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Background Stimulus-response compatibility (SRC) plays a major role in choice-reaction tasks. In specific cases, SRC leads to phenomena like the Spatial Numerical Association of Response Codes (SNARC) or the Spatial Pitch Association of Response Codes (SPARC) effect: small numbers or low pitches lead to faster responses when answered with the left hand, whereas large numbers or high pitches lead to faster responses when answered with the right hand. The previous study, investigating the combination of SNARC and SPARC with numbers spoken in different pitch heights, points towards an interdependency of both SNARC and SPARC compatibility effects, suggesting an automatic process. Methods In the present event-related functional magnetic resonance imaging (fMRI) study, we investigated the underlying neural activity when SNARC and SPARC are combined within the same auditory stimulus (numerical condition). Additionally, we included a categorical condition (the words “small” and “large”) as variation of the stimulus type. Results We found neither an effect for SNARC nor for SPARC Compatibility in the neuronal data, whereas SNARC Compatibility was found in the behavioral data. According to the behavioral as well as the neuronal data, in the bilateral auditory cortex, SNARC and SPARC Compatibility interacts with Stimulus Type, i.e., whether numerical or categorical stimuli were presented. Conclusions We concluded that both effects are interdependent and that this interaction strongly depends on the semantic information.

Processing of speech was investigated by using stimuli gradually changing from speech (vowels) to non-speech (spectral rotated vowels). Stimuli were presented in descending levels of vocalization blends, from pure speech to non-speech, through step-wise combinations, resulting in ambiguous versions of the sounds. Participants performed a two-alternative forced choice task: categorization of sounds were made according to whether they contained more speech or non-speech. Performance feedback was presented visually on each trial. Reaction times (RT) after sound presentation, and functional magnetic resonance imaging (fMRI) data during auditory and visual processing, were analyzed. RT data suggested individual differences with a distinct group, good performers, functioning better in distinguishing stimuli with a higher degree of ambiguous blends compared to poor performers, who were not able to distinguish these stimuli correctly. fMRI data confirmed this finding. During auditory stimulation, good performers showed neural activation in the ventral auditory pathway, including the primary auditory cortex and the anterior superior temporal sulcus (responsible for speech processing). Poor performers, in contrast, showed neural activation in the dorsal auditory pathway, including the bilateral superior temporal gyrus. Group differences were also found for visual feedback processing. Differences observed between the groups were interpreted as reflecting different neural processing strategies.

Previous research has shown a systematic relationship between phonological working memory capacity and second language proficiency for alphabetic languages. However, little is known about the impact of working memory processes on second language learning in a non-alphabetic language such as Mandarin Chinese. Due to the greater complexity of the Chinese writing system we expect that visual working memory rather than phonological working memory exerts a unique influence on learning Chinese characters. This issue was explored in the present experiment by comparing visual working memory training with an active (auditory working memory training) control condition and a passive, no training control condition. Training induced modulations in language-related brain networks were additionally examined using functional magnetic resonance imaging in a pretest-training-posttest design. As revealed by pre- to posttest comparisons and analyses of individual differences in working memory training gains, visual working memory training led to positive transfer effects on visual Chinese vocabulary learning compared to both control conditions. In addition, we found sustained activation after visual working memory training in the (predominantly visual) left infero-temporal cortex that was associated with behavioral transfer. In the control conditions, activation either increased (active control condition) or decreased (passive control condition) without reliable behavioral transfer effects. This suggests that visual working memory training leads to more efficient processing and more refined responses in brain regions involved in visual processing. Furthermore, visual working memory training boosted additional activation in the precuneus, presumably reflecting mental image generation of the learned characters. We, therefore, suggest that the conjoint activity of the mid-fusiform gyrus and the precuneus after visual working memory training reflects an interaction of working memory and imagery processes with complex visual stimuli that fosters the coherent synthesis of a percept from a complex visual input in service of enhanced Chinese character learning.

