Reduced variance analysis of molecular dynamics simulations by linear combination of estimators.

Building upon recent developments of force-based estimators with a reduced variance for the computation of densities, radial distribution functions, or local transport properties from molecular simulations, we show that the variance can be further reduced by considering optimal linear combinations of such estimators. This control variates approach, well known in statistics and already used in other branches of computational physics, has been comparatively much less exploited in molecular simulations. We illustrate this idea on the radial distribution function and the one-dimensional density of a bulk and confined Lennard-Jones fluid, where the optimal combination of estimators is determined for each distance or position, respectively. In addition to reducing the variance everywhere at virtually no additional cost, this approach cures an artifact of the initial force-based estimators, namely, small but non-zero values of the quantities in regions where they should vanish. Beyond the examples considered here, the present work highlights, more generally, the underexplored potential of control variates to estimate observables from molecular simulations.

Mass-zero constrained molecular dynamics for electrode charges in simulations of electrochemical systems.

Classical molecular dynamics simulations have recently become a standard tool for the study of electrochemical systems. State-of-the-art approaches represent the electrodes as perfect conductors, modeling their responses to the charge distribution of electrolytes via the so-called fluctuating charge model. These fluctuating charges are additional degrees of freedom that, in a Born-Oppenheimer spirit, adapt instantaneously to changes in the environment to keep each electrode at a constant potential. Here, we show that this model can be treated in the framework of constrained molecular dynamics, leading to a symplectic and time-reversible algorithm for the evolution of all the degrees of freedom of the system. The computational cost and the accuracy of the new method are similar to current alternative implementations of the model. The advantage lies in the accuracy and long term stability guaranteed by the formal properties of the algorithm and in the possibility to systematically introduce additional kinematic conditions of arbitrary number and form. We illustrate the performance of the constrained dynamics approach by enforcing the electroneutrality of the electrodes in a simple capacitor consisting of two graphite electrodes separated by a slab of liquid water.

SLEEP-GOAL: A multicenter success criteria outcome study on 302 obstructive sleep apnoea (OSA) patients.

OBJECTIVE: To demonstrate SLEEP-GOAL as a more holistic and comprehensive success criterion for Obstructive Sleep Apnoea (OSA) treatment. METHODS: A prospective 7-country clinical trial of 302 OSA patients, who met the selection criteria, and underwent nose, palate and/or tongue surgery. Pre- and post-operative data were recorded and analysed based on both the Sher criteria (apnoea hypopnea index, AHI reduction 50% and <20) and the SLEEP-GOAL. RESULTS: There were 229 males and 73 females, mean age of 42.4±17.3 years, mean BMI 27.9±4.2. The mean VAS score improved from 7.7±1.4 to 2.5±1.7 (p<0.05), mean Epworth score (ESS) improved from 12.2±4.6 to 4.9±2.8 (p<0.05), mean body mass index (BMI) decreased from 27.9±4.2 to 26.1±3.7 (p>0.05), gross weight decreased from 81.9±14.3kg to 76.6±13.3kg. The mean AHI decreased 33.4±18.9 to 14.6±11.0 (p<0.05), mean lowest oxygen saturation (LSAT) improved 79.4±9.2% to 86.9±5.9% (p<0.05), and mean duration of oxygen <90% decreased from 32.6±8.9 minutes to 7.3±2.1 minutes (p<0.05). The overall success rate (302 patients) based on the Sher criteria was 66.2%. Crosstabulation of respective major/minor criteria fulfilment, based on fulfilment of two major and two minor or better, the success rate (based on SLEEP-GOAL) was 69.8%. Based solely on the Sher criteria, 63 patients who had significant blood pressure reduction, 29 patients who had BMI reduction and 66 patients who had clinically significant decrease in duration of oxygen <90% would have been misclassified as "failures". CONCLUSION: AHI as a single parameter is unreliable. Assessing true success outcomes of OSA treatment, requires comprehensive and holistic parameters, reflecting true end-organ injury/function; the SLEEP-GOAL meets these requirements.

Predictors of difficulty in intubation in patients with obstructive sleep apnoea.

