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Accurate prediction of solubility of polymers in solvents a priori is highly desirable in practice. To this end, the Flory-Huggins interaction parameter χ is commonly used and molecular dynamics simulation, a powerful computational tool, has been used for such a purpose. To calculate χ , there exist three possible strategies using molecular dynamics simulation. One is through the calculation of Hildebrand solubility parameters of the pure components while the other two are to calculate the enthalpy of solvation and Gibbs free energy of solvation for the solution, respectively. This study evaluated these three strategies using binary solutions containing a hydrophobic or hydrophilic polymer (polyisobutylene, polystyrene, cis and trans polybutadiene, cis and trans polyisoprene, poly(ethylene oxide), and polyacrylamide) and an aliphatic solvent - cyclohexane. We found that χ determined via solubility parameters predicted the solubility trend but deviated significantly from experimental values. On the other hand, the enthalpy of solvation approach provided the most accurate χ values, compared to experiment, at a reasonable computational demand, especially for hydrocarbon polymers, while the Gibbs free energy of solvation approach, though more computationally intensive, did not significantly improve χ from the enthalpy of solvation approach. In particular, the Gibbs free energy of solvation approach overestimated χ for non-polar polymers. A conformational analysis of the solvated polymers revealed that all polymers collapsed in cyclohexane with polyethylene oxide and polyacrylamide collapsed the most as expected. For the two polar polymers used, the collapse was evidenced by abrupt changes in radius of gyration ( R g ) and solvent accessible surface area (SASA) in the early stage of molecular dynamics simulation trajectories, and plateauing at much lower final values. Conversely, the hydrocarbon polymers exhibited minimal deviation from the expected R g and barely any change in SASA with time. Our findings demonstrated that there exist differences in the accuracy and computational resources used when different molecular dynamics simulation strategies are used in the determination of χ .

Context: To determine the miscibility of liquids at high temperatures using the concept of Hildebrand solubility parameter δ , the current practice is to examine the difference in δ between two liquids at room temperature, assuming that δ is not sensitive to temperature. However, such an assumption may not be valid for certain polymer blends and solutions. Therefore, a knowledge of the δ values of the liquids of interest at high temperatures is desirable. The determination of δ at high temperatures, especially for high-molecular-weight polymers, is impossible, as polymers have vapor pressures of zero. To this end, molecular dynamics (MD) simulations provide a practical means for determining δ over a wide range of temperatures. In this work, we study the temperature dependence of δ of five hydrocarbon polymers: polyethylene (PE), isotactic and atactic polypropylene (i-PP and a-PP), polyisobutylene (PIB), and polyisoprene (PI) in five hydrocarbon solvents: n-pentane, n-hexane, n-dodecane, isobutene, and cyclohexane. The polymers are modeled as monodisperse chains with 100 repeat units. The average δ values of PE, i-PP, a-PP, PIB, and PI at 300 K are determined as 18.6, 14.9, 14.6, 14.3, and 16.4 MPa 1/2 , respectively, in a good agreement with experimental data. The δ values of these polymers at various temperatures are also determined. The temperature dependence of δ is fitted to two linear equations, one above and the other below the polymer's glass transition temperature T g . The δ values are more sensitive to temperature at T ≥ T g . The T g values of the polymers, determined based upon their specific volumes and δ values agree with the experiment qualitatively. The determination of the temperature dependence of δ has a great potential for industrial applications, such as determining miscibility, developing polymeric organogelators as flocculants and oil spill treating agents, and identifying potential solvents and ideal processing temperatures., Methods: The MD simulations are performed using the GROMACS 2022.3 package with optimized potential for liquid simulations-all atom (OPLS-AA) force field parameters. All polymers are built as extended chains using CHARMM-GUI Polymer Builder., (© 2024. His Majesty the King in Right of Canada, as represented by the Minister of Natural Resources.)

Background: At least 20% of strokes involve the posterior circulation (PC). Compared to the anterior circulation, posterior circulation infarction (POCI) are frequently misdiagnosed. CT perfusion (CTP) has advanced stroke care by improving diagnostic accuracy and expanding eligibility for acute therapies. Clinical decisions are predicated upon precise estimates of the ischaemic penumbra and infarct core. Current thresholds for defining core and penumbra are based upon studies of anterior circulation stroke. We aimed to define the optimal CTP thresholds for core and penumbra in POCI., Methods: Data were analyzed from 331-patients diagnosed with acute POCI enrolled in the International-stroke-perfusion-registry (INSPIRE). Thirty-nine patients with baseline multimodal-CT with occlusion of a large PC-artery and follow up diffusion weighted MRI at 24-48 h were included. Patients were divided into two-groups based on artery-recanalization on follow-up imaging. Patients with no or complete recanalisation were used for penumbral and infarct-core analysis, respectively. A Receiver operating curve (ROC) analysis was used for voxel-based analysis. Optimality was defined as the CTP parameter and threshold which maximized the area-under-the-curve. Linear regression was used for volume based analysis determining the CTP threshold which resulted in the smallest mean volume difference between the acute perfusion lesion and follow up MRI. Subanalysis of PC-regions was performed., Results: Mean transit time (MTT) and delay time (DT) were the best CTP parameters to characterize ischaemic penumbra (AUC = 0.73). Optimal thresholds for penumbra were a DT >1 s and MTT>145%. Delay time (DT) best estimated the infarct core (AUC = 0.74). The optimal core threshold was a DT >1.5 s. The voxel-based analyses indicated CTP was most accurate in the calcarine (Penumbra-AUC = 0.75, Core-AUC = 0.79) and cerebellar regions (Penumbra-AUC = 0.65, Core-AUC = 0.79). For the volume-based analyses, MTT >160% demonstrated best correlation and smallest mean-volume difference between the penumbral estimate and follow-up MRI ( R 2 = 0.71). MTT >170% resulted in the smallest mean-volume difference between the core estimate and follow-up MRI, but with poor correlation ( R 2 = 0.11)., Conclusion: CTP has promising diagnostic utility in POCI. Accuracy of CTP varies by brain region. Optimal thresholds to define penumbra were DT >1 s and MTT >145%. The optimal threshold for core was a DT >1.5 s. However, CTP core volume estimates should be interpreted with caution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Edwards, Cappelen-Smith, Cordato, Bivard, Churilov, Lin, Chen, Garcia-Esperon, Butcher, Kleinig, Choi, Cheng, Dong, Aviv and Parsons.)

Covalent linkages between lignin and the surrounding carbohydrate network, often referred to as lignin-carbohydrate complexes (LCCs), have been proposed to affect the organization of the biomass microstructure and directly correlate with the recalcitrant nature of biomass. However, the existence and frequency of these LCC linkages remain controversial and largely unknown, primarily due to the harsh experimental techniques available to characterize them. During the predominant lignin polymerization pathway a reactive intermediate is formed. Though this intermediate can covalently bind to the surrounding cellulose/hemicellulose matrix, it has been traditionally assumed to react exclusively with water, leading to purely physical interactions between lignin and cellulose/hemicellulose in the cell wall. This work, for the first time, provides direct evidence of the molecular mechanism of the formation of benzyl ether and benzyl ester LCC linkages via the speculated lignin polymerization pathway. The formation of these LCC linkages showed thermodynamic favorability, while remaining kinetically facile, compared to the previously assumed mechanism of the lignin intermediate reacting with water. The present work suggests that the surrounding carbohydrate matrix could play a role in the organization of lignin deposition and these covalent linkages could be a key factor in biomass recalcitrance.

