Search

STUDY DESIGN Prospective cohort study. OBJECTIVE The aim of this study was to identify surgical factors that affect adjacent segment kinematics after anterior cervical discectomy and fusion (ACDF) as measured by biplane radiography. SUMMARY OF BACKGROUND DATA Previous studies investigated the effect of surgical factors on spine kinematics as a potential etiology for adjacent segment disease (ASD). Those studies used static flexion-extension radiographs to evaluate range of motion. However, measurements from static radiographs are known to be unreliable. Furthermore, those studies were unable to evaluate the effect of ACDF on adjacent segment axial rotation. METHODS Patients had continuous cervical spine flexion/exten- sion and axial rotation movements captured at 30 images per second in a dynamic biplane radiography system preoperatively and 1 year after ACDF. Digitally reconstructed radiographs generated from subject-specific CT scans were matched to biplane radiographs using a previously validated tracking process. Dynamic kinematics, postoperative segmental kyphosis, and disc distraction were calculated from this tracking process. Plate-to-disc distance was measured on postoperative radiographs. Graft type was collected from the medical record. Multivariate linear regression was performed to identify surgical factors associated with 1-year post-surgery changes in adjacent segment kinematics. A secondary analysis was also performed to compare adjacent segment kinematics between each of the surgical factors and previously defined thresholds believed to be associated with adjacent segment degeneration. RESULTS Fifty-nine patients completed preoperative and postoperative testing. No association was found between any of the surgical factors and change in adjacent segment flexion/exten- sion or axial rotation range of motion (all P > 0.09). The secondary analysis also did not identify differences between adjacent segment kinematics and surgical factors (all P > 0.07). CONCLUSION Following ACDF for cervical spondylosis, factors related to surgical technique were not associated with short-term changes in adjacent segment kinematics that reflect the hypermobility hypothesized to lead to the development of ASD.Level of Evidence: 2.

Study design Prospective cohort. Objective The aim of this study was to determine the effect of graft type on residual motion and the relationship among residual motion, smoking, and patient-reported outcome (PRO) scores following anterior cervical discectomy and fusion (ACDF). Summary of background data Although most patients develop solid fusion based on static imaging following ACDF, dynamic imaging has revealed that many patients continue to have residual motion at the arthrodesis. Methods Forty-eight participants performed dynamic neck flexion/extension and axial rotation within a biplane radiography system 1 year following ACDF (21 one-level, 27 two-level). PRO scores included the Short Form-36, Neck Disability Index, and Cervical Spine Outcomes Questionnaire. An automated model-based tracking process matched subject-specific bone models to the biplane radiographs with sub-millimeter accuracy. Residual motion was measured across the entire arthrodesis site for both one- and two-level fusions in patients who received either allograft or autograft. Patients were divided into "pseudarthrosis" (>3° of flexion/extension residual motion) and "solid fusion" groups. Residual motion and PROs were compared between groups using Student t tests. Results Patients who received allograft showed more total flexion/extension residual motion (4.1° vs. 2.8°, P = 0.12), although this failed to reach significance. No differences were noted in PROs based on graft type (all P > 0.08) or the presence of pseudarthrosis (all P > 0.13). No differences were noted in residual motion between smokers and nonsmokers (all P > 0.15); however, smokers who received allograft reported worse outcomes than nonsmokers who received allograft and smokers who received autograft. Conclusion Allograft may result in slightly more residual motion at the arthrodesis site 1 year after ACDF. However, there is minimal evidence that PROs are adversely affected by slightly increased residual motion, suggesting that the current definition of pseudarthrosis correlates poorly with clinically significant findings. Additionally, autograft appears to result in superior outcomes in patients who smoke.Level of Evidence: 2.

Removal of hardware procedures following posterior spinal fusion is most commonly performed for hardware irritation without overt infection. It is imperative that surgeons realize that serious complications may arise from this procedure. The purpose of this report is to report a case of a pneumothorax that developed in a thoracolumbar removal of hardware case that resulted in a patient death. Retrospective review of a patient’s medical record and imaging. A 74-year-old patient with a history of T4-10 anterior discectomy and fusion with rib autograft and T4-L2 posterior fusion underwent a removal of hardware procedure for delayed surgical site infection. During the procedure, the tip of the bolt cutter jaw broke and entered the pulmonary cavity leading to a pneumothorax. The patient developed pneumonia 1 month postoperatively and passed away. This case report highlights one of the rare but potential complications of spinal removal of hardware surgery. It is essential that surgeons are aware of the possibility of pulmonary complications during thoracolumbar removal of hardware cases so that they may fully counsel their patients on the potential risks.

Study design Cohort study. Objective The aim of this study was to determine the rate of accurate conflict of interest (COI) disclosure within three prominent subspecialty Spine journals during a 4-year period. Summary of background data Industry-physician relationships are crucial for technological advancement in spine surgery but serve as a source of bias in biomedical research. The Open Payments Database (OPD) was established after 2010 to increase financial transparency. Methods All research articles published from 2014 to 2017 in Spine, The Spine Journal (TSJ), and the Journal of Neurosurgery: Spine (JNS) were reviewed in this study. In these articles, all author's COI statements were recorded. The OPD was queried for all author entries within the disclose period of the journal. Discrepancies between the author's self-reported COIs and the documented COIs from OPD were recorded. Results A total of 6816 articles meeting inclusion criteria between 2014 and 2017 in Spine, TSJ, and JNS with 39,869 contributing authors. Overall, 15.8% of all authors were found to have an OPD financial relationship. Of 2633 authors in Spine with financial disclosures, 77.1% had accurate financial disclosures; 42.5% and 41.0% of authors with financial relationships in the OPD had accurate financial disclosures in TSJ and JNS, respectively. The total value of undisclosed conflicts of interest between 2014 and 2017 was $421 million with $1.48 billion in accurate disclosures. Of undisclosed payments, 68.7% were $10,000. Undisclosed payments included $180 million in research funding and $188 million in royalties. Conclusion This study demonstrates that undisclosed COI is highly prevalent for authors in major Spine journals. This study indicates that there remains a need to standardize definitions and financial thresholds for significant COI as well as to shift the reporting burden for COI to journals who actively review potential COIs instead of relying on self-reporting. Level of evidence 3.

Study Design: Retrospective cohort study. Objectives: To evaluate the impact of bariatric surgery on patient outcomes following elective instrumented lumbar fusion. Methods: A retrospective review of a prospectively collected database was performed. Patients who underwent a bariatric procedure prior to an elective instrumented lumbar fusion were evaluated. Lumbar procedures were performed at a large academic medical center from 1/1/2012 to 1/1/2018. The primary outcome was surgical site infection (SSI) requiring surgical debridement. Secondary outcomes were prolonged wound drainage requiring treatment, implant failure requiring revision, revision secondary to adjacent segment disease (ASD), and chronic pain states. A randomly selected, surgeon and comorbidity-matched group of 59 patients that underwent an elective lumbar fusion during that period was used as a control. Statistical analysis was performed using Student’s two-way t-tests for continuous data, with significance defined as P < .05. Results: Twenty-five patients were identified who underwent bariatric surgery prior to elective lumbar fusion. Mean follow-up was 2.4 ± 1.9 years in the bariatric group vs. 1.5 ± 1.3 years in the control group. Patients with a history of bariatric surgery had an increased incidence of SSI that required operative debridement, revision surgery due to ASD, and a higher incidence of chronic pain. Prolonged wound drainage and implant failure were equivalent between groups. Conclusion: In the present study, bariatric surgery prior to elective instrumented lumbar fusion was associated increased risk of surgical site infection, adjacent segment disease and chronic pain when compared to non-bariatric patients.