OBJECTIVE: To evaluate predictors of difficult intubation in patients with obstructive sleep apnoea (OSA). METHODOLOGY: Prospective series of 405 OSA patients (350 males/55 females) who had upper airway surgery. Procedures included functional endoscopic sinus surgery, septoplasty, turbinate reduction, palate/tonsil surgery, and/or tongue base surgery. Intubation difficulty (ID) was assessed using Mallampati grade, Laryngoscopic grade (Cormack and Lehane), and clinical parameters including BMI, neck circumference, thyromental distance, jaw adequacy, neck movements and glidescope grading. RESULTS: Mean age was 41.6 years old; mean BMI 26.6; mean neck circumference 44.5cm; mean Apnea Hypopnea Index (AHI) was 25.0; and mean LSAT 82%. The various laryngeal grades (based on Cormack and Lehane), grade 1 - 53 patients (12.9%), grade 2A - 127 patients (31.0%), grade 2B - 125 patients (30.5%), grade 3 - 93 patients (22.7%) and grade 4 - seven patients (1.7%); hence, 24.4% had difficulties in intubation. Parameters that adversely affected intubation were, age of the patient, opening of mouth, retrognathia, overbite, overjet, limited neck extension, thyromental distance, Mallampati grade, and macroglossia (p<0.001). Body mass index (BMI) (p=0.087), neck circumference (p=0.645), neck aches (p=0.728), jaw aches (p=0.417), tonsil size (p=0.048), and AHI (p=0.047) had poor correlation with intubation. BMI-adjusted for Asians and Caucasians, showed that Asians were more likely to have difficulties in intubation (adjusted OR = 4.6 (95%Confidence Interval: 1.05 to 20.06) (p=0.043), compared to the Caucasian group. CONCLUSION: This study illustrates that difficult intubation can be predicted pre-surgery in order to avert any anaesthetic morbidity.

Canadian Rhinology Working Group consensus statement: biologic therapies for chronic rhinosinusitis.

BACKGROUND: Recent evidence suggests that biologic therapy with targeted activity within the Type 2 inflammatory pathway can improve the clinical signs and symptoms of chronic rhinosinusitis with nasal polyposis (CRSwNP). There remains a population in CRSwNP that despite medical therapy and endoscopic sinus surgery have persistent signs and symptoms of disease. Therefore, biologics, monoclonal antibody agents, could be beneficial therapeutic treatments for these patients. There have been eight randomized, double-blind, placebo-controlled trails performed for CRSwNP targeted components of the Type 2 inflammatory pathway, notably interleukin (IL)-4, IL-5 and IL-13, IL-5R, IL-33, and immunoglobulin (Ig)E. However, there are no formal recommendations for the optimal use of biologics in managing Chronic Rhinosinusitis (CRS) within the Canadian health care environment. METHODS: A Delphi Method process was utilized involving three rounds of questionnaires in which the first two were completed individually online and the third was discussed on a virtual platform with all the panelists. 17 fellowship trained rhinologists across Canada evaluated the 28 original statements on a scale of 1-10 and provided comments. A rating within 1-3 indicated disagreement, 8-10 demonstrated agreement and 4-7 represented being neutral towards a statement. All ratings were quantitively reviewed by mean, median, mode, range and standard deviation. Consensus was defined by removing the highest and lowest of the scores and using the "3 point relaxed system". RESULTS: After three rounds, a total of 11 statements achieved consensus. This white paper only contains the final agreed upon statements and clear rationale and support for the statements regarding the use of biologics in patients with CRS. CONCLUSION: This white paper provides guidance to Canadian physicians on the use of biologic therapy for the management of patients with CRS, but the medical and surgical regimen should ultimately be individualized to the patient. As more biologics become available and additional trials are published we will provide updated versions of this white paper every few years.

Recent advances in the modelling and simulation of electrokinetic effects: bridging the gap between atomistic and macroscopic descriptions.

Electrokinetic phenomena are of great practical importance in fields as diverse as micro-fluidics, colloid science and oil exploration. However, the quantitative prediction of electrokinetic effects was until recently limited to relatively simple geometries that allowed the use of analytical theories. In the past decade, there has been a rapid development in the use of numerical methods that can be used to model electrokinetic phenomena in complex geometries or, more generally, under conditions where the existing analytical approaches fail. The present paper discusses these recent developments, with special emphasis on the advent of coarse-grained models that make it possible to bridge the gap between a purely atomistic and macroscopic descriptions.

