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Data Availability Statement: All data are included in the Supporting Information for publication online. Supporting Information is available online at https://setac.onlinelibrary.wiley.com/doi/10.1002/etc.5620#support-information-section . Copyright © 2023 Crown copyright and The Authors. While chemicals are vital to modern society through materials, agriculture, textiles, new technology, medicines, and consumer goods, their use is not without risks. Unfortunately, our resources seem inadequate to address the breadth of chemical challenges to the environment and human health. Therefore, it is important we use our intelligence and knowledge wisely to prepare for what lies ahead. The present study used a Delphi-style approach to horizon-scan future chemical threats that need to be considered in the setting of chemicals and environmental policy, which involved a multidisciplinary, multisectoral, and multinational panel of 25 scientists and practitioners (mainly from the United Kingdom, Europe, and other industrialized nations) in a three-stage process. Fifteen issues were shortlisted (from a nominated list of 48), considered by the panel to hold global relevance. The issues span from the need for new chemical manufacturing (including transitioning to non-fossil-fuel feedstocks); challenges from novel materials, food imports, landfills, and tire wear; and opportunities from artificial intelligence, greater data transparency, and the weight-of-evidence approach. The 15 issues can be divided into three classes: new perspectives on historic but insufficiently appreciated chemicals/issues, new or relatively new products and their associated industries, and thinking through approaches we can use to meet these challenges. Chemicals are one threat among many that influence the environment and human health, and interlinkages with wider issues such as climate change and how we mitigate these were clear in this exercise. The horizon scan highlights the value of thinking broadly and consulting widely, considering systems approaches to ensure that interventions appreciate synergies and avoid harmful trade-offs in other areas. We recommend further collaboration between researchers, industry, regulators, and policymakers to perform horizon scanning to inform policymaking, to develop our ability to meet these challenges, and especially to extend the approach to consider also concerns from countries with developing economies. Environ Toxicol Chem 2023;00:1–17. © 2023 Crown copyright and The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. This article is published with the permission of the Controller of HMSO and the King's Printer for Scotland. Department for Environment, Food and Rural Affairs

Nitrous oxide (N2O) is a potent greenhouse gas (GHG) with a global warming potential 265 times that of carbon dioxide (CO2) over 100 years. Contributing approximately 70% of global anthropogenic N2O emissions, agriculture represents the largest area of uncertainty for GHG reporting and the most challenging sector for emissions reduction: global N2O emissions are increasing at double the rate estimated by the Intergovernmental Panel on Climate Change (IPCC). The largest source of agricultural N2O emissions is from application of inorganic-N fertilisers, the manufacture of which produces more than 1% of global CO2 emissions and consumes 1% of global energy output.However, typical crop N uptake efficiency (NupE) means approximately half the fertiliser doesn’t reach the target plant, causing further ecological problems, such as biodiversity loss from eutrophication and atmospheric deposition. The extent to which microbial immobilisation of fertiliser N contributes to the NupE value of ca. 60% is currently unknown. If N immobilisation is found to be a large contributor to reducing N available to crops, this offers new opportunities to better manage fertiliser N inputs. Critically, with a growing global population, it is vital that we can increase food crop yields, and more efficient use of water and nutrients could help close the 70% ‘yield gap’ between potential and actual crop yields. Finally, inorganic N is the largest single cost in gross margins for wheat production and prices are rising. Increased NupE therefore represents a key opportunity for farmers to increase their financial sustainability. We hypothesised that under the conventional management of three applications of inorganic N in the spring, crops do not have the ability to outcompete the fast-growing soil microbial community for N, and that by supplying N to the crop in a ‘little and often’ approach, we could increase NupE by reducing immobilisation, and consequentially reduce N2O emissions. We conducted a field study of a winter wheat crop on a northern UK farm to investigate this, which compared conventional N fertiliser management (220 kg N ha-1 over three applications) of ammonium nitrate, to a little and often approach (220 kg N ha-1 over six applications) and an untreated (0 kg N ha-1) control. We followed the crop until harvest, and continuously measured N2O emissions and net ecosystem exchange of CO2 using a skyline2D automated flux system and also measured C and N pools in soil, plants and microbial biomass to assess changes in N uptake and allocation.We will present data which shows the outcome of plant-microbe competition for N in our agricultural system, and discuss the implications of different N fertiliser management for yield, profitability and GHG mitigation.

