Longer Screws Can Reduce the Stress on the Upper Instrumented Vertebra With Long Spinal Fusion Surgery: A Finite Element Analysis Study.

STUDY DESIGN: A finite element analysis study. OBJECTIVE: Of proximal junctional failure, upper instrumented vertebra (UIV) fracture can causes severe spinal cord injury. Previously, we reported that higher occupancy rate of pedicle screw (ORPS) at UIV prevented UIV fracture in adult spinal deformity surgery; we had not yet tested this finding using a biomechanical study. The purpose of present study was to measure the differences in loads on the UIV according to the length of PS and ORPS. METHODS: We designed an FE model of a lumbar spine (L1-S1) using FE software. The PS was set from L2 to S1 and connected the rod. The FE model simulated flexion (8 Nm) to investigate the loads at UIV (L2) according to the length of the PS. There were 5 screw lengths examined: 40 (ORPS 36.4%), 45 (48.5%), 50 (66.7%), 55 (81.8%), and 60 mm (93.9%). RESULTS: Stress with bending motion was likely to occur at the upper front edge of the vertebral body, the pedicles, and the screw insertion point. The maximum equivalent stress according to screw lengths of 40, 45, 50, 55, and 60 mm were 45.6, 37.2, 21.6, 13.3, and 14.8 MPa, respectively. The longer screw, the less stress was applied to UIV. No remarkable change was observed between the screw lengths of 55 and 60 mm. CONCLUSIONS: Increasing ORPS to 81.8% or more reduced the load on the UIV. To prevent UIV fracture, the PS length in the UIV should be more than ORPS 81.8%.

Anxiety, depression, professional fulfilment and burnout: Public and private doctors' differential response to CoVID-19 pandemic.

Introduction: Covid-19 pandemic has been a challenge for healthcare system; the doctors in public and private setups are at the center of this challenge. Public and private doctors differ in personality and some occupational aspects. Do these differences reflect in their response to Covid? Aim: To study the difference in anxiety, depression, burnout, and professional fulfillment between doctors in public and private setup during Covid-19 second wave and to assess their coping strategies. Methods: A cross-sectional Internet-based observational study was conducted using Stanford PFI, GAD-7, PHQ-2, BFI-10, and brief COPE questionnaires. Results: A total of 114 public and 37 private doctors participated in the study. Doctors in private were older in age and deferred in personality profile. Significantly, more private doctors screened for anxiety disorder. 62.2% of private and 41.2% public doctors felt professionally fulfilled. Burnout and depression were not significantly different between groups. Active coping, acceptance, and planning coping were significantly more used by private doctors. Conclusion: There are differences how doctors in different setups respond to Covid-19, and there is need to understand these factors.

Phenylboronic Ester-Activated Aryl Iodide-Selective Buchwald-Hartwig-Type Amination toward Bioactivity Assay.

In this study, a phenylboronic ester-activated aryl iodide-selective Buchwald-Hartwig-type amination was developed. When the reaction of aryl iodides and aryl/aliphatic amines using Ni(acac)2 is carried out in the presence of phenylboronic ester, the Buchwald-Hartwig-type amination proceeds smoothly to afford the corresponding amines in high yields. This reaction does not proceed in the absence of phenylboronic ester. A wide variety of aryl iodides can be applied in the presence of aryl chlorides and bromides, which remain intact during the reaction. The mechanistic studies of this reaction suggest that the phenylboronic ester acts as an activator for the amines to form the ″ate complex″. Chemical kinetics studies show that the reaction of aryl iodides, base, and Ni(acac)2 follows first-order kinetics, while that of amines and phenylboronic ester follows zero-order kinetics. The bioactivity screening of the corresponding products showed that some amination products exhibit antifungal activity.

Design of Experimental Conditions with Machine Learning for Collaborative Organic Synthesis Reactions Using Transition-Metal Catalysts.