INTRODUCTION: The aim of this study was to evaluate the risks of endovascular therapy, aneurysm regrowth, recanalization and the need for reembolization. METHOD: A prospective analysis was performed on 211 aneurysms treated endovascularly from February 2000 to December 2003. Of these 211 aneurysms, 81 were asymptomatic and 130 were ruptured. The risks of endovascular therapy, aneurysm regrowth, recanalization and the need for reembolization were evaluated. RESULTS: The mean observation time was 10 months (ranging from 178 to 830 days). Complete occlusion (100%) in the initial intervention was achieved in 171 of 201 aneurysms (85%), 80-95% occlusion in 24 aneurysms (12%), and

INTRODUCTION: We aimed to test changes in cognitive performance after carotid artery stenting (CAS). METHOD: Ten patients were neuropsychologically tested at least 24 h before and 48 h after CAS. To diminish thromboembolic events, we used a proximal protection device. The following neuropsychological tests were selected: The Mini Mental State Examination (MMSE), symbol digit test and subtests of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery (verbal fluency, constructional practice, word list memory and delayed recall). Affective state was determined by the Beck Depression Score (BDS). RESULTS: No patient suffered from depression (BDS

Working memory training is a useful tool to examine dissociations between specific working memory processes. Although current models propose a distinction between modality-specific working memory processes, to our knowledge no study has directly examined the effects of visual versus auditory working memory training. Functional magnetic resonance imaging was used to investigate whether visual working memory processes can be trained specifically and whether those effects can be separated from across-modal training effects. We found decidedly larger training gains after visual working memory training compared with auditory or no training on a visual 2-back task. These effects were accompanied by specific training-related decreases in the right middle frontal gyrus arising from visual training only. Likewise, visual and auditory training led to decreased activations in the superior portion of the right middle frontal gyrus and the right posterior parietal lobule. We infer that the combination of effects resulted from increased neural efficiency of intra-modal (visual) processes on the one hand and of across-modal (general control) processes on the other hand. Therefore, visual processes of working memory can be trained specifically, and these effects can be functionally dissociated from alterations in general control processes common to both working memory trainings.

Transcranial ultrasound (TCS) has been shown to reveal hyperechogenicity of the substantia nigra (SN) in Parkinsonian patients and in about 10% of healthy controls. It is hypothesized that SN hyperechogenicity in healthy subjects is a vulnerability marker for idiopathic Parkinson's disease (IPD). Although there is strong evidence that the echomarker results from increased local iron content, the exact pathophysiological mechanisms remain incompletely understood. Thus, prognostic impact can only be estimated. We examined 14 subjects with SN hyperechogenicity (SN+) (7 IPD patients and 7 controls) and 7 healthy controls without the echomarker (SN−) by a magnetic resonance imaging method (MRI; T2 relaxation times) known to reveal tissue inhomogeneity following abnormal iron content and by F-Dopa PET to assess nigrostriatal function.

Background Increased total brain volume (TBV) has been reported for children with autism spectrum disorder (ASD) but studies in older ASD subjects have been contradictory. Similarly, studies of corpus callosum (CC) area in ASD differ with regard to inclusion criteria, age, and IQ. Methods In the present study, TBV, gray matter (GM), and white matter (WM) volume as well as midsagittal CC area were compared between 15 medication-naive, high-functioning adolescent and young adult ASD subjects and 15 healthy control individuals, and correlations with visuomotor coordination and imitation abilities were explored. In addition, computational surface-based methods were implemented to encode callosal thickness at high spatial resolution. Results Total brain volume, GM, and WM were increased and CC area was decreased in ASD subjects, a finding that was predominantly due to ASD subjects with lower IQ. Positive correlations of IQ with volume measures were observed only in control subjects. Autism spectrum disorder subjects showed reduced thickness in the posterior part of the CC. White matter volume showed a trend for negative correlation with dynamic balance and imitation abilities across groups. Conclusions This study replicates previous structural magnetic resonance imaging (MRI) findings in ASD, emphasizes the role of IQ differences, and adds some evidence for functional implications of structural findings.

Primary orthostatic tremor (OT) occurs only during standing. We studied whether modification of the condition standing influences OT. In seven patients with OT, surface EMG was recorded from both tibialis anterior and gastrocnemius muscles during two maneuvers: relief, whereby the patient was gradually lifted by a crane, and tilting, whereby the patient was tilted by a tilting table to positions of 90 degrees (upright standing), 45 degrees (diagonal position), and 0 degrees (lying position). We determined the parameters tremor frequency, tremor intensity, coherence, and phase shift between the different muscles. Relief did not influence OT. In contrast, tilting modified significantly tremor intensity and phase shifts; tremor frequencies and coherences were not influenced. We chose both these maneuvers because of their different impact on the standing condition: relief modifies the factors afferent input and muscle forcing but not the factor postural set, whereas tilting modifies all three factors. The fact that tilting modifies OT, whereas relief does not, suggests an important role of postural set in OT generation. Afferent input and muscle forcing seem to play less important role.

