[Coronavirus: from common cold to severe pulmonary failure]. / Coronaviren: von der banalen Erkältung zum schweren Lungenversagen: Chronologie einer Pandemie.

In December 2019 a new human coronavirus emerged in Wuhan, China, which is known as SARS-CoV­2. The clinical course of the disease known as coronavirus disease 2019 (COVID-19) ranges from mild respiratory symptoms to severe lung failure. The virus is currently rapidly spreading around the world and pushing health systems to the limits of their capacity due to the exponential increase in the number of cases. The origin of SARS-CoV­2 lies in the bat coronavirus pool and has now emerged in the human population due to interspecies transmission. Molecular diagnostic methods have been established in a very short time and a number of clinical studies on the effectiveness of different antiviral drugs are ongoing. The development of a vaccine using different approaches is also under investigation.Considering the high number of cases and mortality rates of up to 9% there is an urgent need for action. This article summarizes the current state of knowledge on human coronaviruses with a strong focus on the current data on SARS-CoV­2. Due to the daily changing level of knowledge, the article reflects the status up to 21 March 2020.

A Phase II Study of Pembrolizumab in EGFR-Mutant, PD-L1+, Tyrosine Kinase Inhibitor Naïve Patients With Advanced NSCLC.

BACKGROUND: Despite the significant antitumor activity of pembrolizumab in NSCLC, clinical benefit has been less frequently observed in patients whose tumors harbor EGFR mutations compared to EGFR wild-type patients. Our single-center experience on the KEYNOTE-001 trial suggested that pembrolizumab-treated EGFR-mutant patients, who were tyrosine kinase inhibitor (TKI) naïve, had superior clinical outcomes to those previously treated with a TKI. As TKI naïve EGFR-mutants have generally been excluded from pembrolizumab studies, data to guide treatment decisions in this patient population is lacking, particularly in patients with programmed death ligand 1 (PD-L1) expression ≥50%. METHODS: We conducted a phase II trial (NCT02879994) of pembrolizumab in TKI naive patients with EGFR mutation-positive, advanced NSCLC and PD-L1-positive (≥1%, 22C3 antibody) tumors. Pembrolizumab was administered 200 mg every 3 weeks. The primary endpoint was objective response rate. Secondary endpoints included safety of pembrolizumab, additional pembrolizumab efficacy endpoints, and efficacy and safety of an EGFR TKI after pembrolizumab. RESULTS: Enrollment was ceased due to lack of efficacy after 11 of 25 planned patients were treated. Eighty-two percent of trial patients were treatment naïve, 64% had sensitizing EGFR mutations, and 73% had PD-L1 expression ≥50%. Only 1 patient had an objective response (9%), but repeat analysis of this patient's tumor definitively showed the original report of an EGFR mutation to be erroneous. Observed treatment-related adverse events were similar to prior experience with pembrolizumab, but two deaths within 6 months of enrollment, including one attributed to pneumonitis, were of concern. CONCLUSIONS: Pembrolizumab's lack of efficacy in TKI naïve, PD-L1+, EGFR-mutant patients with advanced NSCLC, including those with PD-L1 expression ≥50%, suggests that it is not an appropriate therapeutic choice in this setting.

Reconciling agriculture, carbon and biodiversity in a savannah transformation frontier.

Rapidly rising populations and likely increases in incomes in sub-Saharan Africa make tens of millions of hectares of cropland expansion nearly inevitable, even with large increases in crop yields. Much of that expansion is likely to occur in higher rainfall savannas, with substantial costs to biodiversity and carbon storage. Zambia presents an acute example of this challenge, with an expected tripling of population by 2050, good potential to expand maize and soya bean production, and large areas of relatively undisturbed miombo woodland and associated habitat types of high biodiversity value. Here, we present a new model designed to explore the potential for targeting agricultural expansion in ways that achieve quantitatively optimal trade-offs between competing economic and environmental objectives: total converted land area (the reciprocal of potential yield); carbon loss, biodiversity loss and transportation costs. To allow different interests to find potential compromises, users can apply varying weights to examine the effects of their subjective preferences on the spatial allocation of new cropland and its costs. We find that small compromises from the objective to convert the highest yielding areas permit large savings in transportation costs, and the carbon and biodiversity impacts resulting from savannah conversion. For example, transferring just 30% of weight from a yield-maximizing objective equally between carbon and biodiversity protection objectives would increase total cropland area by just 2.7%, but result in avoided costs of 27-47% for carbon, biodiversity and transportation. Compromise solutions tend to focus agricultural expansion along existing transportation corridors and in already disturbed areas. Used appropriately, this type of model could help countries find agricultural expansion alternatives and related infrastructure and land use policies that help achieve production targets while helping to conserve Africa's rapidly transforming savannahs.This article is part of the themed issue 'Tropical grassy biomes: linking ecology, human use and conservation'.