To improve product yields in synthetic reactions, it is important to use appropriate catalysts. In this study, we used machine learning to design catalysts for a reaction system in which both Buchwald-Hartwig-type and Suzuki-Miyaura-type cross-coupling reactions proceed simultaneously. First, using an existing dataset, yield prediction models were constructed with machine learning between experimental conditions, including the substrate and catalyst and the yields of the two products. Seven methods for calculating both the substrate and catalyst descriptors were proposed, and the predictive ability of the yield prediction models was discussed in terms of the descriptors and machine learning methods. Then, the constructed models were used to predict the compound yields for new combinations of substrates and catalysts, and the predictions were experimentally validated with high reproducibility, confirming that machine learning can predict yields from experimental conditions with high accuracy. In addition, to design catalysts that will improve the yields in our dataset, we added datasets collected from scientific papers and designed catalyst ligands. The proposed catalyst candidates were tested in actual synthetic experiments, and the experimental results exceeded the existing yields.

Activator-Promoted Aryl Halide-Dependent Chemoselective Buchwald-Hartwig and Suzuki-Miyaura Type Cross-Coupling Reactions.

Herein, we report the development of aryl halide-dependent chemoselective reactions, viz., the Buchwald-Hartwig type coupling reaction of an aryl iodide with an arylboronic acid and an aryl amine in the presence of a heterogeneous and reusable nickel catalyst and the Suzuki-Miyaura type coupling of an aryl chloride under similar conditions. Control experiments revealed that the presence of stoichiometric amounts of the phenylboronic acid/ester and aryl amine are essential for both reactions. NMR and XAFS studies suggested the formation of a boron-amine "ate" complex.

Posterior bone graft in lumbar spine surgery reduces the stress in the screw-rod system- A finite element study.

PURPOSE: Analyze the biomechanical effect of postero-lateral instrumentation with and without posterior bone graft as well as effect of consolidation of the graft. Study objectives are (1) whether bone graft alone will provide enough additional strength to the weakened spine, (2) how the addition of posterior bone graft help in extending the life of the fusion construct, and (3) compare the effect of gradual consolidation of the bone-graft on the spine biomechanics. METHODS: A lumbar spine finite element model was used to analyze the effects of bone-graft alone and varying grades of bone-graft consolidation with postero-lateral instrumentation on spine biomechanics. The spine stiffness and stresses in the posterior rods and screws were determined for moments applied in the three physiological directions in addition to pre-load. RESULTS: Stiffness of a normal lumbar spine with a solid consolidated posterior bone graft was found to be 10 times that of an intact lumbar spine. Posterior instrumentation further increased the spine stiffness by 20 fold. A 50% solid consolidation of the graft reduced the screw-rod maximum von-Mises stress by 45% and a 65% reduction in screw-rod stress was calculated with completely fused graft. CONCLUSION: A fused graft with posterior instrumentation provided a 200 fold increase in stiffness of an intact spine while producing stress shielding to the Ti rod-screw system. Considerable reduction of the maximum von-Mises stresses in the postero-lateral rod and screw fusion system (65%) will contribute to prevention of implant failure under repetitive loading highlighting the importance of consolidation of posterior bone-graft.

Biomechanical Analysis of a Long-Segment Fusion in a Lumbar Spine-A Finite Element Model Study.

Examine the biomechanical effect of material properties, geometric variables, and anchoring arrangements in a segmental pedicle screw with connecting rods spanning the entire lumbar spine using finite element models (FEMs). The objectives of this study are (1) to understand how different variables associated with posterior instrumentation affect the lumbar spine kinematics and stresses in instrumentation, (2) to compare the multidirectional stability of the spinal instrumentation, and (3) to determine how these variables contribute to the rigidity of the long-segment fusion in a lumbar spine. A lumbar spine FEM was used to analyze the biomechanical effects of different materials used for spinal rods (TNTZ or Ti or CoCr), varying diameters of the screws and rods (5 mm and 6 mm), and different fixation techniques (multilevel or intermittent). The results based on the range of motion and stress distribution in the rods and screws revealed that differences in properties and variations in geometry of the screw-rod moderately affect the biomechanics of the spine. Further, the spinal screw-rod system was least stable under the lateral bending mode. Stress analyzes of the screws and rods revealed that the caudal section of the posterior spinal instrumentation was more susceptible to high stresses and hence possible failure. Although CoCr screws and rods provided the greatest spinal stabilization, these constructs were susceptible to fatigue failure. The findings of the present study suggest that a posterior instrumentation system with a 5-mm screw-rod diameter made of Ti or TNTZ is advantageous over CoCr instrumentation system.

