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.).

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.

The effects of palladium coordination complex speciation and concentration upon the ubiquitous bacterial species Pseudomonas aeruginosa.

The toxicity of three different palladium (Pd) species to Pseudomonas aeruginosa, an environmentally ubiquitous bacterial species, is reported. Palladium was added to chemically-defined minimal media as three complex ion salts, namely sodium tetrachloropalladate (Na2[PdCl4]), tetraamminepalladium(II) chloride ([Pd(NH3)4]Cl2), and potassium hexachloropalladate(IV) (K2[PdCl6]), inoculated with log-phase cultures and incubated for 24 h at 25 °C. Toxicity was tested for Pd concentrations ranging from 6.55 µg/L (0.06 µM Pd) to 250 µg/L (2.33 µM Pd). Minimum inhibitory concentrations (MICs) were determined and growth tracked via optical absorption at 600 nm. Viability and minimum bactericidal concentrations (MBCs) were measured in parallel with dilution, plating and colony forming unit (CFU) counting. MICs for all forms of Pd were 62.5 µg Pd/L, approximately 1000 times lower than previously reported values. The MBCs for PdCl42- and Pd(NH3)42+ were 62.5 µg Pd/L and 125 µg Pd/L for PdCl62-. Pd(NH3)42+ and PdCl62- culture viability at 7.8-31.3 µg Pd/L was not different from controls. However, PdCl42- culture viability was different from the other additives, with decreasing viability at sub-MBC concentrations down to 6.55 µg Pd/L. To understand the possible effect of speciation upon toxicity, the equilibrium speciation of Pd was modeled for all solutions using PHREEQC and found to be dominated by Pd(NH3)3Cl+ (65.6 % of total Pd) and Pd(NH3)42+ (34.2 % total Pd). The juxtaposition of the equilibrium calculations and the toxicity results indicates that the kinetics of ligand exchange between the palladium complexes and the growth medium could influence bacterial response.

Diagnosis and Treatment of Lymphatic Complications of the Groin Following Open Lower Extremity Revascularization with Plastic Surgery Closure.

INTRODUCTION: Lymphatic complications following vascular procedures involving the groin require prompt treatment to limit morbidity. Several treatments have been described, including conservative management, aspiration, sclerotherapy, and direct lymphatic ligation with or without a muscle flap have been described. To date, there is no data indicating which treatment results in the shortest time to recovery. We sought to address this gap by conducting a retrospective cohort study. METHODS: We reviewed all patients who developed a lymphatic complication after undergoing an open revascularization procedure in the groin between 2014 and 2020 in which plastic surgery was involved in the closure. A control group consisted of patients from the same timespan who did not develop a lymphatic complication. Demographics, comorbidities, operative details, and outcomes were compared between these groups. For cases identified with a lymphatic complication, the method of diagnosis, culture data, and treatment details were collected, and outcomes were compared for surgical management versus sclerotherapy. RESULTS: There were 27 lymphatic complications and 60 control patients. The complication group had a higher incidence of aortofemoral bypass (25.8% vs. 8.3%, P = 0.04), and a lower incidence of femoral-to-distal bypass (11.1% vs. 45.0%, P < 0.01). Daily drain output volume from postoperative days 1-5, and days 6-10, was significantly higher in the complication group than in the controls (194.0 vs. 44.0, P < 0.01; and 429.5 vs. 35.0, P < 0.01, respectively). In the lymphatic leak group, 16 patients (59.3%) had surgical treatment and six (22.2%) had sclerotherapy. Of those who had surgery, 71.4% had successful outcomes without the need for an additional intervention, whereas all of the patients analyzed who were treated with sclerotherapy had successful outcomes without further intervention. The average time to resolution was significantly shorter for surgery than for sclerotherapy (38.7 vs. 86.0 days, P = 0.03). CONCLUSIONS: Daily postoperative drain volume can assist with early diagnosis of a lymphatic leak in the groin following an open revascularization procedure. Sclerotherapy and surgery were each successful, but surgery resulted in significantly shorter times to resolution. In the appropriate candidates, surgery should be considered first line management of a lymphatic leak.

Prophylactic Muscle Flaps in Primary Vascular Procedures of the Groin.