Urgent endoscopic orbital decompression for vision deterioration in dysthyroid optic neuropathy.

AIMS: To report visual acuity outcomes and potential complications in patients undergoing endoscopic transnasal orbital decompression in the setting of acutely deteriorating sight secondary to dysthyroid optic neuropathy (DON) unresponsive to corticosteroid therapy. No previous reports describe vision outcomes in this specific patient population undergoing urgent endoscopic decompression. MATERIAL AND METHODS: Retrospective case review at a tertiary-care academic hospital. Four patients with DON were identified that underwent urgent endoscopic orbital decompression for acutely deteriorating vision. Three patients underwent a later decompression of the other orbit, yielding seven decompressions in total for acutely deteriorating vision. Operative technique entailed inferior and medial wall decompressions. The posterior limit of medial wall decompression was within the sphenoid, just anterior to the annulus of Zinn to fully decompress the optic nerve. Primary outcome was visual acuity. RESULTS: In all seven decompressions, visual acuity improved substantially. In 5/7 eyes, preoperative vision was severely impaired at 20/150 or worse. Two eyes had mild and moderate impairment at 20/50 and 20/100. Post-operatively, the moderately and severely impaired eyes improved to 20/60 or better. No complications were encountered. CONCLUSION: Transnasal endoscopic orbital decompression is a safe, effective treatment for acutely worsening visual loss from DON. All cases demonstrated significant objective improvement in visual acuity. Given the need for later contralateral decompression in 3 patients, consideration should be given to performing bilateral orbital decompressions at the time of surgery.

Transport Properties of Li-TFSI Water-in-Salt Electrolytes.

Water-in-salts are a new family of electrolytes that may allow the development of aqueous Li-ion batteries. They have a structure that is reminiscent of ionic liquids, and they are characterized by a high concentration of ionic species. In this work, we study their transport properties and how they evolve with concentration by using molecular dynamic simulations. We first focus on the choice of the force field. By comparing the simulated viscosities and self-diffusion coefficients with experimental measurements, we select a set of parameters that reproduces well the transport properties. We then use the selected force field to study in detail the variations of the self and collective diffusivities of all the species as well as the transport number of the lithium ion. We show that correlations between ions and water play an important role over the whole concentration range. In the water-in-salt regime, the anions form a percolating network that reduces the cation-anion correlations and leads to rather large values for the transport number compared to other standard electrolytes.

Anterior palatoplasty in the treatment of obstructive sleep apnoea - a systemic review.

This study seeks to determine the objective and subjective success rates of anterior palatoplasty and its variants for the treatment of obstructive sleep apnoea (OSA). A systematic review with two independent searches of Medline, PubMed, Cochrane Library and Evidence Based Medicine Reviews was performed to identify publications relevant to OSA and anterior palatoplasty. All relevant studies published before 30 June 2015 were included. Six studies were included in the systematic review. The numbers of patients in each paper ranged from 13 to 77 (total = 240), and mean age ranged from 21 to 51 years. Substantial and consistent improvement in polysomnography (PSG) outcomes were observed in patients after the anterior palatoplasty, with or without multilevel surgery. The results showed that the anterior palatoplasty technique provides significantly improvement in the post-operative Apnoea-Hypopnea Index. The mean pre-operative AHI (in the 6 papers) improved from 16.3 to 7.1, the snore visual analogue scale improved from 7.5 to 3.1 and the Epworth score reduced from 11.3 to 7.3 post-operatively. The overall pro-rated pooled success rate for all the patients was 72.5%, with a mean follow-up of 17.3 months. Anterior palatoplasty is an effective option in the management of patients with mild to moderate OSA.

International consensus (ICON) on the ENT role in diagnosis of obstructive sleep apnea syndrome.

During the 2017 IFOS ENT World Congress, an international expert panel was asked to clarify the role of ENT in the diagnosis process of the obstructive sleep apnea syndrome (OSA) in adults around the world. OSA is a major public health issue throughout the world. OSA is a highly prevalent disease with heavy clinical, social and economical outcomes. This high prevalence raises serious difficulties of diagnosis accessibility if only somnologists are able to confirm OSA diagnosis. First of all, the panellists reviewed the impact of OSA. Secondly, they defined the ENT role stressing ENT legitimacy, professional expertise and academic and institutional tasks. They also defined when somnologists were necessary. For the international panel, the ENT is a major player in the OSA diagnosis process.