Monte Carlo studies of bootstrap variability in ROC analysis with data dependency.

ROC analysis involving two large datasets is an important method for analyzing statistics of interest for decision making of a classifier in many disciplines. And data dependency due to multiple use of the same subjects exists ubiquitously in order to generate more samples because of limited resources. Hence, a two-layer data structure is constructed and the nonparametric two-sample two-layer bootstrap is employed to estimate standard errors of statistics of interest derived from two sets of data, such as a weighted sum of two probabilities. In this article, to reduce the bootstrap variance and ensure the accuracy of computation, Monte Carlo studies of bootstrap variability were carried out to determine the appropriate number of bootstrap replications in ROC analysis with data dependency. It is suggested that with a tolerance 0.02 of the coefficient of variation, 2,000 bootstrap replications be appropriate under such circumstances.

The Impact of Data Dependence on Speaker Recognition Evaluation.

The data dependency due to multiple use of the same subjects has impact on the standard error (SE) of the detection cost function (DCF) in speaker recognition evaluation. The DCF is defined as a weighted sum of the probabilities of type I and type II errors at a given threshold. A two-layer data structure is constructed: target scores are grouped into target sets based on the dependency, and likewise for non-target scores. On account of the needed equal probabilities for scores being selected when resampling, target sets must contain the same number of target scores, and so must non-target sets. In addition to the bootstrap method with i.i.d. assumption, the nonparametric two-sample one-layer and two-layer bootstrap methods are carried out based on whether the resampling takes place only on sets, or subsequently on scores within the sets. Due to the stochastic nature of the bootstrap, the distributions of the SEs of the DCF estimated using the three different bootstrap methods are created and compared. After performing hypothesis testing, it is found that data dependency increases not only the SE but also the variation of the SE, and the two-layer bootstrap is more conservative than the one-layer bootstrap. The rationale regarding the different impacts of the three bootstrap methods on the estimated SEs is investigated.

A novel measure and significance testing in data analysis of cell image segmentation.

BACKGROUND: Cell image segmentation (CIS) is an essential part of quantitative imaging of biological cells. Designing a performance measure and conducting significance testing are critical for evaluating and comparing the CIS algorithms for image-based cell assays in cytometry. Many measures and methods have been proposed and implemented to evaluate segmentation methods. However, computing the standard errors (SE) of the measures and their correlation coefficient is not described, and thus the statistical significance of performance differences between CIS algorithms cannot be assessed. RESULTS: We propose the total error rate (TER), a novel performance measure for segmenting all cells in the supervised evaluation. The TER statistically aggregates all misclassification error rates (MER) by taking cell sizes as weights. The MERs are for segmenting each single cell in the population. The TER is fully supported by the pairwise comparisons of MERs using 106 manually segmented ground-truth cells with different sizes and seven CIS algorithms taken from ImageJ. Further, the SE and 95% confidence interval (CI) of TER are computed based on the SE of MER that is calculated using the bootstrap method. An algorithm for computing the correlation coefficient of TERs between two CIS algorithms is also provided. Hence, the 95% CI error bars can be used to classify CIS algorithms. The SEs of TERs and their correlation coefficient can be employed to conduct the hypothesis testing, while the CIs overlap, to determine the statistical significance of the performance differences between CIS algorithms. CONCLUSIONS: A novel measure TER of CIS is proposed. The TER's SEs and correlation coefficient are computed. Thereafter, CIS algorithms can be evaluated and compared statistically by conducting the significance testing.

Assessment of Paraspinal Muscle Cross-sectional Area After Lumbar Decompression: Minimally Invasive Versus Open Approaches.