BACKGROUND: Complications following vascular procedures involving the groin can lead to significant morbidity. Achieving stable soft tissue coverage over sites of revascularization can help mitigate complications. Prior evidence supports the use of muscle flaps in reoperative groins and in high risk patient populations to reduce postoperative complications. Data regarding the use of prophylactic muscle flap coverage of the groin is lacking. Therefore, the purpose of this study is to evaluate the effect of immediate prophylactic muscle flap coverage of vascular wounds involving the groin. METHODS: A retrospective cohort study was performed on all patients undergoing primary open vascular procedures involving the groin for occlusive, aneurysmal, or oncologic disease between 2014 and 2020 at a single institution where plastic surgery was involved in closure. Patient demographics, comorbidities, surgical details, and postoperative complications were compared between patients who had sartorius muscle flap coverage of the vascular repair versus layered closure alone. RESULTS: A total of 133 consecutive groins were included in our analysis. A sartorius flap was used in 115 groins (86.5%) and a layered closure was used in 18 (13.5%). Wound breakdown was similar between groups (25.2% sartorius vs. 38.9% layered closure, P = 0.26). However, the rate of reoperation was significantly higher in the layered closure group (50.0% vs. 12.2%, P < 0.01). Among patients who experienced wound breakdown (N = 36), a larger proportion of layered closure patients required operative intervention (71.4% vs. 20.7%, P = 0.02). Other rates of complications were not statistically different between groups. CONCLUSIONS: In patients undergoing primary open vascular procedures involving the groin, patients who underwent prophylactic sartorius muscle flap closure had lower rates of reoperation. Although incisional breakdown was similar between the groups overall, the presence of a vascularized muscle flap overlying the vascular repair was associated with reduced need for reoperation and allowed more wounds to be managed with local wound care alone. Consideration should be given to this low morbidity local muscle flap in patients undergoing vascular procedures involving the groin.

Diradical Interactions in Ring-Open Isoxazole.

Electron capture by the σ* LUMO of isoxazole triggers the dissociation of the O-N bond and the opening of the ring. Photodetachment of the resulting anion accesses a neutral structure, in which the O· and ·N bond fragments interact through the intact remainder of the molecular ring and via a 3 Å gap created by the bond dissociation. These through-bond and through-space interactions result in a dense manifold of diradical states, including (in the order of increasing energy) a triplet, an open-shell singlet, a closed-shell singlet, and another triplet state. We report photoelectron spectra that reflect partially resolved signatures of these states. Remarkably, the structure of the isoxazole diradical manifold is qualitatively different from that of the analogous system in oxazole. The distinct properties of the two manifolds are explained by using a coupled-fragments molecular-orbital model. Consistent with the past conclusions [Culberson et al. Phys. Chem. Chem. Phys. 2014, 16, 3964-3972], the lingering through-space interactions between the O· and ·C bond fragments in ring-open oxazole are responsible for the relative stabilization of the closed-shell singlet state, which correlates with the ground-state cyclic structure. In contrast, the placement of the N atom in the terminal position within the ring-open structure of isoxazole is the key factor leading to the near degeneracy of the π and σ* orbitals, favoring a triplet-state configuration.

Patient Characteristics and Outcomes Associated with Decline in Stroke Volumes During the Early COVID-19 Pandemic.

BACKGROUND AND PURPOSE: Delayed evaluation of stroke may contribute to COVID-19 pandemic-related morbidity and mortality. This study evaluated patient characteristics, process measures and outcomes associated with the decline in stroke presentation during the early pandemic. METHODS: Volumes of stroke presentations, intravenous thrombolytic administrations, and mechanical thrombectomies from 52 hospitals from January 1-June 30, 2020 were analyzed with piecewise linear regression and linear spline models. Univariate analysis compared pandemic (case) and pre-pandemic (control) groups defined in relation to the nadir of daily strokes during the study period. Significantly different patient characteristics were further evaluated with logistic regression, and significantly different process measures and outcomes were re-analyzed after propensity score matching. RESULTS: Analysis of 7,389 patients found daily stroke volumes decreased 0.91/day from March 12-26 (p < 0.0001), reaching a nadir 35.0% less than expected, and increased 0.15 strokes/day from March 27-June 23, 2020 (p < 0.0001). Intravenous thrombolytic administrations decreased 3.3/week from February 19-March 31 (p = 0.0023), reaching a nadir 33.4% less than expected, and increased 1.4 administrations/week from April 1-June 23 (p < 0.0001). Mechanical thrombectomy volumes decreased by 1.5/week from February 19-March 31, 2020 (p = 0.0039), reaching a nadir 11.3% less than expected. The pandemic group was more likely to ambulate independently at baseline (p = 0.02, OR = 1.60, 95% CI = 1.08-2.42), and less likely to present with mild stroke symptoms (NIH Stroke Scale ≤ 5; p = 0.04, OR = 1.01, 95% CI = 1.00-1.02). Process measures and outcomes of each group did not differ, including door-to-needle time, door-to-puncture time, and successful mechanical thrombectomy rate. CONCLUSION: Stroke presentations and acute interventions decreased during the early COVID-19 pandemic, at least in part due to patients with lower baseline functional status and milder symptoms not seeking medical care. Public health messaging and initiatives should target these populations.