Purpose: To review our institutional experience with the surgical management of prolactinomas through the endoscopic endonasal approach with specific focus on cavernous sinus invasion., Methods: Clinical and radiographic data were collected retrospectively from the electronic medical record of 78 consecutive patients with prolactinomas undergoing endoscopic endonasal resection from 2002 to 2019. Immediate and late post-operative remission were defined as prolactin < 20 ng/mL within 14 days and 1-year of surgery without adjuvant therapy, respectively. Cavernous sinus invasion was quantified by Knosp score., Results: A total of 78 patients with prolactinoma, 59% being male, underwent surgical resection with a mean age of 37 ± 13 years. Indications for surgery were medication resistance in 38 patients (48.7%), medication intolerance in 11 (14.1%), and patient preference in 29 (37.2%). Patients with Knosp 0-2 achieved higher immediate remission rates (83.8%) compared to patients with Knosp 3 (58.8%) and Knosp 4 (41.7%) patients (p = 0.003). Long-term remission rates were 48.7% and increased to 71.8% when combined with adjuvant treatments. Knosp 4 prolactinomas had significantly higher tumor volumes, higher preoperative prolactin levels, higher recurrence rates, higher rates of adjuvant therapy utilization, and were more likely to have failed dopamine agonist therapy compared to other tumor grades (p < 0.05). We encountered 18 complications in our series, and no cerebrospinal fluid leaks., Conclusion: The endoscopic endonasal approach is a safe and effective modality that can be employed in properly selected patients with invasive prolactinomas. It is associated with improved control and remission rates despite cavernous sinus invasion, though at a lower rate than without invasion., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Carotid blister aneurysms remain a formidable surgical challenge with varied surgical options. There have been significant advancements in the endovascular management of these aneurysms with the introduction of flow diverters. The comparative risk profiles for different endovascular options compared to surgical management of these lesions is not completely understood., Methods: The study is a comprehensive systematic review and meta-analysis on the treatment of carotid blood blister aneurysms. Pubmed searches were used to identify relevant articles and patient level data was extracted. Two and three group analyses were conducted comparing surgical and endovascular strategies and surgical, stent coil and flow diversion techniques respectively. Patient outcomes were graded on the modified Rankin Scale with a score of 2 or less defined as favorable., Results: In total, 83 studies (41 and 42 studies on surgical and endovascular interventions, respectively) with 1119 patients met our inclusion criteria. A statistically significant difference (at the 5% level of significance) in the effect among three different interventions was not found (Q = 3.41, p = 0.1815) under the random-effect model. Our results did show summary proportions of favorable outcomes were higher in the stent coil (0.87, 95% CI: 0.79 - 0.94) and flow diversion (0.87, 95% CI: 0.75 - 0.96) than that of surgery (0.76, 95% CI: 0.71 - 0.83)., Conclusions: Our results suggest a trend towards improved patient outcomes with endovascular techniques compared to surgical strategies but statistical significance was not achieved. We also found that endovascular techniques compare favorably. Increasing retreatments were found to negatively affect patient outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Australia and New Zealand have achieved excellent community control of COVID-19 infection. In light of the imminent COVID-19 vaccination roll out in both countries, representatives from the Haematology Society of Australia and New Zealand and infectious diseases specialists have collaborated on this consensus position statement regarding COVID-19 vaccination in patients with haematological disorders. It is our recommendation that patients with haematological malignancies, and some benign haematological disorders, should have expedited access to high-efficacy COVID-19 vaccines, given that these patients are at high risk of morbidity and mortality from COVID-19 infection. Vaccination should not replace other public health measures in these patients, given that the effectiveness of COVID-19 vaccination, specifically in patients with haematological malignancies, is not known. Given the limited available data, prospective collection of safety and efficacy data of COVID-19 vaccination in this patient group is a priority., (© 2021 Royal Australasian College of Physicians.)

The aim of the current research study is to conduct a comparative assessment of biocompatibility of zwitterionic-coated polyether sulfone (PES) clinical hemodialysis (HD) membranes using both theoretical and experimental methods. Fibrinogen plays a key role in assessing membrane hemocompatibility since its membrane-surface adsorption triggers several biological reactions, complete thrombosis and embolism. As a result, adsorption of fibrinogen on the untreated PES surface and novel synthesized PES coated with poly 3-((3-(3-carboxy-2,5-dimethyltridecanamido) propyl) dimethylammonio) propane-1-sulfonate as a zwitterion (ZW) was compared. Specifically, the comparison was conducted using in situ synchrotron based micro computed tomography imaging (SR-μCT), Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectroscopy, and Scanning Electron Microscopy (SEM). The in situ SR-μCT showed that fibrinogen adsorption and membrane fouling were intense on PES membrane surface. However, there was insignificant fouling in the middle layer of zwitterion coated PES membrane (PES-ZW). Moderate shifting of peaks was observed in ATR-FTIR spectra of the adsorbed fibrinogen when compared to the bulk protein spectra, which may be due to the conformational transformations occurring during the adsorption process. The spectral features indicate that PES-ZW surface has a lower adsorption affinity for fibrinogen than that for the PES surface. In this innovative study, the use of molecular modeling docking to evaluate the interaction of fibrinogen active pose with PES-ZW and PES models with the aim of gaining an in depth understanding of the functional group responsible for the interactions was explored. The PES and PES/zwitterion hemodialysis membrane models indicated minimum binding energies with fibrinogen by -6.00 and -6.70 kcal/mol, respectively. Docking studies thus suggest that the membrane's sulfone functional groups play an essential key role during the fibrinogen interaction and adsorption. The HD patients' uremic samples were incubated in vitro with PES and PES-ZW membranes for the inflammatory biomarkers released of Serpin/Antithrombin-III, Properdin, C5a, IL-1α, IL-1β, TNF-α, and IL6. This study's results emphasize that even though a neutral charge of synthesized novel zwitterion PES, which enhances biocompatibility, the sulfone group still significantly affected the interactions with fibrinogen., Competing Interests: Declaration of competing interest No conflict of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

End stage renal disease (ESRD) patients depend on hemodialysis (HD) as a life-sustaining treatment, but HD membrane properties play a critical role in blood activation during HD and can lead to severe patient outcomes. This study reports on a series of investigations on the common clinical HD membranes available in Canadian hospitals to explore the key reasons behind their susceptibility to blood activation and unstable cytokine. Clinical HD membranes composed of cellulose triacetate (CTA) and polyvinylpyrrolidone: polyarylethersulfone (PAES: PVP) were thoroughly characterized in terms of morphology and chemical composition. Membrane-surface interactions with uremic blood samples after HD treatment were probed using Fourier Transform Infra-Red (FTIR) and Raman spectroscopic techniques in order to understand changes in chemistry on membrane fibers. In addition, as part of this innovative study, we utilized Molecular Modeling Docking to examine the interactions of human blood proteins and membrane models to gain an in-depth understanding of functional group types responsible for perceived interactions. In-vitro adsorption of fibrinogen on different clinical HD membranes was compared at similar clinical operating conditions. Samples were collected from dialysis patients to ascertain the extent of inflammatory biomarkers released, before, during (30 and 90 min) and after dialysis (4 h). Collected blood samples were analyzed using Luminex assays for the inflammatory biomarkers of Serpin/Antithrombin-III, Properdin, C5a, 1L-1α, 1L-1β, TNF-α, IL6, and vWF. We have likewise incubated uremic blood in vitro with the two membrane materials to determine the impact that membrane materials pose in favor of activation away from the hydrodynamics influences. The results of our morphological, chemical, spectroscopic, and in vitro incubation analyses indicate that CTA membranes have a smoother surface and higher biocompatibility than PAES: PVP membranes, however, it has smaller pore size distribution, which results in poor clearance of a broad spectrum of uremic toxins. However, the rougher surface and greater hydrophilicity of PAES: PVP membranes increases red blood cell rupture at the membrane surface, which promotes protein adsorption and biochemical cascade reactions. Molecular docking studies indicate sulfone functional groups play an important role in the adsorption of proteins and receptors. PAES: PVP membranes result in slower but greater adsorption of fibrinogen, but are more likely to experience reversible and irreversible fouling as well as backfiltration. Our major finding is that a single dialysis session, even with a more biocompatible membrane such as CTA, increases the levels of complement and inflammation factors, but to a milder extent than dialysis with a PAES membrane.

Based upon the Doolittle concept that viscosity and free volume are inversely related, we used the Boltzmann equation along with a polymer free volume theory to calculate the viscosity (η) of polyethylene with three different molecular structures - linear, ring and four-arm symmetrical star - over a molecular weight (M) range of 420-14 000 g mol-1. Free volume parameters were estimated using the Polymer Reference Interaction Site Model (PRISM) and generic van der Waals (GvdW) equation. The polymer free volume theory was able to describe the crossovers in the molecular weight dependence of the viscosity of the aforementioned molecular structures. In particular, the crossover for the linear structure was predicted at about 3000 g mole-1 with η ∼ M1.5 in the unentangled regime and η ∼ M3.3 in the entangled regime that agree reasonably well with experiment. The predictions for the other two structures also agree with the available simulation data. We also demonstrated that the accuracy of the viscosity prediction was sensitive to the difference between two free volume parameters (i.e., (φ+ - F)). Here, F signifies the probability of a bead finding free volume greater than the critical free volume while the fraction of such beads (φ+) can be used to calculate the activation energy. The theory also reproduced the temperature dependence of η for the linear structure at different M, giving apparent activation energy (Eappa) values in the range of 5.30-7.70 kcal mole-1 that are in good agreement with experimental values of 5.50-6.75 kcal mole-1. This work demonstrates for the first time that viscosity of polymer melts can be determined from the polymer free volume theory.