Nitrous oxide (N2O) is a potent greenhouse gas (GHG) with a global warming potential 298 times that of carbon dioxide (CO2). Measurements of soil N2O emissions typically use manual chambers, with samples taken at low temporal resolution over long durations (months), or at higher temporal resolution (multiple samples per day) over short durations. Automated GHG flux systems have allowed the measurement of high frequency (sub-daily) N2O fluxes over longer periods (weeks to months), revealing that emissions can vary diurnally by up to 400% in agricultural soils.Contributing approximately 70% of global anthropogenic N2O emissions, agriculture represents the largest area of uncertainty for GHG reporting and the most challenging sector for emissions reduction: global N2O emissions are increasing at double the rate estimated by the Intergovernmental Panel on Climate Change (IPCC). Improvements to agricultural GHG emission estimates have increased the accuracy of GHG reporting, but N2O emissions from agricultural soils still contribute 25% of the uncertainty of total GHG emissions across all sectors. Our project, diurnal variation in soil nitrous oxide emissions (DIVINE), combines field and laboratory experiments that exploit high-resolution, robotic and continuous N2O measurement technology, to investigate the drivers and mechanisms underpinning diurnal variation in N2O.We will present work from a field study investigating the effect of soil properties and nitrogen (N) fertiliser management on diurnal variation in N2O emissions from a wheat crop. We assess how N fertiliser application (rate and frequency) and soil gas diffusivity (determined by bulk density and rain events), affect the depth of N2O production and N2O transport in the soil, and resultant impacts on the peak timing and amplitude of diurnal N2O emissions across the crop life cycle and seasons.N2O emissions will be compared in paired transects with contrasting bulk density but similar soil texture and history, with three ammonium nitrate fertiliser scenarios. N2O is being measured continuously using SkyLine2D automated flux chamber technology. To resolve depth/gas transfer coefficients after N fertiliser and rain events, we will measure soil N2O concentration profiles across the rooting zone in discrete campaigns during the crop life cycle.Further, we will discuss how our data will be used to improve the accuracy of N2O emission factors by accounting for environmental and diurnal variation. Bayesian statistical modelling will be used to represent the spatial and temporal distribution of emissions following fertilisation, and the effects of known environmental factors (e.g. temperature, soil moisture, light intensity), as well as the residual effect explicable by the diurnal cycle.

This introduction examines the growing interest in science diplomacy and the parallel lack of in-depth historical studies on this new concept. In particular, we first show how the recent attention toward science diplomacy has led to a proliferation of hagiographic accounts reflecting the urgency to support its growth rather than truly investigate its ancestry. We then turn to consider how our historical understanding of science diplomacy could be improved, and how this knowledge could equally be of significance to science diplomacy practitioners today. This essay is part of a special issue entitled Science Diplomacy, edited by Giulia Rispoli and Simone Turchetti.

This paper is a response to a 2018 call for greater understanding of how previous examples of marine science diplomacy could help shape present day efforts to draft a new law of the sea that protects marine biodiversity and conserves the marine environment. It tackles this through analysis of the various twists, turns, and challenges of early science diplomacy efforts in marine science during the early twentieth century. It looks in turn at questions of defining and agreeing on research objectives, how backchannel science diplomacy can become official government diplomacy, and finally, how careful science diplomacy brought Germany back to the international research arena so as to successfully put in place marine conservation measures during the 1920s. In doing this, it argues that the foundation of the International Council for the Exploration of the Seas in 1902 represented a revolutionary moment where supra-national scientific research, coordination, and conservation politics for the ocean first emerged; with International Council for the Exploration of the Sea becoming a key model for all subsequent marine science diplomacy. This essay is part of a special issue entitled Science Diplomacy, edited by Giulia Rispoli and Simone Turchetti.

‘Science and Technology on a mission’ Motto of the Lawrence Livermore National Laboratory1The Lawrence Livermore National Laboratory (LLNL), or rather the University of California Radiation Laborat...

Despite the Pakistan-Afghan border's importance as the epicentre of regional insurgency, the mechanisms by which Friday sermons may be stimulating Islamic ideology have been understudied. From an analysis of 250 hours of sermons in the local Pashto language, interviews withmullahsand survey work, Robinson argues that sermons are a powerful means by which sectarian tensions and traditional ideologies are propagated. Their influence is derived from an irresistible synergy of both ancient and modern. They gain traction from using a highly credible ancient sermon form - rich in poetics and sparkling oratory - which is multiplied by the use of modern media. The religious ideology they traffic continues to grip the imagination of Pashtuns in ways which shape their society and provides a bulwark against secular intruders.

The Strait of Gibraltar has a long tradition of political and scientific uniqueness. Twentieth-century submarine warfare added the ocean’s depth as a new dimension for those wanting to control and understand the Strait. During the Cold War the surveillance of this chokepoint became urgent and entangled with local disputes predating the two-blocs conflict, in particular the sovereignty of Gibraltar for which Spain and the United Kingdom competed. This paper explores a number of transnational research programs on ocean dynamics at the Strait and discovers a network of collaborating researchers who used, and went beyond, international institutions such the International Geophysical Year and NATO. In the process, the Western Mediterranean was constructed as a key maritime place for global ocean circulation, both as a factor to North Atlantic convection and as a model through which to understand it.

