovered cells. Summary: Targeted research into optimizing the cryopreservation and freeze-thawing routines and the adjunct manufacturing process design may provide crucial advantages to increase both the safety and efficacy of cellular therapeutics in clinical use and to enable effective market deployment strategies to become economically viable and sustainable medicines.
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Background and Objectives: Diagnostic criteria emphasize the use of sensitive and disease-specific tests to distinguish patients with rapidly progressive dementia (RPD) due to Creutzfeldt-Jakob disease (CJD) vs other causes (mimics). These tests are often performed in specialized centers, with results taking days to return. There is a need to leverage clinical features and rapidly reporting tests to distinguish patients with RPD due to CJD from those due to other causes (mimics) early in the symptomatic course. Methods: In this case-control series, clinical features and the results of diagnostic tests were compared between mimics (n = 11) and patients with definite (pathologically proven, n = 33) or probable CJD (with positive real-time quaking-induced conversion [RT-QuIC], n = 60). Patients were assessed at Mayo Clinic Enterprise or Washington University from January 2014 to February 2021. Mimics were enrolled in prospective studies of RPD; mimics met the diagnostic criteria for probable CJD but did not have CJD. Results: Mimics were ultimately diagnosed with autoimmune encephalitis (n = 6), neurosarcoidosis, frontotemporal lobar degeneration with motor neuron disease, dural arteriovenous fistula, cerebral amyloid angiopathy with related inflammation, and systemic lupus erythematous with polypharmacy. Age at symptom onset, sex, presenting features, and MRI and EEG findings were similar in CJD cases and mimics. Focal motor abnormalities (49/93, 11/11), CSF leukocytosis (4/92, 5/11), and protein >45 mg/dL (39/92, 10/11) were more common in mimics (p < 0.01). Positive RT-QuIC (77/80, 0/9) and total tau >1149 pg/mL (74/82, 2/10) were more common in CJD cases (all p < 0.01). Protein 14-3-3 was elevated in 64/89 CJD cases and 4/10 mimics (p = 0.067). Neural-specific autoantibodies associated with autoimmune encephalitis were detected within the serum (5/9) and CSF (5/10) of mimics; nonspecific antibodies were detected within the serum of 9/71 CJD cases. Discussion: Immune-mediated, vascular, granulomatous, and neurodegenerative diseases may mimic CJD at presentation and should be considered in patients with early motor dysfunction and abnormal CSF studies. The detection of atypical features-particularly elevations in CSF leukocytes and protein-should prompt evaluation for mimics and consideration of empiric treatment while waiting for the results of more specific tests.
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Importance: Detection of prion proteins in cerebrospinal fluid (CSF) using real-time quaking-induced conversion (RT-QuIC) assays has transformed the diagnostic approach to sporadic Creutzfeldt-Jakob disease (CJD), facilitating earlier and more complete recognition of affected patients. It is unclear how expanded recognition of affected patients may affect the diagnostic and prognostic relevance of clinical features and diagnostic tests historically associated with CJD. Objective: To evaluate clinical features and diagnostic testing in patients presenting with CJD and determine the associations of these features with prognosis. Design, Setting, and Participants: This cohort study incorporated data from electronic medical records of patients with CJD treated at Mayo Clinic Enterprise tertiary care centers in Rochester, Minnesota; Jacksonville, Florida; and Scottsdale, Arizona. Participants included patients with definite or probable CJD assessed from 2014 to 2021. Data were analyzed October 2021 to January 2022. Exposures: Dominant presentation, clinical features, and diagnostic tests associated with CJD. Main Outcomes and Measures: The outcomes of interest were the sensitivity and prognostic value of clinical features and accessible diagnostic tests at presentation with possible CJD. Results: A total of 115 patients were identified, including 40 patients (35%) with definite CJD. Mean (SD) age at symptom onset was 64.8 (9.4) years, and 68 patients were women (59%). The sensitivity of clinical markers (myoclonus) and tests historically considered in patients with suspected CJD was poor (eg, stereotyped electroencephalography anomalies: 17 of 105 patients [16%]; elevated CSF protein 14-3-3 levels: 54 of 90 patients [60%]). By comparison, biomarkers with good diagnostic sensitivity at presentation included RT-QuIC (66 of 71 patients [93%]), CSF total tau (T-tau) level greater than 1149 pg/mL (81 of 92 patients [88%]), and characteristic signal anomalies on magnetic resonance imaging (88 of 115 patients [77%]). Multivariable linear regression confirmed shorter survival in patients with myoclonus (difference, -125.9 [95% CI, -236.3 to -15.5] days; P = .03), visual or cerebellar signs (difference, -180.2 [95% CI, -282.2 to -78.2] days; P < .001), elevated CSF protein 14-3-3 levels (difference, -193 [95% CI, -304.9 to -82.9] days; P < .001), and elevated T-tau level (difference for every 1000 pg/mL elevation, -9.1 [95% CI, -17.7 to -1.0] days; P = .04). Conclusions and Relevance: These findings suggest that CSF RT-QuIC, elevated CSF T-tau level, and stereotyped magnetic resonance imaging anomalies were associated with the diagnosis of CJD, while other clinical findings (eg, myoclonus), stereotyped electroencephalography anomalies, and CSF protein 14-3-3 levels offered less diagnostic value. Visual or cerebellar features, myoclonus, and CSF 14-3-3 and T-tau levels may be associated with disease duration, justifying continued inclusion in the evaluation of patients suspected to have CJD.