A carotid-cavernous fistula (CCF) is an abnormal connection between the carotid circulation and the cavernous sinus. Treatment of CCFs often consists of obliteration of the fistula by a transarterial or transvenous endovascular approach using embolic agents. However, fistula embolization is often halted due to the potential embolic complications that may arise from the retrograde flow of the embolic agents into the arterial circulation, which often leads to the development of fistula recurrence. Moreover, retreatment of a CCF recurrence is challenging and more complex approaches may be required. In this technical note, we describe our experience with CCF embolization in 25 patients treated at a single center. We utilized a transvenous approach for CCF embolization with simultaneous balloon occlusion of the internal carotid artery during the infusion of the embolic material into the fistula. In our series, this simultaneous protection of the internal carotid artery showed to be a safe technique to prevent embolic complications and to achieve successful obliteration of the fistula. On follow-up, 2 cases presented a recurrence, one due to technical difficulties and the other related to an undetected vascular injury. In conclusion, this technique provides a safe approach in the treatment of CCFs by decreasing the risk of embolic complications and increasing the effectiveness of the embolic agents in accomplishing the obliteration of the CCF., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Epidural hematomas (EDHs) involving the venous sinuses are uncommon and carry the risk of hemorrhage or venous infarction. We report the largest case series for superior sagittal sinus- and transverse sinus-related EDHs including surgical and nonsurgical management. We compare our findings to the relevant literature., Methods: A retrospective review of the EDH cases at our center was performed from 2013-2018. Patients were analyzed by surgical versus conservative management, outcomes, and complications., Results: Of the 268 EDH patients identified, 32 involved the venous sinuses (23 supratentorial and 9 infratentorial). Ten of the patients had surgery, and 22 were managed conservatively. No surgical complications occurred, and all had a Glasgow Outcome Scale score of 5 at follow-up. All of the nonsurgical patients had a Glasgow Outcome Scale score of 4 or 5 at follow-up except for 1 patient with prior disability. The literature search resulted in 39 infratentorial and 47 supratentorial EDHs involving venous sinuses., Conclusions: Surgical and nonsurgical management of EDHs involving the venous sinuses are both viable options with good outcomes. Surgical intervention is based on location, size, neurologic examination, expansion on serial imaging, and vascular imaging findings. Surgery has the potential for significant complications, but all surgical patients in our series had good outcomes at follow-up. Similarly, nonsurgically managed patients had good outcomes and our overall series demonstrates better outcomes with fewer complications than other similar series in the literature., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The effect of temperature on the chain length (N) dependence of the diffusivity of oligomers (with N = 10-60 carbon atoms) was theoretically studied using the free volume theory of Wong and Choi [Soft Matter, 2019, 15, 9300-9309] along with the experimental data of von Meerwall et al. [J. Chem. Phys., 1998, 108, 4299-4304]. Experimental data showed that D cm ∼N v and that becomes less negative as temperature increases but is always stronger than -1 as obtained in the Rouse model. The theory successfully predicts the exponent v as a function of temperature.

A free volume theory of linear polyethylene (PE) melts [Soft Matter, 2019, 15, 9300-9309] was used to describe the crossover in the size dependence of the center-of-mass diffusion coefficients of ring PE melts from Dcm ∼ N-1.03±0.15 to Dcm ∼ N-1.88±0.14 at Nc ≈ 100. Parameters in the theory were determined theoretically by either the polymer reference interaction site model (PRISM) theory or molecular dynamics (MD) simulation data. The former method is computationally less expensive, whereas the latter gives more accurate results in calculating the temperature dependence of Dcm as different intermolecular and intramolecular potentials were explicitly included in the equation of motion. Both approaches were able to describe the dynamics below and above the crossover in the size dependence of Dcm.

A free volume theory was developed to account for the crossover of the chain length dependence of the center-of-mass self-diffusion coefficient of linear polymers from unentangled to entangled regimes. Similar to the original free volume theory of Cohen and Turnbull, this theory requires information about the free volume overlapping factor (α), critical free volume per bead (v), and mean free volume per bead (〈v f,i 〉). However, one additional parameter is needed and it is the critical fraction of beads having free volume greater than or equal to αv termed as φ + . Here, α and v can be readily determined from the intermolecular and intramolecular radial distribution functions (i.e., g(r) and g intra (r)) obtained from molecular dynamics (MD) simulation and they were found to be 0.5 and 0.0257 nm 3 , respectively, for polyethylene melts and it is not dependent on N. 〈v f,i 〉 was determined using the generic van der Waals (GvdW) equation of state and it had a value of 0.01 nm 3 and the volume available to each bead can also be determined by Voronoi tessellation (VT) on the corresponding MD simulation trajectories. VT yielded exact probability of finding a certain amount of free volume and the free volume distribution was found in the form of the gamma distribution that is consistent with the positron annihilation lifetime spectroscopy observation. Finally, φ + was calculated using the experimentally measured activation energies for diffusion per polyethylene molecule with different chain lengths and was found to be approximately 0.22 that was in line with what was found from MD simulations.

Diffusivity and solubility of cyclohexane in nanoscale bitumen films coated on hydrophilic substrates at ambient conditions were studied using a gravimetric analyzer. Three substrates were used, and they are as follows: sample A, monodisperse spherical glass beads; sample B, polydisperse spherical glass beads mixed with polydisperse irregular-shape kaolin clay particles; and sample C, irregular-shape residual solids generated from a solvent extraction process of an oil sand ore. All of the above samples had a mean diameter of 150 μm. Diffusion coefficients were determined based upon the initial rates of cyclohexane absorption when bitumen-coated samples at various amounts (thicknesses) were exposed to a carrier gas with cyclohexane vapors at two levels of relative saturations (RSs), and they were found to be in the range of 10 -18 to 10 -16 m 2 /s. A double-first-order kinetics model fits well to the absorption data, suggesting that there exists a concentration gradient of polar (or nonpolar) bitumen molecules in the nanoscale films. This is because the hydrophilic substrates attract the relatively polar fraction of bitumen molecules to the region close to the substrates and the nonpolar fraction resides in the region near the free surface. As a result, the measured diffusion coefficients exhibited positive thickness dependence when the thickness of the bitumen films was at the nanoscale. The molecules near the substrates tended to diffuse slower than those in the free surface region. However, diffusivity was insensitive to the cyclohexane RS. On the other hand, the measured solubility of cyclohexane in the nanoscale bitumen films exhibited no thickness dependence but strong cyclohexane RS dependence. These results suggest that solubility is not affected by the inhomogeneous distribution of bitumen molecules in the nanoscale films and that it follows more or less Henry's law., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

Stretchable and tough hydrogels have drawn a lot of attention recently. Due to their unique properties, they have great potential in the application in areas such as mechanical sensing, wound healing, and drug delivery. In this review, we will summarize recent developments of stretchable and tough hydrogels in these areas.

Molecular dynamics simulation was used to study the adsorption behavior of inorganic and organic ions at aqueous-cyclohexane interfaces, and that with such systems confined in a kaolinite nanopore. Four aqueous solutions were used, each containing one of the four solutes (NaCl, NaOH, CaCl 2 and Ca(OH) 2 ) at the concentration of 1.0 M. At the interface of each of the solutions with neat cyclohexane, there existed an ion depletion zone. The more strongly hydrated ions, such as calcium and hydroxide, were more intensely depleted from the interface as compared to sodium and chloride. Such surface exclusion led to interfacial tension increases, with greater increments for solutions containing calcium or hydroxide. Upon addition of sodium decanoate to the cyclohexane phase, they partly migrated to the aqueous-organic interface, and the remaining formed inverted micelle complexes. Also, a small fraction of the solvated cations in the aqueous phase drifted to the depletion zone to interact with the organic anions, with their affinity towards the interface still being controlled by their hydration-strength. When such systems were confined in a kaolinite nanopore, behavior of decanoate anions - which were found to be prone to strong adsorption to solid surfaces in the absence of any aqueous solution - was determined by the nature of the solvated ions in water. In these systems, the more weakly-hydrated ionic species exhibited preferential adsorption to the solid surface, while affinity of the more strongly-hydrated ones was towards remaining within the water layers or to the aqueous-organic interface. With the calcium chloride solution, almost all of the organic ions were detached from the surface and adsorbed at the aqueous-cyclohexane interface. This was caused by the release of double amount of inorganic anions by this 1 : 2 salt, the inner-sphere adsorption of majority of chloride anions to the octahedral surface, and the higher charge density of calcium cations.