Earlier observers have speculated on the causal relationships between abnormal CSF circulation and a variety of neurological dysfunctions. Such speculations have been at least partially validated by recent evidence and inquiries contravening the traditional static viewpoint of CSF circulation. More contemporary inquiries establish a number of factors which influence both CSF production and absorption (sleep disturbance, neck position, cerebral metabolism, brain atrophy, medications, etc.). Thus, transient periods of abnormality are possibly mingled with periods of normality. Such episodic alterations suggest that the physiological arrangements which underpin CSF circulation may be in some ways likened to blood pressure alterations, in that long-standing CSF abnormalities may be both unappreciated and gradual, though virulent enough to cause substantial neurological injury. We suggest that cervical stenosis (blocking an important CSF decompressive pathway into the vertebral canal) is among the largely unappreciated causes of abnormal CSF circulation and may play a role in cephalad neuronal dysfunction. Such a blockage is correlated with age and easily assessed by cine MRI study. Indeed, episodic disturbances can diminish CSF cerebral flow circulation increasing deposition in cerebral parenchyma of contrary metabolic products (e.g. beta Amyloid), possibly having a causal influence on senile dementia. Additionally, cervical stenosis, by increasing posterior fossa cerebral pressure, could play a causal role in a number of afflictions, among them sleep apnea, concomitant respiratory and circulatory dysfunction, hypertension, chronic occipital headaches, tinnitus, etc. We further suggest that among those patients with substantial cervical stenosis (extensive enough to block CSF circulation in the cervical area as identified by cine MRI) appropriate comparative clinical studies could be undertaken to demarcate associations with presenile dementia, sleep disturbance and posterior fossa dysfunction. Additionally, we suggest that an intracranial monitoring implant be perfected to chronically monitor both intracranial pressure and CSF flow - a monitoring device comparable to the rather less invasive sphygmometric evaluation of blood pressure. If such speculations prove correct, different therapeutic regimens which might improve outcome could be imagined. Among them better sleep hygiene (to by position maximize CSF flow) and possibly more aggressive operative decompressive intervention to diminish cervical obstruction.

Objectives: To extract from germane literature methodological shortfalls in obtaining cerebrospinal fluid specimens by lumbar puncture. Methods: 20 peer reviewed articles were analyzed in which cerebrospinal fluid (CSF) obtained biomarkers were used to assess Alzheimer’s Disease. Binary assessment of eight variables was performed: albumin, total protein, CSF pressure, cephalad CSF obstruction, obtained but unreported data, inclusion of erythrocyte contaminated samples, exclusion of erythrocyte contaminated samples, exclusion of white blood cell contaminated samples, and failed lumbar puncture attempts. Results: An apparent shortfall exists in the assessment of contravening variables, which could alter CSF results. Conclusions: We suggest that more attention be placed on lumbar puncture methodological difficulties in obtained CSF specimens, and that all practical obtainable data be routinely reported.

INTRODUCTION Despite some evidence that anxiety may affect length of stay (LOS), relatively little inquiry exists regarding this in neurosurgical literature. OBJECTIVE To determine the influence of anxiety on LOS after elective lumbar decompression and fusion (LDF) surgery. METHODS The medical records of 307 patients who consecutively underwent elective LDF surgery from October 1, 2010, through September 30, 2013, were retrospectively reviewed. Each patient's medications and comorbidities were determined using the medical history. The impact of their medications on LOS was studied using multivariate analysis. Linear regression was also used to assess the relationship between anxiolytic use and LOS. An independent sample t test was used to compare the mean LOS of the group of patients receiving muscle relaxants with that of the group who were not. RESULTS Those with a diagnosis of anxiety who were taking anxiolytics (n = 32) stayed 1.8 days longer than those with no diagnosis of anxiety and who were not taking anxiolytics (n = 224) after LDF surgery (p = 0.003). Those with a diagnosis of anxiety who were taking anxiolytics (n = 32) stayed 1.9 days longer than those with no diagnosis of anxiety and who were taking anxiolytics (n = 24) after LDF surgery (p = 0.003). CONCLUSION Our study suggests that those with a diagnosis of anxiety who take medications for that condition have a longer LOS than those with no diagnosis of anxiety and who are not medicated for the condition. This could be because these patients are more vulnerable to states of anxiety when required to be nil per os for 12 hours before surgery.

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Objectives/Hypothesis: To illustrate that the diagnosis of obstructive sleep apnea (OSA) is dependent on the polysomnographic scoring criteria used, and the success rates of treatments for OSA are dependent on the defined outcome measures. Study Design: Retrospective case series with prospective reanalysis of polysomnographic data. Methods: Consecutively treated adult patients (N = 40) with moderate to severe OSA having multilevel pharyngeal surgery in 2007 were studied. All patients underwent submucosal lingualplasty and concurrent or previous uvulopalatopharyngoplasty ± palatal advancement. Full polysomnography (PSG) was performed preoperatively and at a mean of 145 days postoperatively. Pre- and postoperative PSG data were analyzed by two different but widely used scoring systems for the apnea-hypopnea index (AHI): The American Academy of Sleep Medicine (AASM) 1999 Chicago criteria and the AASM 2007 recommended criteria. Results: Follow-up PSG data were available in 31 of 40 patients. Successful surgery was defined as a reduction in AHIRec

Introduction: In this paper we investigate the possible connection between socioeconomic status as demarcated by employment and in-surance status and consumption of healthcare resources in spine surgery patients. Methods: The clinical records of 1599 spine surgery pa-tients counted from 2008-2009 were reviewed. The largest groups of patients belonged to MS-DRG 460 (N = 585) and to MS-DRG 473 (N = 700). These two MS-DRG patient groups were used as the study cohort representing patients who, by definition, did not have serious comor-bidities or complications. Results: Unemployed non-cervical patients tended to stay on average 1.8 days longer in hospital and had on average $5800 higher hospital charges. No major differ-ences were noted in length of stay and hospital cost between government and private insurance patients. However, self-pay non-cervical fusion patients had notable increases in length of stay and hospital cost, especially in the >39 and