Improving the visualization of cryo-EM density reconstructions.

Cryo-electron microscopy yields 3D density maps of macromolecules from single-particle images, tomograms, or 2D crystals. An optimal visualization of the density map is important for its proper interpretation. We have developed a method to improve the visualization of density maps by using general statistical information about proteins for the sharpening process. In particular, the packing density of atoms is highly similar between different proteins, which allows for building a pseudo-atomic model to approximate the true mass distribution. From this model the radial structure factor and density value histogram are estimated and applied as constraints to the 3D reconstruction in reciprocal- and real-space, respectively. Interestingly, similar improvements are obtained when using the correct radial structure factor and density value histogram from a crystal structure. Thus, the estimated pseudo-atomic model yields a sufficiently accurate mass distribution to optimally sharpen a density map.

Movement planning and attentional control of visuospatial working memory: evidence from a grasp-to-place task.

In this study, we have investigated the influence of available attentional resources on the dual-task costs of implementing a new action plan and the influence of movement planning on the transfer of information into visuospatial working memory. To approach these two questions, we have used a motor-memory dual-task design in which participants grasped a sphere and planned a placing movement toward a left or right target according to a directional arrow. Subsequently, they encoded a centrally presented memory stimulus (4 × 4 symbol matrix). While maintaining the information in working memory, a visual stay/change cue (presented on the left, center or right) either confirmed or reversed the planned movement direction. That is, participants had to execute either the prepared or the re-planned movement and finally reported the symbols at leisure. The results show that both, shifts of spatial attention required to process the incongruent stay/change cues and movement re-planning, constitute processing bottlenecks as they both reduced visuospatial working memory performance. Importantly, the spatial attention shifts and movement re-planning appeared to be independent of each other. Further, we found that the initial preparation of the placing movement influenced the report pattern of the central working memory stimulus. Preparing a leftward movement resulted in better memory performance for the left stimulus side, while the preparation of a rightward movement resulted in better memory performance for the right stimulus side. Hence, movement planning influenced the transfer of information into the capacity-limited working memory store. Therefore, our results suggest complex interactions in that the processes involved in movement planning, spatial attention and visuospatial working memory are functionally correlated but not linked in a mandatory fashion.

A novel laboratory set-up for investigating surface and interface reactions during short term annealing cycles at high temperatures.

High temperature oxidation is an important research discipline that covers many topics in steel manufacture and modern energy research. To account for the need of adjusting accurate processing conditions, recent developments of the high temperature laboratory setup at the Max-Planck-Institut für Eisenforschung GmbH will be presented. The experimental assembly has been optimized to investigate surface and interface reactions at elevated temperatures in low oxygen activity gases, covering a large field of experimental possibilities. Many efforts have been taken to enable an accurate control and in situ monitoring of process conditions such as gas flow, gas composition, impurity content, and mass change of the sample.

The functional role of working memory in the (re-)planning and execution of grasping movements.

Three experiments were conducted to dissociate movement planning costs and movement execution costs in working memory (WM). The aim of the study was to clarify what kind of WM processes (verbal, spatial, or both) are recruited during movement planning and movement execution. Therefore, a WM task (verbal and spatial versions) was combined with a high-precision manual action. Participants initially planned a placing movement toward 1 of 2 targets, subsequently encoded verbal or spatial information in WM, and then executed the movement during the retention phase. We tested the impact of movement execution on memory performance (Experiment 1), the role of WM task difficulty as a moderating variable in motor-memory interactions (Experiment 2), and the impact of implementing a new motor plan during memory retention (Experiment 3). Our results show that movement execution disrupted spatial more than verbal memory (Experiment 1) and that this domain-specific interference pattern was independent of WM task difficulty (Experiment 2). Hence, the results of Experiments 1 and 2 demonstrate that executing a prepared movement recruits domain-specific visuospatial memory resources. Experiment 3 involved trials that required the implementation of a new motor plan. The additional planning requirement during the retention phase reduced performance in both WM tasks in equal measure beyond the relative movement execution costs observed in Experiments 1 and 2. These results provide evidence for distinct roles of WM in manual actions, with action execution requiring principally modality-specific capacities and (re-)planning engaging modality-general WM resources.