Background: Premorbid functional status is an important factor in acute stroke treatment decision making. Determining the modified Rankin Score (mRS) accurately may be difficult due to deficits from stroke and lack of collateral information in the acute setting. Data on the reliability of the premorbid mRS in "real-world" practice outside of clinical trial or registry settings are limited., Methods: A retrospective study at a high volume academic primary stroke center. For patients with acute ischemic stroke treated with alteplase between July 2012 and July 2016, hospital electronic records were reviewed for detailed inpatient occupational therapist (OT) assessment of premorbid functional status to determine mRS (OT-mRS). This was compared with premorbid mRS determined at acute emergency department assessment (Acute-mRS). Kappa statistic and Lin's concordance correlation coefficient was used to calculate agreement between Acute-mRS and OT-mRS., Results: Among stroke patients treated with alteplase over the 4 years period, OT-mRS was available for 312 patients (79.0%), the mean age was 75.5 years (male 51.9%). 82.4%, 11.9%, and 5.8% of patients had Acute-mRS of 0-1, 2, and ≥3; while 84.9%, 8.0%, and 6.7% had OT-mRS of 0-1, 2, and ≥3, respectively. The agreement between Acute-mRS and OT-mRS was 83.3%, with κ = .64 and correlation coefficient r = .87 (95% CI .841-.896, P < .05)., Conclusions: There was at least moderate agreement between Acute-mRS prior to thrombolysis and OT-mRS obtained by detailed assessment later. The number of patients with premorbid disability was small and may have positively influenced the agreement between the 2 scores., (Copyright © 2019. Published by Elsevier Inc.)

Pushing the boundaries of the investigation of hydrophobic attraction (HA) to the molecular scale readily ensures the collection of experimental results free of secondary effects, thereby facilitating the unraveling of the underlying mechanism by providing clean experimental results that truly reflect the hydrophobic attraction. Regardless of the feasibility of this approach, investigations using this promising method are stagnant due to the difficulties in determining the individual contributions of HA and van der Waals (vdW) interactions at the molecular scale. Here, a novel approach was proposed for the first time to determine the individual contributions of vdW interactions and HA by studying the single-molecule adhesion forces of a neutral oligo ethylene glycol methacrylate copolymer on a MoS 2 crystal exposed to different water chemistry. The anisotropic surface properties of MoS 2 enabled the partitioning of vdW interactions and hydrophobic attraction in total single-molecule adhesion forces and also enabled determining the contribution of electrostatic interaction (ESI). When the presence of ESI is excluded, the study of single-molecule adhesion forces using single-molecule force spectroscopy (SMFS) revealed that the contribution of vdW interactions to total molecular interactions was smaller than 9 pN. The strong single-molecule adhesion forces of oligo ethylene glycol copolymer on the hydrophobic basal surface of MoS 2 demonstrated that HA plays a dominant role with contribution up to 89% to the total single-molecule adhesion force. By utilizing the derived theoretical model, we quantified the individual contribution of each fundamental interaction under a variety of conditions. This study proposed a facile approach to quantitatively clarify the roles of vdW interactions and HA at the molecular scale, which may help assist future experimental and theoretical investigations of hydrophobic (solvophobic) effects and vdW interactions in aqueous solutions.

Hydrotalcites (HTlcs) or layered double hydroxides (LDHs) have been used in a wide range of applications such as catalysis, electrochemical sensors, wastewater treatment, and carbon dioxide (CO 2 ) capture. In the current study, molecular dynamics simulation was employed to investigate carbon dioxide adsorption behavior on amorphous layered double oxides (LDOs) derived from LDHs at elevated temperatures. The thermal stability of LDHs was first examined by heating the sample up to T = 1700 K. Radial distribution functions confirmed the structural evolution upon heating and the obtained structures were in good agreement with experiments, where periclase was confirmed to be the stable phase in the recrystallized mixed oxides above T = 1200 K. Further, CO 2 adsorption was studied as a function of amorphous HTlc-derived oxide composition, where static and dynamic atomistic measures have been employed to characterize the CO 2 adsorption behavior. The simulation results showed that the CO 2 dynamic residence time on LDH-derived LDOs was sensitive to the Mg/Al molar ratio and the average amount of residence time of CO 2 on the surface of LDOs reached maximum when the Mg/Al molar ratio was equal to 3.0. Meanwhile, the activation energy for diffusion also showed local maximum when the Mg/Al molar ratio was 3.0, suggesting that this particular ratio of Mg/Al mixed oxides possessed the highest CO 2 adsorption capacity. This is consistent with experimental results. Examination of the binding between CO 2 and mixed oxides revealed that both magnesium and oxygen in amorphous LDOs contributed to CO 2 adsorption. Further analysis suggested that the interaction between Mg-O and O(LDO)-C were the most important interactions for the physisorption of CO 2 on amorphous surface and different CO 2 adsorption behavior on different Mg/Al molar ratio surfaces was directly related to their amorphous local structure., Competing Interests: The authors declare no competing financial interest.

Molecular dynamics simulation was used to study the wettability of the hydrophilic sphalerite (110) surface chemically modified by butylthiols made up of normal and branched alkyl tails, referred to as n-butylthiol and i-butylthiol hereafter, at different adsorption site coverages. Butylthiol molecules were grafted onto the adsorption sites of the surface in two different distributions-ordered and random. The results showed that for a given butylthiol at a given site coverage, random surface distribution yielded a slightly larger contact angle. This observation was attributed to the fact that average distances between the first and second nearest neighbors of butylthiol molecules are shorter in the case of random surface distribution, resulting in smaller patches of bare surface exposed to water molecules compared to those of the ordered surface distribution. Regardless of the tail structure, the random surface distribution exhibited hydrophobic character (i.e., contact angle ≥ 90°) at a relatively low site coverage of about 25%. The test area method and the Kirkwood and Buff approach were adopted to estimate surface energies (γ SV ) of the bare sphalerite (110) surface and the collector monolayer, respectively. Using the obtained γ SV values of these two pure states, the apparent surface energy as a function of surface coverage was determined based on Cassie's law. This allowed us to estimate the corresponding values of solid-liquid apparent interfacial tension (γ SL ). Both γ SV and γ SL exhibit a linear inverse dependence on surface coverage with a crossover point at 25% site coverage (about 50% surface coverage), above which γ SV falls below γ SL , leading to contact angles greater than 90°. The results also revealed that contact angles of the two butylthiols are comparable at site coverages below ∼85%, but above that, they are significantly lower for the branched thiols compared to their normal counterparts. Considering the Lennard-Jones interaction energies between the water cluster and the butylthiols, stronger attractive interactions were present in the case of i-butylthiol due to the presence of two methyl groups in its alkyl chain. This difference was the most intense at site coverages above ∼85%.

Specified risk materials (SRM) constitute the proteinaceous waste of slaughterhouses and are currently being disposed off either by incineration or by land filling. Over the last few years, our efforts have focused on developing technology platforms for deployment of this renewable resource for various value-added industrial applications. This report describes a technology for utilization of SRM for the development of an environmentally friendly plywood adhesive with an improved water resistance property. The feedstock (SRM) was first thermally hydrolysed according to a standard protocol, and the hydrolysed protein fragments (peptides) were recovered from the hydrolysate. The recovered peptides were chemically modified through esterification reaction using ethanol, and then chemically crosslinked with polyamideamine-epichlorohydrin (PAE) resin to develop a wood adhesive system. Plywood specimens were then developed using the peptides-PAE resin-based adhesive. The effects of crosslinking time, solid content of the adhesive formulation, ratio of peptides and crosslinking agent in the formulation, and curing conditions of specimen preparation on lap shear strength of resulting plywood specimens were systematically evaluated. Despite the hydrophilic nature of hydrolysed protein fragments, the peptides-PAE resin formulations exhibited remarkable water resistance property after curing. Capping of polar carboxyl groups of peptides by converting them to esters further improved the water resistance property of this adhesive system. Under the optimum conditions of adhesive preparation and curing, the ethyl ester derivative of peptides and PAE resin-based formulations resulted in plywood specimens having comparable dry as well as soaked shear strengths to those of commercial phenol formaldehyde resin., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Molybdenum disulfide (MoS 2 ) has been receiving increasing attention in scientific research due to its unique properties. Up to now, several techniques have been developed to prepare exfoliated nanosize MoS 2 dispersions to facilitate its applications. To improve its desired performance, as-prepared MoS 2 dispersion needs further appropriate modification by polymers. Thus, understanding polymer-MoS 2 interaction is of great scientific importance and practical interest. Here, we report our results on molecular interactions of a biocompatible stimuli-responsive copolymer with the basal plane surface of MoS 2 determined using single molecule force spectroscopy (SMFS). Under isothermal conditions, the single-molecule adhesion force of oligo(ethylene glycol) methacrylate copolymer was found to increase from 50 to 75 pN with increasing NaCl concentration from 1 mM to 2 M, as a result of increasing hydrophobicity of the polymers. The theoretical analysis demonstrated that single-molecule adhesion force is determined by two contributions: the adhesion energy per monomer and the entropic free energy of the stretched polymer chain. Further data analysis revealed a significant increase in the adhesion energy per monomer with a negligible change in the other contribution with increasing salt concentration. The hydrophobic attraction (HA) was found to be the main contribution for the higher adhesion energy in electrolyte solutions of higher NaCl concentrations where the zero-frequency of van der Waals interaction were effectively screened. The results illustrate that oligo(ethylene glycol) methacrylate copolymer is a promising polymer for functionalizing MoS 2 and that one can simply change the salt concentration to modulate the single-molecule interactions for desired applications.