Publication trends in obstructive sleep apnea: Evidence of need for more evidence.

OBJECTIVE: Published research in obstructive sleep apnea (OSA) appears limited despite OSA being a highly prevalent adult and pediatric disease leading to many adverse outcomes if left untreated. We aimed to quantify the deficit in OSA scientific literature in order to provide a novel way of identifying gaps in knowledge and a need for further research inquiry. METHODS: This was a Bibliometric analysis study. Using Ovid Medline database we analyzed and compared research output (medical and surgical) between adult OSA and similarly prevalent chronic conditions (Type II diabetes (T2DM), coronary artery disease (CAD) and osteoarthritis (OA)) from December 2016 up to fifty years prior. Linear graphs were utilized to trend collected data. Utilizing same strategy, we compared publication trends for pediatric OSA to asthma and gastroesophageal reflux (GER). RESULTS: Adult OSA publications (n = 9314) were significantly underrepresented when compared to T2DM (n = 66,023), CAD (n = 31,526) and OA (n = 34,123). Linear plots demonstrated that despite increasing number of publications this disparity persisted annually. Surgical literature composed 10.4% (n = 972) of adult OSA publications and reached a plateau in the last ten years. Pediatric OSA (n = 2994) had less research output when compared to asthma (n = 47,442) and GER (n = 6705). However, over past five years pediatric OSA surpassed GER in annual number of publications. Surgical literature represented 23.1% (n = 693) of pediatric OSA publications and continued increasing over past ten years. Study methodologies for both adult and pediatric OSA showed a lack of randomized controlled trials and meta-analyses in comparison to other diseases. CONCLUSION: Our review shows substantial deficit in total, annual and surgical adult OSA published research compared to similarly prevalent diseases. This trend is not entirely observed in pediatric OSA literature.

Comparing surgical trays with redundant instruments with trays with reduced instruments: a cost analysis.

BACKGROUND: When prearranged standard surgical trays contain instruments that are repeatedly unused, the redundancy can result in unnecessary health care costs. Our objective was to estimate potential savings by performing an economic evaluation comparing the cost of surgical trays with redundant instruments with surgical trays with reduced instruments ("reduced trays"). METHODS: We performed a cost-analysis from the hospital perspective over a 1-year period. Using a mathematical model, we compared the direct costs of trays containing redundant instruments to reduced trays for 5 otolaryngology procedures. We incorporated data from several sources including local hospital data on surgical volume, the number of instruments on redundant and reduced trays, wages of personnel and time required to pack instruments. From the literature, we incorporated instrument depreciation costs and the time required to decontaminate an instrument. We performed 1-way sensitivity analyses on all variables, including surgical volume. Costs were estimated in 2013 Canadian dollars. RESULTS: The cost of redundant trays was $21 806 and the cost of reduced trays was $8803, for a 1-year cost saving of $13 003. In sensitivity analyses, cost savings ranged from $3262 to $21 395, based on the surgical volume at the institution. Variation in surgical volume resulted in a wider range of estimates, with a minimum of $3253 for low-volume to a maximum of $52 012 for high-volume institutions. INTERPRETATION: Our study suggests moderate savings may be achieved by reducing surgical tray redundancy and, if applied to other surgical specialties, may result in savings to Canadian health care systems.

Simulation-based otolaryngology - head and neck surgery boot camp: 'how I do it'.

BACKGROUND: In otolaryngology, surgical emergencies can occur at any time. An annual surgical training camp (or 'boot camp') offers junior residents from across North America the opportunity to learn and practice these skills in a safe environment. The goals of this study were to describe the set-up and execution of a simulation-based otolaryngology boot camp and to determine participants' confidence in performing routine and emergency on-call procedures in stressful situations before and after the boot camp. METHODS: There were three main components of the boot camp: task trainers, simulations and an interactive panel discussion. Surveys were given to participants before and after the boot camp, and their confidence in performing the different tasks was assessed via multiple t-tests. RESULTS: Participants comprised 22 residents from 12 different universities; 10 of these completed both boot camp surveys. Of the nine tasks, the residents reported a significant improvement in confidence levels for six, including surgical airway and orbital haematoma management. CONCLUSION: An otolaryngology boot camp gives residents the chance to learn and practice emergency skills before encountering the emergencies in everyday practice. Their confidence in multiple skillsets was significantly improved after the boot camp. Given the shift towards competency-based learning in medical training, this study has implications for all surgical and procedural specialties.