Deprotonation of Isoxazole: A Photoelectron Imaging Study.

We report a photoelectron imaging study of gas-phase deprotonation of isoxazole in which spectroscopic data are compared to the results of electronic structure calculations for the anion products corresponding to each of three possible deprotonation sites. The observed photoelectron spectra are assigned to a mixture of the anion isomers. Deprotonation at the most acidic (C5) and the least acidic (C4) positions yields the respective C5- and C4-isoxazolide anions, while the reaction at the intermediate-acidity C3 site leads to a cleavage of the O-N bond and an opening of the ring in the anion. Following photodetachment, the ground states of neutral C5- and C4-isoxazolyl are assigned to be σ radicals (X2A'), while the ground-state neutral derived from the ring-open C3-anion is a π radical (X2A″). The relative intensities of the spectral bands exhibit sensitivity to the ion source conditions, giving evidence of competing and varying contributions of the dominant C5 and C3, as well as possible C4, deprotonation pathways.

Seizure Rescue Medication Use among US Pediatric Epilepsy Providers: A Survey of the Pediatric Epilepsy Research Consortium.

OBJECTIVE: To assess how pediatric neurologists prescribe home seizure rescue medications to treat acute prolonged seizures and clusters of seizures in children. STUDY DESIGN: A brief, email survey was sent to the members of the Pediatric Epilepsy Research Consortium assessing seizure rescue medication prescribing practices for patients of different age groups, cognitive abilities, and seizure type. Survey responses were anonymous. RESULTS: Thirty-six respondents (of 76 surveyed; 47% response rate) completed the survey. Rectal diazepam was the most commonly chosen rescue medication for a prolonged convulsive seizure in a severely developmentally delayed 16-year-old (44%) and typical and delayed 7-year-old (44% and 61%, respectively), 3-year-old (78% and 86%, respectively), and 9-month-old (83%) patients. Most responders (69%) indicated that developmentally typical 16-year-olds would be prescribed intranasal midazolam. For clusters of seizures, clonazepam orally disintegrating tablets were the most frequent first-line option in all age groups, except developmentally delayed 3-year-old and 9-month-old children, for whom rectal diazepam was chosen more commonly. Medication dosing generally followed standard dosing guidelines with very few exceptions. CONCLUSIONS: Rectal diazepam remains the most frequently used rescue medication for prolonged seizures for nearly all age groups, except in developmentally typical teenagers, for whom intranasal midazolam is used more often. Clonazepam orally disintegrating tablets are the most frequently used medication for treatment of clusters of seizures, except in younger patients. Further work is necessary to establish best practices for type and administration route of seizure rescue medications.

Photoelectron Spectroscopy of Biacetyl and Its Cluster Anions.