Introduction. Aggressive surgical resection constitutes the optimal treatment for intracranial gliomas. However, the proximity of a tumor to eloquent areas requires exact knowledge of its anatomic relationships to functional cortex. The purpose of our study was to evaluate fMRI’s accuracy by comparing it to intraoperative cortical stimulation (DCS) mapping.Material and Methods. Eighty-seven patients, with presumed glioma diagnosis, underwent preoperative fMRI and intraoperative DCS for cortical mapping during tumor resection. Findings of fMRI and DCS were considered concordant if the identified cortical centers were less than 5 mm apart. Pre and postoperative Karnofsky Performance Scale and Spitzer scores were recorded. A postoperative MRI was obtained for assessing the extent of resection.Results. The areas of interest were identified by fMRI and DCS in all participants. The concordance between fMRI and DCS was 91.9% regarding sensory-motor cortex, 100% for visual cortex, and 85.4% for language. Data analysis showed that patients with better functional condition demonstrated higher concordance rates, while there also was a weak association between tumor grade and concordance rate. The mean extent of tumor resection was 96.7%.Conclusions. Functional MRI is a highly accurate preoperative methodology for sensory-motor mapping. However, in language mapping, DCS remains necessary for accurate localization.

Introduction: Health care expenditures in the United States have rapidly risen in the last decade, including orthopaedic induced expenses. This paper addresses the methodology by which clinical evidence is obtained to better direct orthopaedic practice and encourage cost-efficiency. Questions: We conducted this inquiry to answer these questions: 1) Have orthopaedic expenses increased in the United States? 2) Does high grade clinical evidence prevail in orthopaedic literature? 3) Does clinical orthopaedic research include cost in outcome analysis? 4) Does the increase in orthopaedic expenses correlate with cost awareness in orthopaedic literature? Methods: The aggregate hospital charges (national bill) associated with three major orthopaedic procedures were extracted from the Nationwide Inpatient Sample (NIS) website (data available from 1997 to 2008). Using the biomedical search engine PubMed (launched 1996), different types of literature pertaining to general orthopaedic and three major orthopaedic procedures—hip replacement, knee replacement, and spine fusion, were probed regarding level of evidence and cost inclusion. Results: From 1997 to 2008, the national hospital charges for spine fusion increased by 10.4 times while for total knee replacement it increased by 4.9 times and for total/partial hip replacement by 3.4 times. From 1996 to 2010, PubMed indexed 1113 randomized controlled trials (RCTs) related to hip replacement, 942 related to knee replacement and 357 related to spine fusion. During the same period, RCTs related to total/partial hip replacement, total knee replacement and spine fusion procedures have increased by 3 times, 6 times, and 3.4 times, respectively. The percentage of blinded RCTS with cost analysis among all RCTs related to each procedure were 0%, 0.001% and 0.003% for total/partial hip replacement, total knee replacement and spine fusion procedures respectively. The correlation in the national hospital charges of all three procedures individually and their level I literature with cost element was not significant except for spine fusion. Conclusion: To improve literature shortfalls, substantial attention needs to be focused toward more rigorous studies which consider cost efficiency.

Interleukin-lβ (IL-lβ) is associated with vascular smooth muscle cell (VSMC) migration during neointimal formation following arterial injury, of which matrix metalloproteinase-2 (MMP-2) may have an important role. We investigated whether IL-lβ stimulated migration and MMP-2 production in VSMC, and, if so, whether migration correlated with MMP-2 activity.Modified Boyden chamber assay quantified cultured rat aorta VSMC migration. Methyl-thiazolyl-tetrazolium assay assessed cell growth. Gelatin zymography and Western blotting determined MMP-2 activity and protein levels, respectively.IL-lβ (0.1 - 10 ng/mL) induced migration of VSMC in a concentration-dependent manner without cell proliferation. VSMC released increasing levels of active MMP-2 in a dose-response fashion at IL-1β 1-10 ng/mL (P0.05) while significantly increased levels of latent MMP-2 (pro-MMP-2) were attained more gradually (10 ng/mL, P0.05). There was a dose-dependent increase in the ratio of active MMP-2 to pro-MMP-2 in response to IL-1β (1-10 ng/mL, P0.05), suggesting extracellular activation of pro-MMP-2. Protein levels on Western blot paralleled enzyme activity, with the synthesis of more active MMP-2 than pro-MMP-2 in response to IL-1β. IL-lβ-stimulated VSMC migration was significantly attenuated by both the pan-selective MMP inhibitor GM6001 and cis-9-octadecenoyl-N-hydroxylamide, a MMP-2-selective inhibitor.IL-lβ increases MMP-2 activity in VSMC through increased protein synthesis and activation of pro-MMP-2. VSMC migration induced by IL-lβ requires active MMP-2. IL-lβ may play a role in arterial remodeling following injury.