The purpose of this research was to articulate the pressures faced by USA higher education leaders lived experiences and the relationship to problem definition, attention focus, and strategy choice...

If intervertebral disc degeneration can be identified early, preventative treatments may be initiated before symptoms become disabling and costly. Changes in disc mechanics, such as the decrease in the compressive modulus of the nucleus, are some of the earliest signs of degeneration. Therefore, in vivo changes in the disc response to compressive load may serve as a biomarker for pending or early disc degeneration. The aim of this study was to assess the potential for using in vivo dynamic disc deformation to identify pathologic structural degeneration of the intervertebral disc. A validated model-based tracking technique determined vertebral motion from biplane radiographs collected during dynamic flexion/extension and axial rotation of the cervical spine. A computational model of the subaxial intervertebral discs was developed to identify the dynamic functional nucleus of each disc, that is, the disc region that underwent little to no additional compression during dynamic movements. The size and location of the dynamic functional nucleus was determined for 10 C5/C6 spondylosis patients, 10 C5/C6/C7 spondylosis patients, and 10 asymptomatic controls. The dynamic functional nucleus size was sensitive (significantly smaller than controls in 5 of 6 measurements at the diseased disc) and specific (no difference from controls in 9 of 10 measurements at non-diseased discs) to pathologic disc degeneration. These results provide evidence to suggest that structural disc degeneration, manifested by changes in the disc response to functional loading, may be identified in vivo from dynamic imaging collected during functional movements. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-7, 2019.

Highlights • Targeting VEGFR2 prevents secondary allodynia in inflammatory arthritis models. • Anti-VEGFR2 reduces vascular ICAM-1 and microglia in the dorsal horn. • Anti-VEGFR2 inhibits monocyte attachment to brain endothelial cells. • We propose a novel glio-vascular-immune mechanism that promotes pain. • Therapeutic anti-VEGFR2 may lessen chronic pain in inflammatory arthritis., Chronic pain can develop in response to conditions such as inflammatory arthritis. The central mechanisms underlying the development and maintenance of chronic pain in humans are not well elucidated although there is evidence for a role of microglia and astrocytes. However in pre-clinical models of pain, including models of inflammatory arthritis, there is a wealth of evidence indicating roles for pathological glial reactivity within the CNS. In the spinal dorsal horn of rats with painful inflammatory arthritis we found both a significant increase in CD11b+ microglia-like cells and GFAP+ astrocytes associated with blood vessels, and the number of activated blood vessels expressing the adhesion molecule ICAM-1, indicating potential glio-vascular activation. Using pharmacological interventions targeting VEGFR2 in arthritic rats, to inhibit endothelial cell activation, the number of dorsal horn ICAM-1+ blood vessels, CD11b+ microglia and the development of secondary mechanical allodynia, an indicator of central sensitization, were all prevented. Targeting endothelial VEGFR2 by inducible Tie2-specific VEGFR2 knock-out also prevented secondary allodynia in mice and glio-vascular activation in the dorsal horn in response to inflammatory arthritis. Inhibition of VEGFR2 in vitro significantly blocked ICAM-1-dependent monocyte adhesion to brain microvascular endothelial cells, when stimulated with inflammatory mediators TNF-α and VEGF-A165a. Taken together our findings suggest that a novel VEGFR2-mediated spinal cord glio-vascular mechanism may promote peripheral CD11b+ circulating cell transmigration into the CNS parenchyma and contribute to the development of chronic pain in inflammatory arthritis. We hypothesise that preventing this glio-vascular activation and circulating cell translocation into the spinal cord could be a new therapeutic strategy for pain caused by rheumatoid arthritis.

Chronic pain is highly comorbid with affective disorders, including major depressive disorder. A core feature of major depressive disorder is a loss of interest in previously rewarding activities. Major depressive disorder is also associated with negative affective biases where cognitive processes are modulated by the affective state. Previous work from our laboratory has shown that reward-related learning and memory is impaired in rodent models of depression generated through a variety of different manipulations. This study investigated different aspects of reward-related behaviour in a rodent model of chronic pain, the partial saphenous nerve injury (PSNI). Using our reward-learning assay, an impairment in reward learning was observed with no difference in sucrose preference, consistent with a lack of effect on reward sensitivity and similar to the effects seen in depression models. In a successive negative contrast task, chronic pain was not associated with changes in motivation for reward either under normal conditions or when reward was devalued although both sham and PSNI groups exhibited the expected negative contrast effect. In the affective bias test, PSNI rats developed a positive affective bias when treated with gabapentin, an effect not seen in the controls suggesting an association with the antinociceptive effects of the drug inducing a relatively more positive affective state. Together, these data suggest that there are changes in reward-related cognition in this chronic pain model consistent with previous findings in rodent models of depression. The effects seen with gabapentin suggest that pain-associated negative affective state may be remediated by this atypical analgesic.

Metamorphic testing requires the availability of a suitable set of metamorphic relations (MRs) for the application domain of interest. A software testing practitioner interested in using metamorphic testing is thus blocked unless they can devise a suitable set of MRs. In this paper we offer some practical advice on sources of inspiration for MRs, based on our experience building three fuzzing tools based on metamorphic testing: MF++, which supports automated testing of C++11 libraries, C4, which tests concurrency support in C11 compilers, and spirv-fuzz, which aims to find bugs in compilers for the SPIR-V programming language (mainly used in computer graphics). The MRs we have devised have taken inspiration from three main sources: (1) careful study of specification documents related to the libraries and programming languages that these tools target, (2) consultation of prior work and discussion with domain experts, and (3) manual inspection of the results of automated code coverage analysis on the systems under test. We describe these sources of inspiration in detail, giving a range of concrete examples for each. We hope that this experience report will help to inform developers of future metamorphic testing tools as to the steps they can take to discover MRs in their domains of interest.