Background: Somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) are frequently used to monitor neurologic function during spinal deformity surgery. The sensitivity and specificity of intraoperative neurophysiologic monitoring (IONM) in patients undergoing posterior spinal fusion (PSF) is debatable., Methods: A retrospective review of all patients undergoing PSF with IONM from October 2008 to December 2012 was performed. Factors including sex, operative time, and spinal levels of posterior fusion were analyzed as risk factors for intraoperative alerts., Results: A total of 784 consecutive patients who underwent PSF with IONM without any baseline deficits were analyzed. Patients included 45% men (n = 356) and 55% women (n = 428), with a mean age of 56 years. The mean procedure time was 7 hours. Intraoperative alerts were noted for 3.3% (n = 26) of patients. In this cohort, the average number of levels involved per procedure was approximately 7, ranging from 1 to 16 levels. Of all the spinal levels, the cervicothoracic region had the highest incidence of intraoperative alerts (6 of 97 cervicothoracic cases, P = 0.06). Among these patients, age (P = 0.32), sex (P = 0.66), and procedure time (P = 0.63) were not predictive factors. Four out of 26 (15%) patients had neurologic deficits despite surgeon intervention after neuromonitoring alerts., Conclusions: SSEP and MEP changes occurred in 3.3% of patients undergoing PSF, with the highest incidence at the cervicothoracic level. Twenty-three out of 26 patients with intraoperative neuromonitoring changes had improvements in IONM signals after interventions during surgery. Further studies using larger patient numbers may be useful in establishing the utility of neuromonitoring in PSF., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Premorbid antithrombotic medication may worsen intracranial injury and outcome after traumatic brain injury (TBI). Routine laboratory tests are insufficient to evaluate platelet activity., Objective: To profile the spectrum of platelet inhibition, as measured by aspirin and P2Y12 response unit assays, in a TBI population on antiplatelet therapy., Methods: This single-center, prospective cohort study included patients presenting to our institution between November 2010 and January 2015 with a clinical history of TBI. Serum platelet reactivity levels were determined immediately on admission and analyzed using the aspirin and P2Y12 response unit assays; test results were reported as aspirin response units and P2Y12 response units. We report congruence between assay results and clinical history as well as differences in assay results between types of antiplatelet therapy., Results: A sample of 317 patients was available for analysis, of which 87% had experienced mild TBI, 7% moderate, and 6% severe; the mean age was 71.5 years. The mean aspirin response units in patients with a history of any aspirin use was 456 ± 67 (range, 350-659), with 88% demonstrating therapeutic platelet inhibition. For clopidogrel, the mean P2Y12 response unit was 191 ± 70 (range, 51-351); 77% showed therapeutic response., Conclusion: Rapid measurement of antiplatelet function using the aspirin and P2Y12 response assays indicated as many as one fourth of patients on antiplatelet therapy do not have platelet dysfunction. Further research is required to develop guidelines for the use of these assays to guide platelet transfusion in the setting of TBI., (Copyright © 2016 by the Congress of Neurological Surgeons)

OBJECTIVE Application for a residency position in neurosurgery is a highly competitive process. Visiting subinternships and interviews are integral parts of the application process that provide applicants and programs with important information, often influencing rank list decisions. However, the process is an expensive one that places significant financial burden on applicants. In this study, the authors aimed to quantify expenses incurred by 1st-year neurosurgery residents who matched into a neurosurgery residency program in 2014 and uncover potential trends in expenses. METHODS A 10-question survey was distributed in partnership with the Society of Neurological Surgeons to all 1st-year neurosurgery residents in the United States. The survey asked respondents about the number of subinternships, interviews, and second looks (after the interview) attended and the resultant costs, the type of program match, preferences for subinternship interviews, and suggestions for changes they would like to see in the application process. In addition to compiling overall results, also examined were the data for differences in cost when stratifying for region of the medical school or whether the respondent had contact with the program they matched to prior to the interview process (matched to home or subinternship program). RESULTS The survey had a 64.4% response rate. The mean total expenses for all components of the application process were US $10,255, with interview costs comprising the majority of the expenses (69.0%). No difference in number of subinternships, interviews, or second looks attended, or their individual and total costs, was seen for applicants from different regions of the United States. Respondents who matched to their home or subinternship program attended fewer interviews than respondents who had no prior contact with their matched program (13.5 vs 16.4, respectively, p = 0.0023) but incurred the same overall costs (mean $9774 vs $10,566; p = 0.58). CONCLUSIONS Securing a residency position in neurosurgery is a costly process for applicants. No differences are seen when stratifying by region of medical school attended or contact with a program prior to interviewing. Interview costs comprise the majority of expenses for applicants, and changes to the application process are needed to control costs incurred by applicants.

Background: At present, guidelines are lacking on platelet transfusion in patients with a traumatic intracranial bleed and history of antiplatelet therapy. The aspirin and P2Y 12 response unit (ARU and PRU, respectively) assays detect the effect of aspirin and P2Y 12 inhibitors in the cardiac population., Objective: To describe the reversal of platelet inhibition after platelet transfusion using the ARU and PRU assays in patients with traumatic brain injury., Methods: Between 2010 and 2015, we conducted a prospective comparative cohort study of patients presenting with a positive head computed tomography and a history of antiplatelet therapy. ARU and PRU assays were performed on admission and 6 hours after transfusion, with a primary end point of detection of disinhibition after platelet transfusion., Results: One hundred seven patients were available for analysis. Seven percent of patients taking aspirin and 27% of patients taking clopidogrel were not therapeutic on admission per the ARU and PRU, respectively. After platelet transfusion, 51% of patients on any aspirin and 67% of patients on any clopidogrel failed to be reversed. ARU increased by 71 ± 76 per unit of apheresis platelets for patients taking any aspirin, and PRU increased by 48 ± 46 per unit of apheresis platelets for patients taking any clopidogrel., Conclusion: A significant percentage of patients taking aspirin or clopidogrel were not therapeutic and thus would be unlikely to benefit from a platelet transfusion. In patients with measured platelet inhibition, a single platelet transfusion was not sufficient to reverse platelet inhibition in almost half., (Copyright © 2016 by the Congress of Neurological Surgeons)

The early-stage competitive co-adsorption of interfacially active naphthenic acids (NAs) and polyaromatic (PA) molecules to a toluene-water interface from the bulk toluene phase was studied using molecular dynamics (MD) simulation. The NA molecules studied had the same polar functional group but different cycloaliphatic nonpolar tails, and a perylene bisimide (PBI)-based molecule was used as a representative PA compound. The results from our simulations suggest that the size and structural features of NA molecules greatly influence the interfacial activity of PA molecules and partitioning of NA molecules at the toluene-water interface. At low concentrations of PA (∼2.3 wt %) and NA (∼0.4 wt %) molecules, NA molecules containing large cycloaliphatic rings (e.g., four rings) or with a very long aliphatic tail (e.g., carbon chain length of 14) were observed to impede the migration of PA molecules to the interface, whereas small NA molecules containing two cycloaliphatic rings had little effect on the adsorption of PA molecules at the toluene-water interface. At high NA concentrations, the adsorption of PA molecules (∼5.75-17.25 wt %) was greatly hindered by the presence of small NA molecules (∼1.6-4.8 wt %) due to the solvation of PA nanoaggregates in the bulk. Adsorption mechanisms of PA and NA molecules at toluene-water interfaces were clarified through a detailed analysis on the interactions among different species in the system. The results obtained from this work provide insights into designing appropriate chemical demulsifiers or co-demulsifiers for breaking water-in-oil emulsions of great industrial applications.

The current production of wood composites relies mostly on formaldehyde-based adhesives such as urea formaldehyde (UF) and phenol formaldehyde (PF) resins. As these resins are produced from non-renewable resources, and there are some ongoing issues with possible health hazard due to formaldehyde emission from such products, the purpose of this research was to develop a formaldehyde-free plywood adhesive utilizing waste protein as a renewable feedstock. The feedstock for this work was specified risk material (SRM), which is currently being disposed of either by incineration or by landfilling. In this report, we describe a technology for utilization of SRM for the development of an environmentally friendly plywood adhesive. SRM was thermally hydrolyzed using a Canadian government-approved protocol, and the peptides were recovered from the hydrolyzate. The recovered peptides were chemically crosslinked with polyamidoamine-epichlorohydrin (PAE) resin to develop an adhesive system for bonding of plywood specimens. The effects of crosslinking time, peptides/crosslinking agent ratio, and temperature of hot pressing of plywood specimens on the strength of formulated adhesives were investigated. Formulations containing as much as 78% ( wt / wt) peptides met the ASTM (American Society for Testing and Materials) specifications of minimum dry and soaked shear strength requirement for UF resin type adhesives. Under the optimum conditions tested, the peptides⁻PAE resin-based formulations resulted in plywood specimens having comparable dry as well as soaked shear strength to that of commercial PF resin.