An analytical model for probing ion dynamics in clays with broadband dielectric spectroscopy.

A simple two-state model is proposed to explicitly derive the ionic contribution to the frequency-dependent dielectric permittivity of clay. This model is based on a separation of time scales and accounts for two possible solvation modes (inner/outer-sphere complexes) for ions in the interlayer spacing and a possible chemical exchange between both forms. The influence on the permittivity of thermodynamic (distribution constant K(d)) and dynamic (diffusion coefficient, chemical relaxation rate) parameters is discussed. In turn, this model is used to analyze experimental data obtained with Na-montmorillonite for two relative humidities. The values of the parameters extracted from these measurements, and their variation with water content, show that the proposed model is at least reasonable.

Squeeze bottle versus saline spray after endoscopic sinus surgery for chronic rhinosinusitis: a pilot multicentre trial.

BACKGROUND: There is a need for controlled trials to guide the perioperative management of patients undergoing endoscopic sinus surgery (ESS). The authors performed a pilot multicenter trial to compare two types of saline delivery devices in this population. METHODS: Patients were randomized to high volume saline irrigation with a squeeze bottle and low volume saline spray after ESS in patients with chronic rhinosinusitis (CRS). Surgeons were blinded to treatment, and one-month postoperative scores for sinonasal outcomes [Sinonasal Outcome Test-22 (SNOT-22)] scale, nasal and sinus symptom score (NSS), and perioperative sinus endoscopy (POSE) scale were compared with preoperative scores. RESULTS: Nine centers provided data for 86 patients. All three outcomes measures improved significantly for both groups. Saline spray: SNOT-22 48.8 versus. 23.7, treatment effect 25.1 (95% confidence interval [CI], 17.9-32.2), POSE 21.1 versus. 8.4, treatment effect 12.7 (95% CI, 9.2-16.1), and NSS 8.2 versus 5.0, treatment effect 3.1 (95% CI, 1.4-4.9) pre- and postoperatively, respectively (all p < 0.0001). Squeeze bottle: SNOT-22 49.5 versus 23.6, treatment effect 25.9 (95% CI, 20.3-31.6), POSE 18.6 versus 9.2, treatment effect 9.3, (95% CI 6.7-12.0), and NSS 9.0 versus 5.7, treatment effect 3.3 (95% CI, 2.3-4.3) pre- and postoperatively, respectively (all p < 0.0001). Analysis of variance did not identify a difference between the two treatment groups. Subgroup analysis based on preoperative disease severity did not change the nonassociation of saline bottle with outcome measures. Post hoc sample size calculation determined that 176 patients is required to detect an 8.9-point difference in SNOT-22 scores. CONCLUSION: In this pilot multicenter trial examining patients with chronic rhinosinusitis undergoing ESS, both squeeze bottle and saline spray showed significant improvement in SNOT-22, POSE, and NSS scores at one-month postoperatively. Because the study was nonpowered, we cannot rule out a potential difference between the two treatment groups.

Tamoxifen attenuates glucocorticoid actions on bone formation in vitro.

Tamoxifen is a synthetic estrogen analog which may regulate osteogenesis in vivo by virtue of its antiglucocorticoid properties. We have examined tamoxifen regulation of glucocorticoid-induced osteogenesis in two different in vitro bone systems: the chicken periosteal osteogenesis model (CPO) and rat bone marrow stromal cells (RBMC). Hormone uptake studies were conducted with the osteosarcoma cell line, ROS 17/2.8. In the CPO model, alkaline phosphatase (AP) activity and collagen synthesis were stimulated by the glucocorticoid dexamethasone (Dex; 0.1 microM). These Dex-mediated effects were inhibited by increasing concentrations of tamoxifen (10-100 microM). Similarly, in the RBMC model, Dex-dependent (0.01 microM Dex) mineralized tissue formation and AP activity were blocked by tamoxifen (0.1 microM). Although tamoxifen inhibited Dex-mediated increases of AP activity in ROS 17/2.8 cells, it did not inhibit uptake of 3H-Dex or of 3H-estrogen. Northern analyses showed that tamoxifen did not affect messenger RNAs (mRNAs) for AP. Tamoxifen did seem to reduce mRNA for collagen type I, but not bone sialoprotein, osteopontin, and osteocalcin. Dex-induced increases for all proteins mRNAs in the RBMC model were not reduced by tamoxifen. Similarly, tamoxifen had no effects on cellular proliferation. We conclude that tamoxifen has no direct effect on gene expression of bone-related proteins of osteoblastic cells. Further, in the ROS 17/2.8 cell line, the antiglucocorticoid properties of tamoxifen do not appear to be mediated through either Dex or estrogen receptors.