BackgroundThe field of bioinformatics has grown at such a rapid pace that a gap in standardization exists when reporting an analysis. In response, the BioCompute project was created to standardize the type and method of information communicated when describing a bioinformatic analysis. Once the project became established, its goals shifted to broadening awareness and usage of BioCompute, and soliciting feedback from a larger audience. To address these goals, the BioCompute project collaborated with precisionFDA on a crowdsourced challenge that ran from May 2019 to October 2019. This challenge had a beginner track where participants submitted BCOs based on a pipeline of their choosing, and an advanced track where participants submitted applications supporting the creation of a BCO and verification of BCO conformance to specifications.ResultsIn total, there were 28 submissions to the beginner track (including submissions from a bioinformatics master’s class at George Washington University) and three submissions to the advanced track. Three top performers were selected from the beginner track, while a single top performer was selected for the advanced track. In the beginner track, top performers differentiated themselves by submitting BCOs that included more than the minimally compliant content. Advanced track submissions were very impressive. They included a complete web application, a command line tool that produced a static result, and a dockerized container that automatically created the BCO as the tool was run. The ability to harmonize the correct function, a simple user experience, and the aesthetics of the tool interface differentiated the tools.ConclusionsDespite being new to the concept, most beginner track scores were high, indicating that most users understood the fundamental concepts of the BCO specification. Novice bioinformatics students were an ideal cohort for this Challenge because of their lack of familiarity with BioCompute, broad diversity of research interests, and motivation to submit high-quality work. This challenge was successful in introducing the BCO to a wider audience, obtaining feedback from that audience, and resulting in a tool novices may use for BCO creation and conformance. In addition, the BCO specification itself was improved based on feedback illustrating the utility of a “wisdom of the crowd” approach to standards development.

ObjectivesInforming research participants of the results of studies in which they took part is viewed as an ethical imperative. However, there is little guidance in the literature about how to do this. The Fluoxetine Or Control Under Supervision trial randomised 3127 patients with a recent acute stroke to 6 months of fluoxetine or placebo and was published in the Lancet on 5 December 2018. The trial team decided to inform the participants of the results at exactly the same time as the Lancet publication, and also whether they had been allocated fluoxetine or placebo. In this report, we describe how we informed participants of the results.DesignIn the 6-month and 12-month follow-up questionnaires, we invited participants to provide an email address if they wished to be informed of the results of the trial. We re-opened our trial telephone helpline between 5 December 2018 and 31 March 2019.SettingUK stroke services.Participants3127 participants were randomised. 2847 returned 6-month follow-up forms and 2703 returned 12-month follow-up forms; the remaining participants had died (380), withdrawn consent or did not respond.ResultsOf those returning follow-up questionnaires, a total of 1845 email addresses were provided and a further 50 people requested results to be sent by post. Results were sent to all email and postal addresses provided; 309 emails were returned unrecognised. Seventeen people replied, of whom three called the helpline and the rest responded by email.ConclusionIt is feasible to disseminate results of large trials to research participants, though only around 60% of those randomised wanted to receive the results. The system we developed was efficient and required very little resource, and could be replicated by trialists in the future.Trial registration numberISRCTN83290762; Post-results.

Randomised compiler testing techniques require a means of generating programs that are free from undefined behaviour (UB) in order to reliably reveal miscompilation bugs. Existing program generators such as Csmith heavily restrict the form of generated programs in order to achieve DB-freedom. We hypothesise that the idiomatic nature of such programs limits the test coverage they can offer. Our idea is to generate less restricted programs that are still UB-free-programs that get closer to the edge of UB, but that do not quite cross the edge. We present preliminary support for our idea via a prototype tool, Csmithedge, which uses simple dynamic analysis to determine where Csmith has been too conservative in its use of safe math wrappers that guarantee UB-freedom for arithmetic operations. By eliminating redundant wrappers, Csmithedge was able to discover two new miscompilation bugs in GCC that could not be found via intensive testing using regular Csmith, and to achieve substantial differences in code coverage on GCC compared with regular Csmith. CCS CONCEPTS • Software and its engineering →Compilers; Software verification and validation.

Seroclearance of hepatitis B surface antigen (HBsAg) is the desired end point of treatment for chronic hepatitis B virus (HBV) infection, according to guidelines. We performed a systematic review and meta-analysis to evaluate the strength of the association between HBsAg seroclearance and long-term clinical outcomes.We performed a systematic review of the PubMed, EMBASE, and Cochrane Library databases for articles that assessed HBsAg status and reported the incidence of hepatocellular carcinoma (HCC), liver decompensation, liver transplantation, and/or all-cause mortality during follow-up evaluation. We performed a meta-analysis of rate ratios (RR) using a random-effects model independently for each end point and for a composite end point.We analyzed data from 28 studies, comprising a total of 188,316 patients with chronic HBV infection (treated and untreated), and 1,486,081 person-years (PY) of follow-up evaluation; 26 reported data on HCC, 7 on liver decompensation, and 13 on liver transplantation and/or death. The composite event rates were 0.19/1000 PY for the HBsAg seroclearance group and 2.45/1000 PY for the HBsAg-persistent group. Pooled RRs for the HBsAg seroclearance group were 0.28 for liver decompensation (95% CI, 0.13-0.59; P = .001), 0.30 for HCC (95% CI, 0.20-0.44; P.001), 0.22 for liver transplantation and/or death (95% CI, 0.13-0.39; P.001), and 0.31 for the composite end point (95% CI, 0.23-0.43; P.001). No differences in RR estimates were observed among subgroups of different study or patient characteristics.In a systematic review and meta-analysis, we found seroclearance of HBsAg to be associated significantly with improved patient outcomes. The results are consistent among different types of studies, in all patient subpopulations examined, and support the use of HBsAg seroclearance as a primary end point of trials of patients with chronic HBV infection.

In vitro biomechanical studies of the osteoligamentous spine are widely used to characterize normal biomechanics, identify injury mechanisms, and assess the effects of degeneration and surgical instrumentation on spine mechanics. The objective of this study was to determine how well four standards in vitro loading paradigms replicate in vivo kinematics with regards to the instantaneous center of rotation and arthrokinematics in relation to disc deformation. In vivo data were previously collected from 20 asymptomatic participants (45.5 ± 5.8 years) who performed full range of motion neck flexion-extension (FE) within a biplane x-ray system. Intervertebral kinematics were determined with sub-millimeter precision using a validated model-based tracking process. Ten cadaveric spines (51.8 ± 7.3 years) were tested in FE within a robotic testing system. Each specimen was tested under four loading conditions: pure moment, axial loading, follower loading, and combined loading. The in vivo and in vitro bone motion data were directly compared. The average in vitro instant center of rotation was significantly more anterior in all four loading paradigms for all levels. In general, the anterior and posterior disc heights were larger in the in vitro models than in vivo. However, after adjusting for gender, the observed differences in disc height were not statistically significant. This data suggests that in vitro biomechanical testing alone may fail to replicate in vivo conditions, with significant implications for novel motion preservation devices such as cervical disc arthroplasty implants.