In this work, a series of molecular dynamics simulations were performed to investigate the effect of naphthenic acids (NAs) in early stage self-assembly of polyaromatic (PA) molecules in toluene. By exploiting NA molecules of the same polar functional group but different aliphatic/cycloaliphatic nonpolar tails, it was found that irrespective of the presence of the NA molecules in the system, the dominant mode of π-π stacking is a twisted, offset parallel stacking of a slightly larger overlapping area. Unlike large NA molecules, the presence of small NA molecules enhanced the number of π-π stacked PA molecules by suppressing the hydrogen bonding interactions among the PA molecules. Smaller NA molecules were found to have a higher tendency to associate with PA molecules than larger NA molecules. Moreover, the size and distribution of π-π stacking structures were affected to different degrees by changing the size and structural features of the NA molecules in the system. It was further revealed that the association between NA and PA molecules, mainly through hydrogen bonding, creates a favorable local environment for the overlap of PA cores (i.e., π-π stacking growth) by depressing the hydrogen bonding between PA molecules, which results in the removal of some toluene molecules from the vicinity of the PA molecules.

Background: Treatment of low-pressure hydrocephalus (LPH) may require prolonged external ventricular drainage (EVD) at sub-zero pressures to reverse ventriculomegaly. Endoscopic third ventriculostomy (ETV) has been used in the treatment of noncommunicating hydrocephalus; however, indications for ETV are expanding., Methods: Patients with the diagnosis of LPH as defined by the Pang and Altschuler criteria who underwent sub-zero drainage treatment over an 8-year period were included. Patients were divided into two cohorts based on whether or not ETV was employed during their treatment. Time from EVD placement to internalization of shunt was recorded for both groups; time from ETV to placement of shunt was recorded for the patients undergoing ETV., Results: Sixteen adult patients with LPH were managed with sub-zero drainage method. Ten (62.5%) patients did not undergo ETV and the average time from first ventriculostomy to shunting was 73 days (range 14-257 days). Six (37.5%) patients underwent ETV during the course of their treatment; average time from initial ventriculostomy to shunt was 114 days (range 0-236 days) (P = 0.16). Time from development of LPH to ETV ranged from 28 days to 6.5 months. In the ETV group, of the 4 patients who underwent shunting, the average time to shunting following ETV was 15.25 days., Conclusions: ETV can be used successfully in the management of refractory LPH to decrease the duration of EVD.

Importance: Salvage surgery for recurrent head and neck squamous cell carcinoma (HNSCC) carries substantial risks of morbidity and mortality. Risk factors for death within 1 year should be better defined., Objectives: To report preoperative oncologic prognostic factors predictive of short-term (<1 year) survival after salvage surgery in patients with HNSCC, to assess whether preoperative age and comorbidity predicts 1-year mortality, and to report hospital courses after salvage surgery within 1 year., Design, Setting, and Participants: A retrospective medical record review of 191 patients with recurrent HNSCC treated with salvage surgery from January 1, 2003, through December 31, 2013, at a tertiary academic center., Interventions: Surgical salvage of HNSCC (larynx, oral cavity, oropharynx, or hypopharynx) with curative intent., Main Outcomes and Measures: Primary outcome was survival 1 year after salvage surgery. Secondary outcomes were length of inpatient hospital stay, days of admissions, and skilled nursing facility disposition within 1 year stratified by survival status. Presalvage Charlson-Age Comorbidity Index (CACI) was calculated. Associations among CACI, oncologic risk factors, and risk of death within 1 year after salvage surgery are investigated using multivariable analysis., Results: Of 191 patients studied, 53 (27.7%) died within 1 year after salvage surgery. Patients who died within 1 year had more total inpatient admissions (P < .001), longer total length of stay (P < .001), and higher risk of discharge to a skilled nursing facility (P < .001) and spent 17.3% (interquartile range, 5.2-36.3) of their remaining days in the hospital. Independent risk factors for death within 1 year are CACI (relative risk [RR], 1.43; 95% CI, 1.16-1.76), primary T3 or T4 stage (RR, 2.34; 95% CI, 1.27-4.31), and disease-free interval of less than 6 months (RR, 5.61; 95% CI, 1.78-16.7)., Conclusions and Relevance: Medical comorbidity and age as measured by the CACI, primary T3 or T4 stage, and short disease-free interval must be considered in selecting patients ideal for surgical salvage surgery for recurrent HNSCC. Patients with these risk factors should be more strongly considered for palliative measures.

Background: The endoscopic endonasal approach (EEA) for craniocervical lesions involving the lower clivus and occipital condyles carries an unclear risk of atlanto-occipital (AO) instability requiring arthrodesis., Objective: Elucidate risk factors for AO instability following EEA for clival lesions., Methods: We reviewed patients with clival tumors who underwent EEA at our institution between 2002 and 2012. Resection of the lower clivus, foramen magnum, AO joint, and occipital condyles were evaluated on fine-cut postoperative computed tomography., Results: Two hundred twelve patients (mean age 47.9 years, 57.1% male) underwent transclival EEA for lower clival lesions. In addition to the lower clivus, resection involved the condyle in 14.2% of patients, the foramen magnum in 16.5%, and the AO joint in 1.4%. Quantification of condyle resection revealed complete resection in 3 cases, 75% resection in 8 cases, 50% resection in 6 cases, and 25% resection in 13 cases. Seven of these patients had EEA combined with an open, far-lateral approach. In total, 7 patients required arthrodesis following EEA (3.3%), 4 of them after a combined approach. All patients who underwent arthrodesis had primary bone tumors such as chordoma, chondrosarcoma, or osteosarcoma (P = .022). Degree of condyle resection was a significant factor predisposing to occipitocervical instability (P = .001 and P < .001 for 75% and 100% condyle resection, respectively). Use of a combined approach was significantly associated with arthrodesis (P < .001)., Conclusion: EEA resection of the occipital condyles that results in greater than 75% condyle resection or EEA in combination with an open approach significantly increases the risk of AO instability and likely necessitates AO fixation., Abbreviations: AO, atlanto-occipitalEEA, endoscopic endonasal approachOC, occipitocervical.

To circumvent the problem of burst drug release from polymeric micelles, we designed three layered ABC micelles consisting of methoxy poly(ethylene oxide) (PEO) as the shell layer (A block); poly(lactic acid) (PLA) of different stereo-chemistries as the outer core (B block) and poly(α-benzylcarboxylate-ε-caprolactone) (PBCL) or poly(ε-caprolactone) (PCL) as the inner core (C block). The micelles were used to encapsulate a model hydrophobic drug, nimodipine. The effect of PLA (B block) incorporation and stereochemistry on the formation of semi crystalline outer cores in ABC triblock copolymer micelles, micelle stability, drug loading and release was then assessed in comparison to diblock copolymer micelles. The PLA outer core was expected to act as a barrier lowering the rate of drug diffusion out of the micellar carrier owing to a high Flory Huggins interaction parameter between nimodipine and PLA (χ=1.35). Introduction of PLA outer cores in ABC block copolymer micelles reduced the burst release of nimodipine from polymeric micelles without jeopardizing its high encapsulation efficiency. In ABC polymeric micelles with stereo-regular PLA blocks; semi-crystalline outer PLA cores were not formed, which was in contrast to PEO-PLA diblock copolymer micelles. Accordingly, PLA stereo-chemistry had no significant effect on drug release in ABC polymeric micelles. In contrast to diblock copolymers, no sign of stereo-complexation in mixed micelles composed of a 50:50 mixture of PdLA and PlLA containing ABC triblock copolymers was observed. The results showed the capability of properly designed ABC triblock copolymer micelles as reservoirs for drug solubilization and depot release at nanoscale dimensions., Statement of Significance: Polymeric micelles are core-shell nanostructures that are widely used for drug delivery. Their hydrophobic core accommodates poor water soluble drugs and their hydrophilic shell allows the whole structure to be water soluble. A common problem with the use of polymeric micelles is leakage of the incorporated drug from these carriers. Here we have shown that a properly designed three layered (ABC) block copolymer micelle with drug compatible blocks at the inner core and drug incompatible blocks at the outer core can be used to reduce the initial fast rate of drug release while providing high amount of drug encapsulated in the core. Moreover, changes in the chemical structure of the inner core may be used to modify the stability of these systems., (Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: Femoral artery injuries are known complications of percutaneous vascular closure devices (VCDs). We studied the incidence of delayed femoral artery angiographic irregularities after neurointerventional procedures in which the EXOSEAL extravascular closure device was used for femoral arterial puncture closure., Methods: Adult patients who underwent femoral arterial puncture closures with an EXOSEAL VCD and had a follow-up femoral artery angiogram from June 2012 through August 2013 were reviewed. A blinded radiologist compared pre-deployment and follow-up femoral arteriograms for the presence of femoral artery stenosis, dissection, pseudoaneurysm, or development of an arteriovenous fistula. Hospital records were reviewed for major or minor complications of the groin site or femoral artery., Results: The EXOSEAL VCD achieved hemostasis, without evidence of a groin hematoma or requiring subsequent prolonged manual compression, in 400 of 441 closures following transfemoral arterial access, representing a device success rate of 90.7%. A total of 98 patients underwent 102 repeat angiograms following closure with the EXOSEAL VCD. The average time to the repeat angiogram was 73.5 days (range 0-488, median 28). Follow-up femoral arteriography demonstrated an irregularity in seven cases, all of which were vessel stenoses of <50%. There were no dissections, pseudoaneurysms, infections, or ischemic events in the study population., Conclusions: Angiographic irregularities were seen in 6.86% of cases after closure with the EXOSEAL VCD. There were no clinically significant vascular complications. Thus, femoral artery closure with EXOSEAL carries a low risk of clinically significant delayed angiographic findings., (© The Author(s) 2015.)