A comparison of two methods of infiltration in breast reduction surgery.

The superwet technique has been shown in previous studies to dramatically reduce blood loss in breast reduction surgery, compared with standard infiltration. A retrospective chart review of 303 consecutive patients undergoing bilateral breast reduction surgery was undertaken to demonstrate additional differences in complication rate, operative time, or sponge use in the operating room. In this series, 132 consecutive patients received standard infiltration along incision lines (25 cc per breast of 1:100,000 epinephrine), and 171 patients received superwet infiltration with 240 cc per breast of 1:1,000,000 epinephrine. The average operative time was significantly reduced in the superwet group, from 78.5 minutes to 70.7 minutes (p < 0.01 level). The average number of sponges used intraoperatively was also decreased significantly (p < 0.01), from 26 to 20 sponges. Complication rates were equally low in both groups, demonstrating the safety of the superwet technique. In addition to limiting blood loss, the superwet infiltration effectively reduces operative time and sponge use without increasing complications in breast reduction surgery.

Numerical study of density functional theory with mean spherical approximation for ionic condensation in highly charged confined electrolytes.

We investigate numerically a density functional theory (DFT) for strongly confined ionic solutions in the canonical ensemble by comparing predictions of ionic concentration profiles and pressure for the double-layer configuration to those obtained with Monte Carlo (MC) simulations and the simpler Poisson-Boltzmann (PB) approach. The DFT consists of a bulk (ion-ion) and an ion-solid part. The bulk part includes nonideal terms accounting for long-range electrostatic and short-range steric correlations between ions and is evaluated with the mean spherical approximation and the local density approximation. The ion-solid part treats the ion-solid interactions at the mean-field level through the solution of a Poisson problem. The main findings are that ionic concentration profiles are generally better described by PB than by DFT, although DFT captures the nonmonotone co-ion profile missed by PB. Instead, DFT yields more accurate pressure predictions than PB, showing in particular that nonideal effects are important to describe highly confined ionic solutions. Finally, we present a numerical methodology capable of handling nonconvex minimization problems so as to explore DFT predictions when the reduced temperature falls below the critical temperature.

Highly confined ions store charge more efficiently in supercapacitors.

Liquids exhibit specific properties when they are adsorbed in nanoporous structures. This is particularly true in the context of supercapacitors, for which an anomalous increase in performance has been observed for nanoporous electrodes. This enhancement has been traditionally attributed in experimental studies to the effect of confinement of the ions from the electrolyte inside sub-nanometre pores, which is accompanied by their partial desolvation. Here we perform molecular dynamics simulations of realistic supercapacitors and show that this picture is correct at the microscopic scale. We provide a detailed analysis of the various environments experienced by the ions. We pick out four different adsorption types, and we, respectively, label them as edge, planar, hollow and pocket sites upon increase of the coordination of the molecular species by carbon atoms from the electrode. We show that both the desolvation and the local charge stored on the electrode increase with the degree of confinement.

Molecular simulation of aqueous solutions at clay surfaces.

We report a molecular simulation study of aqueous solutions at montmorillonite clay surfaces. Unlike most previous studies, ours does not focus on the interlayer nanopores, but looks at both kinds of external surfaces of clay particles: basal surfaces along the clay layers, and lateral surfaces through which interlayer and larger interparticle pores are linked. We present results on structural, dynamic and thermodynamic properties and phenomena, including hydration complexes of ions, H bonding networks, modification of the water dynamics with respect to the bulk, and the role of water in the cation exchange between interlayer and interparticle pores.