Cervical radiculopathy is a relatively common neurological disorder, often resulting from mechanical compression of the nerve root within the neural foramen. Anterior cervical discectomy and fusion (ACDF) is a common treatment for radicular symptoms that do not resolve after conservative treatment. One mechanism by which ACDF is believed to resolve symptoms is by replacing degenerated disc tissue with bone graft to increase the neural foramen area, however in vivo evidence demonstrating this is lacking. The aim of this study was to evaluate the effects of age, pathology, and fusion on bony neural foramen area. Participants included 30 young adult controls (

Several highly effective, interferon-free, direct-acting antiviral (DAA)-based regimens are available for the treatment of chronic hepatitis C virus (HCV) infection. Despite impressive efficacy overall, a small proportion of patients in registrational trials experienced treatment failure, which in some cases was associated with the detection of HCV resistance-associated substitutions (RASs) at baseline. In this article, we describe methods and key findings from independent regulatory analyses investigating the impact of baseline nonstructural (NS) 3 Q80K and NS5A RASs on the efficacy of current United States Food and Drug Administration (FDA)-approved regimens for patients with HCV genotype (GT) 1 or GT3 infection. These analyses focused on clinical trials that included patients who were previously naive to the DAA class(es) in their investigational regimen and characterized the impact of baseline RASs that were enriched in the viral population as natural or transmitted polymorphisms (i.e., not drug-selected RASs). We used a consistent approach to optimize comparability of results across different DAA regimens and patient populations, including the use of a 15% sensitivity cutoff for next-generation sequencing results and standardized lists of NS5A RASs. These analyses confirmed that detection of NS3 Q80K or NS5A baseline RASs was associated with reduced treatment efficacy for multiple DAA regimens, but their impact was often minimized with the use of an intensified treatment regimen, such as a longer treatment duration and/or addition of ribavirin. We discuss the drug resistance-related considerations that contributed to pretreatment resistance testing and treatment recommendations in drug labeling for FDA-approved DAA regimens. Conclusion Independent regulatory analyses confirmed that baseline HCV RASs can reduce the efficacy of certain DAA-based regimens in selected patient groups. However, highly effective treatment options are available for patients with or without baseline RASs. (Hepatology 2018;67:2430-2448).

Degenerative spondylolisthesis (DS) in the setting of symptomatic lumbar spinal stenosis is commonly treated with spinal fusion in addition to decompression with laminectomy. However, recent studies have shown similar clinical outcomes after decompression alone, suggesting that a subset of DS patients may not require spinal fusion. Identification of dynamic instability could prove useful for predicting which patients are at higher risk of post-laminectomy destabilization necessitating fusion. The goal of this study was to determine if static clinical radiographs adequately characterize dynamic instability in patients with lumbar degenerative spondylolisthesis (DS) and to compare the rotational and translational kinematics in vivo during continuous dynamic flexion activity in DS versus asymptomatic age-matched controls. Seven patients with symptomatic single level lumbar DS (6 M, 1 F; 66 ± 5.0 years) and seven age-matched asymptomatic controls (5 M, 2 F age 63.9 ± 6.4 years) underwent biplane radiographic imaging during continuous torso flexion. A volumetric model-based tracking system was used to track each vertebra in the radiographic images using subject-specific 3D bone models from high-resolution computed tomography (CT). In vivo continuous dynamic sagittal rotation (flexion/extension) and AP translation (slip) were calculated and compared to clinical measures of intervertebral flexion/extension and AP translation obtained from standard lateral flexion/extension radiographs. Static clinical radiographs underestimate the degree of AP translation seen on dynamic in vivo imaging (1.0 vs 3.1 mm; p = 0.03). DS patients demonstrated three primary motion patterns compared to a single kinematic pattern in asymptomatic controls when analyzing continuous dynamic in vivo imaging. 3/7 (42%) of patients with DS demonstrated aberrant mid-range motion. Continuous in vivo dynamic imaging in DS reveals a spectrum of aberrant motion with significantly greater kinematic heterogeneity than previously realized that is not readily seen on current clinical imaging. Level V data These slides can be retrieved under Electronic Supplementary Material.

The development and approval of brincidofovir for the treatment of smallpox, a disease that was eradicated from the world over 40 years ago, has resulted in the second antiviral approved via the Medical Countermeasure Initiative (MCMi) to combat this disease. Approval of brincidofovir required a unique regulatory approach based on the FDA Animal Rule, and development was supported by many years of research and collaboration among academic investigators, the pharmaceutical industry and multiple government agencies. This article summarizes the FDA regulatory pathway and describes the challenges involved.

Adjacent segment disease can be a clinically significant complication following lumbar spinal arthrodesis. This disease is traditionally addressed surgically via a posterior approach, which can be associated with significant morbidity and complication. In recent years, the minimally invasive lateral approach has evolved as an effective surgical option for arthrodesis in the lumbar spine. We detail our use of this approach as an alternative treatment for adjacent segment disease, as it allows for placement of a large interbody graft and indirect decompression of the adjacent segment.

Diagnosing dysfunctional atlantoaxial motion is challenging given limitations of current diagnostic imaging techniques. Three-dimensional imaging during upright functional motion may be useful in identifying dynamic instability not apparent on static imaging. Abnormal atlantoaxial motion has been linked to numerous pathologies including whiplash, cervicogenic headaches, C2 fractures, and rheumatoid arthritis. However, normal C1/C2 rotational kinematics under dynamic physiologic loading have not been previously reported owing to imaging difficulties. The objective of this study was to determine dynamic three-dimensional in vivo C1/C2 kinematics during upright axial rotation. Twenty young healthy adults performed full head rotation while seated within a biplane X-ray system while radiographs were collected at 30 images per second. Six degree-of-freedom kinematics were determined for C1 and C2 via a validated volumetric model-based tracking process. The maximum global head rotation (to one side) was 73.6±8.3°, whereas maximum C1 rotation relative to C2 was 36.8±6.7°. The relationship between C1/C2 rotation and head rotation was linear through midrange motion (±20° head rotation from neutral) in a nearly 1:1 ratio. Coupled rotation between C1 and C2 included 4.5±3.1° of flexion and 6.4±8.2° of extension, and 9.8±3.8° of contralateral bending. Translational motion of C1 relative to C2 was 7.8±1.5mm ipsilaterally, 2.2±1.2mm inferiorly, and 3.3±1.0mm posteriorly. We believe this is the first study describing 3D dynamic atlantoaxial kinematics under true physiologic conditions in healthy subjects. C1/C2 rotation accounts for approximately half of total head axial rotation. Additionally, C1 undergoes coupled flexion/extension and contralateral bending, in addition to inferior, lateral and posterior translation.

Study DesignRetrospective clinical study.PurposeThe purpose of this study was to determine what percentage of patients who underwent nonoperative management of unilateral non-displaced or minimally displaced facet fractures progressed radiographically and to determine what percentage of patients required surgical intervention and to identify risk factors for failure of conservative management.Overview of LiteratureAccording to most commonly used classification systems, unilateral, non-and minimally displaced facet fractures are be amendable to nonoperative management.MethodsA retrospective review of the Trauma Registry of a Level I trauma center was performed to identify all patients diagnosed with a non- or minimally displaced unilateral facet fracture which was managed nonoperatively. Several demographic variables and clinical outcomes were recorded. Using computed tomography scanning and plain radiographs, fracture pattern, listhesis, displacement, angle and percentage of the facet that included the fracture were determined. Radiographic progression was defined as the occurrence of listhesis of more than 10% of the anterior-posterior dimensions of the inferior vertebral body during radiographic follow-up. Failure of conservative management was defined as a patient requiring surgical intervention after initially being managed nonoperatively.ResultsSeventy-four patients were included. Fifteen patients (20%) progressed radiographically. However, only 2 developed radicular symptoms and none developed myelopathy or other catastrophic cord related symptoms. Seven patients (9%) underwent surgery. Indications for surgery included significant radiographic progression and/or radicular symptoms. Risk factors for failure of conservative management included presence of radiculopathy at the time of presentation, a higher body mass index, increased Injury Severity Score, greater initial fracture displacement and more than 2 mm of listhesis.ConclusionsPatients with non-displaced or minimally displaced facet fractures who do not have neurological symptoms at the time of presentation can safely be managed conservatively with careful observation and follow-up.