It is well-known that properties of poly(vinyl alcohol) (PVA) in the pure and solution states depend largely on the hydrogen bonding networks formed. In the context of molecular simulation, such networks are handled through the Coulombic interactions. Therefore, a good set of partial atom charges (PACs) for simulations involving PVA is highly desirable. In this work, we calculated the PACs for PVA using a few commonly used population analysis schemes with a hope to identify an accurate set of PACs for PVA monomers. To evaluate the quality of the calculated parameters, we have benchmarked their predictions for free energy of solvation (FES) in selected solvents by molecular dynamics simulations against the ab initio calculated values. Selected solvents were water, ethanol and benzene as they covered a range of size and polarity. Also, PVA with different tacticities were used to capture their effect on the calculated FESs. Based on our results, neither PACs nor FESs are affected by the chain tacticity. While PACs predicted by the Merz-Singh-Kollman scheme were close to original values in the OPLS-AA force field in way that no significant difference in properties of pure PVA was observed, free energy of solvation calculated using such PACs showed greater agreement with ab initio calculated values than those calculated by OPLS-AA (and all other schemes used in this work) in all three solvents considered.

Delayed toxicity after whole brain radiation therapy (WBRT) is of increasing concern in patients who survive more than one year with brain metastases from breast cancer. Radiation-related white matter toxicity is detected by magnetic resonance imaging (MRI) and has been correlated with neurocognitive dysfunction. This study assessed the risk of developing white matter changes (WMC) in breast cancer patients who underwent either WBRT plus stereotactic radiosurgery (SRS) or SRS alone. We retrospectively compared 35 patients with breast cancer brain metastases who received WBRT and SRS to 30 patients who only received SRS. All patients had evaluable imaging at a median of one year after their initial management. The development of white matter T2 prolongation as detected by T2 or FLAIR imaging was graded: grade 1 = little or no white matter T2 hyperintensity; grade 2 = limited periventricular hyperintensity; and grade 3 = diffuse white matter hyperintensity. After WBRT plus SRS, patients demonstrated a significantly higher incidence of WMC (p < 0.0001). After one year, 71.5 % of patients whose treatment included WBRT demonstrated WMC (42.9 % grade 2; 28.6 % grade 3). Only one patient receiving only SRS developed WMC. In long-term survivors of breast cancer, the risk of WMC was significantly reduced when SRS alone was used for management. Further prospective studies are necessary to determine how these findings correlate with neurocognitive toxicity. WBRT usage as initial management of limited brain disease should be replaced by SRS alone to reduce the risk of delayed white matter toxicity.

The authors present the case of a boy who was successfully managed through the spontaneous thrombosis of a cavernous internal carotid artery (ICA) aneurysm, the subsequent occlusion of the ICA, its recanalization, and ultimate endovascular sacrifice, using only two angiograms because of the diagnostic capability of CT angiography. Spontaneous recanalization of the ICA following occlusion in the setting of a giant aneurysm has not been previously reported.

Isobaric-isothermal molecular dynamics simulation was used to study the diffusion of a hydrophobic drug Cucurbitacin B (CuB) in pseudomicelle environments consisting of poly(ethylene oxide-b-caprolactone) (PEO-b-PCL) swollen by various amounts of water. Two PEO-b-PCL configurations, linear and branched, with the same total molecular weight were used. For the branched configuration, the block copolymer contained one linear block of PEO with the same molecular weight as that of the PEO block used in the linear configuration but with one end connecting to three PCL blocks with the same chain length, hereafter denoted PEO-b-3PCL. Regardless of the configuration, the simulation results showed that the diffusivity of CuB was insensitive to the water concentration up to ∼8 wt % while that of water decreased with an increasing water concentration. The diffusivity of CuB (10(-8) cm(2)/s) was 3 orders of magnitude lower than that of water (10(-5) cm(2)/s). This is attributed to the fact that CuB relied on the wiggling motion of the block copolymers to diffuse while water molecules diffused via a hopping mechanism. The rates at which CuB and water diffused into PEO-b-PCL were twice those in PEO-b-3PCL because the chain mobility and the degree of swelling are higher and there are fewer intermolecular hydrogen bonds in the case of PEO-b-PCL. The velocity autocorrelation functions of CuB show that the free volume holes formed by PEO-b-3PCL are more rigid than those formed by PEO-b-PCL, making CuB exhibit higher-frequency collision motion in PEO-b-3PCL than in PEO-b-PCL, and the difference in frequency is insensitive to water concentration.

Objectives: A "chiral switch" occurs in the pharmaceutical market when a drug made up of 2 enantiomer forms is replaced with a purified single-enantiomer version, often in the context of a patent expiration. We studied the prevalence of chiral switching in the United States over the past decade, including trends in use of, and expenditures on, these products in Medicaid., Study Design: Retrospective analysis., Methods: We used US Adopted Names prefixes (lev/levo/ar/es/dex/dextro) to identify all single-enantiomer drugs approved from 2001 to 2011. From publicly available US Food and Drug Administration (FDA) approval documents, we extracted the characteristics of the pivotal premarket trials for the single enantiomers. Specifically, we evaluated whether the single enantiomer was directly compared with the precursor racemic drug and whether there was evidence of superior efficacy. We used quarterly drug expenditure data from each state Medicaid program to chart trends in use of, and spending on, the single-enantiomer products and their racemic precursors during the study period., Results: From 2001 to 2011, the FDA approved 9 single-enantiomer products: dexlansoprazole, levoleucovorin, levocetirizine, armodafinil, arformoterol, eszopiclone, escitalopram, dexmethylphenidate, and esomeprazole. Of those 9 drugs, 3 had at least 1 pre-approval randomized trial that included the racemic precursor as a direct comparator, but there was no evidence of superiority of the single enantiomer over the racemic at comparable doses. Between 2001 and 2011, US Medicaid programs spent approximately $6.3 billion on these 9 single-enantiomer drugs., Conclusions: Recently approved single-enantiomer drugs showed no evidence of superior efficacy over the older racemic precursors in the pivotal trials leading to their approval, and in a majority of cases, they were not directly compared.