AIMS: The aim was to determine the incidence of new ischaemic lesions on diffusion-weighted MR imaging (DWI) in a non-randomised cohort of patients after protected and unprotected carotid artery stent placement using the Parodi Anti-Emboli System (PAES). METHODS AND RESULTS: A retrospective review was conducted on 269 patients who received DWI prior to, and 24-72 hours after, stent placement. All patients were enrolled in one centre. Forty patients stented with the PAES device were matched with 229 patients stented without protection (control group). New diffusion restriction on DWI was detected in 25.8% (PAES) versus 32.3% (control group); p=0.64. On average there were 0.7 lesions (PAES) versus 0.8 lesions (control group) per patient. The area of lesions was 1.7 (PAES) versus 5.6 mm2. In a subanalysis of patients (32 PAES, 148 non-protected) with >80% stenosis, the area of restricted diffusion was less when proximal protection was used (p

Atypical visual processing of biological motion contributes to social impairments in autism spectrum disorders (ASD). However, the exact temporal sequence of deficits of cortical biological motion processing in ASD has not been studied to date. We used 64-channel electroencephalography to study event-related potentials associated with human motion perception in 17 children and adolescents with ASD and 21 typical controls. A spatio-temporal source analysis was performed to assess the brain structures involved in these processes. We expected altered activity already during early stimulus processing and reduced activity during subsequent biological motion specific processes in ASD. In response to both, random and biological motion, the P100 amplitude was decreased suggesting unspecific deficits in visual processing, and the occipito-temporal N200 showed atypical lateralization in ASD suggesting altered hemispheric specialization. A slow positive deflection after 400 ms, reflecting top-down processes, and human motion-specific dipole activation differed slightly between groups, with reduced and more diffuse activation in the ASD-group. The latter could be an indicator of a disrupted neuronal network for biological motion processing in ADS. Furthermore, early visual processing (P100) seems to be correlated to biological motion-specific activation. This emphasizes the relevance of early sensory processing for higher order processing deficits in ASD.

Background: Bradydiadochokinesia is one main clinical symptom in idiopathic Parkinson's disease (IPD). The pathogenesis of bradydiadochokinesia is not completely clear. Methods: Fifteen patients with IPD and 15 age-matched healthy volunteers had to perform rhythmic alternating flexion and extension movements in the elbow joint. The rhythm was provided auditorily by a click tone stimulator. Six maneuvers (spatial extents of 48 and 83° at frequencies of 0.45, 0.75 and 1.25 Hz) had to be absolved. The potentiometer converted the horizontal forearm movements into a variable voltage. Results: The duration of single movements varied more significantly in patients than in controls (p < 0.05; Mann-Whitney U test). Patients executed all conditions more slowly than controls, but this difference was only significant at the most difficult condition (83° at 1.25 Hz; p < 0.01). The movement amplitudes or their variability were not significantly different at any condition. No parameter correlated significantly with the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS) or with the duration of disease. Conclusion: An insufficient temporal coordination contributes to bradydiadochokinesia in IPD. This deficit occurs independently of other parkinsonian cardinal motor symptoms.

This study sought to assess the feasibility and safety of a recently described technique of mechanical recanalization with the help of a stent-like device.In the special group of acute stroke patients with an intracranial large vessel occlusion, intravenous tissue-type plasminogen activator on its own leads to a good clinical outcome (mRS ≤ 2) in only 15% to 25% of cases. The aforementioned technique of mechanical recanalization showed very promising clinical results.Forty patients presenting within 6 h from stroke symptom onset were enrolled. Mechanical recanalization was performed using a Solitaire FR revascularization device. The primary endpoint of the study was the clinical outcome rated with the help of the modified Rankin Scale (mRS) after 90 days.Twenty-four patients (60%) showed a good clinical outcome (mRS ≤ 2) at 90 days. One symptomatic hemorrhage was detected on follow-up computed tomography. The death rate was 12.5% (5 patients). Successful recanalization (Thrombolysis In Cerebral Infarction score ≥ 2b) of the target vessel was achieved in 95% of the patients with a mean of 1.8 runs with the device.The ReFlow (Mechanical Recanalization With Flow Restoration in Acute Ischemic Stroke) study shows that mechanical recanalization with flow restoration is highly effective in stroke patients with a large intracranial vessel occlusion presenting within 4.5 h after symptom onset. (Mechanical Recanalization With Flow Restoration in Acute Ischemic Stroke [ReFlow]; NCT01210729).