Bone mineral density (BMD) measured using quantitative computed tomography (QCT) has been shown to correlate with bone mechanical properties. Knowledge of BMD within specific anatomic regions of the spine is valuable to surgeons who must secure instrumentation to the vertebrae, to medical device developers who design screws and disc replacements, and to researchers who assign mechanical properties to computational models. The objective of this study was to comprehensively characterize BMD in the cervical spine of young healthy adults.QCT was used to determine BMD in the cervical spines of 31 healthy adults (age 20-35). Subject-specific 3D models of each vertebra were created from CT scans, and anatomic regions of interest were identified in each bone (C1: 3 regions; C2: 9 regions, C3-C7: 13 regions). Statistical tests were performed to identify differences in BMD according to vertebral level, anatomic regions within vertebrae, and sex.BMD varied significantly among vertebral levels and among anatomic regions within each vertebra. Females had higher BMD than males (p = .041) primarily due to higher BMD in the posterior regions of each vertebra.These data can serve as a baseline to identify BMD changes in older and symptomatic patients. This data set is also the first report of volumetric bone density within different anatomic regions of the atlas and axis of the cervical spine. The finding of higher BMD in females is in agreement with the previous QCT results but contradicts DEXA results that are known to be dependent upon bone size.

Higher education is more complex than most in the academy understand. The purpose of this article is to explore administrator perceptions of the external pressures affecting higher education, the strategies they were using to address the pressures, and the internal barriers to dealing with the pressures successfully. Information comes from twenty-one administrators from nine different institutions (most “comprehensive regional colleges and universities”) with whom we talked.

Study design A longitudinal study using biplane radiography to measure in vivo intervertebral range of motion (ROM) during dynamic flexion/extension, and rotation. Objective To longitudinally compare intervertebral maximal ROM and midrange motion in asymptomatic control subjects and single-level arthrodesis patients. Summary of background data In vitro studies consistently report that adjacent segment maximal ROM increases superior and inferior to cervical arthrodesis. Previous in vivo results have been conflicting, indicating that maximal ROM may or may not increase superior and/or inferior to the arthrodesis. There are no previous reports of midrange motion in arthrodesis patients and similar-aged controls. Methods Eight single-level (C5/C6) anterior arthrodesis patients (tested 7 ± 1 months and 28 ± 6 months postsurgery) and six asymptomatic control subjects (tested twice, 58 ± 6 months apart) performed dynamic full ROM flexion/extension and axial rotation whereas biplane radiographs were collected at 30 images per second. A previously validated tracking process determined three-dimensional vertebral position from each pair of radiographs with submillimeter accuracy. The intervertebral maximal ROM and midrange motion in flexion/extension, rotation, lateral bending, and anterior-posterior translation were compared between test dates and between groups. Results Adjacent segment maximal ROM did not increase over time during flexion/extension, or rotation movements. Adjacent segment maximal rotational ROM was not significantly greater in arthrodesis patients than in corresponding motion segments of similar-aged controls. C4/C5 adjacent segment rotation during the midrange of head motion and maximal anterior-posterior translation were significantly greater in arthrodesis patients than in the corresponding motion segment in controls on the second test date. Conclusion C5/C6 arthrodesis appears to significantly affect midrange, but not end-range, adjacent segment motions. The effects of arthrodesis on adjacent segment motion may be best evaluated by longitudinal studies that compare maximal and midrange adjacent segment motion to corresponding motion segments of similar-aged controls to determine if the adjacent segment motion is truly excessive. Level of evidence 3.

Retrospective cohort study.Compare a novel two-step algorithm for indicating a computed tomography angiography (CTA) in the setting of a cervical spine fracture with established gold standard criteria.As CTA permits the rapid detection of blunt cerebrovascular injuries (BCVI), screening criteria for its use have broadened. However, more recent work warns of the potential for the overdiagnosis of BCVI, which must be considered with the adoption of broad criteria.A novel two-step metric for indicating CTA screening was compared with the American College of Surgeons guidelines and the expanded Denver Criteria using patients who presented with cervical spine fractures to a tertiary-level 1 trauma center from January 1, 2012 to January 1, 2016. The ability for each metric to identify BCVI and posterior circulation strokes that occurred during this period was assessed.A total of 721 patients with cervical fractures were included, of whom 417 underwent CTAs (57.8%). Sixty-eight BCVIs and seven strokes were diagnosed in this cohort. All algorithms detected an equivalent number of BCVIs (52 with the novel metric, 54 with the ACS and Denver Criteria, P = 0.84) and strokes (7/7, 100% with the novel metric, 6/7, 85.7% with the ACS and Denver Criteria, P = 1.0). However, 63% fewer scans would have been needed with the proposed screening algorithm compared with the ACS or Denver Criteria (261/721, 36.2% of all patients with our criteria vs. 413/721, 57.3% with the ACS standard and 417/721, 57.8%) with the Denver Criteria, P 0.0002 for each).A two-step criterion based on mechanism of injury and patient factors is a potentially useful guide for identifying patients at risk of BCVI and stroke after cervical spine fractures. Further prospective analyses are required prior to widespread clinical adoption.4.

The pathogenesis of lumbar adjacent segment disease is thought to be secondary to altered biomechanics resulting from fusion. Direct in vivo evidence for altered biomechanics following lumbar fusion is lacking. This study’s aim was to describe in vivo kinematics of the superior adjacent segment relative to the fused segment before and after lumbar fusion. This study analyzed seven patients with symptomatic lumbar degenerative spondylolisthesis (5 M, 2F; age 65 ± 5.1 years) using a biplane radiographic imaging system. Each subject performed two to three trials of continuous flexion of their torso according to established protocols. Synchronized biplane radiographs were acquired at 20 images per second one month before and six months after single-level fusion at L4-L5 or L5-S1, or two-level fusion at L3-L5 or L4-S1. A previously validated volumetric model-based tracking process was used to track the position and orientation of vertebrae in the radiographic images. Intervertebral flexion/extension and AP translation (slip) at the superior adjacent segment were calculated over the entire dynamic flexion activity. Skin-mounted surface markers were tracked using conventional motion analysis and used to determine torso flexion. Change in adjacent segment kinematics after fusion was determined at corresponding angles of dynamic torso flexion. Changes in adjacent segment motion varied across patients, however, all patients maintained or increased the amount of adjacent segment slip or intervertebral flexion/extension. No patients demonstrated both decreased adjacent segment slip and decreased rotation. This study suggests that short-term changes in kinematics at the superior adjacent segment after lumbar fusion appear to be patient-specific.