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Síndrome de Creutzfeldt-Jakob , Mioclonia , Proteínas 14-3-3/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Estudos de Coortes , Síndrome de Creutzfeldt-Jakob/diagnóstico , Testes Diagnósticos de Rotina , Feminino , Humanos , Masculino , Sensibilidade e EspecificidadeRESUMO
B7 family proteins serve as checkpoint molecules that protect tumors from T cell mediated lysis. Tryptophan degrading enzymes indoleamine 2,3 dioxygenase (IDO) and tryptophan 2,3 dioxygenase (TDO) also induce T cell immune tolerance. However, little is known about the relative contribution of B7 molecules, tryptophan degrading enzymes, as well as the impact of tumor and stromal cell interactions to the development of immunosuppressive tumor microenvironment. To investigate such interactions, we used a tripartite model of human hepatocellular carcinoma cell line (HepG2) and mesenchymal stromal cells (MSCs) co-cultured with peripheral blood mononuclear cells (PBMCs). Co-culture of HepG2 cells and activated PBMCs demonstrate that HepG2 cells undergo PBMC mediated cytolysis, despite constitutive expression of B7-H3 and upregulation of PD-L1 by IFNγ. Knockdown of B7-H3, PD-L1 or IDO does not modulate PBMC mediated lysis of HepG2 cells. However, TNFα preactivation enhances lysis of HepG2 cells, and blocking of TNFα production from PBMCs protects HepG2 cells. On the other hand, MSCs protect HepG2 cells from PBMC mediated lysis, even in the presence of TNFα. Further investigation showed that MSC mediated protection is associated with the unique secretome profile of upregulated and downregulated cytokines and chemokines. IFNγ activated MSCs are superior to TNFα activated or control MSCs in protecting HepG2 cells. Blockade of IFNγ driven IDO activity completely abolishes the ability of MSCs to protect HepG2 cells from cytolysis by PBMCs. These results suggest that inhibition of IFNγ activation of IDO induction in stromal cells, combined with usage of TNFα, could be a novel immunotherapeutic strategy to induce regression of hepatocellular carcinoma.
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BACKGROUND: Congenital hypoplasia or absence of the A1 segment of the anterior cerebral artery (ACA) has been associated with increased incidence of berry aneurysms at the anterior communicating artery (Acom) complex. It is not known, however, whether this anatomic variant also predisposes patients to complications after aneurysmal subarachnoid hemorrhage. METHODS: Patients were included for analysis if they presented to our institution for clipping or coiling of an Acom aneurysm between the years of 2001 and 2013. Patients were deemed to have cerebral infarction if a new hypodensity in a vascular distribution was visualized on CT imaging. The association between A1 segmental abnormalities and radiologic infarction was subsequently evaluated in a risk-adjusted manner using stepwise multivariable logistic regression analysis. RESULTS: Of 145 patients who presented with aneurysmal subarachnoid hemorrhage after rupture of an Acom aneurysm, 31 (21.4%) had a hypoplastic or absent A1 segment. On univariate analysis, there was a trend toward an increased rate of radiologic infarction in patients with A1 segment abnormalities (OR=2.11, 95% CI: 0.93-4.79; P=0.0757). On multivariable analysis, a hypoplastic or absent A1 segment was significantly associated with an increased rate of radiologic infarction (OR=2.54, 95% CI: 1.02-6.43; P=0.0466). CONCLUSIONS: Our results suggest that a hypoplastic or absent A1 segment is associated with cerebral infarction following subarachnoid hemorrhage from ruptured Acom aneurysms, indicating a potential need for heightened vigilance and a reduced threshold for therapeutic intervention in patients harboring this abnormality.