Background: Most studies evaluating long-term efficacy after coil embolisation of intracranial aneurysms have not differentiated between ruptured and unruptured aneurysms. Objectives: The aim of this study was to analyse factors that influence recanalisation in ruptured and unruptured aneurysms. Methods: We performed a retrospective analysis of 182 (98 ruptured, 84 unruptured) aneurysms, treated with coil embolisation alone that received follow-up with digital substraction angiography (DSA). Results: At 6 months 26% of the aneurysms showed recanalisation. Multivariate variance analysis revealed that different factors influenced recanalisation in ruptured and unruptured aneurysms. In ruptured aneurysms patient age was a determinant, with younger patients recanalising more frequently than older ones (p = 0.016). Also, low initial packing density led to higher recanalisation rates (p = 0.015) than higher packing. In the unruptured aneurysm group these factors were not significant. Here, only a larger aneurysm volume led to higher recanalisation rates (p = 0.027). Conclusions: Our data suggest that in ruptured aneurysms, high packing density is a key factor to prevent recanalisation, while in unruptured aneurysms, aneurysm volume is the main predictor for recanalisation.

We assume that working memory is provided by a network comprising domain-general anterior and different domain-specific posterior brain areas depending on the type of stimulus and the task demands. Based on imaging studies from perception, we hypothesized that dynamic spatial (motion) and static spatial (position) information can be dissociated during retention in working memory. Participants were presented with a moving dot. About one second after stimulus presentation, a cue indicated whether its motion or end position should be held in memory. Six seconds later, a second stimulus was shown which was to be compared with the first one with respect to identity on the cued dimension. In the baseline condition, the cue indicated that no memory task would follow. We contrasted activity during maintenance of the different features. Differential activations in regions related to motion perception (area hMT/V5+, superior temporal sulcus) were observed in the motion working memory task. For position working memory, enhanced activations in a right brain region at the temporo-parieto-occipital junction emerged. The results are discussed with respect to domain-specific regions active in perception and how they can be also involved in short term retention for those very features. It is suggested that two types of spatial information categories can be dissociated: dynamic spatial (motion) and static spatial (position) information seem to be processed by different working memory structures.

INTRODUCTION: There have only been a few studies on cognitive changes in patients with carotid occlusive disease, and the results of these show major discrepancies in the extent to which treatment affects neuropsychological function. We sought to clarify these discrepancies by evaluating the effects of carotid artery stenting (CAS) on the cognitive function. METHODS: Forty-one asymptomatic CAS patients were administered a test battery of neuropsychological tests measuring cognitive speed and memory function before and 3 months after the procedure. A control group was also evaluated. To test for thromboembolic lesions, diffusion-weighted imaging was used. RESULTS: CAS led to a significant increase in cognitive speed (p

Attention deficit hyperactivity disorder (ADHD) is a common, genetically transmitted common childhood-onset disorder with a high rate of persistence in adulthood. Although many studies have shown anatomical and functional abnormalities in children and adolescents, studies with adult patients are rare. Nineteen adults with ADHD (11 ADHD, combined type; 8 ADHD, partially remitted) and 17 controls were included in this functional magnetic resonance imaging (fMRI) study. Brain activation was investigated with a continuous performance test (CPT). Impaired activation of a fronto-striatal and a parietal attentional network was observed during the NoGo condition in ADHD subjects. Correlations of reduced activity of the caudate nuclei, the anterior cingulate cortex, and parietal cortical structures, as well as increased activity in the insular cortex, with inattention and impulsivity symptom scores were found. The activation patterns were similar to those known from children and adolescents with ADHD. In conclusion we found not only a widespread dysfunction of brain regions that are involved in cognitive processing in adults with ADHD compared with controls, but also correlations between symptom severity and dysfunction of neuronal systems across adult subjects with a history of ADHD in childhood but whose symptoms did (persistent ADHD) and did not (not persistent ADHD) qualify for a full diagnosis of ADHD in adulthood.