Confrontation of rodents by natural predators provides a number of advantages as a model for traumatic or stressful experience. Using this approach, one of the aims of this study was to investigate a model for the study of post-traumatic stress disorder (PTSD)-related behaviour in mice. Moreover, because PTSD can facilitate the establishment of chronic pain (CP), and in the same way, patients with CP have an increased tendency to develop PTSD when exposed to a traumatic event, our second aim was to analyse whether this comorbidity can be verified in the new paradigm. C57BL/6 male mice underwent chronic constriction injury of the sciatic nerve (CCI), a model of neuropathic CP, or not (sham groups) and were submitted to different threatening situations. Threatened mice exhibited enhanced defensive behaviours, as well as significantly enhanced risk assessment and escape behaviours during context reexposure. Previous snake exposure reduced open-arm time in the elevated plus-maze test, suggesting an increase in anxiety levels. Sham mice showed fear-induced antinociception immediately after a second exposure to the snake, but 1 week later, they exhibited allodynia, suggesting that multiple exposures to the snake led to increased nociceptive responses. Moreover, after reexposure to the aversive environment, allodynia was maintained. CCI alone produced intense allodynia, which was unaltered by exposure to either the snake stimuli or reexposure to the experimental context. Together, these results specifically parallel the behavioural symptoms of PTSD, suggesting that the snake/exuvia/reexposure procedure may constitute a useful animal model to study PTSD.

My MET 2019 invited talk will focus on GraphicsFuzz, a technique and tool for automated metamorphic testing of the shader compiler components of graphics drivers. Starting out as a research project at Imperial College London, GraphicsFuzz led to a spin-out company of the same name, which was acquired by Google in 2018. The technology has since been open sourced and is being used by Google to test Vulkan and OpenGL ES graphics drivers and supporting tools.

A personalized approach based on a patient's or pathogen’s unique genomic sequence is the foundation of precision medicine. Genomic findings must be robust and reproducible, and experimental data capture should adhere to findable, accessible, interoperable, and reusable (FAIR) guiding principles. Moreover, effective precision medicine requires standardized reporting that extends beyond wet-lab procedures to computational methods. The BioCompute framework (https://w3id.org/biocompute/1.3.0) enables standardized reporting of genomic sequence data provenance, including provenance domain, usability domain, execution domain, verification kit, and error domain. This framework facilitates communication and promotes interoperability. Bioinformatics computation instances that employ the BioCompute framework are easily relayed, repeated if needed, and compared by scientists, regulators, test developers, and clinicians. Easing the burden of performing the aforementioned tasks greatly extends the range of practical application. Large clinical trials, precision medicine, and regulatory submissions require a set of agreed upon standards that ensures efficient communication and documentation of genomic analyses. The BioCompute paradigm and the resulting BioCompute Objects (BCOs) offer that standard and are freely accessible as a GitHub organization (https://github.com/biocompute-objects) following the “Open-Stand.org principles for collaborative open standards development.” With high-throughput sequencing (HTS) studies communicated using a BCO, regulatory agencies (e.g., Food and Drug Administration [FDA]), diagnostic test developers, researchers, and clinicians can expand collaboration to drive innovation in precision medicine, potentially decreasing the time and cost associated with next-generation sequencing workflow exchange, reporting, and regulatory reviews., This Community Page article presents a communication standard for the provenance of high-throughput sequencing data; a BioCompute Object (BCO) can serve as a history of what was computed, be used as part of a validation process, or provide clarity and transparency of an experimental process to collaborators.

Several patient-related risk factors for postoperative spine infections exist. Those modifiable risk factors, such as malnutrition and glucose control, should be optimized before surgery with the hopes of lessening any associated infection risk. Furthermore, other operative variables, such as antibiotic administration, should also be closely monitored. However, postoperative infections always remain inevitable. Prompt diagnosis and proper treatment is the key to reduce any associated morbidity for the patient. The tenants of treatments remain surgical debridement with and without implant removal, and antibiotic therapy.

Modern accelerator programming frameworks, such as OpenCL, organise threads into work-groups. Remote-scope promotion (RSP) is a language extension recently proposed by AMD researchers that is designed to enable applications, for the first time, both to optimise for the common case of intra-work-group communication (using memory scopes to provide consistency only within a work-group) and to allow occasional inter-work-group communication (as required, for instance, to support the popular load-balancing idiom of work stealing). We present the first formal, axiomatic memory model of OpenCL extended with RSP. We have extended the Herd memory model simulator with support for OpenCL kernels that exploit RSP, and used it to discover bugs in several litmus tests and a work-stealing queue, that have been used previously in the study of RSP. We have also formalised the proposed GPU implementation of RSP. The formalisation process allowed us to identify bugs in the description of RSP that could result in well-synchronised programs experiencing memory inconsistencies. We present and prove sound a new implementation of RSP that incorporates bug fixes and requires less non-standard hardware than the original implementation. This work, a collaboration between academia and industry, clearly demonstrates how, when designing hardware support for a new concurrent language feature, the early application of formal tools and techniques can help to prevent errors, such as those we have found, from making it into silicon.

Diabetic peripheral neuropathy affects up to half of diabetic patients. This neuronal damage leads to sensory disturbances, including allodynia and hyperalgesia. Many growth factors have been suggested as useful treatments for prevention of neurodegeneration, including the vascular endothelial growth factor (VEGF) family. VEGF-A is generated as two alternative splice variant families. The most widely studied isoform, VEGF-A165a is both pro-angiogenic and neuroprotective, but pro-nociceptive and increases vascular permeability in animal models. Streptozotocin (STZ)-induced diabetic rats develop both hyperglycaemia and many of the resulting diabetic complications seen in patients, including peripheral neuropathy. In the present study, we show that the anti-angiogenic VEGF-A splice variant, VEGF-A165b, is also a potential therapeutic for diabetic neuropathy. Seven weeks of VEGF-A165b treatment in diabetic rats reversed enhanced pain behaviour in multiple behavioural paradigms and was neuroprotective, reducing hyperglycaemia-induced activated caspase 3 (AC3) levels in sensory neuronal subsets, epidermal sensory nerve fibre loss and aberrant sciatic nerve morphology. Furthermore, VEGF-A165b inhibited a STZ-induced increase in Evans Blue extravasation in dorsal root ganglia (DRG), saphenous nerve and plantar skin of the hind paw. Increased transient receptor potential ankyrin 1 (TRPA1) channel activity is associated with the onset of diabetic neuropathy. VEGF-A165b also prevented hyperglycaemia-enhanced TRPA1 activity in an in vitro sensory neuronal cell line indicating a novel direct neuronal mechanism that could underlie the anti-nociceptive effect observed in vivo. These results demonstrate that in a model of Type I diabetes VEGF-A165b attenuates altered pain behaviour and prevents neuronal stress, possibly through an effect on TRPA1 activity.