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Aneurisma Roto/complicações , Infarto Cerebral/complicações , Aneurisma Intracraniano/complicações , Hemorragia Subaracnóidea/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma Roto/cirurgia , Artéria Cerebral Anterior/cirurgia , Angiografia Cerebral/métodos , Infarto Cerebral/diagnóstico , Feminino , Humanos , Aneurisma Intracraniano/cirurgia , Masculino , Pessoa de Meia-IdadeAssuntos
Prática Avançada de Enfermagem , Promoção da Saúde , Papel do Profissional de Enfermagem , Abandono do Hábito de Fumar , Adulto , Humanos , Profissionais de Enfermagem , Relações Enfermeiro-Paciente , Fumar/fisiopatologia , Fumar/psicologia , Transtornos Relacionados ao Uso de Substâncias/psicologiaRESUMO
INTRODUCTION: Pilocytic astrocytoma is a classically benign tumor that most often affects pediatric patients. Rarely, it occurs during adulthood. We present a case series and systematic literature review of adult pilocytic astrocytoma (APA) to examine the clinical presentation, extent of resection, and recurrence rate associated with this tumor in this population. MATERIALS AND METHODS: Our institutional records were retrospectively reviewed for cases of pilocytic astrocytoma in adults. A PubMed search identified English-language studies of pathology-proven APA. A meta-analysis was performed to determine the relationship between extent of tumor resection and recurrence. RESULTS: Forty-six patients with APA were diagnosed at our institution (mean age 33.6 ± 13.3; 24 [52%] female). Twenty-four patients (52%) underwent gross total resection, 11 (24%) subtotal resection, 4 (9%) near total resection, 4 (9%) observation after biopsy, and 3 (6%) radiotherapy alone. Tumors recurred or progressed in 6 (13%) patients, of whom 4 were treated by STR and 2 were treated by radiotherapy alone. Thirty-nine (95%) patients were still alive at last follow-up. A systematic literature review identified 415 patients with APA in 38 studies. Including our case series, 7 studies reported extent of resection, follow-up, and recurrence. Of 254 patients with a weighted mean follow-up of 77.7 ± 49.6 (31-250) months, 129 (51%) were treated with gross total resection, and 125 (49%) underwent subtotal resection. Tumor recurred in 79 (31%) patients, 22 (27%) after gross total resection and 57 (73%) after subtotal resection (P < 0.001). CONCLUSIONS: Pilocytic astrocytoma rarely presents during adulthood. Overall, prognosis is favorable and survival rates are high. APA recurrence is more likely after STR, and the goal of surgery should always be GTR when feasible.
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Astrocitoma/cirurgia , Neoplasias Encefálicas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PubMed/estatística & dados numéricos , Adulto JovemRESUMO
Vascular epiphytes are a major biomass component of forests across the globe and they contribute to 9% of global vascular plant diversity. To improve our understanding of the whole-plant response of epiphytes to future climate change, we investigated for the first time both individual and combined effects of elevated CO2 (560 ppm) and light on the physiology and growth of two epiphyte species [Tillandsia brachycaulos (CAM) and Phlebodium aureum (C3)] grown for 272 days under controlled conditions. We found that under elevated CO2 the difference in water loss between the light (650 µmol m-2s-1) and shade (130 µmol m-2s-1) treatment was strongly reduced. Stomatal conductance (g s) decreased under elevated CO2, resulting in an approximate 40-45% reduction in water loss over a 24 h day/night period under high light and high CO2 conditions. Under lower light conditions water loss was reduced by approximately 20% for the CAM bromeliad under elevated CO2 and increased by approximately 126% for the C3 fern. Diurnal changes in leaf turgor and water loss rates correlated strong positively under ambient CO2 (400 ppm) and high light conditions. Future predicted increases in atmospheric CO2 are likely to alter plant water-relations in epiphytes, thus reducing the canopy cooling potential of epiphytes to future increases in temperature.