Photoelectron spectroscopy of the biacetyl (dimethylglyoxal) anion reveals the properties of the ground singlet and lowest triplet electronic states of the neutral biacetyl (BA) molecule. Due to the broad and congested nature of the singlet transition, which peaks at a vertical detachment energy VDE = 1.12(5) eV, only an upper bound of the adiabatic electron affinity of BA could be determined: EA(BA) < 0.7 eV. A narrower and more structured triplet band peaking at VDE = 3.17(2) eV reveals the adiabatic electron binding energy of the triplet to be 3.05(2) eV. These results are in good agreement with ab initio (coupled-cluster) calculations. The lowest-energy structures of the anion, singlet, and triplet states of biacetyl are characterized by different orientations of the methyl groups within the molecular frame. In the ground singlet state of neutral BA, the methyl torsion is offset by ∼60° compared to that of the anion, while in the triplet the methyl orientation is similar to that of the anion. Photoelectron spectra of the cluster anions reveal that the intermolecular interactions in the homogeneously solvated (BA) n- clusters are significantly stronger than the interactions of BA- with N2O or even of BA- with H2O. To account for these observations, π-π bonded structures of the dimer and trimer anions of biacetyl are proposed based on density-functional theory calculations. The analysis of the proposed structures indicates that the negative charge in the (BA) n- cluster anions, at least in the dimer and the trimer, is significantly delocalized between all BA moieties present and there is a significant degree of covalent bonding within the cluster.

Unilateral Phrenic Nerve Palsy in Infants with Congenital Zika Syndrome.

Since the first identification of neonatal microcephaly cases associated with congenital Zika virus infection in Brazil in 2015, a distinctive constellation of clinical features of congenital Zika syndrome has been described. Fetal brain disruption sequence is hypothesized to underlie the devastating effects of the virus on the central nervous system. However, little is known about the effects of congenital Zika virus infection on the peripheral nervous system. We describe a series of 4 cases of right unilateral diaphragmatic paralysis in infants with congenital Zika syndrome suggesting peripheral nervous system involvement and Zika virus as a unique congenital infectious cause of this finding. All the patients described also had arthrogryposis (including talipes equinovarus) and died from complications related to progressive respiratory failure.

Percutaneous Thermal Ablation of Spinal Metastases: Recent Advances and Review.

OBJECTIVE: The purpose of this study was to review the available armamentarium and most recent advances in minimally invasive, image-guided percutaneous thermal ablation for treatment of spinal metastases. CONCLUSION: Minimally invasive percutaneous spine thermal ablation technologies have proved safe and effective in management of selected patients with spinal metastases. Special attention to procedure techniques including choice of ablation modality, thermoprotection, adequacy of treatment, and postablation imaging is essential for improved patient outcomes.

Degradation of Glyphosate by Mn-Oxide May Bypass Sarcosine and Form Glycine Directly after C-N Bond Cleavage.

Glyphosate is the active ingredient of the common herbicide Roundup. The increasing presence of glyphosate and its byproducts has raised concerns about its potential impact on the environment and human health. In this research, we investigated abiotic pathways of glyphosate degradation as catalyzed by birnessite under aerobic and neutral pH conditions to determine whether certain pathways have the potential to generate less harmful intermediate products. Nuclear magnetic resonance (NMR) spectroscopy and high-performance liquid chromatography (HPLC) were utilized to identify and quantify reaction products, and density functional theory (DFT) calculations were used to investigate the bond critical point (BCP) properties of the C-N bond in glyphosate and Mn(IV)-complexed glyphosate. We found that sarcosine, the commonly recognized precursor to glycine, was not present at detectable levels in any of our experiments despite the fact that its half-life (∼13.6 h) was greater than our sampling intervals. Abiotic degradation of glyphosate largely followed the glycine pathway rather than the AMPA (aminomethylphosphonic acid) pathway. Preferential cleavage of the phosphonate adjacent C-N bond to form glycine directly was also supported by our BCP analysis, which revealed that this C-N bond was disproportionately affected by the interaction of glyphosate with Mn(IV). Overall, these results provide useful insights into the potential pathways through which glyphosate may degrade via relatively benign intermediates.

Isolated Internal Carotid Artery Thrombus and Cerebral Infarction in a Patient with Necrotizing Pancreatitis: Case Report.

Isolated internal carotid artery (ICA) thrombus in the absence of underlying atherosclerotic disease is a rare entity. We report a case of a patient presenting with right arm weakness, slurred speech, and altered mental status in the setting of acute on chronic pancreatitis. The patient was found to have scattered left cerebral hemisphere cortical infarctions, and catheter angiography confirmed the presence of intraluminal left ICA thrombus, with no evidence of atherosclerotic disease in the cervical or intracranial vasculature. Further workup also demonstrated the presence of anemia of chronic disease. The patient was initiated on anticoagulation, and follow-up imaging demonstrated a complete resolution of the left ICA thrombus. In the reported case, coagulopathy in the setting of acute on chronic pancreatitis was presumably the primary etiology. Anemia of chronic disease, related to a proinflammatory state, may also play a contributory role.