Chronic back pain is commonly associated with physical and mental comorbidities, which create a considerable burden on the healthcare system. We examined the differences in comorbidity rates of 619 spinal surgery patients of employment age, and the impact of comorbidity rates on length of hospital stay and cost. The charts of patients aged >25 years and

Surgical approaches for alleviating snoring and/or obstructive sleep apnea (OSA) have been questioned because of a lack of evidence from high-quality randomized controlled trials (RCTs). An ethical requirement for RCTs is that they must test questions where community equipoise (ie, uncertainty) exists as to the correct treatment. We aimed to measure perceived importance, community equipoise, and willingness to enroll patients in 5 potential trial targets among members of the Australian Society for Otolaryngology Head and Neck Surgery (ASOHNS). STUDY DESIGN, SETTING, AND SUBJECTS: All ASOHNS members were surveyed using a multistage mail, email, Internet, and phone-based questionnaire.Equipoise was measured for each of the scenarios using a bidirectional linear scale comparing 2 treatments. Responses were categorized into 1 of 3 groups: (A) preferred treatment 1, (B) completely undecided, and (C) preferred treatment 2. The resulting proportions are called equipoise ratios: A:B:C. Using tick boxes, the authors queried the general clinical importance and willingness to enroll patients for all scenarios.A total of 167 of 313 surgeons responded (53.4%). Three of the 5 trial scenarios exhibited evidence of community equipoise, but 2 scenarios, radiofrequency ablation plus uvulopalatopharyngoplasty (UPPP) versus UPPP alone and upper-airway reconstruction versus mandibular advancement splint (MAS), did not have strong support for enrolling patients. Informal feedback indicates one of these may be feasible in a smaller number of specifically trained surgeons.We suggest 2 potential RCT targets: septoplasty and turbinate reduction versus conservative measures for snoring and airway reconstruction versus MAS for OSA, where importance, clinical equipoise, and willingness all exist.

Complex shifts in demography combined with drastic advancements in spinal surgery have led to a steep increase in often expensive spinal interventions in older and obese patients. A cost analysis, based on hospital charges, was performed retrospectively on the spinal surgery of 787 randomly selected patients who were operated at The Medical Center of Central Georgia, a large urban hospital in Central Georgia. The types of surgery included anterior cervical decompression and fusion (ACDF), lumbar decompression and fusion (LDF), and lumbar microdiscectomy (LMD). The distribution of patient age followed a Gaussian form. The peak age for patients was 50–59 years (28.8%), and there was no statistical difference in age between men and women. The body mass index (BMI) differed ( p 2 ; range: 18–47 kg/m 2 ) and females (30.69 kg/m 2 ; range: 17–58 kg/m 2 ). The BMI data did not follow a Gaussian distribution for either gender. The hospital cost for spinal surgery increased with age except for male patients who underwent ACDF. For male patients who underwent LDF, the increase in hospital cost was statistically significant between the 40–49-year and the ⩾70-year age groups. Univariate analysis with type of surgery as a covariate showed that age was a significant determinant of hospital cost ( p = 0.000), and BMI was not ( p = 0.110); however, the interaction between age and BMI was significant ( p = 0.000). Older patients undergoing spinal surgery had lower BMI, more so in males ( r = −0.047, p = 0.426) than in females ( r = −0.038, p = 0.485). There were linear trends in all gender–spinal surgery categories between age, BMI and hospital cost. Older female patients who underwent LDF tended to have a lower BMI but higher hospital cost, confirming that age was more important than BMI in determining hospital cost in these patients. The increments in cost of spinal surgery in relation to age especially and BMI were, nevertheless, small. We believe that spinal surgery in the elderly should be viewed as a public investment, as the modern concept of retirement involves people working intermittently up to their 80s. Thus, where clinical research on medical costs is to be conducted, cost analysis needs to be expanded to include returns to government in the form of taxes.

Object Comorbidities in patients undergoing spine surgery may reasonably be factors that increase health care costs. To verify this hypothesis, the authors conducted the following study. Methods Major comorbidities and age-adjusted Charlson Comorbidity Index scores were retrospectively analyzed for 816 patients who underwent spine surgery at the authors' institutions between 2005 and 2008, and treatment costs (hospital charges) were assessed with the help of statistical software. The sample was collected by a nonmedical staff (hired at the beginning of 2006). Patients underwent one of the three most common types of spine surgery: lumbar microdiscectomy (20.5%), anterior cervical decompression and fusion (ACDF; 60.3%), or lumbar decompression and fusion (LDF; 19.2%). Patients were nearly equally divided by sex (53% were female and 47% male), and 78% were Caucasian versus 21% who were African American; the rest were of mixed or unidentified race. The average age was 54 years, with an SD of ± 14 years. Results There were significant differences in the prevalence of major comorbidities between male and female and between severely obese and nonseverely obese patients. The impact of comorbidities on the cost of spine surgery was more prominent in older patients, and an additive effect from some comorbidities was recorded in various types of spine surgery. For instance, in the ACDF group, female patients with both severe obesity and diabetes mellitus (DM) had significantly higher hospital charges than those with only one or neither of these conditions ($34,943 for both severe obesity and DM vs $25,633 for severe obesity only; $25,826 for DM only; and $25,153 for those with neither condition [p < 0.05]). In the LDF group, female patients with both DM and a history of depression had significantly higher hospital charges than those with only one or neither of these conditions ($65,782 for both DM and depression vs $53,504 for DM only; $55,990 for depression only; and $52,249 for those with neither condition [p < 0.05]). A significant difference was also found in hospital cost ($16,472 [p < 0.01]; 32% increase over baseline) in the LDF group between patients with the lowest and highest scores on the Charlson Index. Conclusions Comorbidities additively increase hospital costs for patients who undergo spine surgery, and should be considered in payment arrangements.