Level iii retrospective cohort study. Objective The aim of this study was to determine the rate of revision surgery and the occurrence of adjacent segment disease of patients undergoing ACDF for cervical radiculopathy and myelopathy using more modern-day instrumentation techniques. Summary of background data Anterior cervical discectomy and fusion (ACDF) has long been the preferred treatment for cervical radiculopathy and myelopathy. Methods All patients undergoing ACDF between January of 2000 and December of 2010 were included. Age, sex, height, weight, body mass index, symptoms at presentation, number of levels fused, graft type, and smoking status were recorded. Outcomes included revision rate, reason for revision surgery, time to revision surgery, presence and grade of adjacent segment disease, distance from the instrumentation to the cranial and caudal endplate (plate-to-disc distance), and reporting of symptoms of adjacent segment disease at the final follow-up. Results A total of 672 patients were included in this study. The average duration of follow-up was 31 months. One hundred one (15%) patients underwent revision surgery. The reason for revision surgery was adjacent segment disease in 47 (47.5%), pseudarthrosis in 45 (45.5%) and a new problem at a nonadjacent level in 7 (7.1%) of those patients. The need for revision surgery was not affected by patient age, sex, body mass index, smoking status, symptoms at presentation, number of levels fused, plate-to-disc distance or graft type. Conclusion The revision rate after ACDF is 15%. Most revisions were done for either adjacent segment disease or pseudarthrosis. No specific risk factors for revision surgery were identified in this study. Level of evidence 3.

Little is known about the experiences that influence entering medical students’ internal concepts of themselves as future physicians. During orientation to medical school, students were asked to write stories in response to the cue, “Tell a story about a person or experience that inspired you to consider a career of service in medicine.” Qualitative methodology was employed to analyze 190 student stories. Thematic analysis identified descriptive details about content and allowed comparison between the students’ and School’s expectations. Inspirational settings, contexts, and individuals were identified. Nine different inspirational events were described. Student and School expectations for the kinds of physicians they hoped to become were generally consistent. The study demonstrates that students do indeed bring to medical school visions of the kinds of physicians they hope to become. Linking that vision with medical school activities including the White Coat Ceremony provides a bridge between medical school and students’ earlier lives, thus explicitly linking orientation to professional formation.

Study design Retrospective review. Objective To evaluate key risk factors for the development of C5 palsy after cervical corpectomy, including resection of the posterior longitudinal ligament (PLL). Summary of background data Postoperative C5 palsy is a well-known complication after cervical spine surgery. It is unknown whether resection of the PLL affects the incidence of C5 palsy. Methods We performed a retrospective review of 459 consecutive patients undergoing anterior cervical corpectomies over a 15-year period. Medical records were reviewed to gather demographic data, operative details, and the incidence of C5 palsy. We performed regression analyses to identify variables that predicted the development of C5 palsy. Results Our final analysis included 397 patients (females 51.4%, mean age 55.6 ± 11.6 yrs). Anterior corpectomy alone was performed in 255 (64.2%) patients, and combined anterior and posterior fusion was performed in 142 (35.8%) patients. Twenty-four patients (6.0%) developed C5 nerve palsy. Univariable regression demonstrated age greater than 65 (odds ratio, OR 2.7, 95% confidence interval, CI 1.2 to 6.3), corpectomy of three or more levels (OR 6.3, 95% CI 2.1 to 18.9), presence of ossification of the PLL (OR 4.3, 95% CI 1.6 to 11.7), and complete or partial resection of the PLL (OR 2.6, 95% CI 1.0 to 6.7) predicted development of C5 palsy. Multivariable regression demonstrated that the odds of getting C5 palsy with complete or partial resection of the PLL is 4.0 times (95% CI 1.5 to 10.5) higher compared with patients with an intact PLL. There were no significant differences in C5 palsy rates based on surgical approach (anterior vs. anterior plus posterior), sex, smoking status, or diabetes. Conclusion Age greater than 65 years, corpectomy of three or more levels, presence of ossification of the PLL, and complete or partial resection of the PLL significantly predicted the development of C5 palsy. Level of evidence 4.

Hepatitis B infection remains a significant disease burden around the world, with an estimated two billion individuals infected and 350 million living with chronic hepatitis B. Current antivirals are efficacious, but require lifelong treatment for the majority of infected individuals. The field is galvanised to improve diagnostics and treatment with the goal to develop shorter, finite treatments leading to viral control after treatment discontinuation. Achievement of complete and functional cure is challenged by the complexity of the virus life cycle, the lack of adequate preclinical models, the cccDNA-mediated persistence of HBV in liver cells, the lack of validated biomarkers to predict viral control and cure, and the probable need for combination treatment involving antiviral- and immune-based strategies. Experts from diverse stakeholder groups participating in the HBV Forum (a project of the Forum for Collaborative Research) contributed their expertise and perspective to resolving issues and overcoming barriers in the regulatory path for novel HBV therapeutic strategies; addressing gaps in preclinical models, diagnostics, clinical trial design, biomarkers and endpoints, and public health efforts. Interviewees highlighted the need for open and collaborative ongoing dialogues among stakeholders in a neutral space as a critical process to move the field forwards. The Forum model facilitates dialogue and deliberation of this nature, with dedicated experts from all stakeholder groups participating. The promise of an HBV cure is exciting. Now is the time to work together toward that goal.

Graphics processing units (GPU)-accelerated computing is being adopted increasingly in a number of areas, ranging from high-end scientific computing to mobile and embedded computing. While GPU programs routinely provide high computational throughput in a number of areas, they also prove to be notoriously difficult to write and optimize correctly, largely because of the subtleties of GPU concurrency. This chapter discusses several issues that make GPU programming difficult and examines recent progress on rigorous methods for formal analysis of GPU software. Our key observation is that given the fast-paced advances in GPU programming, the use of rigorous specification and verification methods must be an integral part of the culture of programming and training, and not an afterthought.

Introduction: Patient-centered approaches have a positive impact on adherence to treatment, self-management of chronic disease, and patient satisfaction. We seek to graduate physicians who provide effective Patient-Centered Care (PCC). The aims of this research were to (a) include the patients’ perspectives in describing behaviors essential to effective PCC, (b) create an authentic, credible tool to assess these behaviors in third-year medical students, and (c) validate the assessment tool through the eyes of our patients. Methods: To develop and validate PCC behaviors we (a) developed PCC descriptors that included patient perspectives, (b) developed scenarios for students to demonstrate PCC, (c) administered the PCC-Objective Structured Clinical Exam, and (d) used the patient perspective to validate results. Results: Faculty and students found the PCC-OSCE to be an authentic experience. Students received abundant individualized feedback and demonstrated strong performance in communicating effectively, avoiding medical jargon, listening actively, demonstrating empathy, and leading critical conversations. Patient critiques of exemplary performances confirmed that the PCC-OSCE assesses elements the patients viewed as essential to PCC. Conclusion: Incorporating the patients’ perspective aids in better understanding professional competencies and legitimizes the assessment.