STUDY DESIGN: A retrospective, blinded analysis of imaging studies. SUMMARY OF BACKGROUND DATA: To evaluate changes in paraspinal muscle cross-sectional area (CSA) after surgical treatment for lumbar stenosis and to compare these changes between minimally invasive and standard open approaches. The open approach to lumbar stenosis is effective, but it involves retraction and resection of muscle from the spinous process, which can result in ischemia and denervation of paraspinal musculature and may lead to muscle atrophy and pain. OBJECTIVE: It is hypothesized that the microendoscopic decompression of stenosis (MEDS) technique will better preserve the paraspinal muscles compared with the open procedure. MATERIALS AND METHODS: A total of 18 patients underwent a 1-level posterior decompression for lumbar stenosis, (9 open, 9 MEDS). Lumbar magnetic resonance imaging was obtained before surgery and after surgery (open approach average 16.3 mo; MEDS average 16.6 mo). CSA of paraspinal muscles were averaged over the distance of the surgical site. RESULTS: The mean age of patients treated with the open and MEDS approaches were 55.2 and 66.4 years, respectively (P=0.07). Paraspinal muscle CSA decreased by an average of 5.4% (SD=10.6%; range, -24.5% to +7.7%) in patients treated with the open approach and increased by an average of 9.9% (SD=14.4%; range, -9.8% to +33.1%) in patients treated with MEDS (P=0.02). For the open approach, changes in CSA did not differ significantly between the left and right sides for erector spinae (P=0.35) or multifidus muscles (P=0.90). After the MEDS approach there were no significant differences between the dilated and contralateral sides with regard to change in CSA for erector spinae (P=0.85) or multifidus muscles (P=0.95). CONCLUSIONS: Compared with the open approach for lumbar stenosis, MEDS had significantly less negative impact on the paraspinal muscle CSA. Previous reports have documented negative effects of paraspinal muscle injury, including weakness, disability, and pain. Collectively, these data suggest that the MEDS approach for lumbar decompression is less destructive to the paraspinous muscles than the open approach and may facilitate better clinical outcomes.

Lumbar disc degeneration is an equally important risk factor as lumbar fusion for causing adjacent segment disc disease.

Treatment of degenerative spinal disorders by fusion produces abnormal mechanical conditions at mobile segments above or below the site of spinal disorders and is clinically referred to as adjacent segments disc disease (ASDD) or transition syndrome in the case of a previous surgical treatment. The aim of the current study is to understand with the help of poro-elastic finite element models how single or two level degeneration of lower lumbar levels influences motions at adjacent levels and compare the findings to motions produced by single or two level fusions when the adjacent disk has varying degree of degeneration. Validated grade-specific finite element models including varying grades of disc degeneration at lower lumbar levels with and without fusion were developed and used to determine motions at all levels of the lumbar spine due to applied moment loads. Results showed that adjacent disc motions do depend on severity of disc degeneration, number of disc degenerated or fused, and level at which degeneration or fusion occurred. Furthermore, single level degeneration and single level fusion produced similar amount of adjacent disc motions. The pattern of increase in adjacent segment motions due to disc degeneration and increase in motions at segment adjacent to fusion was similar. Based on the current study, it can be concluded that disc degeneration should also be considered as a risk factor in addition to fusion for generating adjacent disc degeneration. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:123-130, 2017.

Validation of Nonparametric Two-Sample Bootstrap in ROC Analysis on Large Datasets.

The nonparametric two-sample bootstrap is applied to computing uncertainties of measures in ROC analysis on large datasets in areas such as biometrics, speaker recognition, etc., when the analytical method cannot be used. Its validation was studied by computing the SE of the area under ROC curve using the well-established analytical Mann-Whitney-statistic method and also using the bootstrap. The analytical result is unique. The bootstrap results are expressed as a probability distribution due to its stochastic nature. The comparisons were carried out using relative errors and hypothesis testing. They match very well. This validation provides a sound foundation for such computations.

Measuring and Specifying Combinatorial Coverage of Test Input Configurations.