Introduction Vitamin B12 is very vital for the nervous system. Its deficiency can manifest with neurological symptoms like pain and paresthesias and in severe cases may cause not completely restorable neurological damage, especially in elderly patients. Methods The charts of 702 patients who underwent cervical spine surgery retrospectively reviewed and data collected . All patients were preoperatively seen by an internist who ordered Vit B12 levels for some of them. We used two thresholds for the diagnosis of vitamin B12 deficiency, 200 and 300 pg/mL as recommended by Yao et al. 1992. Data were also collected on gender, payor status, myelopathy, hemoglobin level, corpuscular parameters and glycosylated hemoglobin level (HbA1c). Vitamin B12 levels were compared between patients with HbA1c levels ≥ 6.1% and

Clinical information suggests that opioid dependence is a major contributor to poor outcomes involving health status and to increased length of stay in hospital settings. Before spine surgery, 150 patients who were using an opioid medication for pain relief were interviewed using the six World Health Organization (WHO) guidelines for the diagnosis of opioid dependence. Three groups were defined: opioid-dependent, nonopioid-dependent, and a subclinical group. Results revealed an average of 20% of patients ( N = 30) who met the WHO criteria for the diagnosis of opioid dependence. There were significant positive correlations between age and number of positive WHO criteria, length of stay, and time under surgery. Length of stay was significantly higher for the older age group (> 55 yr.). ANCOVA analysis using two opioid dependence groups (+ and -) and age group as independent variables affecting length of stay, after controlling for type of surgery, pain intensity, and number of previous spine surgeries, revealed that effects of opioid dependence status and age were significant but their interaction was not. Age did add length of stay independently of opioid dependence status; older adults remain in the hospital longer for various reasons probably associated with comorbidities.

Background context Somatosensory evoked potential (SSEP) is used to monitor integrity of the brain, spinal cord, and nerve roots during spinal surgery. It records the electrical potentials from the scalp after electrical stimulation of the peripheral nerves of the upper or lower limbs. The standard monitoring modality in lumbosacral spine surgery includes lower-limb SSEP and electromyography (EMG). Upper-limb SSEP monitoring has also been used to detect and prevent brachial plexopathy and peripheral nerve injury in thoracic and lumbosacral spine surgeries. We routinely monitor lower-limb SSEP and EMG in lumbosacral spine procedures at our institution. However, a few patients experienced postoperative numbness and/or pain in their ulnar distribution with uneventful lower-limb SSEP and EMG. Purpose We hypothesized that the postoperative upper extremity paresis in lumbosacral surgeries may result from compression and/or stretch of the brachial plexus and/or ulnar nerve while the patients were in prone position. Using upper-limb SSEP, we investigated whether we observe any significant change in the SSEP, and if so, whether we can prevent or reduce frequency of postoperative upper extremity deficits. Study design/setting In this prospective study, we monitored upper-limb SSEP, in addition to lower-limb SSEP and EMG, in 230 elective, posterior lumbosacral spinal procedures. All operations were performed by a group of four neurosurgeons. Patient sample One hundred and thirty-one female and 99 male with an age range of 28 to 86 years between January 2004 and December 2005 were studied. Outcome measures Amplitude and latency of upper-limb or ulnar SSEP were continuously compared with those of the baseline. A greater than or equal to 50% decrease in SSEPs amplitude and/or a greater than or equal to 10% increase in latency were considered to be significant. Methods After intubation, patients were positioned prone on Jackson or Andrews spinal table. Anesthesia was maintained with inhalant gas (desflurane or sevoflurane) and propofol infusion with and without minimal infusion of narcotics (fentanyl, sufentanyl, or remifentanil). Intraoperative neurophysiologic monitoring of upper-limb or ulnar SSEP was achieved by continuously recording cortical and subcortical responses after alternate stimulation of the ulnar nerve at the wrist. In our institutional protocol, a greater than or equal to 50% decrease in SSEPs amplitude and/or a greater than or equal to 10% increase in latency were considered to be significant to alert the operating surgeons. When significant changes occurred, the surgeon was immediately notified. Also, reevaluation of vital signs, depth of anesthesia, and patient's position, and technical troubleshootings were subsequently followed. Results We observed a greater than or equal to 50% decrease in amplitude of ulnar SSEP in 10 patients without significant changes in lower-limb SSEP (peroneal or posterior tibial nerve SSEP) or EMG during surgery. Eight patients had changes in unilateral limbs, and two patients had changes in bilateral limbs. Two patients with significant changes in unilateral limbs showed changes twice. The mean SSEP amplitude for the 14 changes was 29.2±3.1% (mean±SEM, standard error of mean) of the baseline value at the average surgical time of 60±1.5 minutes. With repositioning of the arms, the amplitudes were immediately restored with the average of 70.2±7.1% (n=14) of the baseline value. The mean amplitude of upper-limb SSEP was 73.4±8.7% (n=12) of the baseline at wound closure. The average surgical time was 154±29.2 minutes per case for the 10 patients. There was no documented postoperative upper extremity paresis in all 230 patients. Conclusions The present study demonstrates that upper-limb SSEP monitoring could detect position-related ulnar neuropathy in 5.2% of the patients undergoing lumbosacral spine surgery.