Background context Vertebral artery injuries (VAIs) are rare but serious complications of cervical spine surgery, with the potential to cause catastrophic bleeding, permanent neurologic impairment, and even death. The present literature regarding incidence of this complication largely comprises a single surgeon or small multicenter case series. Purpose We sought to gather a large sample of high-volume surgeons to adequately characterize the incidence and risk factors for VAI, management strategies used, and patient outcomes after VAI. Study design The study was constructed as a cross-sectional study comprising all cervical spine patients operated on by the members of the international Cervical Spine Research Society (CSRS). Patient sample All patients who have undergone cervical spine surgery by a current member of CSRS as of the spring of 2012. Outcome measures For each surgeon surveyed, we collected self-reported measures to include the number of cervical cases performed in the surgeon's career, the number of VAIs encountered, the stage of the case during which the injury occurred, the management strategies used, and the overall patient outcome after injury. Methods An anonymous 10-question web-based survey was distributed to the members of the CSRS. Statistical analysis was performed using Student t tests for numerical outcomes and chi-squared analysis for categorical variables. Results One hundred forty-one CSRS members (of 195 total, 72%) responded to the survey, accounting for a total of 163,324 cervical spine surgeries performed. The overall incidence of VAI was 0.07% (111/163,324). Posterior instrumentation of the upper cervical spine (32.4%), anterior corpectomy (23.4%), and posterior exposure of the cervical spine (11.7%) were the most common stages of the case to result in an injury to the vertebral artery. Discectomy (9%) and anterior exposure of the spine (7.2%) were also common time points for an arterial injury. One-fifth (22/111) of all VAI involved an anomalous course of the vertebral artery. The most common management of VAI was by direct tamponade. The outcomes of VAIs included no permanent sequelae in 90% of patients, permanent neurologic sequelae in 5.5%, and death in 4.5%. Surgeons at academic and private centers had nearly identical rates of VAIs. However, surgeons who had performed 300 or fewer cervical spine surgeries in their career had a VAI incidence of 0.33% compared with 0.06% in those with greater than 300 lifetime cases (p=.028). Conclusions The overall incidence of VAI during cervical spine surgery reported from this survey was 0.07%. Less experienced surgeons had a higher rate of VAI compared with their more experienced peers. The results of VAI are highly variable, resulting in no permanent harm most of the time; however, permanent neurologic injury or death occur in 10% of cases.

Retrospective matched cohort study.To compare mortality in elderly patients with odontoid fractures after operative and nonoperative treatment. In addition, to evaluate potential factors that may increase the risk of mortality in the geriatric population after odontoid fracture.Odontoid fractures represent the most common cervical spine fracture in patients over 70. In this population controversy exists as to the optimal treatment of odontoid fractures, especially type II fractures.A retrospective review of all odontoid fractures in patients 75 years of age or older at our institution from 1996 to 2010 was performed. Comorbidities were stratified using the Charlson comorbidity index. Mortality was determined at 3 months, 1, and 5 years.A total of 96 patients were identified of which 75 met inclusion criteria. The average age of patients included was 82.3 years. The average Charlson comorbidity score for those operated on (2.37) was not significantly different from the nonoperative group (2.46), (P=0.45). At 3 months the operative group had a significantly lower mortality rate than the nonoperative group (P=0.024). There was no significant difference in 1-year (P=0.42) or 5-year (P=0.21) mortality between the operative and nonoperative cohorts. Of the patients treated nonoperatively, those who died within 3 months of treatment had a significantly higher Charlson score (3.98) than those who survived (2.14). Patients who survived at least 1 year after surgery had a significantly lower Charlson score (1.53) than those who died (3.22) within that time frame after surgery (P=0.05).There was no significant difference between 1- and 5-year mortality in patients treated operatively or nonoperatively. Regardless of treatment Charlson score had a significant impact on mortality. Age significantly affected mortality in patients treated surgically.

We develop a practical solution to the problem of automatic verification of the interface between device drivers and the operating system. Our solution relies on a combination of improved driver architecture and verification tools. Unlike previous proposals for verification-friendly drivers, our methodology supports drivers written in C and can be implemented in any existing OS. Our Linuxbased evaluation shows that this methodology amplifies the power of existing model checking tools in detecting driver bugs, making it possible to verify properties that are beyond the reach of traditional techniques.

We present the first independent empirical study on schedule bounding techniques for systematic concurrency testing (SCT). We have gathered 52 buggy concurrent software benchmarks, drawn from public code bases, which we call SCTBench. We applied a modified version of an existing concurrency testing tool to SCTBench to attempt to answer several research questions, including: How effective are the two main schedule bounding techniques, preemption bounding and delay bounding, at bug finding? What challenges are associated with applying SCT to existing code? How effective is schedule bounding compared to a naive random scheduler at finding bugs? Our findings confirm that delay bounding is superior to preemption bounding and that schedule bounding is more effective at finding bugs than unbounded depth-first search. The majority of bugs in SCTBench can be exposed using a small bound (1-3), supporting previous claims, but there is at least one benchmark that requires 5 preemptions. Surprisingly, we found that a naive random scheduler is at least as effective as schedule bounding for finding bugs. We have made SCTBench and our tools publicly available for reproducibility and use in future work.

Objective We review the English literature between 1980 and 2013 and summarize the clinical classification, aetiology, physiology, and pathophysiology of paediatric priapism. We propose a clinical guideline for the management of priapism in children. Patients Male patients aged ≤18 years. Results Priapism, a prolonged penile erection lasting >4 h, is a rare condition in childhood. There are 3 widely accepted types of priapism: 1) ischaemic priapism, the commonest type seen in children; 2) stuttering priapism, recurrent, self-limiting prolonged erections; and 3) non-ischaemic priapism, rare in children, usually due to trauma. Neonatal priapism has also been described. Ischaemic priapism is a urological emergency causing fibrosis of the corpora cavernosa, subsequent erectile dysfunction and penile disfigurement. The commonest causes of priapism in children are sickle cell disease (65%), leukaemia (10%), trauma (10%), idiopathic (10%), and pharmacologically induced (5%). Conclusions Priapism in children must be assessed urgently. Rapid resolution of ischaemic priapism prevents permanent cavernosal structural damage and is associated with improved prognosis for potency later in life. Stuttering priapism requires careful counselling for episodic management. Chronic prophylaxis may be obtained using α-adrenergic sympathomimetics, phosphodiesterase type 5 inhibitors and, in sickle cell disease, hydroxyurea. Non-ischaemic and neonatal priapism may generally be treated less urgently.

Advances in high-throughput sequencing (HTS) technologies have greatly increased the availability of genomic data and potential discovery of clinically significant genomic variants. However, numerous issues still exist with the analysis of these data, including data complexity, the absence of formally agreed upon best practices, and inconsistent reproducibility. Toward a more robust and reproducible variant-calling paradigm, we propose a series of selective noise filtrations and post-alignment quality control (QC) techniques that may reduce the rate of false variant calls. We have implemented both novel and refined post-alignment QC mechanisms to augment existing pre-alignment QC measures. These techniques can be used independently or in combination to identify and correct issues caused during data generation or early analysis stages. The adoption of these procedures by the broader scientific community is expected to improve the identification of clinically significant variants both in terms of computational efficiency and in the confidence of the results. Availability: https://hive.biochemistry.gwu.edu /