In individuals with autism or autism-spectrum-disorder (ASD), conflicting results have been reported regarding the processing of biological motion tasks. As biological motion perception and recognition might be related to impaired imitation, gross motor skills and autism specific psychopathology in individuals with ASD, we performed a functional MRI study on biological motion perception in a sample of 15 adolescent and young adult individuals with ASD and typically developing, age, sex and IQ matched controls. Neuronal activation during biological motion perception was compared between groups, and correlation patterns of imitation, gross motor and behavioral measures with neuronal activation were explored. Differences in local gray matter volume between groups as well as correlation patterns of psychopathological measures with gray matter volume were additionally compared. On the behavioral level, recognition of biological motion was assessed by a reaction time (RT) task. Groups differed strongly with regard to neuronal activation and RT, and differential correlation patterns with behavioral as well as with imitation and gross motor abilities were elicited across and within groups. However, contrasting with the initial hypothesis, additional differences between groups were observed during perception and recognition of spatially moving point lights in general irrespective of biological motion. Results either point towards difficulties in higher-order motion perception or in the integration of complex motion information in the association cortex. This interpretation is supported by differences in gray matter volume as well as correlation with repetitive behavior bilaterally in the parietal cortex and the right medial temporal cortex. The specific correlation of neuronal activation during biological motion perception with hand-finger imitation, dynamic balance and diadochokinesis abilities emphasizes the possible relevance of difficulties in biological motion perception or impaired self-other matching for action imitation and gross motor difficulties in individuals with ASD.

INTRODUCTION: To evaluate the flow reversal efficacy of the Parodi antiembolism system (PAES) in the prevention of distal emboli during carotid stenting. METHODS: A total of 90 patients were treated for internal carotid artery (ICA) stenosis with a stent device. A PAES device was used in 31 symptomatic and 5 asymptomatic patients (total 36 patients) with ICA stenosis, and 54 patients were stented without any protection device. Diffusion-weighted (DW) imaging was performed before and after stenting. RESULTS: In the group without PAES protection, 23 out of 54 patients showed new lesions on DW images after stenting. Of the lesions seen, 147 (2.72 lesions/patient) were in the vessel-dependent area. In the group with protection, 19 out of 36 patients had new lesions, and only 34 (0.94 lesions/patient) were noted in the vessel-dependent area. The number of new lesions in the nondependent vessel area did not differ if a protection system was used (P = 0.671). The use of PAES led to a significant reduction (P = 0.024) in the incidence of the most frequently seen lesions (size

Using functional magnetic resonance imaging, the neural correlates of context-specific memories and invariant memories about regularities across episodes were investigated. Volunteers had to learn conjunctions between objects and positions. In an invariant learning condition, positions were held constant, enabling subjects to learn regularities across trials. By contrast, in a context-specific condition object-position conjunctions were trial unique. Performance increase in the invariant learning condition was paralleled by a learning-related increase of inferior frontal gyrus activation and ventral striatal activation and a decrease of hippocampus activation. Conversely, in the context-specific condition hippocampal activation was constant across trials. We argue that the learning-related hippocampal activation pattern might be due to reduced relational binding requirements once regularities are extracted. Furthermore, we propose that the learning-related prefrontal modulation reflects the requirement to extract and maintain regularities across trials and the adjustment of object-position conjunctions on the basis of the extracted knowledge. Finally, our data suggest that the ventral striatum encodes the increased predictability of spatial features as a function of learning. Taken together, these results indicate a transition of the relative roles of distinct brain regions during learning regularities across multiple episodes: regularity learning is characterized by a shift from a hippocampal to a prefrontal-striatal brain system.