A key issue in testing is how many tests are needed for a required level of coverage or fault detection. Estimates are often based on error rates in initial testing, or on code coverage. For example, tests may be run until a desired level of statement or branch coverage is achieved. Combinatorial methods present an opportunity for a different approach to estimating required test set size, using characteristics of the test set. This paper describes methods for estimating the coverage of, and ability to detect, t-way interaction faults of a test set based on a covering array. We also develop a connection between (static) combinatorial coverage and (dynamic) code coverage, such that if a specific condition is satisfied, 100% branch coverage is assured. Using these results, we propose practical recommendations for using combinatorial coverage in specifying test requirements.

Removing divergence of JCGM documents from the GUM ( 1993) and repairing other defects.

The mission of the Joint Committee for Guides in Metrology (JCGM) is to maintain and promote the use of the Guide to the Expression of Uncertainty in Measurement (GUM) and the International Vocabulary of Metrology (VIM, second edition). The JCGM has produced the third edition of the VIM (referred to as VIM3) and a number of documents; some of which are referred to as supplements to the GUM. We are concerned with the Supplement 1 (GUM-S1) and the document JCGM 104. The signal contribution of the GUM is its operational view of the uncertainty in measurement (as a parameter that characterizes the dispersion of the values that could be attributed to an unknown quantity). The operational view promulgated by the GUM had disconnected the uncertainty in measurement from the unknowable quantities true value and error. The GUM-S1 has diverged from the operational view of the uncertainty in measurement. Either the disparities should be removed or the GUM-S1 should not be referred to as a supplement to the GUM. Also, the GUM-S1 has misinterpreted the Bayesian concept of a statistical parameter and the VIM3 definitions of coverage interval and coverage probability are mathematically defective. We offer practical suggestions for revising the GUM-S1 and the VIM3 to remove their divergence from the GUM and to repair their defects.

Significant stabilization of palladium by gold in the bimetallic nanocatalyst leading to an enhanced activity in the hydrodechlorination of aryl chlorides.

The stabilization effect of Au towards Pd changed the reactivity of Pd in Au/Pd bimetallic nanoclusters, altering the reaction mechanism from homogeneous to heterogeneous in dechlorination reaction of aryl chlorides. This phenomenon was illustrated by the observed enhancement of the rate of reaction by in situ generated Au-rich bimetallic Au/Pd nanoclusters.

Comparative technoeconomic analysis of a softwood ethanol process featuring posthydrolysis sugars concentration operations and continuous fermentation with cell recycle.

Economical production of second generation ethanol from Ponderosa pine is of interest due to widespread mountain pine beetle infestation in the western United States and Canada. The conversion process is limited by low glucose and high inhibitor concentrations resulting from conventional low-solids dilute acid pretreatment and enzymatic hydrolysis. Inhibited fermentations require larger fermentors (due to reduced volumetric productivity) and low sugars lead to low ethanol titers, increasing distillation costs. In this work, multiple effect evaporation (MEE) and nanofiltration (NF) were evaluated to concentrate the hydrolysate from 30 g/l to 100, 150, or 200 g/l glucose. To ferment this high gravity, inhibitor containing stream, traditional batch fermentation was compared with continuous stirred tank fermentation (CSTF) and continuous fermentation with cell recycle (CSTF-CR). Equivalent annual operating cost (EAOC = amortized capital + yearly operating expenses) was used to compare these potential improvements for a local-scale 5 MGY ethanol production facility. Hydrolysate concentration via evaporation increased EAOC over the base process due to the capital and energy intensive nature of evaporating a very dilute sugar stream; however, concentration via NF decreased EAOC for several of the cases (by 2 to 15%). NF concentration to 100 g/l glucose with a CSTF-CR was the most economical option, reducing EAOC by $0.15 per gallon ethanol produced. Sensitivity analyses on NF options showed that EAOC improvement over the base case could still be realized for even higher solids removal requirements (up to two times higher centrifuge requirement for the best case) or decreased NF performance.