Study design Prospective, clinical study. Objective The objective of our study was to evaluate the role of laryngeal intraoperative electromyography (IEMG) in predicting the development of postoperative recurrent laryngeal nerve (RLN) palsy in patients undergoing anterior cervical discectomy and fusion (ACDF). We also attempted to develop a method to quantify the total IEMG irritation of the RLN. Summary of background data RLN injury has been recognized as the most common ACDF-associated neurologic injury. It has been postulated, that the employment of laryngeal IEMG may identify the operative events leading to RLN injury and subsequent postoperative palsy. Methods Laryngeal IEMG monitoring was performed in 298 patients undergoing ACDF. Preexistent baseline EMG activity, amplitude, and duration of IEMG activity were recorded. The total amount of RLN irritation was expressed as an Irritation Score (IS) applying a specially designed mathematical equation incorporating the amplitude, the duration, and the presence of any baseline EMG irritation. The relationship of IEMG activity with parameters such as the number of operative levels, the duration of the procedure, the presence of any previous neck surgeries, and the type of the used retractor was examined. Results IEMG activity was recorded in 14.4% of our patients. Postoperative RLN injury occurred in 2.3% of our patients. The sensitivity of IEMG was 100%, the specificity 87%, the positive predictive value 16%, and its negative predictive value 97%. The calculated IS ranged between 0.28 and 3.47 (mean IS: 2.09). Significantly increased IEMG activity was found in patients with previous surgical intervention, patients undergoing multilevel procedures, long-lasting procedures, and cases in which self-retained retractors were used. Likewise, significantly increased IS were observed in patients with previous surgeries and in cases where self-retained retractors were used. Conclusions Our study indicates that laryngeal IEMG is a high-sensitivity modality that can provide real-time information and can potentially minimize the risk of operative RLN injury.

Acute pain is reported as a presenting symptom in over 80% of physician visits. Chronic pain affects an estimated 76.2 million Americans--more than diabetes, heart disease, and cancer combined. It has been estimated to be undertreated in up to 80% of patients in some settings. Pain costs the American public more than $100 billion each year in health care, compensation, and litigation. That's why pain was officially declared "The Fifth Vital Sign." Henceforth the evaluation of pain became a requirement of proper patient care as important and basic as the assessment and management of temperature, blood pressure, respiratory rate, and heart rate. The numeric pain scale certainly has a place in care and in pain management; however, it is important to assess the patient's communication and self-management style and to recognize that patients, like pain, are on a continuum with varied styles of communication and adaptation. It is easy to get lost in the process, even when the process is initiated with the best of intentions. In the quest for individualized medicine, it might be best to keep pain assessment in the individualization arena.

Object The association of vitreous and/or subhyaloid hemorrhage with aneurysmal subarachnoid hemorrhage (SAH) has been frequently identified since the original description by Terson in 1900. In this prospective clinical study the authors examined the actual incidence of Terson hemorrhage in patients suffering aneurysmal SAH, they attempted to identify those parameters that could predispose its development, and they evaluated its prognostic significance in the overall patients' outcome. Methods A total of 174 patients suffering aneurysmal SAH were included in this study. The admitting Glasgow Coma Scale scores (GCS), World Federation of Neurological Societies (WFNS) scale scores, Hunt and Hess grades, and Fisher grades were recorded. A careful ophthalmological evaluation was performed in all participants. The exact anatomical locations and the largest diameter of the dome of the ruptured aneurysms were also recorded. Surgical clipping or endovascular coiling was used in 165 patients. Clinical outcome was evaluated at discharge from the hospital by using the Glasgow Outcome Scale and the modified Rankin Scale. Periodic ophthalmological evaluations were performed for 2 years. Results In this series, the observed incidence of Terson hemorrhage was 12.1%. Statistical analysis of our data demonstrated that patients with low GCS scores and high WFNS scores, Hunt and Hess grades, and Fisher grades had an increased incidence of Terson hemorrhage. The mortality rate for patients with Terson hemorrhage was 28.6%, whereas that for patients without Terson hemorrhage was 2.0%. Moreover, patients with Terson hemorrhage who survived had significantly worse outcomes than those in patients without Terson hemorrhage. Conclusions Terson hemorrhage constitutes a common SAH-associated complication. Its incidence is increased in patients with low GCS and high WFNS scores, and high Hunt and Hess and Fisher grades. Its presence is associated with increased mortality and morbidity rates.

The purpose of our current study is to describe the guidelines regarding trephination as suggested in the Hippocratic writer's book, "Peri ton en cephali traumaton" ("On Head Wounds"). The ancient Greek text was reviewed as well as two English translations. The Hippocratic author described the indications, timing, and techniques of trephination for patients with head injury. He emphasized that attention should be paid to the details of the employed technique. He also commented on the difference of skull thickness at different anatomical sites and also between different age groups. The Hippocratic recommendations provided details for the performance of trephination by the ancient Greek physicians that are still considered important in modern neurosurgery.

We present the results of a retrospective study employing intraoperative micro-Doppler ultrasonography (MDU) in verifying proper clip placement during cerebral aneurysmal surgery. One hundred and thirty-four patients surgically treated for 147 intracranial aneurysms were studied. Thirteen patients harboring 17 aneurysms were surgically treated on an elective basis, while 121 patients with 130 aneurysms, presented with subarachnoid hemorrhage (SAH). Blood flow velocities of the parent and adjacent vessels as well as the aneurysmal sac were measured using a Conforma Micro-Doppler (Cook Vascular Inc., Leechburg, PA, USA). Pre- and post-operative cerebral angiography was obtained in all our patients. In 23 aneurysms (15.6%) there was decreased or absent flow in the parent vessel or in one of the adjacent vessels after clipping. In another 19 aneurysms (12.9%), MDU demonstrated flow through the aneurysmal dome even though the aneurysmal neck appeared to be totally obliterated. Presence of SAH, anatomic location and size of the aneurysm were associated with improper clip placement in a statistically significant fashion. The false positive rate for MDU was 2% while there were no false negative findings in our study. MDU appears to be a non-invasive, reliable alternative methodology to intra-operative angiography. This inexpensive method may lend itself to routine usage in aneurysm surgery.