Clinical and angiographic outcomes in patients with intracranial aneurysms treated with the pipeline embolization device: intra-procedural technical difficulties, major morbidity, and neurological mortality decrease significantly with increased operator experience in device deployment and patient management.

PURPOSE: Flow diversion constitutes a pivotal advancement in endovascular intracranial aneurysm treatment, but requires development of a new skill set. The aim of this study is to determine whether outcomes after treatment with the Pipeline Embolization Device improve with experience. METHODS: We retrospectively reviewed all patients with intracranial aneurysms treated with Pipeline at two centers over a 4.5-year period. Baseline patient and aneurysm characteristics, complications, and angiographic outcomes were analyzed. RESULTS: One hundred forty patients underwent 150 Pipeline procedures to treat 167 intracranial aneurysms during the study period, 109 women, mean age 55.4 years. One hundred twenty-six aneurysms were ICA, mean size 10.2 mm and mean neck 6.4 mm. Intra-procedural technical difficulties were higher during the first 75 procedures compared with the subsequent 75 (13.3 vs 2.7%; p = 0.03), as combined major morbidity and neurological mortality (14.7 vs 4%; p = 0.046). In multivariate regression analysis, increased operator experience with Pipeline remained an independent predictor of intra-procedural technical difficulties (p = 0.02, odds ratio (OR) 0.015, 95% CI 0.0004-0.55) and combined major morbidity and neurological mortality (p = 0.03, OR 0.16, 95% CI 0.03-0.84). At last follow-up, 123 aneurysms were completely occluded (81.5%, mean 24 months). In our cohort, age ≤ 53 years was an independent predictor of complete aneurysm occlusion at last follow-up (p = 0.001, OR 0.92, 95% CI 0.88-0.97). Five aneurysms were retreated (3.3%). CONCLUSION: The Pipeline embolization device is an effective treatment for intracranial aneurysms. The risk of intra-procedural technical difficulties and combined major morbidity and neurological mortality decreases significantly with increased operator experience in Pipeline deployment and patient management.

Electron affinity and excited states of methylglyoxal.

Using photoelectron imaging spectroscopy, we characterized the anion of methylglyoxal (X2A″ electronic state) and three lowest electronic states of the neutral methylglyoxal molecule: the closed-shell singlet ground state (X1A'), the lowest triplet state (a3A″), and the open-shell singlet state (A1A″). The adiabatic electron affinity (EA) of the ground state, EA(X1A') = 0.87(1) eV, spectroscopically determined for the first time, compares to 1.10(2) eV for unsubstituted glyoxal. The EAs (adiabatic attachment energies) of two excited states of methylglyoxal were also determined: EA(a3A″) = 3.27(2) eV and EA(A1A″) = 3.614(9) eV. The photodetachment of the anion to each of these two states produces the neutral species near the respective structural equilibria; hence, the a3A″ ← X2A″ and A1A″ ← X2A″ photodetachment transitions are dominated by intense peaks at their respective origins. The lowest-energy photodetachment transition, on the other hand, involves significant geometry relaxation in the X1A' state, which corresponds to a 60° internal rotation of the methyl group, compared to the anion structure. Accordingly, the X1A' ← X2A″ transition is characterized as a broad, congested band, whose vertical detachment energy, VDE = 1.20(4) eV, significantly exceeds the adiabatic EA. The experimental results are in excellent agreement with the ab initio predictions using several equation-of-motion methodologies, combined with coupled-cluster theory.

CdiA promotes receptor-independent intercellular adhesion.