Safety of Novel Protein Sources (Insects, Microalgae, Seaweed, Duckweed, and Rapeseed) and Legislative Aspects for Their Application in Food and Feed Production.

Novel protein sources (like insects, algae, duckweed, and rapeseed) are expected to enter the European feed and food market as replacers for animal-derived proteins. However, food safety aspects of these novel protein sources are not well-known. The aim of this article is to review the state of the art on the safety of major novel protein sources for feed and food production, in particular insects, algae (microalgae and seaweed), duckweed, and rapeseed. Potential hazards for these protein sources are described and EU legislative requirements as regard to food and feed safety are explained. Potential hazards may include a range of contaminants, like heavy metals, mycotoxins, pesticide residues, as well as pathogens. Some safety aspects of novel protein sources are intrinsic to the product, but many potential hazards can also be due to production methods and processing conditions. These aspects should be considered in advance during product development. European law is unclear on several issues regarding the use of novel protein sources in food and feed products. For food product applications, the most important question for food producers is whether or not the product is considered a novel food. One of the major unclarities for feed applications is whether or not products with insects are considered animal-derived products or not. Due to the unclarities in European law, it is not always clear which Regulation and maximum levels for contaminants apply. For market introduction, European legislation should be adjusted and clarified.

The costs of changing an intended action: movement planning, but not execution, interferes with verbal working memory.

How much cognitive effort does it take to change a movement plan? In previous studies, it has been shown that humans plan and represent actions in advance, but it remains unclear whether or not action planning and verbal working memory share cognitive resources. Using a novel experimental paradigm, we combined in two experiments a grasp-to-place task with a verbal working memory task. Participants planned a placing movement toward one of two target positions and subsequently encoded and maintained visually presented letters. Both experiments revealed that re-planning the intended action reduced letter recall performance; execution time, however, was not influenced by action modifications. The results of Experiment 2 suggest that the action's interference with verbal working memory arose during the planning rather than the execution phase of the movement. Together, our results strongly suggest that movement planning and verbal working memory share common cognitive resources.

A 2D driven 3D vessel segmentation algorithm for 3D digital subtraction angiography data.

Cerebrovascular disease is among the leading causes of death in western industrial nations. 3D rotational angiography delivers indispensable information on vessel morphology and pathology. Physicians make use of this to analyze vessel geometry in detail, i.e. vessel diameters, location and size of aneurysms, to come up with a clinical decision. 3D segmentation is a crucial step in this pipeline. Although a lot of different methods are available nowadays, all of them lack a method to validate the results for the individual patient. Therefore, we propose a novel 2D digital subtraction angiography (DSA)-driven 3D vessel segmentation and validation framework. 2D DSA projections are clinically considered as gold standard when it comes to measurements of vessel diameter or the neck size of aneurysms. An ellipsoid vessel model is applied to deliver the initial 3D segmentation. To assess the accuracy of the 3D vessel segmentation, its forward projections are iteratively overlaid with the corresponding 2D DSA projections. Local vessel discrepancies are modeled by a global 2D/3D optimization function to adjust the 3D vessel segmentation toward the 2D vessel contours. Our framework has been evaluated on phantom data as well as on ten patient datasets. Three 2D DSA projections from varying viewing angles have been used for each dataset. The novel 2D driven 3D vessel segmentation approach shows superior results against state-of-the-art segmentations like region growing, i.e. an improvement of 7.2% points in precision and 5.8% points for the Dice coefficient. This method opens up future clinical applications requiring the greatest vessel accuracy, e.g. computational fluid dynamic modeling.

Prospective validation of a simple laboratory score to predict outcome after orthotopic liver transplantation.