Continuous enzymatic hydrolysis of lignocellulosic biomass with simultaneous detoxification and enzyme recovery.

Recovering hydrolysis enzymes and/or alternative enzyme addition strategies are two potential mechanisms for reducing the cost during the biochemical conversion of lignocellulosic materials into renewable biofuels and biochemicals. Here, we show that enzymatic hydrolysis of acid-pretreated pine wood with continuous and/or fed-batch enzyme addition improved sugar conversion efficiencies by over sixfold. In addition, specific activity of the hydrolysis enzymes (cellulases, hemicellulases, etc.) increased as a result of continuously washing the residual solids with removal of glucose (avoiding the end product inhibition) and other enzymatic inhibitory compounds (e.g., furfural, hydroxymethyl furfural, organic acids, and phenolics). As part of the continuous hydrolysis, anion exchange resin was tested for its dual application of simultaneous enzyme recovery and removal of potential enzymatic and fermentation inhibitors. Amberlite IRA-96 showed favorable adsorption profiles of inhibitors, especially furfural, hydroxymethyl furfural, and acetic acid with low affinity toward sugars. Affinity of hydrolysis enzymes to adsorb onto the resin allowed for up to 92 % of the enzymatic activity to be recovered using a relatively low-molar NaCl wash solution. Integration of an ion exchange column with enzyme recovery into the proposed fed-batch hydrolysis process can improve the overall biorefinery efficiency and can greatly reduce the production costs of lignocellulosic biorenewable products.

A biomechanical comparison of three different posterior fixation constructs used for c6-c7 cervical spine immobilization: a finite element study.

The intralaminar screw construct has been recently introduced in C6-C7 fixation. The aim of the study is to compare the stability afforded by three different C7 posterior fixation techniques using a three-dimensional finite element model of a C6-C7 cervical spine motion segment. Finite element models representing three different cervical anchor types (C7 intralaminar screw, C7 lateral mass screw, and C7 pedicle screw) were developed. Range of motion (ROM) and maximum von Mises stresses in the vertebra for the three screw techniques were compared under pure moments in flexion, extension, lateral bending, and axial rotation. ROM for pedicle screw construct was less than the lateral mass screw construct and intralaminar screw construct in the three principal directions. The maximum von Misses stress was observed in the C7 vertebra around the pedicle in all the three screw constructs. Maximum von Mises stress in pedicle screw construct was less than the lateral mass screw construct and intralaminar screw construct in all loading modes. This study demonstrated that the pedicle screw fixation is the strongest instrumentation method for C6-C7 fixation. Pedicle screw fixation resulted in least stresses around the C7 pedicle-vertebral body complex. However, if pedicle fixation is not favorable, the laminar screw can be a better option compared to the lateral mass screw because the stress around the pedicle-vertebral body complex and ROM predicted for laminar screw construct was smaller than those of lateral mass screw construct.

Damage accumulation location under cyclic loading in the lumbar disc shifts from inner annulus lamellae to peripheral annulus with increasing disc degeneration.

It is difficult to study the breakdown of lumbar disc tissue over several years of exposure to bending and lifting by experimental methods. In our earlier published study we have shown how a finite element model of a healthy lumbar motion segment was used to predict the damage accumulation location and number of cyclic to failure under different loading conditions. The aim of the current study was to extend the continuum damage mechanics formulation to the degenerated discs and investigate the initiation and progression of mechanical damage. Healthy disc model was modified to represent degenerative discs (Thompson grade III and IV) by incorporating both geometrical and biochemical changes due to degeneration. Analyses predicted decrease in the number of cycles to failure with increasing severity of disc degeneration. The study showed that the damage initiated at the posterior inner annulus adjacent to the endplates and propagated outwards towards its periphery in healthy and grade III degenerated discs. The damage accumulated preferentially in the posterior region of the annulus. However in grade IV degenerated disc damage initiated at the posterior outer periphery of the annulus and propagated circumferentially. The finite element model predictions were consistent with the infrequent occurrence of rim lesions at early age but a much higher incidence in severely degenerated discs.