We used molecular dynamics (MD) simulation to study the diffusion of water at low concentrations in a series of chemically modified xylans, a major hemicellulose, including hydroxypropyl xylan (HPX) and acetoxypropyl xylan (APX) which is essentially acetylated HPX, with different degrees of acetylation (i.e., different degrees of hydrophobicity) at 400 K, a temperature well above the glass transition temperatures of the materials. We used one HPX and three APX models. The three APX models were constructed using the HPX model by substituting 1, 2 or 3 hydroxyl moieties on its repeating units, respectively. The simulation results showed that the diffusivity of water at low concentrations in the chemically modified xylans decreased slightly (~20%) from HPX to APX with 3 acetylated hydroxyl moieties, a trend that has been experimentally observed for xylans and other cellulosic type materials. Further data analysis shows that acetylation decreases the ability of the xylan to form hydrogen bonds with water and its degree of swelling. And these two factors exert opposite effects on the diffusivity of water. In particular, the first factor increases the mobility (lower activation energy) of the water molecules, while the second factor reduces the free volumes available for diffusion, thereby decreasing the water mobility. This finding implies that it is not likely to obtain orders of magnitude change to the water diffusivity simply by the acetylation of all hydroxyl moieties on xylan. The high degree of swelling observed for HPX compared to those of APXs is attributed to the fact that many hydrogen bonds in HPX are broken by water. It is interesting to note that water in most of the hydrogen bonds formed between water and xylans acted as hydrogen bond acceptors rather than donors., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Active layer nanomorphology is a major factor that determines the efficiency of bulk heterojunction polymer solar cells (PSCs). Synthesizing diblock copolymers in which acceptor and donor materials are the constituent blocks is the most recent method to control the structure of the active layer. In the current work, a computational method is proposed to predict the nanomorphology of the active layer consisting of a diblock copolymer. Diblock copolymers have a tendency to self-organize and form well-defined nanostructures. The shape of the structure depends on the Flory-Huggins interaction parameter (i.e., χ), the total degree of polymerization (N) and volume fractions of the constituent blocks (φi). In this work, molecular dynamics (MD) simulations were used to calculate χ parameters for two different block copolymers used in PSCs: P3HT-b-poly(S8A2)-C60 and P3HT-b-poly(n-butyl acrylate-stat-acrylate perylene) also known as P3HT-b-PPerAcr. Such calculations indicated strong segregation of blocks into cylindrical structure for P3HT-b-poly(S8A2)-C60 and intermediate segregation into cylindrical structure for P3HT-b-PPerAcr. Experimental results of P3HT-b-poly(S8A2)-C60 and P3HT-b-PTP4AP, a diblock copolymer having very similar structure to P3HT-b-PPerAcr, validate our predictions.

Background: Despite a growing need for primary care physicians in the United States, the proportion of medical school graduates pursuing primary care careers has declined over the past decade., Objective: To assess the association of medical school research funding with graduates matching in family medicine residencies and practicing primary care., Design: Observational study of United States medical schools., Participants: One hundred twenty-one allopathic medical schools., Main Measures: The primary outcomes included the proportion of each school's graduates from 1999 to 2001 who were primary care physicians in 2008, and the proportion of each school's graduates who entered family medicine residencies during 2007 through 2009. The 25 medical schools with the highest levels of research funding from the National Institutes of Health in 2010 were designated as "research-intensive.", Key Results: Among research-intensive medical schools, the 16 private medical schools produced significantly fewer practicing primary care physicians (median 24.1% vs. 33.4%, p < 0.001) and fewer recent graduates matching in family medicine residencies (median 2.4% vs. 6.2%, p < 0.001) than the other 30 private schools. In contrast, the nine research-intensive public medical schools produced comparable proportions of graduates pursuing primary care careers (median 36.1% vs. 36.3%, p = 0.87) and matching in family medicine residencies (median 7.4% vs. 10.0%, p = 0.37) relative to the other 66 public medical schools., Conclusions: To meet the health care needs of the US population, research-intensive private medical schools should play a more active role in promoting primary care careers for their students and graduates.

A method is proposed for creating a non-equilibrium ensemble with a constant number of molecules, constant temperature and constant pressures with different target values in two reservoirs [referred to as NT(P(1)-P(2)) ensemble] that are connected by a finite length nanopore. This method includes two steps. The first step places a partition between the two reservoirs and then creates a static pressure field and a proper system volume by using two self-adjusting plates on which two external forces/pressures with different target values are exerted. The second step removes the partition and the two self-adjusting plates and the pressure difference between the two reservoirs is maintained by a "pump" designed to simultaneously create a periodic boundary condition between the two reservoirs and supply the necessary force (work) to a subset of molecules for a steady state flow. To examine this method, several cases using liquid argon with a truncated and shift Lennard-Jones potential under different target pressures and pump sizes were studied. Results show that the method proposed in this paper works well. In addition, the method proposed in this paper was compared with the other external force field methods. The results show that as long as the external force is applied to a restricted set of molecules away from the channel a constant pressure difference between two reservoirs is maintained. The advantage of the algorithm proposed here also sets the absolute pressures with different target levels in two reservoirs instead of it being arbitrary. Studies show that the fluid flow rate or permeability through a nanopore depends not only on the pressure difference between two reservoirs, but also on the absolute pressures in two reservoirs.

Conformations of model high-density polyethylene (HDPE) and linear low-density polyethylene (LLDPE) chains with different intramolecular branch distributions adsorbed on a relaxed octahedral surface of kaolinite, a major clay mineral, at 463 K (190 degrees C) were studied by using classical molecular dynamics (MD) simulation. Prior to the MD simulations, first-principle density functional theory (DFT) calculations were carried out to relax the inorganic surface that was created by cleaving the corresponding kaolinite crystal structure. The high-temperature MD simulation results showed that an ordered polyethylene region with a thickness of about one to three layers of chain segments developed rapidly near the clay surface. On the other hand, chain segments in the far field slowly evolved into another ordered region with a higher degree of order than the one adjacent to the surface. It was observed that the melt morphology in the far field depends on the architecture of the chains. Also, in between the two ordered regions, a region that contained no apparent order formed. The above observation is attributed to the fact that the mobility of chain segments adjacent to the surface was greatly reduced as a result of their strong affinity for the surface, while those in the far field were not. Despite the fact that the results are for the melt state, they suggest that nucleation and lamellar growth of polymer chains nearby an inorganic surface may proceed from the chain segments in the ordered region in the far field rather than from the organic/inorganic interface. This is because chain segments in the three described regions, upon cooling, should not have sufficient thermal energy to reorient themselves drastically to form a single lamella under normal crystallization conditions. However, it should be noted that the above speculation is made based on a rather short equilibration time (approximately 10 ns) used in the simulations.

Molecular dynamics simulation was used to study the potential of using a block copolymer containing three poly(epsilon-caprolactone) (PCL) blocks of equal length connected to one end of a poly(ethylene oxide) (PEO) block, designated as PEO-b-3PCL, to encapsulate two classes of hydrophobic drugs with distinctively different molecular structures. In particular, the first class of drugs consisted of two cucurbitacin drugs (CuB and CuI) that contain multiple hydrogen bond donors and acceptors evenly distributed on their molecules while the other class of drugs (fenofibrate and nimodipine) contain essentially only clustered hydrogen bond acceptors. In the case of cucurbitacin drugs, the results showed that PEO-b-3PCL lowered the Flory-Huggins interaction parameters (chi) considerably (i.e., increased the drug solubility) compared to the linear di-block copolymer PEO-b-PCL with the same PCL/PEO (w/w) ratio of 1.0. However, the opposite effect was observed for fenofibrate and nimodipine. Analysis of the intermolecular interactions indicates that the number of hydrogen bonds formed between the three PCL blocks and cucurbitacin drugs is significantly higher than that of the linear di-block copolymer. On the other hand, owing to the absence of hydrogen bond donors and the clustering of the hydrogen bond acceptors on the fenofibrate and nimodipine molecules, this significantly reduces the number of hydrogen bonds formed in the multi-PCL block environment, leading to unfavourable chi values. The findings of the present work suggest that multi-hydrophobic block architecture could potentially increase the drug loading for hydrophobic drugs with structures containing evenly distributed multiple hydrogen bond donors and acceptors., ((c) 2009 Elsevier Ltd. All rights reserved.)

Molecular dynamics (MD) simulation was used to investigate the solubility of two hydrophobic drugs Cucurbitacin B (CuB) and Cucurbitacin I (CuI) in poly(ethylene oxide)-b-poly(alpha-benzyl carboxylate epsilon-caprolactone) (PEO-b-PBCL) block copolymers with different tacticities. In particular, di-block copolymer with three different tacticities viz. PEO-b-iPBCL, PEO-b-sPBCL, and PEO-b-aPBCL were used. The solubility was quantified by calculating the corresponding Flory-Huggins interaction parameters (chi) using random binary mixture models with 10wt% of drug. The tacticity of the di-block copolymer was found to influence significantly the solubility of two drugs in it. In particular, based on MD simulation results, only PEO-b-sPBCL exhibited solubility while the other two did not. Given the fact that the drugs were shown to be soluble in PEO-b-PBCL experimentally, it is predicted that the tacticity of the di-block copolymer synthesized in experiment is syndiotactic. This predication matches well with the dominant ring opening polymerization of cyclic lactones to syndiotactic polymers by stannous octoate as catalyst used to prepare PEO-b-PBCL block copolymers in our previous experiments. The simulation results showed that the solubility of the drugs in PEO-b-sPBCL is attributed to the favorable intra-molecular interaction of the di-block copolymer and favorable intermolecular interaction between the di-block copolymer and the drugs. Radial distribution function analysis provides useful insights into the nature and type of the intermolecular interactions.