OBJECTIVE: To establish a score to predict 30-day mortality and graft loss retrospectively and to validate the score prospectively. PATIENTS AND METHODS: Retrospectively in 296 liver transplant recipients, a score was developed that included the peak aspartate aminotransferase concentration within the first week and γ-glutamyltransferase and bilirubin concentrations at day 7 to predict graft loss or patient death within 30 days. The score was then prospectively validated in 86 patients undergoing liver transplantation. RESULTS: From the retrospective training cohort, cut-off values for prediction of adverse outcomes were determined using receiver operating characteristic curve analysis for peak aspartate aminotransferase (>1870 IU/mL), γ-glutamyltransferase (<214 IU/mL), and bilirubin (>5.75 mg/dL). Sensitivity and specificity of the score to predict an end point from the retrospective cohort were excellently reproduced in the prospective cohort. Overall, fulfillment of at least 2 criteria predicted graft loss or death within 30 days with sensitivity of 0.70 and specificity of 0.78. No patients with values that remained below all 3 thresholds experienced graft loss or death within 30 days. CONCLUSIONS: This simple score calculated from standard laboratory values within the first week after liver transplantation enables prediction of graft loss and patient death within 30 days after transplantation. Early identification of patients at risk may help to improve outcomes by observing these patients more closely and allocating resources for them.

Classification-based summation of cerebral digital subtraction angiography series for image post-processing algorithms.

X-ray-based 2D digital subtraction angiography (DSA) plays a major role in the diagnosis, treatment planning and assessment of cerebrovascular disease, i.e. aneurysms, arteriovenous malformations and intracranial stenosis. DSA information is increasingly used for secondary image post-processing such as vessel segmentation, registration and comparison to hemodynamic calculation using computational fluid dynamics. Depending on the amount of injected contrast agent and the duration of injection, these DSA series may not exhibit one single DSA image showing the entire vessel tree. The interesting information for these algorithms, however, is usually depicted within a few images. If these images would be combined into one image the complexity of segmentation or registration methods using DSA series would drastically decrease. In this paper, we propose a novel method automatically splitting a DSA series into three parts, i.e. mask, arterial and parenchymal phase, to provide one final image showing all important vessels with less noise and moving artifacts. This final image covers all arterial phase images, either by image summation or by taking the minimum intensities. The phase classification is done by a two-step approach. The mask/arterial phase border is determined by a Perceptron-based method trained from a set of DSA series. The arterial/parenchymal phase border is specified by a threshold-based method. The evaluation of the proposed method is two-sided: (1) comparison between automatic and medical expert-based phase selection and (2) the quality of the final image is measured by gradient magnitudes inside the vessels and signal-to-noise (SNR) outside. Experimental results show a match between expert and automatic phase separation of 93%/50% and an average SNR increase of up to 182% compared to summing up the entire series.

An early increase in gamma glutamyltranspeptidase and low aspartate aminotransferase peak values are associated with superior outcomes after orthotopic liver transplantation.

BACKGROUND: Prediction of prognosis after liver transplantation (OLT) remains difficult. The present study determines if standard laboratory parameters measured within the first week after OLT correlate with outcome. PATIENTS AND METHODS: Laboratory parameters measured within the first weak after OLT of 328 patients were grouped either graft loss or death within 90 days after (group 1: graft loss; group 2: death; group 3: neither graft loss nor death within 90 days). RESULTS: Peak AST and ALT were significantly lower in group 3 (1867 and 1252 U/L) than in group 1 (4474 and 2077 U/L) or 2 (3121 and 1865 U/L). Bilirubin was significantly lower and gamma-GT significantly higher in group 3 compared to groups 1 and 2. In multivariate analysis, high AST peaks were independently associated with death or graft loss within 90 days. An increase in gamma-GT and low bilirubin early after transplantation were found to be independently associated with superior outcome. DISCUSSION: Unexpectedly, a disproportionate rise in gamma-GT was associated with graft and patient survival of more than 90 days. This might be explained by regeneration phenomena in the liver indicative of a well functioning graft.

A Microbial Assessment Scheme to measure microbial performance of Food Safety Management Systems.