It is a topic of current interest whether learning in humans relies on the acquisition of abstract rule knowledge (rule-based learning) or whether it depends on superficial item-specific information (instance-based learning). Here, we identified brain regions that mediate either of the two learning mechanisms by combining fMRI with an experimental protocol shown to be able to dissociate both learning mechanisms. Subjects had to learn object-position conjunctions in several trials and blocks. In a learning condition, either objects (Experiment 1) or positions (Experiment 2) were held constant within-blocks. In contrast to a control condition in which object–position conjunctions were trial-unique, a performance increase within and across-blocks was observed in the learning condition of both experiments. We hypothesized that within-block learning mainly relies on instance-based processes, whereas across-block learning might depend on rule-based mechanisms. A within-block parametric fMRI analysis revealed a learning-related increase of lateral prefrontal and striatal activity and a learning-related decrease of hippocampal activity in both experiments. By contrast, across-block learning was associated with an activation modulation in distinct prefrontal-striatal brain regions, but not in the hippocampus. These data indicate that hippocampal and prefrontal-striatal brain regions differentially contribute to instance-based and rule-based learning.

Previous studies have shown a modification of parkinsonian tremor (PT) by proprioceptive input induced by passive joint movements. The authors investigated the impact of electrically evoked proprioceptive input on PT. In eight patients with PT they recorded surface EMG from the opponens pollicis muscle, and forearm extensors and flexors. Rhythmic electrical stimulation was applied to the ipsilateral median nerve at the wrist using a submaximal stimulus intensity and stimulus frequencies between two stimuli per second and five stimuli per second. The tremor frequency did not adapt to the stimulus frequency. Tremor frequency of parkinsonian resting tremor increased significantly in the directly stimulated opponens pollicis muscle (mean +/- standard deviation, 4.35 +/- 0.64 Hz without stimulation versus 4.53 +/- 0.68 Hz with stimulation; P < 0.05, paired t-test), the not directly stimulated forearm muscles (4.90 +/- 0.72 Hz versus 5.18 +/- 0.73 Hz, P < 0.001), and the upper arm muscles (5.13 +/- 0.61 Hz versus 5.36 +/- 0.68 Hz, P < 0.01). Furthermore, the parkinsonian postural tremor accelerated significantly during ipsilateral median nerve stimulation (5.31 +/- 0.99 Hz versus 5.44 +/- 1.03 Hz, P < 0.05). Parkinsonian resting tremor in the forearm muscles also accelerated significantly during ipsilateral ulnar nerve stimulation (4.85 +/- 0.57 Hz versus 5.05 +/- 0.65 Hz, P < 0.05). Contralateral median nerve stimulation had no significant effect. These results suggest a close interaction between proprioceptive input and PT generation.

Purpose To determine whether the size and configuration of the optic chiasm in humans with albinism is different from that in normal control subjects. Methods Seventeen patients and 15 control subjects underwent magnetic resonance imaging of the entire head. Images were reformatted to the chiasm region and analyzed with observer-independent morphometry and measurements by a blinded observer. Results The albino group showed significantly smaller chiasmatic widths, smaller optic nerves and tracts, and wider angles between nerves and tracts. Statistical morphometry showed a different configuration of the optic chiasm. Conclusions Size and configuration of the optic chiasm in humans with albinism are distinctly different from those in normal control subjects and reflect the atypical crossing of optic fibers.

Objective: This study evaluates the correlation between closed, semi-closed and open-cell stent design and the association between stent type and clinical outcome as well as magnetic resonance imaging (MRI) findings. Design: A total of 194 patients who underwent unprotected carotid artery stenting (CAS) as well as diffusion-weighted magnetic resonance imaging (DW-MRI) before and after intervention were retrospectively reviewed. Materials and methods: Three stent designs were studied: closed cell, semi-closed cell and open cell. Spearman's Rho test was performed between the stent free cell area and the number and area of ischaemic lesions found after intervention. Adverse events were evaluated. Results: There was no significant difference in clinical outcome between the three stent groups (Zilver, Cook Europe, Denmark; Smart, Codman, MA; and Wallstent, Stryker, MN, USA). A significant correlation was found between the stent free cell area and the number and area of new ischaemic lesions on DW-MRI (P = 0.023). There were significantly fewer new lesions with an open-cell design (Zilver; 12.76 mm 2 free cell area) than with a closed-cell design (Wallstent; 1.08 mm 2 free cell area). Conclusions: Open-cell stent was related to a lower number and area of silent cerebral ischaemic lesions after unprotected CAS. However, clinical outcome, measured by incidence of adverse events and clinical neurologic assessment, was not significantly different between patients with different stent designs. © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.