Objective: This study describes a single-site investigation on the effects of a randomized double-blind placebo trial targeting duloxetine added to opioid use (duloxetine + opioid) against a comparator (placebo + opioid) in spine surgery patients, independent of major depression. Design: The double-blind comparator study assessed two groups on opioids: one using duloxetine and the other a placebo. Subjects were administered the respective medication 2 weeks prior to surgery and continued on this for more than 3 months. Subjects were assessed at three times: prior to surgery, 4 weeks postsurgery, and 12 weeks postsurgery. They completed a battery of tests assessing for pain, adjustment, and psychiatric problems. Setting: Neurosurgical outpatient and inpatient setting. Patients: Sixty-eight patients completed the study. They received one of three types of elective spine surgery. Interventions: Subjects were given duloxetine or placebo 2 weeks prior to surgery and continued with the regimen for more than 3 months. Outcomes: The primary focus was pain and second on adjustment factors and psychiatric symptoms: depression and anxiety. The amount of opioid use presurgery and postsurgery was also evaluated. Results: There were differences among the groups on Brief Pain Inventory (BPI)-Average, the core pain marker, and BPI-Sleep. Within-subject analyses showed that duloxetine subjects improved significantly from baseline. For function, post-CIBIC and post-Functional Adjustment Questionnaire were significant, favoring duloxetine. Reduction of opioid use was not a factor; both groups' utilization declined. For affect, both groups were significantly improved over time. Conclusions: Duloxetine seems to improve pain, assist with maintaining function, and reduce intensity of affect.

Gastrointestinal Preparation May Reduce Length of Stay in Spine Surgery: Quality Improvement Project In a healthcare system troubled by escalating demands escalating costs, the last decade has seen a marked increase in both volume and cost of surgical spine procedures. Probing methodologies to reduce such costs without jeopardizing patient outcome would generate substantial benefit. This paper assesses the effect of administering milk of magnesia (MOM) for bowel preparation on the length of hospital stay (LOS).

Traumatic epidural hematoma (EDH) represents a rare head injury complication in infants. Its diagnosis can be quite challenging because its clinical presentation is usually subtle and nonspecific. In our current communication, we present our data regarding the presentation of infants with EDH, their management, and their long-term outcome. In a retrospective study, the hospital and outpatient clinic charts and imaging studies (head CT and skull X-rays) of 31 infants with pure, supratentorial EDH of traumatic origin were meticulously reviewed. Children Coma Scale score and Trauma Infant Neurologic Score (TINS) were also reviewed. The most common presenting symptom was irritability, which occurred in 18/31 (58.1%) of our patients. Pallor (in 30/31 patients) and cephalhematoma (in 21/31 patients) were the most commonly occurring clinical signs upon admission; both signs represent signs of significant clinical importance. Surgical evacuation via a craniotomy was required in 24/31 of our patients, while 7/31 patients were managed conservatively. The mortality rate in our series was 6.5% (2/31 patients), and our long-term morbidity rate was 3.2% (1/31 patients). EDH in infants represents a life-threatening complication of head injury, which requires early identification and prompt surgical or conservative management depending on the patient’s clinical condition, size of EDH, and presence of midline structure shift on head CT scan. Mortality and long-term morbidity are low with early diagnosis and prompt treatment.

The fusion rate represents one of the most commonly used criteria for evaluating the efficacy of spinal surgical techniques and the effectiveness of newly developed instrumentation and spinal implants. Reported fusion rates are not frequently supported by adequate information regarding by whom and how fusion was defined. In our prospective study we examined the fusion rate in patients undergoing first time anterior cervical discectomy and fusion for degenerative disease. Separate, well-defined radiographic fusion criteria were used and the 12-month post-operative X-rays were reviewed independently by a neurosurgeon, a neuroradiologist and an orthopedic surgeon, who were not involved in the patients' management. The observed fusion rates were 77.3, 87.8 and 84.7% respectively. Statistical analysis demonstrated concordance rates of 87.8, 91 and 91.4% and Kappa coefficients of 0.585, 0.620 and 0.723 for each pair of evaluators. Another set of ratings of the same radiographs, by the same interviewers, was obtained 6 weeks after the initial one. The reported fusion rates were 78.2% for the neurosurgeon, 87.4% for the orthopedic surgeon, and 86.1% for the neuroradiologist. Statistical analysis demonstrated intra-observer concordance rates of 98.7, 92.2 and 97.9% respectively, while the Kappa coefficients were 0.963, 0.677 and 0.907 for each reviewer. Our findings confirm the necessity of defining and describing criteria for fusion whenever this rate is reported in clinical series. The lack of widely accepted, well-defined criteria makes comparison of these results difficult. The development of a well organized, prospective clinical study in which fusion and outcome will be assessed by both clinical and radiographic parameters could significantly contribute to a more accurate evaluation of overall outcome of cervical spinal procedures.