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Little to no research has been conducted on the gut microbiome of the Pekin duck, yet over 24.5 million ducks are raised for human consumption each year in the United States alone. Knowledge of the microbiome could lead to an understanding of the effects of growing conditions such as the use of prebiotics, probiotics, and enzymes in feeding practices, the use of antibiotics, and the sources of pathogenic bacteria in diseased ducks. In order to characterize changes in the caecal microbiome that occur as ducks develop through a typical industry grow-out period, a 16S rRNA community analysis of caecal contents collected over a 6-week period was conducted using a next generation sequencing approach. Transitions in the composition of the caecal microbiome occurred throughout the lifespan, with a large shift during days 4 through 10 posthatch. Two major phyla of bacteria were found to be present within the caeca of aviary raised ducks, with the relative abundance of each phylum varying by age of the duck. Proteobacteria is dominant for the first 3 days of age, and Firmicutes increases and dominates beginning at day 4. Barn raised ducks contained a significant population of Bacteroidetes in addition to Proteobacteria and Firmicutes at later developmental time points, though this phylum was absent in aviary raised ducks. Genera containing pathogens of anseriformes most often found in industry settings were either absent or found as normal parts of the caecal microbial populations. The high level differences in phylum abundance highlight the importance of well-designed sampling strategies for microbiome based studies. Results showed clear distinctions between Pekin Duck caecal contents and those of Broiler Chickens and Turkey in a qualitative comparison. These data provide a reference point for studies of the Pekin Duck through industry grow-out ages, provide a foundation for understanding the types of bacteria that promote health, and may lead to improved methods to increase yields and decrease instances of disease in agricultural production processes.
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In order to be successful in a given environment a plant should invest in a vein network and stomatal distribution that ensures balance between both water supply and demand. Vein density (Dv) and stomatal density (SD) have been shown to be strongly positively correlated in response to a range of environmental variables in more recently evolved plant species, but the extent of this relationship has not been confirmed in earlier diverging plant lineages. In order to examine the effect of a changing atmosphere on the relationship between Dv and SD, five early-diverging plant species representing two different reproductive plant grades were grown for 7 months in a palaeo-treatment comprising an O2:CO2 ratio that has occurred multiple times throughout plant evolutionary history. Results show a range of species-specific Dv and SD responses to the palaeo-treatment, however, we show that the strong relationship between Dv and SD under modern ambient atmospheric composition is maintained following exposure to the palaeo-treatment. This suggests strong inter-specific co-ordination between vein and stomatal traits for our study species even under relatively extreme environmental change. This co-ordination supports existing plant function proxies that use the distance between vein endings and stomata (Dm) to infer plant palaeo-physiology.
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OBJECTIVE: A large national surgical registry was used to establish national benchmarks and associated predictors of major neurologic complications (i.e., coma and stroke) after surgical clipping of unruptured intracranial aneurysms. METHODS: The American College of Surgeons National Surgical Quality Improvement Program data set between 2007 and 2013 was used for this retrospective cohort analysis. Demographic, comorbidity, and operative characteristics associated with the development of a major neurologic complication (i.e., coma or stroke) were elucidated using a backward selection stepwise logistic regression analysis. This model was subsequently used to fit a predictive score for major neurologic complications. RESULTS: Inclusion criteria were met by 662 patients. Of these patients, 57 (8.61%) developed a major neurologic complication (i.e., coma or stroke) within the 30-day postoperative period. On multivariable analysis, operative time (log odds 0.004 per minute; 95% confidence interval [CI], 0.002-0.007), age (log odds 0.05 per year; 95% CI, 0.02-0.08), history of chronic obstructive pulmonary disease (log odds 1.26; 95% CI, 0.43-2.08), and diabetes (log odds 1.15; 95% CI, 0.38-1.91) were associated with an increased odds of major neurologic complications. When patients were categorized according to quartile of a predictive score generated from the multivariable analysis, rates of major neurologic complications were 1.8%, 4.3%, 6.7%, and 21.2%. CONCLUSIONS: Using a large, national multi-institutional cohort, this study established representative national benchmarks and a predictive scoring system for major neurologic complications following operative management of unruptured intracranial aneurysms. The model may assist with risk stratification and tailoring of decision making in surgical candidates.