A Food Safety Management System (FSMS) implemented in a food processing industry is based on Good Hygienic Practices (GHP), Hazard Analysis Critical Control Point (HACCP) principles and should address both food safety control and assurance activities in order to guarantee food safety. One of the most emerging challenges is to assess the performance of a present FSMS. The objective of this work is to explain the development of a Microbial Assessment Scheme (MAS) as a tool for a systematic analysis of microbial counts in order to assess the current microbial performance of an implemented FSMS. It is assumed that low numbers of microorganisms and small variations in microbial counts indicate an effective FSMS. The MAS is a procedure that defines the identification of critical sampling locations, the selection of microbiological parameters, the assessment of sampling frequency, the selection of sampling method and method of analysis, and finally data processing and interpretation. Based on the MAS assessment, microbial safety level profiles can be derived, indicating which microorganisms and to what extent they contribute to food safety for a specific food processing company. The MAS concept is illustrated with a case study in the pork processing industry, where ready-to-eat meat products are produced (cured, cooked ham and cured, dried bacon).

Two independent chromosomal rearrangements, a very small (550 kb) duplication of the 7q subtelomeric region and an atypical 17q11.2 (NF1) microdeletion, in a girl with neurofibromatosis.

Most patients with neurofibromatosis (NF1) are endowed with heterozygous mutations in the NF1 gene. Approximately 5% show an interstitial deletion of chromosome 17q11.2 (including NF1) and in most cases also a more severe phenotype. Here we report on a 7-year-old girl with classical NF1 signs, and in addition mild overgrowth (97th percentile), relatively low OFC (10th-25th percentile), facial dysmorphy, hoarse voice, and developmental delay. FISH analysis revealed a 17q11.2 microdeletion as well as an unbalanced 7p;13q translocation leading to trisomy of the 7q36.3 subtelomeric region. The patient's mother and grandmother who were phenotypically normal carried the same unbalanced translocation. The 17q11.2 microdeletion had arisen de novo. Array comparative genomic hybridization (CGH) demonstrated gain of a 550-kb segment from 7qter and loss of 2.5 Mb from 17q11.2 (an atypical NF1 microdeletion). We conclude that the patient's phenotype is caused by the atypical NF1 deletion, whereas 7q36.3 trisomy represents a subtelomeric copy number variation without phenotypic consequences. To our knowledge this is the first report that a duplication of the subtelomeric region of chromosome 7q containing functional genes (FAM62B, WDR60, and VIPR2) can be tolerated without phenotypic consequences. The 17q11.2 microdeletion (containing nine more genes than the common NF1 microdeletions) and the 7qter duplication were not accompanied by unexpected clinical features. Most likely the 7qter trisomy and the 17q11.2 microdeletion coincide by chance in our patient.

Recanalization after thrombolysis in stroke patients: predictors and prognostic implications.

OBJECTIVE: To estimate rates, predictors, and prognostic importance of recanalization in an unselected series of patients with stroke treated with IV thrombolysis. METHODS: We performed a CT angiography or transcranial Doppler (TCD) follow-up examination 24 hours after IV thrombolysis in 64 patients with documented occlusion of the intracranial internal carotid or middle cerebral artery (MCA). Complete recanalization was defined by a rating of 3 on the Thrombolysis in Myocardial Infarction or 4/5 on the Thrombolysis in Brain Ischemia grading scales. Information about risk factors, clinical features, and outcome was prospectively collected by standardized procedures. RESULTS: Complete recanalization was achieved in 36 of the 64 patients (56.3%). There was a nonsignificant trend of recanalization rates to decline with a more proximal site of occlusion: 68.4% (M2 segment of MCA), 53.1% (M1 segment), and 46.2% (carotid T) (p for trend = 0.28). Frequencies of vessel reopening were markedly reduced in subjects with diabetes (9.1% vs 66.0% in nondiabetics, p < 0.001) and less so in subjects with additional extracranial carotid occlusion (p = 0.03). Finally, complete recanalization predicted a favorable stroke outcome at day 90 independently of the information provided by age, NIH Stroke Scale, and onset-to-needle time. CONCLUSIONS: We found a high rate of vessel recanalization after IV thrombolysis occlusion. However, recanalization was infrequent in patients with diabetes and extracranial carotid occlusion. Information on recanalization was a powerful, early predictor for clinical outcome.

Menstrual cycle dependent right-to-left shunting: a single-blinded transcranial Doppler sonography study.