CdiB/CdiA proteins mediate inter-bacterial competition in a process termed contact-dependent growth inhibition (CDI). Filamentous CdiA exoproteins extend from CDI(+) cells and bind specific receptors to deliver toxins into susceptible target bacteria. CDI has also been implicated in auto-aggregation and biofilm formation in several species, but the contribution of CdiA-receptor interactions to these multi-cellular behaviors has not been examined. Using Escherichia coli isolate EC93 as a model, we show that cdiA and bamA receptor mutants are defective in biofilm formation, suggesting a prominent role for CdiA-BamA mediated cell-cell adhesion. However, CdiA also promotes auto-aggregation in a BamA-independent manner, indicating that the exoprotein possesses an additional adhesin activity. Cells must express CdiA in order to participate in BamA-independent aggregates, suggesting that adhesion could be mediated by homotypic CdiA-CdiA interactions. The BamA-dependent and BamA-independent interaction domains map to distinct regions within the CdiA filament. Thus, CdiA orchestrates a collective behavior that is independent of its growth-inhibition activity. This adhesion should enable 'greenbeard' discrimination, in which genetically unrelated individuals cooperate with one another based on a single shared trait. This kind-selective social behavior could provide immediate fitness benefits to bacteria that acquire the systems through horizontal gene transfer.

A cluster of acute flaccid paralysis and cranial nerve dysfunction temporally associated with an outbreak of enterovirus D68 in children in Colorado, USA.

BACKGROUND: Clusters of acute flaccid paralysis or cranial nerve dysfunction in children are uncommon. We aimed to assess a cluster of children with acute flaccid paralysis and cranial nerve dysfunction geographically and temporally associated with an outbreak of enterovirus-D68 respiratory disease. METHODS: We defined a case of neurological disease as any child admitted to Children's Hospital Colorado (Aurora, CO, USA) with acute flaccid paralysis with spinal-cord lesions involving mainly grey matter on imaging, or acute cranial nerve dysfunction with brainstem lesions on imaging, who had onset of neurological symptoms between Aug 1, 2014, and Oct 31, 2014. We used Poisson regression to assess whether the numbers of cases during the outbreak period were significantly greater than baseline case numbers from a historical control period (July 31, 2010, to July 31, 2014). FINDINGS: 12 children met the case definition (median age 11·5 years [IQR 6·75-15]). All had a prodromal febrile illness preceding neurological symptoms by a median of 7 days (IQR 5·75-8). Neurological deficits included flaccid limb weakness (n=10; asymmetric n=7), bulbar weakness (n=6), and cranial nerve VI (n=3) and VII (n=2) dysfunction. Ten (83%) children had confluent, longitudinally extensive spinal-cord lesions of the central grey matter, with predominant anterior horn-cell involvement, and nine (75%) children had brainstem lesions. Ten (91%) of 11 children had cerebrospinal fluid pleocytosis. Nasopharyngeal specimens from eight (73%) of 11 children were positive for rhinovirus or enterovirus. Viruses from five (45%) of 11 children were typed as enterovirus D68. Enterovirus PCR of cerebrospinal fluid, blood, and rectal swabs, and tests for other causes, were negative. Improvement of cranial nerve dysfunction has been noted in three (30%) of ten children. All ten children with limb weakness have residual deficits. INTERPRETATION: We report the first geographically and temporally defined cluster of acute flaccid paralysis and cranial nerve dysfunction in children associated with an outbreak of enterovirus-D68 respiratory illness. Our findings suggest the possibility of an association between enterovirus D68 and neurological disease in children. If enterovirus-D68 infections continue to happen in an endemic or epidemic pattern, development of effective antiviral or immunomodulatory therapies and vaccines should become scientific priorities. FUNDING: National Center for Advancing Translational Sciences, National Institutes of Health.

Drill-Assisted Biopsy of the Axial and Appendicular Skeleton: Safety, Technical Success, and Diagnostic Efficacy.

The purpose of this study was to evaluate the safety, technical success rate, and diagnostic efficacy of drill-assisted axial and appendicular bone biopsies. During a 3-y period, 703 drill-assisted biopsies were performed. The cohort included 54.2% men, with a mean age of 57.6 y ± 17.1. Median lesion volume was 10.9 mL (interquartile range, 3.4-30.2 mL). Lesions were lytic (31.7%), sclerotic (21.2%), mixed lytic and sclerotic (27.7%), or normal radiographic bone quality (19.3%). No complications were reported. The technical biopsy success rate was 99.9%. Crush artifact was present in 5.8% of specimens submitted for surgical pathologic examination, and 2.1% of specimens were inadequate for histologic evaluation.