BACKGROUND AND PURPOSE: Menstruation has been described as risk factor for neurological decompression sickness in divers. In considering this for paradoxical gas embolism, we hypothesized that there may be a link between cycle-dependent hormonal changes and the manifestation of a right-to-left shunt (RLS). METHODS: 40 women with a regular cycle of 28 days underwent transcranial Doppler sonography examinations (TCD) on day 1 and on day 15 of the menstrual cycle. Cerebral high intensity transient signs (HITS) proved a RLS. RESULTS: We found a 25% RLS incidence consistent with the literature. In 7 of 10 shunt-positive women it was detected mainly or exclusively on day 15. This difference in PFO detection rate is statistically significant (p = 0.031), indicating more RLS during the peri-ovulatory period. CONCLUSIONS: Our results do not support menstruation as a risk factor for neurological decompression sickness. The peri-ovulatory estrogen peak, which leads to systemic vasodilation, may explain our data. Factors that increase the risk for developing a RLS and thereby paradoxical embolism should be avoided, perhaps including diving during the peri-ovulatory period of the menstrual cycle. Furthermore, contrast PFO testing in fertile females may be most sensitive if conducted mid-cycle.

Refractory status epilepticus due to acute hepatic porphyria in a pregnant woman: induced abortion as the sole therapeutic option?

A 22-years old, 55 kg female patient in the twelfth week of pregnancy developed neuropsychiatric syndromes and in the following status epilepticus. Raised porphyrines and porphyrine precursors were found in the patient's urine. Despite intravenous glucose infusions and appropriate medication no reduction in seizure-frequency and neuropsychiatric syndromes was observed. An abortion was induced. After the interruption and starting of haem arginate therapy, seizure activity stopped and porphyrine precursors returned to normal levels, and after 6 weeks the patient was discharged in excellent clinical condition. This report describes a status epilepticus caused by acute hepatic porphyria, triggered by pregnancy, in a 22-years old woman. To our knowledge this is the first report of induced abortion as successful treatment in acute hepatic porphyria induced status epilepticus.

Evaluation of performance measurement instruments on their use for food quality systems.

Due to regular challenges of food safety, consumers put high demands on the performance of food quality systems. To deal with these requirements, food manufacturers need effective quality management. Performance of food quality systems can be partly realized by quality assurance systems, such as HACCP (hazard analysis and critical control point), ISO (international organization for standardization), and BRC (british retail consortium). However, it is still unknown to what extent these systems factually contribute to the realization of quality in the wider sense. Therefore, an instrument is needed that measures the effectiveness of quality systems. This article describes the evaluation of instruments on their suitability for the development of a diagnostic instrument that measures the effectiveness of food quality systems. For this evaluation, perspectives of quality, typical characteristics of agrifood production, quantification, and performance measurement of quality management were studied. Instruments that measure the performance of both quality management and production quality were identified and evaluated on the basis of the defined criteria. The criteria for the performance of production quality were 6 quality dimensions, i.e., product quality, availability, costs,flexibility, reliability, and service. The criteria for performance of quality management were analyses of the relationships between quality management, context of the organization, and production quality, a normative procedure, validation, applicability, classification, and a process approach. Finally, for the final instrument, the evaluation resulted in an integrated approach i.e., a technomanagerial approach, and 3 suitable instruments i.e., Wageningen Management Approach, Extended Quality Triangle, and the quality concept of Noori and Radford.

Remifentanil and nitrous oxide reduce changes in cerebral blood flow velocity in the middle cerebral artery caused by pain.

BACKGROUND: Cerebral blood flow is affected by painful stimuli, and analgesic agents may alter the response of cerebral blood flow to pain. We set out to quantify the effects of remifentanil and nitrous oxide on blood flow changes caused by experimental pain. METHODS: We simulated surgical pain in 10 conscious volunteers using increasing mechanical pressure to the tibia. We measured changes in cerebral blood flow velocity in the middle cerebral artery (CBFV(MCA)) caused by the pain, using transcranial Doppler sonography. We gave increasing doses of remifentanil (0.025, 0.05 and 0.1 micro g kg(-1) min(-1)) or nitrous oxide [20%, 35% and 50% end-tidal concentration (FE'(N(2)O))] and compared these effects on blood flow changes. RESULTS: Nitrous oxide increased CBFV(MCA) only when given at 50% FE'(N(2)O). Remifentanil did not affect CBFV(MCA). Pain increased CBFV(MCA). Both agents attenuated this pain-induced change in CBFV(MCA) with the exception of nitrous oxide at 20% FE'(N(2)O). CONCLUSIONS: Inhalation of nitrous oxide or adminstration of remifentanil attenuated pain-induced changes in CBFV(MCA).